Compositions, Formulations and Methods for Treating Skin

Abstract

Compositions and formulations for skin treatment are provided herein.Methods for skin treatment, such as methods for preventing or treating skin conditions, disorders or diseases, are also provided herein.Methods can increase skin collagen production or the proliferation of cells that collagen deposits, can increase fibroblast proliferation, and / or can prevent or reduce wrinkle(s) or fine line(s), can increase skin firmness, or can moisturize skin.

Description

[Technical field]

[0001] cross reference This application claims the benefit of U.S. Provisional Patent Application No. 63 / 297,413, filed January 7, 2022, the entirety of which is incorporated by reference herein. [Background technology]

[0002] overview Skin conditions, disorders, or diseases (whether or not a diagnosis of the skin condition, disorder, or disease has been made) are a common problem, for example, occurring naturally or chemically promoted through the long-term use of certain chemicals (e.g., commercial or therapeutic products). Summary of the Invention [Means for solving the problem]

[0003] The present disclosure provides a method for preventing or treating a skin condition, disorder, or disease (whether or not a diagnosis of the skin condition, disorder, or disease has been made), comprising administering to a subject in need thereof a composition comprising a compound having the structure of a compound of Formula (I), (II), (III), (IV), (V), (VI), or (VII). The compound or salt thereof may be selected from those set forth in Tables 1-8, or any subset thereof.

[0004] Provided herein is a method for preventing or treating a skin condition, disorder, or disease. In some embodiments, the method comprises administering to a subject in need thereof an agonist having formula (V): [ka] [In the formula, Y 1 is O, S or NR 1 and R 1 is H, alkyl, or haloalkyl; R 2is selected from H, alkyl, haloalkyl, alkenyl, haloalkenyl, aryl, and aralkyl; R 3 is H, alkyl, haloalkyl, -(CH2) m1 -OR a1 , -(CH2) m2 -O-(CH2) m3 -OR a2 , -(CH2) m4 -NR b1 R b2 , (CH2) m5 -C(O)OR c is selected from R a1 , R a2 , R b1 , R b2 , and R c are each independently selected from H, alkyl, and haloalkyl; m1, m2, m3, m4, and m5 are each independently selected from 1, 2, 3, and 4. The method includes administering a composition comprising a compound having the structure:

[0005] In some embodiments, Y 1 is O or S. In some embodiments, Y 1 is O. In some embodiments, R a1 , R a2 , R b1 , R b2 , and R c are each independently C1-C6 alkyl, such as C1-C3 alkyl. a1 , R a2 , R b1 , R b2 , and R c are each independently C alkyl or C alkyl. In some embodiments, m1, m2, m3, and m4 are each independently 2 or 3. In some embodiments, m5 is 1. In some embodiments, R 2 is H.

[0006] In some embodiments, the compound of formula (V) or salt thereof is [ka] and any one of salts thereof.

[0007] Provided herein is a method for preventing or treating a skin condition, disorder, or disease, comprising administering to a subject in need thereof a compound represented by formula (IV): [ka] [In the formula, R 1 is selected from alkyl or heterocycloalkyl; R 1 The alkyl or heterocycloalkyl of is heterocycloalkyl, -C(O)NR x1 R x2 , alkoxy, -(C1-C3 alkylene)-C(O)OR y1 , -C(O)OR y2 , and -OR z and optionally substituted with one or more substituents independently selected from R x1 , R x2 , R y1 , R y2 , and R z are each independently selected from H, alkyl, and haloalkyl; R A is H or alkyl, X is -O-, -S-, or -NR B - and R B is H, alkyl, or haloalkyl; R 2 and R 3 are each independently selected from H, straight chain C1-C6 alkyl, branched chain C1-C6 alkyl, or R 2 and R 3 together with the atom to which they are attached form a C4-C6 cycloalkyl or aryl, the cycloalkyl or aryl being optionally substituted with one or more substituents independently selected from halogen, alkyl, and haloalkyl; Dotted lines indicate the presence of single or double bonds.] or a salt thereof.

[0008] In some embodiments, the compound of Formula (IV) has the structural formula: [ka] has.

[0009] In some embodiments, the compound of Formula (IV) has the structural formula: [ka] has.

[0010] In some embodiments, the compound of Formula (IV) has the structural formula: [ka] has.

[0011] In some embodiments, the compound of Formula (IV) has the structural formula: [ka] has.

[0012] In some embodiments, R 2 and R 3 are each independently selected from C1 to C6 alkyl.

[0013] In some embodiments, R 2 and R 3 together with the atom to which they are attached form a C4-C6 cycloalkyl, optionally substituted with one or more substituents independently selected from halogen, alkyl, and haloalkyl.

[0014] In some embodiments, R 2 and R 3together with the atom to which they are attached form a cyclohexyl optionally substituted with one or more substituents independently selected from halogen, alkyl, and haloalkyl.

[0015] In some embodiments, R 2 and R 3 are optionally substituted, together with the atoms to which they are attached, with one or more substituents independently selected from halogen, alkyl, and haloalkyl. 5~8 Form an aryl.

[0016] In some embodiments, R 2 and R 3 together with the atom to which they are attached form a phenyl that is optionally substituted with one or more substituents independently selected from halogen, alkyl, and haloalkyl.

[0017] In some embodiments, R A is H.

[0018] In some embodiments, X is -O-. In some embodiments, X is -NR B - and R if necessary B is H.

[0019] In some embodiments, R 1 is -(CH2) a C(O)OH, -(CH2) a OCH3, -(CH2) a CH(OH)CH3, [ka] and a is 0, 1, 2, or 3.

[0020] In some embodiments, R 1 is -CH2C(O)OH, -(CH2)2OCH3, -CH2CH(OH)CH3, [ka] is selected from.

[0021] In some embodiments, R x1 and R x2 are each independently C1 to C6 alkyl.

[0022] In some embodiments, R x1 and R x2 are each independently C1 to C3 alkyl.

[0023] In some embodiments, R y1 is H.

[0024] In some embodiments, R y2 is H.

[0025] In some embodiments, R z is H.

[0026] In some embodiments, the compound of formula (IV) or salt thereof is [ka] and any one of salts thereof.

[0027] Provided herein is a method for preventing or treating a skin condition, disorder, or disease, comprising administering to a subject in need thereof a compound represented by formula (VII): [ka] [In the formula, A is selected from O, NH, and S; R 1 is hydrogen, C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 2~10 Alkynyl, C 3~12 selected from a carbocycle, and a 3- to 12-membered heterocycle; R2 is selected from 6- to 10-membered heterocycles, the 6- to 10-membered heterocycles being selected from halogen, C 1~6 Alkyl, C 2~6 Alkenyl, and C 2~6 Alkynyl, -OR 11 , -SR 11 , -NO2, =O, =NH, -CN, -C(O)R 11 , -C(O)OR 11 , -OC(O)R 11 , -OC(O)N(R 11 )2, -NR 11 S(O)2R 11 , -C(O)N(R 11 )2, -N(R 11 )C(O)R 11 , -N(R 11 )C(O)N(R 11 )2, -N(R 11 )C(O)OR 11 , -S(O)2(R 11 ), -S(O)2N(R 11 )2, C 1~10 Alkyl, C3-C 12 is optionally substituted with one or more substituents independently selected from a carbocycle and a 5- to 12-membered heterocycle; n is selected from 1, 2, 3, 4, 5, and 6; Each R 11 is hydrogen, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, and C 3~12 carbocycles, each of which is optionally substituted with one or more substituents selected from 3- to 6-membered heterocycles. or a salt thereof.

[0028] In some embodiments, A is O.

[0029] In some embodiments, R 1 is C 1~6 In some embodiments, R 1 is a C1 alkyl.

[0030] In some embodiments, n is selected from 1 and 3. In some embodiments, n is 1. In some embodiments, n is 3.

[0031] In some embodiments, R 2 The 6- to 10-membered heterocycle is selected from pyran, pyridine, piperidine, imidazole, thiazole, dioxane, morpholine, pyrimidine, benzimidazole, piperazine, thiadiazine, oxepane, thiepin, azocine, indole, isoindole, indolizine, quinoline, isoquinoline, purine, carbazole, and dibesofuran.

[0032] In some embodiments, R 2 is selected from benzimidazole and piperazine. 2 teeth [ka] In some embodiments, R 2 is piperazine. In some embodiments, piperazine is selected from the group consisting of =O and -C(O)R 11 In some embodiments, R 11 is a 3- to 6-membered heterocycle substituted with one or more substituents selected from C 1~6 In some embodiments, C 1~6 The alkyl is a C1 alkyl or a C2 alkyl. In some embodiments, the 3-6 membered heterocycle is [ka] It is.

[0033] In some embodiments, each R 2 teeth [ka] is selected from.

[0034] In some embodiments, the compound of formula (VII) or salt thereof is [ka] and any one of salts thereof.

[0035] Also provided herein is a method for preventing or treating a skin condition, disorder, or disease, comprising administering to a subject in need thereof a compound represented by formula (III): [ka] [In the ceremony L 1 , L 2 and L 3 are each independently a bond, a linear C 1~6 Alkyl or branched chain C 1~6 alkyl, A is N-amide, -NH-C(O)-, or -C(O)-NH-; Ring B is C 4~6 Cycloalkyl, 5- or 6-membered heterocyclyl, C 5~8 selected from aryl, heteroaryl, and aralkyl; R x and R y are each independently selected from halogen, alkyl, haloalkyl, alkenyl, haloalkenyl, hydroxyl, alkoxy, haloalkoxy, nitro, -NH2, alkylamino, dialkylamino, and haloalkylamino; m is 0, 1, or 2; n is 0 or 1. or a salt thereof.

[0036] In some embodiments, ring B is C 5~8 In some embodiments, ring B is selected from aryl, heteroaryl, and aralkyl. 5~8aryl and heteroaryl. In some embodiments, C 5~8 The aryl is phenyl and the heteroaryl is imidazolyl.

[0037] In some embodiments, R x is C1-C3 alkoxy. In some embodiments, R x is -OCH3.

[0038] In some embodiments, ring B is [ka] In some embodiments, ring B is [ka] It is.

[0039] In some embodiments, m is 0 or 1. In some embodiments, n is 0.

[0040] In some embodiments, the compound of formula (III) or salt thereof is [ka] [ka] and any one of salts thereof.

[0041] Provided herein is a method for preventing or treating a skin condition, disorder, or disease, comprising administering to a subject in need thereof a compound represented by formula (II): [ka] [In the formula, R 1a and R 1b are each independently H, alkyl, haloalkyl, alkenyl, haloalkenyl, C 5~8 aryl, and aralkyl; R xare each independently selected from halogen, alkyl, haloalkyl, alkenyl, haloalkenyl, -OH, alkoxy, haloalkoxy, nitro, -NH2, alkylamino, dialkylamino, and haloalkylamino; p is 1, 2, or 3; q is 0, 1, or 2; R 2 is selected from H, alkyl, alkenyl, haloalkyl, haloalkenyl, nitro, -NH2, alkylamino, dialkylamino, alkyl-dialkylamino, and haloalkylamino; R 3 is selected from H, alkyl, and haloalkyl. or a salt thereof.

[0042] In some embodiments, R 1a and R 1b H and C 1~6 In some embodiments, R 1a and R 1b is H.

[0043] In some embodiments, R x is C1-C6 alkoxy. In some embodiments, R x is -OCH3.

[0044] In some embodiments, q is 0 or 1. In some embodiments, p is 1.

[0045] In some embodiments, R 2 is C 1~6 alkyl, alkyl-di(C1-C6)alkylamino, mono(C1-C6)alkylamino, and di(C1-C6)alkylamino. In some embodiments, R 2 is methyl, ethyl, propyl, butyl, isopropyl, isobutyl, and [ka] is selected from.

[0046] In some embodiments, R 3 is H.

[0047] In some embodiments, the compound of formula (II) or salt thereof is [ka] [ka] and any one of salts thereof.

[0048] Provided herein is a method for preventing or treating a skin condition, disorder, or disease, comprising administering to a subject in need thereof a compound represented by formula (I): [ka] [In the formula, R 1a and R 1b is independently selected from H, alkyl, and haloalkyl; R 3 is selected from cycloalkyl, heterocyclyl, aryl, heteroaryl, and aralkyl, wherein the cycloalkyl, heterocyclyl, aryl, heteroaryl, or aralkyl is optionally substituted with one or more substituents independently selected from halogen, alkyl, alkoxy, and haloalkoxy; R x are each independently selected from halogen, alkyl, haloalkyl, alkenyl, haloalkenyl, -OH, alkoxy, haloalkoxy, -NH2, alkylamino, dialkylamino, and haloalkylamino; p is 1, 2, or 3; q is 0, 1, or 2; Q is O, S, and NR 2 Selected from R 2is selected from H, alkyl, alkenyl, haloalkyl, haloalkenyl, nitro, -NH2, alkylamino, dialkylamino, and haloalkylamino. or a salt thereof.

[0049] In some embodiments, Q is NR 2 It is.

[0050] In some embodiments, R 2 is amino, C 1~3 Alkyl, and C 1~3 alkenyl.

[0051] In some embodiments, R 1a and R 1b , H, C 1~6 Alkyl, and C 1~6 haloalkyl. In some embodiments, R 1a and R 1b , H, C 1~4 Alkyl, and C 1~4 haloalkyl. In some embodiments, R 1a and R 1b is H.

[0052] In some embodiments, R 3 is C 4~6 In some embodiments, R is selected from cycloalkyl, 5- or 6-membered heterocyclyl, aryl, heteroaryl, alkylaryl, and aralkyl. 3 teeth [ka] In some embodiments, R 3 teeth [ka] It is.

[0053] In some embodiments, q is 0.

[0054] In some embodiments, the compound of formula (I) or salt thereof is [ka] and any one of salts thereof.

[0055] Provided herein is a method for preventing or treating a skin condition, disorder, or disease, comprising administering to a subject in need thereof a compound represented by formula (VI): [ka] [In the formula, R a are each independently selected from alkyl, haloalkyl, alkenyl, haloalkenyl, and alkoxy; R 1 and R 2 is H or alkyl, R 1 and R 2 The other is H, alkyl, alkoxy, -(C1-C6 alkylene)-C(O)NR x1 -(C1-C6 alkylene)-aryl, and -(C1-C6 alkylene)-C(O)NR x2 -(C1-C6 alkyl), R x1 and R x2 are each independently H, alkyl, or haloalkyl; p is 0, 1, or 2. or a salt thereof.

[0056] In some embodiments, R x1 is H. In some embodiments, R x2 is H.

[0057] In some embodiments, R 1 and R 2 is H. In some embodiments, R 1 and R 2the other is C1-C6 alkyl, [ka] In some embodiments, R 1 and R 2 The other is isopropyl, [ka] is selected from.

[0058] In some embodiments, p is 0. In some embodiments, p is 1.

[0059] In some embodiments, R a is C1-C6 alkyl or C1-C6 alkoxy. In some embodiments, R a is C1-C3 alkyl or C1-C3 alkoxy. In some embodiments, R a is -CH3 or -OCH3.

[0060] In some embodiments, the compound of formula (VI) or salt thereof is [ka] and any one of salts thereof.

[0061] Provided herein are methods for preventing or treating a skin condition, disorder, or disease, comprising administering to a subject in need thereof a [ka] [ka] [ka] and any one of salts thereof.

[0062] In some embodiments, the subject has been diagnosed with a skin condition, disorder, or disease. In some embodiments, the subject has not been diagnosed with a skin condition, disorder, or disease.

[0063] In some embodiments, the composition is a pharmaceutical composition.In some embodiments, the composition further comprises at least one additive selected from the group consisting of pharma- ceutically acceptable carriers, additives, adjuvants, diluents, and combinations thereof.

[0064] In some embodiments, the composition is a cosmetic composition. In some embodiments, the composition further comprises at least one additive selected from the group consisting of cosmetically acceptable carriers, additives, adjuvants, diluents, and combinations thereof.

[0065] In some embodiments, the composition is formulated as a toner, cream, emulsion, lotion, ointment, paste, gel, suspension, serum, oil, spray, emulsion, mousse, or mist.

[0066] In some embodiments, the administering comprises administering the composition to a skin area of ​​the subject. In some embodiments, the skin area comprises facial skin, elbow skin, neck skin, hand skin, periarticular skin, or a combination thereof. In some embodiments, the facial skin comprises skin of the forehead, temporal region, cheek area, nasolabial folds, marionette lines, chin, jaw, midface, preauricular zone, periorbital folds, cheeks, jawline, lips, or any combination thereof.

[0067] In some embodiments, the method prevents or reduces wrinkle(s) or fine line(s). In some embodiments, the method increases skin firmness. In some embodiments, the method moisturizes / hydrates the skin. In some embodiments, the method increases dermal collagen production or proliferation of cells that deposit collagen. In some embodiments, the method increases fibroblast proliferation.

[0068] Further aspects and advantages of the present disclosure will become readily apparent to those skilled in the art from the following detailed description, in which only exemplary embodiments of the present disclosure are shown and described. As will be understood, the present disclosure is capable of other and different embodiments, and its several details are capable of modification in various obvious respects, all without departing from the present disclosure. Accordingly, the drawings and description are illustrative in nature, and not restrictive. Incorporation by Reference

[0069] All publications, patents, and patent applications mentioned in this specification are herein incorporated by reference to the same extent as if each individual publication, patent, or patent application was specifically and individually indicated to be incorporated by reference.

[0070] The novel features of the invention are set forth with particularity in the appended claims. A better understanding of the features and advantages of the present invention will be obtained by reference to the following detailed description of the invention that sets forth illustrative embodiments, in which the principles of the invention are utilized, and the accompanying drawings (also referred to herein as "Figure" and "FIG."). [Brief description of the drawings]

[0071] [Figure 1] FIG. 1 shows an exemplary diagram of the dose-response curve for compound I-1.

[0072] [Diagram 2] FIG. 2 shows an exemplary diagram of the dose-response curve for compound II-1.

[0073] [Diagram 3] FIG. 3 shows an exemplary diagram of the dose-response curve for compound IV-2.

[0074] [Figure 4] FIG. 4 shows an exemplary diagram of the dose-response curve for compound V-1.

[0075] [Figure 5A]Figures 5A-5E show exemplary compounds that do not exhibit genotoxic transformation potential. Figure 5A shows an exemplary plot of TK.6 cells treated with compound V-1. Methyl methanesulfonate, an alkylating agent that is genotoxic, was used as a positive control for micronucleus detection. Figure 5B shows quantification of TK.6 micronucleus assays following treatment with various exemplary compounds across a range of concentrations. Figure 5C shows normalized β-galactosidase activity (quantified by absorbance) from the SOS chromotest using a genotoxic agent (4-NQ; 4-nitroquinoline-1-oxide) and exemplary compounds at various concentrations. The SOS chromotest is a bacteria-based test for genotoxicity. Figure 5D shows normalized reactive oxygen species (ROS) activity in human dermal papilla cells treated with exemplary compounds at 5 μg / mL versus vehicle control (0.1% v / v DMSO) after 24 hours. All tested exemplary compounds induced minimal changes in ROS activity compared to baseline vehicle controls. Figure 5E shows normalized caspase 3 / 7 activity in HepG2 cells, an immortalized hepatic cell line used to test small molecule-induced apoptosis. [Figure 5B] Same as above. [Figure 5C] Same as above. [Figure 5D] Same as above. [Figure 5E] Same as above.

[0076] [Figure 6A] Figures 6A-E show exemplary compounds that do not exhibit any skin sensitization potential or immunogenicity. Figure 6A shows normalized ARE-luciferase activity using a sensitizing compound (cinnamaldehyde) and an exemplary compound across a range of concentrations. Figure 6B describes an in vitro dendritic cell sensitization study. Dendritic cell activation is widely associated with downstream immunogenicity. Figures 6C-E are exemplary plots showing changes in HLA-DR expression. Expression of CD80 (Figure 6C), PDL-1 (Figure 6D), and CD141 (Figure 6E) as quantified by mean fluorescence intensity (MFI) after dosing of an exemplary compound. [Figure 6B]Same as above. [Figure 6C] Same as above. [Figure 6D] Same as above. [Figure 6E] Same as above.

[0077] [Figure 7] FIG. 7 shows exemplary photographs of subjects in a clinical trial. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0078] Detailed Description of the Invention While preferred embodiments of the present invention have been shown and described herein, it will be apparent to those skilled in the art that such embodiments are provided by way of example only. Numerous changes, changes, and substitutions will occur to those skilled in the art without departing from the invention. It should be understood that various alternatives to the embodiments of the invention described herein may be utilized in practicing the invention. It is intended that the following claims define the scope of the invention, and that methods and structures within the scope of these claims and their equivalents be covered thereby.

[0079] In certain aspects, the present disclosure provides compositions and compounds useful for preventing or treating hair loss or thinning. The compounds may include the structure of a compound of formula (I), (II), (III), (IV), (V), (VI), or (VII) or a salt thereof. The compounds may include the structure in Table 1, Table 2, Table 3, Table 4, Table 5, Table 6, Table 7, or Table 8 or a salt thereof. The compounds may be included in pharmaceutical or cosmetic compositions or formulations.

[0080] In certain aspects, the disclosure provides methods for preventing or treating hair loss or thinning (e.g., whether or not a diagnosis of hair loss or thinning has been made). Some aspects include methods for preventing or treating a skin condition, disorder, or disease. Some embodiments include methods for treating a skin condition, disorder, or disease. The skin condition, disorder, or disease can be in a subject. The subject may or may not have been diagnosed with a skin condition, disorder, or disease. The method can include administering to a subject in need thereof a composition comprising a compound comprising a structure of a compound of formula (I), (II), (III), (IV), (V), (VI), or (VII), or a salt thereof. The method can include administering to a subject in need thereof a composition comprising a compound having a structure in Table 1, Table 2, Table 3, Table 4, Table 5, Table 6, Table 7, or Table 8, or a salt thereof. definition

[0081] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs.

[0082] As used in this specification and claims, the singular forms "a," "an," and "the" include plural references unless the context clearly dictates otherwise.

[0083] Whenever the terms "at least," "more," or "more than or equal to" are placed before or after the first number in a series of two or more numerical values, the terms "at least," "more," or "more than or equal to" apply to each and every numerical value in the series. For example, more than or equal to 1, 2, or 3 is equivalent to more than or equal to 1, more than or equal to 2, or more than or equal to 3.

[0084] Whenever the terms "less than", "less than", or "less than or equal to" are placed before or after the first number in a series of two or more numbers, the terms "less than", "less than", or "less than or equal to" apply to each and every number in the series. For example, less than or equal to 3, 2, or less than or equal to 1 is equivalent to less than or equal to 3, less than or equal to 2, or less than or equal to 1.

[0085] The phrases "at least one of A and B" and "at least one of A or B" can be interpreted to mean at least A, at least B, or at least A and B (i.e., a set that includes A and B, which set can include one or more additional elements). The term "A and / or B" can be interpreted to mean only A, only B, or both A and B.

[0086] The phrases "at least about A, B, and C" and "at least about A, B, or C" can be interpreted to mean at least about A, at least about B, or at least about C. The phrases "at most about A, B, and C" and "at most about A, B, or C" can be interpreted to mean at most about A, at most about B, or at most about C.

[0087] The phrase "between about A and B, C and D, and E and F" can be interpreted to mean between about A and about B, between about C and about D, and between about E and about F. The phrase "between about A and B, C and D, or E and F" can be interpreted to mean between about A and about B, between about C and about D, or between about E and about F.

[0088] The phrase "about A-B and C-D" can be interpreted to mean between about A and about B and between about C and about D. The phrase "about A-B or C-D" can be interpreted to mean between about A and about B or between about C and about D.

[0089] The term "exemplary" as used herein means "serving as an example, instance, or illustration." Any embodiment described herein as "exemplary" is not to be construed as preferred or advantageous over other embodiments.

[0090] The term “C x~y " or "C x ~C y " when used with a chemical moiety such as alkyl, alkenyl, or alkynyl, means that the group contains from x to y carbons in the chain. For example, the term "C 1~6 "Alkyl" refers to substituted or unsubstituted saturated hydrocarbon groups, including straight-chain and branched-chain alkyl groups containing 1 to 6 carbons.

[0091] The term “C x~y alkenyl" and "C x~y "Alkynyl" refers to substituted or unsubstituted unsaturated aliphatic groups analogous in length and possible substitution to the alkyls described above, but which contain at least one double or triple bond respectively.

[0092] The term "aryl" refers to an aromatic monocyclic or aromatic polycyclic hydrocarbon ring system. An aromatic monocyclic or aromatic polycyclic hydrocarbon ring system contains only hydrogen and carbon, has 5 to 18 carbon atoms, and at least one of the rings in the ring system is aromatic, i.e., contains a cyclic delocalized (4n+2) π-electron system according to the Hückel rule. Ring systems from which aryl groups are derived include, but are not limited to, groups such as benzene, fluorene, indane, indene, tetralin, and naphthalene.

[0093] The term "cycloalkyl" refers to a saturated ring in which each atom of the ring is carbon. Cycloalkyls can include monocyclic and polycyclic rings, such as 3-10 membered monocyclic rings, 5-12 membered bicyclic rings, spiro bicycles, and 5-12 membered bridged rings. In certain embodiments, cycloalkyls contain 3-10 carbon atoms. In other embodiments, cycloalkyls contain 5-7 carbon atoms. Cycloalkyls can be attached to the remainder of the molecule by a single bond. Examples of monocyclic cycloalkyls include, for example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and cyclooctyl.

[0094] The term "halo", or alternatively "halogen" or "halide" means fluoro, chloro, bromo, or iodo. In some embodiments, halo is fluoro, chloro, or bromo.

[0095] The term "haloalkyl" refers to an alkyl radical, as defined above, that is substituted with one or more halo radicals, e.g., trifluoromethyl, dichloromethyl, bromomethyl, 2,2,2-trifluoroethyl, 1-chloromethyl-2-fluoroethyl, etc. In some embodiments, the alkyl portion of the haloalkyl radical is optionally further substituted as described herein.

[0096] The term "heterocycle" as used herein refers to a saturated, unsaturated, or aromatic ring containing one or more heteroatoms. Exemplary heteroatoms include N, O, Si, P, B, and S atoms. Heterocycles include 3-10 membered monocyclic rings, 6-12 membered bicyclic rings, 5-12 membered spiro bicyclic rings, and 5-12 membered bridged rings. Bicyclic heterocycles include any combination of saturated, unsaturated, and aromatic bicyclic rings that valences permit. In exemplary embodiments, an aromatic ring, such as pyridyl, may be fused to a saturated or unsaturated ring, such as cyclohexane, cyclopentane, morpholine, piperidine, or cyclohexene. Bicyclic heterocycles include any combination of ring sizes such as 4-5 fused ring systems, 5-5 fused ring systems, 5-6 fused ring systems, 6-6 fused ring systems, 5-7 fused ring systems, 6-7 fused ring systems, 5-8 fused ring systems, and 6-8 fused ring systems. Bicyclic heterocycles further include spiro bicyclic rings, for example 5-12 membered spiro bicycles.

[0097] The term "heterocycloalkyl" refers to a stable 3- to 12-membered non-aromatic ring radical containing 2-12 carbon atoms and at least one heteroatom, each of which may be selected from N, O, Si, P, B, and S atoms. Heterocycloalkyls may be selected from monocyclic or bicyclic and fused or bridged ring systems. The heteroatoms in a heterocycloalkyl radical are optionally oxidized. The nitrogen atom or atoms, if present, are optionally quaternized. The heterocycloalkyl radical is partially or fully saturated. The heterocycloalkyl is attached to the remainder of the molecule through any atom of the heterocycloalkyl where valence permits, such as any carbon or nitrogen atom of the heterocycloalkyl. Examples of heterocycloalkyl radicals include, but are not limited to, dioxolanyl, thienyl[1,3]dithianyl, decahydroisoquinolyl, imidazolinyl, imidazolidinyl, isothiazolidinyl, isoxazolidinyl, morpholinyl, octahydroindolyl, octahydroisoindolyl, 2-oxopiperazinyl, 2-oxopiperidinyl, 2-oxopyrrolidinyl, oxazolidinyl, piperidinyl, piperazinyl, 4-piperidonyl, pyrrolidinyl, pyrazolidinyl, quinuclidinyl, thiazolidinyl, tetrahydrofuryl, trithianyl, tetrahydropyranyl, thiomorpholinyl, thiamorpholinyl, 1-oxo-thiomorpholinyl, and 1,1-dioxo-thiomorpholinyl.

[0098] The term "heteroaryl" refers to a radical derived from a 5-18 membered aromatic ring radical containing 2-17 carbon atoms and 1-6 heteroatoms selected from nitrogen, oxygen and sulfur. As used herein, a heteroaryl radical is a monocyclic, bicyclic, tricyclic or tetracyclic ring system in which at least one of the rings in the ring system is aromatic, i.e., contains a cyclic delocalized (4n+2) π-electron system according to Hückel's rule. Heteroaryl includes fused or bridged ring systems. The heteroatom(s) in the heteroaryl radical are optionally oxidized. One or more nitrogen atoms, if present, are optionally quaternized. The heteroaryl is attached to the remainder of the molecule through any atom of the ring(s). Examples of heteroaryl include, but are not limited to, azepinyl, acridinyl, benzimidazolyl, benzoindolyl, 1,3-benzodioxolyl, benzofuranyl, benzoxazolyl, and thiophenyl (i.e., thienyl).

[0099] The term "substituted" refers to a moiety having a substituent replacing a hydrogen on one or more carbon or substitutable heteroatoms of a compound, e.g., NH or NH2. It is understood that "substituted" or "substituted with" includes the implicit proviso that such substitution is in accordance with the permissible valences of the atom and substituent being replaced, and that the substitution results in a stable compound, i.e., a compound that does not spontaneously undergo transformations such as rearrangement, cyclization, elimination, and the like. In certain embodiments, substituted refers to a moiety having a substituent replacing two hydrogen atoms on the same carbon atom, e.g., replacing two hydrogen atoms on a single carbon with an oxo, imino, or thioxo group. As used herein, the term "substituted" is intended to include all permissible substituents of organic compounds. In a broad aspect, permissible substituents include acyclic and cyclic, branched and unbranched, carbocyclic and heterocyclic, aromatic and nonaromatic substituents of organic compounds. Permissible substituents can be one or more and can be the same or different for appropriate organic compounds.

[0100] In some embodiments, the substituents may include any of the substituents described herein, for example, halogen, hydroxy, oxo (=O), thioxo (=S), cyano (-CN), nitro (-NO2), imino (=NH), oximo (=N-OH), hydrazino (=N-NH2), -R bb -OR aa , -R bb -OC(O)-R aa , -R bb -OC(O)-OR aa , -R bb -OC(O)-N(R aa )2, -R bb -N(R aa )2, -R bb -C(O)R aa , -R bb -C(O)OR aa , -R bb -C(O)N(R aa )2, -R bb -OR cc -C(O)N(R aa )2, -R bb -N(R aa )C(O)OR aa , -R bb -N(R aa )C(O)R aa , -R bb -N(R aa )S(O) t R aa (wherein t is 1 or 2), -R bb -S(O) t R aa (wherein t is 1 or 2), -R bb -S(O) t OR aa (wherein t is 1 or 2), and -R bb -S(O) t N(R aa)2, where t is 1 or 2; and alkyl, alkenyl, alkynyl, aryl, aralkyl, aralkenyl, aralkynyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, heterocycloalkylalkyl, heteroaryl, and heteroarylalkyl, any of which may optionally be alkyl, alkenyl, alkynyl, halogen, haloalkyl, haloalkenyl, haloalkynyl, oxo (=O), thioxo (=S), cyano (-CN), nitro (-NO2), imino (=NH), oximo (=N-OH), hydrazine (=N-NH2), -R bb -OR aa , -R bb -OC(O)-R aa , -R bb -OC(O)-OR aa , -R bb -OC(O)-N(R aa )2, -R bb -N(R aa )2, -R bb -C(O)R aa , -R bb -C(O)OR aa , -R bb -C(O)N(R aa )2, -R bb -OR cc -C(O)N(R aa )2, -R bb -N(R aa )C(O)OR aa , -R bb -N(R aa )C(O)R aa , -R bb -N(R aa )S(O) t R aa (wherein t is 1 or 2), -R bb -S(O) t R aa (wherein t is 1 or 2), -R bb -S(O) t OR aa (wherein t is 1 or 2) and -R bb -S(O) t N(R aa)2 (wherein t is 1 or 2), each R aa is independently selected from hydrogen, alkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heterocycloalkyl, heterocycloalkylalkyl, heteroaryl, or heteroarylalkyl, and each R aa is an alkyl, alkenyl, alkynyl, halogen, haloalkyl, haloalkenyl, haloalkynyl, oxo (=O), thioxo (=S), cyano (-CN), nitro (-NO2), imino (=NH), oximo (=N-OH), hydrazine (=N-NH2), -R bb -OR aa , -R bb -OC(O)-R aa , -R bb -OC(O)-OR aa , -R bb -OC(O)-N(R aa )2, -R bb -N(R aa )2, -R bb -C(O)R aa , -R bb -C(O)OR aa , -R bb -C(O)N(R aa )2, -R bb -OR cc -C(O)N(R aa )2, -R bb -N(R aa )C(O)OR aa , -R bb -N(R aa )C(O)R aa , -R bb -N(R aa )S(O) t R aa (wherein t is 1 or 2), -R bb -S(O) t R aa (wherein t is 1 or 2), -R bb -S(O) t OR aa (wherein t is 1 or 2) and -R bb -S(O) t N(R aa)2, where t is 1 or 2, and each R bb is independently selected from a direct bond or a straight or branched alkylene, alkenylene, or alkynylene chain; each R cc is a straight or branched alkylene, alkenylene or alkynylene chain.

[0101] A double bond to an oxygen atom, e.g., an oxo group, is represented herein as both "=O" and "(O)". A double bond to a nitrogen atom is represented herein as both "=NR" and "(NR)". A double bond to a sulfur atom is represented herein as both "=S" and "(S)".

[0102] The phrase "pharmacologically acceptable" is used herein to refer to compounds, materials, compositions, and / or dosage forms that are suitable for use in contact with the tissues of human beings and animals without excessive toxicity, irritation, allergic response, or other problem or complication, within the scope of sound medical judgment, commensurate with a reasonable benefit / risk ratio.

[0103] The phrase "pharmacologically acceptable excipient" or "pharmacologically acceptable carrier" as used herein means a pharma- ceutically acceptable material, composition, or vehicle, such as a liquid or solid filler, diluent, excipient, solvent, or encapsulating material. Each carrier must be "acceptable" in that it is compatible with the other ingredients of the formulation and not deleterious to the patient. Some examples of materials that can serve as pharma-ceutically acceptable carriers include: (1) sugars, such as lactose, glucose, and sucrose; (2) starches, such as corn starch and potato starch; (3) cellulose and its derivatives, such as sodium carboxymethylcellulose, ethylcellulose, and cellulose acetate; (4) powdered tragacanth; (5) malt; (6) gelatin; (7) talc; (8) excipients, such as cocoa butter and suppository wax; (9) oils, such as peanut oil, cottonseed oil, safflower oil, sesame oil, olive oil, corn oil, and soybean oil; (10) glycols, such as propylene glycol; (11) polyols, such as glycerin, sorbitol, mannitol, and polyethylene glycol; (12) esters, such as ethyl oleate and ethyl laurate; (13) agar; (14) buffers, such as magnesium hydroxide and aluminum hydroxide; (15) alginic acid; (16) pyrogen-free water; (17) isotonic saline; (18) Ringer's solution; (19) ethyl alcohol; (20) phosphate buffer solutions; and (21) other non-toxic, compatible substances utilized in pharmaceutical preparations.

[0104] The term "salt" or "pharmaceutically acceptable salt" refers to salts derived from various organic and inorganic counterions well known in the art. Pharmaceutically acceptable acid addition salts can be formed with inorganic and organic acids. Inorganic acids from which salts can be derived include, for example, hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, and the like. Organic acids from which salts can be derived include, for example, acetic acid, propionic acid, glycolic acid, pyruvic acid, oxalic acid, maleic acid, malonic acid, succinic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, cinnamic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, p-toluenesulfonic acid, salicylic acid, and the like. Pharmaceutically acceptable base addition salts can be formed with inorganic and organic bases. Inorganic bases from which salts can be derived include, for example, sodium, potassium, lithium, ammonium, calcium, magnesium, iron, zinc, copper, manganese, aluminum, and the like. Organic bases from which salts may be derived include, for example, primary, secondary and tertiary amines, substituted amines including naturally occurring substituted amines, cyclic amines, basic ion exchange resins, and the like, specifically, for example, isopropylamine, trimethylamine, diethylamine, triethylamine, tripropylamine, and ethanolamine. In some embodiments, the pharma-ceutically acceptable base addition salts are selected from ammonium, potassium, sodium, calcium, and magnesium salts.

[0105] In certain embodiments, the term "cosmetically acceptable salt" refers to any salt that is cosmetically acceptable when used appropriately in cosmetic treatment, particularly when used or applied to humans and / or mammals.In certain embodiments, these salts include, but are not limited to, the salts used to form base addition salts, for example, inorganic, such as, for example, but not limited to, lithium, sodium, potassium, calcium, magnesium or aluminum, or organic, such as, for example, but not limited to, ethylamine, diethylamine, ethylenediamine, ethanolamine, diethanolamine, arginine, lysine, histidine or piperazine; or acid addition salts, for example, organic, such as, for example, but not limited to, acetate, citrate, lactate, malonate, maleate, tartrate, fumarate, benzoate, aspartate, glutamate, succinate, oleate, trifluoroacetate, oxalate, pamoate or gluconate, or inorganic, such as, for example, but not limited to, chloride, sulfate, borate or carbonate.

[0106] A "cosmetically effective amount," as used herein, refers to an amount of a compound sufficient to improve the physical appearance of a subject. It is understood that a "cosmetically effective" amount may vary from subject to subject, depending on many factors, including, for example, the subject's age, weight, general condition, the condition being treated, the severity of the condition being treated, and the judgment of the prescribing physician.

[0107] The phrase "cosmetically acceptable excipient" or "cosmetically acceptable carrier" as used herein includes as pharmaceutical cream bases, oil-in-water emulsions, water-in-oil emulsions, gels, etc. Those skilled in the art will understand that suitable carriers typically contain ingredients such as those typically found in the cosmetic and cosmeceutical arts: oils, waxes or other standard fatty substances, or conventional gelling and / or thickening agents; emulsifiers; moisturizers; emollients; sunscreens; hydrophilic or lipophilic active agents; agents for combating free radicals; preservatives; basifying or acidifying agents; fragrances; surfactants; fillers; natural products or extracts of natural products, such as aloe or green tea extracts; vitamins; or coloring materials.

[0108] The term "in vivo" generally refers to events that take place within the body of a subject.

[0109] The term "in vitro" generally refers to events that occur outside the subject's body. For example, in vitro assays include any assays that are performed outside the subject. In vitro assays include cell-based assays that utilize cells, whether living or dead. In vitro assays also include cell-free assays that do not utilize intact cells.

[0110] "Optionally" or "optionally" means that the subsequently described circumstance event may or may not occur, and that the description includes instances where the event or circumstance occurs and instances where they do not occur. For example, "optionally substituted aryl" means that the aryl group may or may not be substituted, and that the description includes both substituted aryl groups and aryl groups without substitution.

[0111] A "pharmaceutically acceptable carrier, diluent, or excipient" includes, but is not limited to, any adjuvant, carrier, excipient, glidant, sweetener, diluent, preservative, dye, coloring agent, flavor enhancer, surfactant, wetting agent, dispersing agent, suspending agent, stabilizer, isotonic agent, solvent, or emulsifier approved by the U.S. Food and Drug Administration as acceptable for human or veterinary use. compound

[0112] The present disclosure provides compounds, salts thereof, and compositions and formulations thereof for hair treatment. The compounds or salts thereof may have structural formula (I), (II), (III), (IV), (V), (VI), or (VII). The compounds or salts thereof may be selected from those set forth in Tables 1-8, or any subset thereof. The compounds and salts thereof disclosed herein may be used in the method(s) of the present disclosure.

[0113] Compounds of formula (I) and salts thereof In certain aspects, disclosed herein is a compound having formula (I): [ka] [In the formula, R 1a and R 1b is independently selected from H, alkyl, and haloalkyl; R 3 is selected from cycloalkyl, heterocyclyl, aryl, heteroaryl, and aralkyl, wherein the cycloalkyl, heterocyclyl, aryl, heteroaryl, or aralkyl is optionally substituted with one or more substituents independently selected from halogen, alkyl, alkoxy, and haloalkoxy; R x are each independently selected from halogen, alkyl, haloalkyl, alkenyl, haloalkenyl, -OH, alkoxy, haloalkoxy, -NH2, alkylamino, dialkylamino, and haloalkylamino; p is 1, 2, or 3; q is 0, 1, or 2; Q is O, S, and NR 2 Selected from R 2 is selected from H, alkyl, alkenyl, haloalkyl, haloalkenyl, nitro, -NH2, alkylamino, dialkylamino, and haloalkylamino. or a (eg, pharma- ceutically or cosmetically acceptable) salt thereof.

[0114] In some embodiments of the compound having structural formula (I) (or a salt thereof), Q is NR 2 In some embodiments, R 2 is selected from amino, (e.g., C1-C3) alkyl, and (e.g., C1-C3) alkenyl. 2 is C alkyl. In some embodiments, R 2 is C alkyl. In some embodiments, R 2 is -CHCHCH. In some embodiments, R 2 is -NH2.

[0115] In some embodiments, R 1a and R 1b H, (e.g., C 1~4 Like C 1~6 ) alkyl, and (e.g., C 1~4 Like C 1~6 ) haloalkyl. In some embodiments, R 1a and R 1b is H.

[0116] In some embodiments, R 3 is selected from (e.g., C4-C6)cycloalkyl, (e.g., 5- or 6-membered) heterocyclyl, aryl (e.g., phenyl), heteroaryl (e.g., pyridine), alkylaryl, and aralkyl (e.g., benzyl). 3 teeth [ka] In some embodiments, R 3 teeth [ka] In some embodiments, R 3 teeth [ka] In some embodiments, R 3 teeth [ka] In some embodiments, R 3 teeth [ka] In some embodiments, R 3 teeth [ka] It is.

[0117] In some embodiments, q is 0.

[0118] In some embodiments, the compound having structural formula (I) is selected from those set forth in Table 1, and salts thereof. [Table 1]

[0119] Compounds of formula (II) and salts thereof In certain aspects, disclosed herein is a compound of formula (II): [ka] [In the formula, R 1a and R 1b are each independently selected from H, alkyl, haloalkyl, alkenyl, haloalkenyl, aryl (e.g., phenyl), and aralkyl (e.g., benzyl); R x are each independently selected from halogen, alkyl, haloalkyl, alkenyl, haloalkenyl, -OH, alkoxy, haloalkoxy, nitro, -NH2, alkylamino, dialkylamino, and haloalkylamino; p is 1, 2, or 3; q is 0, 1, or 2; R 2 is selected from H, alkyl, alkenyl, haloalkyl, haloalkenyl, nitro, -NH2, alkylamino, dialkylamino, alkyl-dialkylamino, and haloalkylamino; R 3 is selected from H, alkyl, and haloalkyl. or a (e.g., pharma- ceutically or cosmetically acceptable) salt thereof.

[0120] In some embodiments, R 1a and R 1b is H and (e.g., C 1~4 Like C 1~6 ) alkyl. In some embodiments, R 1a and R 1b is independently 1~4 In some embodiments, R 1a and R 1b is independently C alkyl. In some embodiments, R 1a and R 1b is H.

[0121] In some embodiments, R x is C1-C6 alkoxy. In some embodiments, R x is -OCH3.

[0122] In some embodiments, q is 0 or 1. In some embodiments, q is 0. In some embodiments, q is 1. In some embodiments, p is 1.

[0123] In some embodiments, R 2is (e.g., C1-C6) alkyl, alkyl-dialkylamino, monoalkylamino (e.g., mono(C1-C6) alkylamino), and dialkylamino (e.g., di(C1-C6) alkylamino). In some embodiments, alkyl-dialkylamino is, for example, (CH3CH2)2N(CH2)-. In some embodiments, alkylamino is, for example, -CH2NH-. In some embodiments, dialkylamino is, for example, (CH3CH2)2N-. In some embodiments, R 2 is a straight chain C alkyl. In some embodiments, R 2 is a straight chain C alkyl. In some embodiments, R 2 is a straight chain C4 alkyl. In some embodiments, R 2 is a branched C alkyl. In some embodiments, R 2 is a branched C4 alkyl. In some embodiments, R 2 is a branched C alkyl. In some embodiments, R 2 is methyl, ethyl, propyl, butyl, isopropyl, isobutyl, and [ka] In some embodiments, R 3 is H.

[0124] In some embodiments, the compound having structural formula (II) is selected from those set forth in Table 2, and salts thereof. [Table 2]

[0125] Compounds of formula (III) and salts thereof In certain aspects, disclosed herein is a compound of formula (III): [ka] [In the formula, L 1 , L 2 and L 3are each independently a bond or (e.g., C 1~3 Like C 1~6 ) alkyl (e.g., linear or branched chain); A is N-amide, -NH-C(O)-, or -C(O)-NH-; Ring B is selected from (e.g., C4-C6)cycloalkyl, (e.g., 5- or 6-membered)heterocyclyl, aryl (e.g., phenyl), heteroaryl (e.g., imidazolyl), and aralkyl (e.g., benzyl); R x and R y are each independently selected from halogen, alkyl, haloalkyl, alkenyl, haloalkenyl, hydroxyl, alkoxy, haloalkoxy, nitro, -NH2, alkylamino, dialkylamino, and haloalkylamino; m is 0, 1, or 2; n is 0 or 1. or a (e.g., pharma- ceutically or cosmetically acceptable) salt thereof.

[0126] In some embodiments, L 1 , L 2 and L 3 Each independently is a bond. 1 , L 2 and L 3 are each independently a linear C 1~6 In some embodiments, L is alkyl. 1 , L 2 and L 3 are each independently a branched chain C 1~6 In some embodiments, L is alkyl. 1 , L 2 and L 3 are each independently a linear C 1~3 In some embodiments, L is alkyl. 1 , L 2 and L 3 are each independently a branched chain C 1~3 It is an alkyl.

[0127] In some embodiments, A is N-amide. In some embodiments, A is -NH-C(O)-. In some embodiments, A is -C(O)-NH-.

[0128] In some embodiments, for the compound or salt of formula (III), ring B is selected from aryl (e.g., phenyl), heteroaryl (e.g., imidazolyl), and aralkyl (e.g., benzyl). In some embodiments, ring B is selected from aryl (e.g., phenyl), and heteroaryl (e.g., imidazolyl). In some embodiments, ring B is selected from phenyl and imidazolyl. In some embodiments, ring B is [ka] In some embodiments, ring B is [ka] It is.

[0129] In some embodiments, R x is C1-C3 alkoxy. In some embodiments, R x is -OCH3.

[0130] In some embodiments, m is 0. In some embodiments, m is 1. In some embodiments, n is 0.

[0131] In some embodiments, the compound having structural formula (III) is selected from those set forth in Table 3, and salts thereof. [Table 3]

[0132] Compounds of formula (IV) and salts thereof In certain aspects, disclosed herein is a compound of formula (IV): [ka] [In the formula, R 1 is selected from alkyl or heterocycloalky; R 1 The alkyl or heterocycloalkyl of [ka] , -C(O)NR x1 R x2 , alkoxy, -(C1-C3 alkylene)-C(O)OR y1 , -C(O)OR y2 , and -OR z and optionally substituted with one or more substituents independently selected from R x1 , R x2 , R y1 , R y2 , and R z are each independently selected from H, alkyl, and haloalkyl; X is -O-, -S-, or -NR B - and R A is H, alkyl, or haloalkyl; R 2 and R 3 are each independently H, (e.g., C 1~3 Like C 1~6 ) alkyl (e.g., straight or branched chain), or R 2 and R 3 together with the atoms to which they are attached form a (e.g., C4-C6) cycloalkyl or aryl (e.g., phenyl), the cycloalkyl or aryl being optionally substituted with one or more substituents independently selected from halogen, alkyl, and haloalkyl; Dotted lines indicate the presence of single or double bonds.] or a (e.g., pharma- ceutically or cosmetically acceptable) salt thereof.

[0133] In some embodiments, the compound of Formula (IV) has the structural formula: [ka] has.

[0134] In some embodiments, the compound of Formula (IV) has the structural formula: [ka] has.

[0135] In some embodiments, the compound of Formula (IV) has the structural formula: [ka] has.

[0136] In some embodiments, the compound of Formula (IV) has the structural formula: [ka] has.

[0137] In some embodiments, X is -O-. In some embodiments, X is -NR B - and R if necessary B is H.

[0138] In some embodiments, R 1 is -(CH2) a C(O)OH, -(CH2) a OCH3, -(CH2) a CH(OH)CH3, [ka] and a is 0, 1, 2, or 3. In some embodiments, R 1 is -(CH2) a C(O)OH, -(CH2) a OCH3, -(CH2) a CH(OH)CH3, [ka] and a is 0, 1, 2, or 3. In some embodiments, R 1 is -CH2C(O)OH, -(CH2)2OCH3, CH2CH(OH)CH3, [ka] In some embodiments, R x1 and R x2 are each independently C1-C6 (e.g., C1-C3) alkyl. In some embodiments, R y1 is H. In some embodiments, R y2 is H. In some embodiments, R z is H.

[0139] In some embodiments, R 1 is heterocycloalkyl [ka] , -C(O)NR x1 R x2 , alkoxy, -(C1-C3 alkylene)-C(O)OR y1 , -C(O)OR y2 , and -OR z C optionally substituted with one or more substituents independently selected from 1~4 In some embodiments, R 1 is one or more heterocycloalkyl [ka] In some embodiments, R is a C alkyl optionally substituted with 1 is one heterocycloalkyl [ka] In some embodiments, R is a C alkyl optionally substituted with 1 teeth [ka] In some embodiments, one or more -C(O)NR x1 R x2 In some embodiments, R 1 is a C alkyl optionally substituted with one or more -C(O)NCHCH. In some embodiments, R 1 is one [ka] In some embodiments, R is a C alkyl optionally substituted with 1 teeth [ka] In some embodiments, R 1 is alkyl optionally substituted with one or more alkoxy. In some embodiments, R 1 Ha-(CH2) a OCH3, and a is 0, 1, 2, or 3. In some embodiments, R 1 is -(CH2)OCH3. In some embodiments, R 1 is -(CH2)2OCH3. In some embodiments, R 1 is -(CH2)3OCH3. In some embodiments, R 1 can be one or more -OR z In some embodiments, R is an alkyl group optionally substituted with 1 can be one or more -OR z is a C3 alkyl substituted with R z is H. In some embodiments, R 1 is CHCH(OH)CH. In some embodiments, R 1 is heterocycloalkyl [ka] , -C(O)NR x1 R x2 , alkoxy, -(C1-C3 alkylene)-C(O)OR y1, -C(O)OR y2 , and -OR z In some embodiments, R is a heterocycloalkyl optionally substituted with one or more substituents independently selected from 1 is -(C1-C3 alkylene)-C(O)OR y1 and R is a heterocycloalkyl optionally substituted with one or more substituents independently selected from y1 is H. In some embodiments, heterocycloalkyl is [ka] In some embodiments, R 1 teeth [ka] In some embodiments, R 1 is one or more -C(O)OR y2 is a C alkyl optionally substituted with R y2 is H. In some embodiments, R 1 is -CC(O)OH.

[0140] In some embodiments, R 2 and R 3 are each independently selected from C1-C6 alkyl. 2 and R 3 taken together with the atom to which they are attached form a C4-C6 cycloalkyl (e.g., cyclohexyl) optionally substituted with one or more substituents independently selected from halogen, alkyl, and haloalkyl. In some embodiments, R 2 and R 3 together with the atom to which they are attached form a cyclohexyl, optionally substituted with one or more substituents independently selected from halogen, alkyl, and haloalkyl. 2 and R 3together with the atom to which they are attached form an aryl (e.g., phenyl), optionally substituted with one or more substituents independently selected from halogen, alkyl, and haloalkyl. In some embodiments, R 2 and R 3 together with the atom to which they are attached form a phenyl optionally substituted with one or more substituents independently selected from halogen, alkyl, and haloalkyl. A is H.

[0141] In some embodiments, the compound having structural formula (IV) is selected from those set forth in Table 4, and salts thereof. [Table 4]

[0142] Compounds of formula (V) and salts thereof In certain aspects, disclosed herein is a compound of formula (V): [ka] [In the formula, Y 1 is O, S or NR 1 and R 1 is H, alkyl, or haloalkyl; R 2 is selected from H, alkyl, haloalkyl, alkenyl, haloalkenyl, aryl (e.g., phenyl), and aralkyl (e.g., benzyl); R 3 is H, alkyl, haloalkyl, -(CH2) m1 -OR a1 , -(CH2) m2 -O-(CH2) m3 -OR a2 , -(CH2) m4 -NR b1 R b2 , (CH2) m5 -C(O)OR c is selected from R a1 , R a2 , R b1 , R b2 , and R c are each independently selected from H, alkyl, and haloalkyl; m1, m2, m3, m4, and m5 are each independently selected from 1, 2, 3, and 4. or a (e.g., pharma- ceutically or cosmetically acceptable) salt thereof.

[0143] In some embodiments, with respect to the compound or salt of formula (V), Y 1 is O or S. In some embodiments, Y 1 is O. In some embodiments, R a1 , R a2 , R b1 , R b2 , and R c are each independently C1-C6 alkyl, such as C1-C3 alkyl. a1 is C alkyl. In some embodiments, R a1 is C alkyl. In some embodiments, R a1 is C alkyl. In some embodiments, R a2 is C alkyl. In some embodiments, R a2 is C alkyl. In some embodiments, R a2 is C alkyl. In some embodiments, R b1 is C alkyl. In some embodiments, R b1 is C alkyl. In some embodiments, R b1 is C alkyl. In some embodiments, R b2 is C alkyl. In some embodiments, R b2 is C alkyl. In some embodiments, R b2 is C alkyl. In some embodiments, R c is C alkyl. In some embodiments, R c is C alkyl. In some embodiments, R cis C alkyl. In some embodiments, R 2 is H.

[0144] In some embodiments, m1 is selected from 1, 2, 3, and 4. In some embodiments, m1 is 1. In some embodiments, m1 is 2. In some embodiments, m1 is 3. In some embodiments, m1 is 4. In some embodiments, m2 is selected from 1, 2, 3, and 4. In some embodiments, m2 is 1. In some embodiments, m2 is 2. In some embodiments, m2 is 3. In some embodiments, m2 is 4. In some embodiments, m3 is selected from 1, 2, 3, and 4. In some embodiments, m3 is 1. In some embodiments, m3 is 2. In some embodiments, m3 is 3. In some embodiments, m3 is 4. In some embodiments, m4 is selected from 1, 2, 3, and 4. In some embodiments, m4 is 1. In some embodiments, m4 is 2. In some embodiments, m4 is 3. In some embodiments, m4 is 4. In some embodiments, m5 is selected from 1, 2, 3, and 4. In some embodiments, m5 is 1. In some embodiments, m5 is 2. In some embodiments, m5 is 3. In some embodiments, m5 is 4.

[0145] In some embodiments, the compound having structural formula (V) is selected from those set forth in Table 5, and salts thereof. [Table 5]

[0146] Compounds of formula (VI) and salts thereof In certain aspects, disclosed herein is a compound of formula (VI): [ka] [In the formula, R a(when present) are each independently selected from alkyl, haloalkyl, alkenyl, haloalkenyl, and alkoxy; R 1 and R 2 is H or alkyl, R 1 and R 2 The other is H, alkyl, alkoxy, -(C1-C6 alkylene)-C(O)NR x1 -(C1-C6 alkylene)-aryl, and -(C1-C6 alkylene)-C(O)NR x2 -(C1-C6 alkyl), R x1 and R x2 are each independently H, alkyl, or haloalkyl; p is 0, 1, or 2. or a (e.g., pharma- ceutically or cosmetically acceptable) salt thereof.

[0147] In certain embodiments, for a compound or salt of formula (VI), R x1 is H. In some embodiments, R x2 is H.

[0148] In some embodiments, R 1 and R 2 is H. In some embodiments, R 1 and R 2 the other is C1-C6 (e.g., C1-C3) alkyl; [ka] In some embodiments, R 1 and R 2 The other is isopropyl, [ka] In some embodiments, R 1 and R 2 The other is isopropyl. In some embodiments, R 1 and R2 The other is, [ka] In some embodiments, R 1 and R 2 The other is, [ka] It is.

[0149] In some embodiments, p is 0. In some embodiments, p is 1.

[0150] In some embodiments, R a is C1-C6 (e.g., C1-C3) alkyl or C1-C6 (e.g., C1-C3) alkoxy. a is -CH3. In some embodiments, R a is -OCH3.

[0151] In some embodiments, the compound having structural formula (VI) is selected from those set forth in Table 6, and salts thereof. [Table 6]

[0152] Compounds of formula (VII) and salts thereof In certain aspects, disclosed herein is a compound of formula (VII): [ka] [In the formula, A is selected from O, NH, and S; R 1 is hydrogen, halogen, C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 2~10 Alkynyl, C 3~12 selected from a carbocycle, and a 3- to 12-membered heterocycle; R2 is selected from 6- to 10-membered heterocycles, the 6- to 10-membered heterocycles being selected from halogen, C 1~6 Alkyl, C 2~6 Alkenyl, and C 2~6 Alkynyl, -OR 11 , -SR 11 , -NO2, =O, =NH, -CN, -C(O)R 11 , -C(O)OR 11 , -OC(O)R 11 , -OC(O)N(R 11 )2, -NR 11 S(O)2R 11 , -C(O)N(R 11 )2, -N(R 11 )C(O)R 11 , -N(R 11 )C(O)N(R 11 )2, -N(R 11 )C(O)OR 11 , -S(O)2(R 11 ), -S(O)2N(R 11 )2, C 1~10 Alkyl, C3-C 12 is optionally substituted with one or more substituents independently selected from a carbocycle and a 5- to 12-membered heterocycle; n is selected from 1, 2, 3, 4, 5, and 6; Each R 11 is hydrogen, C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, and C 3~12 carbocycles, each of which is optionally substituted with one or more substituents selected from 3- to 6-membered heterocycles. or a (e.g., pharma- ceutically or cosmetically acceptable) salt thereof.

[0153] In some embodiments, A is oxygen. In some embodiments, R 1 is C 1~6 In some embodiments, C 1~6 Alkyl is a C alkyl. In some embodiments, R 1 is -CH3.

[0154] In some embodiments, n is selected from 1 and 3. In some embodiments, n is selected from 1. In some embodiments, n is selected from 3.

[0155] In some embodiments, R 2 The 6-10 membered heterocycle of is selected from pyran, pyridine, piperidine, imidazole, thiazole, dioxane, morpholine, pyrimidine, benzimidazole, piperazine, thiadiazine, oxepane, thiepin, azocine, indole, isoindole, indolizine, quinoline, isoquinoline, purine, carbazole, and dibenzofuran. 2 The 6- to 10-membered heterocycle is benzimidazole, [ka] In some embodiments, the 6- to 10-membered heterocycle R 2 , piperazine, [ka] In some embodiments, the piperazine is selected from the group consisting of ═O and —C(O)R 11 and optionally substituted with one or more substituents independently selected from:

[0156] In some embodiments, R 11 is a 3- to 6-membered heterocycle substituted with one or more substituents selected from C 1~6 In some embodiments, R 11 is a C1 alkyl or a C2 alkyl. In some embodiments, the 3-6 membered heterocycle is [ka] It is.

[0157] In some embodiments, each R 2 teeth [ka] is selected from.

[0158] In some embodiments, the compound having structural formula (VII) is selected from those set forth in Table 7, and salts thereof. [Table 7]

[0159] Other compounds and their salts In some embodiments, the compounds disclosed herein are selected from those set forth in Table 8, and salts thereof. [Table 8-1] [Table 8-2] [Table 8-3] [Table 8-4]

[0160] In some embodiments, the compounds disclosed herein are selected from those set forth in any one or combination of Tables 1 to 8 (or any subset thereof), and salts thereof.

[0161] The compounds of the present invention may also include crystalline and amorphous forms of these compounds, including, for example, polymorphs, pseudopolymorphs, solvates, hydrates, nonsolvated polymorphs (including anhydrates), conformational polymorphs, and amorphous forms of the compounds, and mixtures thereof, pharma- ceutically acceptable salts, and active metabolites of these compounds having the same type of activity.

[0162] The present disclosure includes the salts of the compounds described herein, particularly pharma-ceutically acceptable salts.The compounds of the present disclosure that have sufficiently acidic, sufficiently basic, or both functional groups can react with any of several inorganic bases and inorganic and organic acids to form salts.Alternatively, compounds that are originally charged, such as those that contain quaternary nitrogen, can form salts with suitable counterions, for example halides such as bromide, chloride, or fluoride, particularly bromide.

[0163] The compounds described herein may in some cases exist as diastereomers, enantiomers, or other stereoisomeric forms. The compounds presented herein include all diastereomeric, enantiomeric, and epimeric forms, and the appropriate mixtures thereof. Separation of stereoisomers can be carried out by chromatography, or by forming diastereomers and separating them by recrystallization or chromatography, or any combination thereof (Jean Jacques, Andre Collet, Samuel H. Wilen, "Enantiomers, Racemates and Resolutions", John Wiley and Sons, Inc., 1981, incorporated herein by reference for this disclosure). Stereoisomers can also be obtained by stereoselective synthesis.

[0164] The methods and compositions described herein include the use of amorphous and crystalline forms (also known as polymorphs). The compounds described herein may be in the form of pharmaceutically acceptable salts. Similarly, in some embodiments, the active metabolites of these compounds with the same type of activity are included within the scope of this disclosure. In addition, the compounds described herein may exist in unsolvated form as well as solvated form with pharmaceutically acceptable solvents such as water, ethanol, etc. The solvated form of the compounds presented herein is also considered to be disclosed herein.

[0165] Synthetic chemistry transformations and methodologies useful for synthesizing the compounds described herein are known in the art and include, for example, those described in R. Larock, Comprehensive Organic Transformations (1989), TW Greene and PGM Wuts, Protective Groups in Organic Synthesis, 2d. Ed. (1991), L. Fieser and M. Fieser, Fieser and Fieser's Reagents for Organic Synthesis (1994), and L. Paquette, ed., Encyclopedia of Reagents for Organic Synthesis (1995). composition

[0166] The present disclosure provides compositions of the compounds disclosed herein and salts thereof.

[0167] In some embodiments, the composition is for preventing or treating a skin condition, disorder, or disease comprising a compound having a structure of formula (I), (II), (III), (IV), (V), (VI), (VII), or Table 8. In some embodiments, the composition is for treating a skin condition, disorder, or disease comprising a compound having a structure of formula (I), (II), (III), (IV), (V), (VI), (VII), or Table 8. In some embodiments, the weight percent of the compound in the composition ranges from about 0.05% to about 10.0% by weight based on the total weight of the composition. In some embodiments, the weight percent of the compound in the composition ranges from about 0.01% to about 5%. In some embodiments, the weight percent of the compound in the composition ranges from about 0.01% to about 2.0%. In some embodiments, the weight percent of the compound in the composition ranges from about 0.01% to about 10% by weight based on the total weight of the composition. In some embodiments, the weight percent of the compound in the composition is at least about 0.01, 0.02, 0.03, 0.04, 0.05, 0.06, 0.07, 0.08, 0.09, 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10% by weight based on the total weight of the composition. In some embodiments, the weight percent of the compound in the composition is at most about 0.01, 0.02, 0.03, 0.04, 0.05, 0.06, 0.07, 0.08, 0.09, 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10% by weight based on the total weight of the composition. In some embodiments, the weight percent of the compound in the composition is in the range of about 0.01-10, 0.02-9, 0.03-8, 0.04-7, 0.05-6, 0.06-5, 0.07-4, 0.08-3, 0.09-2, 0.1-1, 0.2-0.9, 0.3-0.8, 0.4-0.7, or 0.5-0.6 weight percent based on the total weight of the composition.

[0168] The compositions disclosed herein may further comprise at least one additive selected from the group consisting of, but not limited to, water, preservatives, antioxidants, sunscreens, surfactants, emulsifiers, opacifiers, volatiles, propellants, liquid vehicles, carriers, salts, pH adjusters, neutralizers, buffers, natural extracts, humectants, fragrances, flavors, oils, emollients, lubricants, butters, penetrants, thickeners, viscosity modifiers, polymers, resins, film formers, absorbents, oils, moisturizers, whitening agents, anti-wrinkle agents, and acne relievers, atopic relievers, sunscreens, hair growth agents, vitamins and derivatives, amino acids or polypeptides, anti-inflammatory agents, female hormones, exfoliants, fungicides, placenta, allantoin, yeast extract, collagen, elastin, DHA, EPA, ceramides, and combinations thereof, to achieve a close approximation of the form of the commercially available product. The compositions disclosed herein for preventing or treating skin conditions, disorders, or diseases can be formulated in any suitable physical form.For example, in some embodiments, suitable physical forms include, but are not limited to, toners, emulsions, creams, gels, conditioners, soaps, serums, sprays, low to medium viscosity liquids, lotions, emulsions, mousses, oils, etc.In some embodiments, the compositions are formulated to be administered by misting, rubbing, wiping, wetting, dropping, or spraying.

[0169] In some embodiments, the composition is a pharmaceutical composition. In some embodiments, the pharmaceutical composition comprises a compound having the structure of formula (I), (II), (III), (IV), (V), (VI), or (VII) or a salt thereof. In some embodiments, the pharmaceutical composition comprises a compound having the structure in Table 1, Table 2, Table 3, Table 4, Table 5, Table 6, Table 7, or Table 8 or a salt thereof. The pharmaceutical composition may further comprise at least one additive selected from the group consisting of pharma- ceutically acceptable carriers, additives, adjuvants, diluents, and combinations thereof to achieve a close approximation of the form of the commercial product.

[0170] In some embodiments, the composition is a cosmetic composition. In some embodiments, the cosmetic composition comprises a compound having a structure of formula (I), (II), (III), (IV), (V), (VI), or (VII) or a salt thereof. In some embodiments, the cosmetic composition comprises a compound having a structure in Table 1, Table 2, Table 3, Table 4, Table 5, Table 6, Table 7, or Table 8 or a salt thereof. The cosmetic composition may further comprise at least one additive selected from the group consisting of cosmetically acceptable carriers, additives, adjuvants, diluents, and combinations thereof to achieve a close approximation of the form of a commercially available product. The composition may be formulated as a liquid solution. The cosmetic compositions disclosed herein may be formulated in any suitable physical form. For example, in some embodiments, suitable physical forms include, but are not limited to, toners, emulsions, creams, gels, conditioners, soaps, serums, sprays, low to medium viscosity liquids, lotions, emulsions, mousses, oils, and the like. In some embodiments, the composition may be used as a spray. In some embodiments, the composition may be used as a mist.

[0171] In some embodiments, non-limiting examples of skin include facial skin, elbow skin, neck skin, hand skin, peri-joint skin, or combinations thereof. In some embodiments, facial skin includes skin on the forehead, temporal region, cheek area, nasolabial folds, marionette lines, chin, jaw, mid-face, preauricular zone, periorbital folds, cheeks, jawline, lips, or any combination thereof.

[0172] In some embodiments, the compositions disclosed herein prevent or reduce wrinkle(s) or fine line(s). In some embodiments, the compositions disclosed herein increase skin firmness. In some embodiments, the compositions disclosed herein fade age spot(s). In some embodiments, the compositions disclosed herein soften rough skin spot(s). In some embodiments, the compositions disclosed herein moisturize / hydrate the skin. In some embodiments, the compositions disclosed herein protect the skin from UV damage. In some embodiments, the compositions disclosed herein increase dermal collagen production or proliferation of cells where collagen is deposited. In some embodiments, the compositions disclosed herein increase fibroblast proliferation. In some embodiments, the compositions disclosed herein heal wound(s).

[0173] Non-limiting examples of compositions are shown in Tables 9 to 13. The composition may include any embodiment or combination of embodiments from any of these tables. A, B, C, D, and E in Tables 9 to 13 represent exemplary ranges of weight percent of each component. For example, A refers to a value less than about 0.5, B refers to a value equal to or greater than about 0.5% and less than about 2%, C refers to a value equal to or greater than about 2% and less than about 10%, and D refers to a value equal to or greater than about 10%. Based on these examples, the composition may include any embodiment in Tables 9 to 13 in the amounts shown herein. [Table 9] [Table 10] [Table 11] [Table 12] [Table 13]

[0174] In Tables 9-13, "compounds disclosed herein" can include compounds having a structure of formula (I), (II), (III), (IV), (V), (VI), (VII), or Table 8, or a salt thereof. In Tables 9-13, "compounds disclosed herein" can include compounds having a structure in Table 1, Table 2, Table 3, Table 4, Table 5, Table 6, Table 7, or Table 8, or a salt thereof.

[0175] Disclosed herein, in some embodiments, is a formulation comprising an embodiment or combination of embodiments in any of Tables 9-13. An embodiment or combination of embodiments in any of Tables 9-13 may each comprise 0.001%, 0.002%, 0.003%, 0.004%, 0.005%, 0.006%, 0.007%, 0.008%, 0.009%, 0.01%, 0.02%, 0.03%, 0.04%, 0.05%, 0.06%, 0.07%, 0.08%, 0.09%, or 0.1% of the composition, or a range defined by any two of the foregoing percentages. The percentages may be weight / weight or weight / volume. Any of the embodiments or combinations of embodiments in Tables 9-13 may each constitute about 0.001%, about 0.002%, about 0.003%, about 0.004%, about 0.005%, about 0.006%, about 0.007%, about 0.008%, about 0.009%, about 0.01%, about 0.02%, about 0.03%, about 0.04%, about 0.05%, about 0.06%, about 0.07%, about 0.08%, about 0.09%, or about 0.1% of the composition, or a range defined by any two of the foregoing percentages. An embodiment or combination of embodiments in any of Tables 9-13 may each constitute at least 0.001%, at least 0.002%, at least 0.003%, at least 0.004%, at least 0.005%, at least 0.006%, at least 0.007%, at least 0.008%, at least 0.009%, at least 0.01%, at least 0.02%, at least 0.03%, at least 0.04%, at least 0.05%, at least 0.06%, at least 0.07%, at least 0.08%, at least 0.09%, or at least 0.1% of the composition. Any of the embodiments or combinations of embodiments in Tables 9-13 may constitute 0.001% or less, 0.002% or less, 0.003% or less, 0.004% or less, 0.005% or less, 0.006% or less, 0.007% or less, 0.008% or less, 0.009% or less, 0.01% or less, 0.02% or less, 0.03% or less, 0.04% or less, 0.05% or less, 0.06% or less, 0.07% or less, 0.08% or less, 0.09% or less, or 0.1% or less of the composition, respectively.An embodiment or combination of embodiments in any of Tables 9-13 may each constitute 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1%, 2.5%, 5%, 7.5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 100% of the composition, or a range defined by any two of the foregoing percentages. The percentages may be weight / weight or weight / volume. An embodiment or combination of embodiments in any of Tables 9-13 may each constitute about 0.1%, about 0.2%, about 0.3%, about 0.4%, about 0.5%, about 0.6%, about 0.7%, about 0.8%, about 0.9%, about 1%, about 2.5%, about 5%, about 7.5%, about 10%, about 15%, about 20%, about 25%, about 30%, about 35%, about 40%, about 45%, about 50%, about 55%, about 60%, about 65%, about 70%, about 75%, about 80%, about 85%, about 90%, about 95%, or about 100% of the composition, or a range defined by any two of the foregoing percentages. An embodiment or combination of embodiments in any of Tables 9-13 may each constitute at least 0.1%, at least 0.2%, at least 0.3%, at least 0.4%, at least 0.5%, at least 0.6%, at least 0.7%, at least 0.8%, at least 0.9%, at least 1%, at least 2.5%, at least 5%, at least 7.5%, at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, or at least 95% of the composition.An embodiment or combination of embodiments in any of Tables 9-13 may constitute 0.1% or less, 0.2% or less, 0.3% or less, 0.4% or less, 0.5% or less, 0.6% or less, 0.7% or less, 0.8% or less, 0.9% or less, 1% or less, 2.5% or less, 5% or less, 7.5% or less, 10% or less, 15% or less, 20% or less, 25% or less, 30% or less, 35% or less, 40% or less, 45% or less, 50% or less, 55% or less, 60% or less, 65% or less, 70% or less, 75% or less, 80% or less, 85% or less, 90% or less, or 95% or less of the composition, respectively. method

[0176] Also provided herein are methods for treating the skin with the compound(s) or salt(s) disclosed herein.

[0177] In certain aspects, disclosed herein are methods for preventing or treating a skin condition, disorder, or disease (whether or not a diagnosis of the skin condition, disorder, or disease has been made). In some embodiments, the method is for treating a skin condition, disorder, or disease. In some embodiments, the method comprises administering to a subject in need thereof a composition comprising a compound or salt described herein, or a composition described herein. The compound(s) or salt(s) thereof may have a structural formula of (I), (II), (III), (IV), (V), (VI), (VII), or Table 8. The compound(s) or salt(s) thereof may be selected from those described in any one of Tables 1-8, or any subset thereof, or any combination thereof. In some embodiments, the method comprises the use, administration, or application of a compound having a structure of formula (I), (II), (III), (IV), (V), (VI), or (VII), or a salt thereof. In some embodiments, the method comprises the use, administration, or application of a compound having a structure in Table 1, Table 2, Table 3, Table 4, Table 5, Table 6, Table 7, or Table 8, or a salt thereof.

[0178] A diagnosis of a skin condition, disorder, or disease may or may not have been made. In some embodiments of any of the methods described herein, the subject may have been diagnosed with a skin condition, disorder, or disease. In some embodiments of any of the methods described herein, the subject may not have been diagnosed with a skin condition, disorder, or disease.

[0179] In some embodiments, the method comprises administering the composition to a skin area of ​​the subject. In some embodiments, the skin area is facial skin, elbow skin, neck skin, hand skin, or periarticular skin. In some embodiments, the facial skin comprises the skin of the forehead, temporal region, cheek area, nasolabial fold, marionette lines, chin, jaw, midface, preauricular zone, periorbital fold, cheek, jawline, lips, or any combination thereof.

[0180] In some embodiments, the method prevents or reduces wrinkle(s) or fine line(s). In some embodiments, the method increases skin firmness. In some embodiments, the method fades age spot(s). In some embodiments, the method softens rough skin spot(s). In some embodiments, the method moisturizes / hydrates the skin. In some embodiments, the method protects the skin from UV damage. In some embodiments, the method increases dermal collagen production or proliferation of cells in which collagen is deposited. In some embodiments, the method increases fibroblast proliferation. In some embodiments, the method heals wound(s).

[0181] In some embodiments, the method comprises administering the composition to the skin area of ​​the subject.In some embodiments, the composition is a pharmaceutical composition.In some embodiments, the pharmaceutical composition can further comprise at least one additive selected from the group consisting of pharmaceutically acceptable carriers, additives, adjuvants, diluents, and combinations thereof, to achieve a close approximation of the form of commercial product.

[0182] In some embodiments, the pharmaceutical composition is administered one to three times per day. In some embodiments, the pharmaceutical composition is administered once per day. In some embodiments, the pharmaceutical composition is administered twice per day. In some embodiments, the pharmaceutical composition is administered three times per day. In some embodiments, the pharmaceutical composition is administered every other day. In some embodiments, the pharmaceutical composition is administered for at least two consecutive days. In some embodiments, the pharmaceutical composition is administered for at least three consecutive days. In some embodiments, the pharmaceutical composition is administered for at least four consecutive days. In some embodiments, the pharmaceutical composition is administered for at least five consecutive days. In some embodiments, the pharmaceutical composition is administered for at least seven consecutive days.

[0183] In some embodiments, the pharmaceutical composition is administered for at least about 2 days, 3 days, 5 days, 7 days, 10 days, 15 days, 20 days, 30 days, 50 days, 60 days, 80 days, 90 days, 5 months, 6 months, 7 months, 8 months, 9 months, 10 months, 11 months, 1 year, 2 years, or 3 years. In some embodiments, the pharmaceutical composition is administered for at most about 2 days, 3 days, 5 days, 7 days, 10 days, 15 days, 20 days, 30 days, 50 days, 60 days, 80 days, 90 days, 5 months, 6 months, 7 months, 8 months, 9 months, 10 months, 11 months, 1 year, 2 years, or 3 years. In some embodiments, the pharmaceutical composition is administered for about 2 days to 3 years, 3 days to 2 years, 5 days to 1 year, 7 days to 11 months, 10 days to 10 months, 15 days to 9 months, 20 days to 8 months, 30 days to 7 months, 50 days to 6 months, 60 days to 5 months, 80 days to 4 months, or 90 days to 3 years.

[0184] In some embodiments, the composition is a cosmetic composition. In some embodiments, the cosmetic composition further comprises at least one additive selected from the group consisting of cosmetically acceptable carriers, additives, adjuvants, diluents, and combinations thereof to achieve a close approximation of the form of a commercial product. The composition can be formulated as a liquid solution. The cosmetic composition disclosed herein can be formulated in any suitable physical form. For example, in some embodiments, suitable physical forms include, but are not limited to, toners, emulsions, creams, gels, conditioners, soaps, serums, sprays, low to medium viscosity liquids, lotions, emulsions, mousses, oils, and the like.

[0185] Numbered embodiments Some aspects include any of the following numbered embodiments. 1. A method for preventing or treating a skin condition, disorder, or disease, comprising administering to a subject in need thereof a compound of formula (V): [ka] [In the formula, Y 1 is O, S or NR 1 and R 1 is H, alkyl, or haloalkyl; R 2 is selected from H, alkyl, haloalkyl, alkenyl, haloalkenyl, aryl, and aralkyl; R 3 is H, alkyl, haloalkyl, -(CH2) m1 -OR a1 , -(CH2) m2 -O-(CH2) m3 -OR a2 , -(CH2) m4 -NR b1 R b2 , (CH2) m5 -C(O)OR c is selected from R a1 , R a2 , R b1 , Rb2 , and R c are each independently selected from H, alkyl, and haloalkyl; m1, m2, m3, m4, and m5 are each independently selected from 1, 2, 3, and 4. or a salt thereof. 2. Y 1 is O or S. 3. Y 1 The method of embodiment 1 or 2, wherein 4. R a1 , R a2 , R b1 , R b2 , and R c The method of any one of embodiments 1-3, wherein each is independently C1-C6 alkyl. 5. R a1 , R a2 , R b1 , R b2 , and R c The method of any one of embodiments 1-4, wherein each is independently C1-C3 alkyl. 6. R a1 , R a2 , R b1 , R b2 , and R c is each independently a C1 alkyl or a C2 alkyl. 7. The method of any one of embodiments 1 to 6, wherein m1, m2, m3, and m4 are each independently 2 or 3. 8. The method of any one of embodiments 1 to 7, wherein m5 is 1. 9. R 2 The method of any one of the preceding embodiments, wherein 10. The compound of formula (V) or a salt thereof [ka] and any one of salts thereof. 11. A method for preventing or treating a skin condition, disorder, or disease, comprising administering to a subject in need thereof a compound of formula (IV): [ka] [In the formula, R 1 is selected from alkyl or heterocycloalkyl; R 1 The alkyl or heterocycloalkyl of the formula (I) is a heterocycloalkyl, -C(O)NR x1 R x2 , alkoxy, -(C1-C3 alkylene)-C(O)OR y1 , -C(O)OR y2 , and -OR z and optionally substituted with one or more substituents independently selected from R x1 , R x2 , R y1 , R y2 , and R z are each independently selected from H, alkyl, and haloalkyl; R A is H or alkyl, X is -O-, -S-, or -NR B - and R B is H, alkyl, or haloalkyl; R 2 and R 3 are each independently selected from H, straight chain C1-C6 alkyl, branched chain C1-C6 alkyl, or R 2 and R 3 together with the atom to which they are attached form a C4-C6 cycloalkyl or aryl, said cycloalkyl or aryl being optionally substituted with one or more substituents independently selected from halogen, alkyl, and haloalkyl; Dotted lines indicate the presence of single or double bonds.] or a salt thereof. 12. The compound of formula (IV) has the structural formula: [ka] 12. The method of embodiment 11, comprising: 13. The compound of formula (IV) has the structural formula: [ka] 13. The method of embodiment 12, comprising: 14. The compound of formula (IV) has the structural formula: [ka] 12. The method of embodiment 11, comprising: 15. The compound of formula (IV) has the structural formula: [ka] 15. The method of embodiment 14, comprising: 16. R 2 and R 3 is each independently selected from C1 to C6 alkyl. 17. R 2 and R 3 taken together with the atom to which they are attached form a C4-C6 cycloalkyl, optionally substituted with one or more substituents independently selected from halogen, alkyl, and haloalkyl. 18. R 2 and R 3 together with the atom to which they are attached form a cyclohexyl optionally substituted with one or more substituents independently selected from halogen, alkyl, and haloalkyl. 19. R 2 and R 3 are optionally substituted, together with the atoms to which they are attached, with one or more substituents independently selected from halogen, alkyl, and haloalkyl. 5~816. The method of any one of embodiments 11 to 15, wherein an aryl is formed. 20. R 2 and R 3 taken together with the atom to which they are attached form a phenyl optionally substituted with one or more substituents independently selected from halogen, alkyl, and haloalkyl. 21. R A The method of any one of embodiments 11-20, wherein 22. The method of any one of embodiments 11 to 21, wherein X is -O-. 23. X is -NR B - and R if necessary B The method of any one of embodiments 11-22, wherein 24. R 1 But -(CH2) a C(O)OH, -(CH2) a OCH3, -(CH2) a CH(OH)CH3, [ka] and a is 0, 1, 2, or 3. 25. R 1 is -CH2C(O)OH, -(CH2)2OCH3, -CH2CH(OH)CH3, [ka] The method according to any one of embodiments 11 to 24, wherein the method is selected from the group consisting of: 26. R x1 and R x2 The method of any one of embodiments 11-25, wherein each is independently C1-C6 alkyl. 27. R x1 and R x2 is each independently a C1-C3 alkyl group. 28. R y1The method of any one of embodiments 11-27, wherein 29. R y2 The method of any one of embodiments 11-28, wherein 30. R z The method of any one of embodiments 11-29, wherein 31. The compound of formula (IV) or a salt thereof [ka] and any one of salts thereof. 32. A method for preventing or treating a skin condition, disorder, or disease, comprising administering to a subject in need thereof a compound of formula (VII): [ka] [In the formula, A is selected from O, NH, and S; R 1 is hydrogen, C 1~6 Alkyl, C 1~6 Haloalkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, C 2~10 Alkynyl, C 3~12 selected from a carbocycle, and a 3- to 12-membered heterocycle; R 2 is selected from a 6- to 10-membered heterocycle, and the 6- to 10-membered heterocycle is selected from halogen, C 1~6 Alkyl, C 2~6 Alkenyl, and C 2~6 Alkynyl, -OR 11 , -SR 11 , -NO2, =O, =NH, -CN, -C(O)R 11 , -C(O)OR 11 , -OC(O)R 11 , -OC(O)N(R 11 )2, -NR 11 S(O)2R 11 , -C(O)N(R 11 )2, -N(R 11 )C(O)R 11 , -N(R 11)C(O)N(R 11 )2, -N(R 11 )C(O)OR 11 , -S(O)2(R 11 ), -S(O)2N(R 11 )2, C 1~10 Alkyl, C3-C 12 is optionally substituted with one or more substituents independently selected from a carbocycle and a 5- to 12-membered heterocycle; n is selected from 1, 2, 3, 4, 5, and 6; Each R 11 is hydrogen; C 1~6 Alkyl, C 2~6 Alkenyl, C 2~6 Alkynyl, and C 3~12 carbocycles, each of which is optionally substituted with one or more substituents selected from 3- to 6-membered heterocycles. or a salt thereof. 33. The method of embodiment 32, wherein A is O. 34. R 1 C 1~6 The method of embodiment 32 or 33, wherein the alkyl group is alkyl. 35. R 1 is C alkyl. 36. The method of any one of embodiments 32 to 35, wherein n is selected from 1 and 3. 37. The method of embodiment 36, wherein n is 1. 38. The method of embodiment 37, wherein n is 3. 39. R 2 The method of any one of embodiments 32-38, wherein said 6-10 membered heterocycle is selected from pyran, pyridine, piperidine, imidazole, thiazole, dioxane, morpholine, pyrimidine, benzimidazole, piperazine, thiadiazine, oxepane, thiepin, azocine, indole, isoindole, indolizine, quinoline, isoquinoline, purine, carbazole, and dibenzofuran. 40. R 240. The method of embodiment 39, wherein is selected from benzimidazole and piperazine. 41. R 2 but [ka] 41. The method of embodiment 40, wherein 42. R 2 The method of embodiment 40, wherein is piperazine. 43. Piperazine is =O and -C(O)R 11 43. The method of embodiment 42, optionally substituted with one or more substituents independently selected from: 44. R 11 is substituted with one or more substituents selected from 3- to 6-membered heterocycles; 1~6 The method of any one of embodiments 32-43, wherein the alkyl group is alkyl. 45. C 1~6 The method of embodiment 44, wherein the alkyl is a C1 alkyl or a C2 alkyl. 46. ​​The 3- to 6-membered heterocycle is [ka] 46. ​​The method of embodiment 44 or 45, wherein 47. Each R 2 but [ka] The method according to any one of embodiments 32 to 46, wherein the method is selected from the group consisting of: 48. The compound of formula (VII) or a salt thereof [ka] and any one of salts thereof. 49. A method for preventing or treating a skin condition, disorder, or disease, comprising administering to a subject in need thereof a compound of formula (III): [ka] [In the ceremony L 1 , L 2 and L 3 are each independently a bond, a linear C 1~6 Alkyl or branched chain C 1~6 alkyl, A is N-amide, -NH-C(O)-, or -C(O)-NH-; Ring B is C 4~6 Cycloalkyl, 5- or 6-membered heterocyclyl, C 5~8 selected from aryl, heteroaryl, and aralkyl; R x and R y are each independently selected from halogen, alkyl, haloalkyl, alkenyl, haloalkenyl, hydroxyl, alkoxy, haloalkoxy, nitro, -NH2, alkylamino, dialkylamino, and haloalkylamino; m is 0, 1, or 2; n is 0 or 1. or a salt thereof. 50. Ring B is C 5~8 50. The method of embodiment 49, wherein the alkyl group is selected from aryl, heteroaryl, and aralkyl. 51. Ring B is C 5~8 51. The method of embodiment 49 or 50, wherein said alkyl group is selected from aryl and heteroaryl. 52. C 5~8 The method of embodiment 51, wherein the aryl is phenyl and the heteroaryl is imidazolyl. 53. R x The method of any one of embodiments 49-52, wherein is C1-C3 alkoxy. 54. R x The method of embodiment 53, wherein is -OCH3. 55. Ring B [ka] The method of any one of embodiments 49 to 54, wherein 56. Ring B [ka] The method of any one of embodiments 49 to 55, wherein 57. The method of any one of embodiments 49 to 56, wherein m is 0 or 1. 58. The method of any one of embodiments 49 to 57, wherein n is 0. 59. The compound of formula (III) or a salt thereof [ka] and any one of salts thereof. 60. A method for preventing or treating a skin condition, disorder, or disease, comprising administering to a subject in need thereof a compound of formula (II): [ka] [In the formula, R 1a and R 1b are each independently H, alkyl, haloalkyl, alkenyl, haloalkenyl, C 5~8 aryl, and aralkyl; R x are each independently selected from halogen, alkyl, haloalkyl, alkenyl, haloalkenyl, -OH, alkoxy, haloalkoxy, nitro, -NH2, alkylamino, dialkylamino, and haloalkylamino; p is 1, 2, or 3; q is 0, 1, or 2; R 2 is selected from H, alkyl, alkenyl, haloalkyl, haloalkenyl, nitro, -NH2, alkylamino, dialkylamino, alkyl-dialkylamino, and haloalkylamino; R 3 is selected from H, alkyl, and haloalkyl. or a salt thereof. 61. R 1a and R 1b but independently, H and C 1~6 61. The method of embodiment 60, wherein the alkyl group is selected from alkyl. 62. R 1a and R 1b The method of embodiment 60 or 61, wherein 63. R x The method of any one of embodiments 60-62, wherein is C1-C6 alkoxy. 64. R x The method of embodiment 62, wherein is -OCH3. 65. The method of any one of embodiments 60 to 64, wherein q is 0 or 1. 66. The method of any one of embodiments 60 to 65, wherein p is 1. 67. R 2 But, C 1~6 The method of any one of embodiments 60-66, wherein the alkyl is alkyl, alkyl-di(C1-C6)alkylamino, mono(C1-C6)alkylamino, and di(C1-C6)alkylamino. 68. R 2 isopropyl, isobutyl, and [ka] 68. The method according to any one of embodiments 60 to 67, wherein said method is selected from the group consisting of: 69. R 3 The method of any one of embodiments 60-68, wherein 70. The compound of formula (II) or a salt thereof [ka] and any one of salts thereof. 71. A method for preventing or treating a skin condition, disorder, or disease, comprising administering to a subject in need thereof a compound of formula (I): [ka] [In the formula, R 1a and R 1b is independently selected from H, alkyl, and haloalkyl; R 3 is selected from cycloalkyl, heterocyclyl, aryl, heteroaryl, and aralkyl, wherein said cycloalkyl, heterocyclyl, aryl, heteroaryl, or aralkyl is optionally substituted with one or more substituents independently selected from halogen, alkyl, alkoxy, and haloalkoxy; R x are each independently selected from halogen, alkyl, haloalkyl, alkenyl, haloalkenyl, -OH, alkoxy, haloalkoxy, -NH2, alkylamino, dialkylamino, and haloalkylamino; p is 1, 2, or 3; q is 0, 1, or 2; Q is O, S, and NR 2 Selected from R 2 is selected from H, alkyl, alkenyl, haloalkyl, haloalkenyl, nitro, -NH2, alkylamino, dialkylamino, and haloalkylamino. or a salt thereof. 72. Q is NR 2 72. The method of embodiment 71, wherein 73. R 2 But, Amino, C 1~3 Alkyl, and C 1~3 73. The method of embodiment 71 or 72, wherein said alkenyl is selected from the group consisting of aryl, ... and alkenyl. 74. R 1a and R 1b But, H, C 1~6 Alkyl, and C 1~6 The method of any one of embodiments 71-73, wherein haloalkyl is independently selected. 75. R 1aand R 1b But, H, C 1~4 Alkyl, and C 1~4 The method of any one of embodiments 71-74, wherein haloalkyl is independently selected from: 76. R 1a and R 1b The method of any one of embodiments 71-75, wherein 77. R 3 But, C 4~6 The method of any one of embodiments 71-76, wherein the aryl is selected from cycloalkyl, 5- or 6-membered heterocyclyl, aryl, heteroaryl, alkylaryl, and aralkyl. 78. R 3 but, [ka] The method of any one of embodiments 71 to 77, wherein 79. R 3 but, [ka] The method of any one of embodiments 71 to 78, wherein 80. The method of any one of embodiments 71 to 79, wherein q is 0. 81. The compound of formula (I) or a salt thereof [ka] [ka] and any one of salts thereof. 82. A method for preventing or treating a skin condition, disorder, or disease, comprising administering to a subject in need thereof a compound of formula (VI): [ka] [In the formula, R aare each independently selected from alkyl, haloalkyl, alkenyl, haloalkenyl, and alkoxy; R 1 and R 2 is H or alkyl, R 1 and R 2 The other is H, alkyl, alkoxy, -(C1-C6 alkylene)-C(O)NR x1 -(C1-C6 alkylene)-aryl, and -(C1-C6 alkylene)-C(O)NR x2 -(C1-C6 alkyl), R x1 and R x2 are each independently H, alkyl, or haloalkyl; p is 0, 1, or 2. or a salt thereof. 83. R x1 The method of embodiment 82, wherein 84. R x2 The method of embodiment 82 or 83, wherein 85. R 1 and R 2 The method of any one of embodiments 82-84, wherein one of is H. 86. R 1 and R 2 the other is C1-C6 alkyl, [ka] 86. The method of embodiment 85, wherein the method is selected from the group consisting of: 87. R 1 and R 2 The other is isopropyl, [ka] 86. The method of embodiment 85, wherein the method is selected from the group consisting of: 88. The method of any one of embodiments 82 to 87, wherein p is 0. 89. The method of any one of embodiments 82 to 87, wherein p is 1. 90. R a is C1-C6 alkyl or C1-C6 alkoxy. 91. R a is C1-C3 alkyl or C1-C3 alkoxy. 92. R a The method of any one of embodiments 82-91, wherein is -CH3 or -OCH3. 93. The compound of formula (VI) or a salt thereof [ka] and any one of salts thereof. 94. A method for preventing or treating a skin condition, disorder, or disease, comprising administering to a subject in need thereof. [ka] [ka] [ka] and any one of salts thereof. 95. The method of any one of embodiments 1 to 94, wherein the subject has been diagnosed with the skin condition, disorder, or disease. 96. The method of any one of embodiments 1 to 94, wherein the subject has not been diagnosed with the skin condition, disorder, or disease. 97. The method of any one of embodiments 1 to 96, wherein the composition is a pharmaceutical composition. 98. The method of embodiment 97, further comprising at least one additive selected from the group consisting of pharma- ceutically acceptable carriers, additives, adjuvants, diluents, and combinations thereof. 99. The method of any one of embodiments 1 to 96, wherein the composition is a cosmetic composition. 100. The method of embodiment 99, further comprising at least one additive selected from the group consisting of cosmetically acceptable carriers, additives, adjuvants, diluents, and combinations thereof. 101. The method of any one of the preceding embodiments, wherein the composition is formulated as a lotion, cream, emulsion, lotion, ointment, paste, gel, suspension, serum, oil, spray, emulsion, mousse, or mist. 102. The method of any one of the preceding embodiments, wherein the administering comprises administering the composition to a skin area of ​​the subject. 103. The method of any one of the preceding embodiments, wherein the skin area comprises facial skin, elbow skin, neck skin, hand skin, skin around a joint, or a combination thereof. 104. The method of embodiment 103, wherein the facial skin includes skin of the frontal, temporal, cheek region, nasolabial folds, marionette lines, chin, jaw, mid-face, preauricular zone, periorbital cavity, cheeks, jawline, lips, or any combination thereof. 105. The method of any one of the preceding embodiments, wherein the method prevents or reduces wrinkle(s) or fine line(s). 106. The method of any one of the preceding embodiments, wherein the method increases skin firmness. 107. The method of any one of the preceding embodiments, wherein the method moisturizes / hydrates the skin. 108. A method according to any one of the preceding embodiments, wherein the method increases dermal collagen production or proliferation of cells that deposit collagen. 109. The method of any one of the preceding embodiments, wherein the method increases fibroblast proliferation. EXAMPLES

[0186] Having now generally described the invention, it will be more readily understood by reference to the following examples, which are included merely for the purpose of illustrating certain aspects and embodiments of the invention, and are not intended to limit the invention in any manner. Example 1 Human dermal fibroblast (hDFC) proliferation assay The ability of the compounds or salts of the present disclosure to increase the proliferation of human dermal fibroblasts was tested using cell viability assays, such as Promega CellTiter-Glo® luminescent cell viability assay, MTT cell proliferation assay (ATCC® 30-1010K) or manual cell counting. In some cases, Promega CellTiter-Glo® and manual cell counting were used.

[0187] Compounds or salts were added at different concentrations spanning at least a 2 log range. Fibroblasts were cultured on tissue culture treated plastic using a predefined growth medium (i.e., Fibroblast Growth Medium; Promocell) containing basic fibroblast growth factor (FGFβ). In Table 14, "activity" refers to the percent (%) increase in proliferation of hFDPC. With respect to activity, "A" represents an increase in proliferation of less than 1% of hFDPC, "B" represents an increase in proliferation equal to or greater than 1% of hFDPC and less than 4%, "C" represents an increase in proliferation equal to or greater than 4% of hFDPC and less than 8%, and "D" represents an increase in proliferation equal to or greater than 8% of hFDPC. [Table 14-1] [Table 14-2] [Table 14-3] * The control is DMSO.

[0188] Example 2 Assays on human dermal microvascular endothelial cells (HDMEC) The ability of the compounds or salts of the present disclosure to affect the proliferation of adult human dermal capillary endothelial cells is tested after 48 hours using cell viability assays, such as Promega CellTiter-Glo® luminescent cell viability assay, MTT cell proliferation assay (ATCC® 30-1010K) or cell counting. Compounds or salts are added at different concentrations covering at least 2 log ranges.

[0189] Example 3 Assays in keratinocytes Adult human epidermal keratinocytes were cultured on poly-L-lysine treated plates and the ability of the compounds or salts of the present disclosure to affect proliferation was measured after 48 hours using a cell viability assay, such as the Promega CellTiter-Glo® luminescent cell viability assay, the MTT cell proliferation assay (ATCC® 30-1010K) or cell counting. Compounds or salts were added at different concentrations over at least a 2 log range.

[0190] Example 4 Assay on primary epidermal melanocytes; normal human adult (HEMa) The ability of the compounds or salts of the present disclosure to affect the proliferation of adult human epidermal melanocytes was tested using a cell viability assay, such as the Promega CellTiter-Glo® luminescent cell viability assay, the MTT cell proliferation assay (ATCC® 30-1010K) or cell counting after 48 hours. The compounds or salts were added at different concentrations spanning at least a two log range. Melanocytes from at least two different donors with various degrees of basal skin pigmentation were used.

[0191] Example 5 In silico safety / toxicity testing The in silico safety / toxicity profiles of compounds were determined by screening chemical structures against a series of computational models, including the Pred-hERG 4.2 cardiotoxicity model and the NeuroDeRisk IL Profiler neurotoxicity model from the QSAR Toolbox, as well as models for reproductive and developmental toxicity, carcinogenicity (genotoxicity and non-genotoxicity), skin sensitization, DNA mutation, and chromosomal aberrations.

[0192] Example 6 Safety / Toxicity Testing The safety / toxicity profile of the compounds or salts of the present disclosure was evaluated by a series of in vitro genotoxicity assays, including the SOS chromotest to determine bacterial genotoxicity, and the TK.6 micronucleus assay to determine chromosomal damage and forward mutations. Standard reactive oxygen species (ROS) and caspase 3 / 7 assays were performed to determine overall cytotoxicity. In addition, a series of sensitization tests were performed to predict any potential skin sensitization. These include a direct peptide reactivity assay to evaluate haptenization, a KeratinoSens reporter assay to determine potential sensitization via activation of cytoprotective pathways, and an immunological assay using human immature monocyte-derived dendritic cells to evaluate any potential immunogenicity.

[0193] Exemplary compounds did not exhibit genotoxic transformation potential (Figures 5A-5E). TK.6 lymphoblasts are a cell line used for gene mutation analysis. TK.6 lymphoblasts are heterozygous for the thymidine kinase gene (TK), allowing for the detection of forward mutations and chromosomal damage manifested as micronuclei. TK.6 lymphoblasts are detectable by flow cytometry. TK.6 cells were dosed with compounds or vehicle control (0.1% v / v DMSO) and cultured without S9 metabolic activation for 24 hours. Figures 5A-5E show the results of in vitro genotoxicity assays and TK.6 micronucleus assays. Figure 5A is an exemplary plot of TK.6 cells treated with compound V-1. Methyl methanesulfonate, an alkylating agent that is genotoxic, was used as a positive control for micronucleus detection. Figure 5B shows quantification of the TK.6 micronucleus assay following treatment with various compounds over a range of concentrations. FIG. 5C shows normalized β-galactosidase activity (quantified by absorbance) from the SOS chromotest using a genotoxic agent (4-NQ; 4-nitroquinoline-1-oxide) and exemplary compounds at various concentrations. The SOS chromotest is a bacteria-based test for genotoxicity. The results in FIG. 5B and FIG. 5C show that exemplary compound V-1 did not exhibit any genotoxic transforming potential, while compounds IV-2, I-1, II-1, III-1, and IV-1 exhibited mild genotoxicity at higher concentrations. FIG. 5D shows normalized reactive oxygen species (ROS) activity in human dermal papilla cells treated with 5 μg / mL exemplary compounds versus vehicle control (0.1% v / v DMSO) after 24 hours. All tested exemplary compounds induced minimal or no change in ROS activity compared to baseline vehicle control. Figure 5E shows normalized caspase 3 / 7 activity in HepG2 cells, an immortalized hepatic cell line used to test apoptosis induced by small molecules. Cells were treated with either compounds or vehicle control containing the corresponding %v / v matching amount of DMSO. High represents 10 μg / mL and low represents 1 μg / mL.Test compounds did not induce caspase 3 / 7 activation or only slightly induced caspase 3 / 7 activation at low and high concentrations. In Figures 5A-5E, data represent the mean ± sd and are representative of at least two repeated experiments.

[0194] Future tests will include metabolism and transport tests focusing on the ability of the disclosed compounds or salts to induce or inhibit cytochrome P450, mechanism-directed tests including passive / active transport using the Caco-2 cell line, a well-established compound transport assay. Additional safety and toxicity tests will include functional cardiotoxicity and neurotoxicity in human iPSC-derived cardiomyocytes and neurons, respectively. Finally, a repetitive injury patch test will be performed with the disclosed compounds or salts in 200 human subjects to predict any potential induced allergic contact dermatitis and related responses.

[0195] Example 7 Skin sensitization potential or immunogenicity The exemplary compounds do not exhibit any skin sensitization potential or immunogenicity (Figures 6A-6E). The Nrf2-ARE pathway is a master regulator of cytoprotective responses to oxidative stress and is an early indicator of skin sensitization. Nrf2 (nuclear factor erythroid 2-related factor) is a transcription factor that binds to antioxidant response elements (AREs). By fusing ARE to a luminescent luciferase gene, the KeratinoSens Nrf2-ARE reporter assay was constructed, where the luciferase signal directly correlates to Nrf2-ARE pathway activation. Figure 6A shows normalized ARE-luciferase activity using a sensitizing compound (cinnamaldehyde) and exemplary compounds across a range of concentrations. Compound IV-1 exhibited sensitization potential, whereas compounds I-1, II-1, III-1, IV-2, V-1, and VII-34 did not exhibit apparent Nrf2-ARE pathway activation. Figure 6B illustrates the in vitro dendritic cell sensitization study. Dendritic cell activation is widely associated with downstream immunogenicity. CD14+ cells derived from peripheral mononuclear cells of human donors were harvested and differentiated into immature monocyte-derived DCs using granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin 4 (IL-4), then treated with lead compounds. Killed E. Coli and TNF-α were used as positive controls. Figures 6C-E are exemplary plots showing changes in HLA-DR expression. Expression of CD80 (Figure 6C), PDL-1 (Figure 6D), and CD141 (Figure 6E) as quantified by mean fluorescence intensity (MFI) after dosing of exemplary compounds. Figures 6C-E show that none of the exemplary compounds exhibit any mo-DC activation potential. In Figures 6A-E, data represent mean ± sd and are representative of at least two repeated experiments.

[0196] Example 8 Clinical Trials The clinical trial was conducted at Eurofins|CRL, Inc. The study was designed to ensure the health of clinical test subjects and the generation of reliable test data and followed standard procedures established for clinical trials. A total of 120 male and female subjects ranging in age from 18 to 70 years were selected for study participation. The purpose of the study was to determine the potential of the test material, containing 0.01% v / v of Compound V-1 (in the formulation), to induce skin irritation and / or induce sensitization after repeated patch applications. [Table 15]

[0197] A clinical consumer perception test was conducted using compound V-1. In a third cell (cell 3), the compatibility and irritation of a typical formulation of both compound V-1 and low dose retinol in the formulation was tested. As reported, there were zero adverse effects in all cells, including cell 3. The test results are shown in Table 16. [Table 16]

[0198] Photographs were taken using a Canfield Visia-CR system after 8 weeks (Figure 7). Subjects were female and ranged in age from 51 to 70 years. A simple water-based formulation containing exemplary compound V-1 (at 0.5% w / v) was used. Subjects were instructed to apply the formulation 1-2 times per day after cleansing with Cetaphil daily cleanser. Sunscreen application was required (Neutrogena Oil Free Moisture with SPF 35) and avoidance of direct sunlight was recommended. Randomization was not required for the study and subjects were blinded to the name of the test material. Based on skin viscoelasticity measuring device readings, subjects using the formulation containing compound V-1 exhibited a 2-fold improvement in skin elasticity versus the gold standard 0.5% retinol formulation. Subjects also reported relatively fewer side effects compared to 0.5% retinol.

[0199] A total of 43 healthy female subjects consented to, enrolled, and completed the clinical trial. In Table 17, Cell 1 represents the cohort of participants who used the gold standard 0.5% retinol formulation. Cell 2 represents the cohort of participants who used a simple aqueous formulation containing exemplary compound V-1 (at 0.5% w / v). Cell 3 represents the cohort of participants who used a combination formulation of exemplary compound V-1 and low dose retinol (0.3% retinol). [Table 17]

[0200] Example 9 Efficacy Testing The functional profile of the compounds or salts of the present disclosure continues to be investigated in several ex vivo models and observational clinical trials. In addition, transcriptome and proteome analysis is performed on related genes and proteins, such as collagen, with well-established functional roles in cells exposed to the compounds or salts of the present disclosure. The compounds or salts of the present disclosure are treated on live human skin grafts excised from cosmetic surgery to evaluate targeted activation of human skin fibroblasts in histological studies. Additional mechanical tests, including measurements of stiffness and viscoelasticity, are performed to further evaluate the functional benefits of the compounds of the present disclosure salts. Finally, efficacy clinical trials are performed on at least 30 human subjects to determine the efficacy of the compounds or salts of the present disclosure in improving the appearance of skin tightening. Additional tests can be followed on more subjects and across a wider range of age groups and demographics.

[0201] Example 10 mechanical analysis Using the transcriptome data set, a series of mechanistic computational analyses are performed to identify possible mechanisms of action. These may include DE analysis to characterize the biological signatures of our lead chemicals, followed by GO term and pathway enrichment. In addition, we perform pseudotime and cell cycle analysis to probe the developmental effects of these chemicals in target cells. We may use various models to validate the extracted insights in further investigation.

[0202] Example 11 Synthesis of Compound V-1 [ka] Step A: Compound 1 (20 g, 0.2 mol) was dissolved in 150 ml of dichloromethane and compound 2 (34.3 g, 0.2 mol) was added. The mixture was shaken vigorously for 12 hours. The solvent was evaporated in vacuum. 150 ml of n-hexane was added to the remaining solid and the mixture was shaken vigorously for 20 minutes. The solvent was decanted from the solid residue and the solid was dried in vacuum. Yield: 43 g.

[0203] Step B: To a solution of compound 3 (43 g, 0.15 mol) in MeOH (155 ml) at room temperature was added an aqueous solution of 1 M KOH (2 eq.). The reaction mixture was refluxed until the starting material was completely consumed as monitored by liquid chromatography mass spectrometry (LCMS). The aqueous layer was washed with CH2Cl2 (300 ml) and then acidified with concentrated HCl to pH 2 to give a solid precipitate, which was collected by filtration. The precipitate was thoroughly washed with water (3 x 100 ml) to give the product. The yield is 32 g.

[0204] Example 12 Synthesis of compound IV-2 [ka] Step A: Compound 2 (20 g, 0.1 mol) was dissolved in 150 ml of acetonitrile and NaHCO3 (0.2 mol) was added. The mixture was stirred at room temperature for 30 min and compound 1 (12.4 g, 0.11 mol) was added. The reaction mixture was stirred at room temperature for 12 h (thin layer chromatography and LCMS control), the solvent was evaporated in vacuum and 150 ml of water was added at 10° C. The precipitate was filtered, washed with cold water (3×100 ml) and dried in vacuum for 10 h. The yield is 9.8 g.

[0205] While preferred embodiments of the present invention have been shown and described herein, it will be apparent to those skilled in the art that such embodiments are provided by way of example only. Numerous changes, changes, and substitutions will occur to those skilled in the art without departing from the invention. It should be understood that various alternatives to the embodiments of the invention described herein may be utilized in practicing the invention. It is intended that the following claims define the scope of the invention, and that methods and structures within the scope of these claims and their equivalents be covered thereby.

Claims

1. In the manufacture of a medicament for preventing or treating a skin condition, disorder, or disease in a subject in need thereof, comprising a compound of formula (V): 【Chemistry 113】 [In the formula, Y １ is O, S or NR １ and R １ is H, alkyl, or haloalkyl; R ２ is selected from H, alkyl, haloalkyl, alkenyl, haloalkenyl, aryl, and aralkyl; R ３ is H, alkyl, haloalkyl, -(CH ２ ) ｍ１ -OR ａ１ , -(CH ２ ) ｍ２ -O-(CH ２ ) ｍ３ -OR ａ２ , -(CH ２ ) ｍ４ -NR ｂ１ R ｂ２ , and (CH ２ ) ｍ５ -C(O)OR ｃ is selected from R ａ１ , R ａ２ , R ｂ１ , R ｂ２ , and R ｃ are each independently selected from H, C 1 -C 6 alkyl, and haloalkyl; m1, m2, m3, m4, and m5 are each independently selected from 1, 2, 3, and 4. or a salt thereof.

2. The compound of formula (V) or a salt thereof 【Chemistry 114】 and any one of salts thereof.

3. In the manufacture of a medicament for preventing or treating a skin condition, disorder, or disease in a subject in need thereof, comprising administering to a subject a compound represented by formula (IV): 【Chemical 115】 [In the formula, R １ is selected from alkyl or heterocycloalkyl; R １ The alkyl or heterocycloalkyl in the formula (I) is a heterocycloalkyl, —C(O)NR ｘ１ R ｘ２ , alkoxy, -(C １ ~C ３ alkylene)-C(O)OR ｙ１ , -C(O)OR ｙ２ , and -OR ｚ and optionally substituted with one or more substituents independently selected from R ｘ１ , R ｘ２ , R ｙ１ , R ｙ２ , and R ｚ are each independently selected from H, C 1 -C 6 alkyl, and haloalkyl; R Ａ is H or alkyl, X is —O—, —S—, or —NR Ｂ - and R Ｂ is H, alkyl, or haloalkyl; R ２ and R ３ are each independently H, linear C １ ~C ６ Alkyl, branched chain C １ ~C ６ alkyl, or R ２ and R ３ together with the atoms to which they are attached, ４ ~C ６ forming a cycloalkyl or aryl, said cycloalkyl or aryl being optionally substituted with one or more substituents independently selected from halogen, alkyl, and haloalkyl; A dotted line indicates the presence of a single or double bond. or a salt thereof.

4. The compound of formula (IV) has the structural formula: 【Chemistry 116】 or 【Chemistry 117】 or 【Chemistry 118】 or 【Chemical 119】 4. The use according to claim 3, wherein

5. R ２ and R ３ However, each independently, C １ ~C ６ The use according to claim 3, wherein R 2 and R 3 together with the atom to which they are attached form a C 4 -C 6 cycloalkyl, optionally substituted with one or more substituents independently selected from halogen, alkyl, and haloalkyl, or R 2 and R 3 together with the atom to which they are attached form a C 5-8 aryl, optionally substituted with one or more substituents independently selected from halogen, alkyl, and haloalkyl, or R 2 and R 3 together with the atom to which they are attached form a cyclohexyl, optionally substituted with one or more substituents independently selected from halogen, alkyl, and haloalkyl, or R 2 and R 3 together with the atom to which they are attached form a phenyl, optionally substituted with one or more substituents independently selected from halogen, alkyl, and haloalkyl.

6. R １ が、-(CH ２ ) ａ C(O)OH、-(CH ２ ) ａ OCH ３ ,-(EH ２ ) ａ CH(OH)CH ３ 、 【Chemical 120】 and a is 0, 1, 2, or 3.

7. The compound of formula (IV) or a salt thereof 【Chemistry 122】 and any one of salts thereof.

8. The method of claim 7, wherein the compound of formula (VII) is a compound of formula (VII): 【Chemical 123】 [In the formula, A is selected from O, NH, and S; R １ is hydrogen, C １～６ Alkyl, C １～６ Haloalkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, C ２～１０ Alkynyl, C ３～１２ selected from carbocycles, and 3- to 12-membered heterocycles; R ２ is selected from 6- to 10-membered heterocycles, wherein the 6- to 10-membered heterocycles are selected from pyran, pyridine, piperidine, imidazole, thiazole, dioxane, morpholine, pyrimidine, benzimidazole, piperazine, thiadiazine, oxepane, thiepine, azocine, indole, isoindole, indolizine, quinoline, isoquinoline, purine, carbazole, and dibenzofuran, and are selected from halogen, C １～６ Alkyl, C ２～６ alkenyl, and C ２～６ Alkynyl, -OR １１ , -SR １１ , -NO ２ , =O, =NH, -CN, -C(O)R １１ , -C(O)OR １１ , -OC(O)R １１ , -OC(O)N(R １１ ) ２ , -NR １１ S (O) ２ R １１ , -C(O)N(R １１ ) ２ , -N(R １１ ) C(O)R １１ , -N(R １１ )C(O)N(R １１ ) ２ , -N(R １１ )C(O)OR １１ , -S(O) ２ (R １１ ), -S(O) ２ N (R １１ ) ２ , C １～１０ Alkyl, C ３ ~C １２ optionally substituted with one or more substituents independently selected from carbocycle and 5- to 12-membered heterocycle; n is selected from 1, 2, 3, 4, 5, and 6; Each R １１ is hydrogen; C １～６ Alkyl, C ２～６ Alkenyl, C ２～６ Alkynyl, and C ３～１２ carbocycles, each of which is optionally substituted with one or more substituents selected from 3- to 6-membered heterocycles. or a salt thereof.

9. R ２ but 【Chemistry 124】 or R 2 is piperazine, optionally substituted with one or more substituents independently selected from ═O and —C(O)R 11 , wherein R 11 is C 1-6 alkyl substituted with one or more substituents selected from 3- to 6-membered heterocycles.

10. Each R ２ but 【Chemistry 126】 The use according to claim 8, wherein the compound is selected from the group consisting of:

11. The compound of formula (VII) or a salt thereof 【Chemistry 127】 and any one of salts thereof.

12. The method of claim 1, in the manufacture of a medicament for preventing or treating a skin condition, disorder, or disease in a subject in need thereof, comprising administering to a subject a compound of formula (III): 【Chemistry 128】 [During the ceremony L １ , L ２ and L ３ each independently represents a bond, a linear C １～６ Alkyl or branched chain C １～６ alkyl, A is N-amide, —NH—C(O)—, or —C(O)—NH—; Ring B is C ４～６ cycloalkyl, 5- or 6-membered heterocyclyl, C ５～８ selected from aryl, heteroaryl, and aralkyl; R ｘ and R ｙ are each independently halogen, alkyl, haloalkyl, alkenyl, haloalkenyl, hydroxyl, alkoxy, haloalkoxy, nitro, -NH ２ , alkylamino, dialkylamino, and haloalkylamino; m is 0, 1, or 2; n is 0 or 1. or a salt thereof.

13. The compound of formula (III) or a salt thereof 【Chemistry 131】 and any one of salts thereof.

14. In the manufacture of a medicament for preventing or treating a skin condition, disorder, or disease in a subject in need thereof, comprising administering to a subject a compound of formula (II): 【Chemistry 132】 [In the formula, R １ａ and R １ｂ are each independently H, C 1-6 alkyl, haloalkyl, alkenyl, haloalkenyl, C ５～８ aryl, and aralkyl; R ｘ are each independently halogen, alkyl, haloalkyl, alkenyl, haloalkenyl, —OH, C 1-6 alkoxy, haloalkoxy, nitro, —NH ２ , alkylamino, dialkylamino, and haloalkylamino; p is 1, 2, or 3; q is 0, 1, or 2; R ２ is H, C 1-6 alkyl, alkenyl, haloalkyl, haloalkenyl, nitro, —NH ２ , mono(C 1 -C 6 )alkylamino, di(C 1 -C 6 )alkylamino, alkyl-di(C 1 -C 6 )alkylamino, and halo(C 1 -C 6 )alkylamino; R ３ is selected from H, alkyl, and haloalkyl. or a salt thereof.

15. R ２ isopropyl, isobutyl, and 【Chemistry 133】 The use according to claim 14, wherein the compound is selected from the group consisting of:

16. The compound of formula (II) or a salt thereof 【Chemistry 134】 and any one of salts thereof.

17. The method of claim 1, wherein the compound of formula (I) is a compound of formula (I): 【Chemistry 135】 [In the formula, R １ａ and R １ｂ are independently selected from H, C 1-6 alkyl, and C 1-6 haloalkyl; R ３ is selected from C 4-6 cycloalkyl, or 5- or 6-membered heterocyclyl, aryl, heteroaryl, and aralkyl, wherein said cycloalkyl, heterocyclyl, aryl, heteroaryl, or aralkyl is optionally substituted with one or more substituents independently selected from halogen, alkyl, alkoxy, and haloalkoxy; R ｘ are each independently a halogen, an alkyl, a haloalkyl, an alkenyl, a haloalkenyl, —OH, an alkoxy, a haloalkoxy, —NH ２ , alkylamino, dialkylamino, and haloalkylamino; p is 1, 2, or 3; q is 0, 1, or 2; Q is O, S, and N-R ２ and R ２ is H, C 1-3 alkyl, C 1-3 alkenyl, haloalkyl, haloalkenyl, nitro, —NH ２ , alkylamino, dialkylamino, and haloalkylamino. or a salt thereof.

18. The compound of formula (I) or a salt thereof 【Chemistry 138】 and any one of salts thereof.

19. The method of claim 19, wherein the compound of formula (VI): 【Chemistry 139】 [In the formula, R ａ are each independently selected from C 1 -C 6 alkyl, haloalkyl, alkenyl, haloalkenyl, and C 1 -C 6 alkoxy; R １ and R ２ is H or alkyl; R １ and R ２ The other is H, alkyl, alkoxy, -(C １ ~C ６ alkylene)-C(O)NR ｘ１ -(C １ ~C ６ alkylene)-aryl, and -(C １ ~C ６ alkylene)-C(O)NR ｘ２ -(C １ ~C ６ alkyl), and R ｘ１ and R ｘ２ are each independently H, alkyl, or haloalkyl; p is 0, 1, or 2. or a salt thereof.

20. R １ and R ２ one of R 1 and R 2 is H and the other of R 1 and R 2 is C 1 -C 6 alkyl; [Chemical 140] 20. The use according to claim 19, wherein the compound is selected from the group consisting of:

21. R １ and R ２ The other is isopropyl, 【Chemistry 141】 21. The use according to claim 20, wherein the compound is selected from the group consisting of:

22. The compound of formula (VI) or a salt thereof 【Chemistry 142】 and any one of salts thereof.

23. Use of a composition comprising a compound or a salt thereof in the manufacture of a medicament for preventing or treating a skin condition, disorder, or disease in a subject in need thereof, wherein the compound is: 【Chemistry 143】 【Chemistry 144】 【Chemistry 145】 【Chemistry 146】 and any one of salts thereof.

24. 24. The use of claim 23, wherein the subject has been diagnosed with the skin condition, disorder, or disease, or wherein the subject has not been diagnosed with the skin condition, disorder, or disease.

25. 24. The use of claim 23, wherein the composition is a pharmaceutical composition and further comprises at least one additive selected from the group consisting of a pharmaceutically acceptable carrier, additive, adjuvant, diluent, and combinations thereof.

26. 24. The use of claim 23, wherein the composition is a cosmetic composition and further comprises at least one additive selected from the group consisting of cosmetically acceptable carriers, additives, adjuvants, diluents, and combinations thereof.

27. 24. The use of claim 23, wherein the composition is formulated as a toner, cream, emulsion, lotion, ointment, paste, gel, suspension, serum, oil, spray, emulsion, mousse, or mist.

28. The use of claim 23, wherein the composition is administered to a skin area of ​​the subject, wherein the skin area comprises facial skin, elbow skin, neck skin, hand skin, peri-articular skin, or a combination thereof, and wherein the facial skin comprises skin of the forehead, temporal region, cheek area, nasolabial folds, marionette lines, chin, jawline, mid-face, preauricular zone, periorbital folds, cheeks, jawline, lips, or any combination thereof.

29. 24. The use according to claim 23, wherein the medicament prevents or reduces wrinkle(s) or fine line(s), or wherein the medicament increases skin firmness, or wherein the medicament moisturizes / hydrates the skin.

30. 24. The use according to claim 23, wherein the medicament increases dermal collagen production or the proliferation of cells that deposit collagen, or wherein the medicament increases fibroblast proliferation.

31. A composition for use in preventing or treating a skin condition, disorder, or disease in a subject in need thereof, said composition comprising a compound represented by formula (V): 【Chemistry 113】 [In the formula, Y 1 is O, S or NR 1 , where R 1 is H, alkyl, or haloalkyl; R 2 is selected from H, alkyl, haloalkyl, alkenyl, haloalkenyl, aryl, and aralkyl; R 3 is selected from H, alkyl, haloalkyl, —(CH 2 ) m1 —OR a1 , —(CH 2 ) m2 —O—(CH 2 ) m3 —OR a2 , —(CH 2 ) m4 —NR b1 R b2 , and (CH 2 ) m5 —C(O)OR c ; R a1 , R a2 , R b1 , R b2 , and R c are each independently selected from H, C 1 -C 6 alkyl, and haloalkyl; m1, m2, m3, m4, and m5 are each independently selected from 1, 2, 3, and 4. or a salt thereof.

32. The compound of formula (V) or a salt thereof, 【Chemistry 114】 and any one of salts thereof.

33. A composition for use in preventing or treating a skin condition, disorder, or disease in a subject in need thereof, said composition comprising a compound represented by formula (IV): 【Chemical 115】 [In the formula, R 1 is selected from alkyl or heterocycloalkyl, wherein said alkyl or heterocycloalkyl of R 1 is optionally substituted with one or more substituents independently selected from heterocycloalkyl, —C(O)NR x1 R x2 , alkoxy, —(C 1 -C 3 alkylene)-C(O)OR yl , —C(O)OR y2 , and —OR z ; R x1 , R x2 , R y1 , R y2 , and R z are each independently selected from H, C 1 -C 6 alkyl, and haloalkyl; R A is H or alkyl; X is —O—, —S—, or —NR B —, where R B is H, alkyl, or haloalkyl; R 2 and R 3 are each independently selected from H, straight chain C 1 -C 6 alkyl, branched chain C 1 -C 6 alkyl, or R 2 and R 3 together with the atom to which they are attached form a C 4 -C 6 cycloalkyl or aryl, said cycloalkyl or aryl being optionally substituted with one or more substituents independently selected from halogen, alkyl, and haloalkyl; A dotted line indicates the presence of a single or double bond. or a salt thereof.

34. The compound of formula (IV) having the structural formula: 【Chemistry 116】 or 【Chemistry 117】 or 【Chemistry 118】 or 【Chemical 119】 34. The composition for use according to claim 33, having:

35. The composition for use described in claim 33, wherein R 2 and R 3 are each independently selected from C 1 to C 6 alkyl, or R 2 and R 3 together with the atom to which they are attached form a C 4 to C 6 cycloalkyl, optionally substituted with one or more substituents independently selected from halogen, alkyl, and haloalkyl, or R 2 and R 3 together with the atom to which they are attached form a C 5-8 aryl, optionally substituted with one or more substituents independently selected from halogen, alkyl, and haloalkyl, or R 2 and R 3 together with the atom to which they are attached form a cyclohexyl, optionally substituted with one or more substituents independently selected from halogen, alkyl, and haloalkyl, or R 2 and R 3 together with the atom to which they are attached form a phenyl, optionally substituted with one or more substituents independently selected from halogen, alkyl, and haloalkyl.

36. The compound according to claim 36, wherein R 1 is —(CH 2 ) a C(O)OH, —(CH 2 ) a OCH 3 , —(CH 2 ) a CH(OH)CH 3 , 【Chemical 120】 and a is 0, 1, 2, or 3.

37. The compound of formula (IV) or a salt thereof, 【Chemistry 122】 and any one of salts thereof.

38. A composition for use in preventing or treating a skin condition, disorder, or disease in a subject in need thereof, said composition comprising a compound represented by formula (VII): 【Chemical 123】 [In the formula, A is selected from O, NH, and S; R 1 is selected from hydrogen, C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 2-10 alkynyl, C 3-12 carbocycle, and a 3- to 12-membered heterocycle; R 2 is selected from 6- to 10-membered heterocycles, said 6- to 10-membered heterocycles being selected from pyran, pyridine, piperidine, imidazole, thiazole, dioxane, morpholine, pyrimidine, benzimidazole, piperazine, thiadiazine, oxepane, thiepine, azocine, indole, isoindole, indolizine, quinoline, isoquinoline, purine, carbazole, and dibenzofuran, as well as halogen, C 1-6 alkyl, C 2-6 alkenyl, and C 2-6 alkynyl, —OR 11 , —SR 11 , —NO 2 , ═O, ═NH, —CN, —C(O)R 11 , —C(O)OR 11 , —OC(O)R 11 , —OC(O)N(R 11 ) 2 , —NR 11 optionally substituted with one or more substituents independently selected from S(O) 2 R 11 , —C(O)N(R 11 ) 2 , —N(R 11 )C(O)R 11 , —N(R 11 )C(O)N(R 11 ) 2 , —N(R 11 )C(O)OR 11 , —S(O) 2 (R 11 ), —S(O) 2 N(R 11 ) 2 , C 1-10 alkyl, C 3 -C 12 carbocycle, and 5-12 membered heterocycle; n is selected from 1, 2, 3, 4, 5, and 6; each R 11 is independently selected at each occurrence from hydrogen; C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, and C 3-12 carbocycle, each of which is optionally substituted with one or more substituents selected from 3- to 6-membered heterocycle; or a salt thereof.

39. R 2 is 【Chemistry 124】 or R 2 is piperazine, said piperazine being optionally substituted with one or more substituents independently selected from ═O and —C(O)R 11 , wherein R 11 is C 1-6 alkyl substituted with one or more substituents selected from 3- to 6-membered heterocycles.

40. Each R 2 is 【Chemistry 126】 39. The composition for use according to claim 38, selected from:

41. The compound of formula (VII) or a salt thereof, 【Chemistry 127】 and any one of salts thereof.

42. A composition for use in preventing or treating a skin condition, disorder, or disease in a subject in need thereof, said composition comprising a compound represented by formula (III): 【Chemistry 128】 [During the ceremony L 1 , L 2 and L 3 are each independently selected from a bond, a straight chain C 1-6 alkyl, or a branched chain C 1-6 alkyl; A is N-amide, —NH—C(O)—, or —C(O)—NH—; Ring B is selected from C 4-6 cycloalkyl, 5- or 6-membered heterocyclyl, C 5-8 aryl, heteroaryl, and aralkyl; R x and R y are each independently selected from halogen, alkyl, haloalkyl, alkenyl, haloalkenyl, hydroxyl, alkoxy, haloalkoxy, nitro, —NH 2 , alkylamino, dialkylamino, and haloalkylamino; m is 0, 1, or 2; n is 0 or 1. or a salt thereof.

43. The compound of formula (III) or a salt thereof, 【Chemistry 131】 and any one of salts thereof.

44. A composition for use in preventing or treating a skin condition, disorder, or disease in a subject in need thereof, said composition comprising a compound represented by formula (II): 【Chemistry 132】 [In the formula, R 1a and R 1b are each independently selected from H, C 1-6 alkyl, haloalkyl, alkenyl, haloalkenyl, C 5-8 aryl, and aralkyl; each R x is independently selected from halogen, alkyl, haloalkyl, alkenyl, haloalkenyl, —OH, C 1-6 alkoxy, haloalkoxy, nitro, —NH 2 , alkylamino, dialkylamino, and haloalkylamino; p is 1, 2, or 3; q is 0, 1, or 2; R 2 is selected from H, C 1-6 alkyl, alkenyl, haloalkyl, haloalkenyl, nitro, —NH 2 , mono(C 1 -C 6 )alkylamino, di(C 1 -C 6 )alkylamino, alkyl-di(C 1 -C 6 )alkylamino, and halo-(C 1 -C 6 )alkylamino; R 3 is selected from H, alkyl, and haloalkyl. or a salt thereof.

45. The compound according to claim 45, wherein R 2 is methyl, ethyl, propyl, butyl, isopropyl, isobutyl, and 【Chemistry 133】 45. The composition for use according to claim 44, selected from:

46. ​​The compound of formula (II) or a salt thereof, 【Chemistry 134】 and any one of salts thereof.

47. A composition for use in preventing or treating a skin condition, disorder, or disease in a subject in need thereof, said composition comprising a compound represented by formula (I): 【Chemistry 135】 [In the formula, R 1a and R 1b are independently selected from H, C 1-6 alkyl, and C 1-6 haloalkyl; R 3 is selected from C 4-6 cycloalkyl, or 5- or 6-membered heterocyclyl, aryl, heteroaryl, and aralkyl, wherein said cycloalkyl, heterocyclyl, aryl, heteroaryl, or aralkyl is optionally substituted with one or more substituents independently selected from halogen, alkyl, alkoxy, and haloalkoxy; each R x is independently selected from halogen, alkyl, haloalkyl, alkenyl, haloalkenyl, -OH, alkoxy, haloalkoxy, -NH 2 , alkylamino, dialkylamino, and haloalkylamino; p is 1, 2, or 3; q is 0, 1, or 2; Q is selected from O, S, and N-R 2 , where R 2 is selected from H, C 1-3 alkyl, C 1-3 alkenyl, haloalkyl, haloalkenyl, nitro, —NH 2 , alkylamino, dialkylamino, and haloalkylamino. or a salt thereof.

48. The compound of formula (I) or a salt thereof, 【Chemistry 138】 and any one of salts thereof.

49. A composition for use in preventing or treating a skin condition, disorder, or disease in a subject in need thereof, said composition comprising a compound represented by formula (VI): 【Chemistry 139】 [In the formula, each R a is independently selected from C 1 -C 6 alkyl, haloalkyl, alkenyl, haloalkenyl, and C 1 -C 6 alkoxy; one of R 1 and R 2 is H or alkyl; the other of R 1 and R 2 is selected from H, alkyl, alkoxy, —(C 1 -C 6 alkylene)-C(O)NR x1 —(C 1 -C 6 alkylene)-aryl, and —(C 1 -C 6 alkylene)-C(O)NR x2 —(C 1 -C 6 alkyl), wherein R x1 and R x2 are each independently H, alkyl, or haloalkyl; p is 0, 1, or 2. or a salt thereof.

50. A compound according to claim 50, wherein one of R 1 and R 2 is H, and the other of R 1 and R 2 is C 1 -C 6 alkyl; [Chemical 140] 50. The composition for use according to claim 49, selected from:

51. The compound according to claim 51, wherein the other of R 1 and R 2 is isopropyl. 【Chemistry 141】 51. The composition for use according to claim 50, selected from:

52. The compound of formula (VI) or a salt thereof, 【Chemistry 142】 and any one of salts thereof.

53. A composition for use in preventing or treating a skin condition, disorder, or disease in a subject in need thereof, said composition comprising a compound or a salt thereof, 【Chemistry 143】 【Chemistry 144】 【Chemistry 145】 【Chemistry 146】 and any one of salts thereof.

54. The composition for use according to claim 53, wherein the subject has been diagnosed with the skin condition, disorder, or disease, or the subject has not been diagnosed with the skin condition, disorder, or disease.

55. The composition for use according to claim 53, wherein the composition is a pharmaceutical composition and further comprises at least one additive selected from the group consisting of pharmaceutically acceptable carriers, additives, adjuvants, diluents, and combinations thereof.

56. The composition for use according to claim 53, wherein the composition is a cosmetic composition and further comprises at least one additive selected from the group consisting of cosmetically acceptable carriers, additives, adjuvants, diluents, and combinations thereof.

57. The composition for use according to claim 53, wherein the composition is formulated as a lotion, cream, emulsion, lotion, ointment, paste, gel, suspension, serum, oil, spray, emulsion, mousse, or mist.

58. The composition for use according to claim 53, wherein the composition is administered to a skin area of ​​the subject, wherein the skin area comprises facial skin, elbow skin, neck skin, hand skin, peri-articular skin, or a combination thereof, and wherein the facial skin comprises skin of the forehead, temporal region, cheek region, nasolabial folds, marionette lines, chin, jawline, mid-face, preauricular zone, periorbital folds, cheeks, jawline, lips, or any combination thereof.

59. A composition for use according to claim 53, wherein the composition prevents or reduces wrinkle(s) or fine lines(s), or the medicament increases skin firmness, or the composition moisturizes / hydrates the skin.

60. A composition for use as described in claim 53, wherein the composition increases dermal collagen production or the proliferation of cells that deposit collagen, or the composition increases fibroblast proliferation.

Images