Insect repellants attachable to keratinous tissues

Abstract

The present disclosure relates to novel compounds and topical formulations for covalently binding an insect repellent to skin and / or hair and applications. The novel compounds are represented by formula (Ia) or (Ib),, or a tautomer and / or a pharmaceutically acceptable salt thereof, wherein the compound of formula (Ia) or (Ib) comprises a 1,5-dicarbonyl moiety, or a tautomer thereof, and is capable of covalently binding to the skin and / or the hair after being topically applied to skin and / or hair by the reaction of its 1,5-dicarbonyl moiety, or of the tautomer thereof, with amino groups present on the skin and / or the hair; wherein L represents a group selected from —(CH2)-O-, —C(=O)-O-, or —CH(OR)(OR') and wherein the em-dash ("—") represents the bond attaching L to the remainder of the insect repellent; wherein R represents hydrogen or a first hydrocarbon moiety; wherein R' represents a second hydrocarbon moiety; wherein R' is further attached to DC, or wherein CH(OR)(OR') represents a cyclic acetal moiety which is further attached to DC; and wherein DC represents the remainder of the compound and comprises the 1,5-dicarbonyl moiety, or the tautomer thereof.

Description

[0001] Insect repellants atachable to keratinous tissues

[0002] CROSS REFERENCE TO RELATED APPLICATIONS

[0003] This application claims benefit from the European Patent Applications No.s EP24219629.3, 24219630.1, 24219631.9, and 24219632.7, all titled: “Compounds attachable to keratinous tissues” and all filed on December 12, 2024, their content being incorporated herein in their entirety by reference thereto; as well as the benefit of the European Patent Applications EP25177118.4, and EP25194313.0, both titled: “Compounds attachable to keratinous tissues”, filed on May 16, 2025, their content also being incorporated herein in their entirety by reference thereto. The contents of disclosure of the PCT applications filed by the present applicant on the same day with the Canadian Patent Office having the titles “Bicyclic compounds attachable to keratinous tissues”, “Dimeric compounds attachable to keratinous tissues”, “1,5-Dicarbonylic compounds attachable to keratinous tissues”, “Derivatives of elenolic acid attachable to keratinous tissues” and “Retinal derivatives attachable to keratinous tissues” are also being incorporated herein in their entirety by reference thereto.

[0004] TECHNICAL FIELD

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

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

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

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

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

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

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

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

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

[0014] Ring-open dialdehydic tautomer Glutaraldehyde

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

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

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

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

[0019] SUMMARY OF THE INVENTION

[0020] In a first aspect, the present disclosure relates to a compound of formula (la) or (lb),

[0021] (la) (lb) or a tautomer and / or a pharmaceutically acceptable salt thereof, for covalently binding an insect repellent to skin and / or hair; wherein the compound of formula (la) or (lb) comprises a 1,5- dicarbonyl moiety, or a tautomer thereof, and is capable of covalently binding to the skin and / or the hair after being topically applied to skin and / or hair by the reaction of its 1,5-dicarbonyl moiety, or of a tautomer thereof, with amino groups present on the skin and / or the hair; wherein L represents a group selected from — (CH2)-O-, — C(=O)-O-, or — CH(OR)(OR') and wherein the em-dash (“ — “) represents the bond attaching L to the remainder of the insect repellent; wherein R represents hydrogen or a first hydrocarbon moiety; wherein R' represents a second hydrocarbon moiety; wherein R' is further attached to DC or wherein CH(OR)(OR') represents a cyclic acetal moiety which is further attached to DC; and wherein DC represents the remainder of the compound and comprises the 1,5-dicarbonyl moiety, or a tautomer thereof. In a second aspect, the present disclosure relates to the use a compound of formula (la) or (lb),

[0022] (la) (lb) or a tautomer and / or a pharmaceutically acceptable salt thereof, for covalently binding an insect repellent to skin and / or hair; wherein the compound of formula (la) or (lb) comprises a 1,5- dicarbonyl moiety, or a tautomer thereof, and covalently binds to the skin and / or the hair after being topically applied to skin and / or hair by the reaction of its 1,5-dicarbonyl moiety, or of a tautomer thereof, with amino groups present on the skin and / or the hair; wherein L represents a group selected from — (CH2)-O-, — C(=O)-O-, or — CH(OR)(OR') and wherein the em-dash (“ — “) represents the bond attaching L to the remainder of the insect repellent; wherein R represents hydrogen or a first hydrocarbon moiety; wherein R' represents a second hydrocarbon moiety; wherein R' is further attached to DC, or wherein CH(OR)(OR') represents a cyclic acetal moiety which is further attached to DC; and wherein DC represents the remainder of the compound and comprises the 1,5-dicarbonyl moiety, or a tautomer thereof.

[0023] In a third aspect, the present disclosure relates to atopical composition comprising one or more of the compounds recited in the first aspect of the present disclosure.

[0024] In a fourth aspect, the present disclosure relates to a method of preparing a topical composition comprising one or more of the compounds recited in the first aspect of the present disclosure.

[0025] DESCRIPTION OF THE DRAWING

[0026] Fig. 1 shows the results of molecular docking of IR3535 and DEET to odorant protein AaegOBPl. (A) is a representation of AaegOBPl's hydrophobic surface and ribbons (surface at 40% transparency). Surface colors correspond to the Kyte-Doolittle scale (Yellow: hydrophobic zone; Blue: hydrophilic zone). (B) shows IR3535 in the hydrophobic cavity at distances of 2.8 A, 7.5 A, and 9.6 A from residues Ilel25, Tyr54, and Arg23, respectively. (C) shows DEET in hydrophobic cavity at distances of 2.6 A, 8.1 A, and 10.5 A from residues Ilel25, Tyr54, and Arg23, respectively.

[0027] DETAILED DESCRIPTION

[0028] The present invention relates to optimizing and expanding the aforementioned platform for the insect repellents DEET ( V, V-diethyl-m-toluamide) and IR3535 (ethyl 3-(N-butylacetamido) propanoate).

[0029] DEET and IR3535 are some of the most effective and widely used insect repellents, and their mechanism of action is complex in that they act in three distinct ways and on different organs: through smell, taste, and on contact and on sensilla located on the mosquitoes’ antennae, their proboscis and the tarsi on their legs. In particular, the olfactory repellent effect of DEET and IR3535 is well-investigated: The behavioral effect begins with the reception of volatile DEET and IR3535 captured by trichoid sensilla, specialized chemoreceptors present in the antennae. The volatilized molecules pass through the sensilla to the sensillar lymph (a hydrophilic medium at pH close to 7), where they are transported by odorant-binding proteins (OBPs). These OBPs are characterized by a binding pocket where molecules are bound via different types of molecular interactions. The protein-ligand complex, formed by the OBP and the odorant molecule, extends to the cellular membrane of olfactory receptor neuron (ORN) dendrites, where odorant receptors (ORs) are found. Interactions between OBPs and ORs take place in a low-pH medium favorable for the conformational change of OBPs and the subsequent release of the odorant molecule in the receptors. ORs are specialized proteins formed by receptor-co-receptor heterodimers that allow for the passage of ions through the neuron membrane, which transforms a chemical signal into an electrical signal that then triggers a behavioral response (i.e. repellence) by the mosquito.

[0030] The odorant-binding proteins (OBPs) are important gate keepers and effective insect repellents such as DEET and IR3535 are known to bind well to these OBPs. One of best characterized OBPs in mosquitoes is AaegOBPl which is located on the maxillary antennae and palps. This globular protein is composed of 125 amino acid residues of an approximate cavity depth of 2.3 nm, and the odorant-binding site is composed of arginine 23 (Arg23), tyrosine 54 (Tyr54), and isoleucine 125 (Ilel25). These residues interact with DEET and IR3535 via hydrophobic and hydrophilic interactions, facilitating their transport through the sensillar lymph.

[0031] The article by Portilla-Pulido et al., Journal of Medical Entomology, 57(2), 2020, 463-476, provides an in-silico analysis of the molecular docketing of DEET and IR3535 to the odorantbinding site which is located in a hydrophobic pocket. Present Fig. 1 reproduces Fig. 4 of this article. For DEET, Fig. 1 shows that the A, A-diethyl amide moiety is primarily interacting with He 125 whereas the methylphenyl moiety is extending relatively far out of the hydrophobic pocket and has a relatively high degree of rotational freedom. For IR3535, Fig. 1 shows that the 3-(N-butylacetamido) moiety is primarily interacting with He 125 whereas the ethyl ester moiety is again extending relatively far out of the hydrophobic pocket and has a relatively high degree of rotational freedom.

[0032] The present inventors have therefore concluded that the methylphenyl moiety of DEET and the ester moiety of IR3535 are promising candidates for modifying DEET and IR3535 for their attachment to the anchoring moieties of the present disclosure.

[0033] As a further consideration, the present inventors have investigated the metabolic pathways of DEET and IR3535. The main metabolite of DEET is AA-diethyl-m-(hydroxymethyl) benzamide, i.e. DEET in which the aromatic methyl group has been oxidized to hydroxymethyl. Further metabolites include the further oxidized products AA-diethyl-m-formylbenzamide and the corresponding carboxylic acid. For IR3535, the main metabolite is 3-(N- butylacetamido)propanoic acid. Thus, the metabolization of DEET and IR3535 provides functional groups on both DEET and IR3535 which can be utilized to attach these compounds to the anchoring moieties of the present disclosure. Moreover, for both DEET and IR3535, the utilized functional groups are on the moieties extending relatively far out of the hydrophobic pocket of AaegOBPl, so a high retention of insect repellency can be expected.

[0034] Utilizing the metabolites of DEET and IR3535 has the further benefit that cytotoxicity and skin irritancy of conjugates of these compounds with the anchoring moieties of the present disclosure can be expected to be similar to the well-tolerated DEET and IR3535 since cleavage and degradation of the conjugates will liberate these metabolites.

[0035] The present inventors have further concluded on the basis of their unpublished work that not only 3,4-saturated 2H-pyran derivatives are effective and reliable in coupling to skin and hair, but that 1,5-dicarbonyl moieties in general are also effectively and reliable in coupling to skin and hair. The coupling is also of similar stability, which is explainable when considering that the entire class of 1,5-dicarbonyls can react with amines to the aforementioned very stable 1,4- dihydropyridine moiety. Therefore, the present inventors have concluded that 1,5-dicarbonyl moieties in general are representing an attractive platform of compounds which are suitable for topically coupling a very diverse range of active ingredients to keratinous tissues such as skin or hair.

[0036] Finally, the present inventors have realized that this new platform does not only allow to covalently bind an active ingredient to skin or hair, but that the irreversibly bound 3,4-saturated 2H-pyran derivative can be provided with linkers or functional groups which are cleavable to release the active ingredient over time, for instance by hydrolysis or enzymatic cleavage. Suitable functional groups providing such sustained release properties are well-known in the art and readily available to the skilled person, see for instance V. Redasani, and S. Bariwidely, Prodrug Design - Perspectives, Approaches and Applications in Medicinal Chemistry, 1sted., 2015, ISBN: 9780128035191, which is incorporated herein in its entirety by reference thereto.

[0037] The ability to liberate insect repellents in a sustained release over time can be expected to improve their performance since both DEET and IR3535 are extensively lost by evaporation of the compound on the skin. This means that, in a conventional topical application, a large excess of the compounds is initially applied to ensure that a sufficient concentration of DEET and IR3535 remains throughout the intended protection period. This is wasteful and represents an unnecessarily high exposure to (thankfully slightly) cytotoxic and skin irritating substances. Moreover, at higher concentrations, both DEET and IR3535 leave an oily feel on the skin which many users consider to be unpleasant. The sustained release of DEET and IR3535 metabolites allows to provide the dosage actually required for insect repellency at each given point while minimizing unnecessary losses due to evaporation.

[0038] Accordingly, in a first aspect, the present disclosure relates to a compound of formula (la) or

[0039] (lb), or a tautomer and / or a pharmaceutically acceptable salt thereof, for covalently binding an insect repellent to skin and / or hair.

[0040] As part of the moiety DC, the compound of formula (la) or (lb) comprises a 1,5-dicarbonyl moiety or a tautomer thereof. The term “1,5-dicarbonyl moiety” is attributed its ordinary meaning in the art and refers to a chemical moiety that comprises two carbonyl groups in respective 1,5-position to each other. Alternatively, this positioning can be described as an a, 5- dicarbonyl, i.e. the second carbonyl group is on the 5-carbon to the first carbonyl group. In some embodiments, the 1,5-dicarbonyl moiety can be a 1, 5-dial dehy de moiety, a 1-aldehyde- 5-keto moiety, a l-keto-5-aldehyde moiety, or a 1,5-diketo moiety. The term “tautomer” in this context specifically refers to the tautomers of the 1,5-dicarbonyl moiety and is meant to also encompass those constitutional isomers in which the 1,5-dicarbonyl moiety is present as a 6- membered cyclic enolether moiety that is accessible by an intramolecular nucleophilic ringclosure, as well as its respective tautomers.

[0041] The compound of formula (la) or (lb) is capable of covalently binding to the skin and / or the hair after being topically applied to skin and / or hair by the reaction of its 1,5-dicarbonyl moiety, or of a tautomer thereof, with amino groups present on the skin and / or the hair.

[0042] In formulae (la) and (lb), L represents a group selected from — (CH2)-0-, — C(=O)-O-, or — CH(OR)(OR'). The em-dash (“ — “) represents the bond attaching L to the remainder of the insect repellent. R represents hydrogen or a first hydrocarbon moiety and R' represents a second hydrocarbon moiety. In some embodiments, R' is further attached to DC (and is not attached to R). Alternatively, CH(OR)(OR') represents a cyclic acetal moiety which is further attached to DC. In other words, in this case, R represents the first hydrocarbon moiety, R and R' are attached to each other and form, together with the CH-group, a cyclic acetal moiety which is further attached to DC (via R' which is part of the cyclic acetal moiety). In still other words, CH(OR)(OR') represents a cyclic acetal moiety which is further attached to DC and in which the first and second hydrocarbon moieties are attached to each other.

[0043] The first hydrocarbon moiety is not particularly limited. In some embodiments, the first hydrocarbon moiety comprises, in combination with its optional substituents, 1 to 7, more specifically 1 to 4, and in particular 1 or 2, carbon atoms; 0 to 3, more specifically 0 to 2, and in particular 0 or 1 oxygen atoms; 0 or 1 nitrogen atoms; 0 or 1 sulfur atoms; and 0 to 3, more specifically 0 to 2, and in particular 0 or 1 halogen atoms.

[0044] The second hydrocarbon moiety is not particularly limited. In some embodiments, the second hydrocarbon moiety comprises, in combination with its optional substituents, 1 to 7, more specifically 1 to 4, and in particular 1 or 2, carbon atoms; 0 to 3, more specifically 0 to 2, and in particular 0 or 1 oxygen atoms; 0 or 1 nitrogen atoms; 0 or 1 sulfur atoms; and 0 to 3, more specifically 0 to 2, and in particular 0 or 1 halogen atoms.

[0045] The cyclic acetal moiety may, besides the substitution(s) necessary for attaching the cyclic acetal to DC, be further substituted. In some embodiments, the cyclic acetal moiety comprises, in combination with its optional substituents, 1 to 7, more specifically 1 to 4, and in particular 1 or 2, carbon atoms; 0 to 3, more specifically 0 to 2, and in particular 0 or 1 oxygen atoms; 0 or 1 nitrogen atoms; 0 or 1 sulfur atoms; and 0 to 3, more specifically 0 to 2, and in particular 0 or 1 halogen atoms. In some embodiments, the cyclic acetal moiety is a 5-membered ring or a 6-membered ring.

[0046] DC represents the remainder of the compound and comprises the 1,5-dicarbonyl moiety, or the aforementioned tautomeric moiety / moieties thereof.

[0047] When referring to R' being further attached to DC, it should be understood that the second hydrocarbon moiety, besides being attached to the CH-group via an oxygen atom, is also attached to DC by one or more additional covalent bonds. When referring to the cyclic acetal moiety being further attached to DC, it should be understood that the cyclic acetal moiety, besides being attached to the CH-group via the two oxygen atoms, is also attached to DC by one or more additional covalent bonds. In both cases, the further attachment to DC is not particularly limited and can include single, double and / or triple bonds. Moreover, the further attachment to DC can be an attachment via different atoms of the hydrocarbon moiety and the cyclic acetal moiety, respectively. For instance, in the following example, the DEET derivative can comprise L as the cyclic acetal moiety, wherein the cyclic acetal moiety is formed with hydroxy tyrosol. The further attachment to DC is in this case provided by two covalent bonds provided by different carbon atoms of the cyclic acetal moiety. The broken bond indicates the bond to the remainder of DC.

[0048] In some embodiments, the compound of formula (la) or (lb), in the form as it is bound to the skin and / or hair, is cleavable to release the insect repellent.

[0049] When referring to a compound of formula (la) or (lb) which is cleavable to release the insect repellent, it should be understood that “cleavable” in this context in particular means that, after the compound of formula (la) or (lb) has covalently bound to the skin and / or the hair, one or more bonds of the compound of formula (la) or (lb), in the form as it is present on the skin and / or the hair, can be broken such that the insect repellent is released. In some embodiments, it may be particularly advantageous that the compound of formula (la) or (lb) can be cleaved under physiological conditions to provide the insect repellent 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. It should be understood that, when referring in this context or another context to “physiological conditions”, it is in particular referred to the ambient conditions, in particular pH, enzymatic and temperature conditions, encountered at the locus where the compound of formula (la) or (lb) is binding to keratinous tissues in skin and / or hair of the (mammalian, in particular human) subject to be treated.

[0050] In some embodiments, the compound of formula (la) or (lb), in the form as it is bound to the skin and / or hair, is hydrolysable to release the insect repellent in the presence of water 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 (la) or (lb) for 24 hours at 37°C in any of the following three solutions: a) a phosphate buffer solution, pH 5.5; an aqueous solution of bovine collagen type 1 (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 compound in question qualifies as hydrolysable if a notable amount of the respective insect repellent is released (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.

[0051] It should be understood that the group L serves to join the insect repellent to the remainder of the compound DC. Accordingly, the group L can be considered to be part of the insect repellent and is cleaved to provide the respective groups -(CTbj-OH, -CHO and -COOH, or a salt thereof, to the insect repellent of formula (la) and -(CH2)-OH, -CHO -COOH, or a salt thereof, or an ester of -COOH to the insect repellent of formula (lb).

[0052] In some embodiments, the compound of formula (la) or (lb), in the form as it is bound to the skin and / or hair, is enzymatically cleavable by enzymes natively present on mammalian skin and / or hair, to release the insect repellent. The skin and / or hair is advantageously human skin and / or human hair. In some embodiments, the compound of formula (la) or (lb), in the form as it is bound to the skin and / or hair, is cleavable to release the insect repellent by esterase enzymes. In some embodiments, the compound of formula (la) or (lb) is enzymatically cleavable under physiological conditions by enzymes present in the mammalian, more specifically human skin. A suitable in-vitro test is placing 0.1 mol / L of the compound of formula (la) or (lb), optionally after having been converted with lysine to the corresponding cyclic enamine derivative, 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 compound in question qualifies as enzymatically cleavable if a notable amount of the insect repellent is liberated (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.

[0053] In some embodiments, the compound of formula (la) or (lb) is a compound of formula (la) and the compound is cleavable to any one of the compounds of formulae (Ila), (lib) and (lie):

[0054] It may be particularly advantageous that the compound of formula (la) is cleavable to the compound of formula (Ila) since this compound represents the main metabolite of DEET and can potentially form a hydrogen bridge with Tyr54 in AaegOBPl.

[0055] In some embodiments, the compound of formula (la) or (lb) is a compound of formula (lb) and the compound is cleavable to any one of the compounds of formulae (Illa), (Illb), (IIIc) and (Illd),

[0056]

[0057] (lllc) (Hid)

[0058] Mi in the above formula (Hid) represents an optionally substituted hydrocarbon moiety comprising, in combination with its optional substituents, 1 to 7, more specifically 1 to 4, and in particular 1 or 2, carbon atoms; 0 to 3, more specifically 0 to 2, and in particular 0 or 1 oxygen atoms; 0 or 1 nitrogen atoms; 0 or 1 sulfur atoms; and 0 to 3, more specifically 0 to 2, and in particular 0 or 1 halogen atoms. In some embodiments, Mi represents C1-C4 alkyl or C2-C4- alkenyl, both of which are optionally substituted with one, two or three hydroxyl groups, one amino group, and / or 0 to 3, more specifically 0 to 2, and in particular 0 or 1 halogen atoms.

[0059] It may be particularly advantageous that the compound of formula (lb) is cleavable to the compound of formula (Illa) since this is the main metabolite of IR3535. It may also be particularly advantageous that the compound of formula (lb) is cleavable to the compound of formula (Hid) and in particular wherein Mi represents C2-C4 alkyl, which is optionally substituted with one, two or three hydroxyl groups, one amino group, and / or 0 to 3, more specifically 0 to 2, and in particular 0 or 1 halogen atoms, since these compounds are structurally very similar to IR3535.

[0060] In some embodiments, the compound of formula (lb) is cleavable to any one of the following compounds:

[0061] n=1 or 2

[0062] In some embodiments, DC comprises a 1,5-dialdehyde moiety, or a tautomer thereof; a 1- aldehyde-5-keto moiety, or a tautomer thereof; a l-keto-5-aldehyde moiety, or a tautomer thereof; or a 1,5-diketo moiety, or a tautomer thereof; and in particular a 1,5-dialdehyde moiety, or a tautomer thereof; a 1 -aldehy de-5-keto moiety, or a tautomer thereof; or a 1 -keto-5-aldehy de moiety, or a tautomer thereof.

[0063] In some embodiments, DC represents a Cs-Ceo moiety, in particular a Cs-Ceo moiety comprising 5 to 60, more specifically 8 to 48, and in particular 10 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.

[0064] Specific compounds

[0065] As said, DC may comprise the 1,5-dicarbonyl moiety in its tautomeric form. Accordingly, in some embodiments, the compound of formula (la) or (lb) is a compound which comprises a cyclic enolether and which is represented by formula (IV), or a tautomer and / or a pharmaceutically acceptable salt thereof, for covalently binding the insect repellent.

[0066] The compound of formula (IV) is capable of covalently binding to the skin and / or the hair after being topically applied to skin and / or hair by the reaction of its cyclic enolether with amino groups present on the skin and / or the hair.

[0067] The compound of formula (IV) may optionally also further comprise one or more active ingredients. The one or more active ingredients are independently from each other selected from a moisturizer, a pesticide, a UVA- and / or UVB-absorbing moiety and a color-imparting moiety.

[0068] The compound of formula (IV) comprises the optional one or more active ingredients, independently from each other, a) as the active ingredient, or b) as a precursor of the active ingredient, and the compound of formula (IV) is cleavable to release the active ingredient from the precursor after the application of the compound of formula (IV) to the skin and / or the hair (in the following: “the precursor thereof’). In formula (IV), Li, L2, L3, L4, L5, Lg and L7 represent, independently from each other, a linker group or are absent. In formula (IV), one or more of Ai, A2, A3, A4, As, As and A7 represent: a) the moiety (IVa) or the moiety (IVb),

[0069] (IVa) (IVb) and the broken bond indicates the attachment to the corresponding linker group Li, L2, L3, L4, Ls, Le and L7, or if the respective linker group is absent, to the corresponding ring atom of the cyclic enolether; and, if present, b) the one or more active ingredients and precursors thereof.

[0070] Each of Ai, A2, A3, A4, As, As and A7 not representing the moiety (IVa), the moiety (IVb) or one of the optional one or more active ingredients and precursors thereof is defined as follows:

[0071] Ai represents hydrogen, a C1-C30 moiety, hydroxyl, amino, or a halogen;

[0072] A2 and A3 are, independently from each other, defined as indicated for Ai or L2-A2 and L3- A3 jointly represent oxo;

[0073] A4 and As are, independently from each other, defined as indicated for Ai;

[0074] As and A7 represent, independently from each other, hydrogen or a C1-C30 moiety.

[0075] In formula (IV), R1represents hydrogen or a protective group hydrolysable under physiological conditions after application of the compound of formula (IV) to the skin and / or the hair. Finally, in formula (IV), the dashed line represents a bond or is absent and, in case dashed line represents a bond, -L5-A5 and -O-R1are absent.

[0076] The one or more active ingredients are selected from a moisturizer, a pesticide, a UVA- and / or UVB-absorbing moiety and a color-imparting moiety.

[0077] The compound of formula (IV) is topically applied to skin and / or hair. It comprises a 3,4- saturated 2H-pyran moiety which, once the compound of formula (IV) 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.

[0078] The compound of formula (IV) comprises one or more active ingredients which are, independently from each other, present in the compound: a) as the active ingredient, or b) as a precursor of the active ingredient, wherein the compound of formula (IV) is cleavable to release the active ingredient from the precursor after the application of the compound of formula (I) to the skin and / or the hair.

[0079] It should be understood that the compound of formula (IV) 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 skin and / or hair (more precisely while being attached to the remainder of the compound of formula (IV) in the form as it is covalently bound to skin and / or hair). As an example, a polyhydroxy-based skin moisturizer is able to provide its moisturizing effect while being bound to the skin since its hydroxyl groups provide their water-retaining effect irrespective of whether the moisturizer is bound to the skin or not. However, this should not be understood as excluding the possibility that the active ingredient is chemically modified while being bound to skin. For instance, a polyhydroxy-based skin moisturizer may be acetylated at a terminal hydroxyl group to make it more lipophilic and allow a deeper penetration into the epidermis before the compound of formula (IV) binds to the skin. The acetylated hydroxyl group may be subsequently hydrolyzed or cleaved by esterase enzymes which are natively present on skin such that the polyhydroxybased skin moisturizer provides, over time, its moisturizing effect as a chemically modified active ingredient.

[0080] 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 (IV) in the form as it is covalently bound to skin and / or hair. Alternative terms include e.g. the term “prodrug” in case the active ingredient is a pharmaceutical. It should also be understood that a precursor will be cleaved to the corresponding active ingredient. For brevity, the precursor corresponding to an active ingredient will in the following also be referred to as “the corresponding precursor thereof” or simply “precursor”. However, it should be understood that, unless specified otherwise, the term “precursor” is meant to refer to the precursor corresponding to the active ingredient which is mentioned in the respective context. It should also be understood that an active ingredient may have multiple precursors, i.e. the term “precursor” will often refer to a group of moi eties.

[0081] Moreover, it should be understood that the compound of formula (IV) comprising a precursor of an active ingredient means that the active ingredient is providing its effect or activity after its corresponding active ingredient has been cleaved from the remainder of the compound of formula (IV) in the form as it is covalently bound to skin and / or hair. 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 (IV) in the form as it is covalently bound to skin and / or hair. For instance, the precursor of an insect repellent may already act as contact repellent while being bound as a precursor, but may provide as a more potent olfactory repellent effect after being cleaved from the remainder of the compound of formula (IV) in the form as it is covalently bound to skin and / or hair.

[0082] In the compound of formula (IV), the substituents are defined as follows:

[0083] One or more of Ai, A2, A3, A4, As, As and A7 may represent one of the one or more active ingredients and precursors. In other words: In case the compound of formula (IV) comprises one active ingredient, one of Ai, A2, A3, A4, As, As and A7 represents said active ingredient. In case the compound of formula (IV) comprises one precursor, one of Ai, A2, A3, A4, As, As and A7 represents said precursor. In case the compound of formula (IV) 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 (IV) comprises one active ingredient and one precursor of another active ingredient, one of Ai, A2, A3, A4, As, As and A7 represents the active ingredient and another one of Ai, A2, A3, A4, As, As and A7 represents the precursor, and so on.

[0084] Li, L2, L3, L4, Ls, Ls and L7 represent, independently from each other, a linker group or are absent. Each of Ai, A2, A3, A4, A5, As and A7 not representing one of the one or more active ingredients and precursors is defined as follows:

[0085] Ai represents hydrogen, a C1-C30 moiety, hydroxyl, amino, or a halogen.

[0086] A2 and A3 are, independently from each other, defined as indicated for Ai or L2-A2 and L3-A3 jointly represent oxo.

[0087] A4 and As are, independently from each other, defined as indicated for Ai.

[0088] As and A7 represent, independently from each other, hydrogen or a C1-C30 moiety.

[0089] R1represents hydrogen or a protective group hydrolysable under physiological conditions after application of the compound of formula (IV) to the skin and / or the hair. The primary purpose of providing a protective group hydrolysable under physiological conditions is to increase the storage stability of the compound of formula (IV), at least in a neutral or slightly alkaline formulation, more specifically in a formulation having a pH of 7.0 or higher, of 7.5 or higher, of 8.0 or higher or of 8.5 or higher. However, once applied to skin or hair with their lower pH environment, R1should be hydrolysed to the more reactive hemi-acetal which then binds to the skin and / or the hair. When referring in this context to “physiological conditions” it should be understood that this refers to the pH conditions encountered at the locus where the compound of formula (IV) is supposed to bind to in the subject to be treated (skin or hair). Moreover, it should be understood that the hydrolysis under physiological conditions takes place in an amino-acid rich environment such as collagen which is the predominant skin protein. Collagen comprises a complex mixture of the following amino acids: alanine, arginine, asparagine, aspartate, cysteine, glutamate, glutamine, glycine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, serine, threonine, tyrosine, and valine. These amino-acids, and in particular those with nucleophilic side chains such as lysine, will further facilitate hydrolysis.

[0090] Accordingly, a group qualifies as “protective group hydrolysable under physiological conditions after application of the compound of formula (IV) to the skin and / or the hair”, if the compound of formula (IV) comprising the group in question as R1hydrolyses to the corresponding hemi-acetal (and its tautomers) by more than 10 mol-%, more specifically by more than 50 mol%, and in particular by more than 80 mol%, when incubating 0.1 mmol / mL of the compound of formula (IV) for 24 hours at 37°C in any one of the following three solutions: a) a phosphate buffer solution, pH 5.5; an aqueous solution of bovine collagen type I (1 mg / mL, adjusted to pH 5.5); and c) an aqueous solution of lysine (1 mg / mL, adjusted to pH 5.5 using a phosphate buffer solution). The conversion can be monitored by any suitable means, including nuclear magnetic resonance spectroscopy (NMR), high-performance liquid chromatography (HPLC), optionally coupled to mass spectrometer (MS) or a UV / vis. The aforementioned conversion ratio in mol% can also be determined using any suitable means, including the aforementioned methods. Additionally or alternatively, a group qualifies as “protective group hydrolysable under physiological conditions after application of the compound of formula (IV) 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.

[0091] As said, the compound of formula (IV) is 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.

[0092] As also said, the compound of formula (IV), once it has been topically applied to skin and / or hair, can covalently bind to the skin and / or the hair by the reaction of its 3,4-saturated 2H-pyran moiety with amino groups which are present on the skin and / or the hair. Whether the compound of formula (IV) has covalently bound to the skin and / or the hair by reaction of its 3,4-saturated 2H-pyran moiety can be determined by any suitable means. For instance, if the compound cannot be comprehensively washed off from an (explanted) sample of porcine skin or from a hair sample by water, soap, and / or isopropanol after incubating the compound of formula (IV) (or a topical composition comprising said compound) on the respective porcine skin or hair sample at 37°C for 24 hours, the compound of formula (IV) can be considered to have covalently bound by reaction of its 3,4-saturated 2H-pyran moiety to skin or hair. Additionally or alternatively, the compound can be considered to realize this feature if it passes a suitable in-vitro test, in particular placing 0.1 mol / L of the compound of formula (IV) in an aqueous or methanolic solution having a pH of about 5.5 and further containing 0.1 mmol / mL lysine at 37°C for 24 hours, wherein the compound of formula (IV) passes the test if it is converted by more than 10 mol%, more specifically by more than 50 mol%, and in particular by more than 75 mol%, to its corresponding 1 ,4-dihydropyridine derivative. The conversion can be monitored by any suitable means, including nuclear magnetic resonance spectroscopy (NMR), high- performance liquid chromatography (HPLC), optionally coupled to mass spectrometer (MS) or a UV / vis detector. The aforementioned conversion ratio in mol% can also be determined using any suitable means, including the aforementioned methods. It should further be understood that the reaction of the compound of formula (IV) proceeds via its 3,4-saturated 2H-pyran moiety in its hemiacetal form, i.e. when R1represents hydrogen. Accordingly, the aforementioned in- vitro test may, for those compounds of formula (IV) in which R1does not represent hydrogen, also alternatively be performed with the corresponding derivative of formula (IV) in which R1represents hydrogen.

[0093] 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.

[0094] The term “pesticide” refers to its common meaning in the art and in particular refers compounds capable of killing, incapacitating, repelling or in any other way ameliorating a risk to mammalian (human) health, comfort or well-being posed by invertebrates, in particular insects. It should be understood that this refers to a further optional pesticide comprised by the compound of formula (IV) in addition to the insect repellent referenced in formula (I).

[0095] The term “UVA- and / or UVB-absorbing moiety” refers to the common meaning in the art and in particular refers to a moiety which reduces the amount of UVA- and / or UVB-radiation that can pass through the compound of formula (IV).

[0096] The term “color-imparting moiety” refers to the common meaning in the art and in particular refers to moiety which imparts a color-impression perceivable by the human eye.

[0097] In the following, further specific embodiments of the first aspect will be described. The terms “at least one of the one or more active ingredients or of the corresponding precursors thereof’ and “at least one of the one or more active ingredients or of the precursors thereof’ will be used interchangeably. Moreover, for reasons of conciseness, many embodiments will specify a feature for “at least one of the one or more active ingredients or of the (corresponding) precursors thereof’. However, it should be understood that, in case that the compound of formula (IV) comprises multiple active ingredients and / or precursors, and unless expressly stated otherwise, this is meant to also disclose the embodiment in which more than one and in particular all, active ingredients and / or precursors are provided with that feature.

[0098] In some embodiments, at least one of the one or more active ingredients or of the corresponding precursors thereof is a Ci-Ceo moiety. In some embodiments, the Ci-Ceo moiety comprises 1 to 60, more specifically 1 to 48, and in particular 1 to 36 carbon atoms; 0 to 24, more specifically 0 to 16, and in particular 0 to 12 oxygen atoms; 0 to 8, more specifically 0 to 6, and in particular 0 to 4 nitrogen atoms; 0 to 6, more specifically 0 to 4, and in particular 0 to 3 sulfur atoms; 0 to 6, more specifically 0 to 4, and in particular 0 to 3 phosphorus atoms, 0 to 4, more specifically 0 to 3, and in particular 0 to 2 boron atoms; and 0 to 12, more specifically 0 to 10, and in particular 0 to 8 halogen atoms. In some embodiments, the Ci-Ceo moiety is a Cs-Ceo moiety, Cio-Ceo moiety, a Cis-Ceo moiety or a C20-C60 moiety, all of which may optionally comprise the same aforementioned heteroatoms.

[0099] 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 a H, O, N and others may be contained in the polymeric moiety.

[0100] In some embodiments, all of the one or more active ingredients or of the corresponding precursors thereof represent either Ci-Ceo moieties or polymeric moieties. In some embodiments, all of the one or more active ingredients or of the corresponding precursors thereof represent Ci-Ceo moieties. In some embodiments, all of the one or more active ingredients or of the corresponding precursors thereof represent polymeric moieties.

[0101] In some embodiments, the compound of formula (IV) 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 (IV) comprises only the insect repellent depicted in formula (la) or (lb). However, there may also be cases where it is advantageous that the compound of formula (IV) further comprises one or more active ingredients, one or more precursors, or a mixture of one or more active ingredients and one or more precursors.

[0102] Specifically, in some embodiments, the compound of formula (IV) 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.

[0103] In some embodiments, it may be particularly advantageous that the compound of formula (IV) 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 the further active ingredient or precursor thereof and reduce photodegradation.

[0104] In some embodiments, it may be particularly advantageous that the compound of formula (IV) 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.

[0105] In some embodiments, it may be particularly advantageous that the compound of formula (IV) 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.

[0106] In some embodiments, L7-A7 represents hydrogen or the C1-C30 moiety. In some embodiments, Le-Ae represents hydrogen or the C1-C30 moiety. In some embodiments, L7-A7 represents hydrogen and Le-Ae represents the C1-C30 moiety. In some embodiments, L7-A7 represents the C1-C30 moiety and Le-Ae represents hydrogen. In some embodiments, L7-A7 represents the Ci- C30 moiety and Le-Ae represents the C1-C30 moiety. It may be particularly advantageous, in some embodiments, that L7-A7 represents hydrogen and Le-Ae represents hydrogen. It may be particularly advantageous, in some embodiments, that L7-A7 represents hydrogen and Le-Ae represents the C1-C30 moiety or that L7-A7 represents the C1-C30 moiety and Le-Ae represents hydrogen. In these substitution patterns the initial high reactivity of the aldehyde group(s) is provided.

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

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

[0109] When referring to a compound of formula (IV) 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 (IV) has covalently bound to the skin and / or the hair, that one or more bonds of the compound of claim (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.

[0110] Accordingly, in some embodiments, the compound of formula (IV) 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 (IV) and wherein the functional group comprises a carbon atom, an oxygen atom, a nitrogen atom, a sulfur atom, a phosphorus atom, a boron atom, or a combination thereof; more specifically a carbon atom, an oxygen atom, a nitrogen atom, or a combination thereof; and in particular a carbon atom and / or an oxygen atom.

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

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

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

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

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

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

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

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

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

[0120] In some embodiments, after the compound of formula (IV) 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 (IV) 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 (IV) for applying a pharmaceutical to skin, wherein the functional group is a coumarin moiety which photodegrades to liberate the pharmaceutical from its prodrug moiety upon exposure to daylight. The use of coumarin-based linkers for light-triggered drug release is reviewed in e.g. Johan et al., Pharmaceuticals (Basel), 2022, 15(6):655, which is incorporated herein in its entirety by reference thereto.

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

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

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

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

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

[0126] In some embodiments, the functional group comprises a carbon ester, in particular a monoester, 1,1 -diester, a carbonate, or a carbamate; an ether or thioether, in particular an acetal, a hemiacetal, a glycosidic group or a thioacetal; a disulfide; a carbon amide, in particular a peptide or a N-Mannich base; an enol; an enamine; an imine; an oxime; a sulfate ester; a sulfonic acid ester; a sulfonic acid amide; a phosphoric acid ester; a phosphonic acid ester; a phosphoric acid amide; a phosphonic acid amide; a boronic ester, a borinic ester, a boric ester; an oxazol, a triazole, a benzothiazole, or a coumarin.

[0127] 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.

[0128] Further specific compounds

[0129] In some embodiments, the compound of formula (IV) is a compound of formula (V), or a tautomer and / or a pharmaceutically acceptable salt thereof; wherein R1, Ai, A2, A3, A4, As, A7, Li, L2, L3, L4, Lg, and L7 are defined for any of the above embodiments.

[0130] In some embodiments, it may be particularly advantageous that, in the above formula (V), Li- Ai and L4-A4 do not represent hydrogen. Like glutardialdehyde, 3,4-saturated 2H-pyran derivatives may undergo side-reactions which result in oligomerized or polymerized sideproducts which are undesirable in view of a potential skin irritation or skin sensitization. One major pathway for the generation of these side products is that, once the ring-opened form of the 3,4-saturated 2H-pyran derivatives has reacted to an imine, its tautomeric enamine can bind - via the nucleophilic carbon atom of the enamine - to other 3,4-saturated 2H-pyran derivatives. However, if both C-3 and C-5 (i.e. the carbon atoms to which L1-A1 and L4-A4 are attached) are not carrying a hydrogen atom, the subsequent elimination of hydrogen to a stable intermediate is no longer possible and this reaction pathway to oligomerized and polymerized side products is effectively suppressed.

[0131] In some embodiments, in the above formula (V), it may further be particularly advantageous that L7-A7 represents hydrogen and Lg-Ag represents the C1-C30 moiety or that L7-A7 represents the C1-C30 moiety and Lg-Ag represents hydrogen since this substitution pattern retains the initial high reactivity of an aldehyde group. It may be further particularly advantageous, in some embodiments, that L7-A7 represents hydrogen and Lg-Ag represents the C1-C30 moiety since this substitution pattern is conveniently synthetically accessible, as discussed below in the experimental section.

[0132] In some embodiments, in the above formula (V), 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.

[0133] 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.

[0134] 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.

[0135] In some embodiments, A4 represents one of the one or more active ingredients or of the corresponding precursors thereof, and: A2 represents hydrogen and A3 represents hydrogen; or A2 represents the C1-C30 moiety and A3 represents hydrogen; or A2 represents hydrogen and A3 represents the C1-C30 moiety; or A2 represents the C1-C30 moiety and A3 represents the C1-C30 moiety.

[0136] Linkers LI to L8

[0137] In some embodiments, Li, L2, L3, L4, Ls, Ls, L7 and Ls (Ls will be introduced below) independently from each other are absent or are present and represent an optionally substituted hydrocarbon moiety comprising, in combination with its optional substituents, 1 to 18 carbon atoms, more specifically 1 to 12 carbon atoms, more specifically 1 to 10 carbon atoms, and in particular 1 to 8 carbon atoms.

[0138] In some embodiments,

[0139] It may be particularly advantageous that, independently from each other:

[0140] 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

[0141] 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

[0142] 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

[0143] 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

[0144] 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

[0145] 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 L? 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

[0146] 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.

[0147] In some embodiments, Li may be present and represent an optionally substituted hydrocarbon moiety comprising, in combination with its optional substituents, 1 to 8 carbon atoms and the functional group may be attached to Li. Alternatively or additionally, in some embodiments, L2 may be present and represent an optionally substituted hydrocarbon moiety comprising, in combination with its optional substituents, 1 to 8 carbon atoms and the functional group may be attached to L2. Alternatively or additionally, in some embodiments, L3 may be present and represent an optionally substituted hydrocarbon moiety comprising, in combination with its optional substituents, 1 to 8 carbon atoms and the functional group may be attached to L3. It should be understood that the term “optionally substituted hydrocarbon moiety”, here and elsewhere in the specification, is not meant to exclude the presence of heteroatoms (i.e. atoms besides C and H).

[0148] Alternatively or additionally, in some embodiments, L4 may be present and represent an optionally substituted hydrocarbon moiety comprising, in combination with its optional substituents, 1 to 8 carbon atoms and the functional group may be attached to L4. Alternatively or additionally, in some embodiments, Ls may be present and represent an optionally substituted hydrocarbon moiety comprising, in combination with its optional substituents, 1 to 8 carbon atoms and the functional group may be attached to Ls. Alternatively or additionally, in some embodiments, Lg may be present and represent an optionally substituted hydrocarbon moiety comprising, in combination with its optional substituents, 1 to 8 carbon atoms and the functional group may be attached to Lg. Alternatively or additionally, in some embodiments, L7 may be present and represent an optionally substituted hydrocarbon moiety comprising, in combination with its optional substituents, 1 to 8 carbon atoms and the functional group may be attached to L7. In some embodiments, each of Li, L2, L3, L4, Ls, Lg, L7 and Ls comprises, optionally and independently from each other further, 1 to 8, more specifically 1 to 6, and in particular 1 to 4 oxygen atoms; 1 to 8, more specifically 1 to 6, and in particular 1 to 4 nitrogen atoms; 1 to 6, more specifically 1 to 4, and in particular 1 to 3 sulfur atoms; 1 to 6, more specifically 1 to 4, and in particular 1 to 3 phosphorus atoms, 1 to 4, more specifically 1 to 3, and in particular 1 or 2 boron atoms; and 1 to 10, more specifically 1 to 8, and in particular 1 to 6 halogen atoms. In some embodiments, independently from each other further, each of Li, L2, L3, L4, Ls, Lg, L7 and Ls does not comprise any further atoms species besides carbon, the (optional) aforementioned atom species and hydrogen.

[0149] In some embodiments, each of Li, L2, L3, L4, Ls, Lg, L7 and Ls is attached to its respective ring carbon atom by a carbon atom, by an oxygen atom, or by a nitrogen atom, more specifically by a carbon atom, or by an oxygen atom, and in particular by a carbon atom.

[0150] In some embodiments, two linkers may also jointly form a ring. In some embodiments, Li and Lg are present and form a ring; Alternatively or additionally, Li and L2 are present and form a ring. Alternatively or additionally, L2 and L4 are present and form a ring. Alternatively or additionally, L4 and L7 are present and form a ring. Alternatively or additionally, L4 and R1are present and form a ring. The presence of such rings, more specifically of rings formed by Li and L2, by L2 and L4, and by L4 and L7, and in particular of rings formed by L2 and L4, restrict the conformational freedom of the ring-opened 1,5-dicarbonyl tautomer and favors the close proximity of the 1,5-dicarbony positions, thus, may facilitate the ring-closing reaction to form the 1,4-dihydropyridine.

[0151] In some embodiments, in case Ai, A3, As, Ag and A7 do not represent one of the one or more active ingredients or of the precursors thereof, Li, L3, Ls,Lg and L7 are absent.

[0152] In some embodiments, the ring is a 5-, 6-, 7- or 8-membered ring, more specifically a 5-, 6-, or 7-membered ring, and in in particular a 5- or 6-membered ring.

[0153] In some embodiments, the ring is an optionally substituted cyclopentyl ring, an optionally substituted cyclohexyl ring, an optionally substituted pyrrolidinyl ring, an optionally substituted piperidinyl ring, an optionally substituted tetrahydrofuranyl ring or an optionally substituted tetrahydropyranyl ring.

[0154] In some embodiments, L3 and L4 are present and form an optionally substituted 5-, 6-, 7- or 8- membered ring comprising, in combination with its optional substituents, 1 to 12 carbon atoms, more specifically 1 to 10 carbon atoms, and in particular 1 to 8 carbon atoms, in particular an optionally substituted cyclopentyl, an optionally substituted cyclohexyl ring, an optionally substituted pyrrolidinyl ring, an optionally substituted piperidinyl ring, an optionally substituted tetrahydrofuranyl ring or an optionally substituted tetrahydropyranyl ring. These substitution patterns may be particularly advantageous in view of skin irritation potential since they mimic the well-tolerated genipin structure. In some embodiments, it may be particularly advantageous that L3 and L4 are present and represent an optionally substituted 5-or 6-membered ring, in particular cyclopentyl, cyclopentenyl, tetrahydrofuranyl, cyclohexyl, or cyclohexenyl, to which A3 and A4 are attached, optionally via a group selected from: -O-, -S-, -C(O)-, -CO2-, -O-C(O)- , -NH-C(O)-, -C(O)-NH-, -(CH2)I-4-, -(CH2)I-4-O- and -O-(CH2)I-4-, or combinations thereof.

[0155] 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.

[0156] In some embodiments, it may be particularly advantageous in view of facilitating a deeper skin penetration of the compound prior to anchoring that none of Li to Ls represents a polymeric moiety.

[0157] C1-C30 moiety

[0158] In any of the embodiments of the present disclosure, and independently from each other for each occurrence of the C1-C30 moiety in the present disclosure, it may be particularly advantageous that: the C1-C30 moiety comprises 1 to 30, more specifically 1 to 16, and in particular 1 to 12 carbon atoms; 0 to 12, more specifically 0 to 8, and in particular 0 to 6 oxygen atoms; 0 to 8, more specifically 0 to 6, and in particular 0 to 4 nitrogen atoms; 0 to 6, more specifically 0 to 4, and in particular 0 to 3 sulfur atoms; 0 to 6, more specifically 0 to 4, and in particular 0 to 3 phosphorus atoms, and 0 to 10, more specifically 0 to 8, and in particular 0 to 6 halogen atoms; and / or the C1-C30 moiety is bound a) to the respective Li, L2, L3, L4, L5, Lg, L7 and Ls, if it is present, via a carbon atom, an oxygen atom, a nitrogen atom or a sulfur atom, or b) if the respective Li, L2, L3, L4, L5, Lg, L7 and Ls, is absent, via a carbon atom, an oxygen atom, a nitrogen atom or a sulfur atom to the carbon atom of ring to which the C1-C30 moiety is attached.

[0159] In some embodiments, it may further be advantageous that, again independently from each other, for each occurrence of the C1-C30 moiety in the present disclosure: the C1-C30 moiety is selected from a saturated or unsaturated, cyclic or acylic (hetero)alkyl or (hetero)aryl, each comprising 1 to 30, more specifically 1 to 16, and in particular 1 to 12, carbon atoms; 0 to 12, more specifically 0 to 8, and in particular 0 to 6 oxygen atoms; 0 to 8, more specifically 0 to 6, and in particular 0 to 4 nitrogen atoms; 0 to 6, more specifically 0 to 4, and in particular 0 to 3 sulfur atoms; and 0 to 10, more specifically 0 to 8, and in particular 0 to 6 halogen atoms; and / or the C1-C30 moiety is bound a) to the respective Li, L2, L3, L4, Ls, Lg, L7 and Ls, if it is present, via a carbon atom, an oxygen atom, a nitrogen atom or a sulfur atom, or b) if the respective Li, L2, L3, L4, Ls, Lg, L7 and Ls, is absent, via a carbon atom, an oxygen atom, a nitrogen atom or a sulfur atom to the carbon atom of ring to which the C1-C30 moiety is attached.

[0160] In some further embodiments, it may be particularly advantageous that, again independently from each other, for each occurrence of the C1-C30 moiety in the present disclosure: the C1-C30 moiety is selected from a saturated or unsaturated (hetero)alkyl comprising 1 to 12, more specifically 1 to 8, and in particular 1 to 4, carbon atoms; 0 to 6, more specifically 0 to 4, and in particular 0 to 3 oxygen atoms; 0 to 4, more specifically 0 to 3, and in particular 0 to 2 nitrogen atoms; 0 or 1 sulfur atoms; and 0 to 5, more specifically 0 to 4, and in particular 0 to 3 halogen atoms; and the C1-C30 moiety is bound: a) to the respective Li, L2, L3, L4, Ls, Lg, L7 and Ls, if it is present, via a carbon atom, an oxygen atom, a nitrogen atom or a sulfur atom, or b) if the respective Li, L2, L3, L4, Ls, Le, L7 and Ls, is absent, via a carbon atom, an oxygen atom, a nitrogen atom or a sulfur atom to the carbon atom of ring to which the C1-C30 moiety is attached.

[0161] Physiologically hydrolysable protective group R1

[0162] In some embodiments, it is most advantageous that R1represents hydrogen.

[0163] In some alternative embodiments, R1may also represent the protective group hydrolysable under physiological conditions. The choice of said protective group is not particularly limited. Of note, glucoside moieties such as pyranosyl were found to not be suitable as protective groups since the glucosidic bond between the glucoside moiety and the 3,4-saturated 2H-pyran moiety (which is part of two acetals) is not readily hydrolyzed. However, suitable leaving groups can be readily determined by following one or more of the following principles: 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. 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. c) Protective groups which themselves can be hydrolysed or decompose under conversion of the ether bond to the 3,4-saturated 2H-pyran moiety can also be utilized. Examples include silylgroups.

[0164] In some embodiments, R1represents C1-6 acyl, in particular C1-3 acyl or trifluoracetyl; C1-6 alkyl, in particular methyl or ethyl; or a silylgroup, in particular trimethoxysilyl triethoxysilyl, and / -butyldi methylsil l.

[0165] Further specific compounds

[0166] In some embodiments, the compound of formula (IV) is a compound of formula (VI), or a tautomer and / or a salt thereof; wherein R1, Ai, A2, A3, A4, Ae, A7, L2, L3, L4, Le and L7 are defined as in any preceding embodiment; wherein X represents O or S, and in particular O; and wherein Lxis absent or represents -O-, -NH-, or an optionally substituted hydrocarbon moiety comprising, in combination with its optional substituents, 1 to 12 carbon atoms, more specifically 1 to 10 carbon atoms, and in particular 1 to 8 carbon atoms, 0 to 8, more specifically 0 to 6, and in particular 0 to 4 oxygen atoms; 0 to 6, more specifically 0 to 4, and in particular 0 to 3 nitrogen atoms; 0 to 6, more specifically 0 to 4, and in particular 0 to 3 sulfur atoms; and 0 to 8, more specifically 0 to 6, and in particular 0 to 5 halogen atoms, and wherein the hydrocarbon moiety is attached to the (C=X)-moiety via a carbon atom, an oxygen atom, a nitrogen atom, or a sulfide atom. Compounds of formula (VI) 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 as previously mentioned and allows to delocalize charge in the cascade of reactions towards the 1,4-dihydropyridine derivative, both of which is beneficial in suppressing the formation of oligomers and polymers as previously mentioned.

[0167] In some embodiments, Ai represents the C1-C30 moiety, more specifically a C1-C16 moiety selected from a saturated or unsaturated, cyclic or acylic (hetero)alkyl comprising 1 to 16, more specifically 1 to 12, and in particular 1 to 8, carbon atoms; 0 to 6, more specifically 0 to 4, and in particular 0 to 3 oxygen atoms; 0 to 6, more specifically 0 to 4, and in particular 0 to 3 nitrogen atoms; 0 to 6, more specifically 0 to 4, and in particular 0 to 3 sulfur atoms; and 0 to 6, more specifically 0 to 4, and in particular 0 to 3 halogen atoms.

[0168] In some embodiments, Lx-Ai represents a C1-C16 moiety selected from a carboxylic acid or a salt thereof, a carboxylic acid ester; a ketone; more specifically a moiety selected from: -COOH or a salt thereof; -COORa, -C(O)-Ra, -C(O)-NH2, -C(O)NHRa, -C(O)NRa2, wherein Ra represents a moiety comprising 1 to 10 carbon atoms, and optionally one or more of: 1 to 6 oxygen atoms, 1 to 4 nitrogen atoms, 1 to 3 sulfur atoms, and 1 to 5 halogen atoms, more specifically a moiety comprising 1 to 6 carbon atoms, and optionally one or more of: 1 to 4 oxygen atoms, 1 to 3 nitrogen atoms, 1 or 2 sulfur atoms, and 1 to 3 halogen atoms, and in particular Ci-Ce-alkyl or phenyl; and wherein NRa2 may alternatively represent an optionally substituted saturated or unsaturated nitrogen heterocycle comprising, in combination with its optional substituents, 1 to 12, more specifically 1 to 10, and in particular 1 to 8, carbon atoms; 0 to 6, more specifically 0 to 4, and in particular 0 to 3 oxygen atoms; 1 to 4, more specifically 1 to 3, and in particular 1 or 2 nitrogen atoms; 0 to 3, more specifically 0 to 2, and in particular 0 or 1 sulfur atoms; and 0 to 5, more specifically 0 to 4, and in particular 0 to 3 halogen atoms. Compounds of this embodiment may be particularly beneficial since they mimic genipin, oleuropein and elenolic acid which are generally regarded as safe.

[0169] No or low color compounds

[0170] The compounds of the present disclosure do not necessarily have to be colorless when bound to skin or hair. For instance, if the compounds are used to bind active ingredients to farm animals, color does not play a prominent role. However, in particular in uses for humans, it may be beneficial that the compounds of formula (la) or (lb), 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.

[0171] Accordingly, in some embodiments, the compound of formula (la) or (lb), 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.

[0172] Suitable test conditions include a visual inspection, optionally by a test panel of 5 of more panelists, in a dark room under artificial light conditions of 3000 Kelvin and an intensity of 1000 Lux. The test sample may be prepared by applying a methanolic solution of the compound of formula (la) or (lb) onto explanted porcine skin at a concentration of 1 pmol / in2(=0.156 pmol / cm2), followed by incubation at 25°C and at 50% relative humidity for 24 hours. At the concentration of 1 pmol / in2. hydrogenated genipin and oleuropein aglycone bind to skin without being visually perceivable whereas skin-bound genipin is still perceivable at about 0.07 pmol / in2. For compounds of formula (la) or (lb) 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 formula (IV) comprising oligomeric or polymeric active ingredients or precursors, the test sample may also be prepared by applying the equivalent of 3 mg of the compound of formula (IV) 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.

[0173] Alternatively or additionally, a comparative test can be performed: The compound of formula (la) or (lb) can be considered to have bound to the skin and / or the hair as not observable to the human eye, if the compound of formula (la) or (lb) is not observable at such a high concentration that oleuropein aglycone is starting to be observable. Suitable test conditions again include a visual inspection, optionally by a test panel of 5 of more panelists, in a dark room under artificial light conditions of 3000 Kelvin and an intensity of 1000 Lux. The test samples may be prepared by applying a methanolic solution of the compounds onto samples of explanted porcine skin at a series of diluted concentrations, optionally including concentrations of 5 and 10 pmol / in2(=0.780 pmol / cm2and 1.56 pmol / cm2), followed by incubation of each sample at 25°C and at 50% relative humidity for 24 hours.

[0174] In some embodiments, the compound of formula (la) or (lb), 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.

[0175] In some embodiments, the compound of formula (la) or (lb), 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. In some embodiments, L2-A2, L3-A3 and L4-A4 do not represent moieties (or form a moiety) comprising an unsaturated C-C or C-N bond in alpha-position to the respective carbon atom(s) of the 3,4-saturated 2H-pyran moiety to which they are bound.

[0176] The present inventors have also found that a large variety of 3,4-saturated 2H-pyran derivatives will unobtrusively bind to skin or hair as long as the 3,4-saturated 2H-pyran derivatives are selected such that the formation of larger conjugated 7i-electron systems involving the skinbound 1,4-dihydropyridine moiety is avoided.

[0177] Accordingly, in some embodiments, L1-A1 and Lg-Ag do not represent moieties (or form a moiety) comprising an unsaturated C-C or C-N bond in alpha-position to the respective carbon atom(s) of the 3,4-saturated 2H-pyran moiety to which they are bound.

[0178] In some embodiments, L4-A4 and L7-A7 do not represent moieties (or form a moiety) comprising an unsaturated C-C or C-N bond in alpha-position to the respective carbon atom(s) of the 3,4-saturated 2H-pyran moiety to which they are bound.

[0179] In some embodiments, L1-A1 and L2-A2 do not represent moieties (or form a moiety) comprising an unsaturated C-C or C-N bond in alpha-position to the respective carbon atom(s) of the 3,4-saturated 2H-pyran moiety to which they are bound.

[0180] In some embodiments, the 3,4-saturated 2H-pyran moiety of the compound of formula (V) covalently binds to the skin and / or the hair forming a compound of formulae (Vc) and / or (Vd), or a tautomer and / or a salt thereof; wherein the broken bond represents the covalent bond to the skin and / or the hair; and wherein Ai, A2, A3, A4, As, A7, Li, L2, L3, L4, Lg and L7 are defined as indicated in any of the preceding embodiments. Moreover, it may be particularly advantageous that, after the 3,4-saturated 2H-pyran moiety has covalently bound to the skin and / or hair forming a compound of formulae (Vc) and / or (Vd), no more than one, and in particular none, of L1-A1, L2-A2, L3-A3, L4-A4, Lg-Ag and L7-A7 of the compound of formula (V) forms a conjugated 71-electron system comprising more than 6 double bonds, more specifically more than 5 double bonds, and in particular more than 4 double bonds, with the heterocycle marked by letters a to e in the formula (V) and more than 7 double bonds, more specifically more than 6 double bonds, and in particular more than 5 double bonds, with the heterocycle marked by letters a to e in the formula (Vc).

[0181] In some embodiments, the combination of all of L1-A1, L2-A2, L3-A3, L4-A4, Lg-Ag and L7-A7 of the compound of formula (V), after the 3,4-saturated 2H-pyran moiety has covalently bound to the skin and / or the hair forming a compound of formula (Vc) and / or (Vd) does not form a conjugated 71-electron system with the heterocycles marked by letters a to e in the formulae (Vc) and (Vd). In some embodiments, the combination of all of L1-A1, L2-A2, L3-A3, L4-A4, Lg- Ag and L7-A7 of the compound of formula (V), after the 3,4-saturated 2H-pyran moiety has covalently bound to the skin and / or hair forming a compound of formula (Vc) and / or (Vd) forms a conjugated 71-electron system with the heterocycle marked by letters a to e in the formula (la) which comprises less than 7 double bonds, more specifically less than 6 double bonds, and in particular less than 5 double bonds, and forms a conjugated 71-electron system with the heterocycle marked by letters a to e in the formula (Vd) which comprises less than 8 double bonds, more specifically less than 7 double bonds, and in particular less than 6 double bonds.

[0182] It may also be particularly advantageous that no more than three, more specifically no more than two, and in particular no more than one, of L1-A1, L2-A2, L4-A4, Lg-Ag and L7-A7 of the compound of formula (V) comprise a carbonyl group which forms or is part of a conjugated 71- electron system with the heterocycles marked by letters a to e in the formulae (Vc) and (Vd).

[0183] It may also be particularly advantageous that L1-A1, L2-A2, L4-A4, Lg-Ag and L7-A7 of the compound of formula (V) are selected such that - after the compound has bound to skin or hair - they do not provide a combination of electron-withdrawing and electron-donating groups to the conjugated 71-electron system formed with the respective heterocycles marked by letters a to e in the formulae (Vc) and (Vd).

[0184] Further specific compounds

[0185] In some embodiments, the compound of formula (IV) is a compound of formula (VII), or a tautomer and / or a pharmaceutically acceptable salt thereof; wherein R1, Ai, A2, A3, A4, Li, L2, L3 and L4 are defined as indicated in any of the preceding embodiments; wherein R2represents hydrogen or a C1-C16 moiety; more specifically hydrogen or a C1-C16 moiety comprising 1 to 16, and in particular 1 to 12, carbon atoms; 0 to 12, more specifically 0 to 8, and in particular 0 to 6 oxygen atoms; 0 to 8, more specifically 0 to 6, and in particular 0 to 4 nitrogen atoms; 0 to 6, more specifically 0 to 4, and in particular 0 to 3 sulfur atoms; and 0 to 10, more specifically 0 to 8, and in particular 0 to 6 halogen atoms; and in particular hydrogen or a saturated or unsaturated, cyclic or acylic (hetero)alkyl or a (hetero)aryl moiety comprising 1 to 10 carbon atoms, and optionally one or more of: 1 to 6 oxygen atoms, 1 to 4 nitrogen atoms, 1 to 3 sulfur atoms, and 1 to 5 halogen atoms; and wherein R3represents hydrogen or a C1-C16 moiety; more specifically hydrogen or a C1-C16 moiety comprising 1 to 16, and in particular 1 to 12, carbon atoms; 0 to 12, more specifically 0 to 8, and in particular 0 to 6 oxygen atoms; 0 to 8, more specifically 0 to 6, and in particular 0 to 4 nitrogen atoms; 0 to 6, more specifically 0 to 4, and in particular 0 to 3 sulfur atoms; and 0 to 10, more specifically 0 to 8, and in particular 0 to 6 halogen atoms; and in particular hydrogen or a saturated or unsaturated, cyclic or acylic (hetero)alkyl or a (hetero)aryl moiety comprising 1 to 10 carbon atoms, and optionally one or more of: 1 to 6 oxygen atoms, 1 to 4 nitrogen atoms, 1 to 3 sulfur atoms, and 1 to 5 halogen atoms. In some embodiments, in the above formula (VII), it may be advantageous that R2represents Ci-Ce alkyl or C6-C12 aryl, both of which may be optionally further substituted with the proviso that the entirety of R2does not comprise more than 16 carbon atoms, 6 oxygen atoms, 4 nitrogen atoms, 3 sulfur atoms, and 5 halogen atoms; and R3represents hydrogen or Ci-Ce alkyl or Ce- C12 aryl, both of which may be optionally further substituted with the proviso that the entirety of R3does not comprise more than 16 carbon atoms, 6 oxygen atoms, 4 nitrogen atoms, 3 sulfur atoms, and 5 halogen atoms.

[0186] In some embodiments, R2represents a Ci-Ce alkyl which may be optionally further substituted with the proviso that the entirety of R2does not comprise more than 12 carbon atoms, 4 oxygen atoms, 3 nitrogen atoms, 2 sulfur atoms, and 3 halogen atoms; and R3represents hydrogen or C1-C4 alkyl.

[0187] In some embodiments, R2represents an aliphatic C1-C4 moiety, optionally comprising a carboxylic acid or a salt thereof, a carboxylic acid ester, a ketone, an alcohol, an ether, or combinations thereof; and wherein R3represents hydrogen.

[0188] In some embodiments, the compound of formula (IV) is a compound of formula (VIII), or a tautomer and / or a pharmaceutically acceptable salt thereof; wherein R1, R2, R3, A2, A3, A4, L2, L3 and L4 are defined as indicated in any of the preceding embodiments; and wherein R4represents hydrogen or a C1-C16 moiety selected from a carboxylic acid or a salt thereof, a carboxylic acid ester; a ketone or an amide; more specifically a moiety selected from: -COOH or a salt thereof; -COORa, -C(O)-Ra, -C(0)-NH2, -C(O)NHRa, and -C(0)NRa2; wherein each instance of Ra represents a moiety comprising 1 to 10 carbon atoms, and optionally one or more of: 1 to 6 oxygen atoms, 1 to 4 nitrogen atoms, 1 to 3 sulfur atoms, and 1 to 5 halogen atoms, more specifically a moiety comprising 1 to 6 carbon atoms, and optionally one or more of: 1 to 4 oxygen atoms, 1 to 3 nitrogen atoms, 1 or 2 sulfur atoms, and 1 to 3 halogen atoms, and in particular Ci-Ce-alkyl or phenyl; and wherein NRa2 may alternatively represent an optionally substituted saturated or unsaturated nitrogen heterocycle comprising, in combination with its optional substituents, 1 to 12, more specifically 1 to 10, and in particular 1 to 8, carbon atoms; 0 to 6, more specifically 0 to 4, and in particular 0 to 3 oxygen atoms; 1 to 4, more specifically 1 to 3, and in particular 1 or 2 nitrogen atoms; 0 to 3, more specifically 0 to 2, and in particular 0 or 1 sulfur atoms; and 0 to 5, more specifically 0 to 4, and in particular 0 to 3 halogen atoms.

[0189] In some embodiments, in the above formula (VIII), it may be advantageous that R4represents -COOH or a salt thereof, -COORb, -C(O)-Rb, C(O)-NH2, -C(O)NHRb, -C(O)NRb2, wherein Rbrepresents a moiety comprising 1 to 6 carbon atoms, and optionally one or more of: 1 to 3 oxygen atoms, 1 or 2 nitrogen atoms, 1 or 2 sulfur atoms, and 1 to 3 halogen atoms, more specifically a moiety comprising 1 to 4 carbon atoms, and optionally one or more of: 1 to 3 oxygen atoms, 1 or 2 nitrogen atoms, and 1 to 3 halogen atoms. It may be particular advantageous that Rbrepresents -Ci-C4-alkyl, more specifically methyl or ethyl and in particular methyl.

[0190] In some embodiments, the compound of formula (IV) is a compound of formula (IXa) or (IXb), or a tautomer and / or a pharmaceutically acceptable salt thereof; wherein R1, R2, R3, and R4are defined as indicated in any of the preceding embodiments; wherein each of R5, independently from each other, represents hydrogen or a Ci-Ce moiety which optionally further comprises 1- 3 oxygen atoms, 1-3 nitrogen atoms, and 1-2 sulfur atoms; wherein for formula (IXa) Ls is defined as L2 and in any of the preceding embodiments and As represents the moiety of formula (IVa) or the moiety of formula (IVb); and wherein for formula (IXb) Ls is defined as L4 in any of the preceding embodiments and As represents the moiety of formula (IVa) or the moiety of formula (IVb).

[0191] In some embodiments, in formulae (IXa) or (IXb), it may be advantageous that Ls represents a saturated Ci-Ce-alkyl moiety which is optionally substituted with a group selected from: -O-, - C(O)-, -CO2-, -O-C(O)-, -NH-, -N(Ci-C4-alkyl)-, -NH-C(O)-, -C(O)-NH-, -(CH2)I-4-, -(CH2)I-4-O-, -O-(CH2)I-4-, -S(O)-, -SO2-, or combinations thereof. It may be particularly advantageous that each of R5, independently from each other, represents hydrogen or a C1-C4 alkyl.

[0192] In some embodiments, the compound of formula (IV) is a compound of formula (Xa) or (Xb), or a tautomer and / or a pharmaceutically acceptable salt thereof; wherein R1, R2, R3, R4, and R5are defined as indicated in any of the preceding embodiments; wherein the dashed line represents a bond or is absent; wherein n is an integer between 0 and 6, more specifically between 0 and 4, and in particular between 0 and 3; and m is an integer between 0 and 8, more specifically between 0 and 4, and in particular between 0 and 3; wherein Ls is defined as L4in any of the preceding embodiments, and wherein As represents the moiety of formula (IVa) or the moiety of formula (IVb).

[0193] In some embodiments, in formulae (Xa) or (Xb), it may be advantageous that R2represents H or Ci-C4alkyl, R3represents H or C1-C4 alkyl, R4represents -COOH or a salt thereof, -COORa, -C(O)-Ra, C(O)-NH2, -C(O)NHRa, -C(O)NRa2, wherein Ra and NRa2are defined as in any preceding embodiment.

[0194] In the following, the active components linked to the remainder of the compounds according to the present disclosure will be discussed. For reasons of simplicity of language, in some instances, reference to the active ingredient will be made as if the active ingredient is an individual compound instead of a moiety attached to the remainder of the compound of formula (I). It should be understood that this is to be interpretated as a reference to a moiety that is attached to the remainder of the compound of formula (IV), by e.g. elimination of a hydrogen atom from the active ingredient.

[0195] It should further be understood that the below mentioned disclosure regarding the active components is freely combinable with the above disclosure relating to the compounds according to formulae (Ia) / (Ib) to (Xb). Indeed, these combinations represent preferred embodiments of the present disclosure, although it should also be understood that the present disclosure is not limited thereto.

[0196] Humectants, Emollients., Occlusives

[0197] In some embodiments, at least one of Ai, A2, A3, A4, As, As and A7 represents the active ingredient or the precursor of the active ingredient, and the active ingredient is the moisturizer, the skin moisturizer or the hair moisturizer, respectively. In some embodiments, the active ingredient comprises a plurality of hydrogen bonding groups selected from the group consisting of hydroxyl groups, ether groups, carboxylic acids, amines and amides; and their salts. In some embodiments, the plurality of hydrogen bonding groups comprises three or more, more specifically 4 or more, and in particular 6 or more hydrogen bonding groups. In some embodiments, the ratio of C-atoms to the sum of hydrogen bonding groups comprised in the active ingredient is between about 4:1 to 1: 1, more specifically between about 3: 1 to about 1:1 and in particular between about 2:1 to about 1:1. In some embodiments, the active ingredient has a molecular weight of at least 60 g / mol, more specifically at least 90 g / mol, and in particular at least 120 g / mol. In some embodiments, the active ingredient has a molecular weight of 60 g / mol to 2000 g / mol, more specifically 90 g / mol to 1600 g / mol, and in particular 120 g / mol to 1200 g / mol. In some embodiments, the ratio of C-atoms to the sum of heteroatoms comprised in the active ingredient is between about 4: 1 to 1:2, more specifically between about 3:1 to about 1:1.5, and in particular between about 2:1 to about 1:1, wherein the heteroatoms are selected from nitrogen and oxygen. In some embodiments, the active ingredient comprises: a polyol, more specifically a polyol having n hydroxyl groups with n being 2 or more, 3 or more, 4 or more, 5 or more, 6 or more, 8 or more, 10 or more, 12 or more, or 16 or more; a mono- or polyvalent carboxylic acid comprising one or more hydroxyl groups, more specifically glycolic acid, lactic acid, malic acid, tartaric acid or citric acid; a sugar, more specifically a triose, a tetrose, a pentose a hexose, a monosaccharide, a disaccharide, a trisaccharide, or an oligosaccharide; a sugar alcohol, more specifically a sugar alcohol comprising between 2 and 24 carbon atoms, in particular ethylene glycol, glycerol, erythritol, threitol, arabitol, xylitol, ribitol, mannitol, sorbitol, galactitol, fucitol, iditol, inositol, volemitol, isomalt, maltitol, lactitol, maltotriitol, or maltotetraitol; a sugar acid, more specifically an aldonic acid, an ulosonic acid, an uronic acid or an aldaric acid; or a salt thereof; or an ester thereof, in particular a Ci-C4-alkylester thereof; or an amide thereof; or

[0198] - a polysaccharide; more specifically a glycosaminoglycan, such as chondroitin sulfate, dermatan sulfate, keratan sulfate, and hyaluronic acid; and in particular hyaluronic acid; and copolymers thereof, in particular copolymers comprising polyethylene glycol; and, in particular, hyaluronic acid, more specifically a hyaluronic acid having a weight-average or a number-average, and in particular a number-average, molecular weight of between 3000 and 3 million kDa, more specifically between 5000 and 2 million kDa, and in particular between 10,000 and 1.5 million kDa

[0199] In some embodiments, the active ingredient is an emollient or an occlusive.

[0200] In some embodiments, the active ingredient comprises: a Cio-Ceo moiety, more specifically a C15-C60 moiety and in particular a C20-C60 moiety; or an oligo- or polysiloxane, in particular a poly(di-Ci-C4-alkyl)siloxane. In some embodiments, the active ingredient is the Ci-Ceo moiety and has a molecular weight of 140 g / mol to 2000 g / mol, more specifically 160 g / mol to 1600 g / mol, and in particular 180 g / mol to 1200 g / mol. In some embodiments, the active ingredient has more than 30 carbon atoms. In some embodiments, the active ingredient comprises a saturated or unsaturated Cio-Ceo aliphatic moiety, more specifically a Cis-Ceo aliphatic moiety, and in particular a C20-C60 aliphatic moiety. In some embodiments, the ratio of C-atoms to the sum of heteroatoms comprised in the active ingredient is between about 60:1 to 5:1, more specifically between about 50:1 to about 10:1, and in particular between about 40:1 to about 20: 1, wherein the heteroatoms are selected from nitrogen and oxygen. In some embodiments, the Ci-Ceo moiety is a sphingosine or a derivative thereof, in particular a ceramide or a sphingomyelin.

[0201] In some embodiments, at least one of Ai, A2, A3, A4, As, As and A7 represents the moisturizer, the skin moisturizer or the hair moisturizer, respectively.

[0202] In some embodiments, at least one of Ai, A2, A3, A4, As, As and A7 represents the precursor of the moisturizer, the skin moisturizer or the hair moisturizer, respectively.

[0203] Pesticides

[0204] In some embodiments, at least one of Ai, A2, A3, A4, As, As and A7 represents the active ingredient or the precursor of the active ingredient, and the active ingredient is the pesticide.

[0205] In some embodiments, the pesticide may be an insect repellent. 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 repellent is applied) less attractive to the insect.

[0206] 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.

[0207] In some embodiments, the insect repellent 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.

[0208] In some embodiments, the pesticide may be an insect repellent which may be selected from isoprenoids, tertiary amides, and phenylpropanoids.

[0209] In some embodiments, the insect repellent may be an isoprenoid, more specifically a monoterpenoid, a diterpenoid or a triterpenoid, and in particular a terpineol or derivative thereof, a monoterpenoid aldehyde or a derivative thereof, a limonoid or a derivative thereof; or a pyrethrin or a derivative thereof. In some embodiments, the isoprenoid may be selected from citronellal, hydroxy citronellal, citronellol, citral A, citral B, or a derivative thereof; a necrodane, in particular a-necrodol, or a derivative thereof; a limonoid, in particular azadirachtine, or a derivative thereof; or a pyrethrin, in particular a jasmolin, a cinerin, or a derivative thereof.

[0210] In some embodiments, the insect repellent may comprise a tertiary amide. In some embodiments, the tertiary amide may be selected from picaridine, an N,N-di(Ci-Cs-alkyl)- toluamide, ethyl 3-(V-butylacetamido)propanoate; and derivatives thereof.

[0211] In some embodiments, the insect repellent may be selected from one of the following compounds and moieties / derivatives thereof: diethyl phenyl acetamide, N-butylacetanilide, picaridine, N-(2-methylpiperidin-l-yl)cyclohex-3-ene-l-carboxamide, and l-[3-cyclo-hexen-l- ylcarbonyl]-2-methylpiperidine or l-[3-cyclohexen-l-ylcarbonyl] piperidine.

[0212] In some embodiments, the insect repellent may be a phenylpropanoid, in particular eugenol or a derivative thereof.

[0213] In some embodiments, at least one of Ai, A2, A3, A4, As, As and A7 represents a moiety of formula (Villa) or formula (Vlllb),

[0214] (Villa) (Vlllb).

[0215] In some embodiments, the insect repellent comprises a tertiary amide. It may be particularly advantages that the tertiary amide is selected from picaridine, an N,N-di(Ci-Cs-alkyl)- toluamide, in particular N,N-diethyl-meta-toluamide, p-menthane-3,8-diol, ethyl 3-(N- butylacetamido)propanoate; and derivatives thereof. In some embodiments, the insect repellent is selected from one of the following compounds and moieties / derivatives thereof: N,N-diethyl-meta-toluamide, diethyl phenyl acetamide, N- butylacetanilide, ethyl butylacetylaminopropionate, picaridine, N-(2-methylpiperidin-l- yl)cyclohex-3-ene-l -carboxamide, and l-[3-cyclo-hexen-l-ylcarbonyl]-2-methylpiperidine or l-[3-cyclohexen-l-ylcarbonyl] piperidine.

[0216] In some embodiments, at least one of Ai, A2, A3, A4, As, As and A7 represents a moiety of formula (IX),

[0217] In some embodiments, at least one of Ai, A2, As, A4, As, As and A7 represents a moiety of formula (X),

[0218] In some embodiments, the pesticide is a topical insecticide, in particular a topical insecticide which is selected from permethrine; cypermethrin; deltamethrin; ivermectin; amidines, in particular amitraz; bendiocarb; malathion; carbaryl; diazinon; DDT; fenthion; fipronil; imidacloprid; nitenpyram; and propoxur.

[0219] In some embodiments, at least one of Ai, A2, A3, A4, As, As and A7 represents the pesticide, in particular the insect repellent. In some embodiments, at least one of Ai, A2, A3, A4, As, As and A7 represents the precursor of the pesticide, in particular the insect repellent.

[0220] UVA and / or UVB-absorbing moieties and a color-imparting moieties

[0221] In some embodiments, at least one of Ai, A2, A3, A4, As, Ar, and A7 represents one of the one or more active ingredients, and the active ingredient is the color-imparting moiety or the UVA and / or UVB-absorbing moiety.

[0222] 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.

[0223] 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.

[0224] In some embodiments, at least one of Ai, A2, A3, A4, As, As and A7 represents the colorimparting moiety, and said moiety is: a) an optionally substituted (hetero)aromatic moiety comprising, in combination with its optional substituents, 4 to 40 carbon atoms; or b) an optionally substituted conjugated moiety comprising, in combination with its optional substituents, 6 to 40 carbon atoms and at least 3 conjugated C-C double bonds.

[0225] In some embodiments, at least one of Ai, A2, A3, A4, As, As and A7 represents a UVA and / or UVB absorbing moiety, wherein said moiety is: a) an optionally substituted (hetero)aromatic moiety comprising, in combination with its optional substituents, 4 to 36 carbon atoms; or b) an optionally substituted conjugated moiety comprising, in combination with its optional substituents, 4 to 36 carbon atoms, and at least 2 conjugated C-C double bonds.

[0226] In some embodiments, at least one of Ai, A2, A3, A4, As, As and A7 represents a chromophore (dye moiety) selected from an azo group; a diazo group; a diphenylamine group; a nitroarylamine group; an azine group; an oxazine group; an acridine group; an indoline group; a sulfur dye group, in particular a thiazine group, a thiazole group, a thiazone group, a thianthrene group, or a phenothiazonethioanthrone group; a quinoid or quinone group; an anthraquinoid or anthraquinone group; a xanthene group; a naphthostyryl group; a diaryl methyl or triarylmethyl group; a benzodifuranone-based group; a formazan group; a phthalocyanine group; or a metal complex.

[0227] In some embodiments, at least one of Ai, A2, A3, A4, As, As and A7 represents a UVA- and / or UVB-absorbing moiety as one of the active ingredients or of the precursors thereof which is selected / derived from: a benzophenone group, a benzotriazole group, a benzone group, salicylic acid or a salicylic acid derivative, a benzocaine group, an esculin or an esculin derivative, a ferulic acid or a ferulic acid derivative, octinoxate or an octinoxate derivative, or octocrylene or an octocrylene derivative.

[0228] In some embodiments, at least one of Ai, A2, A3, A4, As, As and A7 represents a moiety which is selected from the following group of moieties:

[0229]

[0230] In some embodiments, the compound of formula (I) is a compound of formula (XIV),

[0231] (XIV), or a tautomer and / or a pharmaceutically acceptable salt thereof, wherein R1, Ai, A3, A4, Ae, A7, Lg and L7 are defined as in any preceding embodiment. X represents O or S, and in particular O.

[0232] Lxis absent or represents -O-, -NH-, or an optionally substituted hydrocarbon moiety comprising, in combination with its optional substituents, 1 to 12 carbon atoms, more specifically 1 to 10 carbon atoms, and in particular 1 to 8 carbon atoms, 0 to 8, more specifically 0 to 6, and in particular 0 to 4 oxygen atoms; 0 to 6, more specifically 0 to 4, and in particular 0 to 3 nitrogen atoms; 0 to 6, more specifically 0 to 4, and in particular 0 to 3 sulfur atoms; and 0 to 8, more specifically 0 to 6, and in particular 0 to 5 halogen atoms. Said hydrocarbon moiety is attached to the (C=X)-moiety via a carbon atom, an oxygen atom, a nitrogen atom, or a sulfide atom.

[0233] One moiety selected from L3, and L4 represents an optionally substituted (hetero)aromatic C3- C12 moiety, more specifically an optionally substituted (hetero)aromatic C4-C12 moiety comprising, in combination with its optional substituents, 4 to 16, more specifically 4 to 12, and in particular 4 to 10, carbon atoms; 0 to 6, more specifically 0 to 4, and in particular 0 to 3 oxygen atoms; 0 to 6, more specifically 0 to 4, and in particular 0 to 3 nitrogen atoms; 0 to 6, more specifically 0 to 4, and in particular 0 to 3 sulfur atoms; and 0 to 6, more specifically 0 to 4, and in particular 0 to 3 halogen atoms.

[0234] The other moiety amongst L3 and L4 represents a C1-C30 moiety, more specifically a C1-C16 moiety selected from a saturated or unsaturated, acylic (hetero)alkyl comprising 1 to 16, more specifically 1 to 12, and in particular 1 to 8, carbon atoms; 0 to 6, more specifically 0 to 4, and in particular 0 to 3 oxygen atoms; 0 to 6, more specifically 0 to 4, and in particular 0 to 3 nitrogen atoms; 0 to 6, more specifically 0 to 4, and in particular 0 to 3 sulfur atoms; and 0 to 6, more specifically 0 to 4, and in particular 0 to 3 halogen atoms.

[0235] Compounds of formula (XIV) may be particularly advantageous since they are conveniently accessible by total synthesis, i.e.not relying on complex naturally occurring compounds. Moreover, the (thio-)carbonyl group may facilitate the ring-opening to the reactive 1,5- dicarbonyl tautomer. Moreover, the C-5 position is blocked in these compounds and a delocalization of charge in the cascade of reactions towards the 1,4-dihydropyridine derivative is realized, both of which is beneficial in suppressing the formation of potentially cytotoxic oligomers and polymers as side products.

[0236] In some embodiments, L3 represents the optionally substituted (hetero)aromatic C3-C12 moiety, more specifically an optionally substituted (hetero)aromatic C4-C12 moiety comprising, in combination with its optional substituents, 4 to 16, more specifically 4 to 12, and in particular 4 to 10, carbon atoms; 0 to 6, more specifically 0 to 4, and in particular 0 to 3 oxygen atoms; 0 to 6, more specifically 0 to 4, and in particular 0 to 3 nitrogen atoms; 0 to 6, more specifically 0 to 4, and in particular 0 to 3 sulfur atoms; and 0 to 6, more specifically 0 to 4, and in particular 0 to 3 halogen atoms.

[0237] In some embodiments, L3 represents an optionally substituted phenyl moiety comprising, in combination with its optional substituents, 6 to 12, more specifically 6 to 10, and in particular 6 to 8, carbon atoms; 0 to 6, more specifically 0 to 4, and in particular 0 to 3 oxygen atoms; 0 to 6, more specifically 0 to 4, and in particular 0 to 3 nitrogen atoms; 0 to 3, more specifically 0 to 2, and in particular 0 or 1 sulfur atoms; and 0 to 6, more specifically 0 to 4, and in particular 0 to 3 halogen atoms. In some embodiments, the phenyl moiety is optionally substituted with - OH; -O-Ci-C4-alkyl; -N(Ci-C4-alkyl)2; one or more halogen atoms, each independently from each other selected from Cl, Br, and F; -NO2; and -CF3.

[0238] In some embodiments, L4 represents an optionally substituted aliphatic moiety comprising, in combination with its optional substituents, 1 to 12, more specifically 1 to 10, and in particular 1 to 8, carbon atoms; 0 to 6, more specifically 0 to 4, and in particular 0 to 3 oxygen atoms; 0 to 6, more specifically 0 to 4, and in particular 0 to 3 nitrogen atoms; 0 to 3, more specifically 0 to 2, and in particular 0 or 1 sulfur atoms; and 0 to 6, more specifically 0 to 4, and in particular 0 to 3 halogen atoms. In some embodiments, the aliphatic moiety is a Ci-Ce-alkyl, more specifically a linear or branched Ci-C4-alkyl; and in particular a linear Ci-C4-alkyl.

[0239] In some embodiments, Ai represents the C1-C30 moiety, more specifically a C1-C16 moiety selected from a saturated or unsaturated, cyclic or acylic (hetero)alkyl comprising 1 to 16, more specifically 1 to 12, and in particular 1 to 8, carbon atoms; 0 to 6, more specifically 0 to 4, and in particular 0 to 3 oxygen atoms; 0 to 6, more specifically 0 to 4, and in particular 0 to 3 nitrogen atoms; 0 to 6, more specifically 0 to 4, and in particular 0 to 3 sulfur atoms; and 0 to 6, more specifically 0 to 4, and in particular 0 to 3 halogen atoms.

[0240] In some embodiments, Lx-Ai represents a C1-C16 moiety selected from a carboxylic acid or a salt thereof, a carboxylic acid ester; a ketone; more specifically a moiety selected from: -COOH or a salt thereof; -COORa, -C(O)-Ra, -C(O)-NH2, -C(O)NHRa, -C(O)NRa2, wherein Ra represents a moiety comprising 1 to 10 carbon atoms, and optionally one or more of: 1 to 6 oxygen atoms, 1 to 4 nitrogen atoms, 1 to 3 sulfur atoms, and 1 to 5 halogen atoms, more specifically a moiety comprising 1 to 6 carbon atoms, and optionally one or more of: 1 to 4 oxygen atoms, 1 to 3 nitrogen atoms, 1 or 2 sulfur atoms, and 1 to 3 halogen atoms, and in particular Ci-Ce-alkyl or phenyl; and wherein NRa2 may alternatively represent an optionally substituted saturated or unsaturated nitrogen heterocycle comprising, in combination with its optional substituents, 1 to 12, more specifically 1 to 10, and in particular 1 to 8, carbon atoms; 0 to 6, more specifically 0 to 4, and in particular 0 to 3 oxygen atoms; 1 to 4, more specifically 1 to 3, and in particular 1 or 2 nitrogen atoms; 0 to 3, more specifically 0 to 2, and in particular 0 or 1 sulfur atoms; and 0 to 5, more specifically 0 to 4, and in particular 0 to 3 halogen atoms.

[0241] In some embodiments, the compound of formula (IV) does not include an active ingredient that is a color-imparting moiety; or a color-imparting moiety having at least one absorption peak within the wavelength range of 380 to 790 nm; or a color-imparting moiety having at least one absorption peak within the wavelength range of 380 to 790 nm having an absorbance value of more than 0.5 when measured at a concentration of 2 mM.

[0242] In some embodiments, the compound of formula (IV) does not include an active ingredient that is a UV-absorbing moiety; or UVA- and / or UVB-absorbing moiety; or a UVA- and / or UVB- absorbing moiety having at least one absorption peak within the wavelength range of 280 to 379 nm; or a UVA- and / or UVB-absorbing moiety having at least one absorption peak within the wavelength range of 280 to 379 nm having an absorbance value of more than 0.5 when measured at a concentration of 2 mM.

[0243] In some embodiments, it may be advantageous that, in formula (I), -L-DC does not represent a polymeric moiety, more specifically not a polymeric moiety having a molecular weight of 500 g / mol or more than 500 g / mol. Such compounds have a large molecular size and, thus, a reduced tendency to migrate into the skin. In other words, these compounds stay bind to the surface layers of the skin and are lost earlier due to natural desquamation.

[0244] In some embodiments, it may be advantageous that, in formula (I), -L-DC does not comprise (an) isocyanate group(s), i.e. does not comprise one or more than one isocyanate groups. These groups, although capable of linking to skin, are well-known to be cytotoxic and skin-irritating.

[0245] It should also be understood that the active ingredients and precursors thereof recited above for the compounds of formulae (IV)-(Xb) may also be moieties of the compounds of formula (la) or (lb). More specifically, the compound of formula (la) or (lb) may further comprise one or more of the active ingredients and precursors thereof, wherein the respective linker and moiety -Li-Ai to -Ls-As is attached to the moiety DC.

[0246] In some embodiments, the compounds of the present disclosure are for use in medicine, more specifically for preventing diseases transmitted by insect bites, and in particular for preventing malaria, dengue, schistosomiasis, human African trypanosomiasis, leishmaniasis, Chagas disease, yellow fever, Japanese encephalitis and onchocerciasis, chikungunya, and Zika

[0247] Second aspect of the present disclosure

[0248] In a second aspect, the present disclosure relates to the use a compound of formula (la) or (lb),

[0249] (la) (lb) or a tautomer and / or a pharmaceutically acceptable salt thereof, for covalently binding an insect repellent to skin and / or hair; wherein the compound of formula (la) or (lb) comprises a 1,5- dicarbonyl moiety, or a tautomer thereof, and covalently binds to the skin and / or the hair after being topically applied to skin and / or hair by the reaction of its 1,5-dicarbonyl moiety, or of a tautomer thereof, with amino groups present on the skin and / or the hair; wherein L represents a group selected from — (CH2)-0-, — C(=O)-O-, or — CH(OR)(OR') and wherein the em-dash (“ — “) represents the bond attaching L to the remainder of the insect repellent; wherein R represents hydrogen or a first hydrocarbon moiety; wherein R' represents a second hydrocarbon moiety; wherein R' is further attached to DC, or wherein CH(OR)(OR') represents a cyclic acetal moiety which is further attached to DC; and wherein DC represents the remainder of the compound and comprises the 1,5-dicarbonyl moiety, or a tautomer thereof.

[0250] Specifically, in some embodiments, there is provided the use the compound of formula (la) or (lb) is a compound which comprises a cyclic enolether and which is represented by formula (IV), or a tautomer and / or a pharmaceutically acceptable salt thereof, for covalently binding the insect repellent and optionally one or more active ingredients to skin and / or hair; wherein the one or more active ingredients are independently from each other selected from a moisturizer, a pesticide, a UVA- and / or UVB-absorbing moiety and a color-imparting moiety; wherein the compound of formula (IV) covalently binds to the skin and / or the hair after being topically applied to skin and / or hair by the reaction of its cyclic enolether with amino groups present on the skin and / or the hair; wherein the compound of formula (IV) comprises the optional one or more active ingredients, independently from each other, a) as the active ingredient, or b) as a precursor of the active ingredient, wherein the compound of formula (IV) is cleavable to release the active ingredient from the precursor after the application of the compound of formula (IV) to the skin and / or the hair; wherein Li, L2, L3, L4, L5, Lg and L7 represent, independently from each other, a linker group or are absent; wherein one or more of Ai, A2, A3, A4, As, Ar, and A 7 represent: the moiety (IVa) or the moiety (IVb),

[0251] (IVa) (IVb) wherein the broken bond indicates the attachment to the corresponding linker group Li, L2, L3, L4, L5, Lg and L7, or if the respective linker group is absent, to the corresponding ring atom of the cyclic enolether; and, if present, the one or more active ingredients and precursors thereof; wherein each of Ai, A2, A3, A4, As, As and A7 not representing the moiety (IVa), the moiety (IVb) or one of the optional one or more active ingredients and precursors thereof is defined as follows:

[0252] Ai represents hydrogen, a C1-C30 moiety, hydroxyl, amino, or a halogen;

[0253] A2 and A3 are, independently from each other, defined as indicated for Ai or L2-A2 and L3-A3 jointly represent oxo;

[0254] A4 and As are, independently from each other, defined as indicated for Ai;

[0255] As and A7 represent, independently from each other, hydrogen or a C1-C30 moiety; wherein R1represents hydrogen or a protective group hydrolysable under physiological conditions after application of the compound of formula (IV) to the skin and / or the hair; and wherein the dashed line represents a bond or is absent and wherein, in case dashed line represents a bond, -L5-A5 and -O-R1are absent.

[0256] Any of the specific compounds which are disclosed for the first aspect of the present disclosure also represent specific embodiments according to this second aspect of the present disclosure.

[0257] Topical application in the uses of the present disclosure

[0258] In some embodiments, the use further comprises applying the compounds of the present disclosure to the skin and / or hair as a topical composition which comprises one or more of said compounds. In some embodiments, the topical composition is left in contact with the skin and / or the hair for at least 30 minutes. In some embodiments, the use includes cleaning, optionally with an acidic cleaning solution, or chemically peeling the skin and / or the hair prior to applying the topical composition onto the skin.

[0259] Treating domestic and farm animals

[0260] In some embodiments, the use comprises applying the compounds of the present disclosure to the skin and / or fur of domestic or farm animals, in particular wherein said compound comprises an active ingredient or precursor thereof which is selected from pesticides and UVA- and / or UVB-absorbing moieties.

[0261] Cosmetic uses, non-therapeutic uses and other uses

[0262] In some embodiments, the use according to the second aspect of the present disclosure is anon- therapeutic use. In some embodiments, the use according to the first aspect of the present disclosure is a cosmetic use. In some embodiments, the use according to the second aspect of the present disclosure is for preventing insect bites, in particular mosquito bites. In some embodiments, the use according to the second aspect of the present disclosure is for preventing diseases transmitted by insect bites, in particular malaria, dengue, schistosomiasis, human African trypanosomiasis, leishmaniasis, Chagas disease, yellow fever, Japanese encephalitis and onchocerciasis, chikungunya, and Zika.

[0263] Third aspect of the present disclosure

[0264] In a third aspect, the present disclosure relates to the topical composition comprising one or more of the compounds recited in the first aspect of the present disclosure.

[0265] Any of the specific compounds which are disclosed for the first and second aspect of the present disclosure also represent specific embodiments according to this third aspect of the present disclosure.

[0266] The topical composition is not particularly limited and includes any such composition for topical administration. Topical administration in the sense of the present disclosure refers to any local (i.e. not systemic) administration, whether through ointments, gels, creams, lotions, or other similar formulations, of the compounds or compositions of the present disclosure, including administration directly to the external epidermis or dermis of a subject, including administration to skin appendages such as hair but excluding oral, rectal, intrapulmonary and intranasal administration.

[0267] As one form of topical composition, the present disclosure further pertains in some embodiments to the compounds or compositions of the present disclosure for use as a cosmetic.

[0268] In the present application, a cosmetic or a cosmetic use means that the composition is suitable for external use (i.e. extracorporeal use, e.g. not ingested) and is in particular suitable for application to the skin or hair. In some embodiments, the term “cosmetic” is referring to an article intended to be applied to the human body for cleansing, beautifying, promoting attractiveness, or altering the appearance. In some embodiments, the reference to a cosmetic use is excluding a medical use. In some embodiments, the reference to a cosmetic use means that the compounds of the present disclosure, and / or the composition comprising them, complies with with Regulation (EC) N° 1223 / 2009 of the European Union and / or The Modernization of Cosmetics Regulation Act of 2022 of the USA.

[0269] 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, towel ette, 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).

[0270] 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.

[0271] 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.

[0272] The topical composition according to the present disclosure further comprises an excipient suitable for topical administration. The excipient is not particularly limited. In some embodiments, the excipient suitable for topical administration comprises one or more excipients selected from water, ethanol, isopropanol, n-propanol, ethylene glycol, diethylene glycol, a propylene glycol, pentylene glycol, diethylene glycol monoethyl ether, DMSO, and glycerol.

[0273] 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.

[0274] In some embodiments, the topical composition may contain water and / or organic solvents as suitable carriers and excipients. In one example, the liquid composition can be sterile and / or prepared from a sterile aqueous solution for infusion. In some embodiments, the composition may also include a surface-active agent, such as an alkylbenzene sulfonate, an alkyl sulfate, an alkyl ether sulfate, a soap, an ethoxylate, an alkyl alcohol, a lignosulfonate, or a triglyceride. The composition may also include a solid matrix. Suitable examples of a matrix component include a sugar, a sugar alcohol (e.g., sorbitol, mannitol, xylitol, isomalt, hydrogenated starch hydrolysates), a polymer, or a combination of two or more thereof.

[0275] 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.

[0276] 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 compounds of the present disclosure into the deeper layers of the skin, thereby enhancing the attachment and long-lasting effect of the compounds of the present disclosure.

[0277] In some embodiments, the composition may also include a preservative, a thickening agent, a film-forming agent and / or a humectant.

[0278] 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. 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.

[0279] 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.

[0280] As used herein, a “film-forming agent” refers to a compound that can produce a continuous fdm on skin, more specifically a continuous film on skin upon drying of the topical composition. Non-limiting examples of film-forming agents include (volatile) silicone resins, polyvinylpyrrolidone, (meth)acrylates, acrylamides, copolymers of (meth)acrylates and / or acrylamides, isododecane resins, and combinations thereof. Non-limiting examples of (volatile) silicone resins include polymethylsilsesquioxane, trimethylsiloxysilicate, polypropylsilsesquioxane, dimethicone, cyclopentasiloxane, dimethiconol crosspolymer, polysilicone-6, polysilicone-8, polysilicone-11, and polysilicone-14. Non-limiting examples of copolymers include acrylates copolymer, styrene / acrylates copolymer, acrylates / C 12-22 alkyl methacrylate copolymer, acrylates / polytrimethylsiloxymethacrylate copolymer, polyvinylpyrrolidone / vinyl acetate (VP / VA) copolymer, VP / dimethiconylacrylate / polycarbamyl / polyglycol ester, VP / dimethylaminoethylmethacrylate copolymer, VP / dimethyl amino ethylmethacrylate / polycarbamyl polyglycol ester, VP / eicosene copolymer, VP / hexadecene copolymer, VP / methacrylamide / vinyl imidazole copolymer, VP / polycarbamyl poly glycol ester, VP / VA copolymer, polyester- 1, polyester-2, polyester-3, polyester-4, polyester-5, polyester-7, polyester-8, and polyester-10.

[0281] 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.

[0282] The topical compositions can be applied to the skin of the subject using inkjet printing directly onto a skin transfer substrate such as a patch. The composition in this case is applied to the transfer substrate using printer nozzles. In some embodiments, the composition may also be contained in a pen-like applicator since this may allow more selective localized delivery.

[0283] In some embodiments, the topical formulation comprising the compound of formula (I) is storage stable (i.e., the compound of formula (I) retains its original chemical structure at greater than 95 mol.-%) for a period of time from greater than 1 month, more specifically greater than 3 months, and in particular greater than 6 months, when stored at 21 °C and 25% RH. In some embodiments, aqueous solubility of the compound of formula (I) is from about 1 g / L to about 100 g / L, from about 5 g / L to about 50 g / L, or from about 10 g / L to about 100 g / L.

[0284] In some embodiments, it may be particularly advantageous that the topical composition is not too “runny” in order to facilitate that the topical formulation is retained locally on the skin at the site of administration. Accordingly, it may be particularly advantageous that the topical composition is having a dynamic viscosity, measured at 37°C, of more than 2 mPa s, more specifically more than 10 mPa- s, and in particular more than 50 mPa- s, for instance, in the range of 2 mPa s to 50,000 mPa s, more specifically in the range of 10 mPa s to 20,000 mPa s, and in particular in the range of 50 mPa s to 10,000 mPa s. Suitable measuring methods are well- known in the art and include ASTM D-2196-20, using test method A at 30 rpm, or DIN EN ISO 2555:2018-09, at 30 rpm, on a rotational viscosimeter, for instance ViscoQC 100, optionally equipped with a PTD 100 Cone-Plate for smaller sample sizes, obtainable from Anton Paar GmbH, Germany.

[0285] 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.

[0286] Fourth aspect of the present disclosure

[0287] In a fourth aspect, the present disclosure relates to a method of preparing a topical composition comprising a compound of formula (I) as defined in the first aspect of the present disclosure.

[0288] Any of the specific compounds which are disclosed for the first and third aspect of the present disclosure also represent specific embodiments according to this fourth aspect of the present disclosure.

[0289] Methods of preparing the compounds of the present disclosure

[0290] The methods of preparing the compounds of the present disclosure are not particularly limited.

[0291] Particularly suitable are the methods disclosed in WO 2023 / 102652 Al, which is incorporated herein in their entirety by reference thereto, the methods described in the co-pending patent applications PCT / CA2024 / 050763 and PCT / CA2024 / 050764, which are incorporated herein in their entirety by reference thereto, and in the patent applications filed with the European Patent Office in the name of the applicant under the titles “COMPOUNDS ATTACHABLE TO KERATINOUS TISSUES” on the same day as the present disclosure. All of these applications are incorporated herein in their entirety by reference thereto.

[0292] Further Definitions

[0293] 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.

[0294] 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 “C1-6 alkyl” is specifically intended to individually disclose methyl, ethyl, C3 alkyl, C4 alkyl, C5 alkyl, and Ce alkyl.

[0295] As used herein, the term “carboxy” refers to a -C(O)OH group.

[0296] 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, C1-6, and the like.

[0297] As used herein, the term “Cn-Cmmoiety”, as it is used in e.g. C1-C30 moiety, C1-C16 moiety, Ci- Ceo moiety etc., refers to any carbon-containing moiety having the referenced number of carbon atoms. It should be understood that the reference to a “Cn-Cmmoiety” is a closed definition and defines a finite moiety, i.e. a “Cn-Cmmoiety” is a moiety which, with respect to the number of carbon atoms, contains between n and m carbon atoms, but not more or less carbon atoms. However, it should be further understood that a “Cn-Cmmoiety” may optionally comprise further atom species not being C, i.e. atom species such a H, O, S, and N and others may be contained in the Ci-Ceo moiety.

[0298] As used herein, any reference to a moiety comprising a specified number or a specified range of an atom species, such as e.g. “a C1-C30 moiety comprising 1 to 12 oxygen atoms”, should be understood as defining a finite moiety, i.e. a moiety which, with respect to said atom species, contains said atom species in said specified amount. So, the aforementioned “C1-C30 moiety comprising 1 to 12 oxygen atoms” refers to a C1-C30 moiety containing between 1 to 12 oxygen atoms. However, it should be further understood that said moiety may optionally comprise further atom species besides the specified atom species, i.e. the aforementioned “C1-C30 moiety containing between 1 to 12 oxygen atoms” may optionally comprise further atom species not being C and not being O, i.e. atom species such H, S, and N and others. In case a specified range of a specified atom species starts with zero (“0”), the presence of the referenced atom species is optional. To give an example, a “C1-C30 moiety comprising 0 to 12 oxygen atoms and 0 to 4 nitrogen atoms” is to be understood a s reference to a C1-C30 moiety optionally containing 1 to 12 oxygen atoms and optionally containing 1 to 4 nitrogen atoms. As used herein, the term “Cn-m alkyl”, employed alone or in combination with other terms, refers to a saturated hydrocarbon group that may be straight-chained or branched, having n to m carbons. Examples of alkyl moieties include, but are not limited to, chemical groups such as methyl, ethyl, «-propyl, isopropyl, / 7-butyl. / c / 7-buty I. isobutyl, sec-butyl; higher homologs such as 2-methyl-l -butyl, «-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.

[0299] 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.

[0300] As used herein, the term “Cn-mhaloalkyl”, employed alone or in combination with other terms, refers to an alkyl group having from one halogen atom to 2s+l halogen atoms which may be the same or different, where “s” is the number of carbon atoms in the alkyl group, wherein the alkyl group has n to m carbon atoms. In some embodiments, the haloalkyl group is fluorinated only. In some embodiments, the alkyl group has 1 to 6, 1 to 4, or 1 to 3 carbon atoms.

[0301] As used herein, “Cn-malkenyl” refers to an alkyl group having one or more double carboncarbon bonds and having n to m carbons. Example alkenyl groups include, but are not limited to, ethenyl, w-propenyl, isopropenyl, / 7-butenyl. scc-butenyl. and the like. In some embodiments, the alkenyl moiety contains 2 to 6, 2 to 4, or 2 to 3 carbon atoms.

[0302] As used herein, “Cn-malkynyl” refers to an alkyl group having one or more triple carbon-carbon bonds and having n to m carbons. Example alkynyl groups include, but are not limited to, ethynyl, propyn-l-yl, propyn-2-yl, and the like. In some embodiments, the alkynyl moiety contains 2 to 6, 2 to 4, or 2 to 3 carbon atoms.

[0303] As used herein, the term “Cn-malkylene”, employed alone or in combination with other terms, refers to a divalent alkyl linking group having n to m carbons. Examples of alkylene groups include, but are not limited to, ethan- 1,1 -diyl, ethan-l,2-diyl, propan-1,1, -diyl, propan- 1,3-diyl, propan- 1,2-diyl, butan-l,4-diyl, butan-l,3-diyl, butan-l,2-diyl, 2-methyl-propan-l,3-diyl, and the like. In some embodiments, the alkylene moiety contains 2 to 6, 2 to 4, 2 to 3, 1 to 6, 1 to 4, or 1 to 2 carbon atoms.

[0304] As used herein, the term “amino” refers to a group of formula -NH2.

[0305] As used herein, the term “halogen” refers in particular to F, Cl, Br and I.

[0306] 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.

[0307] 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.

[0308] 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.

[0309] As used herein, a “salt” or “pharmaceutically acceptable salt” of a compound of any one of the formulae disclosed herein is formed between an acid and a basic group of the compound, such as an amino functional group, or a base and an acidic group of the compound, such as a carboxyl functional group. According to another embodiment, the compound is a pharmaceutically acceptable acid addition salt. In some embodiments, acids commonly employed to form pharmaceutically acceptable salts of the compounds of any one of the formulae include inorganic acids such as hydrogen bisulfide, hydrochloric acid, hydrobromic acid, hydroiodic acid, sulfuric acid and phosphoric acid, as well as organic acids such as para-toluenesulfonic acid, salicylic acid, tartaric acid, bitartaric acid, ascorbic acid, maleic acid, besylic acid, fumaric acid, gluconic acid, glucuronic acid, formic acid, glutamic acid, methanesulfonic acid, ethanesulfonic acid, benzenesulfonic acid, lactic acid, oxalic acid, para-bromophenylsulfonic acid, carbonic acid, succinic acid, citric acid, benzoic acid and acetic acid, as well as related inorganic and organic acids. Such pharmaceutically acceptable salts thus include sulfate, pyrosulfate, bisulfate, sulfite, bisulfite, phosphate, monohydrogenphosphate, dihydrogenphosphate, metaphosphate, pyrophosphate, chloride, bromide, iodide, acetate, propionate, decanoate, caprylate, acrylate, formate, isobutyrate, caprate, heptanoate, propiolate, oxalate, mal onate, succinate, suberate, sebacate, fumarate, maleate, butyne- 1,4-dioate, hexyne- 1,6-dioate, benzoate, chlorobenzoate, methylbenzoate, dinitrobenzoate, hydroxybenzoate, methoxybenzoate, phthalate, terephthalate, sulfonate, xylene sulfonate, phenylacetate, phenylpropionate, phenylbutyrate, citrate, lactate, -hydroxybutyrate, glycolate, maleate, tartrate, methanesulfonate, propanesulfonate, naphthalene- 1 -sulfonate, naphthal ene-2- sulfonate, mandelate and other salts. In one embodiment, pharmaceutically acceptable acid addition salts include those formed with mineral acids such as hydrochloric acid and hydrobromic acid, and especially those formed with organic acids such as maleic acid. In some embodiments, bases commonly employed to form pharmaceutically acceptable salts of the compounds of any one of the formulae disclosed herein include hydroxides of alkali metals, including sodium, potassium, and lithium; hydroxides of alkaline earth metals such as calcium and magnesium; hydroxides of other metals, such as aluminum and zinc; ammonia, organic amines such as unsubstituted or hydroxyl-substituted mono-, di-, or tri-alkylamines, dicyclohexylamine; tributyl amine; pyridine; N-methyl, N-ethylamine; diethylamine; tri ethyl amine; 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. The terms “protecting group” and “protective group” refer to a moiety that reversibly chemically modifies a functional group in order to obtain chemoselectivity or in order to reduce degradation in one or more subsequent chemical reactions. Suitable protecting groups are well known in the art (see, e.g., Greene and Wuts, Protective Groups in Organic Synthesis, 3rd Ed., John Wiley & Sons, New York, N.Y., 1999, which is incorporated herein by reference in its entirety).

[0310] 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.

[0311] OTHER EMBODIMENTS

[0312] 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.

[0313] The present disclosure also relates to the following embodiments which are supplementary to and freely combinable with the above specification:

[0314] 1. A compound of formula (la) or (lb), or a tautomer and / or a pharmaceutically acceptable salt thereof, for covalently binding an insect repellent to skin and / or hair; wherein the compound of formula (la) or (lb) comprises a 1,5-dicarbonyl moiety, or a tautomer thereof, and is capable of covalently binding to the skin and / or the hair after being topically applied to skin and / or hair by the reaction of its 1,5-dicarbonyl moiety, or of the tautomer thereof, with amino groups present on the skin and / or the hair; wherein L represents a group selected from — (CH2)-0-, — C(=O)-O-, or — CH(OR)(OR') and wherein the em-dash (“ — “) represents the bond attaching L to the remainder of the insect repellent; wherein R represents hydrogen or a first hydrocarbon moiety; wherein R' represents a second hydrocarbon moiety; wherein R' is further attached to DC, or wherein CH(OR)(OR') represents a cyclic acetal moiety which is further attached to DC; and wherein DC represents the remainder of the compound and comprises the 1,5-dicarbonyl moiety, or the tautomer thereof. The compound according to embodiment 1, wherein the compound of formula (la) or (lb), in the form as it is bound to the skin and / or hair, is cleavable to release the insect repellent. The compound according to embodiment 1 or embodiment 2, wherein the compound of formula (la) or (lb), in the form as it is bound to the skin and / or hair, is hydrolysable to release the insect repellent in the presence of water at a pH of between about 5 to about 6. The compound according to any one of embodiments 1 to 3, wherein the compound of formula (la) or (lb), in the form as it is bound to the skin and / or hair, is enzymatically cleavable by enzymes natively present on mammalian, and in particular human, skin and / or hair, to release the insect repellent; and in particular cleavable to release the insect repellent by esterase enzymes. The compound according to any one of embodiments 1 to 4, wherein the compound of formula (la) or (lb) is a compound of formula (la) and wherein the compound is cleavable to any one of the compounds of formulae (Ila), (lib) and (lie): The compound according to any one of embodiments 1 to 4, wherein the compound of formula (la) or (lb) is a compound of formula (lb) and wherein the compound is cleavable to any one of the compounds of formulae (Illa), (Illb), (IIIc) and (Illd),

[0315] (Hlc) (Hid) wherein Mi represents an optionally substituted hydrocarbon moiety comprising, in combination with its optional substituents, 1 to 7, more specifically 1 to 4, and in particular 1 or 2, carbon atoms; 0 to 3, more specifically 0 to 2, and in particular 0 or 1 oxygen atoms; 0 or 1 nitrogen atoms; 0 or 1 sulfur atoms; and 0 to 3, more specifically 0 to 2, and / or in particular 0 or 1 halogen atoms. The compound according to embodiment 6, wherein Mi represents C1-C4 alkyl or C2-C4- alkenyl, both of which are optionally substituted with one, two or three hydroxyl groups, one amino group, and 0 to 3, more specifically 0 to 2, and in particular 0 or 1 halogen atoms. The compound according to embodiment 6 or embodiment 7, wherein the compound of formula (lb) is cleavable to any one of the following compounds: n=1 or 2 The compound according to any preceding embodiment, wherein DC comprises a 1,5- dialdehyde moiety, or a tautomer thereof; a l-aldehyde-5-keto moiety, or a tautomer thereof; a l-keto-5 -aldehyde moiety, or a tautomer thereof; or a 1,5-diketo moiety, or a tautomer thereof; and in particular a 1, 5-dial dehy de moiety, or a tautomer thereof; a 1- aldehyde-5-keto moiety, or a tautomer thereof; or a l-keto-5-aldehyde moiety, or a tautomer thereof. The compound according to any preceding embodiment, wherein the DC represents a Cs- Ceo moiety, in particular a Cs-Ceo moiety comprising 5 to 60, more specifically 8 to 48, and in particular 10 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. The compound according to any preceding embodiment, wherein the compound of formula (la) or (lb) is a compound which comprises a cyclic enolether and which is represented by formula (IV), (IV), or a tautomer and / or a pharmaceutically acceptable salt thereof, for covalently binding the insect repellent and optionally one or more active ingredients to skin and / or hair; wherein the one or more active ingredients are independently from each other selected from a moisturizer, a pesticide, a UVA- and / or UVB-absorbing moiety and a colorimparting moiety; wherein the compound of formula (IV) is capable of covalently binding to the skin and / or the hair after being topically applied to skin and / or hair by the reaction of its cyclic enolether with amino groups present on the skin and / or the hair; wherein the compound of formula (IV) comprises the optional one or more active ingredients, independently from each other, a) as the active ingredient, or b) as a precursor of the active ingredient, wherein the compound of formula (IV) is cleavable to release the active ingredient from the precursor after the application of the compound of formula (IV) to the skin and / or the hair (in the following: “the precursor thereof’); wherein Li, L2, L3, L4, L5, Lg and L7 represent, independently from each other, a linker group or are absent; wherein one or more of Ai, A2, A3, A4, As, Ae and A 7 represent:

[0316] - the moiety (IVa) or the moiety (IVb),

[0317] (IVa) (IVb) wherein the broken bond indicates the attachment to the corresponding linker group Li, L2, L3, L4, Ls, Lg and L7, or if the respective linker group is absent, to the corresponding ring atom of the cyclic enolether; and, if present, the one or more active ingredients and precursors thereof; wherein each of Ai, A2, A3, A4, As, Ae and A 7 not representing the moiety (IVa), the moiety (IVb) or one of the optional one or more active ingredients and precursors thereof is defined as follows:

[0318] Ai represents hydrogen, a C1-C30 moiety, hydroxyl, amino, or a halogen;

[0319] A2 and A3 are, independently from each other, defined as indicated for Ai or L2-A2 and L3-A3 jointly represent oxo;

[0320] A4 and As are, independently from each other, defined as indicated for Ai;

[0321] As and A7 represent, independently from each other, hydrogen or a C1-C30 moiety; wherein R1represents hydrogen or a protective group hydrolysable under physiological conditions after application of the compound of formula (IV) to the skin and / or the hair; and wherein the dashed line represents a bond or is absent and wherein, in case dashed line represents a bond, -L5-A5 and -O-R1are absent. The compound according to any preceding embodiment, wherein the compound of formula (IV) comprises at least one of the optional one or more active ingredients and precursors thereof and wherein the compound of formula (IV) 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 (IV) 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. The compound according to embodiment 12, 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:

[0322] - 1 to 12 carbon atoms, more specifically 1 to 8 carbon atoms, and in particular 1 to 4carbon atoms;

[0323] - 1 to 4 oxygen atoms, more specifically 1 to 3 oxygen atoms, and in particular 1 or 2 oxygen atoms;

[0324] - 1 to 4 nitrogen atoms, more specifically 1 to 3 nitrogen atoms, and in particular lor 2 nitrogen atoms;

[0325] - 1 to 3 sulfur atoms, more specifically 1 or 2 sulfur atoms, and in particular 1 sulfur atom;

[0326] - 1 to 3 phosphorus atoms, more specifically 1 or 2 phosphorus atoms, and in particular 1 phosphorus atom

[0327] - 1 or 2 boron atoms, and in particular 1 boron atom. The compound according to embodiment 12 or 13, wherein, after the compound of formula (IV) has bound to the skin and / or the hair, the functional group is:

[0328] (i) biostable; or (ii) cleavable, more specifically cleavable under physiological conditions encountered after its application to the skin and / or the hair, and / or cleavable under conditions preselected for said use, in particular cleavable upon elevation of temperature to higher than 42 °C, cleavable upon exposure to daylight, cleavable upon exposure to UVA- and / or UVB-light, cleavable upon exposure to acids, cleavable upon exposure to an oxidizing agent suitable for oxidizing said functional group, cleavable upon exposure to a reducing agent suitable for reducing said functional group, or cleavable upon exposure to salts. The compound according to any one of embodiments 12 to 14, 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. The compound according to any one of embodiments 12 to 15, wherein the functional group is enzymatically cleavable under physiological conditions after the compound of formula (IV) is topically applied onto mammalian, more specifically human skin, in particular enzymatically cleavable by enzymes present in the mammalian, more specifically human skin. The compound according to any one of embodiments 14 to 16, 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, aphosphonic acid, an olefine, aboronic acid, aborinic acid, a boric acid, or an oxime; or salts thereof; after cleavage of the functional group. The compound according to any one of embodiments 14 to 17, 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, aphosphonic acid, an olefine, aboronic acid, aborinic acid, a boric acid, or an oxime; or salts thereof; to said active ingredient after cleavage of the functional group. The compound according to embodiment 18, wherein, after cleavage of the functional group: the functional group provides a hydroxyl group, a primary or secondary amine group, a carboxylic acid, a thiol, an aldehyde, a ketone, a thiocarbonic acid, a sulfonic acid, a sulfinic acid, a phosphoric acid, a phosphonic acid, an olefine, a boronic acid, a borinic acid, a boric acid, or an oxime to said active ingredient; and the functional group provides a hydroxyl group, a primary or secondary amine group, a carboxylic acid, a thiol, an aldehyde, a ketone, a thiocarbonic acid, a sulfonic acid, a sulfinic acid, a phosphoric acid, a phosphonic acid, an olefine, a boronic acid, a borinic acid, a boric acid, or an oxime to the remainder of the compound of formula (IV). The compound according to any one of embodiments 12 to 19, 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. The compound according to any one of embodiments 11 to 20, wherein the compound of formula (IV) is a compound of formula (V), or a tautomer and / or a pharmaceutically acceptable salt thereof; wherein R1, Ai, A2, A3, A4, Ag, A7, Li, L2, L3, L4, Lg, and L7 are defined as in any preceding embodiment; and in particular wherein L1-A1 and L4-A4 do not represent hydrogen. The compound according to any one of embodiments 11 to 21, wherein Ai represents the moiety of formula (IVa) or the moiety of formula (IVb) and A2, A3 and A4 represent independently from each other hydrogen or the C1-C30 moiety. The compound according to any one of embodiments 11 to 21, wherein Ai represents the C1-C30 moiety and A2, A3 or A4 represents the moiety of formula (IVa) or the moiety of formula (IVb). The compound according to embodiment 23, wherein A2 represents the moiety of formula (IVa) or the moiety of formula (IVb), wherein A3 represents the C1-C30 moiety, and wherein A4 represents the C1-C30 moiety. The compound according to embodiment 23, wherein A4 represents the moiety of formula (IVa) or the moiety of formula (IVb), and wherein:

[0329] A2 represents hydrogen and A3 represents hydrogen; or

[0330] A2 represents the C1-C30 moiety and A3 represents hydrogen; or

[0331] A2 represents hydrogen and A3 represents the C1-C30 moiety; or

[0332] A2 represents the C1-C30 moiety and A3 represents the C1-C30 moiety. The compound according to any one of embodiments 11 to 25, wherein Li, L2, L3, L4, L5 Lg and L7 independently from each other are absent or represent an optionally substituted hydrocarbon moiety comprising, in combination with its optional substituents, 1 to 12 carbon atoms, more specifically 1 to 10 carbon atoms, and in particular 1 to 8 carbon atoms. The compound according to any one of embodiments 11 to 26, wherein:

[0333] Li is present and represents an optionally substituted hydrocarbon moiety comprising, in combination with its optional substituents, 1 to 18 carbon atoms, more specifically 1 to 12 carbon atoms, still more specifically 1 to 10 carbon atoms, and in particular 1 to 8 carbon atoms; and / or L2 is present and represents an optionally substituted hydrocarbon moiety comprising, in combination with its optional substituents, 1 to 18 carbon atoms, more specifically 1 to 12 carbon atoms, still more specifically 1 to 10 carbon atoms, and in particular 1 to 8 carbon atoms; and / or

[0334] L3 is present and represents an optionally substituted hydrocarbon moiety comprising, in combination with its optional substituents, 1 to 18 carbon atoms, more specifically 1 to 12 carbon atoms, still more specifically 1 to 10 carbon atoms, and in particular 1 to 8 carbon atoms; and / or

[0335] L4 is present and represents an optionally substituted hydrocarbon moiety comprising, in combination with its optional substituents, 1 to 18 carbon atoms, more specifically 1 to 12 carbon atoms, still more specifically 1 to 10 carbon atoms, and in particular 1 to 8 carbon atoms; and / or

[0336] L5 is present and represents an optionally substituted hydrocarbon moiety comprising, in combination with its optional substituents, 1 to 18 carbon atoms, more specifically 1 to 12 carbon atoms, still more specifically 1 to 10 carbon atoms, and in particular 1 to 8 carbon atoms;

[0337] Lr, is present and represents an optionally substituted hydrocarbon moiety comprising, in combination with its optional substituents, 1 to 18 carbon atoms, more specifically 1 to 12 carbon atoms, still more specifically 1 to 10 carbon atoms, and in particular 1 to 8 carbon atoms; and / or

[0338] L7 is present and represents an optionally substituted hydrocarbon moiety comprising, in combination with its optional substituents, 1 to 18 carbon atoms, more specifically 1 to 12 carbon atoms, still more specifically 1 to 10 carbon atoms, and in particular 1 to 8 carbon atoms. The compound according to any one of embodiments 11 to 27, wherein:

[0339] Li and Lg are present and form a ring; and / or

[0340] Li and L2 are present and form a ring; and / or

[0341] L2 and L4 are present and form a ring; and / or

[0342] L4 and L7 are present and form a ring; and / or

[0343] L4 and R1are present and form a ring. The compound according to embodiment 28, wherein the ring is a 5-, 6-, 7- or 8-membered ring, more specifically a 5-, 6-, or 7-membered ring, and in in particular a 5- or 6-membered ring. The compound according to embodiment 28, wherein the ring is an optionally substituted cyclopentyl ring, an optionally substituted cyclohexyl ring, an optionally substituted pyrrolidinyl ring, an optionally substituted piperidinyl ring, an optionally substituted tetrahydrofuranyl ring or an optionally substituted tetrahydropyranyl ring. The compound according to any one of embodiments 11 to 30, wherein L3 and L4 are present and form an optionally substituted 5-, 6-, 7- or 8-membered ring comprising, in combination with its optional substituents, 1 to 12 carbon atoms, more specifically 1 to 10 carbon atoms, and in particular 1 to 8 carbon atoms, in particular an optionally substituted cyclopentyl, an optionally substituted cyclohexyl ring, an optionally substituted pyrrolidinyl ring, an optionally substituted piperidinyl ring, an optionally substituted tetrahydrofuranyl ring or an optionally substituted tetrahydropyranyl ring. The compound according to embodiment 31, wherein L3 and L4 are present and form an optionally substituted 5-or 6-membered ring, in particular cyclopentyl, cyclopentenyl, tetrahydrofuranyl, cyclohexyl, or cyclohexenyl, to which A3 and A4 are attached, optionally via a group selected from: -O-, -S-, -C(O)-, -CO2-, -O-C(O)-, -NH-C(O)-, -C(O)-NH-, - (CH2)I-4-, -(CH2)I-4-O- and -O-(CH2)I-4-, or combinations thereof. The compound according to any one of embodiments 11 to 32, 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, and 0 to 10, more specifically 0 to 8, and in particular 0 to 6 halogen atoms; and / or wherein the C1-C30 moiety is bound a) to the respective Li, L2, L3, L4, L5, Lg, L7 and Ls, if it is present, via a carbon atom, an oxygen atom, a nitrogen atom or a sulfur atom, or b) if the respective Li, L2, L3, L4, Ls, Lg, L7 and Ls, is absent, via a carbon atom, an oxygen atom, a nitrogen atom or a sulfur atom to the carbon atom of ring to which the C1-C30 moiety is attached. The compound according to embodiment 33, wherein each occurrence of the C1-C30 moiety is, independently from each other, selected from a saturated or unsaturated, cyclic or acylic (hetero)alkyl or (hetero)aryl, each comprising 1 to 30, more specifically 1 to 16, and in particular 1 to 12, carbon atoms; 0 to 12, more specifically 0 to 8, and in particular 0 to 6 oxygen atoms; 0 to 8, more specifically 0 to 6, and in particular 0 to 4 nitrogen atoms; 0 to 6, more specifically 0 to 4, and in particular 0 to 3 sulfur atoms; and 0 to 10, more specifically 0 to 8, and in particular 0 to 6 halogen atoms; and / or wherein the C1-C30 moiety is bound a) to the respective Li, L2, L3, L4, L5, Lg. L7 and Ls, if it is present, via a carbon atom, an oxygen atom, a nitrogen atom or a sulfur atom, or b) if the respective Li, L2, L3, L4, L5, Lg, L7 and Ls, is absent, via a carbon atom, an oxygen atom, a nitrogen atom or a sulfur atom to the carbon atom of ring to which the C1-C30 moiety is attached. The compound according to embodiment 34, 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 atoms; and 0 to 5, more specifically 0 to 4, and in particular 0 to 3 halogen atoms; and wherein the C1-C30 moiety is bound a) to the respective Li, L2, L3, L4, Ls, Lg, L7 and Ls, if it is present, via a carbon atom, an oxygen atom, a nitrogen atom or a sulfur atom, or b) if the respective Li, L2, L3, L4, Ls, Lg, L7 and Ls, is absent, via a carbon atom, an oxygen atom, a nitrogen atom or a sulfur atom to the carbon atom of ring to which the C1-C30 moiety is attached The compound according to any one of embodiments 11 to 35, wherein Ai, A3, As, Ag and A7 do not represent one of the one or more active ingredients or of the corresponding precursors thereof, and wherein Li, L3, Ls,Lg and L7 are absent. The compound according to any one of embodiments 11 to 37, wherein the compound of formula (IV) is a compound of formula (VI), or a tautomer and / or a pharmaceutically acceptable salt thereof; wherein R1, Ai, A2, A3, A4, As, A7, L2, L3, L4, Lg and L7 are defined as in any preceding embodiment; wherein X represents O or S, and in particular O; and wherein Lxis absent or represents -O-, -NH-, or an optionally substituted hydrocarbon moiety comprising, in combination with its optional substituents, 1 to 12 carbon atoms, more specifically 1 to 10 carbon atoms, and in particular 1 to 8 carbon atoms, 0 to 8, more specifically 0 to 6, and in particular 0 to 4 oxygen atoms; 0 to 6, more specifically 0 to 4, and in particular 0 to 3 nitrogen atoms; 0 to 6, more specifically 0 to 4, and in particular 0 to 3 sulfur atoms; and 0 to 8, more specifically 0 to 6, and in particular 0 to 5 halogen atoms, and wherein the hydrocarbon moiety is attached to the (C=X)-moiety via a carbon atom, an oxygen atom, a nitrogen atom, or a sulfide atom. The compound according to any one of embodiments 11 to 37, and in particular embodiment 37, wherein Ai represents the C1-C30 moiety, more specifically a Ci-Cig moiety selected from a saturated or unsaturated, cyclic or acylic (hetero)alkyl comprising 1 to 16, more specifically 1 to 12, and in particular 1 to 8, carbon atoms; 0 to 6, more specifically 0 to 4, and in particular 0 to 3 oxygen atoms; 0 to 6, more specifically 0 to 4, and in particular 0 to 3 nitrogen atoms; 0 to 6, more specifically 0 to 4, and in particular 0 to 3 sulfur atoms; and 0 to 6, more specifically 0 to 4, and in particular 0 to 3 halogen atoms. The compound according to embodiment 37 or 38, wherein Lx-Ai represents a Ci-Cie moiety selected from a carboxylic acid or a salt thereof, a carboxylic acid ester; a ketone; more specifically a moiety selected from:

[0344] -COOH or a salt thereof;

[0345] -COORa, -C(O)-Ra,

[0346] -C(O)-NH2, -C(O)NHRa, -C(O)NRa2, wherein Ra represents a moiety comprising 1 to 10 carbon atoms, and optionally one or more of: 1 to 6 oxygen atoms, 1 to 4 nitrogen atoms, 1 to 3 sulfur atoms, and 1 to 5 halogen atoms, more specifically a moiety comprising 1 to 6 carbon atoms, and optionally one or more of: 1 to 4 oxygen atoms, 1 to 3 nitrogen atoms, 1 or 2 sulfur atoms, and 1 to 3 halogen atoms, and in particular Ci-Ce-alkyl or phenyl; and wherein NRa2may alternatively represent an optionally substituted saturated or unsaturated nitrogen heterocycle comprising, in combination with its optional substituents, 1 to 12, more specifically 1 to 10, and in particular 1 to 8, carbon atoms; 0 to 6, more specifically 0 to 4, and in particular 0 to 3 oxygen atoms; 1 to 4, more specifically 1 to 3, and in particular 1 or 2 nitrogen atoms; 0 to 3, more specifically 0 to 2, and in particular 0 or 1 sulfur atoms; and 0 to 5, more specifically 0 to 4, and in particular 0 to 3 halogen atoms. The compound according to any one of embodiments 11 to 39, wherein R1represents hydrogen, C1-6 acyl, a silyl group, or C1-6 alkyl; and in particular hydrogen. The compound according to any one of embodiments 1 to 40, wherein the compound of formula (la) or (lb), after having covalently bound to the skin and / or the hair, is not observable to the human eye on the skin and / or hair when illuminated with artificial light of 3000 Kelvin and an intensity of 1000 Lux. The compound according to any one of embodiments 1 to 41, wherein the compound of formula (la) or (lb), after having covalently bound to lysine, does not show absorption peaks having an extinction of more than 0.5 within the wavelength range of 380 to 790 nm in a 2 mM methanolic solution. The compound according to any one of embodiments 11 to 42, wherein L2-A2, L3-A3 and L4-A4 do not represent moi eties (or form a moiety) comprising an unsaturated C-C or C-N bond in alpha-position to the respective carbon atom(s) of the 3,4-saturated 2H-pyran moiety to which they are bound. The compound according to any one of embodiments 11 to 43, wherein L1-A1 and Lg-Ag do not represent moieties (or form a moiety) comprising an unsaturated C-C or C-N bond in alpha-position to the respective carbon atom(s) of the 3,4-saturated 2H-pyran moiety to which they are bound. The compound according to any one of embodiments 11 to 44, wherein L4-A4 and L7-A7 do not represent moieties (or form a moiety) comprising an unsaturated C-C or C-N bond in alpha-position to the respective carbon atom(s) of the 3,4-saturated 2H-pyran moiety to which they are bound. The compound according to any one of embodiments 11 to 45, wherein L1-A1 and L2-A2 do not represent moieties (or form a moiety) comprising an unsaturated C-C or C-N bond in alpha-position to the respective carbon atom(s) of the 3,4-saturated 2H-pyran moiety to which they are bound. The compound according to any of embodiments 21 to 46, wherein the 3,4-saturated 2H- pyran moiety of the compound of formula (V) covalently binds to the skin and / or the hair forming a compound of formulae (Vc) and / or (Vd),

[0347] or a tautomer and / or a salt thereof; wherein the broken bond represents the covalent bond to the skin and / or the hair; wherein Ai, A2, A3, A4, As, A7, Li, L2, L3, L4, Lg and L7 are defined as indicated in any of the preceding embodiments. The compound according to embodiment 47, wherein no more than one, and in particular none, of L1-A1, L2-A2, L3-A3, L4-A4, Lg-Ag and L7-A7 of the compound of formula (V) forms, after the 3,4-saturated 2H-pyran moiety has covalently bound to the skin and / or hair forming a compound of formula (Vc) and / or (Vd), a conjugated 71-electron system comprising more than 6 double bonds, more specifically more than 5 double bonds, and in particular more than 4 double bonds, with the heterocycle marked by letters a to e in the formula (Vc) and more than 7 double bonds, more specifically more than 6 double bonds, and in particular more than 5 double bonds, with the heterocycle marked by letters a to e in the formula (Vd). The compound according to embodiment 47 or 48, wherein the combination of all of Li- Ai, L2-A2, L3-A3, L4-A4, Lg-Ag and L7-A7 of the compound of formula (V), after the 3,4- saturated 2H-pyran moiety has covalently bound to the skin and / or hair forming a compound of formula (Vc) and / or (Vd): does not form a conjugated 71-electron system with the heterocycles marked by letters a to e in the formulae (Vc) and (Vd); or forms a conjugated 71-electron system with the heterocycle marked by letters a to e in the formula (Vc) which comprises less than 7 double bonds, more specifically less than 6 double bonds, and in particular less than 5 double bonds, and forms a conjugated 71-electron system with the heterocycle marked by letters a to e in the formula (Vd) which comprises less than 8 double bonds, more specifically less than 7 double bonds, and in particular less than 6 double bonds. The compound according to any one of embodiments 47 to 49, wherein no more than three, more specifically no more than two, and in particular no more than one, of Li-Ai, L2-A2, L4-A4, Le-Ae and L7-A7 of the compound of formula (V) comprise a carbonyl group which forms or is part of a conjugated 71-electron system with the heterocycles marked by letters a to e in the formulae (Vc) and (Vd). The compound according to any one of embodiments 47 to 50, wherein L1-A1, L2-A2, L4- A4, Le-Ae and L7-A7 of the compound of formula (V) are selected such that, after the compound has bound to skin or hair, they do not provide a combination of electronwithdrawing and electron-donating groups to the conjugated 71-electron system formed with the respective heterocycles marked by letters a to e in the formulae (Vc) and (Vd). The compound according to any preceding embodiment, wherein the compound of formula (I) is a compound of formula (VII), or a tautomer and / or a pharmaceutically acceptable salt thereof; wherein R1, Ai, A2, A3, A4, Li, L2, L3 and L4 are defined as indicated in any of the preceding embodiments; wherein R2represents hydrogen or a C1-C16 moiety; more specifically hydrogen or a C1-C16 moiety comprising 1 to 16, and in particular 1 to 12, carbon atoms; 0 to 12, more specifically 0 to 8, and in particular 0 to 6 oxygen atoms; 0 to 8, more specifically 0 to 6, and in particular 0 to 4 nitrogen atoms; 0 to 6, more specifically 0 to 4, and in particular 0 to 3 sulfur atoms; and O to 10, more specifically 0 to 8, and in particular 0 to 6 halogen atoms; and in particular hydrogen or a saturated or unsaturated, cyclic or acylic (hetero)alkyl or a (hetero)aryl moiety comprising 1 to 10 carbon atoms, and optionally one or more of: 1 to 6 oxygen atoms, 1 to 4 nitrogen atoms, 1 to 3 sulfur atoms, and 1 to 5 halogen atoms; and wherein R3represents hydrogen or a Ci-Cie moiety; more specifically hydrogen or a C1-C16 moiety comprising 1 to 16, and in particular 1 to 12, carbon atoms; 0 to 12, more specifically 0 to 8, and in particular 0 to 6 oxygen atoms; 0 to 8, more specifically 0 to 6, and in particular 0 to 4 nitrogen atoms; 0 to 6, more specifically 0 to 4, and in particular 0 to 3 sulfur atoms; and 0 to 10, more specifically 0 to 8, and in particular 0 to 6 halogen atoms; and in particular hydrogen or a saturated or unsaturated, cyclic or acylic (hetero)alkyl or a (hetero)aryl moiety comprising 1 to 10 carbon atoms, and optionally one or more of: 1 to 6 oxygen atoms, 1 to 4 nitrogen atoms, 1 to 3 sulfur atoms, and 1 to 5 halogen atoms. The compound according to embodiment 52, wherein R2represents Ci-Ce alkyl or C6-C12 aryl, both of which may be optionally further substituted with the proviso that the entirety of R2does not comprise more than 16 carbon atoms, 6 oxygen atoms, 4 nitrogen atoms, 3 sulfur atoms, and 5 halogen atoms; and wherein R3represents hydrogen or Ci-Ce alkyl or C6-C12 aryl, both of which may be optionally further substituted with the proviso that the entirety of R3does not comprise more than 16 carbon atoms, 6 oxygen atoms, 4 nitrogen atoms, 3 sulfur atoms, and 5 halogen atoms. The compound according to embodiment 52 or 53, wherein R2represents a Ci-Ce alkyl which may be optionally further substituted with the proviso that the entirety of R2does not comprise more than 12 carbon atoms, 4 oxygen atoms, 3 nitrogen atoms, 2 sulfur atoms, and 3 halogen atoms; and wherein R3represents hydrogen or C1-C4 alkyl. The compound according to any one of embodiments 52 to 54, wherein R2represents an aliphatic C1-C4 moiety, optionally comprising a carboxylic acid or a salt thereof, a carboxylic acid ester, a ketone, an alcohol, an ether, or combinations thereof; and wherein R3represents hydrogen. The compound according to any one of embodiments 11 to 55, wherein the compound of formula (IV) is a compound of formula (VIII), or a tautomer and / or a pharmaceutically acceptable salt thereof; wherein R1, R2, R3, A2, A3, A4, L2, L3 and L4 are defined as indicated in any of the preceding embodiments; and wherein R4represents hydrogen or a C1-C16 moiety selected from a carboxylic acid or a salt thereof, a carboxylic acid ester; a ketone or an amide; more specifically a moiety selected from:

[0348] -COOH or a salt thereof;

[0349] -COORa, -C(O)-Ra,

[0350] -C(O)-NH2, -C(O)NHRa, -C(O)NRa2, wherein Ra represents a moiety comprising 1 to 10 carbon atoms, and optionally one or more of: 1 to 6 oxygen atoms, 1 to 4 nitrogen atoms, 1 to 3 sulfur atoms, and 1 to 5 halogen atoms, more specifically a moiety comprising 1 to 6 carbon atoms, and optionally one or more of: 1 to 4 oxygen atoms, 1 to 3 nitrogen atoms, 1 or 2 sulfur atoms, and 1 to 3 halogen atoms, and in particular Ci-Ce-alkyl or phenyl; and wherein NRa2 may alternatively represent an optionally substituted saturated or unsaturated nitrogen heterocycle comprising, in combination with its optional substituents, 1 to 12, more specifically 1 to 10, and in particular 1 to 8, carbon atoms; 0 to 6, more specifically 0 to 4, and in particular 0 to 3 oxygen atoms; 1 to 4, more specifically 1 to 3, and in particular 1 or 2 nitrogen atoms; 0 to 3, more specifically 0 to 2, and in particular 0 or 1 sulfur atoms; and 0 to 5, more specifically 0 to 4, and in particular 0 to 3 halogen atoms. The compound according to embodiment 56, wherein R4represents COOH or a salt thereof, -COORb, -C(O)-Rb, C(0)-NH2, -C(O)NHRb, -C(O)NRb2, wherein Rb represents a moiety comprising 1 to 6 carbon atoms, and optionally one or more of: 1 to 3 oxygen atoms, 1 or 2 nitrogen atoms, 1 or 2 sulfur atoms, and 1 to 3 halogen atoms, more specifically a moiety comprising 1 to 4 carbon atoms, and optionally one or more of: 1 to 3 oxygen atoms, 1 or 2 nitrogen atoms, and 1 to 3 halogen atoms. The compound according to embodiment 57, wherein Rb represents -Ci-C4-alkyl, more specifically methyl or ethyl and in particular methyl. The compound according to any one of embodiments 11 to 58, wherein the compound of formula (IV) is a compound of formula (IXa) or (IXb), or a tautomer and / or a pharmaceutically acceptable salt thereof; wherein R1, R2, R3, and R4are defined as indicated in any of the preceding embodiments; wherein each of R5, independently from each other, represents hydrogen or a Ci-Ce moiety which optionally further comprises 1-3 oxygen atoms, 1-3 nitrogen atoms, and 1-2 sulfur atoms; wherein for formula (IXa) Ls is defined as L2 and in any of the preceding embodiments and As represents the moiety of formula (IVa) or the moiety of formula (IVb); and wherein for formula (IXb) Ls is defined as L4 in any of the preceding embodiments and As represents the moiety of formula (IVa) or the moiety of formula (IVb). The compound according to embodiment 59, wherein Ls represents a saturated Ci-Ce-alkyl moiety which is optionally substituted with a group selected from: -O-, -C(O)-, -CO2-, -O- C(O)-, -NH-, -N(Ci-C4-alkyl)-, -NH-C(O)-, -C(O)-NH-, -(CH2)I-4-> -(CH2)I-4-O-, -O- (CH2)I-4-, -S(O)-, -SO2-, or combinations thereof. The compound according to embodiment 59 or 60, wherein each of R5, independently from each other, represents hydrogen or a C1-C4 alkyl. The compound according to any one of embodiments 11 to 58, wherein the compound of formula (IV) is a compound of formula (Xa) or (Xb), or a tautomer and / or a pharmaceutically acceptable salt thereof; wherein R1, R2, R3, R4, and R5are defined as indicated in any of the preceding embodiments; wherein the dashed line represents a bond or is absent; wherein n is an integer between 0 and 6, more specifically between 0 and 4, and in particular between 0 and 3; and m is an integer between 0 and 8, more specifically between 0 and 4, and in particular between 0 and 3; wherein Ls is defined as L4in any of the preceding embodiments: and wherein As represents the moiety of formula (IVa) or the moiety of formula (IVb). The compound according to embodiment 62 wherein

[0351] R2represents H or C1-C4 alkyl,

[0352] R3represents H or C1-C4 alkyl,

[0353] R4represents -COOH or a salt thereof, -COORa -C(O)-Ra, C(O)-NH2, -C(O)NHRa, - C(O)NRa2, wherein Ra is as defined in any preceding embodiment. The compound according to any one of embodiments 11 to 63, wherein at least one of Ai, A2, A3, A4, A5, As and A7 represents the active ingredient or the precursor of the active ingredient, wherein the active ingredient is the moisturizer, the skin moisturizer or the hair moisturizer, respectively. The compound according to embodiment 64, wherein the active ingredient comprises a plurality of hydrogen bonding groups selected from the group consisting of hydroxyl groups, ether groups, carboxylic acids, amines and amides; and their salts. he compound according to embodiment 65, wherein the plurality of hydrogen bonding groups comprises three or more, more specifically 4 or more, and in particular 6 or more hydrogen bonding groups. The compound according to embodiment 64 or embodiment 65, wherein the ratio of C- atoms to the sum of hydrogen bonding groups comprised in the active ingredient is between about 4: 1 to 1 : 1, more specifically between about 3: 1 to about 1 : 1 and in particular between about 2: 1 to about 1:1. The compound according to any one of embodiments 64 to 67, wherein the active ingredient has a molecular weight of at least 60 g / mol, more specifically at least 90 g / mol, and in particular at least 120 g / mol. The compound according to any one of embodiments 64 to 68, wherein the ratio of C- atoms to the sum of heteroatoms comprised in the active ingredient is between about 4: 1 to 1:2, more specifically between about 3:1 to about 1:1.5, and in particular between about 2: 1 to about 1: 1, wherein the heteroatoms are selected from nitrogen and oxygen. The compound according to any one of embodiments 64 to 69, wherein the active ingredient comprises: a polyol, more specifically a polyol having n hydroxyl groups with n being 2 or more, 3 or more, 4 or more, 5 or more, 6 or more, 8 or more, 10 or more, 12 or more, or 16 or more; a mono- or polyvalent carboxylic acid comprising one or more hydroxyl groups, more specifically glycolic acid, lactic acid, malic acid, tartaric acid or citric acid; a sugar, more specifically a triose, a tetrose, a pentose a hexose, a monosaccharide, a disaccharide, a trisaccharide, or an oligosaccharide; a sugar alcohol, more specifically a sugar alcohol comprising between 2 and 24 carbon atoms, in particular ethylene glycol, glycerol, erythritol, threitol, arabitol, xylitol, ribitol, mannitol, sorbitol, galactitol, fucitol, iditol, inositol, volemitol, isomalt, maltitol, lactitol, maltotriitol, or maltotetraitol; a sugar acid, more specifically an aldonic acid, an ulosonic acid, an uronic acid or an aldaric acid; or a salt thereof; or an ester thereof, in particular a Ci-C4-alkylester thereof; or an amide thereof; or a polysaccharide; more specifically a glycosaminoglycan, such as chondroitin sulfate, dermatan sulfate, keratan sulfate, and hyaluronic acid; and in particular hyaluronic acid; and copolymers thereof, in particular copolymers comprising polyethylene glycol; and, in particular, hyaluronic acid, more specifically a hyaluronic acid having a weight-average or a 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. The compound according to embodiment 70, wherein the active ingredient has a molecular weight of 60 g / mol to 2000 g / mol, more specifically 90 g / mol to 1600 g / mol, and in particular 120 g / mol to 1200 g / mol. The compound according to embodiment 64, wherein the active ingredient is an emollient or an occlusive. The compound according to embodiment 72, wherein the active ingredient comprises: a Cio-Ceo moiety, more specifically a Cis-Ceo moiety and in particular a C20-C60 moiety; or an oligo- or polysiloxane, in particular a poly(di-Ci-C4-alkyl)siloxane. The compound according to embodiment 72, wherein the active ingredient is the Ci-Cso 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. The compound according to embodiment 72 or embodiment 73, wherein the active ingredient has more than 30 carbon atoms. The compound according to any one of embodiments 72 to 75, wherein the active ingredient comprises a saturated or unsaturated Cio-Cso aliphatic moiety, more specifically a C15-C60 aliphatic moiety, and in particular a C20-C60 aliphatic moiety. The compound according to any one of embodiments 72 to 76, wherein the ratio of C- atoms to the sum of heteroatoms comprised in the active ingredient is between about 60:1 to 5: 1, more specifically between about 50: 1 to about 10: 1, and in particular between about 40: 1 to about 20: 1, wherein the heteroatoms are selected from nitrogen and oxygen. The compound according to any one of embodiments 72 to 77, wherein the Ci-Cso moiety is a sphingosine or a derivative thereof, in particular a ceramide or a sphingomyelin. The compound according to any one of embodiments 64 to 78, wherein one of Ai, A2, A3, and A4 represents the moisturizer, the skin moisturizer or the hair moisturizer, respectively. The compound according to any one of embodiments 64 to 79, wherein one of A2, A3 and A4 represents the precursor of the moisturizer, the skin moisturizer or the hair moisturizer, respectively. The compound according to any one of embodiments 11 to 63, wherein at least one of Ai, A2, A3, 4, A5, As and A7 represents the active ingredient or the precursor of the active ingredient, and wherein the active ingredient is the pesticide. The compound according to embodiment 81, wherein the pesticide is an insect repellent. The compound according to embodiment 81, wherein the pesticide is an insecticide. The compound according to embodiment 82 or 83, wherein the insect repellent or insecticide acts against an ectoparasite and / or a hematophagous insect, in particular a hematophagous insect selected from the group consisting of mosquitoes, ticks, mites, gnats, fleas, chiggers, leeches and bugs. The compound according to embodiment 82 or embodiment 84, wherein the pesticide is an insect repellent which is selected from isoprenoids, tertiary amides, and phenylpropanoids. The compound according to embodiment 85, wherein the insect repellent is an isoprenoid, more specifically a monoterpenoid, a diterpenoid or a triperpenoid, and in particular a terpineol or derivative thereof, a monoterpenoid aldehyde or a derivative thereof, a limonoid or a derivative thereof; or a pyrethrin or a derivative thereof. The compound according to embodiment 86, wherein the isoprenoid is selected from citronellal, hydroxy citronellal, citronellol, citral A, citral B, or a derivative thereof; a necrodane, in particular a-necrodol, or a derivative thereof; a limonoid, in particular azadirachtine, or a derivative thereof; or a pyrethrin, in particular ajasmolin, a cinerin, or a derivative thereof. The compound according to embodiment 86, wherein at least one of Ai, A2, A3, A4, As, As and A7 represents a moiety of formula (Xia) or formula (Xlb), The compound according to embodiment 86, wherein the insect repellent is a phenylpropanoid, in particular eugenol or a derivative thereof. The compound according to embodiment 86, wherein the insect repellent is comprising a tertiary amide. The compound according to embodiment 90, wherein the tertiary amide is selected from picaridine, an N,N-di(Ci-C6-alkyl)-toluamide, in particular p-menthane-3,8-diol; and derivatives thereof. The compound according to embodiment 90, wherein the insect repellent is selected from one of the following compounds and moieties / derivatives thereof: diethyl phenyl acetamide, N-butylacetanilide, picaridine, N-(2-methylpiperidin-l-yl)cyclohex-3-ene-l- carboxamide, and l-[3-cyclo-hexen-l-ylcarbonyl]-2-methylpiperidine or l-[3-cyclohexen- 1-ylcarbonyl] piperidine. The compound according to embodiment 90, wherein at least one of Ai, A2, A3, A4, As, As and A7 represents a moiety of formula (XII),

[0354] (XII). The compound according to embodiment 90, wherein at least one of Ai, A2, A3, A4, As, As and A7 represents a moiety of formula (XIII),

[0355] The compound according to embodiment 81, wherein the pesticide is a topical insecticide, in particular a topical insecticide which is selected from permethrine; cypermethrin; deltamethrin; ivermectin; amidines, in particular amitraz; bendiocarb; malathion; carbaryl; diazinon; DDT; fenthion; fipronil; imidacloprid; nitenpyram; and propoxur. The compound according to any one of embodiments 81 to 95, wherein one of Ai, A2, A3, and A4 represents the pesticide, in particular the insect repellent. The compound according to any one of embodiments 81 to 86, wherein one of Ai, A2, A3, and A4 represents the precursor of the pesticide, in particular the insect repellent. The compound according to any one of embodiments 11 to 63, wherein at least one of Ai, A2, A3, A4, A5, As and A7 represents the active ingredient which is the color-imparting moiety or the UVA and / or UVB-absorbing moiety. The compound according to embodiment 98, wherein the color-imparting moiety has at least one absorption peak within the wavelength range of 380 to 790 nm, more specifically at least one absorption peak within the wavelength range of 380 to 790 nm having an absorbance value of more than 0.5 when measured at a concentration of 2 mM. The compound according to embodiment 98, wherein the UVA- and / or UVB-absorbing moiety has at least one absorption peak within the wavelength range of 280 to 379 nm, more specifically at least one absorption peak within the wavelength range of 280 to 379 nm having an absorbance value of more than 0.5 when measured at a concentration of 2 mM. The compound according to any one of embodiments 11 to 63 and 98 or 99, wherein at least one of Ai, A2, A3, A4, As, As and A7 represents the color-imparting moiety, and wherein said moiety is: a) an optionally substituted (hetero)aromatic moiety comprising, in combination with its optional substituents, 4 to 40 carbon atoms, or b) an optionally substituted conjugated moiety comprising, in combination with its optional substituents, 6 to 40 carbon atoms and at least 3 conjugated C-C double bonds. The compound according to any one of embodiments 11 to 63 and 98 to 101, wherein at least one of Ai, A2, A3, A4, As, As and A7 represents a UVA and / or UVB absorbing moiety, wherein said moiety is: a) an optionally substituted (hetero)aromatic moiety comprising, in combination with its optional substituents, 4 to 36 carbon atoms, or b) an optionally substituted conjugated moiety comprising, in combination with its optional substituents, 4 to 36 carbon atoms, and at least 2 conjugated C-C double bonds. The compound according to any one of embodiments 11 to 63 and 98 to 102, wherein at least one of Ai, A2, A3, A4, As, As and A7 represents a chromophore (dye moiety) selected from an azo group; a diazo group; a diphenylamine group; a nitroarylamine group; an azine group; an oxazine group; an acridine group; an indoline group; a sulfur dye group, in particular a thiazine group, a thiazole group, a thiazone group, a thianthrene group, or a phenothiazonethioanthrone group; a quinoid or quinone group; an anthraquinoid or anthraquinone group; a xanthene group; a naphthostyryl group; a diaryl methyl or triarylmethyl group; a benzodifuranone-based group; a formazan group; a phthalocyanine group; or a metal complex. The compound according to any one of embodiments 11 to 103, wherein at least one of Ai, A2, A3, A4, As, As and A7 represents a UVA- and / or UVB-absorbing moiety which is being selected / derived from: a benzophenone group, a benzotriazole group, a benzone group, salicylic acid or a salicylic acid derivative, a benzocaine group, an esculin or an esculin derivative, a ferulic acid or a ferulic acid derivative, octinoxate or an octinoxate derivative, or octocrylene or an octocrylene derivative. The compound according to any one of embodiments 11 to 104, wherein at least one of Ai, A2, As, A4, As, As and A7 represents a moiety which is selected from the following group of moieties:

[0356] The compound according to any preceding embodiment, wherein the compound is a compound of formula (XIV),

[0357] (XIV), or a tautomer and / or a pharmaceutically acceptable salt thereof, wherein R1, Ai, A3, A4, As, A7, Lg and L7 are defined as in any preceding embodiment; X represents O or S, and in particular O;

[0358] Lxis absent or represents -O-, -NH-, or an optionally substituted hydrocarbon moiety comprising, in combination with its optional substituents, 1 to 12 carbon atoms, more specifically 1 to 10 carbon atoms, and in particular 1 to 8 carbon atoms, 0 to 8, more specifically 0 to 6, and in particular 0 to 4 oxygen atoms; 0 to 6, more specifically 0 to 4, and in particular 0 to 3 nitrogen atoms; 0 to 6, more specifically 0 to 4, and in particular 0 to 3 sulfur atoms; and 0 to 8, more specifically 0 to 6, and in particular 0 to 5 halogen atoms; wherein said hydrocarbon moiety is attached to the (C=X)-moiety via a carbon atom, an oxygen atom, a nitrogen atom, or a sulfide atom; wherein one moiety selected from L3 and L4 represents an optionally substituted (hetero)aromatic C3-C12 moiety, more specifically an optionally substituted (hetero)aromatic C4-C12 moiety comprising, in combination with its optional substituents, 4 to 16, more specifically 4 to 12, and in particular 4 to 10, carbon atoms; 0 to 6, more specifically 0 to 4, and in particular 0 to 3 oxygen atoms; 0 to 6, more specifically 0 to 4, and in particular 0 to 3 nitrogen atoms; 0 to 6, more specifically 0 to 4, and in particular 0 to 3 sulfur atoms; and 0 to 6, more specifically 0 to 4, and in particular 0 to 3 halogen atoms; and wherein the other moiety amongst L3 and L4 represents a C1-C30 moiety, more specifically a C1-C16 moiety selected from a saturated or unsaturated, acylic (hetero)alkyl comprising 1 to 16, more specifically 1 to 12, and in particular 1 to 8, carbon atoms; 0 to 6, more specifically 0 to 4, and in particular 0 to 3 oxygen atoms; 0 to 6, more specifically 0 to 4, and in particular 0 to 3 nitrogen atoms; 0 to 6, more specifically 0 to 4, and in particular 0 to 3 sulfur atoms; and 0 to 6, more specifically 0 to 4, and in particular 0 to 3 halogen atoms. The compound according to embodiment 106, wherein L3 represents the optionally substituted (hetero)aromatic C3-C12 moiety, more specifically an optionally substituted (hetero)aromatic C4-C12 moiety comprising, in combination with its optional substituents, 4 to 16, more specifically 4 to 12, and in particular 4 to 10, carbon atoms; 0 to 6, more specifically 0 to 4, and in particular 0 to 3 oxygen atoms; 0 to 6, more specifically 0 to 4, and in particular 0 to 3 nitrogen atoms; 0 to 6, more specifically 0 to 4, and in particular 0 to 3 sulfur atoms; and 0 to 6, more specifically 0 to 4, and in particular 0 to 3 halogen atoms. The compound according to embodiment 107, wherein L3 represents an optionally substituted phenyl moiety comprising, in combination with its optional substituents, 6 to 12, more specifically 6 to 10, and in particular 6 to 8, carbon atoms; 0 to 6, more specifically 0 to 4, and in particular 0 to 3 oxygen atoms; 0 to 6, more specifically 0 to 4, and in particular 0 to 3 nitrogen atoms; 0 to 3, more specifically 0 to 2, and in particular 0 or 1 sulfur atoms; and 0 to 6, more specifically 0 to 4, and in particular 0 to 3 halogen atoms. The compound according to embodiment 108, wherein the phenyl moiety is optionally substituted with -OH; -O-Ci-C4-alkyl; -N(Ci-C4-alkyl)2; one or more halogen atoms, each independently from each other selected from Cl, Br, and F; -NO2; and -CF3. The compound according to any one of embodiments 106 to 109, wherein L4 represents an optionally substituted aliphatic moiety comprising, in combination with its optional substituents, 1 to 12, more specifically 1 to 10, and in particular 1 to 8, carbon atoms; 0 to 6, more specifically 0 to 4, and in particular 0 to 3 oxygen atoms; 0 to 6, more specifically 0 to 4, and in particular 0 to 3 nitrogen atoms; 0 to 3, more specifically 0 to 2, and in particular 0 or 1 sulfur atoms; and 0 to 6, more specifically 0 to 4, and in particular 0 to 3 halogen atoms. The compound according to embodiment 110, wherein the aliphatic moiety is a Ci-Ce- alkyl, more specifically a linear or branched Ci-C4-alkyl; and in particular a linear C1-C4- alkyl. The compound according to any one of embodiments 106 to 111, wherein Ai represents the C1-C30 moiety, more specifically a C1-C16 moiety selected from a saturated or unsaturated, cyclic or acylic (hetero)alkyl comprising 1 to 16, more specifically 1 to 12, and in particular 1 to 8, carbon atoms; 0 to 6, more specifically 0 to 4, and in particular 0 to 3 oxygen atoms; 0 to 6, more specifically 0 to 4, and in particular 0 to 3 nitrogen atoms; 0 to 6, more specifically 0 to 4, and in particular 0 to 3 sulfur atoms; and 0 to 6, more specifically 0 to 4, and in particular 0 to 3 halogen atoms. The compound according to any one of embodiments 106 to 112, wherein Lx-Ai represents a C1-C16 moiety selected from a carboxylic acid or a salt thereof, a carboxylic acid ester; a ketone; more specifically a moiety selected from: -COOH or a salt thereof; - COORa, -C(O)-Ra, -C(O)-NH2, -C(O)NHRa, -C(O)NRa2, wherein Ra represents a moiety comprising 1 to 10 carbon atoms, and optionally one or more of: 1 to 6 oxygen atoms, 1 to 4 nitrogen atoms, 1 to 3 sulfur atoms, and 1 to 5 halogen atoms, more specifically a moiety comprising 1 to 6 carbon atoms, and optionally one or more of: 1 to 4 oxygen atoms, 1 to 3 nitrogen atoms, 1 or 2 sulfur atoms, and 1 to 3 halogen atoms, and in particular Ci-Ce-alkyl or phenyl; and wherein NRa2 may alternatively represent an optionally substituted saturated or unsaturated nitrogen heterocycle comprising, in combination with its optional substituents, 1 to 12, more specifically 1 to 10, and in particular 1 to 8, carbon atoms; 0 to 6, more specifically 0 to 4, and in particular 0 to 3 oxygen atoms; 1 to 4, more specifically 1 to 3, and in particular 1 or 2 nitrogen atoms; 0 to 3, more specifically 0 to 2, and in particular 0 or 1 sulfur atoms; and 0 to 5, more specifically 0 to 4, and in particular 0 to 3 halogen atoms. Use of a compound of formula (la) or (lb),

[0359] (la) (lb) or a tautomer and / or a pharmaceutically acceptable salt thereof, for covalently binding an insect repellent to skin and / or hair; wherein the compound of formula (la) or (lb) comprises a 1,5-dicarbonyl moiety, or a tautomer thereof, and covalently binds to the skin and / or the hair after being topically applied to skin and / or hair by the reaction of its 1,5-dicarbonyl moiety, or of a tautomer thereof, with amino groups present on the skin and / or the hair; wherein L represents a group selected from — (CH2)-O-, — C(=O)- O-, or — CH(OR)(OR') and wherein the em-dash (“ — “) represents the bond attaching L to the remainder of the insect repellent; wherein R represents hydrogen or a first hydrocarbon moiety; wherein R' represents a second hydrocarbon moiety; wherein R' is further attached to DC, or wherein CH(OR)(OR') represents a cyclic acetal moiety which is further attached to DC; and wherein DC represents the remainder of the compound and comprises the 1,5-dicarbonyl moiety, or a tautomer thereof. The use according to embodiment 106, wherein the compound of formula (I) is a compound of any one of embodiments 2 to 114. 116. A topical composition comprising the compound of formula (la) or (lb) as defined in any one of embodiments 1 to 114.

[0360] 117. A method of preparing a topical composition, wherein the method comprises combining a compound of formula (la) or (lb) as defined in any one of embodiments 1 to 114 with an excipient suitable for topical administration.

[0361] 118. The use of the compound, the compound, the composition comprising the compound, and the method for preparing the composition according to an preceding embodiment, wherein the compound is a compound of formula (I) in which -L-DC does not represent a polymeric moiety, or does not represent a polymeric moiety having a molecular weight of 500 g / mol or more than 500 g / mol.

[0362] 119. The use of the compound, the compound, the composition comprising the compound, and the method for preparing the composition according to an preceding embodiment, wherein the compound is a compound of formula (I) in which -L-DC does not comprise (an) isocyanate group(s).

Claims

CLAIMS1. A compound of formula (la) or (lb),or a tautomer and / or a pharmaceutically acceptable salt thereof, for covalently binding an insect repellent to skin and / or hair; wherein the compound of formula (la) or (lb) comprises a 1,5-dicarbonyl moiety, or a tautomer thereof, and is capable of covalently binding to the skin and / or the hair after being topically applied to skin and / or hair by the reaction of its 1,5-dicarbonyl moiety, or of the tautomer thereof, with amino groups present on the skin and / or the hair; wherein L represents a group selected from — (CH2)-0-, — C(=O)-O-, or — CH(OR)(OR') and wherein the em-dash (“ — “) represents the bond attaching L to the remainder of the insect repellent; wherein R represents hydrogen or a first hydrocarbon moiety; wherein R' represents a second hydrocarbon moiety; wherein R' is further attached to DC, or wherein CH(OR)(OR') represents a cyclic acetal moiety which is further attached to DC; and wherein DC represents the remainder of the compound and comprises the 1,5-dicarbonyl moiety, or the tautomer thereof.

2. The compound according to claim 1, wherein the compound of formula (la) or (lb), in the form as it is bound to the skin and / or hair, is cleavable to release the insect repellent; and / or wherein the compound of formula (la) or (lb), in the form as it is bound to the skin and / or hair, is hydrolysable to release the insect repellent in the presence of water at a pH of between about 5 to about 6; and / or wherein the compound of formula (la) or (lb), in the form as it is bound to the skin and / or hair, is enzymatically cleavable by enzymesnatively present on mammalian, and in particular human, skin and / or hair, to release the insect repellent; and in particular cleavable to release the insect repellent by esterase enzymes.

3. The compound according claim 1 or claim 2, wherein the compound of formula (la) or (lb) is a compound of formula (la) and wherein the compound is cleavable to any one of the compounds of formulae (Ila), (lib) and (lie):wherein the compound of formula (la) or (lb) is a compound of formula (lb) and wherein the compound is cleavable to any one of the compounds of formulae (Illa), (Illb), (IIIc) and (Illd),(lllc) (Hid) wherein Mi represents an optionally substituted hydrocarbon moiety comprising, in combination with its optional substituents, 1 to 7, more specifically 1 to 4, and in particular 1 or 2, carbon atoms; 0 to 3, more specifically 0 to 2, and in particular 0 or 1oxygen atoms; 0 or 1 nitrogen atoms; 0 or 1 sulfur atoms; and 0 to 3, more specifically 0 to 2, and / or in particular 0 or 1 halogen atoms.

4. The compound according to any preceding claim, wherein the compound of formula (la) or (lb) is a compound which comprises a cyclic enolether and which is represented by formula (IV),(IV), or a tautomer and / or a pharmaceutically acceptable salt thereof, for covalently binding the insect repellent and optionally one or more active ingredients to skin and / or hair; wherein the one or more active ingredients are independently from each other selected from a moisturizer, a pesticide, a UVA- and / or UVB-absorbing moiety and a colorimparting moiety; wherein the compound of formula (IV) is capable of covalently binding to the skin and / or the hair after being topically applied to skin and / or hair by the reaction of its cyclic enolether with amino groups present on the skin and / or the hair; wherein the compound of formula (IV) comprises the optional one or more active ingredients, independently from each other, a) as the active ingredient, or b) as a precursor of the active ingredient, wherein the compound of formula (IV) is cleavable to release the active ingredient from the precursor after the application of the compound of formula (IV) to the skin and / or the hair; wherein Li, L2, L3, L4, Ls, Le and L7 represent, independently from each other, a linker group or are absent;wherein one or more of Ai, A2, A3, A4, As, As and A7 represent:- the moiety (IVa) or the moiety (IVb),(IVa) (IVb) wherein the broken bond indicates the attachment to the corresponding linker group Li, L2, L3, L4, Ls, Lg and L7, or if the respective linker group is absent, to the corresponding ring atom of the cyclic enolether; and, if present, the one or more active ingredients and precursors thereof; wherein each of Ai, A2, A3, A4, As, As and A7 not representing the moiety (IVa), the moiety (IVb) or one of the optional one or more active ingredients and precursors thereof is defined as follows:Ai represents hydrogen, a C1-C30 moiety, hydroxyl, amino, or a halogen;A2 and A3 are, independently from each other, defined as indicated for Ai or L2-A2 and L3-A3 jointly represent oxo;A4 and As are, independently from each other, defined as indicated for Ai;As and A7 represent, independently from each other, hydrogen or a C1-C30 moiety; wherein R1represents hydrogen or a protective group hydrolysable under physiological conditions after application of the compound of formula (IV) to the skin and / or the hair; and wherein the dashed line represents a bond or is absent and wherein, in case dashed line represents a bond, -L5-A5 and -O-R1are absent.

5. The compound according to claim 4, wherein the compound of formula (IV) comprises at least one of the optional one or more active ingredients and precursors thereof and wherein the compound of formula (IV) 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 (IV) and wherein the functional group comprises a carbon atom, an oxygen atom, a nitrogen atom, a sulfur atom, a phosphorus atom, aboron 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.

6. The compound according to claim 4 or claim 5, wherein the compound of formula (IV) is a compound of formula (V),or a tautomer and / or a pharmaceutically acceptable salt thereof; wherein R1, Ai, A2, A3, A4, As, A7, Li, L2, L3, L4, Lg, and L7 are defined as in claim 5; and in particular wherein L1-A1 and L4-A4 do not represent hydrogen.

7. The compound according to any one of claims 4 to 6, wherein Ai represents the moiety of formula (IVa) or the moiety of formula (IVb) and A2, A3 and A4 represent independently from each other hydrogen or the C1-C30 moiety; or wherein Ai represents the C1-C30 moiety and A2, A3 or A4 represents the moiety of formula (IVa) or the moiety of formula (IVb); or wherein A2 represents the moiety of formula (IVa) or the moiety of formula (IVb), wherein A3 represents the C1-C30 moiety, and wherein A4 represents the C1-C30 moiety; or wherein A4 represents the moiety of formula (IVa) or the moiety of formula (IVb), and wherein:A2 represents hydrogen and A3 represents hydrogen, orA2 represents the C1-C30 moiety and A3 represents hydrogen, orA2 represents hydrogen and A3 represents the C1-C30 moiety, orA2 represents the C1-C30 moiety and A3 represents the C1-C30 moiety.

8. The compound according to any one of claims 4 to 7, wherein Li, L2, L3, L4, Ls Lg and L7 independently from each other are absent or represent an optionally substituted hydrocarbon moiety comprising, in combination with its optional substituents, 1 to 12, more specifically 1 to 10 carbon atoms, and in particular 1 to 8 carbon atoms.

9. The compound according to any one of claims 4 to 8, wherein:Li and Lg are present and form a ring; and / orLi and L2 are present and form a ring; and / orL2 and L4 are present and form a ring; and / or L4 and L7 are present and form a ring; and / or L4 and R1are present and form a ring.

10. The compound according to any one of claims 4 to 9, wherein each occurrence of the Ci- C30 moiety independently from each other comprises 1 to 30, more specifically 1 to 16, and in particular 1 to 12 carbon atoms; 0 to 12, more specifically 0 to 8, and in particular 0 to 6 oxygen atoms; 0 to 8, more specifically 0 to 6, and in particular 0 to 4 nitrogen atoms; 0 to 6, more specifically 0 to 4, and in particular 0 to 3 sulfur atoms; 0 to 6, more specifically 0 to 4, and in particular 0 to 3 phosphorus atoms, and 0 to 10, more specifically 0 to 8, and in particular 0 to 6 halogen atoms; and / or wherein the C1-C30 moiety is bound a) to the respective Li, L2, L3, L4, L5, Lg, L7 and Ls, if it is present, via a carbon atom, an oxygen atom, a nitrogen atom or a sulfur atom, or b) if the respective Li, L2, L3, L4, Ls, Lg, L7 and Ls, is absent, via a carbon atom, an oxygen atom, a nitrogen atom or a sulfur atom to the carbon atom of ring to which the C1-C30 moiety is attached.

11. The compound according to any one of claims 4 to 10, wherein the compound of formula (IV) is a compound of formula (VI),or a tautomer and / or a pharmaceutically acceptable salt thereof; wherein R1, Ai, A2, A3, A4, As, A7, L2, L3, L4, Lg and L7 are defined as in any preceding claim; wherein X represents O or S, and in particular O; and wherein Lxis absent or represents -O-, -NH-, or an optionally substituted hydrocarbon moiety comprising, in combination with its optional substituents, 1 to 12 carbon atoms, more specifically 1 to 10 carbon atoms, and in particular 1 to 8 carbon atoms, 0 to 8, more specifically 0 to 6, and in particular 0 to 4 oxygen atoms; 0 to 6, more specifically 0 to 4, and in particular 0 to 3 nitrogen atoms; 0 to 6, more specifically 0 to 4, and in particular 0 to 3 sulfur atoms; and 0 to 8, more specifically 0 to 6, and in particular 0 to 5 halogen atoms, and wherein the hydrocarbon moiety is attached to the (C=X)-moiety via a carbon atom, an oxygen atom, a nitrogen atom, or a sulfide atom.

12. The compound according to claim 11, wherein Lx-Ai represents a Ci-Cig moiety selected from a carboxylic acid or a salt thereof, a carboxylic acid ester; a ketone; more specifically a moiety selected from:-COOH or a salt thereof;-COORa, -C(O)-Ra,-C(O)-NH2, -C(O)NHRa, -C(O)NRa2, wherein Ra represents a moiety comprising 1 to 10 carbon atoms, and optionally one or more of: 1 to 6 oxygen atoms, 1 to 4 nitrogen atoms, 1 to 3 sulfur atoms, and 1 to 5 halogen atoms, more specifically a moiety comprising 1 to 6 carbon atoms, and optionally one or more of: 1 to 4 oxygen atoms, 1 to 3 nitrogen atoms, 1 or 2 sulfur atoms, and 1 to 3 halogen atoms, and in particular Ci-Cs-alkyl or phenyl; andwherein NRa2 may alternatively represent an optionally substituted saturated or unsaturated nitrogen heterocycle comprising, in combination with its optional substituents, 1 to 12, more specifically 1 to 10, and in particular 1 to 8, carbon atoms; 0 to 6, more specifically 0 to 4, and in particular 0 to 3 oxygen atoms; 1 to 4, more specifically 1 to 3, and in particular 1 or 2 nitrogen atoms; 0 to 3, more specifically 0 to 2, and in particular 0 or 1 sulfur atoms; and 0 to 5, more specifically 0 to 4, and in particular 0 to 3 halogen atoms.

13. The compound according to any one of claims 4 to 12, wherein R1represents hydrogen, Ci-6 acyl, a silyl group, or Ci-6 alkyl; and in particular hydrogen.

14. The compound according to any one of claims 4 to 13, wherein the compound of formula (IV) is a compound of formula (Xa) or (Xb),or a tautomer and / or a pharmaceutically acceptable salt thereof; wherein R1is defined as indicated in any of the preceding claims; wherein R2represents hydrogen or a Ci-Cie moiety; more specifically hydrogen or a Ci- Ci6 moiety comprising 1 to 16, and in particular 1 to 12, carbon atoms; 0 to 12, more specifically 0 to 8, and in particular 0 to 6 oxygen atoms; 0 to 8, more specifically 0 to 6, and in particular 0 to 4 nitrogen atoms; 0 to 6, more specifically 0 to 4, and in particular 0 to 3 sulfur atoms; and 0 to 10, more specifically 0 to 8, and in particular 0 to 6 halogen atoms; and in particular hydrogen or a saturated or unsaturated, cyclic or acylic (hetero)alkyl or a (hetero)aryl moiety comprising 1 to 10 carbon atoms, and optionally one or more of: 1 to 6 oxygen atoms, 1 to 4 nitrogen atoms, 1 to 3 sulfur atoms, and 1 to 5 halogen atoms; wherein R3represents hydrogen or a C1-C16 moiety; more specifically hydrogen or a Ci- Ci6 moiety comprising 1 to 16, and in particular 1 to 12, carbon atoms; 0 to 12, more specifically 0 to 8, and in particular 0 to 6 oxygen atoms; 0 to 8, more specifically 0 to 6,and in particular 0 to 4 nitrogen atoms; 0 to 6, more specifically 0 to 4, and in particular 0 to 3 sulfur atoms; and 0 to 10, more specifically 0 to 8, and in particular 0 to 6 halogen atoms; and in particular hydrogen or a saturated or unsaturated, cyclic or acylic (hetero)alkyl or a (hetero)aryl moiety comprising 1 to 10 carbon atoms, and optionally one or more of: 1 to 6 oxygen atoms, 1 to 4 nitrogen atoms, 1 to 3 sulfur atoms, and 1 to 5 halogen atoms; wherein R4represents hydrogen or a Ci-Cie 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 10 carbon atoms, and optionally one or more of: 1 to 6 oxygen atoms, 1 to 4 nitrogen atoms, 1 to 3 sulfur atoms, and 1 to 5 halogen atoms, more specifically a moiety comprising 1 to 6 carbon atoms, and optionally one or more of: 1 to 4 oxygen atoms, 1 to 3 nitrogen atoms, 1 or 2 sulfur atoms, and 1 to 3 halogen atoms, and in particular Ci-Ce-alkyl or phenyl; and wherein NRa2may alternatively represent an optionally substituted saturated or unsaturated nitrogen heterocycle comprising, in combination with its optional substituents, 1 to 12, more specifically 1 to 10, and in particular 1 to 8, carbon atoms; 0 to 6, more specifically 0 to 4, and in particular 0 to 3 oxygen atoms; 1 to 4, more specifically 1 to 3, and in particular 1 or 2 nitrogen atoms; 0 to 3, more specifically 0 to 2, and in particular 0 or 1 sulfur atoms; and 0 to 5, more specifically 0 to 4, and in particular 0 to 3 halogen atoms; wherein each of R5, independently from each other, represents hydrogen or a Ci-Ce moiety which optionally further comprises 1-3 oxygen atoms, 1-3 nitrogen atoms, and 1-2 sulfur atoms; wherein the dashed line represents a bond or is absent; wherein n is an integer between 0 and 6, more specifically between 0 and 4, and in particular between 0 and 3; wherein m is an integer between 0 and 8, more specifically between 0 and 4, and in particular between 0 and 3; and wherein Ls and As are defined as L4 and A4 in any of the preceding claims; and wherein As represents the moiety of formula (IVa) or the moiety of formula (IVb).

15. The compound according to any one of claims 4 to 14, wherein at least one of Ai, A2, A3, A4, A5, As and A7 represents the active ingredient which is the UVA and / or UVB-absorbing moiety, in particular wherein the UVA- and / or UVB-absorbing moiety has at least one absorption peak within the wavelength range of 280 to 379 nm, more specifically at least one absorption peak within the wavelength range of 280 to 379 nm having an absorbance value of more than 0.5 when measured at a concentration of 2 mM.

16. The compound according to any one of claims 1 to 14, wherein -L-DC does not represent a polymeric moiety, or does not represent a polymeric moiety having a molecular weight of 500 g / mol or more than 500 g / mol; and / or wherein -L-DC does not comprise (an) isocyanate group(s).

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