Photoprotective composition containing compounds derived from malassezia and / or their chemical analogs.

Abstract

To provide a method for treating a disease. [Solution] The present invention relates to compounds, compositions and methods for modulating skin pigmentation in a subject, and for treating or preventing UV-induced skin damage, erythema, skin aging, sunburn and hyperpigmentation. The compounds, compositions and methods of the present invention generally include compounds derived from Malassezia, including malassezin and indirubin, and / or their chemical analogues. Other uses of the compounds and compositions disclosed herein include, but are not limited to, improvement of hyperpigmentation caused by hyperpigmentation disorders, including melanocyte apoptosis, and modulation of aromatic hydrocarbon receptor (AhR) activity, melanogenesis, melanin production, melanosome biogeneration, melanosome transport, melanocyte activity and melanin concentration.

Description

[Technical Field]

[0001] Cross-reference of related applications The present invention claims benefit to U.S. Provisional Application No. 62 / 656,769 filed April 12, 2018, U.S. Provisional Application No. 62 / 668,007 filed May 7, 2018, U.S. Provisional Application No. 62 / 685,800 filed June 15, 2018, U.S. Provisional Application No. 62 / 686,912 filed June 19, 2018, U.S. Provisional Application No. 62 / 722,412 filed August 24, 2018, and U.S. Provisional Application No. 62 / 742,657 filed October 8, 2018. The entire contents of the above applications are incorporated herein by reference.

[0002] This invention relates to compounds produced by or derived from Malassezia yeast, and their chemical analogues. The compounds of the present invention, and compositions containing such compounds, possess, among other beneficial properties, photoprotective properties. Methods of using the compounds and compositions of the present invention are also intended. [Background technology]

[0003] Individuals worldwide use skin whitening agents to achieve several cosmetic purposes, including anti-aging effects, repairing sun damage, and meeting certain cultural standards of beauty. Many commercially available skin whitening products contain harmful ingredients, some of which are linked to cancer, although their effectiveness varies. Therefore, there is a need for novel skin whitening agents and formulations that demonstrate higher levels of safety and / or efficacy than currently available agents.

[0004] Malassezia is a genus of lipophilic yeast commonly found in the normal bacterial flora of human skin. Malassezia is associated with several skin conditions, including tinea versicolor (pityriasis versicolor), seborrheic dermatitis, and atopic dermatitis. It is the cause.

[0005] The natural habitat of M. furfur is the upper layer of the epidermis. However, exposure to ultraviolet light destroys organisms in its natural habitat. Therefore, UV filtering agents may be necessary for the survival of the organism. Two such UV-filtering indoles produced by the organism have been identified: pityriacitrin and pityrialactone. Pityriacitrin, first described in Mayser et al., 2002, is synthesized by M. furfur. Pityriacitrin is a stable, yellow, lipophilic compound that exhibits broad absorption in the UVA, UVB, and UVC spectra. Similar compounds from the genus Paracoccus have been isolated and patented as UV protective agents (Zhang et al., 2018).

[0006] Gambichler et al., 2007, investigated the UV protective effect of piciria citrin in humans using in vitro and in vivo testing methods. Spectrophotometric measurements were performed on piciria citrin cream and vehicles in the wavelength range of 290–400 nm. UV transmittance and sun protection index ("SPF") for various cream formulations were evaluated. The authors used colorimetric analysis to assess erythema and hyperpigmentation after irradiation of cream-protected and unprotected skin in healthy subjects. UVB and UVA transmittance decreased with increasing piciria citrin concentration. Increases in piciria citrin concentrations of 1.25%, 2.5%, and 5% resulted in slight improvements in SPF of 1.4, 1.5, and 1.7, respectively. In vivo testing confirmed the in vitro determination of piciria citrin The effectiveness of the 5% cream's SPF was confirmed. Overall, the UV protection effect of pitiliacitrin was very weak, suggesting that pitiliacitrin is probably only a recessive cofactor for the development of hypopigmentation in tinea versicolor lesions after sun exposure.

[0007] Further investigations into the UV filtering effect of pitiliacitrin were conducted on the human skin microbiome (Machowinski et al., 2006). These authors concluded that pitiliacitrin is effective in the test. Within the range tested, it was determined that it has a UV protective effect against non-toxic Candida albicans and staphylococci. The UV protective properties of pityrialactone were also confirmed in a yeast model (Mayser et al., 2003). Pityrialactone appears to be the cause of the yellow fluorescence of tinea versicolor in the Wood's lamp test.

[0008] Tinea versicolor is a non-contagious skin disease caused by the overgrowth of Malassezia, which locally alters the level of pigmentation. Malassezia yeast has two metabolic pathways for synthesizing indole pigments derived from melanin and tryptophan. Malassezin and indirubin are tryptophan metabolites of Malassezia that may contribute to the depigmentation characteristic of Malassezia overgrowth. [Overview of the project] [Problems that the invention aims to solve]

[0009] The inventions disclosed herein utilize compounds produced by or derived from Malassezia yeast, including malassezin and indirubin, and their chemical analogs, as basic raw materials for safe and effective skin whitening and skin pigmentation compositions. Photoprotective compositions containing malassezin, indirubin, and their chemical analogs are also disclosed herein. [Means for solving the problem]

[0010] One embodiment of the present invention is a skin-whitening compound. The compound is a chemical analog of a compound produced by Malassezia yeast, or its crystalline form, hydrate, or a cosmetic or pharmaceutically acceptable salt thereof.

[0011] Another embodiment of the present invention is a compound that induces melanocyte apoptosis. The compound is a chemical analog of a compound produced by Malassezia yeast, or its crystalline form, hydrate, or a salt that is cosmetically or pharmaceutically acceptable.

[0012] Further embodiments of the present invention are compounds that modulate melanocyte activity. These compounds are chemical analogs of compounds produced by Malassezia yeast, or their crystalline form, hydrate, or salts that are cosmetically or pharmaceutically acceptable.

[0013] An additional embodiment of the present invention is a compound that acts on an aromatic hydrocarbon acceptor (AhR). The compound is a chemical analog of a compound produced by Malassezia yeast, or its crystalline form, hydrate, or a salt that is cosmetically or pharmaceutically acceptable.

[0014] Another embodiment of the present invention is a compound that improves hyperpigmentation caused by hyperpigmentation disorder. The compound is a chemical analog of the compound produced by Malassezia yeast, or its crystalline form, hydrate, or a salt that is cosmetically or pharmaceutically acceptable.

[0015] A further embodiment of the present invention is a compound that modulates melanin production. The compound is a chemical analog of a compound produced by Malassezia yeast, or It is a crystalline form, hydrate, or a salt that is acceptable for cosmetic or pharmaceutically acceptable use.

[0016] An additional embodiment of the present invention is a compound that modulates melanosome biogenesis. The compound is a chemical analog of a compound produced by Malassezia yeast, or its crystalline form, hydrate, or a cosmetic or pharmaceutically acceptable salt thereof.

[0017] Another embodiment of the present invention is a compound that modulates melanosome transport. The compound is a chemical analog of a compound produced by Malassezia yeast, or its crystalline form, hydrate, or a salt that is cosmetically or pharmaceutically acceptable.

[0018] Further embodiments of the present invention are compositions. These compositions comprise Malassezia yeast and a vehicle, diluent, or carrier that is cosmetically or pharmaceutically acceptable.

[0019] Another embodiment of the present invention is a composition. This composition comprises any of the compounds, including the analogs disclosed herein, and a vehicle, diluent, or carrier that is cosmetically or pharmaceutically acceptable.

[0020] A further embodiment of the present invention is a method for whitening skin in a subject. This method includes the step of contacting the subject with one of the compounds or compositions disclosed herein.

[0021] An additional embodiment of the present invention is a method for inducing melanocyte apoptosis in a subject. This method includes the step of contacting the subject with one of the compounds or compositions disclosed herein.

[0022] Another embodiment of the present invention is a method for modulating melanocyte activity in a subject. This method includes the step of contacting the subject with one of the compounds or compositions disclosed herein.

[0023] A further embodiment of the present invention is a method for activating an aromatic hydrocarbon acceptor (AhR) in a subject. This method includes the step of contacting the subject with one of the compounds or compositions disclosed herein.

[0024] An additional embodiment of the present invention is a method for improving hyperpigmentation caused by hyperpigmentation disorder in a subject requiring such improvement. This method includes the step of contacting the subject with one of the compounds or compositions disclosed herein.

[0025] Another embodiment of the present invention is a method for modulating melanin production in a subject. This method includes the step of contacting the subject with one of the compounds or compositions disclosed herein.

[0026] A further embodiment of the present invention is a method for modulating melanosome biogeneration in a subject. This method includes the step of contacting the subject with one of the compounds or compositions disclosed herein.

[0027] An additional embodiment of the present invention is a method for modulating melanosome transport in a subject. The method includes the step of contacting a subject with one of the compounds or compositions disclosed herein.

[0028] Another embodiment of the present invention is a compound. This compound has the structure of formula (II): [ka] (In the formula, R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, and R11 are independently selected from the group consisting of hydrogen and methyl, and at least one of R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, and R11 is methyl) or are crystalline forms thereof, hydrates, or salts that are acceptable as cosmetic or pharmaceutically acceptable.

[0029] A further embodiment of the present invention is a compound. This compound has the structure of formula (III): [ka] (wherein R1, R2, R3, R4, R5, R6, R7, R8, R9, and R10 are independently selected from the group consisting of hydrogen and methyl, and at least one of R1, R2, R3, R4, R5, R6, R7, R8, R9, and R10 is methyl) or a crystalline form thereof, hydrate, or a salt that is acceptable as a cosmetic or pharmaceutically acceptable product.

[0030] An additional embodiment of the present invention is a skin-whitening compound. This compound has the structure of formula (II): [ka] (wherein R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, and R11 are independently selected from the group consisting of hydrogen and methyl) or the crystalline form thereof, hydrate, or a salt that is acceptable for cosmetic or pharmaceutically acceptable purposes.

[0031] Another embodiment of the present invention is a skin-whitening compound. This compound has the structure of formula (III): [ka] (wherein R1, R2, R3, R4, R5, R6, R7, R8, R9, and R10 are independently selected from the group consisting of hydrogen and methyl) or the crystalline form thereof, hydrate, or a salt that is acceptable for cosmetic or pharmaceutically acceptable purposes.

[0032] A further embodiment of the present invention is a compound that induces melanocyte apoptosis. This compound has the structure of formula (II): [ka] (wherein R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, and R11 are independently selected from the group consisting of hydrogen and methyl) or the crystalline form thereof, hydrate, or a salt that is acceptable for cosmetic or pharmaceutically acceptable purposes.

[0033] An additional embodiment of the present invention is a compound that induces melanocyte apoptosis. This compound has the structure of formula (III): [ka] (wherein R1, R2, R3, R4, R5, R6, R7, R8, R9, and R10 are independently selected from the group consisting of hydrogen and methyl) or the crystalline form thereof, hydrate, or a salt that is acceptable for cosmetic or pharmaceutically acceptable purposes.

[0034] Another embodiment of the present invention is a compound that activates an aromatic hydrocarbon acceptor (AhR). This compound has the structure of formula (II): [ka] (wherein R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, and R11 are independently selected from the group consisting of hydrogen and methyl) or the crystalline form thereof, hydrate, or a salt that is acceptable for cosmetic or pharmaceutically acceptable purposes.

[0035] A further embodiment of the present invention is a compound that activates an aromatic hydrocarbon acceptor (AhR). This compound has the structure of formula (III): [ka] (wherein R1, R2, R3, R4, R5, R6, R7, R8, R9, and R10 are independently selected from the group consisting of hydrogen and methyl) or the crystalline form thereof, hydrate, or a salt that is acceptable for cosmetic or pharmaceutically acceptable purposes.

[0036] An additional embodiment of the present invention is a composition. This composition is a compound having the structure of formula (II): [ka] (wherein R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, and R11 are independently selected from the group consisting of hydrogen and methyl) or their crystalline form, hydrate, or a cosmetic or pharmaceutically acceptable salt, and a cosmetic or pharmaceutically acceptable vehicle, diluent, or carrier.

[0037] Another embodiment of the present invention is a composition. This composition is a compound having the structure of formula (III): [ka] (wherein R1, R2, R3, R4, R5, R6, R7, R8, R9, and R10 are independently selected from the group consisting of hydrogen and methyl) or their crystalline form, hydrate, or a cosmetic or pharmaceutically acceptable salt, and a cosmetic or pharmaceutically acceptable vehicle, diluent, or carrier.

[0038] A further embodiment of the present invention is a method for whitening the skin of a subject. This method involves applying a compound having the structure of formula (II) to the subject: [ka] The process includes contacting (wherein R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, and R11 are independently selected from the group consisting of hydrogen and methyl) or its crystalline form, hydrate, or a salt that is cosmetically or pharmaceutically acceptable.

[0039] An additional embodiment of the present invention is a method for whitening the skin in a subject. This method involves applying a compound having the structure of formula (III) to the subject: [ka] The process includes contacting (wherein R1, R2, R3, R4, R5, R6, R7, R8, R9, and R10 are independently selected from the group consisting of hydrogen and methyl) or its crystalline form, hydrate, or a salt that is acceptable for cosmetic or pharmaceutically acceptable purposes.

[0040] Another embodiment of the present invention is a method for inducing melanocyte apoptosis in a subject. This method involves applying a compound having the structure of formula (II) to the subject: [ka] The process includes contacting (wherein R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, and R11 are independently selected from the group consisting of hydrogen and methyl) or its crystalline form, hydrate, or a salt that is cosmetically or pharmaceutically acceptable.

[0041] A further embodiment of the present invention is a method for inducing melanocyte apoptosis in a subject. This method involves applying a compound having the structure of formula (III) to the subject: [ka] The process includes contacting (wherein R1, R2, R3, R4, R5, R6, R7, R8, R9, and R10 are independently selected from the group consisting of hydrogen and methyl) or its crystalline form, hydrate, or a salt that is acceptable for cosmetic or pharmaceutically acceptable purposes.

[0042] Another embodiment of the present invention is a method for activating an aromatic hydrocarbon acceptor (AhR) in a subject. This method involves applying a compound having the structure of formula (II) to the subject: [ka] The process includes contacting (wherein R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, and R11 are independently selected from the group consisting of hydrogen and methyl) or its crystalline form, hydrate, or a salt that is cosmetically or pharmaceutically acceptable.

[0043] A further embodiment of the present invention is a method for activating an aromatic hydrocarbon acceptor (AhR) in a subject. This method involves applying a compound having the structure of formula (III) to the subject: [Chemical formula] (wherein, R1, R2, R3, R4, R5, R6, R7, R8, R9 and R10 are independently selected from the group consisting of hydrogen and methyl), or a step of contacting its crystalline form, hydrate, or a cosmetic or pharmaceutically acceptable salt thereof.

[0044] One embodiment of the present invention is a compound. This compound has the structure of the following formula: [Chemical formula] (wherein, X is selected from the group consisting of NR 14 and O, Y is a covalent bond, CR5R6, O or NR 15 , R1, R2, R3, R4, R7, R8, R9, R 10 and R 11 are independently selected from the group consisting of hydrogen, halogen, CN, hydroxyl, R 16 or OR 16 , R 13 , R 14 and R 15 are independently hydrogen or R 16 , R5 and R6 are independently selected from the group consisting of hydrogen, hydroxyl, OR 16 , R 16 and C 3~6 cycloalkyl, or R5 and R6 together form an oxo (=O) group or C 3~6 cycloalkyl, R 12 is selected from the group consisting of hydrogen, -COR a and R 16 , R 16 are each independently formyl, C 1~9 alkyl, C 2~9 alkenyl or C 2~9 alkynyl, R a is selected from the group consisting of hydrogen, hydroxyl and OR 16 , when R a is hydrogen, Y is CR5R6, R 13 and R14 However, if both are hydrogen, then R1, R2, R3, R4, R5, R6, R7, R8, R9, R 10 and R 11 At least one of them is R 16 Or, R5 is hydroxyl, OR 16 , R 16 and C 3~6 Selected from the group consisting of cycloalkyl groups, or R5 and R6 together form an oxo (=O) group or C 3~6 It has (forming a cycloalkyl group), or its crystalline form, hydrate, or a salt that is acceptable for cosmetic or pharmaceutically acceptable purposes.

[0045] Another embodiment of the present invention is a compound. This compound has the following structure: [ka] (In the formula, R1, R4, R5, R6, R9 and R 10 These are hydrogen, hydroxyl, and halogen. , CN, R 13 , OR 13 , OCOR 13 R2 and R3 are independently selected from the group consisting of -CHO, and R2 and R3 are hydrogen, hydroxyl, halogen, CN, R 13 , OR 13 , OCOR 13 R2 and R3 are independently selected from the group consisting of -CHO, or R2 and R3 combine to form a 5-membered or 6-membered heterocycline, and R7 and R8 are hydrogen, hydroxyl, halogen, CN, R 13 , OR 13 , OCOR 13 R7 and R8 are independently selected from the group consisting of -CHO, or R7 and R8 combine to form a 5-membered or 6-membered heterocycline, 11 and R 12 These are, independently, hydrogen or R 13 And R 13 Each of them is independent of C 1~9 Alkyl, C 2~9 Alkenyl or C 2~9It is an alkynyl, R1, R2, R3, R4, R5, R6, R7, R8, R9 and R 10 It has at least one of which is not hydrogen, or is a crystalline form thereof, a hydrate, or a salt that is acceptable for cosmetic or pharmaceutically acceptable purposes.

[0046] An additional embodiment of the present invention is a skin-whitening compound. This compound has the following structure: [ka] (In the formula, X is NR 14 Y is selected from the group consisting of and O, and Y is a covalent bond, CR5R6, O, or NR 15 And R1, R2, R3, R4, R7, R8, R9, R 10 and R 11 is hydrogen, halogen, CN, hydroxyl, R 16 OR 16 Independently selected from the group consisting of R 13 , R 14 and R 15 These are, independently, hydrogen or R 16 R5 and R6 are hydrogen, hydroxyl, OR 16 , R 16 and C 3~6 R5 and R6 are independently selected from the group consisting of cycloalkyl groups, or together they form an oxo (=O) group or a C group. 3~6 Forming a cycloalkyl group, R 12 is hydrogen, -COR a and R 16 Selected from the group consisting of R 16 These are, independently, formil and C 1~9 Alkyl, C 2~9 Alkenyl or C 2~9 It is alkinyl, R a These are hydrogen, hydroxyl, and OR 16 It has (selected from the group consisting of) or is a crystalline form thereof, a hydrate, or a salt that is acceptable as a cosmetic or pharmaceutically acceptable substance.

[0047] A further embodiment of the present invention is a compound for whitening the skin. This compound has the structure of the following formula: [Chemical formula] (wherein, R1, R4, R5, R6, R9 and R 10 are independently selected from the group consisting of hydrogen, hydroxyl, halogen, CN, R 13 , OR 13 , OCOR 13 and -CHO, R2 and R3 are independently selected from the group consisting of hydrogen, hydroxyl, halogen, CN, R 13 , OR 13 , OCOR 13 and -CHO or R2 and R3 together form a 5- or 6-membered heterocyclyl, R7 and R8 are independently selected from the group consisting of hydrogen, hydroxyl, halogen, CN, R 13 , OR 13 , OCOR 13 and -CHO or R7 and R8 together form a 5- or 6-membered heterocyclyl, R 11 and R 12 are independently hydrogen or R 13 , R 13 are each independently C 1~9 alkyl, C 2~9 alkenyl or C 2~9 alkynyl), or its crystalline form, hydrate, or a cosmetic or pharmaceutically acceptable salt.

[0048] Another embodiment of the present invention is a compound for whitening the skin. This compound is [Chemical formula] selected from the group consisting of.

[0049] An additional embodiment of the present invention is a compound that induces melanocyte apoptosis. This compound has the structure of the following formula: [Chemical formula] (wherein, X is selected from the group consisting of NR 14 and O, Y is a covalent bond, CR5R6, O or NR 15 , R1, R2, R3, R4, R7, R8, R9, R 10 and R 11 are independently selected from the group consisting of hydrogen, halogen, CN, hydroxyl, R 16 or OR 16 , R 13 , R 14 and R 15 are independently hydrogen or R 16 , R5 and R6 are independently selected from the group consisting of hydrogen, hydroxyl, OR 16 , R 16 and C 3~6 cycloalkyl, or R5 and R6 together form an oxo (=O) group or C 3~6 cycloalkyl, R 12 is selected from the group consisting of hydrogen, -COR a and R 16 , R 16 are each independently formyl, C 1~9 alkyl, C 2~9 alkenyl or C 2~9 alkynyl, R a is selected from the group consisting of hydrogen, hydroxyl and OR 16 (having), or a crystalline form, hydrate, or a cosmetic or pharmaceutically acceptable salt thereof.)

[0050] A further embodiment of the present invention is a compound that induces melanocyte apoptosis. This compound has the structure of the following formula: [Chemical formula] (wherein, R1, R4, R5, R6, R9 and R 10 are hydrogen, hydroxyl, halogen, CN, R 13 , OR 13 , OCOR 13R2 and R3 are independently selected from the group consisting of -CHO, and R2 and R3 are hydrogen, hydroxyl, halogen, CN, R 13 , OR 13 , OCOR 13 R2 and R3 are independently selected from the group consisting of -CHO, or R2 and R3 combine to form a 5-membered or 6-membered heterocycline, and R7 and R8 are hydrogen, hydroxyl, halogen, CN, R 13 , OR 13 , OCOR 13 R7 and R8 are independently selected from the group consisting of -CHO, or R7 and R8 combine to form a 5-membered or 6-membered heterocycline, 11 and R 12 These are, independently, hydrogen or R 13 And R 13 Each of them is independent of C 1~9 Alkyl, C 2~9 Alkenyl or C 2~9 It is an alkynyl compound, or a crystalline form thereof, a hydrate, or a salt that is acceptable for cosmetic or pharmaceutically acceptable purposes.

[0051] Another embodiment of the present invention is a compound that induces melanocyte apoptosis. This compound is [ka] It is selected from the group consisting of the following.

[0052] An additional embodiment of the present invention is a compound that modulates aromatic hydrocarbon acceptor (AhR) activity. The compound has the following structure: [ka] (In the formula, X is NR 14 Y is selected from the group consisting of and O, and Y is a covalent bond, CR5R6, O, or NR 15 And R1, R2, R3, R4, R7, R8, R9, R 10 and R 11 is hydrogen, halogen, CN, hydroxyl, R 16 OR16 Independently selected from the group consisting of R 13 , R 14 and R 15 These are, independently, hydrogen or R 16 R5 and R6 are hydrogen, hydroxyl, OR 16 , R 16 and C 3~6 R5 and R6 are independently selected from the group consisting of cycloalkyl groups, or together they form an oxo (=O) group or a C group. 3~6 Forming a cycloalkyl group, R 12 is hydrogen, -COR a and R 16 Selected from the group consisting of R 16 These are, independently, formil and C 1~9 Alkyl, C 2~9 Alkenyl or C 2~9 It is alkinyl, R a These are hydrogen, hydroxyl, and OR 16 It has (selected from the group consisting of) or is a crystalline form thereof, a hydrate, or a salt that is acceptable as a cosmetic or pharmaceutically acceptable substance.

[0053] A further embodiment of the present invention is a compound that modulates aromatic hydrocarbon acceptor (AhR) activity. The compound has the following structure: [ka] (In the formula, R1, R4, R5, R6, R9 and R 10 is hydrogen, hydroxyl, halogen, CN, R 13 , OR 13 , OCOR 13 R2 and R3 are independently selected from the group consisting of -CHO, and R2 and R3 are hydrogen, hydroxyl, halogen, CN, R 13 , OR 13 , OCOR 13 R2 and R3 are independently selected from the group consisting of -CHO, or R2 and R3 combine to form a 5-membered or 6-membered heterocycline, and R7 and R8 are hydrogen, hydroxyl, halogen, CN, R 13 , OR 13, OCOR 13 R7 and R8 are independently selected from the group consisting of -CHO, or R7 and R8 combine to form a 5-membered or 6-membered heterocycline, 11 and R 12 These are, independently, hydrogen or R 13 And R 13 Each of them is independent of C 1~9 Alkyl, C 2~9 Alkenyl or C 2~9 It is an alkynyl compound, or a crystalline form thereof, a hydrate, or a salt that is acceptable for cosmetic or pharmaceutically acceptable purposes.

[0054] Another embodiment of the present invention is a compound that modulates aromatic hydrocarbon acceptor (AhR) activity. This compound is [ka] It is selected from the group consisting of the following.

[0055] An additional embodiment of the present invention is a compound that modulates melanin formation. The compound has the following structure: [ka] (In the formula, X is NR 14 Y is selected from the group consisting of and O, and Y is a covalent bond, CR5R6, O, or NR 15 And R1, R2, R3, R4, R7, R8, R9, R 10 and R 11 is hydrogen, halogen, CN, hydroxyl, R 16 OR 16 Independently selected from the group consisting of R 13 , R 14 and R 15 These are, independently, hydrogen or R 16 R5 and R6 are hydrogen, hydroxyl, OR 16 , R 16 and C 3~6 R5 and R6 are independently selected from the group consisting of cycloalkyl groups, or together they form an oxo (=O) group or a C group.3~6 Forming a cycloalkyl group, R 12 is hydrogen, -COR a and R 16 Selected from the group consisting of R 16 These are, independently, formil and C 1~9 Alkyl, C 2~9 Alkenyl or C 2~9 It is alkinyl, R a These are hydrogen, hydroxyl, and OR 16 It has (selected from the group consisting of) or is a crystalline form thereof, a hydrate, or a salt that is acceptable as a cosmetic or pharmaceutically acceptable substance.

[0056] A further embodiment of the present invention is a compound that modulates melanin formation. The compound has the following structure: [ka] (In the formula, R1, R4, R5, R6, R9 and R 10 is hydrogen, hydroxyl, halogen, CN, R 13 , OR 13 , OCOR 13 R2 and R3 are independently selected from the group consisting of -CHO, and R2 and R3 are hydrogen, hydroxyl, halogen, CN, R 13 , OR 13 , OCOR 13 R2 and R3 are independently selected from the group consisting of -CHO, or R2 and R3 combine to form a 5-membered or 6-membered heterocycline, and R7 and R8 are hydrogen, hydroxyl, halogen, CN, R 13 , OR 13 , OCOR 13 R7 and R8 are independently selected from the group consisting of -CHO, or R7 and R8 combine to form a 5-membered or 6-membered heterocycline, 11 and R 12 These are, independently, hydrogen or R 13 And R 13 Each of them is independent of C 1~9 Alkyl, C 2~9 Alkenyl or C 2~9It is an alkynyl compound, or a crystalline form thereof, a hydrate, or a salt that is acceptable for cosmetic or pharmaceutically acceptable purposes.

[0057] Another embodiment of the present invention is a compound that modulates melanin formation. This compound is [ka] It is selected from the group consisting of the following.

[0058] An additional embodiment of the present invention is a compound that modulates melanin concentration. The compound has the following structure: [ka] (In the formula, X is NR 14 Y is selected from the group consisting of and O, and Y is a covalent bond, CR5R6, O, or NR 15 And R1, R2, R3, R4, R7, R8, R9, R 10 and R 11 is hydrogen, halogen, CN, hydroxyl, R 16 OR 16 Independently selected from the group consisting of R 13 , R 14 and R 15 These are, independently, hydrogen or R 16 R5 and R6 are hydrogen, hydroxyl, OR 16 , R 16 and C 3~6 R5 and R6 are independently selected from the group consisting of cycloalkyl groups, or together they form an oxo (=O) group or a C group. 3~6 Forming a cycloalkyl group, R 12 is hydrogen, -COR a and R 16 Selected from the group consisting of R 16 These are, independently, formil and C 1~9 Alkyl, C 2~9 Alkenyl or C 2~9 It is alkinyl, R a These are hydrogen, hydroxyl, and OR 16It has (selected from the group consisting of) or is a crystalline form thereof, a hydrate, or a salt that is acceptable as a cosmetic or pharmaceutically acceptable substance.

[0059] A further embodiment of the present invention is a compound that modulates melanin concentration. The compound has the following structure: [ka] (In the formula, R1, R4, R5, R6, R9 and R 10 is hydrogen, hydroxyl, halogen, CN, R 13 , OR 13 , OCOR 13 R2 and R3 are independently selected from the group consisting of -CHO, and R2 and R3 are hydrogen, hydroxyl, halogen, CN, R 13 , OR 13 , OCOR 13 R2 and R3 are independently selected from the group consisting of -CHO, or R2 and R3 combine to form a 5-membered or 6-membered heterocycline, and R7 and R8 are hydrogen, hydroxyl, halogen, CN, R 13 , OR 13 , OCOR 13 R7 and R8 are independently selected from the group consisting of -CHO, or R7 and R8 combine to form a 5-membered or 6-membered heterocycline, 11 and R 12 These are, independently, hydrogen or R 13 And R 13 Each of them is independent of C 1~9 Alkyl, C 2~9 Alkenyl or C 2~9 It is an alkynyl compound, or a crystalline form thereof, a hydrate, or a salt that is acceptable for cosmetic or pharmaceutically acceptable purposes.

[0060] Another embodiment of the present invention is a compound that modulates melanin concentration. This compound is [ka] It is selected from the group consisting of the following.

[0061] An additional embodiment of the present invention is a composition. This composition is a compound having the structure of the following formula: [ka] (In the formula, X is NR 14 Y is selected from the group consisting of and O, and Y is a covalent bond, CR5R6, O, or NR 15 And R1, R2, R3, R4, R7, R8, R9, R 10 and R 11 is hydrogen, halogen, CN, hydroxyl, R 16 OR 16 Independently selected from the group consisting of R 13 , R 14 and R 15 These are, independently, hydrogen or R 16 R5 and R6 are hydrogen, hydroxyl, OR 16 , R 16 and C 3~6 R5 and R6 are independently selected from the group consisting of cycloalkyl groups, or together they form an oxo (=O) group or a C group. 3~6 Forming a cycloalkyl group, R 12 is hydrogen, -COR a and R 16 Selected from the group consisting of R 16 These are, independently, formil and C 1~9 Alkyl, C 2~9 Alkenyl or C 2~9 It is alkinyl, R a These are hydrogen, hydroxyl, and OR 16 (Selected from the group consisting of) or its crystalline form, hydrate, or salt that is acceptable as a cosmetic or pharmaceutically acceptable substance.

[0062] A further embodiment of the present invention is a composition. This composition is a compound having the structure of the following formula: [ka] (In the formula, R1, R4, R5, R6, R9 and R 10 is hydrogen, hydroxyl, halogen, CN, R13 , OR 13 , OCOR 13 R2 and R3 are independently selected from the group consisting of -CHO, and R2 and R3 are hydrogen, hydroxyl, halogen, CN, R 13 , OR 13 , OCOR 13 R2 and R3 are independently selected from the group consisting of -CHO, or R2 and R3 combine to form a 5-membered or 6-membered heterocycline, and R7 and R8 are hydrogen, hydroxyl, halogen, CN, R 13 , OR 13 , OCOR 13 R7 and R8 are independently selected from the group consisting of -CHO, or R7 and R8 combine to form a 5-membered or 6-membered heterocycline, 11 and R 12 These are, independently, hydrogen or R 13 And R 13 Each of them is independent of C 1~9 Alkyl, C 2~9 Alkenyl or C 2~9 This includes alkynnyls (or their crystalline forms, hydrates, or salts that are acceptable for cosmetic or pharmaceutically acceptable purposes).

[0063] Another embodiment of the present invention is a composition. This composition is [ka] It includes compounds selected from the group consisting of the following.

[0064] An additional embodiment of the present invention is a method for whitening the skin in a subject. This method involves applying a compound having the structure of the following formula to the subject: [ka] (In the formula, X is NR 14 Y is selected from the group consisting of and O, and Y is a covalent bond, CR5R6, O, or NR 15 And R1, R2, R3, R4, R7, R8, R9, R 10 and R 11 is hydrogen, halogen, CN, hydroxyl, R16 OR 16 Independently selected from the group consisting of R 13 , R 14 and R 15 These are, independently, hydrogen or R 16 R5 and R6 are hydrogen, hydroxyl, OR 16 , R 16 and C 3~6 R5 and R6 are independently selected from the group consisting of cycloalkyl groups, or together they form an oxo (=O) group or a C group. 3~6 Forming a cycloalkyl group, R 12 is hydrogen, -COR a and R 16 Selected from the group consisting of R 16 These are, independently, formil and C 1~9 Alkyl, C 2~9 Alkenyl or C 2~9 It is alkinyl, R a These are hydrogen, hydroxyl, and OR 16 The process includes the step of contacting a salt selected from the group consisting of (or a crystalline form thereof, a hydrate, or a salt that is acceptable for cosmetic or pharmaceutically acceptable purposes).

[0065] A further embodiment of the present invention is a method for whitening the skin of a subject. This method involves applying a compound having the structure of the following formula to the subject: [ka] (In the formula, R1, R4, R5, R6, R9 and R 10 is hydrogen, hydroxyl, halogen, CN, R 13 , OR 13 , OCOR 13 R2 and R3 are independently selected from the group consisting of -CHO, and R2 and R3 are hydrogen, hydroxyl, halogen, CN, R 13 , OR 13 , OCOR 13 R2 and R3 are independently selected from the group consisting of -CHO, or R2 and R3 combine to form a 5-membered or 6-membered heterocycline, and R7 and R8 are hydrogen, hydroxyl, halogen, CN, R 13, OR 13 , OCOR 13 R7 and R8 are independently selected from the group consisting of -CHO, or R7 and R8 combine to form a 5-membered or 6-membered heterocycline, 11 and R 12 These are, independently, hydrogen or R 13 And R 13 Each of them is independent of C 1~9 Alkyl, C 2~9 Alkenyl or C 2~9 The process includes the step of contacting an alkynyl (or a crystalline form thereof, a hydrate, or a salt that is cosmetically or pharmaceutically acceptable).

[0066] Another embodiment of the present invention is a method for whitening the skin of a subject. This method involves applying a compound selected from the group consisting of the following to the subject: [ka] This includes the step of bringing them into contact.

[0067] An additional embodiment of the present invention is a method for inducing melanocyte apoptosis in a subject. This method involves applying a compound having the structure of the following formula to the subject: [ka] (In the formula, X is NR 14 Y is selected from the group consisting of and O, and Y is a covalent bond, CR5R6, O, or NR 15 And R1, R2, R3, R4, R7, R8, R9, R 10 and R 11 is hydrogen, halogen, CN, hydroxyl, R 16 OR 16 Independently selected from the group consisting of R 13 , R 14 and R 15 These are, independently, hydrogen or R 16 R5 and R6 are hydrogen, hydroxyl, OR 16 , R 16 and C 3~6R5 and R6 are independently selected from the group consisting of cycloalkyl groups, or together they form an oxo (=O) group or a C group. 3~6 Forming a cycloalkyl group, R 12 is hydrogen, -COR a and R 16 Selected from the group consisting of R 16 These are, independently, formil and C 1~9 Alkyl, C 2~9 Alkenyl or C 2~9 It is alkinyl, R a These are hydrogen, hydroxyl, and OR 16 The process includes the step of contacting a salt selected from the group consisting of (or a crystalline form thereof, a hydrate, or a salt that is acceptable for cosmetic or pharmaceutically acceptable purposes).

[0068] A further embodiment of the present invention is a method for inducing melanocyte apoptosis in a subject. This method involves applying a compound having the structure of the following formula to the subject: [ka] (In the formula, R1, R4, R5, R6, R9 and R 10 is hydrogen, hydroxyl, halogen, CN, R 13 , OR 13 , OCOR 13 R2 and R3 are independently selected from the group consisting of -CHO, and R2 and R3 are hydrogen, hydroxyl, halogen, CN, R 13 , OR 13 , OCOR 13 R2 and R3 are independently selected from the group consisting of -CHO, or R2 and R3 combine to form a 5-membered or 6-membered heterocycline, and R7 and R8 are hydrogen, hydroxyl, halogen, CN, R 13 , OR 13 , OCOR 13 R7 and R8 are independently selected from the group consisting of -CHO, or R7 and R8 combine to form a 5-membered or 6-membered heterocycline, 11 and R 12 These are, independently, hydrogen or R 13 And R 13Each of them is independent of C 1~9 Alkyl, C 2~9 Alkenyl or C 2~9 The process includes the step of contacting an alkynyl (or a crystalline form thereof, a hydrate, or a salt that is cosmetically or pharmaceutically acceptable).

[0069] Another embodiment of the present invention is a method for inducing melanocyte apoptosis in a subject. This method involves applying a compound selected from the group consisting of the following to the subject: [ka] This includes the step of bringing them into contact.

[0070] An additional embodiment of the present invention is a method for modulating aromatic hydrocarbon acceptor (AhR) activity in a subject. This method involves applying a compound having the structure of the following formula to the subject: [ka] (In the formula, X is NR 14 Y is selected from the group consisting of and O, and Y is a covalent bond, CR5R6, O, or NR 15 And R1, R2, R3, R4, R7, R8, R9, R 10 and R 11 is hydrogen, halogen, CN, hydroxyl, R 16 OR 16 Independently selected from the group consisting of R 13 , R 14 and R 15 These are, independently, hydrogen or R 16 R5 and R6 are hydrogen, hydroxyl, OR 16 , R 16 and C 3~6 R5 and R6 are independently selected from the group consisting of cycloalkyl groups, or together they form an oxo (=O) group or a C group. 3~6 Forming a cycloalkyl group, R 12 is hydrogen, -COR a and R 16 Selected from the group consisting of R 16These are, independently, formil and C 1~9 Alkyl, C 2~9 Alkenyl or C 2~9 It is alkinyl, R a These are hydrogen, hydroxyl, and OR 16 The process includes the step of contacting a salt selected from the group consisting of (or a crystalline form thereof, a hydrate, or a salt that is acceptable for cosmetic or pharmaceutically acceptable purposes).

[0071] A further embodiment of the present invention is a method for modulating aromatic hydrocarbon acceptor (AhR) activity in a target. This method involves a compound having the structure of the following formula in the target: [ka] (In the formula, R1, R4, R5, R6, R9 and R 10 is hydrogen, hydroxyl, halogen, CN, R 13 , OR 13 , OCOR 13 R2 and R3 are independently selected from the group consisting of -CHO, and R2 and R3 are hydrogen, hydroxyl, halogen, CN, R 13 , OR 13 , OCOR 13 R2 and R3 are independently selected from the group consisting of -CHO, or R2 and R3 combine to form a 5-membered or 6-membered heterocycline, and R7 and R8 are hydrogen, hydroxyl, halogen, CN, R 13 , OR 13 , OCOR 13 R7 and R8 are independently selected from the group consisting of -CHO, or R7 and R8 combine to form a 5-membered or 6-membered heterocycline, 11 and R 12 These are, independently, hydrogen or R 13 And R 13 Each of them is independent of C 1~9 Alkyl, C 2~9 Alkenyl or C 2~9 The process includes the step of contacting an alkynyl (or a crystalline form thereof, a hydrate, or a salt that is cosmetically or pharmaceutically acceptable).

[0072] Another embodiment of the present invention is a method for modulating aromatic hydrocarbon acceptor (AhR) activity in a subject. This method involves applying a compound selected from the group consisting of the following to the subject: [ka] This includes the step of bringing them into contact.

[0073] An additional embodiment of the present invention is a method for modulating melanin formation in a subject. This method involves applying a compound having the structure of the following formula to the subject: [ka] (In the formula, X is NR 14 Y is selected from the group consisting of and O, and Y is a covalent bond, CR5R6, O, or NR 15 And R1, R2, R3, R4, R7, R8, R9, R 10 and R 11 is hydrogen, halogen, CN, hydroxyl, R 16 OR 16 Independently selected from the group consisting of R 13 , R 14 and R 15 These are, independently, hydrogen or R 16 R5 and R6 are hydrogen, hydroxyl, OR 16 , R 16 and C 3~6 R5 and R6 are independently selected from the group consisting of cycloalkyl groups, or together they form an oxo (=O) group or a C group. 3~6 Forming a cycloalkyl group, R 12 is hydrogen, -COR a and R 16 Selected from the group consisting of R 16 These are, independently, formil and C 1~9 Alkyl, C 2~9 Alkenyl or C 2~9 It is alkinyl, R a These are hydrogen, hydroxyl, and OR 16The process includes the step of contacting a salt selected from the group consisting of (or a crystalline form thereof, a hydrate, or a salt that is acceptable for cosmetic or pharmaceutically acceptable purposes).

[0074] A further embodiment of the present invention is a method for modulating melanin formation in a subject. This method involves applying a compound having the structure of the following formula to the subject: [ka] (In the formula, R1, R4, R5, R6, R9 and R 10 is hydrogen, hydroxyl, halogen, CN, R 13 , OR 13 , OCOR 13 R2 and R3 are independently selected from the group consisting of -CHO, and R2 and R3 are hydrogen, hydroxyl, halogen, CN, R 13 , OR 13 , OCOR 13 R2 and R3 are independently selected from the group consisting of -CHO, or R2 and R3 combine to form a 5-membered or 6-membered heterocycline, and R7 and R8 are hydrogen, hydroxyl, halogen, CN, R 13 , OR 13 , OCOR 13 R7 and R8 are independently selected from the group consisting of -CHO, or R7 and R8 combine to form a 5-membered or 6-membered heterocycline, 11 and R 12 These are, independently, hydrogen or R 13 And R 13 Each of them is independent of C 1~9 Alkyl, C 2~9 Alkenyl or C 2~9 The process includes the step of contacting an alkynyl (or a crystalline form thereof, a hydrate, or a salt that is cosmetically or pharmaceutically acceptable).

[0075] Another embodiment of the present invention is a method for modulating melanin formation in a subject. This method involves applying a compound selected from the group consisting of the following to the subject: [ka] This includes the step of bringing them into contact.

[0076] An additional embodiment of the present invention is a method for modulating melanin concentration in a subject. This method involves applying a compound having the structure of the following formula to the subject: [ka] (In the formula, X is NR 14 Y is selected from the group consisting of and O, and Y is a covalent bond, CR5R6, O, or NR 15 And R1, R2, R3, R4, R7, R8, R9, R 10 and R 11 is hydrogen, halogen, CN, hydroxyl, R 16 OR 16 Independently selected from the group consisting of R 13 , R 14 and R 15 These are, independently, hydrogen or R 16 R5 and R6 are hydrogen, hydroxyl, OR 16 , R 16 and C 3~6 R5 and R6 are independently selected from the group consisting of cycloalkyl groups, or together they form an oxo (=O) group or a C group. 3~6 Forming a cycloalkyl group, R 12 is hydrogen, -COR a and R 16 Selected from the group consisting of R 16 These are, independently, formil and C 1~9 Alkyl, C 2~9 Alkenyl or C 2~9 It is alkinyl, R a These are hydrogen, hydroxyl, and OR 16 The process includes the step of contacting a salt selected from the group consisting of (or a crystalline form thereof, a hydrate, or a salt that is acceptable for cosmetic or pharmaceutically acceptable purposes).

[0077] A further embodiment of the present invention is a method for modulating melanin concentration in a subject. This method involves applying a compound having the structure of the following formula to the subject: [ka] (In the formula, R1, R4, R5, R6, R9 and R 10 is hydrogen, hydroxyl, halogen, CN, R 13 , OR 13 , OCOR 13 R2 and R3 are independently selected from the group consisting of -CHO, and R2 and R3 are hydrogen, hydroxyl, halogen, CN, R 13 , OR 13 , OCOR 13 R2 and R3 are independently selected from the group consisting of -CHO, or R2 and R3 combine to form a 5-membered or 6-membered heterocycline, and R7 and R8 are hydrogen, hydroxyl, halogen, CN, R 13 , OR 13 , OCOR 13 R7 and R8 are independently selected from the group consisting of -CHO, or R7 and R8 combine to form a 5-membered or 6-membered heterocycline, 11 and R 12 These are, independently, hydrogen or R 13 And R 13 Each of them is independent of C 1~9 Alkyl, C 2~9 Alkenyl or C 2~9 The process includes the step of contacting an alkynyl (or a crystalline form thereof, a hydrate, or a salt that is cosmetically or pharmaceutically acceptable).

[0078] Another embodiment of the present invention is a method for modulating melanin concentration in a subject. This method involves applying a compound selected from the group consisting of the following to the subject: [ka] This includes the step of bringing them into contact.

[0079] One embodiment of the present invention is a compound that whitens the skin. This compound has the following structure: [ka] It is a compound of, or a chemical analog thereof, crystalline form, hydrate, or a pharmaceutically or cosmetically acceptable salt thereof.

[0080] Another embodiment of the present invention is a compound that induces melanocyte apoptosis. This compound has the following structure: [ka] It is a compound of, or a chemical analog thereof, crystalline form, hydrate, or a pharmaceutically or cosmetically acceptable salt thereof.

[0081] An additional embodiment of the present invention is a compound that modulates aromatic hydrocarbon acceptor (AhR) activity. The compound has the following structure: [ka] It is a compound of, or a chemical analog thereof, crystalline form, hydrate, or a pharmaceutically or cosmetically acceptable salt thereof.

[0082] A further embodiment of the present invention is a compound that modulates melanin formation. The compound has the following structure: [ka] It is a compound of, or a chemical analog thereof, crystalline form, hydrate, or a pharmaceutically or cosmetically acceptable salt thereof.

[0083] Another embodiment of the present invention is a compound that modulates melanin concentration. This compound has the following structure: [ka] It is a compound of, or a chemical analog thereof, crystalline form, hydrate, or a pharmaceutically or cosmetically acceptable salt thereof.

[0084] An additional embodiment of the present invention is a composition comprising a compound. The compound has the following structure: [ka] It is a compound of, or a chemical analog thereof, crystalline form, hydrate, or a pharmaceutically or cosmetically acceptable salt thereof.

[0085] A further embodiment of the present invention is a method for whitening the skin of a subject. This method involves contacting the subject with a compound, wherein the compound has the following structure: [ka] The step comprises having or having a chemical analog, crystalline form, hydrate, or pharmaceutically or cosmetically acceptable salt thereof.

[0086] Another embodiment of the present invention is a method for inducing melanocyte apoptosis in a subject. This method involves contacting a subject with a compound, wherein the compound has the structure of the following formula: [ka] The step comprises having or having a chemical analog, crystalline form, hydrate, or pharmaceutically or cosmetically acceptable salt thereof.

[0087] An additional embodiment of the present invention is a method for modulating aromatic hydrocarbon acceptor (AhR) activity in a subject. The method involves contacting a subject with a compound, wherein the compound has the structure of the following formula: [ka] The step comprises having or having a chemical analog, crystalline form, hydrate, or pharmaceutically or cosmetically acceptable salt thereof.

[0088] A further embodiment of the present invention is a method for modulating melanin formation in a subject. This method involves contacting a subject with a compound, wherein the compound has the structure of the following formula: [ka] The step comprises having or having a chemical analog, crystalline form, hydrate, or pharmaceutically or cosmetically acceptable salt thereof.

[0089] Another embodiment of the present invention is a method for modulating melanin concentration in a subject. This method involves contacting the subject with a compound, wherein the compound has the following structure: [ka] The step comprises having or having a chemical analog, crystalline form, hydrate, or pharmaceutically or cosmetically acceptable salt thereof.

[0090] An additional embodiment of the present invention is a composition, which comprises one or more of the compounds listed in Table 5 or Figure 130, or their chemical analogs, crystalline forms, hydrates, or pharmaceutically or cosmetically acceptable salts.

[0091] A further embodiment of the present invention is a method for whitening skin in a subject. This method comprises the step of contacting the subject with one or more of the compounds listed in Table 5 or Figure 130, or their chemical analogs, crystalline forms, hydrates, or pharmaceutically or cosmetically acceptable salts.

[0092] Another embodiment of the present invention is a method for inducing melanocyte apoptosis in a subject. This method comprises the step of contacting the subject with one or more of the compounds listed in Table 5 or Figure 130, or their chemical analogs, crystalline forms, hydrates, or pharmaceutically or cosmetically acceptable salts.

[0093] An additional embodiment of the present invention is a method for modulating aromatic hydrocarbon acceptor (AhR) activity in a subject. This method comprises the step of contacting the subject with one or more of the compounds listed in Table 5 or Figure 130, or their chemical analogs, crystalline forms, hydrates, or pharmaceutically or cosmetically acceptable salts.

[0094] A further embodiment of the present invention is a method for modulating melanin formation in a subject. This method comprises the step of contacting the subject with one or more of the compounds listed in Table 5 or Figure 130, or their chemical analogs, crystalline forms, hydrates, or pharmaceutically or cosmetically acceptable salts.

[0095] Another embodiment of the present invention is a method for modulating melanin concentration in a subject. This method comprises the step of contacting the subject with one or more of the compounds listed in Table 5 or Figure 130, or their chemical analogs, crystalline forms, hydrates, or pharmaceutically or cosmetically acceptable salts.

[0096] An additional embodiment of the present invention is a composition, which comprises one or more of the compounds listed in Table 5 or Figure 130, or their chemical analogs, crystalline forms, hydrates, or pharmaceutically or cosmetically acceptable salts.

[0097] A further embodiment of the present invention is a skin-whitening composition. This composition comprises one or more of the compounds listed in Table 5 or Figure 130, or their chemical analogs, crystalline forms, hydrates, or pharmaceutically or cosmetically acceptable salts.

[0098] Another embodiment of the present invention is a composition for inducing melanocyte apoptosis. This composition comprises one or more of the compounds listed in Table 5 or Figure 130, or their chemical analogs, crystalline forms, hydrates, or pharmaceutically or cosmetically acceptable salts.

[0099] An additional embodiment of the present invention is a composition that modulates aromatic hydrocarbon acceptor (AhR) activity. The composition comprises one or more of the compounds listed in Table 5 or Figure 130, or their chemical analogs, crystalline forms, hydrates, or pharmaceutically or cosmetically acceptable salts.

[0100] A further embodiment of the present invention is a composition that modulates melanin formation. This composition comprises one or more of the compounds listed in Table 5 or Figure 130, or their chemical analogs, crystalline forms, hydrates, or pharmaceutically or cosmetically acceptable salts.

[0101] Another embodiment of the present invention is a composition for modulating melanin concentration. This composition comprises one or more of the compounds listed in Table 5 or Figure 130, or their chemical analogs, crystalline forms, hydrates, or pharmaceutically or cosmetically acceptable salts.

[0102] An additional embodiment of the present invention is a method for whitening skin in a subject. The method comprises the step of contacting a subject with a composition, wherein the composition comprises one or more of the compounds listed in Table 5 or Figure 130, or their chemical analogs, crystalline forms, hydrates, or pharmaceutically or cosmetically acceptable salts.

[0103] A further embodiment of the present invention is a method for inducing melanocyte apoptosis in a subject. The method comprises the step of contacting a subject with a composition, wherein the composition comprises one or more of the compounds listed in Table 5 or Figure 130, or their chemical analogs, crystalline forms, hydrates, or pharmaceutically or cosmetically acceptable salts.

[0104] Another embodiment of the present invention is a method for modulating aromatic hydrocarbon acceptor (AhR) activity in a subject. This method comprises the step of contacting a subject with a composition, wherein the composition comprises one or more of the compounds listed in Table 5 or Figure 130, or their chemical analogs, crystalline forms, hydrates, or pharmaceutically or cosmetically acceptable salts.

[0105] An additional embodiment of the present invention is a method for modulating melanin formation in a subject. This method comprises the step of contacting a subject with a composition, wherein the composition comprises one or more of the compounds listed in Table 5 or Figure 130, or their chemical analogs, crystalline forms, hydrates, or pharmaceutically or cosmetically acceptable salts. A further embodiment of the present invention is a method for modulating melanin concentration in a subject. The method comprises the step of contacting a subject with a composition, wherein the composition comprises one or more of the compounds listed in Table 5 or Figure 130, or their chemical analogs, crystalline forms, hydrates, or pharmaceutically or cosmetically acceptable salts.

[0106] Another embodiment of the present invention is a composition comprising Malassezia yeast and a vehicle, diluent, or carrier that is cosmetically or pharmaceutically acceptable.

[0107] An additional embodiment of the present invention is a composition. This composition is a compound having the structure of the following formula: [ka] (In the formula, X is NR 14 Y is selected from the group consisting of and O, and Y is a covalent bond, CR5R6, O, or NR 15 And R1, R2, R3, R4, R7, R8, R9, R 10 and R 11 is hydrogen, halogen, CN, hydroxyl, R 16 OR 16Independently selected from the group consisting of R 13 , R 14 and R 15 These are, independently, hydrogen or R 16 R5 and R6 are hydrogen, hydroxyl, OR 16 , R 16 and C 3~6 R5 and R6 are independently selected from the group consisting of cycloalkyl groups, or together they form an oxo (=O) group or a C group. 3~6 Forming a cycloalkyl group, R 12 is hydrogen, -COR a and R 16 Selected from the group consisting of R 16 These are, independently, formil and C 1~9 Alkyl, C 2~9 Alkenyl or C 2~9 It is alkinyl, R a These are hydrogen, hydroxyl, and OR 16 (Selected from the group consisting of) Or its crystalline form, hydrate, or salt that is acceptable as a cosmetic or pharmaceutically acceptable substance. and includes vehicles, diluents, or carriers that are acceptable as cosmetic or pharmaceutically acceptable.

[0108] A further embodiment of the present invention is a composition. This composition has the structure of the following formula. compound: [ka] (In the formula, R1, R4, R5, R6, R9 and R 10 is hydrogen, hydroxyl, halogen, CN, R 13 , OR 13 , OCOR 13 R2 and R3 are independently selected from the group consisting of -CHO, and R2 and R3 are hydrogen, hydroxyl, halogen, CN, R 13 , OR 13 , OCOR 13R2 and R3 are independently selected from the group consisting of -CHO, or R2 and R3 combine to form a 5-membered or 6-membered heterocycline, and R7 and R8 are hydrogen, hydroxyl, halogen, CN, R 13 , OR 13 , OCOR 13 R7 and R8 are independently selected from the group consisting of -CHO, or R7 and R8 combine to form a 5-membered or 6-membered heterocycline, 11 and R 12 These are, independently, hydrogen or R 13 And R 13 Each of them is independent of C 1~9 Alkyl, C 2~9 Alkenyl or C 2~9 (It is alkinyl) Or its crystalline form, hydrate, or salt that is acceptable as a cosmetic or pharmaceutically acceptable substance. and includes vehicles, diluents, or carriers that are acceptable as cosmetic or pharmaceutically acceptable.

[0109] Another embodiment of the present invention is a composition. This composition comprises a compound listed in Table 5 or Figure 130, or its chemical analog, crystalline form, hydrate, or a salt that is cosmetically or pharmaceutically acceptable therefor. and includes vehicles, diluents, or carriers that are acceptable as cosmetic or pharmaceutically acceptable.

[0110] An additional embodiment of the present invention is a method for treating or preventing UV-induced skin damage in a subject. This method includes the step of contacting the subject with one of the compositions disclosed herein.

[0111] A further embodiment of the present invention is a method for treating or preventing UV-induced erythema in a subject. This method includes the step of contacting the subject with one of the compositions disclosed herein.

[0112] Another embodiment of the present invention is a method for treating or preventing UV-induced aging of the skin in a subject. This method includes the step of contacting the subject with one of the compositions disclosed herein.

[0113] An additional embodiment of the present invention is a method for treating or preventing sunburn in a subject. This method includes the step of contacting the subject with one of the compositions disclosed herein.

[0114] A further embodiment of the present invention is a method for treating or preventing UV-induced hyperpigmentation in a subject. This method includes the step of contacting the subject with one of the compositions disclosed herein.

[0115] Another embodiment of the present invention is a method for whitening the skin in a subject. This method is used in a subject This includes the step of bringing one of the compositions disclosed herein into contact with the other.

[0116] An additional embodiment of the present invention is a method for inducing melanocyte apoptosis in a subject. This method includes the step of contacting the subject with one of the compositions disclosed herein.

[0117] A further embodiment of the present invention is a method for modulating aromatic hydrocarbon acceptor (AhR) activity in a subject. This method includes the step of contacting the subject with one of the compositions disclosed herein.

[0118] Another embodiment of the present invention is a method for modulating melanin formation in a subject. This method includes the step of contacting the subject with one of the compositions disclosed herein.

[0119] An additional embodiment of the present invention is a method for modulating melanin concentration in a subject. This method includes the step of contacting the subject with one of the compositions disclosed herein.

[0120] This patent or application file includes at least one drawing created in color. A copy of this patent or patent application publication, including the color drawing, will be provided by the office upon request and payment of the necessary fees. [Brief explanation of the drawing]

[0121] [Figure 1A] Figure 1A is a schematic diagram of the layers of skin components. The inset shows the cellular composition of the epidermis and dermis. Figure 1B is a schematic diagram illustrating the potential mechanism of action of a hypopigmentation inducer. [Figure 1B] Figure 1A is a schematic diagram of the layers of skin components. The inset shows the cellular composition of the epidermis and dermis. Figure 1B is a schematic diagram illustrating the potential mechanism of action of a hypopigmentation inducer.

[0122] [Figure 2A] Figure 2 shows a series of synthetic schemes for malasedin and malasedin derivatives. Figure 2A: Malasedin and indro[3,2-b]carbazole; Figure 2B: Compounds I and IV; Figure 2C: Compound II. [Figure 2B] Figure 2 shows a series of synthetic schemes for malasedin and malasedin derivatives. Figure 2A: Malasedin and indro[3,2-b]carbazole; Figure 2B: Compounds I and IV; Figure 2C: Compound II. [Figure 2C] Figure 2 shows a series of synthetic schemes for malasedin and malasedin derivatives. Figure 2A: Malasedin and indro[3,2-b]carbazole; Figure 2B: Compounds I and IV; Figure 2C: Compound II.

[0123] [Figure 3-1]Figure 3A is a summary chart showing the annexin V-induced EC50 values ​​for certain compounds of the present invention in MeWo and WM115 cells. Figures 3B-3M are line graphs showing the percentage of annexin V-labeled MeWo (Figures 3B-3G) or WM115 (Figures 3H-3M) cells after exposure to various concentrations of the listed compounds. [Figure 3-2] Figure 3A is a summary chart showing the annexin V-induced EC50 values ​​for certain compounds of the present invention in MeWo and WM115 cells. Figures 3B-3M are line graphs showing the percentage of annexin V-labeled MeWo (Figures 3B-3G) or WM115 (Figures 3H-3M) cells after exposure to various concentrations of the listed compounds. [Figure 3-3] Figure 3A is a summary chart showing the annexin V-induced EC50 values ​​for certain compounds of the present invention in MeWo and WM115 cells. Figures 3B-3M are line graphs showing the percentage of annexin V-labeled MeWo (Figures 3B-3G) or WM115 (Figures 3H-3M) cells after exposure to various concentrations of the listed compounds. [Figure 3-4] Figure 3A is a summary chart showing the annexin V-induced EC50 values ​​for certain compounds of the present invention in MeWo and WM115 cells. Figures 3B-3M are line graphs showing the percentage of annexin V-labeled MeWo (Figures 3B-3G) or WM115 (Figures 3H-3M) cells after exposure to various concentrations of the listed compounds. [Figure 3-5] Figure 3A is a summary chart showing the annexin V-induced EC50 values ​​for certain compounds of the present invention in MeWo and WM115 cells. Figures 3B-3M are line graphs showing the percentage of annexin V-labeled MeWo (Figures 3B-3G) or WM115 (Figures 3H-3M) cells after exposure to various concentrations of the listed compounds.

[0124] [Figure 4-1]Figures 4A–4D are charts showing the relative annexin V levels (%) in MeWo and WM115 cells after exposure to various concentrations of the listed compounds for 6, 24, 48, and 72 hours. Figures 4E–4J are histograms showing the results from Figures 4A–4D. Figures 4K and 4L are histograms showing the percentages of annexin V-labeled MeWo (Figure 4K) and WM115 (Figure 4L) cells after exposure to the listed compounds at the indicated concentrations for 6 hours. [Figure 4-2] Figures 4A–4D are charts showing the relative annexin V levels (%) in MeWo and WM115 cells after exposure to various concentrations of the listed compounds for 6, 24, 48, and 72 hours. Figures 4E–4J are histograms showing the results from Figures 4A–4D. Figures 4K and 4L are histograms showing the percentages of annexin V-labeled MeWo (Figure 4K) and WM115 (Figure 4L) cells after exposure to the listed compounds at the indicated concentrations for 6 hours. [Figure 4-3] Figures 4A–4D are charts showing the relative annexin V levels (%) in MeWo and WM115 cells after exposure to various concentrations of the listed compounds for 6, 24, 48, and 72 hours. Figures 4E–4J are histograms showing the results from Figures 4A–4D. Figures 4K and 4L are histograms showing the percentages of annexin V-labeled MeWo (Figure 4K) and WM115 (Figure 4L) cells after exposure to the listed compounds at the indicated concentrations for 6 hours. [Figure 4-4] Figures 4A–4D are charts showing the relative annexin V levels (%) in MeWo and WM115 cells after exposure to various concentrations of the listed compounds for 6, 24, 48, and 72 hours. Figures 4E–4J are histograms showing the results from Figures 4A–4D. Figures 4K and 4L are histograms showing the percentages of annexin V-labeled MeWo (Figure 4K) and WM115 (Figure 4L) cells after exposure to the listed compounds at the indicated concentrations for 6 hours. [Figure 4-5]Figures 4A–4D are charts showing the relative annexin V levels (%) in MeWo and WM115 cells after exposure to various concentrations of the listed compounds for 6, 24, 48, and 72 hours. Figures 4E–4J are histograms showing the results from Figures 4A–4D. Figures 4K and 4L are histograms showing the percentages of annexin V-labeled MeWo (Figure 4K) and WM115 (Figure 4L) cells after exposure to the listed compounds at the indicated concentrations for 6 hours. [Figure 4-6] Figures 4A–4D are charts showing the relative annexin V levels (%) in MeWo and WM115 cells after exposure to various concentrations of the listed compounds for 6, 24, 48, and 72 hours. Figures 4E–4J are histograms showing the results from Figures 4A–4D. Figures 4K and 4L are histograms showing the percentages of annexin V-labeled MeWo (Figure 4K) and WM115 (Figure 4L) cells after exposure to the listed compounds at the indicated concentrations for 6 hours. [Figure 4-7] Figures 4A–4D are charts showing the relative annexin V levels (%) in MeWo and WM115 cells after exposure to various concentrations of the listed compounds for 6, 24, 48, and 72 hours. Figures 4E–4J are histograms showing the results from Figures 4A–4D. Figures 4K and 4L are histograms showing the percentages of annexin V-labeled MeWo (Figure 4K) and WM115 (Figure 4L) cells after exposure to the listed compounds at the indicated concentrations for 6 hours. [Figure 4-8] Figures 4A–4D are charts showing the relative annexin V levels (%) in MeWo and WM115 cells after exposure to various concentrations of the listed compounds for 6, 24, 48, and 72 hours. Figures 4E–4J are histograms showing the results from Figures 4A–4D. Figures 4K and 4L are histograms showing the percentages of annexin V-labeled MeWo (Figure 4K) and WM115 (Figure 4L) cells after exposure to the listed compounds at the indicated concentrations for 6 hours.

[0125] [Figure 5]Figures 5A-5K are micrographs showing the morphology of MeWo cells after treatment with various concentrations of CV-8684, CV-8685, CV-8688, DMSO, and staurosporine for 6 hours.

[0126] [Figure 6] Figures 6A-6K are micrographs showing the morphology of MeWo cells after 24 hours of treatment with various concentrations of CV-8684, CV-8685, CV-8688, DMSO, and staurosporine.

[0127] [Figure 7] Figures 7A-7K are micrographs showing the morphology of MeWo cells after 48 hours of treatment with various concentrations of CV-8684, CV-8685, CV-8688, DMSO, and staurosporine.

[0128] [Figure 8] Figures 8A-8K are micrographs showing the morphology of MeWo cells after 72 hours of treatment with various concentrations of CV-8684, CV-8685, CV-8688, DMSO, and staurosporine.

[0129] [Figure 9] Figures 9A-9K are micrographs showing the morphology of WM115 cells after treatment with various concentrations of CV-8684, CV-8685, CV-8688, DMSO, and staurosporine for 6 hours.

[0130] [Figure 10] Figures 10A-10K are micrographs showing the morphology of WM115 cells after 24 hours of treatment with various concentrations of CV-8684, CV-8685, CV-8688, DMSO, and staurosporine.

[0131] [Figure 11]Figures 11A-11K are micrographs showing the morphology of WM115 cells after 48 hours of treatment with various concentrations of CV-8684, CV-8685, CV-8688, DMSO, and staurosporine.

[0132] [Figure 12] Figures 12A-12K are micrographs showing the morphology of WM115 cells after treatment with various concentrations of CV-8684, CV-8685, CV-8688, DMSO, and staurosporine for 72 hours.

[0133] [Figure 13-1] Figures 13A–13D are charts showing the percentage of viable MeWo and WM115 cells remaining after treatment with various concentrations of CV-8684 (Figure 13A), CV-8685 (Figure 13B), CV-8688 (Figure 13C), or staurosporine (Figure 13D) at 6, 24, 48, and 72 hours. Cell viability was assayed using CellTiter-Glo®. Figures 13E–13J are histograms showing the results from Figures 13A–13D. Figure 13K is a summary chart comparing the percentage of viable MeWo and WM115 cells after exposure at 24, 48, and 72 hours to the listed concentrations of malasedin, indolocarbazole, compound II, and staurosporine. [Figure 13-2] Figures 13A–13D are charts showing the percentage of viable MeWo and WM115 cells remaining after treatment with various concentrations of CV-8684 (Figure 13A), CV-8685 (Figure 13B), CV-8688 (Figure 13C), or staurosporine (Figure 13D) at 6, 24, 48, and 72 hours. Cell viability was assayed using CellTiter-Glo®. Figures 13E–13J are histograms showing the results from Figures 13A–13D. Figure 13K is a summary chart comparing the percentage of viable MeWo and WM115 cells after exposure at 24, 48, and 72 hours to the listed concentrations of malasedin, indolocarbazole, compound II, and staurosporine. [Figure 13-3]Figures 13A–13D are charts showing the percentage of viable MeWo and WM115 cells remaining after treatment with various concentrations of CV-8684 (Figure 13A), CV-8685 (Figure 13B), CV-8688 (Figure 13C), or staurosporine (Figure 13D) at 6, 24, 48, and 72 hours. Cell viability was assayed using CellTiter-Glo®. Figures 13E–13J are histograms showing the results from Figures 13A–13D. Figure 13K is a summary chart comparing the percentage of viable MeWo and WM115 cells after exposure at 24, 48, and 72 hours to the listed concentrations of malasedin, indolocarbazole, compound II, and staurosporine. [Figure 13-4] Figures 13A–13D are charts showing the percentage of viable MeWo and WM115 cells remaining after treatment with various concentrations of CV-8684 (Figure 13A), CV-8685 (Figure 13B), CV-8688 (Figure 13C), or staurosporine (Figure 13D) at 6, 24, 48, and 72 hours. Cell viability was assayed using CellTiter-Glo®. Figures 13E–13J are histograms showing the results from Figures 13A–13D. Figure 13K is a summary chart comparing the percentage of viable MeWo and WM115 cells after exposure at 24, 48, and 72 hours to the listed concentrations of malasedin, indolocarbazole, compound II, and staurosporine. [Figure 13-5] Figures 13A–13D are charts showing the percentage of viable MeWo and WM115 cells remaining after treatment with various concentrations of CV-8684 (Figure 13A), CV-8685 (Figure 13B), CV-8688 (Figure 13C), or staurosporine (Figure 13D) at 6, 24, 48, and 72 hours. Cell viability was assayed using CellTiter-Glo®. Figures 13E–13J are histograms showing the results from Figures 13A–13D. Figure 13K is a summary chart comparing the percentage of viable MeWo and WM115 cells after exposure at 24, 48, and 72 hours to the listed concentrations of malasedin, indolocarbazole, compound II, and staurosporine. [Figure 13-6] Figures 13A–13D are charts showing the percentage of viable MeWo and WM115 cells remaining after treatment with various concentrations of CV-8684 (Figure 13A), CV-8685 (Figure 13B), CV-8688 (Figure 13C), or staurosporine (Figure 13D) at 6, 24, 48, and 72 hours. Cell viability was assayed using CellTiter-Glo®. Figures 13E–13J are histograms showing the results from Figures 13A–13D. Figure 13K is a summary chart comparing the percentage of viable MeWo and WM115 cells after exposure at 24, 48, and 72 hours to the listed concentrations of malasedin, indolocarbazole, compound II, and staurosporine. [Figure 13-7] Figures 13A–13D are charts showing the percentage of viable MeWo and WM115 cells remaining after treatment with various concentrations of CV-8684 (Figure 13A), CV-8685 (Figure 13B), CV-8688 (Figure 13C), or staurosporine (Figure 13D) at 6, 24, 48, and 72 hours. Cell viability was assayed using CellTiter-Glo®. Figures 13E–13J are histograms showing the results from Figures 13A–13D. Figure 13K is a summary chart comparing the percentage of viable MeWo and WM115 cells after exposure at 24, 48, and 72 hours to the listed concentrations of malasedin, indolocarbazole, compound II, and staurosporine.

[0134] [Figure 14-1]Figures 14A–14D are charts showing the release levels of lactate dehydrogenase ("LDH") from MeWo and WM115 cells after treatment for 6, 24, 48, and 72 hours with various concentrations of CV-8684 (Figure 14A), CV-8685 (Figure 14B), CV-8688 (Figure 14C), or staurosporine (Figure 14D). Figures 14E–14J are histograms showing the results from Figures 14A–14D. Figures 14K and 14L are histograms showing lactate dehydrogenase levels after exposure of MeWo (Figure 14K) and WM115 (Figure 14L) cells to the listed concentrations of malasedin, carbazole, compound II, and staurosporine for 24 hours. [Figure 14-2] Figures 14A–14D are charts showing the release levels of lactate dehydrogenase ("LDH") from MeWo and WM115 cells after treatment for 6, 24, 48, and 72 hours with various concentrations of CV-8684 (Figure 14A), CV-8685 (Figure 14B), CV-8688 (Figure 14C), or staurosporine (Figure 14D). Figures 14E–14J are histograms showing the results from Figures 14A–14D. Figures 14K and 14L are histograms showing lactate dehydrogenase levels after exposure of MeWo (Figure 14K) and WM115 (Figure 14L) cells to the listed concentrations of malasedin, carbazole, compound II, and staurosporine for 24 hours. [Figure 14-3] Figures 14A–14D are charts showing the release levels of lactate dehydrogenase ("LDH") from MeWo and WM115 cells after treatment for 6, 24, 48, and 72 hours with various concentrations of CV-8684 (Figure 14A), CV-8685 (Figure 14B), CV-8688 (Figure 14C), or staurosporine (Figure 14D). Figures 14E–14J are histograms showing the results from Figures 14A–14D. Figures 14K and 14L are histograms showing lactate dehydrogenase levels after exposure of MeWo (Figure 14K) and WM115 (Figure 14L) cells to the listed concentrations of malasedin, carbazole, compound II, and staurosporine for 24 hours. [Figure 14-4]Figures 14A–14D are charts showing the release levels of lactate dehydrogenase ("LDH") from MeWo and WM115 cells after treatment for 6, 24, 48, and 72 hours with various concentrations of CV-8684 (Figure 14A), CV-8685 (Figure 14B), CV-8688 (Figure 14C), or staurosporine (Figure 14D). Figures 14E–14J are histograms showing the results from Figures 14A–14D. Figures 14K and 14L are histograms showing lactate dehydrogenase levels after exposure of MeWo (Figure 14K) and WM115 (Figure 14L) cells to the listed concentrations of malasedin, carbazole, compound II, and staurosporine for 24 hours. [Figure 14-5] Figures 14A–14D are charts showing the release levels of lactate dehydrogenase ("LDH") from MeWo and WM115 cells after treatment for 6, 24, 48, and 72 hours with various concentrations of CV-8684 (Figure 14A), CV-8685 (Figure 14B), CV-8688 (Figure 14C), or staurosporine (Figure 14D). Figures 14E–14J are histograms showing the results from Figures 14A–14D. Figures 14K and 14L are histograms showing lactate dehydrogenase levels after exposure of MeWo (Figure 14K) and WM115 (Figure 14L) cells to the listed concentrations of malasedin, carbazole, compound II, and staurosporine for 24 hours. [Figure 14-6] Figures 14A–14D are charts showing the release levels of lactate dehydrogenase ("LDH") from MeWo and WM115 cells after treatment for 6, 24, 48, and 72 hours with various concentrations of CV-8684 (Figure 14A), CV-8685 (Figure 14B), CV-8688 (Figure 14C), or staurosporine (Figure 14D). Figures 14E–14J are histograms showing the results from Figures 14A–14D. Figures 14K and 14L are histograms showing lactate dehydrogenase levels after exposure of MeWo (Figure 14K) and WM115 (Figure 14L) cells to the listed concentrations of malasedin, carbazole, compound II, and staurosporine for 24 hours. [Figure 14-7]Figures 14A–14D are charts showing the release levels of lactate dehydrogenase ("LDH") from MeWo and WM115 cells after treatment for 6, 24, 48, and 72 hours with various concentrations of CV-8684 (Figure 14A), CV-8685 (Figure 14B), CV-8688 (Figure 14C), or staurosporine (Figure 14D). Figures 14E–14J are histograms showing the results from Figures 14A–14D. Figures 14K and 14L are histograms showing lactate dehydrogenase levels after exposure of MeWo (Figure 14K) and WM115 (Figure 14L) cells to the listed concentrations of malasedin, carbazole, compound II, and staurosporine for 24 hours. [Figure 14-8] Figures 14A–14D are charts showing the release levels of lactate dehydrogenase ("LDH") from MeWo and WM115 cells after treatment for 6, 24, 48, and 72 hours with various concentrations of CV-8684 (Figure 14A), CV-8685 (Figure 14B), CV-8688 (Figure 14C), or staurosporine (Figure 14D). Figures 14E–14J are histograms showing the results from Figures 14A–14D. Figures 14K and 14L are histograms showing lactate dehydrogenase levels after exposure of MeWo (Figure 14K) and WM115 (Figure 14L) cells to the listed concentrations of malasedin, carbazole, compound II, and staurosporine for 24 hours.

[0135] [Figure 15A] Figures 15A–15E show raw data and line graphs of aromatic hydrocarbon receptor ("AhR") activation in HepG2 cells stably transfected with AhR-responsive luciferase reporter gene plasmids upon exposure to various concentrations of omeprazole (Figure 15A), CV-8684 (Figure 15B), CV-8685 (Figure 15C), CV-8686 (Figure 15D), and CV-8688 (Figure 15E). Figure 15F shows the EC50 values ​​for each compound tested. [Figure 15B]Figures 15A–15E show raw data and line graphs of aromatic hydrocarbon receptor ("AhR") activation in HepG2 cells stably transfected with AhR-responsive luciferase reporter gene plasmids upon exposure to various concentrations of omeprazole (Figure 15A), CV-8684 (Figure 15B), CV-8685 (Figure 15C), CV-8686 (Figure 15D), and CV-8688 (Figure 15E). Figure 15F shows the EC50 values ​​for each compound tested. [Figure 15C] Figures 15A–15E show raw data and line graphs of aromatic hydrocarbon receptor ("AhR") activation in HepG2 cells stably transfected with AhR-responsive luciferase reporter gene plasmids upon exposure to various concentrations of omeprazole (Figure 15A), CV-8684 (Figure 15B), CV-8685 (Figure 15C), CV-8686 (Figure 15D), and CV-8688 (Figure 15E). Figure 15F shows the EC50 values ​​for each compound tested. [Figure 15D] Figures 15A–15E show raw data and line graphs of aromatic hydrocarbon receptor ("AhR") activation in HepG2 cells stably transfected with AhR-responsive luciferase reporter gene plasmids upon exposure to various concentrations of omeprazole (Figure 15A), CV-8684 (Figure 15B), CV-8685 (Figure 15C), CV-8686 (Figure 15D), and CV-8688 (Figure 15E). Figure 15F shows the EC50 values ​​for each compound tested. [Figure 15E] Figures 15A–15E show raw data and line graphs of aromatic hydrocarbon receptor ("AhR") activation in HepG2 cells stably transfected with AhR-responsive luciferase reporter gene plasmids upon exposure to various concentrations of omeprazole (Figure 15A), CV-8684 (Figure 15B), CV-8685 (Figure 15C), CV-8686 (Figure 15D), and CV-8688 (Figure 15E). Figure 15F shows the EC50 values ​​for each compound tested. [Figure 15F]Figures 15A–15E show raw data and line graphs of aromatic hydrocarbon receptor ("AhR") activation in HepG2 cells stably transfected with AhR-responsive luciferase reporter gene plasmids upon exposure to various concentrations of omeprazole (Figure 15A), CV-8684 (Figure 15B), CV-8685 (Figure 15C), CV-8686 (Figure 15D), and CV-8688 (Figure 15E). Figure 15F shows the EC50 values ​​for each compound tested.

[0136] [Figure 16-1] Figures 16A–16K are photographs of MelanoDerm® matrices on either day 0 or day 7 after exposure to either untreated (Figure 16A), sterile deionized water (Figure 16B), 1% kojic acid (Figure 16C), 0.2% DMSO (Figure 16D), 0.05% DMSO (Figure 16E), 200 μM CV-8684 (Figure 16F), 50 μM CV-8684 (Figure 16G), 200 μM CV-8686 (Figure 16H), 50 μM CV-8686 (Figure 16I), 200 μM CV-8688 (Figure 16J), and 50 μM CV-8688 (Figure 16K). [Figure 16-2] Figures 16A–16K are photographs of MelanoDerm® matrices on either day 0 or day 7 after exposure to either untreated (Figure 16A), sterile deionized water (Figure 16B), 1% kojic acid (Figure 16C), 0.2% DMSO (Figure 16D), 0.05% DMSO (Figure 16E), 200 μM CV-8684 (Figure 16F), 50 μM CV-8684 (Figure 16G), 200 μM CV-8686 (Figure 16H), 50 μM CV-8686 (Figure 16I), 200 μM CV-8688 (Figure 16J), and 50 μM CV-8688 (Figure 16K).

[0137] [Figure 17-1]Figures 17A-17K are 15× magnification micrographs of the MelanoDerm® matrix on either day 0 or day 7 after exposure to either the untreated (Figure 17A), sterile deionized water (Figure 17B), 1% kojic acid (Figure 17C), 0.2% DMSO (Figure 17D), 0.05% DMSO (Figure 17E), 200 μM CV-8684 (Figure 17F), 50 μM CV-8684 (Figure 17G), 200 μM CV-8686 (Figure 17H), 50 μM CV-8686 (Figure 17I), 200 μM CV-8688 (Figure 17J), and 50 μM CV-8688 (Figure 17K). [Figure 17-2] Figures 17A-17K are 15× magnification micrographs of the MelanoDerm® matrix on either day 0 or day 7 after exposure to either the untreated (Figure 17A), sterile deionized water (Figure 17B), 1% kojic acid (Figure 17C), 0.2% DMSO (Figure 17D), 0.05% DMSO (Figure 17E), 200 μM CV-8684 (Figure 17F), 50 μM CV-8684 (Figure 17G), 200 μM CV-8686 (Figure 17H), 50 μM CV-8686 (Figure 17I), 200 μM CV-8688 (Figure 17J), and 50 μM CV-8688 (Figure 17K).

[0138] [Figure 18] Figures 18A–18F are photographs of zebrafish exposed to untreated (Figure 18A), DMSO (Figure 18B), phenylthiourea ("PTU") (Figure 18C), and compound II at concentrations of 2.5 μM (Figure 18D), 5 μM (Figure 18E), and 10 μM (Figure 18F). Red arrows indicate normal melanocytes.

[0139] [Figure 19] Figures 19A–19F are photographs of zebrafish exposed to untreated (Figure 19A), DMSO (Figure 19B), phenylthiourea ("PTU") (Figure 19C), and compound II at 0.3 μM (Figure 19D), 1 μM (Figure 19E), and 3 μM (Figure 19F). Red arrows indicate normal melanocytes. Yellow arrows indicate abnormally small melanocytes.

[0140] [Figure 20] Figure 20 is a summary chart showing the number and percentage of zebrafish with reduced skin pigmentation after exposure to the listed conditions. The last six columns show the effects of various concentrations of compound II. [Figure 21] Figures 21A–21E are photographs of zebrafish treated with untreated (Figure 21A), DMSO (Figure 21B), PTU (Figure 21C), 0.5 μM (Figure 21D), and 1.5 μM (Figure 21E). The bottom panel includes a color scheme inversion area.

[0141] [Figure 22A] Figures 22A and 22B are histograms showing pigment deposition density, measured by colored pixels / mm³ (Figure 22A) and total pixels (Figure 22B) from photographs of zebrafish embryos, as illustrated in Figures 21A-21E. [Figure 22B] Figures 22A and 22B are histograms showing pigment deposition density, measured by colored pixels / mm³ (Figure 22A) and total pixels (Figure 22B) from photographs of zebrafish embryos, as illustrated in Figures 21A-21E.

[0142] [Figure 23A] Figures 23A–23C show the mass spectra of CV-8684 in DMSO (Figure 23A), RPMI medium (Figure 23B), and DMEM (Figure 23C). Figures 23D–23F show the mass spectra of CV-8686 in DMSO (Figure 23D), RPMI medium (Figure 23E), and DMEM (Figure 23F). Figures 23G–23I show the mass spectra of CV-8688 in DMSO (Figure 23G), RPMI medium (Figure 23H), and DMEM (Figure 23I). Figure 23J is a summary chart showing the percentage of test compounds remaining in the listed solvents after 2 hours of incubation. [Figure 23B]Figures 23A–23C show the mass spectra of CV-8684 in DMSO (Figure 23A), RPMI medium (Figure 23B), and DMEM (Figure 23C). Figures 23D–23F show the mass spectra of CV-8686 in DMSO (Figure 23D), RPMI medium (Figure 23E), and DMEM (Figure 23F). Figures 23G–23I show the mass spectra of CV-8688 in DMSO (Figure 23G), RPMI medium (Figure 23H), and DMEM (Figure 23I). Figure 23J is a summary chart showing the percentage of test compounds remaining in the listed solvents after 2 hours of incubation. [Figure 23C] Figures 23A–23C show the mass spectra of CV-8684 in DMSO (Figure 23A), RPMI medium (Figure 23B), and DMEM (Figure 23C). Figures 23D–23F show the mass spectra of CV-8686 in DMSO (Figure 23D), RPMI medium (Figure 23E), and DMEM (Figure 23F). Figures 23G–23I show the mass spectra of CV-8688 in DMSO (Figure 23G), RPMI medium (Figure 23H), and DMEM (Figure 23I). Figure 23J is a summary chart showing the percentage of test compounds remaining in the listed solvents after 2 hours of incubation. [Figure 23D] Figures 23A–23C show the mass spectra of CV-8684 in DMSO (Figure 23A), RPMI medium (Figure 23B), and DMEM (Figure 23C). Figures 23D–23F show the mass spectra of CV-8686 in DMSO (Figure 23D), RPMI medium (Figure 23E), and DMEM (Figure 23F). Figures 23G–23I show the mass spectra of CV-8688 in DMSO (Figure 23G), RPMI medium (Figure 23H), and DMEM (Figure 23I). Figure 23J is a summary chart showing the percentage of test compounds remaining in the listed solvents after 2 hours of incubation. [Figure 23E]Figures 23A–23C show the mass spectra of CV-8684 in DMSO (Figure 23A), RPMI medium (Figure 23B), and DMEM (Figure 23C). Figures 23D–23F show the mass spectra of CV-8686 in DMSO (Figure 23D), RPMI medium (Figure 23E), and DMEM (Figure 23F). Figures 23G–23I show the mass spectra of CV-8688 in DMSO (Figure 23G), RPMI medium (Figure 23H), and DMEM (Figure 23I). Figure 23J is a summary chart showing the percentage of test compounds remaining in the listed solvents after 2 hours of incubation. [Figure 23F] Figures 23A–23C show the mass spectra of CV-8684 in DMSO (Figure 23A), RPMI medium (Figure 23B), and DMEM (Figure 23C). Figures 23D–23F show the mass spectra of CV-8686 in DMSO (Figure 23D), RPMI medium (Figure 23E), and DMEM (Figure 23F). Figures 23G–23I show the mass spectra of CV-8688 in DMSO (Figure 23G), RPMI medium (Figure 23H), and DMEM (Figure 23I). Figure 23J is a summary chart showing the percentage of test compounds remaining in the listed solvents after 2 hours of incubation. [Figure 23G] Figures 23A–23C show the mass spectra of CV-8684 in DMSO (Figure 23A), RPMI medium (Figure 23B), and DMEM (Figure 23C). Figures 23D–23F show the mass spectra of CV-8686 in DMSO (Figure 23D), RPMI medium (Figure 23E), and DMEM (Figure 23F). Figures 23G–23I show the mass spectra of CV-8688 in DMSO (Figure 23G), RPMI medium (Figure 23H), and DMEM (Figure 23I). Figure 23J is a summary chart showing the percentage of test compounds remaining in the listed solvents after 2 hours of incubation. [Figure 23H]Figures 23A–23C show the mass spectra of CV-8684 in DMSO (Figure 23A), RPMI medium (Figure 23B), and DMEM (Figure 23C). Figures 23D–23F show the mass spectra of CV-8686 in DMSO (Figure 23D), RPMI medium (Figure 23E), and DMEM (Figure 23F). Figures 23G–23I show the mass spectra of CV-8688 in DMSO (Figure 23G), RPMI medium (Figure 23H), and DMEM (Figure 23I). Figure 23J is a summary chart showing the percentage of test compounds remaining in the listed solvents after 2 hours of incubation. [Figure 23I] Figures 23A–23C show the mass spectra of CV-8684 in DMSO (Figure 23A), RPMI medium (Figure 23B), and DMEM (Figure 23C). Figures 23D–23F show the mass spectra of CV-8686 in DMSO (Figure 23D), RPMI medium (Figure 23E), and DMEM (Figure 23F). Figures 23G–23I show the mass spectra of CV-8688 in DMSO (Figure 23G), RPMI medium (Figure 23H), and DMEM (Figure 23I). Figure 23J is a summary chart showing the percentage of test compounds remaining in the listed solvents after 2 hours of incubation. [Figure 23J] Figures 23A–23C show the mass spectra of CV-8684 in DMSO (Figure 23A), RPMI medium (Figure 23B), and DMEM (Figure 23C). Figures 23D–23F show the mass spectra of CV-8686 in DMSO (Figure 23D), RPMI medium (Figure 23E), and DMEM (Figure 23F). Figures 23G–23I show the mass spectra of CV-8688 in DMSO (Figure 23G), RPMI medium (Figure 23H), and DMEM (Figure 23I). Figure 23J is a summary chart showing the percentage of test compounds remaining in the listed solvents after 2 hours of incubation.

[0143] [Figure 24-1]Figures 24A to 24S show the synthesis scheme of the malasedin derivatives of the present invention. Figure 24A: Compound C (CV-8802); Figure 24B: Compound K (CV-8803); Figure 24C: Compound A (CV-8804); Figure 24D: Compound E (AB12508); Figure 24E: Compound A5 (CV-8819); Figure 24F: Compound H (AB12509); Figure 24G: Compound B (CV-8877); Figure 24H: Compound B10; Figure 24I: Compound AB11644; Figure 24J: O52 (AB12976); Figure 24K :Malassezia indole A (AB17011); Figure 24L: Picilia citrin (AB17014); Figure 24M: AB17151; Figure 24N: Compound VI (AB17225); Figure 24O: Malassezia lactic acid (AB17227); Figure 24P: AB12507; Figure 24Q: Compound V (AB17219); Figure 24R: Compound VIII (AB17220) and Figure 24S: Compound VII (AB17221). [Figure 24-2] Figures 24A to 24S show the synthesis scheme of the malasedin derivatives of the present invention. Figure 24A: Compound C (CV-8802); Figure 24B: Compound K (CV-8803); Figure 24C: Compound A (CV-8804); Figure 24D: Compound E (AB12508); Figure 24E: Compound A5 (CV-8819); Figure 24F: Compound H (AB12509); Figure 24G: Compound B (CV-8877); Figure 24H: Compound B10; Figure 24I: Compound AB11644; Figure 24J: O52 (AB12976); Figure 24K :Malassezia indole A (AB17011); Figure 24L: Picilia citrin (AB17014); Figure 24M: AB17151; Figure 24N: Compound VI (AB17225); Figure 24O: Malassezia lactic acid (AB17227); Figure 24P: AB12507; Figure 24Q: Compound V (AB17219); Figure 24R: Compound VIII (AB17220) and Figure 24S: Compound VII (AB17221). [Figure 24-3]Figures 24A to 24S show the synthesis scheme of the malasedin derivatives of the present invention. Figure 24A: Compound C (CV-8802); Figure 24B: Compound K (CV-8803); Figure 24C: Compound A (CV-8804); Figure 24D: Compound E (AB12508); Figure 24E: Compound A5 (CV-8819); Figure 24F: Compound H (AB12509); Figure 24G: Compound B (CV-8877); Figure 24H: Compound B10; Figure 24I: Compound AB11644; Figure 24J: O52 (AB12976); Figure 24K :Malassezia indole A (AB17011); Figure 24L: Picilia citrin (AB17014); Figure 24M: AB17151; Figure 24N: Compound VI (AB17225); Figure 24O: Malassezia lactic acid (AB17227); Figure 24P: AB12507; Figure 24Q: Compound V (AB17219); Figure 24R: Compound VIII (AB17220) and Figure 24S: Compound VII (AB17221). [Figure 24-4] Figures 24A to 24S show the synthesis scheme of the malasedin derivatives of the present invention. Figure 24A: Compound C (CV-8802); Figure 24B: Compound K (CV-8803); Figure 24C: Compound A (CV-8804); Figure 24D: Compound E (AB12508); Figure 24E: Compound A5 (CV-8819); Figure 24F: Compound H (AB12509); Figure 24G: Compound B (CV-8877); Figure 24H: Compound B10; Figure 24I: Compound AB11644; Figure 24J: O52 (AB12976); Figure 24K :Malassezia indole A (AB17011); Figure 24L: Picilia citrin (AB17014); Figure 24M: AB17151; Figure 24N: Compound VI (AB17225); Figure 24O: Malassezia lactic acid (AB17227); Figure 24P: AB12507; Figure 24Q: Compound V (AB17219); Figure 24R: Compound VIII (AB17220) and Figure 24S: Compound VII (AB17221). [Figure 24-5]Figures 24A to 24S show the synthesis scheme of the malasedin derivatives of the present invention. Figure 24A: Compound C (CV-8802); Figure 24B: Compound K (CV-8803); Figure 24C: Compound A (CV-8804); Figure 24D: Compound E (AB12508); Figure 24E: Compound A5 (CV-8819); Figure 24F: Compound H (AB12509); Figure 24G: Compound B (CV-8877); Figure 24H: Compound B10; Figure 24I: Compound AB11644; Figure 24J: O52 (AB12976); Figure 24K :Malassezia indole A (AB17011); Figure 24L: Picilia citrin (AB17014); Figure 24M: AB17151; Figure 24N: Compound VI (AB17225); Figure 24O: Malassezia lactic acid (AB17227); Figure 24P: AB12507; Figure 24Q: Compound V (AB17219); Figure 24R: Compound VIII (AB17220) and Figure 24S: Compound VII (AB17221). [Figure 24-6] Figures 24A to 24S show the synthesis scheme of the malasedin derivatives of the present invention. Figure 24A: Compound C (CV-8802); Figure 24B: Compound K (CV-8803); Figure 24C: Compound A (CV-8804); Figure 24D: Compound E (AB12508); Figure 24E: Compound A5 (CV-8819); Figure 24F: Compound H (AB12509); Figure 24G: Compound B (CV-8877); Figure 24H: Compound B10; Figure 24I: Compound AB11644; Figure 24J: O52 (AB12976); Figure 24K :Malassezia indole A (AB17011); Figure 24L: Picilia citrin (AB17014); Figure 24M: AB17151; Figure 24N: Compound VI (AB17225); Figure 24O: Malassezia lactic acid (AB17227); Figure 24P: AB12507; Figure 24Q: Compound V (AB17219); Figure 24R: Compound VIII (AB17220) and Figure 24S: Compound VII (AB17221). [Figure 24-7]Figures 24A to 24S show the synthesis scheme of the malasedin derivatives of the present invention. Figure 24A: Compound C (CV-8802); Figure 24B: Compound K (CV-8803); Figure 24C: Compound A (CV-8804); Figure 24D: Compound E (AB12508); Figure 24E: Compound A5 (CV-8819); Figure 24F: Compound H (AB12509); Figure 24G: Compound B (CV-8877); Figure 24H: Compound B10; Figure 24I: Compound AB11644; Figure 24J: O52 (AB12976); Figure 24K :Malassezia indole A (AB17011); Figure 24L: Picilia citrin (AB17014); Figure 24M: AB17151; Figure 24N: Compound VI (AB17225); Figure 24O: Malassezia lactic acid (AB17227); Figure 24P: AB12507; Figure 24Q: Compound V (AB17219); Figure 24R: Compound VIII (AB17220) and Figure 24S: Compound VII (AB17221). [Figure 24-8] Figures 24A to 24S show the synthesis scheme of the malasedin derivatives of the present invention. Figure 24A: Compound C (CV-8802); Figure 24B: Compound K (CV-8803); Figure 24C: Compound A (CV-8804); Figure 24D: Compound E (AB12508); Figure 24E: Compound A5 (CV-8819); Figure 24F: Compound H (AB12509); Figure 24G: Compound B (CV-8877); Figure 24H: Compound B10; Figure 24I: Compound AB11644; Figure 24J: O52 (AB12976); Figure 24K :Malassezia indole A (AB17011); Figure 24L: Picilia citrin (AB17014); Figure 24M: AB17151; Figure 24N: Compound VI (AB17225); Figure 24O: Malassezia lactic acid (AB17227); Figure 24P: AB12507; Figure 24Q: Compound V (AB17219); Figure 24R: Compound VIII (AB17220) and Figure 24S: Compound VII (AB17221). [Figure 24-9]Figures 24A to 24S show the synthesis scheme of the malasedin derivatives of the present invention. Figure 24A: Compound C (CV-8802); Figure 24B: Compound K (CV-8803); Figure 24C: Compound A (CV-8804); Figure 24D: Compound E (AB12508); Figure 24E: Compound A5 (CV-8819); Figure 24F: Compound H (AB12509); Figure 24G: Compound B (CV-8877); Figure 24H: Compound B10; Figure 24I: Compound AB11644; Figure 24J: O52 (AB12976); Figure 24K :Malassezia indole A (AB17011); Figure 24L: Picilia citrin (AB17014); Figure 24M: AB17151; Figure 24N: Compound VI (AB17225); Figure 24O: Malassezia lactic acid (AB17227); Figure 24P: AB12507; Figure 24Q: Compound V (AB17219); Figure 24R: Compound VIII (AB17220) and Figure 24S: Compound VII (AB17221). [Figure 24-10] Figures 24A to 24S show the synthesis scheme of the malasedin derivatives of the present invention. Figure 24A: Compound C (CV-8802); Figure 24B: Compound K (CV-8803); Figure 24C: Compound A (CV-8804); Figure 24D: Compound E (AB12508); Figure 24E: Compound A5 (CV-8819); Figure 24F: Compound H (AB12509); Figure 24G: Compound B (CV-8877); Figure 24H: Compound B10; Figure 24I: Compound AB11644; Figure 24J: O52 (AB12976); Figure 24K :Malassezia indole A (AB17011); Figure 24L: Picilia citrin (AB17014); Figure 24M: AB17151; Figure 24N: Compound VI (AB17225); Figure 24O: Malassezia lactic acid (AB17227); Figure 24P: AB12507; Figure 24Q: Compound V (AB17219); Figure 24R: Compound VIII (AB17220) and Figure 24S: Compound VII (AB17221). [Figure 24-11]Figures 24A to 24S show the synthesis scheme of the malasedin derivatives of the present invention. Figure 24A: Compound C (CV-8802); Figure 24B: Compound K (CV-8803); Figure 24C: Compound A (CV-8804); Figure 24D: Compound E (AB12508); Figure 24E: Compound A5 (CV-8819); Figure 24F: Compound H (AB12509); Figure 24G: Compound B (CV-8877); Figure 24H: Compound B10; Figure 24I: Compound AB11644; Figure 24J: O52 (AB12976); Figure 24K :Malassezia indole A (AB17011); Figure 24L: Picilia citrin (AB17014); Figure 24M: AB17151; Figure 24N: Compound VI (AB17225); Figure 24O: Malassezia lactic acid (AB17227); Figure 24P: AB12507; Figure 24Q: Compound V (AB17219); Figure 24R: Compound VIII (AB17220) and Figure 24S: Compound VII (AB17221). [Figure 24-12] Figures 24A to 24S show the synthesis scheme of the malasedin derivatives of the present invention. Figure 24A: Compound C (CV-8802); Figure 24B: Compound K (CV-8803); Figure 24C: Compound A (CV-8804); Figure 24D: Compound E (AB12508); Figure 24E: Compound A5 (CV-8819); Figure 24F: Compound H (AB12509); Figure 24G: Compound B (CV-8877); Figure 24H: Compound B10; Figure 24I: Compound AB11644; Figure 24J: O52 (AB12976); Figure 24K :Malassezia indole A (AB17011); Figure 24L: Picilia citrin (AB17014); Figure 24M: AB17151; Figure 24N: Compound VI (AB17225); Figure 24O: Malassezia lactic acid (AB17227); Figure 24P: AB12507; Figure 24Q: Compound V (AB17219); Figure 24R: Compound VIII (AB17220) and Figure 24S: Compound VII (AB17221).

[0144] [Figure 25A] Figures 25A–25D show data tables containing the percentage of annexin V-positive cells at 6 hours (Figure 25A), 24 hours (Figure 25B), 48 hours (Figure 25C), and 72 hours (Figure 25D) after exposure to the indicated treatment. [Figure 25B] Figures 25A–25D show data tables containing the percentage of annexin V-positive cells at 6 hours (Figure 25A), 24 hours (Figure 25B), 48 hours (Figure 25C), and 72 hours (Figure 25D) after exposure to the indicated treatment. [Figure 25C] Figures 25A–25D show data tables containing the percentage of annexin V-positive cells at 6 hours (Figure 25A), 24 hours (Figure 25B), 48 hours (Figure 25C), and 72 hours (Figure 25D) after exposure to the indicated treatment. [Figure 25D] Figures 25A–25D show data tables containing the percentage of annexin V-positive cells at 6 hours (Figure 25A), 24 hours (Figure 25B), 48 hours (Figure 25C), and 72 hours (Figure 25D) after exposure to the indicated treatment.

[0145] [Figure 26A] Figures 26A-26D show data tables containing caspase 3 / 7 induction ratios at 6 hours (Figure 26A), 24 hours (Figure 26B), 48 hours (Figure 26C), and 72 hours (Figure 26D) after exposure to the indicated treatment. [Figure 26B] Figures 26A-26D show data tables containing caspase 3 / 7 induction ratios at 6 hours (Figure 26A), 24 hours (Figure 26B), 48 hours (Figure 26C), and 72 hours (Figure 26D) after exposure to the indicated treatment. [Figure 26C] Figures 26A-26D show data tables containing caspase 3 / 7 induction ratios at 6 hours (Figure 26A), 24 hours (Figure 26B), 48 hours (Figure 26C), and 72 hours (Figure 26D) after exposure to the indicated treatment. [Figure 26D] Figures 26A-26D show data tables containing caspase 3 / 7 induction ratios at 6 hours (Figure 26A), 24 hours (Figure 26B), 48 hours (Figure 26C), and 72 hours (Figure 26D) after exposure to the indicated treatment.

[0146] [Figure 27]Figures 27A and 27B show the residual cell survival percentages for MeWo (Figure 27A) and WM115 (Figure 27B) cells after exposure to AB12508 (compound E).

[0147] [Figure 28] Figures 28A and 28B show the residual cell survival percentages for MeWo (Figure 28A) and WM115 (Figure 28B) cells after exposure to an unknown composition.

[0148] [Figure 29] Figures 29A and 29B show the residual cell survival percentages for MeWo (Figure 29A) and WM115 (Figure 29B) cells after exposure to CV-8803 (compound K).

[0149] [Figure 30] Figures 30A and 30B show the residual cell survival percentages for MeWo (Figure 30A) and WM115 (Figure 30B) cells after exposure to CV-8804 (compound A).

[0150] [Figure 31] Figures 31A and 31B show the residual cell survival percentages for MeWo (Figure 31A) and WM115 (Figure 31B) cells after exposure to CV-8684 (malasedin).

[0151] [Figure 32] Figures 32A and 32B show the residual cell survival percentages for MeWo (Figure 32A) and WM115 (Figure 32B) cells after exposure to CV-8685 (indro[3,2-b]carbazole).

[0152] [Figure 33] Figures 33A and 33B show the residual cell survival percentages for MeWo (Figure 33A) and WM115 (Figure 33B) cells after exposure to CV-8686 (compound I).

[0153] [Figure 34] Figures 34A and 34B show the residual cell survival percentages for MeWo (Figure 34A) and WM115 (Figure 34B) cells after exposure to CV-8688 (compound II).

[0154] [Figure 35] Figures 35A and 35B show the residual cell survival percentages for MeWo (Figure 35A) and WM115 (Figure 35B) cells after exposure to staurosporine.

[0155] [Figure 36] Figure 36A shows the readings of AhR activity from the HepG2-AhR-luciferase assay upon exposure to various concentrations of omeprazole. Figure 36B shows a line graph of the data from Figure 36A, while the inset shows the measured EC50.

[0156] [Figure 37] Figure 37A shows the readings of AhR activity from the HepG2-AhR-luciferase assay upon exposure to various concentrations of CV-8684 (malasedin). Figure 37B shows a line graph of the data from Figure 37A, while the inset shows the measured EC50.

[0157] [Figure 38] Figure 38A shows the readings of AhR activity from the HepG2-AhR-luciferase assay upon exposure to various concentrations of CV-8685 (indro[3,2-b]carbazole). Figure 38B shows a line graph of the data from Figure 38A, while the inset shows the measured EC50.

[0158] [Figure 39] Figure 39A shows the readings of AhR activity from the HepG2-AhR-luciferase assay upon exposure to various concentrations of CV-8686 (compound I). Figure 39B shows a line graph of the data from Figure 39A, while the inset shows the measured EC50.

[0159] [Figure 40] Figure 40A shows the readings of AhR activity from the HepG2-AhR-luciferase assay upon exposure to unknown compositions at various concentrations. Figure 40B shows a line graph of the data from Figure 40A, while the inset shows the measured EC50.

[0160] [Figure 41] Figure 41A shows the readings of AhR activity from the HepG2-AhR-luciferase assay upon exposure to various concentrations of CV-8803 (compound K). Figure 41B shows a line graph of the data from Figure 41A, while the inset shows the measured EC50.

[0161] [Figure 42] Figure 42A shows the readings of AhR activity from the HepG2-AhR-luciferase assay upon exposure to various concentrations of CV-8804 (compound A). Figure 42B shows a line graph of the data from Figure 42A, while the inset shows the measured EC50.

[0162] [Figure 43] Figure 43A shows the readings of AhR activity from the HepG2-AhR-luciferase assay upon exposure to various concentrations of AB12508 (compound E). Figure 43B shows a line graph of the data from Figure 43A, while the inset shows the measured EC50.

[0163] [Figure 44] Figure 44A shows the readings of AhR activity from the HepG2-AhR-luciferase assay upon exposure to various concentrations of CV-8688 (compound II). Figure 44B shows a line graph of the data from Figure 44A, while the inset shows the measured EC50.

[0164] [Figure 45]Figure 45A shows the readings of AhR activity from the HepG2-AhR-luciferase assay upon exposure to various concentrations of omeprazole. Figure 45B shows a line graph of the data from Figure 45A.

[0165] [Figure 46] Figure 46A shows the readings of AhR activity from the HepG2-AhR-luciferase assay upon exposure to unknown compositions at various concentrations. Figure 46B shows a line graph of the data from Figure 46A.

[0166] [Figure 47] Figure 47A shows the readings of AhR activity from the HepG2-AhR-luciferase assay upon exposure to various concentrations of 2,3,7,8-tetrachlorodibenzodioxin (TCDD). Figure 47B shows a line graph of the data from Figure 47A.

[0167] [Figure 48] Figure 48A shows the readings of AhR activity from the HepG2-AhR-luciferase assay upon exposure to various concentrations of CV-8819 (compound A5). Figure 48B shows a line graph of the data from Figure 48A.

[0168] [Figure 49] Figure 49A shows the readings of AhR activity from the HepG2-AhR-luciferase assay upon exposure to various concentrations of CV-8684 (malasedin). Figure 49B shows a line graph of the data from Figure 49A.

[0169] [Figure 50] Figure 50A shows the readings of AhR activity from the HepG2-AhR-luciferase assay upon exposure to various concentrations of AB12508 (compound E). Figure 50B shows a line graph of the data from Figure 50A.

[0170] [Figure 51]Figure 51A shows the readings of AhR activity from the HepG2-AhR-luciferase assay upon exposure to various concentrations of CV-8686 (compound I). Figure 51B shows a line graph of the data from Figure 51A.

[0171] [Figure 52] Figure 52A shows the readings of AhR activity from the HepG2-AhR-luciferase assay upon exposure to various concentrations of AB12509 (compound H). Figure 52B shows a line graph of the data from Figure 52A.

[0172] [Figure 53] Figure 53A shows the readings of AhR activity from the HepG2-AhR-luciferase assay upon exposure to various concentrations of CV-8688 (compound II). Figure 53B shows a line graph of the data from Figure 53A.

[0173] [Figure 54] Figure 54A shows the readings of AhR activity from the HepG2-AhR-luciferase assay upon exposure to various concentrations of CV-8877 (compound B). Figure 54B shows a line graph of the data from Figure 54A.

[0174] [Figure 55] Figure 55A shows the readings of AhR activity from the HepG2-AhR-luciferase assay upon exposure to various concentrations of CV-8685 (indro[3,2-b]carbazole). Figure 55B shows a line graph of the data from Figure 55A.

[0175] [Figure 56] Figure 56A shows the readings of AhR activity from the HepG2-AhR-luciferase assay upon exposure to compound B10 at various concentrations. Figure 56B shows a line graph of the data from Figure 56A.

[0176] [Figure 57]Figure 57A shows the readings of AhR activity from the HepG2-AhR-luciferase assay upon exposure to various concentrations of CV-8687 (compound IV). Figure 57B shows a line graph of the data from Figure 57A.

[0177] [Figure 58] Figure 58A shows the readings of AhR activity from the HepG2-AhR-luciferase assay upon exposure to various concentrations of omeprazole. Figure 58B shows a line graph of the data from Figure 58A.

[0178] [Figure 59] Figure 59A shows the readings of AhR activity from the HepG2-AhR-luciferase assay upon exposure to various concentrations of TCDD. Figure 59B shows a line graph of the data from Figure 59A.

[0179] [Figure 60] Figure 60A shows the readings of AhR activity from the HepG2-AhR-luciferase assay upon exposure to various concentrations of the Malasedin precursor. Figure 60B shows a line graph of the data from Figure 60A.

[0180] [Figure 61] Figure 61A shows the readings of AhR activity from the HepG2-AhR-luciferase assay upon exposure to various concentrations of AB11644. Figure 61B shows a line graph of the data from Figure 61A.

[0181] [Figure 62] Figure 62A shows the readings of AhR activity from the HepG2-AhR-luciferase assay upon exposure to various concentrations of 3-methylcholanthrene (3-MC). Figure 62B shows a line graph of the data from Figure 62A.

[0182] [Figure 63]Figure 63A shows the readings of AhR activity from the HepG2-AhR-luciferase assay upon exposure to various concentrations of AB12976(O52). Figure 63B shows a line graph of the data from Figure 63A.

[0183] [Figure 64] Figure 64A shows the readings of AhR activity from the HepG2-AhR-luciferase assay upon exposure to various concentrations of AB17011 (Malassezia indole A). Figure 64B shows a line graph of the data from Figure 64A.

[0184] [Figure 65] Figure 65A shows the readings of AhR activity from the HepG2-AhR-luciferase assay upon exposure to various concentrations of AB17014 (pitiliacitrin). Figure 65B shows a line graph of the data from Figure 65A.

[0185] [Figure 66] Figure 66A shows the readings of AhR activity from the HepG2-AhR-luciferase assay upon exposure to various concentrations of AB17151. Figure 66B shows a line graph of the data from Figure 66A.

[0186] [Figure 67] Figure 67A shows the readings of AhR activity from the HepG2-AhR-luciferase assay upon exposure to various concentrations of AB17225. Figure 67B shows a line graph of the data from Figure 67A.

[0187] [Figure 68] Figure 68 is a table showing MTT survival rate data derived from MelanoDerm™ substrates treated with various concentrations of the compounds shown.

[0188] [Figure 69]Figure 69 is a table showing melanin concentration data derived from MelanoDerm™ substrates treated with compounds of various concentrations.

[0189] [Figure 70] Figure 70 shows representative macroscopic photographic images of MelanoDerm® samples exposed to CV-8686 (compound I) and AB11644, taken on the specified date, where the samples were exposed to the indicated treatments.

[0190] [Figure 71] Figure 71 shows representative microscopic (15×) images of MelanoDerm® samples exposed to CV-8686 (compound I) and AB11644, taken on the specified date, where the samples were exposed to the indicated treatments.

[0191] [Figure 72] Figure 72 shows representative microscopic (15×) images of MelanoDerm® samples exposed to CV-8686 (compound I) and kojic acid, taken on the specified date, where the samples were exposed to the indicated treatments.

[0192] [Figure 73] Figure 73 shows representative macroscopic photographic images of MelanoDerm® samples exposed to CV-8686 (compound I) and kojic acid, taken on the specified date, where the samples were exposed to the indicated treatments.

[0193] [Figure 74] Figure 74 shows representative macroscopic photographic images of MelanoDerm® samples exposed to CV-8686 (compound I) and kojic acid, taken on the specified date, where the samples were exposed to the indicated treatments.

[0194] [Figure 75]Figure 75 is a table showing mean tissue viability and melanin concentration data elucidated from MelanoDerm® substrates treated with compounds at various concentrations. Where the sponsor's label is blank, the sample was of an unknown composition.

[0195] [Figure 76] Figure 76 shows representative macroscopic photographic images of MelanoDerm® samples exposed to the indicated treatment, taken on the specified date.

[0196] [Figure 77] Figure 77 shows representative macroscopic photographs of MelanoDerm® samples exposed to the indicated treatment, taken seven days after treatment. Where the compound name is blank, the sample was an unknown composition.

[0197] [Figure 78] Figure 78 shows representative microscopic (15×) images of MelanoDerm® samples exposed to the indicated treatment, taken on the specified date.

[0198] [Figure 79] Figure 79 shows representative microscopic (15×) images of MelanoDerm® samples exposed to the indicated treatment, taken on the specified date. Where the compound name is blank, the sample was an unknown composition.

[0199] [Figure 80] Figures 80–87 show representative macroscopic images of MelanoDerm® samples exposed to the indicated treatments, taken on day 7. In Figure 85, if the compound name is blank, the sample was an unknown composition. [Figure 81] Figures 80–87 show representative macroscopic images of MelanoDerm® samples exposed to the indicated treatments, taken on day 7. In Figure 85, if the compound name is blank, the sample was an unknown composition. [Figure 82] Figures 80–87 show representative macroscopic images of MelanoDerm® samples exposed to the indicated treatments, taken on day 7. In Figure 85, if the compound name is blank, the sample was an unknown composition. [Figure 83] Figures 80–87 show representative macroscopic images of MelanoDerm® samples exposed to the indicated treatments, taken on day 7. In Figure 85, if the compound name is blank, the sample was an unknown composition. [Figure 84] Figures 80–87 show representative macroscopic images of MelanoDerm® samples exposed to the indicated treatments, taken on day 7. In Figure 85, if the compound name is blank, the sample was an unknown composition. [Figure 85] Figures 80–87 show representative macroscopic images of MelanoDerm® samples exposed to the indicated treatments, taken on day 7. In Figure 85, if the compound name is blank, the sample was an unknown composition. [Figure 86] Figures 80–87 show representative macroscopic images of MelanoDerm® samples exposed to the indicated treatments, taken on day 7. In Figure 85, if the compound name is blank, the sample was an unknown composition. [Figure 87] Figures 80–87 show representative macroscopic images of MelanoDerm® samples exposed to the indicated treatments, taken on day 7. In Figure 85, if the compound name is blank, the sample was an unknown composition.

[0200] [Figure 88] Figure 88 is a table showing average tissue viability and melanin concentration data derived from MelanoDerm™ substrates treated with compounds at various concentrations.

[0201] [Figure 89-1]Figures 89A–89X show histograms of the survival rate and melanin change rate of B16 melanocytes after the indicated treatment. In Figures 89M–89N, if the compound name is blank, the sample was an unknown composition. [Figure 89-2] Figures 89A–89X show histograms of the survival rate and melanin change rate of B16 melanocytes after the indicated treatment. In Figures 89M–89N, if the compound name is blank, the sample was an unknown composition. [Figure 89-3] Figures 89A–89X show histograms of the survival rate and melanin change rate of B16 melanocytes after the indicated treatment. In Figures 89M–89N, if the compound name is blank, the sample was an unknown composition. [Figure 89-4] Figures 89A–89X show histograms of the survival rate and melanin change rate of B16 melanocytes after the indicated treatment. In Figures 89M–89N, if the compound name is blank, the sample was an unknown composition. [Figure 89-5] Figures 89A–89X show histograms of the survival rate and melanin change rate of B16 melanocytes after the indicated treatment. In Figures 89M–89N, if the compound name is blank, the sample was an unknown composition. [Figure 89-6] Figures 89A–89X show histograms of the survival rate and melanin change rate of B16 melanocytes after the indicated treatment. In Figures 89M–89N, if the compound name is blank, the sample was an unknown composition. [Figure 89-7] Figures 89A–89X show histograms of the survival rate and melanin change rate of B16 melanocytes after the indicated treatment. In Figures 89M–89N, the sample was an unknown composition when the compound name was blank. [Figure 89-8] Figures 89A–89X show histograms of the survival rate and melanin change rate of B16 melanocytes after the indicated treatment. In Figures 89M–89N, if the compound name is blank, the sample was an unknown composition. [Figure 89-9]Figures 89A–89X show histograms of the survival rate and melanin change rate of B16 melanocytes after the indicated treatment. In Figures 89M–89N, if the compound name is blank, the sample was an unknown composition. [Figure 89-10] Figures 89A–89X show histograms of the survival rate and melanin change rate of B16 melanocytes after the indicated treatment. In Figures 89M–89N, if the compound name is blank, the sample was an unknown composition. [Figure 89-11] Figures 89A–89X show histograms of the survival rate and melanin change rate of B16 melanocytes after the indicated treatment. In Figures 89M–89N, if the compound name is blank, the sample was an unknown composition. [Figure 89-12] Figures 89A–89X show histograms of the survival rate and melanin change rate of B16 melanocytes after the indicated treatment. In Figures 89M–89N, if the compound name is blank, the sample was an unknown composition.

[0202] [Figure 90-1] Figures 90A, 90C, and 90E show tables of data containing percentages of annexin V-positive B16F1 cells (Figure 90A), MeWo cells (Figure 90C), and WM115 cells (Figure 90E) at 6, 24, 48, and 72 hours after exposure to staurosporine. Figures 90B, 90D, and 90F show tables of data containing percentages of propidium iodide (PI)-positive B16F1 cells (Figure 90B), MeWo cells (Figure 90D), and WM115 cells (Figure 90F) at 6, 24, 48, and 72 hours after exposure to staurosporine. [Figure 90-2]Figures 90A, 90C, and 90E show tables of data containing percentages of annexin V-positive B16F1 cells (Figure 90A), MeWo cells (Figure 90C), and WM115 cells (Figure 90E) at 6, 24, 48, and 72 hours after exposure to staurosporine. Figures 90B, 90D, and 90F show tables of data containing percentages of propidium iodide (PI)-positive B16F1 cells (Figure 90B), MeWo cells (Figure 90D), and WM115 cells (Figure 90F) at 6, 24, 48, and 72 hours after exposure to staurosporine.

[0203] [Figure 91-1] Figures 91A, 91C, and 91E show tables of data containing percentages of annexin V-positive B16F1 cells (Figure 91A), MeWo cells (Figure 91C), and WM115 cells (Figure 91E) at 6, 24, 48, and 72 hours after exposure to compound H (AB12509). Figures 91B, 91D, and 91F show tables of data containing percentages of propidium iodide (PI)-positive B16F1 cells (Figure 91B), MeWo cells (Figure 91D), and WM115 cells (Figure 91F) at 6, 24, 48, and 72 hours after exposure to compound H (AB12509). [Figure 91-2] Figures 91A, 91C, and 91E show tables of data containing percentages of annexin V-positive B16F1 cells (Figure 91A), MeWo cells (Figure 91C), and WM115 cells (Figure 91E) at 6, 24, 48, and 72 hours after exposure to compound H (AB12509). Figures 91B, 91D, and 91F show tables of data containing percentages of propidium iodide (PI)-positive B16F1 cells (Figure 91B), MeWo cells (Figure 91D), and WM115 cells (Figure 91F) at 6, 24, 48, and 72 hours after exposure to compound H (AB12509).

[0204] [Figure 92-1]Figures 92A, 92C, and 92E show tables of data containing percentages of annexin V-positive B16F1 cells (Figure 92A), MeWo cells (Figure 92C), and WM115 cells (Figure 92E) at 6, 24, 48, and 72 hours after exposure to Malasedin (CV-8684). Figures 92B, 92D, and 92F show tables of data containing percentages of propidium iodide (PI)-positive B16F1 cells (Figure 92B), MeWo cells (Figure 92D), and WM115 cells (Figure 92F) at 6, 24, 48, and 72 hours after exposure to Malasedin (CV-8684). [Figure 92-2] Figures 92A, 92C, and 92E show tables of data containing percentages of annexin V-positive B16F1 cells (Figure 92A), MeWo cells (Figure 92C), and WM115 cells (Figure 92E) at 6, 24, 48, and 72 hours after exposure to Malasedin (CV-8684). Figures 92B, 92D, and 92F show tables of data containing percentages of propidium iodide (PI)-positive B16F1 cells (Figure 92B), MeWo cells (Figure 92D), and WM115 cells (Figure 92F) at 6, 24, 48, and 72 hours after exposure to Malasedin (CV-8684).

[0205] [Figure 93-1] Figures 93A, 93C, and 93E show tables of data containing percentages of annexin V-positive B16F1 cells (Figure 93A), MeWo cells (Figure 93C), and WM115 cells (Figure 93E) at 6, 24, 48, and 72 hours after exposure to compound B (CV-8877). Figures 93B, 93D, and 93F show tables of data containing percentages of propidium iodide (PI)-positive B16F1 cells (Figure 93B), MeWo cells (Figure 93D), and WM115 cells (Figure 93F) at 6, 24, 48, and 72 hours after exposure to compound B (CV-8877). [Figure 93-2]Figures 93A, 93C, and 93E show tables of data containing percentages of annexin V-positive B16F1 cells (Figure 93A), MeWo cells (Figure 93C), and WM115 cells (Figure 93E) at 6, 24, 48, and 72 hours after exposure to compound B (CV-8877). Figures 93B, 93D, and 93F show tables of data containing percentages of propidium iodide (PI)-positive B16F1 cells (Figure 93B), MeWo cells (Figure 93D), and WM115 cells (Figure 93F) at 6, 24, 48, and 72 hours after exposure to compound B (CV-8877).

[0206] [Figure 94-1] Figures 94A, 94C, and 94E show tables of data containing percentages of annexin V-positive B16F1 cells (Figure 94A), MeWo cells (Figure 94C), and WM115 cells (Figure 94E) at 6, 24, 48, and 72 hours after exposure to compound I (CV-8686). Figures 94B, 94D, and 94F show tables of data containing percentages of propidium iodide (PI)-positive B16F1 cells (Figure 94B), MeWo cells (Figure 94D), and WM115 cells (Figure 94F) at 6, 24, 48, and 72 hours after exposure to compound I (CV-8686). [Figure 94-2] Figures 94A, 94C, and 94E show tables of data containing percentages of annexin V-positive B16F1 cells (Figure 94A), MeWo cells (Figure 94C), and WM115 cells (Figure 94E) at 6, 24, 48, and 72 hours after exposure to compound I (CV-8686). Figures 94B, 94D, and 94F show tables of data containing percentages of propidium iodide (PI)-positive B16F1 cells (Figure 94B), MeWo cells (Figure 94D), and WM115 cells (Figure 94F) at 6, 24, 48, and 72 hours after exposure to compound I (CV-8686).

[0207] [Figure 95-1]Figures 95A, 95C, and 95E show tables of data containing percentages of annexin V-positive B16F1 cells (Figure 95A), MeWo cells (Figure 95C), and WM115 cells (Figure 95E) at 6, 24, 48, and 72 hours after exposure to compound B10. Figures 95B, 95D, and 95F show tables of data containing percentages of propidium iodide (PI)-positive B16F1 cells (Figure 95B), MeWo cells (Figure 95D), and WM115 cells (Figure 95F) at 6, 24, 48, and 72 hours after exposure to compound B10. [Figure 95-2] Figures 95A, 95C, and 95E show tables of data containing percentages of annexin V-positive B16F1 cells (Figure 95A), MeWo cells (Figure 95C), and WM115 cells (Figure 95E) at 6, 24, 48, and 72 hours after exposure to compound B10. Figures 95B, 95D, and 95F show tables of data containing percentages of propidium iodide (PI)-positive B16F1 cells (Figure 95B), MeWo cells (Figure 95D), and WM115 cells (Figure 95F) at 6, 24, 48, and 72 hours after exposure to compound B10.

[0208] [Figure 96-1] Figures 96A, 96C, and 96E show tables of data containing percentages of annexin V-positive B16F1 cells (Figure 96A), MeWo cells (Figure 96C), and WM115 cells (Figure 96E) at 6, 24, 48, and 72 hours after exposure to compound II (CV-8688). Figures 96B, 96D, and 96F show tables of data containing percentages of propidium iodide (PI)-positive B16F1 cells (Figure 96B), MeWo cells (Figure 96D), and WM115 cells (Figure 96F) at 6, 24, 48, and 72 hours after exposure to compound II (CV-8688). [Figure 96-2]Figures 96A, 96C, and 96E show tables of data containing percentages of annexin V-positive B16F1 cells (Figure 96A), MeWo cells (Figure 96C), and WM115 cells (Figure 96E) at 6, 24, 48, and 72 hours after exposure to compound II (CV-8688). Figures 96B, 96D, and 96F show tables of data containing percentages of propidium iodide (PI)-positive B16F1 cells (Figure 96B), MeWo cells (Figure 96D), and WM115 cells (Figure 96F) at 6, 24, 48, and 72 hours after exposure to compound II (CV-8688).

[0209] [Figure 97-1] Figures 97A, 97C, and 97E show tables of data containing percentages of annexin V-positive B16F1 cells (Figure 97A), MeWo cells (Figure 97C), and WM115 cells (Figure 97E) at 6, 24, 48, and 72 hours after exposure to the Malasedin precursor. Figures 97B, 97D, and 97F show tables of data containing percentages of propidium iodide (PI)-positive B16F1 cells (Figure 97B), MeWo cells (Figure 97D), and WM115 cells (Figure 97F) at 6, 24, 48, and 72 hours after exposure to the Malasedin precursor. [Figure 97-2] Figures 97A, 97C, and 97E show tables of data containing percentages of annexin V-positive B16F1 cells (Figure 97A), MeWo cells (Figure 97C), and WM115 cells (Figure 97E) at 6, 24, 48, and 72 hours after exposure to the Malasedin precursor. Figures 97B, 97D, and 97F show tables of data containing percentages of propidium iodide (PI)-positive B16F1 cells (Figure 97B), MeWo cells (Figure 97D), and WM115 cells (Figure 97F) at 6, 24, 48, and 72 hours after exposure to the Malasedin precursor.

[0210] [Figure 98-1]Figures 98A, 98C, and 98E show tables of data containing percentages of annexin V-positive B16F1 cells (Figure 98A), MeWo cells (Figure 98C), and WM115 cells (Figure 98E) at 6, 24, 48, and 72 hours after exposure to indro[3,2-b]carbazole (CV-8685). Figures 98B, 98D, and 98F show tables of data containing percentages of propidium iodide (PI)-positive B16F1 cells (Figure 98B), MeWo cells (Figure 98D), and WM115 cells (Figure 98F) at 6, 24, 48, and 72 hours after exposure to indro[3,2-b]carbazole (CV-8685). [Figure 98-2] Figures 98A, 98C, and 98E show tables of data containing percentages of annexin V-positive B16F1 cells (Figure 98A), MeWo cells (Figure 98C), and WM115 cells (Figure 98E) at 6, 24, 48, and 72 hours after exposure to indro[3,2-b]carbazole (CV-8685). Figures 98B, 98D, and 98F show tables of data containing percentages of propidium iodide (PI)-positive B16F1 cells (Figure 98B), MeWo cells (Figure 98D), and WM115 cells (Figure 98F) at 6, 24, 48, and 72 hours after exposure to indro[3,2-b]carbazole (CV-8685).

[0211] [Figure 99-1] Figures 99A, 99C, and 99E show tables of data containing percentages of annexin V-positive B16F1 cells (Figure 99A), MeWo cells (Figure 99C), and WM115 cells (Figure 99E) at 6, 24, 48, and 72 hours after exposure to AB17151. Figures 99B, 99D, and 99F show tables of data containing percentages of propidium iodide (PI)-positive B16F1 cells (Figure 99B), MeWo cells (Figure 99D), and WM115 cells (Figure 99F) at 6, 24, 48, and 72 hours after exposure to AB17151. [Figure 99-2]Figures 99A, 99C, and 99E show tables of data containing percentages of annexin V-positive B16F1 cells (Figure 99A), MeWo cells (Figure 99C), and WM115 cells (Figure 99E) at 6, 24, 48, and 72 hours after exposure to AB17151. Figures 99B, 99D, and 99F show tables of data containing percentages of propidium iodide (PI)-positive B16F1 cells (Figure 99B), MeWo cells (Figure 99D), and WM115 cells (Figure 99F) at 6, 24, 48, and 72 hours after exposure to AB17151.

[0212] [Figure 100-1] Figures 100A, 100C, and 100E show tables of data containing percentages of annexin V-positive B16F1 cells (Figure 100A), MeWo cells (Figure 100C), and WM115 cells (Figure 100E) at 6, 24, 48, and 72 hours after exposure to compound IV (CV-8687). Figures 100B, 100D, and 100F show tables of data containing percentages of propidium iodide (PI)-positive B16F1 cells (Figure 100B), MeWo cells (Figure 100D), and WM115 cells (Figure 100F) at 6, 24, 48, and 72 hours after exposure to compound IV (CV-8687). [Figure 100-2] Figures 100A, 100C, and 100E show tables of data containing percentages of annexin V-positive B16F1 cells (Figure 100A), MeWo cells (Figure 100C), and WM115 cells (Figure 100E) at 6, 24, 48, and 72 hours after exposure to compound IV (CV-8687). Figures 100B, 100D, and 100F show tables of data containing percentages of propidium iodide (PI)-positive B16F1 cells (Figure 100B), MeWo cells (Figure 100D), and WM115 cells (Figure 100F) at 6, 24, 48, and 72 hours after exposure to compound IV (CV-8687).

[0213] [Figure 101-1]Figures 101A, 101C, and 101E show tables of data containing percentages of annexin V-positive B16F1 cells (Figure 101A), MeWo cells (Figure 101C), and WM115 cells (Figure 101E) at 6, 24, 48, and 72 hours after exposure to AB17011. Figures 101B, 101D, and 101F show tables of data containing percentages of propidium iodide (PI)-positive B16F1 cells (Figure 101B), MeWo cells (Figure 101D), and WM115 cells (Figure 101F) at 6, 24, 48, and 72 hours after exposure to AB17011. [Figure 101-2] Figures 101A, 101C, and 101E show tables of data containing percentages of annexin V-positive B16F1 cells (Figure 101A), MeWo cells (Figure 101C), and WM115 cells (Figure 101E) at 6, 24, 48, and 72 hours after exposure to AB17011. Figures 101B, 101D, and 101F show tables of data containing percentages of propidium iodide (PI)-positive B16F1 cells (Figure 101B), MeWo cells (Figure 101D), and WM115 cells (Figure 101F) at 6, 24, 48, and 72 hours after exposure to AB17011.

[0214] [Figure 102-1] Figures 102A, 102C, and 102E show tables of data containing percentages of annexin V-positive B16F1 cells (Figure 102A), MeWo cells (Figure 102C), and WM115 cells (Figure 102E) at 6, 24, 48, and 72 hours after exposure to AB11644. Figures 102B, 102D, and 102F show tables of data containing percentages of propidium iodide (PI)-positive B16F1 cells (Figure 102B), MeWo cells (Figure 102D), and WM115 cells (Figure 102F) at 6, 24, 48, and 72 hours after exposure to AB11644. [Figure 102-2]Figures 102A, 102C, and 102E show tables of data containing percentages of annexin V-positive B16F1 cells (Figure 102A), MeWo cells (Figure 102C), and WM115 cells (Figure 102E) at 6, 24, 48, and 72 hours after exposure to AB11644. Figures 102B, 102D, and 102F show tables of data containing percentages of propidium iodide (PI)-positive B16F1 cells (Figure 102B), MeWo cells (Figure 102D), and WM115 cells (Figure 102F) at 6, 24, 48, and 72 hours after exposure to AB11644.

[0215] [Figure 103-1] Figures 103A, 103C, and 103E show tables of data containing percentages of annexin V-positive B16F1 cells (Figure 103A), MeWo cells (Figure 103C), and WM115 cells (Figure 103E) at 6, 24, 48, and 72 hours after exposure to AB17014. Figures 103B, 103D, and 103F show tables of data containing percentages of propidium iodide (PI)-positive B16F1 cells (Figure 103B), MeWo cells (Figure 103D), and WM115 cells (Figure 103F) at 6, 24, 48, and 72 hours after exposure to AB17014. [Figure 103-2] Figures 103A, 103C, and 103E show tables of data containing percentages of annexin V-positive B16F1 cells (Figure 103A), MeWo cells (Figure 103C), and WM115 cells (Figure 103E) at 6, 24, 48, and 72 hours after exposure to AB17014. Figures 103B, 103D, and 103F show tables of data containing percentages of propidium iodide (PI)-positive B16F1 cells (Figure 103B), MeWo cells (Figure 103D), and WM115 cells (Figure 103F) at 6, 24, 48, and 72 hours after exposure to AB17014.

[0216] [Figure 104-1]Figures 104A, 104C, and 104E show tables of data containing percentages of Annexin V-positive B16F1 cells (Figure 104A), MeWo cells (Figure 104C), and WM115 cells (Figure 104E) at 6, 24, 48, and 72 hours after exposure to the unknown composition. Figures 104B, 104D, and 104F show tables of data containing percentages of propidium iodide (PI)-positive B16F1 cells (Figure 104B), MeWo cells (Figure 104D), and WM115 cells (Figure 104F) at 6, 24, 48, and 72 hours after exposure to the unknown composition. [Figure 104-2] Figures 104A, 104C, and 104E show tables of data containing percentages of Annexin V-positive B16F1 cells (Figure 104A), MeWo cells (Figure 104C), and WM115 cells (Figure 104E) at 6, 24, 48, and 72 hours after exposure to the unknown composition. Figures 104B, 104D, and 104F show tables of data containing percentages of propidium iodide (PI)-positive B16F1 cells (Figure 104B), MeWo cells (Figure 104D), and WM115 cells (Figure 104F) at 6, 24, 48, and 72 hours after exposure to the unknown composition.

[0217] [Figure 105-1] Figures 105A, 105C, and 105E show tables of data containing percentages of annexin V-positive B16F1 cells (Figure 105A), MeWo cells (Figure 105C), and WM115 cells (Figure 105E) at 6, 24, 48, and 72 hours after exposure to AB17225. Figures 105B, 105D, and 105F show tables of data containing percentages of propidium iodide (PI)-positive B16F1 cells (Figure 105B), MeWo cells (Figure 105D), and WM115 cells (Figure 105F) at 6, 24, 48, and 72 hours after exposure to AB17225. [Figure 105-2]Figures 105A, 105C, and 105E show tables of data containing percentages of annexin V-positive B16F1 cells (Figure 105A), MeWo cells (Figure 105C), and WM115 cells (Figure 105E) at 6, 24, 48, and 72 hours after exposure to AB17225. Figures 105B, 105D, and 105F show tables of data containing percentages of propidium iodide (PI)-positive B16F1 cells (Figure 105B), MeWo cells (Figure 105D), and WM115 cells (Figure 105F) at 6, 24, 48, and 72 hours after exposure to AB17225.

[0218] [Figure 106-1] Figures 106A, 106C, and 106E show tables of data containing percentages of annexin V-positive B16F1 cells (Figure 106A), MeWo cells (Figure 106C), and WM115 cells (Figure 106E) at 6, 24, 48, and 72 hours after exposure to compound A5 (CV-8819). Figures 106B, 106D, and 106F show tables of data containing percentages of propidium iodide (PI)-positive B16F1 cells (Figure 106B), MeWo cells (Figure 106D), and WM115 cells (Figure 106F) at 6, 24, 48, and 72 hours after exposure to compound A5 (CV-8819). [Figure 106-2] Figures 106A, 106C, and 106E show tables of data containing percentages of annexin V-positive B16F1 cells (Figure 106A), MeWo cells (Figure 106C), and WM115 cells (Figure 106E) at 6, 24, 48, and 72 hours after exposure to compound A5 (CV-8819). Figures 106B, 106D, and 106F show tables of data containing percentages of propidium iodide (PI)-positive B16F1 cells (Figure 106B), MeWo cells (Figure 106D), and WM115 cells (Figure 106F) at 6, 24, 48, and 72 hours after exposure to compound A5 (CV-8819).

[0219] [Figure 107-1]Figures 107A, 107C, and 107E show tables of data containing percentages of annexin V-positive B16F1 cells (Figure 107A), MeWo cells (Figure 107C), and WM115 cells (Figure 107E) at 6, 24, 48, and 72 hours after exposure to AB12976. Figures 107B, 107D, and 107F show tables of data containing percentages of propidium iodide (PI)-positive B16F1 cells (Figure 107B), MeWo cells (Figure 107D), and WM115 cells (Figure 107F) at 6, 24, 48, and 72 hours after exposure to AB12976. [Figure 107-2] Figures 107A, 107C, and 107E show tables of data containing percentages of annexin V-positive B16F1 cells (Figure 107A), MeWo cells (Figure 107C), and WM115 cells (Figure 107E) at 6, 24, 48, and 72 hours after exposure to AB12976. Figures 107B, 107D, and 107F show tables of data containing percentages of propidium iodide (PI)-positive B16F1 cells (Figure 107B), MeWo cells (Figure 107D), and WM115 cells (Figure 107F) at 6, 24, 48, and 72 hours after exposure to AB12976.

[0220] [Figure 108-1] Figures 108A, 108C, and 108E show tables of data containing percentages of annexin V-positive B16F1 cells (Figure 108A), MeWo cells (Figure 108C), and WM115 cells (Figure 108E) at 6, 24, 48, and 72 hours after exposure to compound E (AB12508). Figures 108B, 108D, and 108F show tables of data containing percentages of propidium iodide (PI)-positive B16F1 cells (Figure 108B), MeWo cells (Figure 108D), and WM115 cells (Figure 108F) at 6, 24, 48, and 72 hours after exposure to compound E (AB12508). [Figure 108-2]Figures 108A, 108C, and 108E show tables of data containing percentages of annexin V-positive B16F1 cells (Figure 108A), MeWo cells (Figure 108C), and WM115 cells (Figure 108E) at 6, 24, 48, and 72 hours after exposure to compound E (AB12508). Figures 108B, 108D, and 108F show tables of data containing percentages of propidium iodide (PI)-positive B16F1 cells (Figure 108B), MeWo cells (Figure 108D), and WM115 cells (Figure 108F) at 6, 24, 48, and 72 hours after exposure to compound E (AB12508).

[0221] [Figure 109] Figures 109A, 109B, and 109C show tables of data including caspase 3 / 7 induction rates in B16F1 cells, MeWo cells, and WM115 cells compared to vehicle controls at 6, 24, 48, and 72 hours after exposure to staurosporine, respectively.

[0222] [Figure 110] Figures 110A, 110B, and 110C show tables of data including caspase 3 / 7 induction rates in B16F1 cells, MeWo cells, and WM115 cells compared to vehicle controls at 6, 24, 48, and 72 hours after exposure to Malasedin (CV-8684), respectively.

[0223] [Figure 111] Figures 111A, 111B, and 111C show tables of data including caspase 3 / 7 induction rates in B16F1 cells, MeWo cells, and WM115 cells compared to vehicle controls at 6, 24, 48, and 72 hours after exposure to compound I (CV-8686), respectively.

[0224] [Figure 112]Figures 112A, 112B, and 112C show tables of data including caspase 3 / 7 induction rates in B16F1 cells, MeWo cells, and WM115 cells compared to vehicle controls at 6, 24, 48, and 72 hours after exposure to compound II (CV-8688), respectively.

[0225] [Figure 113] Figures 113A, 113B, and 113C show tables of data, respectively, including caspase 3 / 7 induction rates in B16F1 cells, MeWo cells, and WM115 cells compared to vehicle controls, at 6, 24, 48, and 72 hours after exposure to indro[3,2-b]carbazole (CV-8685).

[0226] [Figure 114] Figures 114A, 114B, and 114C show tables of data including caspase 3 / 7 induction rates in B16F1 cells, MeWo cells, and WM115 cells compared to vehicle controls at 6, 24, 48, and 72 hours after exposure to compound IV (CV-8687), respectively.

[0227] [Figure 115] Figures 115A, 115B, and 115C show tables of data including caspase 3 / 7 induction rates in B16F1 cells, MeWo cells, and WM115 cells compared to vehicle controls at 6, 24, 48, and 72 hours after exposure to AB11644, respectively.

[0228] [Figure 116] Figures 116A, 116B, and 116C show tables of data including caspase 3 / 7 induction rates in B16F1 cells, MeWo cells, and WM115 cells compared to vehicle controls at 6, 24, 48, and 72 hours after exposure to an unknown composition, respectively.

[0229] [Figure 117]Figures 117A, 117B, and 117C show tables of data, including caspase 3 / 7 induction rates, for B16F1 cells, MeWo cells, and WM115 cells compared to vehicle controls, at 6, 24, 48, and 72 hours after exposure to compound A5 (CV-8819), respectively.

[0230] [Figure 118] Figures 118A, 118B, and 118C show tables of data including caspase 3 / 7 induction rates in B16F1 cells, MeWo cells, and WM115 cells compared to vehicle controls at 6, 24, 48, and 72 hours after exposure to compound E (AB12508), respectively.

[0231] [Figure 119] Figures 119A, 119B, and 119C show tables of data including caspase 3 / 7 induction rates in B16F1 cells, MeWo cells, and WM115 cells compared to vehicle controls at 6, 24, 48, and 72 hours after exposure to compound H (AB12509), respectively.

[0232] [Figure 120] Figures 120A, 120B, and 120C show tables of data including caspase 3 / 7 induction rates in B16F1 cells, MeWo cells, and WM115 cells compared to vehicle controls at 6, 24, 48, and 72 hours, respectively, after exposure to compound B (CV-8877).

[0233] [Figure 121] Figures 121A, 121B, and 121C show tables of data including caspase 3 / 7 induction rates in B16F1 cells, MeWo cells, and WM115 cells compared to vehicle controls at 6, 24, 48, and 72 hours after exposure to compound B10, respectively.

[0234] [Figure 122]Figures 122A, 122B, and 122C show tables of data including caspase 3 / 7 induction rates in B16F1 cells, MeWo cells, and WM115 cells compared to vehicle controls at 6, 24, 48, and 72 hours, respectively, after exposure to the Malasedin precursor.

[0235] [Figure 123] Figures 123A, 123B, and 123C show tables of data including caspase 3 / 7 induction rates in B16F1 cells, MeWo cells, and WM115 cells compared to vehicle controls at 6, 24, 48, and 72 hours after exposure to AB17151, respectively.

[0236] [Figure 124] Figures 124A, 124B, and 124C show tables of data including caspase 3 / 7 induction rates in B16F1 cells, MeWo cells, and WM115 cells compared to vehicle controls at 6, 24, 48, and 72 hours after exposure to AB17011, respectively.

[0237] [Figure 125] Figures 125A, 125B, and 125C show tables of data including caspase 3 / 7 induction rates in B16F1 cells, MeWo cells, and WM115 cells compared to vehicle controls at 6, 24, 48, and 72 hours after exposure to AB17014, respectively.

[0238] [Figure 126] Figures 126A, 126B, and 126C show tables of data including caspase 3 / 7 induction rates in B16F1 cells, MeWo cells, and WM115 cells compared to vehicle controls at 6, 24, 48, and 72 hours after exposure to AB17225, respectively.

[0239] [Figure 127]Figures 127A, 127B, and 127C show tables of data including caspase 3 / 7 induction rates in B16F1 cells, MeWo cells, and WM115 cells compared to vehicle controls at 6, 24, 48, and 72 hours after exposure to AB12976, respectively.

[0240] [Figure 128-1] Figures 128-129 are tables showing average tissue viability and melanin concentration data obtained from individual experiments using MelanoDerm™ substrates treated with test materials of various concentrations. [Figure 128-2] Figures 128-129 are tables showing average tissue viability and melanin concentration data obtained from individual experiments using MelanoDerm™ substrates treated with test materials of various concentrations. [Figure 129-1] Figures 128-129 are tables showing average tissue viability and melanin concentration data obtained from individual experiments using MelanoDerm™ substrates treated with test materials of various concentrations. [Figure 129-2] Figures 128-129 are tables showing average tissue viability and melanin concentration data obtained from individual experiments using MelanoDerm™ substrates treated with test materials of various concentrations.

[0241] [Figure 130-1] Figure 130 shows the compounds produced by Malassezia. [Figure 130-2] Figure 130 shows the compounds produced by Malassezia. [Figure 130-3] Figure 130 shows the compounds produced by Malassezia. [Figure 130-4] Figure 130 shows the compounds produced by Malassezia.

[0242] [Figure 131]Figure 131 is a table showing average tissue viability and melanin concentration data elucidated from individual experiments using MelanoDerm® substrates treated with various concentrations of test articles / compositions. [Figure 132] Figure 132 is a table showing average tissue viability and melanin concentration data obtained from individual experiments using MelanoDerm® substrates treated with various concentrations of test articles / compositions.

[0243] [Figure 133A] Figures 133A to 133B show the composite schemes for AB17590 (Figure 133A) and AB17653, AB17654, AB17655, AB17656, AB17657, and AB17658 (Figure 133B). [Figure 133B] Figures 133A to 133B show the composite schemes for AB17590 (Figure 133A) and AB17653, AB17654, AB17655, AB17656, AB17657, and AB17658 (Figure 133B).

[0244] [Figure 134] Figure 134 is a schematic diagram showing the types of skin treatments for patients with skin type IV. The values ​​represent the UV dose in any region in mJ / cm2 units.

[0245] [Figure 135] Figure 135 is a table showing the Dualight scale for skin types I-VI.

[0246] [Figure 136] Figure 136 is a table showing the mexameter MX16 measurements of melanin and erythema on day 8, following irradiation on day 7.

[0247] [Figure 137-1] Figure 137 is a table showing the mexameter MX16 measurements of melanin and erythema on day 15, following irradiation on day 14. [Figure 137-2] Figure 137 is a table showing the mexameter MX16 measurements of melanin and erythema on day 15, following irradiation on day 14.

[0248] [Figure 138] Figure 138 is a table showing the erythema scale, which is a numerical value related to various degrees of erythema.

[0249] [Figure 139] Figure 139 is a photograph showing the skin of subjects 24 hours after irradiation with various levels of UV, according to the type of skin treatment shown in Figure 7. The minimum erythematous dose ("MED") 24 hours after irradiation was 120 mJ UVB.

[0250] [Figure 140] Figure 140 is a photograph showing the test site on the subject's skin on day 7.

[0251] [Figure 141] Figure 141 is a photograph showing the test site on the skin of the subject 24 hours after irradiation with 120 mJ UVB, on day 8.

[0252] [Figure 142] Figure 142 is a photograph showing the test site on the skin of the subject on day 14, after an additional week of Malasedin treatment. 120 mJ of UVB was administered to the treatment area.

[0253] [Figure 143] Figure 143 is a photograph showing the test site on the target skin on day 15, 24 hours after irradiation with 120 mJ UVB. Note that erythema is present at the vehicle site on days 7 and 9. Note that there is minimal to mild erythema at the Malasezin 1% treatment site on days 1 and 3, and on days 14, 10, and 8, with slight erythema present. [Modes for carrying out the invention]

[0254] One embodiment of the present invention is a skin-whitening compound. The compound is a chemical analog of a compound produced by Malassezia yeast, or its crystalline form, hydrate, or a cosmetic or pharmaceutically acceptable salt thereof.

[0255] In one embodiment of this design, the compound produced by Malassezia yeast has the structure of formula (I): [ka] It has.

[0256] In another aspect of this embodiment, the compound is a chemical analog of malasezin.

[0257] Another embodiment of the present invention is a compound that induces melanocyte apoptosis. The compound is a chemical analog of a compound produced by Malassezia yeast, or its crystalline form, hydrate, or a salt that is cosmetically or pharmaceutically acceptable.

[0258] In one embodiment of this design, the compound produced by Malassezia yeast has the structure of formula (I): [ka] It has.

[0259] In another aspect of this embodiment, the compound is a chemical analog of malasezin.

[0260] Further embodiments of the present invention are compounds that modulate melanocyte activity. These compounds are chemical analogs of compounds produced by Malassezia yeast, or their crystalline form, hydrate, or salts that are cosmetically or pharmaceutically acceptable.

[0261] In one embodiment of this design, the compound produced by Malassezia yeast has the structure of formula (I): [ka] It has.

[0262] In another aspect of this embodiment, the compound is a chemical analog of malasezin.

[0263] An additional embodiment of the present invention is a compound that acts on an aromatic hydrocarbon acceptor (AhR). The compound is a chemical analog of a compound produced by Malassezia yeast, or its crystalline form, hydrate, or a salt that is cosmetically or pharmaceutically acceptable.

[0264] In one embodiment of this design, the compound produced by Malassezia yeast has the structure of formula (I): [ka] It has.

[0265] In another aspect of this embodiment, the compound is a chemical analog of malasezin.

[0266] Another embodiment of the present invention is a compound that improves hyperpigmentation caused by hyperpigmentation disorder. The compound is a chemical analog of the compound produced by Malassezia yeast, or its crystalline form, hydrate, or a salt that is cosmetically or pharmaceutically acceptable.

[0267] In one embodiment of this design, the compound produced by Malassezia yeast has the structure of formula (I): [ka] It has.

[0268] In another aspect of this embodiment, the compound is a chemical analog of malasezin.

[0269] A further embodiment of the present invention is a compound that modulates melanin production. The compound is a chemical analog of a compound produced by Malassezia yeast, or its crystalline form, hydrate, or a salt that is cosmetically or pharmaceutically acceptable.

[0270] In one embodiment of this design, the compound produced by Malassezia yeast has the structure of formula (I): [ka] It has.

[0271] In another aspect of this embodiment, the compound is a chemical analog of malasezin.

[0272] An additional embodiment of the present invention is a compound that modulates melanosome biogenesis. The compound is a chemical analog of a compound produced by Malassezia yeast, This refers to its crystalline form, hydrate, or salt that is acceptable for cosmetic or pharmaceutically use.

[0273] In one embodiment of this design, the compound produced by Malassezia yeast has the structure of formula (I): [ka] It has.

[0274] In another aspect of this embodiment, the compound is a chemical analog of malasezin.

[0275] Another embodiment of the present invention is a compound that modulates melanosome transport. The compound is a chemical analog of a compound produced by Malassezia yeast, or its crystalline form, hydrate, or a cosmetic or pharmaceutically acceptable salt thereof.

[0276] In one embodiment of this design, the compound produced by Malassezia yeast has the structure of formula (I): [ka] It has.

[0277] In another aspect of this embodiment, the compound is a chemical analog of malasezin.

[0278] A further embodiment of the present invention is a composition comprising Malassezia yeast and a vehicle, diluent, or carrier that is cosmetically or pharmaceutically acceptable.

[0279] An additional embodiment of the present invention is a composition comprising a compound isolated or separable from Malassezia yeast, and a vehicle, diluent, or carrier that is cosmetically or pharmaceutically acceptable.

[0280] Another embodiment of the present invention is a composition comprising any of the compounds disclosed herein, including analogs, and a vehicle, diluent, or carrier that is cosmetically or pharmaceutically acceptable.

[0281] A further embodiment of the present invention is a method for whitening skin in a subject. This method includes the step of contacting the subject with one of the compounds or compositions disclosed herein.

[0282] An additional embodiment of the present invention is a method for inducing melanocyte apoptosis in a subject. This method includes the step of contacting the subject with one of the compounds or compositions disclosed herein.

[0283] Another embodiment of the present invention is a method for modulating melanocyte activity in a subject. This method includes the step of contacting the subject with one of the compounds or compositions disclosed herein.

[0284] A further embodiment of the present invention is a method for activating an aromatic hydrocarbon acceptor (AhR). This method includes the step of contacting a subject with one of the compounds or compositions disclosed herein.

[0285] An additional embodiment of the present invention is a method for improving hyperpigmentation caused by hyperpigmentation disorder in a subject requiring such improvement. The method comprises the step of contacting the subject with one of the compounds or compositions disclosed herein.

[0286] Another embodiment of the present invention is a method for modulating melanin production in a subject. This method includes the step of contacting the subject with one of the compounds or compositions disclosed herein.

[0287] A further embodiment of the present invention is a method for modulating melanosome biogeneration in a subject. This method includes the step of contacting the subject with one of the compounds or compositions disclosed herein.

[0288] An additional embodiment of the present invention is a method for modulating melanosome transport in a subject. This method includes the step of contacting the subject with one of the compounds or compositions disclosed herein.

[0289] Another embodiment of the present invention is a compound. This compound has the structure of formula (II): [ka] (wherein R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, and R11 are independently selected from the group consisting of hydrogen and methyl, and at least one of R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, and R11 is methyl) or a crystalline form thereof, hydrate, or a salt that is acceptable as a cosmetic or pharmaceutically acceptable product.

[0290] In one aspect of this embodiment, the compound is [ka] It is selected from the group consisting of the following.

[0291] A further embodiment of the present invention is a compound. This compound has the structure of formula (III): [ka] (wherein R1, R2, R3, R4, R5, R6, R7, R8, R9, and R10 are independently selected from the group consisting of hydrogen and methyl, and at least one of R1, R2, R3, R4, R5, R6, R7, R8, R9, and R10 is methyl) or a crystalline form thereof, hydrate, or a salt that is acceptable as a cosmetic or pharmaceutically acceptable product.

[0292] In one aspect of this embodiment, the compound is [ka] That is the case.

[0293] An additional embodiment of the present invention is a skin-whitening compound. This compound has the structure of formula (II): [ka] (wherein R1, R2, R3, R4, R5, R6, R7, R8, R9, R10 and R11 are independently selected from the group consisting of hydrogen and methyl) or having the following combination It is in crystalline form, hydrate, or as a salt that is acceptable for cosmetic or pharmaceutically acceptable use.

[0294] In one aspect of this embodiment, the compound is [ka] It is selected from the group consisting of the following.

[0295] Another embodiment of the present invention is a skin-whitening compound. This compound has the structure of formula (III): [ka] (wherein R1, R2, R3, R4, R5, R6, R7, R8, R9, and R10 are independently selected from the group consisting of hydrogen and methyl) or the crystalline form thereof, hydrate, or a salt that is acceptable for cosmetic or pharmaceutically acceptable purposes.

[0296] In one aspect of this embodiment, the compound is [ka] It is selected from the group consisting of the following.

[0297] A further embodiment of the present invention is a compound that induces melanocyte apoptosis. This compound has the structure of formula (II): [ka] (wherein R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, and R11 are independently selected from the group consisting of hydrogen and methyl) or the crystalline form thereof, hydrate, or a salt that is acceptable for cosmetic or pharmaceutically acceptable purposes.

[0298] In one aspect of this embodiment, the compound is [ka] It is selected from the group consisting of the following.

[0299] An additional embodiment of the present invention is a compound that induces melanocyte apoptosis. This compound has the structure of formula (III): [ka] (wherein R1, R2, R3, R4, R5, R6, R7, R8, R9, and R10 are independently selected from the group consisting of hydrogen and methyl) or the crystalline form thereof, hydrate, or a salt that is acceptable for cosmetic or pharmaceutically acceptable purposes.

[0300] In one aspect of this embodiment, the compound is [ka] It is selected from the group consisting of the following.

[0301] Another embodiment of the present invention is a compound that activates an aromatic hydrocarbon acceptor (AhR). This compound has the structure of formula (II): [ka] (wherein R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, and R11 are independently selected from the group consisting of hydrogen and methyl) or the crystalline form thereof, hydrate, or a salt that is acceptable for cosmetic or pharmaceutically acceptable purposes.

[0302] In one aspect of this embodiment, the compound is [ka] It is selected from the group consisting of the following.

[0303] A further embodiment of the present invention is a compound that activates an aromatic hydrocarbon acceptor (AhR). This compound has the structure of formula (III): [ka] (wherein R1, R2, R3, R4, R5, R6, R7, R8, R9, and R10 are independently selected from the group consisting of hydrogen and methyl) or the crystalline form thereof, hydrate, or a salt that is acceptable for cosmetic or pharmaceutically acceptable purposes.

[0304] In one aspect of this embodiment, the compound is [ka] It is selected from the group consisting of the following.

[0305] An additional embodiment of the present invention is a composition. This composition is a compound having the structure of formula (II): [ka] (wherein R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, and R11 are independently selected from the group consisting of hydrogen and methyl) or their crystalline form, hydrate, or a cosmetic or pharmaceutically acceptable salt, and a cosmetic or pharmaceutically acceptable vehicle, diluent, or carrier.

[0306] In one aspect of this embodiment, the compound is [ka] It is selected from the group consisting of the following.

[0307] Another embodiment of the present invention is a composition. This composition is a compound having the structure of formula (III): [ka] (wherein R1, R2, R3, R4, R5, R6, R7, R8, R9, and R10 are independently selected from the group consisting of hydrogen and methyl), or their crystalline form, hydrate, or a cosmetic or pharmaceutically acceptable salt, and a cosmetic or pharmaceutically acceptable vehicle, diluent, or carrier.

[0308] In one aspect of this embodiment, the compound is [ka] It is selected from the group consisting of the following.

[0309] A further embodiment of the present invention is a method for whitening the skin of a subject. This method involves applying a compound having the structure of formula (II) to the subject: [ka] The process includes contacting (wherein R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, and R11 are independently selected from the group consisting of hydrogen and methyl) or its crystalline form, hydrate, or a salt that is cosmetically or pharmaceutically acceptable.

[0310] In one aspect of this embodiment, the compound is [ka] It is selected from the group consisting of the following.

[0311] An additional embodiment of the present invention is a method for whitening the skin in a subject. This method involves applying a compound having the structure of formula (III) to the subject: [ka] The process includes contacting (wherein R1, R2, R3, R4, R5, R6, R7, R8, R9, and R10 are independently selected from the group consisting of hydrogen and methyl) or its crystalline form, hydrate, or a salt that is acceptable for cosmetic or pharmaceutically acceptable purposes.

[0312] In one aspect of this embodiment, the compound is [ka] It is selected from the group consisting of the following.

[0313] Another embodiment of the present invention is a method for inducing melanocyte apoptosis in a subject. This method involves applying a compound having the structure of formula (II) to the subject: [ka] The process includes contacting (wherein R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, and R11 are independently selected from the group consisting of hydrogen and methyl) or its crystalline form, hydrate, or a salt that is cosmetically or pharmaceutically acceptable.

[0314] In one aspect of this embodiment, the compound is [ka] It is selected from the group consisting of the following.

[0315] A further embodiment of the present invention is a method for inducing melanocyte apoptosis in a subject. This method involves applying a compound having the structure of formula (III) to the subject: [ka] The process includes contacting (wherein R1, R2, R3, R4, R5, R6, R7, R8, R9, and R10 are independently selected from the group consisting of hydrogen and methyl) or its crystalline form, hydrate, or a salt that is acceptable for cosmetic or pharmaceutically acceptable purposes.

[0316] In one aspect of this embodiment, the compound is [ka] It is selected from the group consisting of the following.

[0317] An additional embodiment of the present invention is a method for activating an aromatic hydrocarbon acceptor (AhR) in a subject. This method involves applying a compound having the structure of formula (II) to the subject: [ka] The process includes contacting (wherein R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, and R11 are independently selected from the group consisting of hydrogen and methyl) or its crystalline form, hydrate, or a salt that is cosmetically or pharmaceutically acceptable.

[0318] In one aspect of this embodiment, the compound is [ka] It is selected from the group consisting of the following.

[0319] Another embodiment of the present invention is a method for activating an aromatic hydrocarbon acceptor (AhR) in a subject. This method involves applying a compound having the structure of formula (III) to the subject: [ka] The process includes contacting (wherein R1, R2, R3, R4, R5, R6, R7, R8, R9, and R10 are independently selected from the group consisting of hydrogen and methyl) or its crystalline form, hydrate, or a salt that is acceptable for cosmetic or pharmaceutically acceptable purposes.

[0320] In one aspect of this embodiment, the compound is [ka] It is selected from the group consisting of the following.

[0321] One embodiment of the present invention is a compound. This compound has the following structure: [ka] (In the formula, X is NR 14 Y is selected from the group consisting of and O, and Y is a covalent bond, CR5R6, O, or NR 15 And R1, R2, R3, R4, R7, R8, R9, R 10 and R 11 is hydrogen, halogen, CN, hydroxyl, R 16 OR 16 Independently selected from the group consisting of R 13 , R 14 and R 15 These are, independently, hydrogen or R 16 R5 and R6 are hydrogen, hydroxyl, OR 16, R 16 and C 3~6 R5 and R6 are independently selected from the group consisting of cycloalkyl groups, or together they form an oxo (=O) group or a C group. 3~6 Forming a cycloalkyl group, R 12 is hydrogen, -COR a and R 16 Selected from the group consisting of R 16 These are, independently, formil and C 1~9 Alkyl, C 2~9 Alkenyl or C 2~9 It is alkinyl, R a These are hydrogen, hydroxyl, and OR 16 Selected from the group consisting of R a However, Y is hydrogen, and Y is CR5R6, and R 13 and R 14 However, if both are hydrogen, then R1, R2, R3, R4, R5, R6, R7, R8, R9, R 10 and R 11 At least one of them is R 16 Or, R5 is hydroxyl, OR 16 , R 16 and C 3~6 Selected from the group consisting of cycloalkyl groups, or R5 and R6 together form an oxo (=O) group or C 3~6 It has (forming a cycloalkyl group), or its crystalline form, hydrate, or a salt that is acceptable for cosmetic or pharmaceutically acceptable purposes.

[0322] In one aspect of this embodiment, the compound has the following structure: [ka] It is a salt that contains, or has the same crystalline form, hydrate, or is cosmetically or pharmaceutically acceptable.

[0323] In another aspect of this embodiment, X is NH.

[0324] In an additional aspect of this embodiment, Y is CR5R6, R5 is hydrogen, R6 is hydrogen, C 1~4 Alkyl, C 3~6 Cycloalkyl or O-(C 1~4 Either it is alkyl, or R5 and R6 combine to form an oxo (=O) group.

[0325] Preferably, CR5R6 is CH2, CHCH3, CHOCH3, C=O, or CH(C3H5).

[0326] In a further embodiment of this design, R1, R2, R3, R4, R7, R8, R9, R 10 and R 11 At least one of them is C 1~4 It is alkyl.

[0327] Preferably, R2 is C 1~4 It is alkyl.

[0328] More preferably, R2 is methyl.

[0329] In another aspect of this embodiment, R1, R2, R3, R4, R7, R8, R9, R 10 and R 11 Each of them is hydrogen.

[0330] In an additional aspect of this embodiment, R 12 -COR a or C 1~4 It is a hydroxyalkyl, R a is hydrogen or C 1~4 It is alkyl.

[0331] Preferably, R 12 These are CHO, CH2OH, or C(=O)-O-(C 1~4 It is alkyl.

[0332] Comfortable, R 12 It is CHO, CH2OH, or CO2CH3.

[0333] In a further aspect of this embodiment, X is NH, Y is CR5R6, and R1, R3, R4, R7, R8, R9, R 10 , R 11 and R 13 Each of these is hydrogen, and R2 is either hydrogen or C 1~4 It is an alkyl group, R5 is hydrogen, R6 is hydrogen, C 1~4 Alkyl, C 3~6 Cycloalkyl or O-(C 1~4 (Alkyl) or R5 and R6 together form an oxo (=O) group, R 12 -COR a or C 1~4 It is a hydroxyalkyl, R a is hydrogen or C 1~4 It is alkyl.

[0334] In another aspect of this embodiment, the compound is [ka] [ka] It is selected from the group consisting of the following.

[0335] Another embodiment of the present invention is a compound. This compound has the following structure: [ka] (In the formula, R1, R4, R5, R6, R9 and R 10 is hydrogen, hydroxyl, halogen, CN, R 13 , OR 13 , OCOR 13 R2 and R3 are independently selected from the group consisting of -CHO, and R2 and R3 are hydrogen, hydroxyl, halogen, CN, R 13 , OR 13 , OCOR 13R2 and R3 are independently selected from the group consisting of -CHO, or R2 and R3 combine to form a 5-membered or 6-membered heterocycline, and R7 and R8 are hydrogen, hydroxyl, halogen, CN, R 13 , OR 13 , OCOR 13 R7 and R8 are independently selected from the group consisting of -CHO, or R7 and R8 combine to form a 5-membered or 6-membered heterocycline, 11 and R 12 These are, independently, hydrogen or R 13 And R 13 Each of them is independent of C 1~9 Alkyl, C 2~9 Alkenyl or C 2~9 It is an alkynyl, R1, R2, R3, R4, R5, R6, R7, R8, R9 and R 10 It has at least one of the elements (which is not hydrogen), or is a crystalline form thereof, a hydrate, or a salt that is acceptable for cosmetic or pharmaceutically acceptable purposes.

[0336] In one embodiment of this design, the compound has a structure according to formula (II): [ka] It is a salt that contains, or has the same crystalline form, hydrate, or is cosmetically or pharmaceutically acceptable.

[0337] In another aspect of this embodiment, R1, R2, R3, R4, R5, R6, R7, R8, R9 and R 10 is hydrogen and C 1~4 It is independently selected from the group consisting of alkyl groups.

[0338] Preferably, R1, R2, R3, R4, R5, R6, R7, R8, R9 and R 10 One or two of them are C 1~4 It is an alkyl group, and the remaining group is hydrogen.

[0339] In an additional aspect of this embodiment, R5 and R 10 One of them is C1~4 One is alkyl, and the other is hydrogen.

[0340] In a further embodiment of this design, one of R1, R2, R3, R4, R6, R7, R8, and R9 is C 1~4 It is an alkyl group, and the remaining group is hydrogen.

[0341] Preferably, R 11 and R 12 Each of these is hydrogen, and R1, R2, R3, R4, R5, R6, R7, R8, R9 and R 10 One, two, three, or four of these groups are methyl groups, and the remaining groups are hydrogen.

[0342] In another aspect of this embodiment, the compound is [ka] It is selected from the group consisting of the following.

[0343] An additional embodiment of the present invention is a skin-whitening compound. This compound has the following structure: [ka] (In the formula, X is NR 14 Y is selected from the group consisting of and O, and Y is a covalent bond, CR5R6, O, or NR 15 And R1, R2, R3, R4, R7, R8, R9, R 10 and R 11 is hydrogen, halogen, CN, hydroxyl, R 16 OR 16 Independently selected from the group consisting of R 13 , R 14 and R 15 These are, independently, hydrogen or R 16 R5 and R6 are hydrogen, hydroxyl, OR 16 , R 16 and C 3~6 R5 and R6 are independently selected from the group consisting of cycloalkyl groups, or together they form an oxo (=O) group or a C group.3~6 Forming a cycloalkyl group, R 12 is hydrogen, -COR a and R 16 Selected from the group consisting of R 16 These are, independently, formil and C 1~9 Alkyl, C 2~9 Alkenyl or C 2~9 It is alkinyl, R a These are hydrogen, hydroxyl, and OR 16 It has (selected from the group consisting of) or is a crystalline form thereof, a hydrate, or a salt that is acceptable as a cosmetic or pharmaceutically acceptable substance.

[0344] In one aspect of this embodiment, the compound has the following structure: [ka] It is a salt that contains, or has the same crystalline form, hydrate, or is cosmetically or pharmaceutically acceptable.

[0345] In another aspect of this embodiment, X is NH.

[0346] In an additional aspect of this embodiment, Y is CR5R6, R5 is hydrogen, R6 is hydrogen, C 1~4 Alkyl, C 3~6 Cycloalkyl or O-(C 1~4 Either it is alkyl, or R5 and R6 combine to form an oxo (=O) group.

[0347] Preferably, CR5R6 is CH2, CHCH3, CHOCH3, C=O, or CH(C3H5).

[0348] In a further embodiment of this design, R1, R2, R3, R4, R7, R8, R9, R 10 and R 11 At least one of them is C 1~4 It is alkyl.

[0349] Preferably, R2 is C1~4 It is alkyl.

[0350] More preferably, R2 is methyl.

[0351] In another aspect of this embodiment, R1, R2, R3, R4, R7, R8, R9, R 10 and R 11 Each of them is hydrogen.

[0352] In an additional aspect of this embodiment, R 12 -COR a or C 1~4 It is a hydroxyalkyl, R a is hydrogen or C 1~4 It is alkyl.

[0353] Preferably, R 12 These are CHO, CH2OH, or C(=O)-O-(C 1~4 It is alkyl.

[0354] Comfortable, R 12 It is CHO, CH2OH, or CO2CH3.

[0355] In a further aspect of this embodiment, X is NH, Y is CR5R6, and R1, R3, R4, R7, R8, R9, R 10 , R 11 and R 13 Each of these is hydrogen, and R2 is either hydrogen or C 1~4 It is an alkyl group, R5 is hydrogen, R6 is hydrogen, C 1~4 Alkyl, C 3~6 Cycloalkyl or O-(C 1~4 (Alkyl) or R5 and R6 together form an oxo (=O) group, R 12 -COR a or C 1~4 It is a hydroxyalkyl, R a is hydrogen or C 1~4 It is alkyl.

[0356] In another aspect of this embodiment, the compound is [ka] It is selected from the group consisting of the following.

[0357] In an additional aspect of this embodiment, R a However, Y is hydrogen, and Y is CR5R6, and R 13 and R 14 If both are hydrogen, then R1, R2, R3, R4, R5, R6, R7, R8, R9, R 10 and R 11 At least one of them is R 16 or R5 is hydroxyl, OR 16 , R 16 and C 3~ R5 and R6 are selected from the group consisting of 6-cycloalkyl groups, or they combine to form an oxo (=O) group or a C3-6 cycloalkyl group.

[0358] A further embodiment of the present invention is a skin-whitening compound. This compound has the following formula: [ka] (In the formula, R1, R4, R5, R6, R9 and R 10 is hydrogen, hydroxyl, halogen, CN, R 13 , OR 13 , OCOR 13 R2 and R3 are independently selected from the group consisting of -CHO, and R2 and R3 are hydrogen, hydroxyl, halogen, CN, R 13 , OR 13 , OCOR 13 R2 and R3 are independently selected from the group consisting of -CHO, or R2 and R3 combine to form a 5-membered or 6-membered heterocycline, and R7 and R8 are hydrogen, hydroxyl, halogen, CN, R 13 , OR 13 , OCOR 13 R7 and R8 are independently selected from the group consisting of -CHO, or R7 and R8 combine to form a 5-membered or 6-membered heterocycline,11 and R 12 These are, independently, hydrogen or R 13 And R 13 Each of them is independent of C 1~9 Alkyl, C 2~9 Alkenyl or C 2~9 It is an alkynyl compound, or a crystalline form thereof, a hydrate, or a salt that is acceptable for cosmetic or pharmaceutically acceptable purposes.

[0359] In one embodiment of this design, the compound has a structure according to formula (II): [ka] It is a salt that contains, or has the same crystalline form, hydrate, or is cosmetically or pharmaceutically acceptable.

[0360] In another aspect of this embodiment, R1, R2, R3, R4, R5, R6, R7, R8, R9 and R 10 is hydrogen and C 1~4 It is independently selected from the group consisting of alkyl groups.

[0361] Preferably, R1, R2, R3, R4, R5, R6, R7, R8, R9 and R 10 One or two of them are C 1~4 It is an alkyl group, and the remaining group is hydrogen.

[0362] In an additional aspect of this embodiment, R5 and R 10 One of them is C 1~4 One is alkyl, and the other is hydrogen.

[0363] In a further embodiment of this design, one of R1, R2, R3, R4, R6, R7, R8, and R9 is C 1~4 It is an alkyl group, and the remaining group is hydrogen.

[0364] In another aspect of this embodiment, R 11 and R 12Each of these is hydrogen, and R1, R2, R3, R4, R5, R6, R7, R8, R9 and R 10 One, two, three, or four of these groups are methyl groups, and the remaining groups are hydrogen.

[0365] In an additional aspect of this embodiment, the compound is [ka] It is selected from the group consisting of the following.

[0366] In a further embodiment of this design, R1, R2, R3, R4, R5, R6, R7, R8, R9 and R 10 At least one of them is not hydrogen.

[0367] Another embodiment of the present invention is a compound that whitens the skin. This compound is [ka] It is selected from the group consisting of the following.

[0368] An additional embodiment of the present invention is a compound that induces melanocyte apoptosis. This compound has the following structure: [ka] (In the formula, X is NR 14 Y is selected from the group consisting of and O, and Y is a covalent bond, CR5R6, O, or NR 15 And R1, R2, R3, R4, R7, R8, R9, R 10 and R 11 is hydrogen, halogen, CN, hydroxyl, R 16 OR 16 Independently selected from the group consisting of R 13 , R 14 and R 15 These are, independently, hydrogen or R 16 R5 and R6 are hydrogen, hydroxyl, OR 16 , R 16 and C 3~6R5 and R6 are independently selected from the group consisting of cycloalkyl groups, or together they form an oxo (=O) group or a C group. 3~6 Forming a cycloalkyl group, R 12 is hydrogen, -COR a and R 16 Selected from the group consisting of R 16 These are, independently, formil and C 1~9 Alkyl, C 2~9 Alkenyl or C 2~9 It is alkinyl, R a These are hydrogen, hydroxyl, and OR 16 It has (selected from the group consisting of) or is a crystalline form thereof, a hydrate, or a salt that is acceptable as a cosmetic or pharmaceutically acceptable substance.

[0369] In one aspect of this embodiment, the compound has the following structure: [ka] It is a salt that contains, or has the same crystalline form, hydrate, or is cosmetically or pharmaceutically acceptable.

[0370] In another aspect of this embodiment, X is NH.

[0371] In an additional aspect of this embodiment, Y is CR5R6, R5 is hydrogen, R6 is hydrogen, C 1~4 Alkyl, C 3~6 Cycloalkyl or O-(C 1~4 Either it is alkyl, or R5 and R6 combine to form an oxo (=O) group.

[0372] Preferably, CR5R6 is CH2, CHCH3, CHOCH3, C=O, or CH(C3H5).

[0373] In a further embodiment of this design, R1, R2, R3, R4, R7, R8, R9, R 10 and R 11 At least one of them is C 1~4 It is alkyl.

[0374] Preferably, R2 is C 1~4 It is alkyl.

[0375] More preferably, R2 is methyl.

[0376] In another aspect of this embodiment, R1, R2, R3, R4, R7, R8, R9, R 10 oh Call R 11 Each of them is hydrogen.

[0377] In an additional aspect of this embodiment, R 12 -COR a or C 1~4 It is a hydroxyalkyl, R a is hydrogen or C 1~4 It is alkyl.

[0378] Preferably, R 12 These are CHO, CH2OH, or C(=O)-O-(C 1~4 It is alkyl.

[0379] Comfortable, R 12 It is CHO, CH2OH, or CO2CH3.

[0380] In a further aspect of this embodiment, X is NH, Y is CR5R6, and R1, R3, R4, R7, R8, R9, R 10 , R 11 and R 13 Each of these is hydrogen, and R2 is either hydrogen or C 1~4 It is an alkyl group, R5 is hydrogen, R6 is hydrogen, C 1~4 Alkyl, C 3~6 Cycloalkyl or O-(C 1~4 (Alkyl) or R5 and R6 together form an oxo (=O) group, R 12 -COR a or C 1~4 It is a hydroxyalkyl, R a is hydrogen or C1~4 It is alkyl.

[0381] In another aspect of this embodiment, the compound is [ka] [ka] It is selected from the group consisting of the following.

[0382] In an additional aspect of this embodiment, R a However, Y is hydrogen, and Y is CR5R6, and R 13 and R 14 If both are hydrogen, then R1, R2, R3, R4, R5, R6, R7, R8, R9, R 10 and R 11 At least one of them is R 16 Or, R5 is hydroxyl, OR 16 , R 16 and C 3~6 Selected from the group consisting of cycloalkyl groups, or R5 and R6 together form an oxo (=O) group or C 3~6 It forms a cycloalkyl group.

[0383] Further embodiments of the present invention include compounds that induce melanocyte apoptosis, the following formula: [ka] (In the formula, R1, R4, R5, R6, R9 and R 10 is hydrogen, hydroxyl, halogen, CN, R 13 , OR 13 , OCOR 13 R2 and R3 are independently selected from the group consisting of -CHO, and R2 and R3 are hydrogen, hydroxyl, halogen, CN, R 13 , OR 13 , OCOR 13R2 and R3 are independently selected from the group consisting of -CHO, or R2 and R3 combine to form a 5-membered or 6-membered heterocycline, and R7 and R8 are hydrogen, hydroxyl, halogen, CN, R 13 , OR 13 , OCOR 13 R7 and R8 are independently selected from the group consisting of -CHO, or R7 and R8 combine to form a 5-membered or 6-membered heterocycline, 11 and R 12 These are, independently, hydrogen or R 13 And R 13 Each of them is independent of C 1~9 Alkyl, C 2~9 Alkenyl or C 2~9 A compound that is an alkynyl compound, or a crystalline form thereof, a hydrate, or a salt that is acceptable for cosmetic or pharmaceutically acceptable purposes.

[0384] In one embodiment of this design, the compound has a structure according to formula (II): [ka] It is a salt that contains, or has the same crystalline form, hydrate, or is cosmetically or pharmaceutically acceptable.

[0385] In another aspect of this embodiment, R1, R2, R3, R4, R5, R6, R7, R8, R9 and R 10 is hydrogen and C 1~4 It is independently selected from the group consisting of alkyl groups.

[0386] Preferably, R1, R2, R3, R4, R5, R6, R7, R8, R9 and R 10 One or two of them are C 1~4 It is an alkyl group, and the remaining group is hydrogen.

[0387] In an additional aspect of this embodiment, R5 and R 10 One of them is C 1~4 One is alkyl, and the other is hydrogen.

[0388] In a further embodiment of this design, one of R1, R2, R3, R4, R6, R7, R8, and R9 is C 1~4 It is an alkyl group, and the remaining group is hydrogen.

[0389] In another aspect of this embodiment, R 11 and R 12 Each of these is hydrogen, and R1, R2, R3, R4, R5, R6, R7, R8, R9 and R 10 One, two, three, or four of these groups are methyl groups, and the remaining groups are hydrogen.

[0390] In an additional aspect of this embodiment, the compound is [ka] [ka] It is selected from the group consisting of the following.

[0391] In a further embodiment of this design, R1, R2, R3, R4, R5, R6, R7, R8, R9 and R 10 At least one of them is not hydrogen.

[0392] Another embodiment of the present invention is a compound that induces melanocyte apoptosis. This compound is [ka] It is selected from the group consisting of the following.

[0393] An additional embodiment of the present invention is a compound that modulates aromatic hydrocarbon acceptor (AhR) activity. The compound has the following structure: [ka] (In the formula, X is NR 14 Y is selected from the group consisting of and O, and Y is a covalent bond, CR5R6, O, or NR 15And R1, R2, R3, R4, R7, R8, R9, R 10 and R 11 is hydrogen, halogen, CN, hydroxyl, R 16 OR 16 Independently selected from the group consisting of R 13 , R 14 and R 15 These are, independently, hydrogen or R 16 R5 and R6 are hydrogen, hydroxyl, OR 16 , R 16 and C 3~6 R5 and R6 are independently selected from the group consisting of cycloalkyl groups, or together they form an oxo (=O) group or a C group. 3~6 Forming a cycloalkyl group, R 12 is hydrogen, -COR a and R 16 Selected from the group consisting of R 16 These are, independently, formil and C 1~9 Alkyl, C 2~9 Alkenyl or C 2~9 It is alkinyl, R a These are hydrogen, hydroxyl, and OR 16 It has (selected from the group consisting of) or is a crystalline form thereof, a hydrate, or a salt that is acceptable as a cosmetic or pharmaceutically acceptable substance.

[0394] In one aspect of this embodiment, the compound has the following structure: [ka] It is a salt that contains, or has the same crystalline form, hydrate, or is cosmetically or pharmaceutically acceptable.

[0395] In another aspect of this embodiment, X is NH.

[0396] In an additional aspect of this embodiment, Y is CR5R6, R5 is hydrogen, R6 is hydrogen, C 1~4 Alkyl, C 3~6 Cycloalkyl or O-(C 1~4Either it is alkyl, or R5 and R6 combine to form an oxo (=O) group.

[0397] Preferably, CR5R6 is CH2, CHCH3, CHOCH3, C=O, or CH(C3H5).

[0398] In a further embodiment of this design, R1, R2, R3, R4, R7, R8, R9, R 10 and R 11 At least one of them is C 1~4 It is alkyl.

[0399] Preferably, R2 is C 1~4 It is alkyl.

[0400] More preferably, R2 is methyl.

[0401] In another aspect of this embodiment, R1, R2, R3, R4, R7, R8, R9, R 10 oh Call R 11 Each of them is hydrogen.

[0402] In an additional aspect of this embodiment, R 12 -COR a or C 1~4 It is a hydroxyalkyl, R a is hydrogen or C 1~4 It is alkyl.

[0403] Preferably, R 12 These are CHO, CH2OH, or C(=O)-O-(C 1~4 It is alkyl.

[0404] Comfortable, R 12 It is CHO, CH2OH, or CO2CH3.

[0405] In a further aspect of this embodiment, X is NH, Y is CR5R6, and R1, R3, R4, R7, R8, R9, R 10 , R 11and R 13 Each of these is hydrogen, and R2 is either hydrogen or C 1~4 It is an alkyl group, R5 is hydrogen, R6 is hydrogen, C 1~4 Alkyl, C 3~6 Cycloalkyl or O-(C 1~4 (Alkyl) or R5 and R6 together form an oxo (=O) group, R 12 -COR a or C 1~4 It is a hydroxyalkyl, R a is hydrogen or C 1~4 It is alkyl.

[0406] In another aspect of this embodiment, the compound is [ka] [ka] It is selected from the group consisting of the following.

[0407] In an additional aspect of this embodiment, R a However, Y is hydrogen, and Y is CR5R6, and R 13 and R 14 If both are hydrogen, then R1, R2, R3, R4, R5, R6, R7, R8, R9, R 10 and R 11 At least one of them is R 16 Or, R5 is hydroxyl, OR 16 , R 16 and C 3~6 Selected from the group consisting of cycloalkyl groups, or R5 and R6 together form an oxo (=O) group or C 3~6 It forms a cycloalkyl group.

[0408] A further embodiment of the present invention is a compound that modulates aromatic hydrocarbon acceptor (AhR) activity. The compound is given by the following formula: [ka] (In the formula, R1, R4, R5, R6, R9 and R 10 is hydrogen, hydroxyl, halogen, CN, R 13 , OR 13 , OCOR 13 R2 and R3 are independently selected from the group consisting of -CHO, and R2 and R3 are hydrogen, hydroxyl, halogen, CN, R 13 , OR 13 , OCOR 13 R2 and R3 are independently selected from the group consisting of -CHO, or R2 and R3 combine to form a 5-membered or 6-membered heterocycline, and R7 and R8 are hydrogen, hydroxyl, halogen, CN, R 13 , OR 13 , OCOR 13 R7 and R8 are independently selected from the group consisting of -CHO, or R7 and R8 combine to form a 5-membered or 6-membered heterocycline, 11 and R 12 These are, independently, hydrogen or R 13 And R 13 Each of them is independent of C 1~9 Alkyl, C 2~9 Alkenyl or C 2~9 It is an alkynyl compound, or a crystalline form thereof, a hydrate, or a salt that is acceptable for cosmetic or pharmaceutically acceptable purposes.

[0409] In one embodiment of this design, the compound has a structure according to formula (II): [ka] It is a salt that contains, or has the same crystalline form, hydrate, or is cosmetically or pharmaceutically acceptable.

[0410] In another aspect of this embodiment, R1, R2, R3, R4, R5, R6, R7, R8, R9 and R 10 is hydrogen and C 1~4 It is independently selected from the group consisting of alkyl groups.

[0411] Preferably, R1, R2, R3, R4, R5, R6, R7, R8, R9 and R 10 One or two of them are C 1~4 It is an alkyl group, and the remaining group is hydrogen.

[0412] In an additional aspect of this embodiment, R5 and R 10 One of them is C 1~4 One is alkyl, and the other is hydrogen.

[0413] In a further embodiment of this design, one of R1, R2, R3, R4, R6, R7, R8, and R9 is C 1~4 It is an alkyl group, and the remaining group is hydrogen.

[0414] In another aspect of this embodiment, R 11 and R 12 Each of these is hydrogen, and R1, R2, R3, R4, R5, R6, R7, R8, R9 and R 10 One, two, three, or four of these groups are methyl groups, and the remaining groups are hydrogen.

[0415] In an additional aspect of this embodiment, the compound is [ka] [ka] It is selected from the group consisting of the following.

[0416] In a further embodiment of this design, R1, R2, R3, R4, R5, R6, R7, R8, R9 and R 10 At least one of them is not hydrogen.

[0417] Another embodiment of the present invention is a compound that modulates aromatic hydrocarbon acceptor (AhR) activity. This compound is [ka] It is selected from the group consisting of the following.

[0418] An additional embodiment of the present invention is a compound that modulates melanogenesis. The compound has the structure of the following formula:

Chemical formula

[0419] In one aspect of this embodiment, the compound has the following structure:

Chemical formula

[0420] In another aspect of this embodiment, X is NH.

[0421] In an additional aspect of this embodiment, Y is CR5R6, R5 is hydrogen, R6 is hydrogen, C 1~4 Alkyl, C 3~6 Cycloalkyl or O-(C 1~4 Either it is alkyl, or R5 and R6 combine to form an oxo (=O) group.

[0422] Preferably, CR5R6 is CH2, CHCH3, CHOCH3, C=O, or CH(C3H5).

[0423] In a further embodiment of this design, R1, R2, R3, R4, R7, R8, R9, R 10 and R 11 At least one of them is C 1~4 It is alkyl.

[0424] Preferably, R2 is C 1~4 It is alkyl.

[0425] More preferably, R2 is methyl.

[0426] In another aspect of this embodiment, R1, R2, R3, R4, R7, R8, R9, R 10 and R 11 Each of them is hydrogen.

[0427] In an additional aspect of this embodiment, R 12 -COR a or C 1~4 It is a hydroxyalkyl, R a is hydrogen or C 1~4 It is alkyl.

[0428] Preferably, R 12These are CHO, CH2OH, or C(=O)-O-(C 1~4 It is alkyl.

[0429] Comfortable, R 12 It is CHO, CH2OH, or CO2CH3.

[0430] In a further aspect of this embodiment, X is NH, Y is CR5R6, and R1, R3, R4, R7, R8, R9, R 10 , R 11 and R 13 Each of these is hydrogen, and R2 is either hydrogen or C 1~4 It is an alkyl group, R5 is hydrogen, R6 is hydrogen, C 1~4 Alkyl, C 3~6 Cycloalkyl or O-(C 1~4 (Alkyl) or R5 and R6 together form an oxo (=O) group, R 12 -COR a or C 1~4 It is a hydroxyalkyl, R a is hydrogen or C 1~4 It is alkyl.

[0431] In another aspect of this embodiment, the compound is [ka] [ka] It is selected from the group consisting of the following.

[0432] In an additional aspect of this embodiment, R a However, Y is hydrogen, and Y is CR5R6, and R 13 and R 14 If both are hydrogen, then R1, R2, R3, R4, R5, R6, R7, R8, R9, R 10 and R 11 At least one of them is R 16 Or, R5 is hydroxyl, OR 16 , R 16and C 3~6 Selected from the group consisting of cycloalkyl groups, or R5 and R6 together form an oxo (=O) group or C 3~6 It forms a cycloalkyl group.

[0433] A further embodiment of the present invention is a compound that modulates melanin formation. This compound has the following formula: [ka] (In the formula, R1, R4, R5, R6, R9 and R 10 is hydrogen, hydroxyl, halogen, CN, R 13 , OR 13 , OCOR 13 R2 and R3 are independently selected from the group consisting of -CHO, and R2 and R3 are hydrogen, hydroxyl, halogen, CN, R 13 , OR 13 , OCOR 13 R2 and R3 are independently selected from the group consisting of -CHO, or R2 and R3 combine to form a 5-membered or 6-membered heterocycline, and R7 and R8 are hydrogen, hydroxyl, halogen, CN, R 13 , OR 13 , OCOR 13 R7 and R8 are independently selected from the group consisting of -CHO, or R7 and R8 combine to form a 5-membered or 6-membered heterocycline, 11 and R 12 These are, independently, hydrogen or R 13 And R 13 Each of them is independent of C 1~9 Alkyl, C 2~9 Alkenyl or C 2~9 It is an alkynyl compound, or a crystalline form thereof, a hydrate, or a salt that is acceptable for cosmetic or pharmaceutically acceptable purposes.

[0434] In one embodiment of this design, the compound has a structure according to formula (II): [ka] It has, or is in its crystalline form, hydrate, or a cosmetic or pharmaceutically acceptable salt.

[0435] In another aspect of this embodiment, R1, R2, R3, R4, R5, R6, R7, R8, R9 and R 10 are independently selected from the group consisting of hydrogen and C 1~4 alkyl.

[0436] Preferably, one or two of R1, R2, R3, R4, R5, R6, R7, R8, R9 and R 10 are C 1~4 alkyl and the remaining groups are hydrogen.

[0437] In another aspect of this embodiment, one of R5 and R 10 is C 1~4 alkyl and the other is hydrogen.

[0438] In a further aspect of this embodiment, one of R1, R2, R3, R4, R6, R7, R8 and R9 is C 1~4 alkyl and the remaining groups are hydrogen.

[0439] In yet another aspect of this embodiment, R 11 and R 12 are each hydrogen, and one, two, three or four of R1, R2, R3, R4, R5, R6, R7, R8, R9 and R 10 are methyl and the remaining groups are hydrogen.

[0440] In another aspect of this embodiment, the compound is

Chem.

Chem.

[0441] In a further embodiment of this design, R1, R2, R3, R4, R5, R6, R7, R8, R9 and R 10 At least one of them is not hydrogen.

[0442] Another embodiment of the present invention is a compound that modulates melanin formation. This compound is [ka] It is selected from the group consisting of the following.

[0443] An additional embodiment of the present invention is a compound that modulates melanin concentration. The compound has the following structure: [ka] (In the formula, X is NR 14 Y is selected from the group consisting of and O, and Y is a covalent bond, CR5R6, O, or NR 15 And R1, R2, R3, R4, R7, R8, R9, R 10 and R 11 is hydrogen, halogen, CN, hydroxyl, R 16 OR 16 Independently selected from the group consisting of R 13 , R 14 and R 15 These are, independently, hydrogen or R 16 R5 and R6 are hydrogen, hydroxyl, OR 16 , R 16 and C 3~6 R5 and R6 are independently selected from the group consisting of cycloalkyl groups, or together they form an oxo (=O) group or a C group. 3~6 Forming a cycloalkyl group, R 12 is hydrogen, -COR a and R 16 Selected from the group consisting of R 16 These are, independently, formil and C 1~9 Alkyl, C 2~9 Alkenyl or C 2~9 It is alkinyl, R a These are hydrogen, hydroxyl, and OR16 It has (selected from the group consisting of) or is a crystalline form thereof, a hydrate, or a salt that is acceptable as a cosmetic or pharmaceutically acceptable substance.

[0444] In one aspect of this embodiment, the compound has the following structure: [ka] It is a salt that contains, or has the same crystalline form, hydrate, or is cosmetically or pharmaceutically acceptable.

[0445] In another aspect of this embodiment, X is NH.

[0446] In an additional aspect of this embodiment, Y is CR5R6, R5 is hydrogen, R6 is hydrogen, C 1~4 Alkyl, C 3~6 Cycloalkyl or O-(C 1~4 Either it is alkyl, or R5 and R6 combine to form an oxo (=O) group.

[0447] Preferably, CR5R6 is CH2, CHCH3, CHOCH3, C=O, or CH(C3H5).

[0448] In a further embodiment of this design, R1, R2, R3, R4, R7, R8, R9, R 10 and R 11 At least one of them is C 1~4 It is alkyl.

[0449] Preferably, R2 is C 1~4 It is alkyl.

[0450] More preferably, R2 is methyl.

[0451] In another aspect of this embodiment, R1, R2, R3, R4, R7, R8, R9, R 10 and R 11 Each of them is hydrogen.

[0452] In an additional aspect of this embodiment, R 12 -COR a or C 1~4 It is a hydroxyalkyl, R a is hydrogen or C 1~4 It is alkyl.

[0453] Preferably, R 12 These are CHO, CH2OH, or C(=O)-O-(C 1~4 It is alkyl.

[0454] Comfortable, R 12 It is CHO, CH2OH, or CO2CH3.

[0455] In a further aspect of this embodiment, X is NH, Y is CR5R6, and R1, R3, R4, R7, R8, R9, R 10 , R 11 and R 13 Each of these is hydrogen, and R2 is either hydrogen or C 1~4 It is an alkyl group, R5 is hydrogen, R6 is hydrogen, C 1~4 Alkyl, C 3~6 Cycloalkyl or O-(C 1~4 (Alkyl) or R5 and R6 together form an oxo (=O) group, R 12 -COR a or C 1~4 It is a hydroxyalkyl, R a is hydrogen or C 1~4 It is alkyl.

[0456] In another aspect of this embodiment, the compound is [ka] [ka] It is selected from the group consisting of the following.

[0457] In an additional aspect of this embodiment, R aHowever, Y is hydrogen, and Y is CR5R6, and R 13 and R 14 If both are hydrogen, then R1, R2, R3, R4, R5, R6, R7, R8, R9, R 10 and R 11 At least one of them is R 16 Or, R5 is hydroxyl, OR 16 , R 16 and C 3~6 Selected from the group consisting of cycloalkyl groups, or R5 and R6 together form an oxo (=O) group or C 3~6 It forms a cycloalkyl group.

[0458] A further embodiment of the present invention is a compound that modulates melanin concentration. This compound has the following formula: [ka] (In the formula, R1, R4, R5, R6, R9 and R 10 is hydrogen, hydroxyl, halogen, CN, R 13 , OR 13 , OCOR 13 R2 and R3 are independently selected from the group consisting of -CHO, and R2 and R3 are hydrogen, hydroxyl, halogen, CN, R 13 , OR 13 , OCOR 13 R2 and R3 are independently selected from the group consisting of -CHO, or R2 and R3 combine to form a 5-membered or 6-membered heterocycline, and R7 and R8 are hydrogen, hydroxyl, halogen, CN, R 13 , OR 13 , OCOR 13 R7 and R8 are independently selected from the group consisting of -CHO, or R7 and R8 combine to form a 5-membered or 6-membered heterocycline, 11 and R 12 These are, independently, hydrogen or R 13 And R 13 Each of them is independent of C 1~9 Alkyl, C 2~9 Alkenyl or C 2~9It is an alkynyl compound, or a crystalline form thereof, a hydrate, or a salt that is acceptable for cosmetic or pharmaceutically acceptable purposes.

[0459] In one embodiment of this design, the compound has a structure according to formula (II): [ka] It is a salt that contains, or has the same crystalline form, hydrate, or is cosmetically or pharmaceutically acceptable.

[0460] In another aspect of this embodiment, R1, R2, R3, R4, R5, R6, R7, R8, R9 and R 10 is hydrogen and C 1~4 It is independently selected from the group consisting of alkyl groups.

[0461] Preferably, R1, R2, R3, R4, R5, R6, R7, R8, R9 and R 10 One or two of them are C 1~4 It is an alkyl group, and the remaining group is hydrogen.

[0462] In an additional aspect of this embodiment, R5 and R 10 One of them is C 1~4 One is alkyl, and the other is hydrogen.

[0463] In a further embodiment of this design, one of R1, R2, R3, R4, R6, R7, R8, and R9 is C 1~4 It is an alkyl group, and the remaining group is hydrogen.

[0464] In another aspect of this embodiment, R 11 and R 12 Each of these is hydrogen, and R1, R2, R3, R4, R5, R6, R7, R8, R9 and R 10 One, two, three, or four of these groups are methyl groups, and the remaining groups are hydrogen.

[0465] In an additional aspect of this embodiment, the compound is [ka] [ka] It is selected from the group consisting of the following.

[0466] In a further embodiment of this design, R1, R2, R3, R4, R5, R6, R7, R8, R9 and R 10 At least one of them is not hydrogen.

[0467] Another embodiment of the present invention is a compound that modulates melanin concentration. This compound is [ka] It is selected from the group consisting of the following.

[0468] An additional embodiment of the present invention is a composition comprising a compound. The compound has the following structure: [ka] (In the formula, X is NR 14 Y is selected from the group consisting of and O, and Y is a covalent bond, CR5R6, O, or NR 15 And R1, R2, R3, R4, R7, R8, R9, R 10 and R 11 is hydrogen, halogen, CN, hydroxyl, R 16 OR 16 Independently selected from the group consisting of R 13 , R 14 and R 15 These are, independently, hydrogen or R 16 R5 and R6 are hydrogen, hydroxyl, OR 16 , R 16 and C 3~6 R5 and R6 are independently selected from the group consisting of cycloalkyl groups, or together they form an oxo (=O) group or a C group. 3~6 Forming a cycloalkyl group, R 12 is hydrogen, -COR aand R 16 Selected from the group consisting of R 16 These are, independently, formil and C 1~9 Alkyl, C 2~9 Alkenyl or C 2~9 It is alkinyl, R a These are hydrogen, hydroxyl, and OR 16 It has (selected from the group consisting of) or is a crystalline form thereof, a hydrate, or a salt that is acceptable as a cosmetic or pharmaceutically acceptable substance.

[0469] In one aspect of this embodiment, the compound has the following structure: [ka] It is a salt that contains, or has the same crystalline form, hydrate, or is cosmetically or pharmaceutically acceptable.

[0470] In another aspect of this embodiment, X is NH.

[0471] In an additional aspect of this embodiment, Y is CR5R6, R5 is hydrogen, R6 is hydrogen, C 1~4 Alkyl, C 3~6 Cycloalkyl or O-(C 1~4 Either it is alkyl, or R5 and R6 combine to form an oxo (=O) group.

[0472] Preferably, CR5R6 is CH2, CHCH3, CHOCH3, C=O, or CH(C3H5).

[0473] In a further embodiment of this design, R1, R2, R3, R4, R7, R8, R9, R 10 and R 11 At least one of them is C 1~4 It is alkyl.

[0474] Preferably, R2 is C 1~4 It is alkyl.

[0475] More preferably, R2 is methyl.

[0476] In another aspect of this embodiment, R1, R2, R3, R4, R7, R8, R9, R 10 and R 11 Each of them is hydrogen.

[0477] In an additional aspect of this embodiment, R 12 -COR a or C 1~4 It is a hydroxyalkyl, R a is hydrogen or C 1~4 It is alkyl.

[0478] Preferably, R 12 These are CHO, CH2OH, or C(=O)-O-(C 1~4 It is alkyl.

[0479] Comfortable, R 12 It is CHO, CH2OH, or CO2CH3.

[0480] In a further aspect of this embodiment, X is NH, Y is CR5R6, and R1, R3, R4, R7, R8, R9, R 10 , R 11 and R 13 Each of these is hydrogen, and R2 is either hydrogen or C 1~4 It is an alkyl group, R5 is hydrogen, R6 is hydrogen, C 1~4 Alkyl, C 3~6 Cycloalkyl or O-(C 1~4 (Alkyl) or R5 and R6 together form an oxo (=O) group, R 12 -COR a or C 1~4 It is a hydroxyalkyl, R a is hydrogen or C 1~4 It is alkyl.

[0481] In another aspect of this embodiment, the compound is [ka] [ka] It is selected from the group consisting of the following.

[0482] A further embodiment of the present invention is a composition comprising a compound. The compound has the following formula: [ka] (In the formula, R1, R4, R5, R6, R9 and R 10 is hydrogen, hydroxyl, halogen, CN, R 13 , OR 13 , OCOR 13 R2 and R3 are independently selected from the group consisting of -CHO, and R2 and R3 are hydrogen, hydroxyl, halogen, CN, R 13 , OR 13 , OCOR 13 R2 and R3 are independently selected from the group consisting of -CHO, or R2 and R3 combine to form a 5-membered or 6-membered heterocycline, and R7 and R8 are hydrogen, hydroxyl, halogen, CN, R 13 , OR 13 , OCOR 13 R7 and R8 are independently selected from the group consisting of -CHO, or R7 and R8 combine to form a 5-membered or 6-membered heterocycline, 11 and R 12 These are, independently, hydrogen or R 13 And R 13 Each of them is independent of C 1~9 Alkyl, C 2~9 Alkenyl or C 2~9 It is an alkynyl compound, or a crystalline form thereof, a hydrate, or a salt that is acceptable for cosmetic or pharmaceutically acceptable purposes.

[0483] In one embodiment of this design, the compound has a structure according to formula (II): [ka] It is a salt that contains, or has the same crystalline form, hydrate, or is cosmetically or pharmaceutically acceptable.

[0484] In another aspect of this embodiment, R1, R2, R3, R4, R5, R6, R7, R8, R9 and R 10 is hydrogen and C 1~4 It is independently selected from the group consisting of alkyl groups.

[0485] Preferably, R1, R2, R3, R4, R5, R6, R7, R8, R9 and R 10 One or two of them are C 1~4 It is an alkyl group, and the remaining group is hydrogen.

[0486] In an additional aspect of this embodiment, R5 and R 10 One of them is C 1~4 One is alkyl, and the other is hydrogen.

[0487] In a further embodiment of this design, one of R1, R2, R3, R4, R6, R7, R8, and R9 is C 1~4 It is an alkyl group, and the remaining group is hydrogen.

[0488] In another aspect of this embodiment, R 11 and R 12 Each of these is hydrogen, and R1, R2, R3, R4, R5, R6, R7, R8, R9 and R 10 One, two, three, or four of these groups are methyl groups, and the remaining groups are hydrogen.

[0489] In an additional aspect of this embodiment, the compound is [ka] It is selected from the group consisting of the following.

[0490] Another embodiment of the present invention is a composition comprising a compound. This compound is [ka] It is selected from the group consisting of the following.

[0491] An additional embodiment of the present invention is a method for whitening the skin of a subject. This method involves contacting the subject with a compound, wherein the compound has the following structure: [ka] (In the formula, X is NR 14 Y is selected from the group consisting of and O, and Y is a covalent bond, CR5R6, O, or NR 15 And R1, R2, R3, R4, R7, R8, R9, R 10 and R 11 is hydrogen, halogen, CN, hydroxyl, R 16 OR 16 Independently selected from the group consisting of R 13 , R 14 and R 15 These are, independently, hydrogen or R 16 R5 and R6 are hydrogen, hydroxyl, OR 16 , R 16 and C 3~6 R5 and R6 are independently selected from the group consisting of cycloalkyl groups, or together they form an oxo (=O) group or a C group. 3~6 Forming a cycloalkyl group, R 12 is hydrogen, -COR a and R 16 Selected from the group consisting of R 16 These are, independently, formil and C 1~9 Alkyl, C 2~9 Alkenyl or C 2~9 It is alkinyl, R a These are hydrogen, hydroxyl, and OR 16 The step comprises having (selected from the group consisting of) or being a crystalline form thereof, hydrate, or a salt that is acceptable as a cosmetic or pharmaceutically acceptable substance.

[0492] In one aspect of this embodiment, the compound has the following structure: [ka] It is a salt that contains, or has the same crystalline form, hydrate, or is cosmetically or pharmaceutically acceptable.

[0493] In another aspect of this embodiment, X is NH.

[0494] In an additional aspect of this embodiment, Y is CR5R6, R5 is hydrogen, R6 is hydrogen, C 1~4 Alkyl, C 3~6 Cycloalkyl or O-(C 1~4 Either it is alkyl, or R5 and R6 combine to form an oxo (=O) group.

[0495] Preferably, CR5R6 is CH2, CHCH3, CHOCH3, C=O, or CH(C3H5).

[0496] In a further embodiment of this design, R1, R2, R3, R4, R7, R8, R9, R 10 and R 11 At least one of them is C 1~4 It is alkyl.

[0497] Preferably, R2 is C 1~4 It is alkyl.

[0498] More preferably, R2 is methyl.

[0499] In another aspect of this embodiment, R1, R2, R3, R4, R7, R8, R9, R 10 and R 11 Each of them is hydrogen.

[0500] In an additional aspect of this embodiment, R 12 -COR a or C 1~4 It is a hydroxyalkyl, R a is hydrogen or C 1~4 It is alkyl.

[0501] Preferably, R12 These are CHO, CH2OH, or C(=O)-O-(C 1~4 It is alkyl.

[0502] Comfortable, R 12 It is CHO, CH2OH, or CO2CH3.

[0503] In a further aspect of this embodiment, X is NH, Y is CR5R6, and R1, R3, R4, R7, R8, R9, R 10 , R 11 and R 13 Each of these is hydrogen, and R2 is either hydrogen or C 1~4 It is an alkyl group, R5 is hydrogen, R6 is hydrogen, C 1~4 Alkyl, C 3~6 Cycloalkyl or O-(C 1~4 (Alkyl) or R5 and R6 together form an oxo (=O) group, R 12 -COR a or C 1~4 It is a hydroxyalkyl, R a is hydrogen or C 1~4 It is alkyl.

[0504] In another aspect of this embodiment, the compound is [ka] It is selected from the group consisting of the following.

[0505] A further embodiment of the present invention is a method for whitening the skin of a subject. This method involves contacting the subject with a compound, wherein the compound has the following formula: [ka] (In the formula, R1, R4, R5, R6, R9 and R 10 is hydrogen, hydroxyl, halogen, CN, R 13 , OR 13 , OCOR 13R2 and R3 are independently selected from the group consisting of -CHO, and R2 and R3 are hydrogen, hydroxyl, halogen, CN, R 13 , OR 13 , OCOR 13 R2 and R3 are independently selected from the group consisting of -CHO, or R2 and R3 combine to form a 5-membered or 6-membered heterocycline, and R7 and R8 are hydrogen, hydroxyl, halogen, CN, R 13 , OR 13 , OCOR 13 R7 and R8 are independently selected from the group consisting of -CHO, or R7 and R8 combine to form a 5-membered or 6-membered heterocycline, 11 and R 12 These are, independently, hydrogen or R 13 And R 13 Each of them is independent of C 1~9 Alkyl, C 2~9 Alkenyl or C 2~9 The step comprises having an alkynyl (or a crystalline form thereof, a hydrate, or a salt that is acceptable for cosmetic or pharmaceutically acceptable purposes).

[0506] In one embodiment of this design, the compound has a structure according to formula (II): [ka] It is a salt that contains, or has the same crystalline form, hydrate, or is cosmetically or pharmaceutically acceptable.

[0507] In another aspect of this embodiment, R1, R2, R3, R4, R5, R6, R7, R8, R9 and R 10 is hydrogen and C 1~4 It is independently selected from the group consisting of alkyl groups.

[0508] Preferably, R1, R2, R3, R4, R5, R6, R7, R8, R9 and R 10 One or two of them are C 1~4 It is an alkyl group, and the remaining group is hydrogen.

[0509] In an additional aspect of this embodiment, R5 and R 10 One of them is C 1~4 One is alkyl, and the other is hydrogen.

[0510] In a further embodiment of this design, one of R1, R2, R3, R4, R6, R7, R8, and R9 is C 1~4 It is an alkyl group, and the remaining group is hydrogen.

[0511] In another aspect of this embodiment, R 11 and R 12 Each of these is hydrogen, and R1, R2, R3, R4, R5, R6, R7, R8, R9 and R 10 One, two, three, or four of these groups are methyl groups, and the remaining groups are hydrogen.

[0512] In an additional aspect of this embodiment, the compound is [ka] It is selected from the group consisting of the following.

[0513] Another embodiment of the present invention is a method for whitening the skin of a subject. This method involves bringing a compound into contact with the subject, wherein the compound is [ka] A step selected from the group consisting of the following:

[0514] An additional embodiment of the present invention is a method for inducing melanocyte apoptosis in a subject. This method involves contacting a subject with a compound, wherein the compound has the structure of the following formula: [ka] (In the formula, X is NR 14 Y is selected from the group consisting of and O, and Y is a covalent bond, CR5R6, O, or NR 15 And R1, R2, R3, R4, R7, R8, R9, R10 and R 11 is hydrogen, halogen, CN, hydroxyl, R 16 OR 16 Independently selected from the group consisting of R 13 , R 14 and R 15 These are, independently, hydrogen or R 16 R5 and R6 are hydrogen, hydroxyl, OR 16 , R 16 and C 3~6 R5 and R6 are independently selected from the group consisting of cycloalkyl groups, or together they form an oxo (=O) group or a C group. 3~6 Forming a cycloalkyl group, R 12 is hydrogen, -COR a and R 16 Selected from the group consisting of R 16 These are, independently, formil and C 1~9 Alkyl, C 2~9 Alkenyl or C 2~9 It is alkinyl, R a These are hydrogen, hydroxyl, and OR 16 The step comprises having (selected from the group consisting of) or being a crystalline form thereof, hydrate, or a salt that is acceptable as a cosmetic or pharmaceutically acceptable substance.

[0515] In one aspect of this embodiment, the compound has the following structure: [ka] It is a salt that contains, or has the same crystalline form, hydrate, or is cosmetically or pharmaceutically acceptable.

[0516] In another aspect of this embodiment, X is NH.

[0517] In an additional aspect of this embodiment, Y is CR5R6, R5 is hydrogen, R6 is hydrogen, C 1~4 Alkyl, C 3~6 Cycloalkyl or O-(C 1~4Either it is alkyl, or R5 and R6 combine to form an oxo (=O) group.

[0518] Preferably, CR5R6 is CH2, CHCH3, CHOCH3, C=O, or CH(C3H5).

[0519] In a further embodiment of this design, R1, R2, R3, R4, R7, R8, R9, R 10 and R 11 At least one of them is C 1~4 It is alkyl.

[0520] Preferably, R2 is C 1~4 It is alkyl.

[0521] More preferably, R2 is methyl.

[0522] In another aspect of this embodiment, R1, R2, R3, R4, R7, R8, R9, R 10 and R 11 Each of them is hydrogen.

[0523] In an additional aspect of this embodiment, R 12 -COR a or C 1~4 It is a hydroxyalkyl, R a is hydrogen or C 1~4 It is alkyl.

[0524] Preferably, R 12 These are CHO, CH2OH, or C(=O)-O-(C 1~4 It is alkyl.

[0525] Comfortable, R 12 It is CHO, CH2OH, or CO2CH3.

[0526] In a further aspect of this embodiment, X is NH, Y is CR5R6, and R1, R3, R4, R7, R8, R9, R 10 , R 11 and R13 Each of these is hydrogen, and R2 is either hydrogen or C 1~4 It is an alkyl group, R5 is hydrogen, R6 is hydrogen, C 1~4 Alkyl, C 3~6 Cycloalkyl or O-(C 1~4 (Alkyl) or R5 and R6 together form an oxo (=O) group, R 12 -COR a or C 1~4 It is a hydroxyalkyl, R a is hydrogen or C 1~4 It is alkyl.

[0527] In another aspect of this embodiment, the compound is [ka] [ka] It is selected from the group consisting of the following.

[0528] A further embodiment of the present invention is a method for inducing melanocyte apoptosis in a subject. This method involves contacting a subject with a compound, wherein the compound has the following formula: [ka] (In the formula, R1, R4, R5, R6, R9 and R 10 is hydrogen, hydroxyl, halogen, CN, R 13 , OR 13 , OCOR 13 R2 and R3 are independently selected from the group consisting of -CHO, and R2 and R3 are hydrogen, hydroxyl, halogen, CN, R 13 , OR 13 , OCOR 13 R2 and R3 are independently selected from the group consisting of -CHO, or R2 and R3 combine to form a 5-membered or 6-membered heterocycline, and R7 and R8 are hydrogen, hydroxyl, halogen, CN, R 13 , OR 13 , OCOR 13R7 and R8 are independently selected from the group consisting of -CHO, or R7 and R8 combine to form a 5-membered or 6-membered heterocycline, 11 and R 12 These are, independently, hydrogen or R 13 And R 13 Each of them is independent of C 1~9 Alkyl, C 2~9 Alkenyl or C 2~9 The step comprises having an alkynyl (or a crystalline form thereof, a hydrate, or a salt that is acceptable for cosmetic or pharmaceutically acceptable purposes).

[0529] In one embodiment of this design, the compound has a structure according to formula (II): [ka] It is a salt that contains, or has the same crystalline form, hydrate, or is cosmetically or pharmaceutically acceptable.

[0530] In another aspect of this embodiment, R1, R2, R3, R4, R5, R6, R7, R8, R9 and R 10 is hydrogen and C 1~4 It is independently selected from the group consisting of alkyl groups.

[0531] Preferably, R1, R2, R3, R4, R5, R6, R7, R8, R9 and R 10 One or two of them are C 1~4 It is an alkyl group, and the remaining group is hydrogen.

[0532] In an additional aspect of this embodiment, R5 and R 10 One of them is C 1~4 One is alkyl, and the other is hydrogen.

[0533] In a further embodiment of this design, one of R1, R2, R3, R4, R6, R7, R8, and R9 is C 1~4 It is an alkyl group, and the remaining group is hydrogen.

[0534] In another aspect of this embodiment, R 11 and R 12 Each of these is hydrogen, and R1, R2, R3, R4, R5, R6, R7, R8, R9 and R 10 One, two, or three of them Alternatively, four of the groups are methyl, and the remaining group is hydrogen.

[0535] In an additional aspect of this embodiment, the compound is [ka] It is selected from the group consisting of the following.

[0536] Another embodiment of the present invention is a method for inducing melanocyte apoptosis in a subject. This method involves contacting a subject with a compound, wherein the compound [ka] A step selected from the group consisting of the following:

[0537] An additional embodiment of the present invention is a method for modulating aromatic hydrocarbon acceptor (AhR) activity in a subject. The method involves contacting a subject with a compound, wherein the compound has the structure of the following formula: [ka] (In the formula, X is NR 14 Y is selected from the group consisting of and O, and Y is a covalent bond, CR5R6, O, or NR 15 And R1, R2, R3, R4, R7, R8, R9, R 10 and R 11 is hydrogen, halogen, CN, hydroxyl, R 16 OR 16 Independently selected from the group consisting of R 13 , R 14 and R 15 These are, independently, hydrogen or R 16 R5 and R6 are hydrogen, hydroxyl, OR 16, R 16 and C 3~6 R5 and R6 are independently selected from the group consisting of cycloalkyl groups, or together they form an oxo (=O) group or a C group. 3~6 Forming a cycloalkyl group, R 12 is hydrogen, -COR a and R 16 Selected from the group consisting of R 16 These are, independently, formil and C 1~9 Alkyl, C 2~9 Alkenyl or C 2~9 It is alkinyl, R a These are hydrogen, hydroxyl, and OR 16 The step comprises having (selected from the group consisting of) or being a crystalline form thereof, hydrate, or a salt that is acceptable as a cosmetic or pharmaceutically acceptable substance.

[0538] In one aspect of this embodiment, the compound has the following structure: [ka] It is a salt that contains, or has the same crystalline form, hydrate, or is cosmetically or pharmaceutically acceptable.

[0539] In another aspect of this embodiment, X is NH.

[0540] In an additional aspect of this embodiment, Y is CR5R6, R5 is hydrogen, R6 is hydrogen, C 1~4 Alkyl, C 3~6 Cycloalkyl or O-(C 1~4 Either it is alkyl, or R5 and R6 combine to form an oxo (=O) group.

[0541] Preferably, CR5R6 is CH2, CHCH3, CHOCH3, C=O, or CH(C3H5).

[0542] In a further embodiment of this design, R1, R2, R3, R4, R7, R8, R9, R 10 and R 11At least one of them is C 1~4 It is alkyl.

[0543] Preferably, R2 is C 1~4 It is alkyl.

[0544] More preferably, R2 is methyl.

[0545] In another aspect of this embodiment, R1, R2, R3, R4, R7, R8, R9, R 10 oh Call R 11 Each of them is hydrogen.

[0546] In an additional aspect of this embodiment, R 12 -COR a or C 1~4 It is a hydroxyalkyl, R a is hydrogen or C 1~4 It is alkyl.

[0547] Preferably, R 12 These are CHO, CH2OH, or C(=O)-O-(C 1~4 It is alkyl.

[0548] Comfortable, R 12 It is CHO, CH2OH, or CO2CH3.

[0549] In a further aspect of this embodiment, X is NH, Y is CR5R6, and R1, R3, R4, R7, R8, R9, R 10 , R 11 and R 13 Each of these is hydrogen, and R2 is either hydrogen or C 1~4 It is an alkyl group, R5 is hydrogen, R6 is hydrogen, C 1~4 Alkyl, C 3~6 Cycloalkyl or O-(C 1~4 (Alkyl) or R5 and R6 together form an oxo (=O) group, R 12 -COR a or C 1~4It is a hydroxyalkyl, R a is hydrogen or C 1~4 It is alkyl.

[0550] In another aspect of this embodiment, the compound is [ka] It is selected from the group consisting of the following.

[0551] A further embodiment of the present invention is a method for modulating aromatic hydrocarbon acceptor (AhR) activity in a subject. The method involves contacting a subject with a compound, wherein the compound has the following formula: [ka] (In the formula, R1, R4, R5, R6, R9 and R 10 is hydrogen, hydroxyl, halogen, CN, R 13 , OR 13 , OCOR 13 R2 and R3 are independently selected from the group consisting of -CHO, and R2 and R3 are hydrogen, hydroxyl, halogen, CN, R 13 , OR 13 , OCOR 13 R2 and R3 are independently selected from the group consisting of -CHO, or R2 and R3 combine to form a 5-membered or 6-membered heterocycline, and R7 and R8 are hydrogen, hydroxyl, halogen, CN, R 13 , OR 13 , OCOR 13 R7 and R8 are independently selected from the group consisting of -CHO, or R7 and R8 combine to form a 5-membered or 6-membered heterocycline, 11 and R 12 These are, independently, hydrogen or R 13 And R 13 Each of them is independent of C 1~9 Alkyl, C 2~9 Alkenyl or C 2~9 The step comprises having an alkynyl (or a crystalline form thereof, a hydrate, or a salt that is acceptable for cosmetic or pharmaceutically acceptable purposes).

[0552] In one embodiment of this design, the compound has a structure according to formula (II): [ka] It is a salt that contains, or has the same crystalline form, hydrate, or is cosmetically or pharmaceutically acceptable.

[0553] In another aspect of this embodiment, R1, R2, R3, R4, R5, R6, R7, R8, R9 and R 10 is hydrogen and C 1~4 It is independently selected from the group consisting of alkyl groups.

[0554] Preferably, R1, R2, R3, R4, R5, R6, R7, R8, R9 and R 10 One or two of them are C 1~4 It is an alkyl group, and the remaining group is hydrogen.

[0555] In an additional aspect of this embodiment, R5 and R 10 One of them is C 1~4 One is alkyl, and the other is hydrogen.

[0556] In a further embodiment of this design, one of R1, R2, R3, R4, R6, R7, R8, and R9 is C 1~4 It is an alkyl group, and the remaining group is hydrogen.

[0557] In another aspect of this embodiment, R 11 and R 12 Each of these is hydrogen, and R1, R2, R3, R4, R5, R6, R7, R8, R9 and R 10 One, two, three, or four of these groups are methyl groups, and the remaining groups are hydrogen.

[0558] In an additional aspect of this embodiment, the compound is [ka] It is selected from the group consisting of the following.

[0559] Another embodiment of the present invention is a method for modulating aromatic hydrocarbon acceptor (AhR) activity in a subject. This method involves contacting a subject with a compound, wherein the compound [ka] A step selected from the group consisting of the following:

[0560] An additional embodiment of the present invention is a method for modulating melanin formation in a subject. This method involves contacting a subject with a compound, wherein the compound has the structure of the following formula: [ka] (In the formula, X is NR 14 Y is selected from the group consisting of and O, and Y is a covalent bond, CR5R6, O, or NR 15 And R1, R2, R3, R4, R7, R8, R9, R 10 and R 11 is hydrogen, halogen, CN, hydroxyl, R 16 OR 16 Independently selected from the group consisting of R 13 , R 14 and R 15 These are, independently, hydrogen or R 16 R5 and R6 are hydrogen, hydroxyl, OR 16 , R 16 and C 3~6 R5 and R6 are independently selected from the group consisting of cycloalkyl groups, or together they form an oxo (=O) group or a C group. 3~6 Forming a cycloalkyl group, R 12 is hydrogen, -COR a and R 16 Selected from the group consisting of R 16 These are, independently, formil and C 1~9 Alkyl, C 2~9 Alkenyl or C 2~9 It is alkinyl, R aThese are hydrogen, hydroxyl, and OR 16 The step comprises having (selected from the group consisting of) or being a crystalline form thereof, hydrate, or a salt that is acceptable as a cosmetic or pharmaceutically acceptable substance.

[0561] In one aspect of this embodiment, the compound has the following structure: [ka] It is a salt that contains, or has the same crystalline form, hydrate, or is cosmetically or pharmaceutically acceptable.

[0562] In another aspect of this embodiment, X is NH.

[0563] In an additional aspect of this embodiment, Y is CR5R6, R5 is hydrogen, R6 is hydrogen, C 1~4 Alkyl, C 3~6 Cycloalkyl or O-(C 1~4 Either it is alkyl, or R5 and R6 combine to form an oxo (=O) group.

[0564] Preferably, CR5R6 is CH2, CHCH3, CHOCH3, C=O, or CH(C3H5).

[0565] In a further embodiment of this design, R1, R2, R3, R4, R7, R8, R9, R 10 and R 11 At least one of them is C 1~4 It is alkyl.

[0566] Preferably, R2 is C 1~4 It is alkyl.

[0567] More preferably, R2 is methyl.

[0568] In another aspect of this embodiment, R1, R2, R3, R4, R7, R8, R9, R 10 and R 11 Each of them is hydrogen.

[0569] In an additional aspect of this embodiment, R 12 -COR a or C 1~4 It is a hydroxyalkyl, R a is hydrogen or C 1~4 It is alkyl.

[0570] Preferably, R 12 These are CHO, CH2OH, or C(=O)-O-(C 1~4 It is alkyl.

[0571] Comfortable, R 12 It is CHO, CH2OH, or CO2CH3.

[0572] In a further aspect of this embodiment, X is NH, Y is CR5R6, and R1, R3, R4, R7, R8, R9, R 10 , R 11 and R 13 Each of these is hydrogen, and R2 is either hydrogen or C 1~4 It is an alkyl group, R5 is hydrogen, R6 is hydrogen, C 1~4 Alkyl, C 3~6 Cycloalkyl or O-(C 1~4 (Alkyl) or R5 and R6 together form an oxo (=O) group, R 12 -COR a or C 1~4 It is a hydroxyalkyl, R a is hydrogen or C 1~4 It is alkyl.

[0573] In another aspect of this embodiment, the compound is [ka] It is selected from the group consisting of the following.

[0574] A further embodiment of the present invention is a method for modulating melanin formation in a subject. This method involves contacting a subject with a compound, wherein the compound has the following formula: [ka] (In the formula, R1, R4, R5, R6, R9 and R 10 is hydrogen, hydroxyl, halogen, CN, R 13 , OR 13 , OCOR 13 R2 and R3 are independently selected from the group consisting of -CHO, and R2 and R3 are hydrogen, hydroxyl, halogen, CN, R 13 , OR 13 , OCOR 13 And are independently selected from the group consisting of -CHO, or R2 and R3 are together. This forms a 5-membered or 6-membered heterocycline, where R7 and R8 are hydrogen, hydroxyl, halogen, CN, R 13 , OR 13 , OCOR 13 R7 and R8 are independently selected from the group consisting of -CHO, or R7 and R8 combine to form a 5-membered or 6-membered heterocycline, 11 and R 12 These are, independently, hydrogen or R 13 And R 13 Each of them is independent of C 1~9 Alkyl, C 2~9 Alkenyl or C 2~9 The step comprises having an alkynyl (or a crystalline form thereof, a hydrate, or a salt that is acceptable for cosmetic or pharmaceutically acceptable purposes).

[0575] In one embodiment of this design, the compound has a structure according to formula (II): [ka] It is a salt that contains, or has the same crystalline form, hydrate, or is cosmetically or pharmaceutically acceptable.

[0576] In another aspect of this embodiment, R1, R2, R3, R4, R5, R6, R7, R8, R9 and R 10 is hydrogen and C 1~4 It is independently selected from the group consisting of alkyl groups.

[0577] Preferably, R1, R2, R3, R4, R5, R6, R7, R8, R9 and R 10 One or two of them are C 1~4 It is an alkyl group, and the remaining group is hydrogen.

[0578] In an additional aspect of this embodiment, R5 and R 10 One of them is C 1~4 One is alkyl, and the other is hydrogen.

[0579] In a further embodiment of this design, one of R1, R2, R3, R4, R6, R7, R8, and R9 is C 1~4 It is an alkyl group, and the remaining group is hydrogen.

[0580] In another aspect of this embodiment, R 11 and R 12 Each of these is hydrogen, and R1, R2, R3, R4, R5, R6, R7, R8, R9 and R 10 One, two, three, or four of these groups are methyl groups, and the remaining groups are hydrogen.

[0581] In an additional aspect of this embodiment, the compound is [ka] It is selected from the group consisting of the following.

[0582] Another embodiment of the present invention is a method for modulating melanin formation in a subject. This method involves contacting a subject with a compound, wherein the compound [ka] A step selected from the group consisting of the following:

[0583] An additional embodiment of the present invention is a method for modulating melanin concentration in a subject. This method involves contacting a subject with a compound, wherein the compound has the structure of the following formula: [ka] (In the formula, X is NR 14 Y is selected from the group consisting of and O, and Y is a covalent bond, CR5R6, O, or NR 15 And R1, R2, R3, R4, R7, R8, R9, R 10 and R 11 is hydrogen, halogen, CN, hydroxyl, R 16 OR 16 Independently selected from the group consisting of R 13 , R 14 and R 15 These are, independently, hydrogen or R 16 R5 and R6 are hydrogen, hydroxyl, OR 16 , R 16 and C 3~6 R5 and R6 are independently selected from the group consisting of cycloalkyl groups, or together they form an oxo (=O) group or a C group. 3~6 Forming a cycloalkyl group, R 12 is hydrogen, -COR a and R 16 Selected from the group consisting of R 16 These are, independently, formil and C 1~9 Alkyl, C 2~9 Alkenyl or C 2~9 It is alkinyl, R a These are hydrogen, hydroxyl, and OR 16 The step comprises having (selected from the group consisting of) or being a crystalline form thereof, hydrate, or a salt that is acceptable as a cosmetic or pharmaceutically acceptable substance.

[0584] In one aspect of this embodiment, the compound has the following structure: [ka] It is a salt that contains, or has the same crystalline form, hydrate, or is cosmetically or pharmaceutically acceptable.

[0585] In another aspect of this embodiment, X is NH.

[0586] In an additional aspect of this embodiment, Y is CR5R6, R5 is hydrogen, R6 is hydrogen, C 1~4 Alkyl, C 3~6 Cycloalkyl or O-(C 1~4 Either it is alkyl, or R5 and R6 combine to form an oxo (=O) group.

[0587] Preferably, CR5R6 is CH2, CHCH3, CHOCH3, C=O, or CH(C3H5).

[0588] In a further embodiment of this design, R1, R2, R3, R4, R7, R8, R9, R 10 and R 11 At least one of them is C 1~4 It is alkyl.

[0589] Preferably, R2 is C 1~4 It is alkyl.

[0590] More preferably, R2 is methyl.

[0591] In another aspect of this embodiment, R1, R2, R3, R4, R7, R8, R9, R 10 and R 11 Each of them is hydrogen.

[0592] In an additional aspect of this embodiment, R 12 -COR a or C 1~4 It is a hydroxyalkyl, R a is hydrogen or C 1~4 It is alkyl.

[0593] Preferably, R 12These are CHO, CH2OH, or C(=O)-O-(C 1~4 It is alkyl.

[0594] Comfortable, R 12 It is CHO, CH2OH, or CO2CH3.

[0595] In a further aspect of this embodiment, X is NH, Y is CR5R6, and R1, R3, R4, R7, R8, R9, R 10 , R 11 and R 13 Each of these is hydrogen, and R2 is either hydrogen or C 1~4 It is an alkyl group, R5 is hydrogen, R6 is hydrogen, C 1~4 Alkyl, C 3~6 Cycloalkyl or O-(C 1~4 (Alkyl) or R5 and R6 together form an oxo (=O) group, R 12 -COR a or C 1~4 It is a hydroxyalkyl, R a is hydrogen or C 1~4 It is alkyl.

[0596] In another aspect of this embodiment, the compound is [ka] It is selected from the group consisting of the following.

[0597] A further embodiment of the present invention is a method for modulating melanin concentration in a subject. This method involves contacting the subject with a compound, wherein the compound has the following formula: [ka] (In the formula, R1, R4, R5, R6, R9 and R 10 is hydrogen, hydroxyl, halogen, CN, R 13 , OR 13 , OCOR 13R2 and R3 are independently selected from the group consisting of -CHO, and R2 and R3 are hydrogen, hydroxyl, halogen, CN, R 13 , OR 13 , OCOR 13 And are independently selected from the group consisting of -CHO, or R2 and R3 are together. This forms a 5-membered or 6-membered heterocycline, where R7 and R8 are hydrogen, hydroxyl, halogen, CN, R 13 , OR 13 , OCOR 13 R7 and R8 are independently selected from the group consisting of -CHO, or R7 and R8 combine to form a 5-membered or 6-membered heterocycline, 11 and R 12 These are, independently, hydrogen or R 13 And R 13 Each of them is independent of C 1~9 Alkyl, C 2~9 Alkenyl or C 2~9 The step comprises having an alkynyl (or a crystalline form thereof, a hydrate, or a salt that is acceptable for cosmetic or pharmaceutically acceptable purposes).

[0598] In one embodiment of this design, the compound has a structure according to formula (II): [ka] It is a salt that contains, or has the same crystalline form, hydrate, or is cosmetically or pharmaceutically acceptable.

[0599] In another aspect of this embodiment, R1, R2, R3, R4, R5, R6, R7, R8, R9 and R 10 is hydrogen and C 1~4 It is independently selected from the group consisting of alkyl groups.

[0600] Preferably, R1, R2, R3, R4, R5, R6, R7, R8, R9 and R 10 One or two of them are C 1~4 It is an alkyl group, and the remaining group is hydrogen.

[0601] In an additional aspect of this embodiment, R5 and R 10 One of them is C 1~4 One is alkyl, and the other is hydrogen.

[0602] In a further embodiment of this design, one of R1, R2, R3, R4, R6, R7, R8, and R9 is C 1~4 It is an alkyl group, and the remaining group is hydrogen.

[0603] In another aspect of this embodiment, R 11 and R 12 Each of these is hydrogen, and R1, R2, R3, R4, R5, R6, R7, R8, R9 and R 10 One, two, three, or four of these groups are methyl groups, and the remaining groups are hydrogen.

[0604] In an additional aspect of this embodiment, the compound is [ka] It is selected from the group consisting of the following.

[0605] Another embodiment of the present invention is a method for modulating melanin concentration in a subject. This method involves contacting a subject with a compound, wherein the compound [ka] A step selected from the group consisting of the following:

[0606] One embodiment of the present invention is a compound that whitens the skin. The compound has the following structure: [ka] It is a compound of, or a chemical analog thereof, crystalline form, hydrate, or a pharmaceutically or cosmetically acceptable salt thereof.

[0607] Another embodiment of the present invention is a compound that induces melanocyte apoptosis. The compound has the following structure: [ka] It is a compound of, or a chemical analog thereof, crystalline form, hydrate, or a pharmaceutically or cosmetically acceptable salt thereof.

[0608] An additional embodiment of the present invention is a compound that modulates aromatic hydrocarbon acceptor (AhR) activity. The compound has the following structure: [ka] It is a compound of, or a chemical analog thereof, crystalline form, hydrate, or a pharmaceutically or cosmetically acceptable salt thereof.

[0609] A further embodiment of the present invention is a compound that modulates melanin formation. The compound has the following structure: [ka] It is a compound of, or a chemical analog thereof, crystalline form, hydrate, or a pharmaceutically or cosmetically acceptable salt thereof.

[0610] Another embodiment of the present invention is a compound that modulates melanin concentration. The compound has the following structure: [ka] It is a compound of, or a chemical analog thereof, crystalline form, hydrate, or a pharmaceutically or cosmetically acceptable salt thereof.

[0611] An additional embodiment of the present invention is a composition comprising a compound, the compound having the following formula: [ka] It is a compound of, or a chemical analog thereof, crystalline form, hydrate, or a pharmaceutically or cosmetically acceptable salt thereof.

[0612] A further embodiment of the present invention is a method for whitening the skin of a subject. This method involves contacting the subject with a compound, wherein the compound has the following structure: [ka] The step comprises having or having a chemical analog, crystalline form, hydrate, or pharmaceutically or cosmetically acceptable salt thereof.

[0613] Another embodiment of the present invention is a method for inducing melanocyte apoptosis in a subject. This method involves contacting a subject with a compound, wherein the compound has the structure of the following formula: [ka] The step comprises having or having a chemical analog, crystalline form, hydrate, or pharmaceutically or cosmetically acceptable salt thereof.

[0614] An additional embodiment of the present invention is a method for modulating aromatic hydrocarbon acceptor (AhR) activity in a subject. The method involves contacting a subject with a compound, wherein the compound has the structure of the following formula: [ka] The step comprises having or having a chemical analog, crystalline form, hydrate, or pharmaceutically or cosmetically acceptable salt thereof.

[0615] A further embodiment of the present invention is a method for modulating melanin formation in a subject. This method involves contacting a subject with a compound, wherein the compound has the structure of the following formula: [ka] The step comprises having or having a chemical analog, crystalline form, hydrate, or pharmaceutically or cosmetically acceptable salt thereof.

[0616] Another embodiment of the present invention is a method for modulating melanin concentration in a subject. This method involves contacting the subject with a compound, wherein the compound has the following structure: [ka] The step comprises having or having a chemical analog, crystalline form, hydrate, or pharmaceutically or cosmetically acceptable salt thereof.

[0617] An additional embodiment of the present invention is a composition. The composition comprises one or more of the compounds listed in Table 5 or Figure 130, or their chemical analogs, crystalline forms, hydrates, or pharmaceutically or cosmetically acceptable salts. In one aspect of this embodiment, the composition comprises a first compound having the structure of the following formula: [ka] or its chemical analog, crystalline form, hydrate, or pharmaceutically or cosmetically acceptable salt; and a second compound having the structure of the following formula: [ka] Or its chemical analog, crystalline form, hydrate, or as a pharmaceutical or cosmetic product. Contains salt.

[0618] A further embodiment of the present invention is a method for whitening skin in a subject. This method comprises the step of contacting the subject with one or more of the compounds listed in Table 5 or Figure 130, or their chemical analogs, crystalline forms, hydrates, or pharmaceutically or cosmetically acceptable salts.

[0619] In one aspect of this embodiment, the subject is a first compound having the structure of the following formula: [ka] or its chemical analog, crystalline form, hydrate, or pharmaceutically or cosmetically acceptable salt; and a second compound having the structure of the following formula: [ka] Alternatively, it may be brought into contact with its chemical analogue, crystalline form, hydrate, or a pharmaceutically or cosmetically acceptable salt.

[0620] Another embodiment of the present invention is a method for inducing melanocyte apoptosis in a subject. This method comprises the step of contacting the subject with one or more of the compounds listed in Table 5 or Figure 130, or their chemical analogs, crystalline forms, hydrates, or pharmaceutically or cosmetically acceptable salts.

[0621] In one aspect of this embodiment, the subject is a first compound having the structure of the following formula: [ka] or its chemical analog, crystalline form, hydrate, or pharmaceutically or cosmetically acceptable salt; and a second compound having the structure of the following formula: [ka] Alternatively, it may be brought into contact with its chemical analogue, crystalline form, hydrate, or a pharmaceutically or cosmetically acceptable salt.

[0622] An additional embodiment of the present invention is a method for modulating aromatic hydrocarbon acceptor (AhR) activity in a subject. This method comprises the step of contacting the subject with one or more of the compounds listed in Table 5 or Figure 130, or their chemical analogs, crystalline forms, hydrates, or pharmaceutically or cosmetically acceptable salts.

[0623] In one aspect of this embodiment, the subject is a first compound having the structure of the following formula: [ka] or its chemical analog, crystalline form, hydrate, or pharmaceutically or cosmetically acceptable salt; and a second compound having the structure of the following formula: [ka] Alternatively, it may be brought into contact with its chemical analogue, crystalline form, hydrate, or a pharmaceutically or cosmetically acceptable salt.

[0624] A further embodiment of the present invention is a method for modulating melanin formation in a subject. This method comprises the step of contacting the subject with one or more of the compounds listed in Table 5 or Figure 130, or their chemical analogs, crystalline forms, hydrates, or pharmaceutically or cosmetically acceptable salts.

[0625] In one aspect of this embodiment, the subject is a first compound having the structure of the following formula: [ka] or its chemical analog, crystalline form, hydrate, or pharmaceutically or cosmetically acceptable salt; and a second compound having the structure of the following formula: [ka] Alternatively, it may be brought into contact with its chemical analogue, crystalline form, hydrate, or a pharmaceutically or cosmetically acceptable salt.

[0626] Another embodiment of the present invention is a method for modulating melanin concentration in a subject. This method comprises the step of contacting the subject with one or more of the compounds listed in Table 5 or Figure 130, or their chemical analogs, crystalline forms, hydrates, or pharmaceutically or cosmetically acceptable salts.

[0627] In one aspect of this embodiment, the subject is a first compound having the structure of the following formula: [ka] or its chemical analog, crystalline form, hydrate, or pharmaceutically or cosmetically acceptable salt; and a second compound having the structure of the following formula: [ka] Alternatively, it may be brought into contact with its chemical analogue, crystalline form, hydrate, or a pharmaceutically or cosmetically acceptable salt.

[0628] An additional embodiment of the present invention is a composition. This composition is one or more of the compounds listed in Table 5 or Figure 130, or their chemical analogs, crystalline forms, hydrates, or Contains salts that are pharmaceutically or cosmetically acceptable.

[0629] A further embodiment of the present invention is a skin-whitening composition. This composition comprises one or more of the compounds listed in Table 5 or Figure 130, or their chemical analogs, crystalline forms, hydrates, or pharmaceutically or cosmetically acceptable salts.

[0630] Another embodiment of the present invention is a composition for inducing melanocyte apoptosis. This composition comprises one or more of the compounds listed in Table 5 or Figure 130, or their chemical analogs, crystalline forms, hydrates, or pharmaceutically or cosmetically acceptable salts.

[0631] An additional embodiment of the present invention is a composition that modulates aromatic hydrocarbon acceptor (AhR) activity. The composition comprises one or more of the compounds listed in Table 5 or Figure 130, or their chemical analogs, crystalline forms, hydrates, or pharmaceutically or cosmetically acceptable salts.

[0632] A further embodiment of the present invention is a composition that modulates melanin formation. This composition comprises one or more of the compounds listed in Table 5 or Figure 130, or their chemical analogs, crystalline forms, hydrates, or pharmaceutically or cosmetically acceptable salts.

[0633] Another embodiment of the present invention is a composition for modulating melanin concentration. This composition comprises one or more of the compounds listed in Table 5 or Figure 130, or their chemical analogs, crystalline forms, hydrates, or pharmaceutically or cosmetically acceptable salts.

[0634] An additional embodiment of the present invention is a method for whitening skin in a subject. The method comprises the step of contacting a subject with a composition, wherein the composition comprises one or more of the compounds listed in Table 5 or Figure 130, or their chemical analogs, crystalline forms, hydrates, or pharmaceutically or cosmetically acceptable salts.

[0635] A further embodiment of the present invention is a method for inducing melanocyte apoptosis in a subject. The method comprises the step of contacting a subject with a composition, wherein the composition comprises one or more of the compounds listed in Table 5 or Figure 130, or their chemical analogs, crystalline forms, hydrates, or pharmaceutically or cosmetically acceptable salts.

[0636] Another embodiment of the present invention is a method for modulating aromatic hydrocarbon acceptor (AhR) activity in a subject. This method comprises the step of contacting a subject with a composition, wherein the composition comprises one or more of the compounds listed in Table 5 or Figure 130, or their chemical analogs, crystalline forms, hydrates, or pharmaceutically or cosmetically acceptable salts.

[0637] An additional embodiment of the present invention is a method for modulating melanin formation in a subject. This method comprises the step of contacting a subject with a composition, wherein the composition comprises one or more of the compounds listed in Table 5 or Figure 130, or their chemical analogs, crystalline forms, hydrates, or pharmaceutically or cosmetically acceptable salts.

[0638] A further embodiment of the present invention is a method for modulating melanin concentration in a subject. The method comprises the step of contacting a subject with a composition, wherein the composition comprises one or more of the compounds listed in Table 5 or Figure 130, or their chemical analogs, crystalline forms, hydrates, or pharmaceutically or cosmetically acceptable salts.

[0639] In preferred embodiments, the composition of the present invention comprises the compounds listed in Table 7.

[0640] In other preferred embodiments, the compositions of the present invention include the compounds listed in Table 8.

[0641] In additional preferred embodiments, the compositions of the present invention include the compounds listed in Table 9.

[0642] In a more preferred embodiment, the composition of the present invention comprises the compounds listed in Table 10.

[0643] In other preferred embodiments, the compositions of the present invention include the compounds listed in Table 11.

[0644] In an additional preferred embodiment, the method of the present invention includes the step of contacting a subject with a composition comprising the compounds listed in Table 7.

[0645] In a more preferred embodiment, the method of the present invention includes the step of contacting a subject with a composition containing the compounds listed in Table 8.

[0646] In other preferred embodiments, the method of the present invention includes the step of contacting a subject with a composition comprising the compounds listed in Table 9.

[0647] In an additional preferred embodiment, the method of the present invention includes the step of contacting a subject with a composition comprising the compounds listed in Table 10.

[0648] In a more preferred embodiment, the method of the present invention includes the step of contacting a subject with a composition containing the compounds listed in Table 11.

[0649] Another embodiment of the present invention is a composition comprising Malassezia yeast and a vehicle, diluent, or carrier that is cosmetically or pharmaceutically acceptable.

[0650] An additional embodiment of the present invention is a composition. This composition is a compound having the structure of the following formula: [ka] (In the formula, X is NR 14 Y is selected from the group consisting of and O, and Y is a covalent bond, CR5R6, O, or NR 15 And R1, R2, R3, R4, R7, R8, R9, R 10 and R 11 is hydrogen, halogen, CN, hydroxyl, R 16 OR 16 Independently selected from the group consisting of R 13 , R 14 and R 15 These are, independently, hydrogen or R 16 R5 and R6 are hydrogen, hydroxyl, OR 16 , R 16 and C 3~6 R5 and R6 are independently selected from the group consisting of cycloalkyl groups, or together they form an oxo (=O) group or a C group. 3~6 Forming a cycloalkyl group, R 12 is hydrogen, -COR a and R 16Selected from the group consisting of R 16 These are, independently, formil and C 1~9 Alkyl, C 2~9 Alkenyl or C 2~9 It is alkinyl, R a These are hydrogen, hydroxyl, and OR 16 (Selected from the group consisting of) Or its crystalline form, hydrate, or salt that is acceptable as a cosmetic or pharmaceutically acceptable substance. and includes vehicles, diluents, or carriers that are acceptable as cosmetic or pharmaceutically acceptable.

[0651] A further embodiment of the present invention is a composition. This composition is a compound having the structure of the following formula: [ka] (In the formula, R1, R4, R5, R6, R9 and R 10 is hydrogen, hydroxyl, halogen, CN, R 13 , OR 13 , OCOR 13 R2 and R3 are independently selected from the group consisting of -CHO, and R2 and R3 are hydrogen, hydroxyl, halogen, CN, R 13 , OR 13 , OCOR 13 R2 and R3 are independently selected from the group consisting of -CHO, or R2 and R3 combine to form a 5-membered or 6-membered heterocycline, and R7 and R8 are hydrogen, hydroxyl, halogen, CN, R 13 , OR 13 , OCOR 13 R7 and R8 are independently selected from the group consisting of -CHO, or R7 and R8 combine to form a 5-membered or 6-membered heterocycline, 11 and R 12 These are, independently, hydrogen or R 13 And R 13 Each of them is independent of C 1~9 Alkyl, C 2~9 Alkenyl or C 2~9 (It is alkinyl) Or its crystalline form, hydrate, or salt that is acceptable as a cosmetic or pharmaceutically acceptable substance. and includes vehicles, diluents, or carriers that are acceptable as cosmetic or pharmaceutically acceptable.

[0652] Another embodiment of the present invention is a composition. This composition is a compound listed in Table 5 or Figure 130, or its chemical analog, crystalline form, hydrate, or a salt that is cosmetically or pharmaceutically acceptable therefor. and includes vehicles, diluents, or carriers that are acceptable as cosmetic or pharmaceutically acceptable.

[0653] In preferred embodiments, any of the compositions of the present invention prevents UV-induced erythema in the subject.

[0654] In preferred embodiments, any of the compositions of the present invention reduces epidermal melanin in the subject.

[0655] In preferred embodiments, any of the compositions of the present invention produces a photoprotective or UV-protective effect on the subject.

[0656] In preferred embodiments, any of the compositions of the present invention filters, absorbs, or reflects UV light.

[0657] In preferred embodiments, any of the compositions of the present invention prevents excessive pigmentation and / or promotes hypopigmentation.

[0658] In preferred embodiments, any of the compositions of the present invention are sunscreens, photoprotective agents, and / or UV protectants.

[0659] An additional embodiment of the present invention relates to treating or preventing UV-induced skin damage in a subject. This is a method. The method includes the step of contacting a subject with one of the compositions disclosed herein.

[0660] A further embodiment of the present invention is a method for treating or preventing UV-induced erythema in a subject. This method includes the step of contacting the subject with one of the compositions disclosed herein.

[0661] Another embodiment of the present invention is a method for treating or preventing UV-induced aging of the skin in a subject. This method includes the step of contacting the subject with one of the compositions disclosed herein.

[0662] An additional embodiment of the present invention is a method for treating or preventing sunburn in a subject. This method includes the step of contacting the subject with one of the compositions disclosed herein.

[0663] A further embodiment of the present invention is a method for treating or preventing UV-induced hyperpigmentation in a subject. This method includes the step of contacting the subject with one of the compositions disclosed herein.

[0664] Another embodiment of the present invention is a method for whitening skin in a subject. This method includes the step of contacting the subject with one of the compositions disclosed herein.

[0665] An additional embodiment of the present invention is a method for inducing melanocyte apoptosis in a subject. This method includes the step of contacting the subject with one of the compositions disclosed herein.

[0666] A further embodiment of the present invention is a method for modulating aromatic hydrocarbon acceptor (AhR) activity in a subject. This method includes the step of contacting the subject with one of the compositions disclosed herein.

[0667] Another embodiment of the present invention is a method for modulating melanin formation in a subject. This method includes the step of contacting the subject with one of the compositions disclosed herein.

[0668] An additional embodiment of the present invention is a method for modulating melanin concentration in a subject. This method includes the step of contacting the subject with one of the compositions disclosed herein. definition

[0669] As used herein, the term “compound” refers to two or more atoms linked by one or more chemical bonds. In this invention, chemical bonds include, but are not limited to, covalent bonds, ionic bonds, hydrogen bonds, and van der Waals interactions. Covalent bonds in this invention include single bonds, double bonds, and triple bonds. Compounds in this invention include, but are not limited to, organic molecules.

[0670] The organic compounds / molecules of the present invention include linear, branched, and cyclic hydrocarbons, with or without functional groups. x~y When used in conjunction with chemical moieties such as alkyl, alkenyl, alkynyl, or alkoxy, the term "C" is intended to include a group containing x to y carbon atoms in the chain. For example, the term "C" x~y "Alkyl" refers to a chain containing x to y haloalkyl groups, including trifluoromethyl and 2,2,2-trifluoroethyl. This refers to substituted or unsubstituted saturated hydrocarbon groups, including linear and branched alkyl groups containing carbon atoms. x~y "Alkenil" and "C x~y "Alkynyl" refers to a substituted or unsubstituted unsaturated aliphatic group that is similar in length and may have substitutions in the alkyl group described above, each containing at least one double or triple bond.

[0671] As used herein, the term "aliphatic" refers to a group consisting of carbon and hydrogen atoms that does not contain an aromatic ring. Therefore, aliphatic groups include alkyl, alkenyl, alkynyl, and carbocykyl groups.

[0672] As used herein, the term "alkyl" means linear and branched acyclic hydrocarbon groups, for example, "C1-C 20 "Alkyl" refers to an alkyl group having 1 to 20 carbon atoms. Alkyl groups may be linear or branched. Examples of alkyl groups include, but are not limited to, methyl, ethyl, n-propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, isopentyl, tert-pentylhexyl, isohexyl, etc. Other alkyl groups are expected to be readily apparent to those skilled in the art who benefit from this disclosure. Alkyl groups may be unsubstituted or substituted with one or more substituents described herein. For example, an alkyl group may be substituted with one or more of halogens, -CO2R', -COOH, -CN, -OH, -OR', -NH2, -NHR', -N(R')2, -SR', or -SO2R' (e.g., one, two, three, four, five, or six independently selected substituents), where each R' is independently a C1-C3 alkyl group. In embodiments, the alkyl group is unsubstituted. In embodiments, the alkyl group is substituted (for example, by one, two, three, four, five, or six substituents as described herein). For example, the term “hydroxyalkyl” means an alkyl group as described herein that includes a hydroxyl (-OH) substituent, including groups such as -CH2OH.

[0673] As used herein, “alkenyl” means any linear or branched hydrocarbon chain having one or more unsaturated carbon-carbon double bonds that can occur at any stable point along the chain, for example, “C2~C 20An "alkenyl" refers to an alkenyl group having 2 to 20 carbon atoms. For example, alkenyl groups include propa-2-enyl, buta-2-enyl, buta-3-enyl, 2-methylpropa-2-enyl, hexa-2-enyl, hexa-5-enyl, and 2,3-dimethylbuta-2-enyl. In embodiments, the alkenyl contains one, two, or three carbon-carbon double bonds. In embodiments, the alkenyl contains one carbon-carbon double bond. In embodiments, multiple double bonds (e.g., two or three) are conjugated. The alkenyl group may be unsubstituted or substituted with one or more substituents described herein. For example, the alkenyl group may be substituted with one or more of the following substituents: halogen, -CO2R', -CN, -OH, -OR', -NH2, -NHR', -N(R')2, -SR', or -SO2R' (e.g., one, two, three, four, five, or six independently selected substituents), where each R' is independently a C1-C3 alkyl group. In embodiments, the alkenyl is unsubstituted. In embodiments, the alkenyl is substituted (e.g., with one, two, three, four, five, or six substituents as described herein).

[0674] As used herein, "alkynyl" means any hydrocarbon chain having one or more carbon-carbon triple bonds occurring at any stable point along the chain, in either a linear or branched configuration, for example, "C2-C 20 "Alkynyl" refers to an alkynyl group having 2 to 20 carbon atoms. Examples of alkynyl groups include propa-2-inyl, buta-2-inyl, buta-3-inyl, penta-2-inyl, and 3-methylpenta-4-inyl. This includes hexa-2-inyl, hexa-5-inyl, and the like. In embodiments, the alkynyl contains one carbon-carbon triple bond. The alkynyl group may be unsubstituted or substituted with one or more substituents as described herein. For example, the alkynyl group may be substituted with one or more of halogens, -CO2R', -CN, -OH, -OR', -NH2, -NHR', -N(R')2, -SR', or -SO2R' (e.g., one, two, three, four, five, or six independently selected substituents), where each R' is independently a C1-C3 alkyl. In embodiments, the alkynyl is unsubstituted. In embodiments, the alkynyl is substituted (e.g., with one, two, three, four, five, or six substituents as described herein).

[0675] As used herein, the term "cycloalkyl" refers to a saturated non-aromatic cyclic group, such as "C3-C3". 10This term means "cycloalkyl." In embodiments, the cycloalkyl is monocyclic. In embodiments, the cycloalkyl is polycyclic (e.g., bicyclic or tricyclic). In polycyclic cycloalkyls, the individual rings can be condensed, crosslinked, or spirocyclic. Examples of cycloalkyls include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, norbornanyl, bicyclo[3.2.1]octanyl, octahydro-pentarenyl, and spiro[4.5]decanyl. The term "cycloalkyl" may be used interchangeably with the term "carbocyclic." Cycloalkyls may be unsubstituted or substituted with one or more substituents as described herein. For example, the cycloalkyl group may be substituted with one or more of the following substituents: halogen, -CO2R', -CN, -OH, -OR', -NH2, -NHR', -N(R')2, -SR', or -SO2R' (e.g., one, two, three, four, five, or six independently selected substituents), where each R' is independently a C1-C3 alkyl group. In embodiments, the cycloalkyl group is unsubstituted. In embodiments, the cycloalkyl group is substituted (e.g., with one, two, three, four, five, or six substituents as described herein).

[0676] As used herein, the term "halogen" means fluorine, chlorine, bromine, or iodine.

[0677] As used herein, compounds containing “aromatic compounds,” “aromatic,” or “aromatic rings” are aryl or heteroaryl compounds. As used herein, the term “aryl” includes substituted or unsubstituted monocyclic aromatic groups in which each atom of the ring is carbon. Preferably, the ring is a 3- to 8-membered ring, more preferably a 6-membered ring. The term “aryl” also includes polycyclic ring systems having two or more cyclic rings in which two or more carbons are common to two adjacent rings, and at least one of the rings is aromatic, for example, the other cyclic ring may be a cycloalkyl, cycloalkenyl, cycloalkynyl, aryl, heteroaryl, and / or heterocyclyl. Examples of aryl groups include benzene, naphthalene, phenanthrene, phenol, and aniline. The term "heteroaryl" includes substituted or unsubstituted aromatic monocyclic structures, preferably 3- to 8-membered rings, more preferably 5- to 7-membered rings, and even more preferably 5- to 6-membered rings, wherein the ring structure contains at least one heteroatom, preferably 1-4 heteroatoms, and more preferably 1 or 2 heteroatoms. The term "heteroaryl" also includes polycyclic ring systems having two or more cyclic rings, wherein two or more carbons are common to two adjacent rings, and at least one of the rings is heteroaromatic, for example, the other cyclic ring can be cycloalkyl, cycloalkenyl, cycloalkynyl, aryl, heteroaryl, and / or heterocyclyl. Examples of heteroaryl groups include pyrrole, furan, thiophene, indole, imidazole, oxazole, thiazole, pyrazole, pyridine, pyrazine, pyridazine, and pyridine. Limidines and the like are included. Preferably, certain compounds of the present invention include at least one, preferably two, indole groups and at least one aldehyde group.

[0678] The term "substituted" refers to a portion having at least one substituent that replaces a hydrogen atom on one or more carbons in the main chain. "Substitution" or "substituted by" should be understood to imply that such substitution follows the allowable valencies of the substituted atom and substituent, and that this substitution results in a stable compound that does not spontaneously undergo transformation, for example, by rearrangement, cyclization, or elimination. The allowable substituents can be one or more and can be the same or different for the relevant organic compound.

[0679] As used herein, the terms “heterocyclic” or “heterocyclic formula” mean a monocyclic, bicyclic, or tricyclic ring system containing at least one heteroatom. Heteroatoms include, but are not limited to, oxygen, nitrogen, and sulfur.

[0680] Monocyclic and heterocyclic rings consist of, for example, 3, 4, 5, 6, 7, 8, 9, or 10-membered rings containing at least one heteroatom. Representative examples of monocyclic and heterocyclic rings include, but are not limited to, azetidinyl, azepanyl, azilidinyl, diazepanyl, 1,3-dioxanyl, 1,3-dioxolanyl, 1,3-dithiolanyl, 1,3-dithianyl, imidazolinyl, imidazolidinyl, isothiazolinyl, isothiazolidinyl, isoxazolinyl, isoxazolidinyl, morpholinyl, oxadiazolinyl, and oxadiazolidinyl. This includes oxazolinil, oxazolidinil, piperazinil, piperidinil, pyranil, pyrazolinil, pyrazolidinil, pyrrolinil, pyrrolidinil, tetrahydrofuranil, tetrahydrothienyl, thiadiazolinil, thiadiazolidinil, thiazolinil, thiazolidinil, thiomorpholinil, 1,1-dioxidethiomorpholinil (thiomorpholine sulfone), thiopyranil, and trithianil.

[0681] Bicyclic heterocyclic rings are, in non-limiting examples, monocyclic heterocyclic rings fused to a distal (distal) aryl ring, monocyclic heterocyclic rings fused to a distal cycloalkyl ring, monocyclic heterocyclic rings fused to a distal cycloalkenyl ring, monocyclic heterocyclic rings fused to a distal monocyclic heterocyclic ring, or monocyclic heterocyclic rings fused to a distal monocyclic heteroaryl ring. Representative examples of bicyclic heterocyclic rings include, but are not limited to, 1,3-benzodioxolyl, 1,3-benzodithiolyl, 2,3-dihydro-1,4-benzodioxynyl, 2,3-dihydro-1-benzofuranyl, 2,3-dihydro-1-benzothienyl, 2,3-dihydro-1H-indolyl, and 1,2,3,4-tetrahydroquinolinyl.

[0682] A tricyclic heterocyclic ring is, in non-limiting examples, a bicyclic heterocyclic ring fused to a phenyl group, or a bicyclic heterocyclic ring fused to a cycloalkyl group, or a bicyclic heterocyclic ring fused to a cycloalkenyl group, or a bicyclic heterocyclic ring fused to another monocyclic heterocyclic ring. Representative examples of tricyclic heterocyclic rings include, but are not limited to, 2,3,4,4a,9,9a-hexahydro-1H-carbazol, 5a,6,7,8,9,9a-hexahydrodibenzo[b,d]furanyl, and 5a,6,7,8,9,9a-hexahydrodibenzo[b,d]thienyl.

[0683] The heterocycles of the present invention include, by non-limiting examples, alkenyl, alkoxy, alkoxyalkyl, alkoxyalkynyl, alkoxycarbonyl, alkoxycarbonylalkyl, alkoxy-NH=C(alkyl)-, alkyl, alkylcarbonyl, alkylcarbonylalkyl, alkylcarbonyloxy, alkylsulfonyl, alkylthio, alkynyl, aryl, arylalkoxy, arylalkyl, arylcarbonyl, and aryl. It can be substituted with substituents independently selected from hydroxy, carboxy, carboxyalkyl, cyano, cyanoalkyl, cycloalkyl, carbonyl, cycloalkylalkyl, formyl, halogen, haloalkyl, hydroxy, hydroxyalkyl, hydroxycycloalkyl, mercapto, nitro, oxo, and phenyl.

[0684] As used herein, “modulates skin pigmentation” and its grammatical variations generally refer to the skin whitening and skin darkening effects of the compounds and compositions of the present invention.

[0685] As used herein, “skin whitening” and its grammatical variations generally refer to any actual or perceived reduction in skin pigmentation. Skin whitening methods are used to reduce hyperpigmentation in areas of skin that are excessively pigmented due to age, sun exposure, or hyperpigmentation disorder. When the compounds and compositions of the present invention are applied, for example, to the skin of a subject, pigmentation can be reduced, and as a result the skin appears lighter or whiter than before the application. Skin pigmentation includes, but is not limited to, the von Luschan chromatic scale, the Fitzpatrick dermatological classification test (Fitzpatrick et al., 1988), and Taylor's hyperpigmentation test. It can be evaluated by several methods, including visual inspection using Kale (Taylor et al., 2005) and reflectance spectrophotometric colorimetric methods (Zonios, et al., 2001). For example, The Tzpatrick skin classification test includes six skin types (I-VI), and where this term is used herein, skin of type VI, which is type V or lower, is considered "whitened." As will be further discussed below, skin whitening can result from several phenomena, including, but not limited to, modulation of melanocyte activity, induction of melanocyte apoptosis, or modulation of aromatic hydrocarbon receptor (AhR) activity, melanin formation, melanosome biogenesis, melanosome transport, or melanin concentration.

[0686] Similarly, as used herein, “skin darkening” and its grammatical variations generally refer to any actual or perceived increase in skin pigmentation. Methods of skin darkening are used, for example, to increase pigmentation in areas of skin where pigmentation has decreased due to hypopigmentation disorders. When the compounds and compositions of the present invention are applied, for example, to the skin in question, pigmentation can be increased, and as a result the skin appears darker than before the application.

[0687] Certain compounds of the present invention are produced by, derived from, isolated from, or can be isolated from Malassezia yeast. Malassezia yeast is a yeast of the genus Malassezia, and includes, but is not limited to, Malassezia globosa, Malassezia restricta, Malassezia furfur, Malassezia sympodialis, Malassezia slooffiae, Malassezia obtusa, Malassezia pachydermatis, Malassezia dermatis, Malassezia japonica, Malassezia nana, Malassezia yamatoensis, Malassezia equine, Malassezia caprae, and Malassezia cuniculi (Gueho, et al., 1996; Gaitanis, et al., 2013). Malassezia yeast is normal. Malassezia yeast is a normal part of the human skin microbiome and is not usually pathogenic. However, Malassezia yeast can cause several conditions, including, but are not limited to, tinea versicolor (both tinea versicolor and tinea leukorrhea), seborrheic dermatitis, dandruff, atopic dermatitis, Malassezia folliculitis, psoriasis, and confluent reticular papillomatosis (Gaitanis, et al., 2013).

[0688] As used herein, the term “chemical analog” refers to a compound that is structurally related to a parent compound and contains different functional groups or substituents. For example, the parent compounds of the present invention include malasedin and indirubin, and the chemical analogs of malasedin and indirubin each contain certain functional groups and substituents that are different from malasedin and indirubin, respectively. The chemical analogs of the present invention may have significant advantages over a given parent compound, including a pharmacokinetic profile suitable for cosmetic or pharmaceutical use. In some embodiments, the chemical analog is generated from the parent molecule by one or more chemical reactions. In other embodiments, the chemical analog of the present invention can be generated using alternative synthesis schemes that do not originate from the parent compound.

[0689] The compounds of the present invention are produced by Malassezia yeast, if Malassezia yeast synthesizes, secretes, accumulates, or otherwise generates them under appropriate growth conditions throughout its life cycle. Malassezia yeast secretes different compounds depending on what is supplied to its growth medium (Nazzaro-Porro, et al.). (al., 1978). The present invention includes any compound produced by Malassezia yeast under any growth conditions, but preferred compounds include, for example, malassezin, indirubin and their chemical analogues.

[0690] If the compound is present on or inside the yeast surface at any point in the yeast life cycle, the compound of the present invention is derived from Malassezia yeast.

[0691] Malassezin is an example of a compound produced by Malassezia yeast in the present invention. Also known as 2-(1H-indole-3-ylmethyl)-1H-indole-3-carbaldehyde, Malassezin is a tryptophan metabolite originally isolated from Malassezia furfur. Malassezin is a known agonist of aromatic hydrocarbon receptors (AhRs), receptors involved in cell growth, differentiation, and gene expression (Wille et al., 2001). Malassezin also exhibits apoptosis in primary human melanocytes. It induces (Kramer, et al., 2005). Recently, a specific chemical analog of malasezin has been found. The compound was synthesized by Winston-McPherson and collaborators, and they tested the AhR agonist activity of its analogue (Winston-McPherson, et al., 2014).

[0692] Indirubin is another example of a compound produced by Malassezia yeast according to the present invention. Indirubin is a metabolite isolated from Malassezia furfur. Indirubin is a known agonist of the aromatic hydrocarbon receptor (AhR), a receptor involved in cell growth, differentiation, and gene expression.

[0693] As used herein, the term “melanocyte” refers to epidermal dendritic cells that typically synthesize tyrosinase and melanin pigment within melanosomes. The melanocytes of the present invention exhibit upregulation of certain genes, including, but not limited to, tyrosinase (oculocutaneous albinism IA), microphthalmia-associated transcription factor, alpha-2-macroglobulin, tyrosinase-associated protein 1, solute carrier family 16, GS3955 protein, v-kit Hardy-Zuckerman 4 feline sarcoma, oculoal albinism 1, Rag D protein, glycogenin 2, G protein-coupled receptor, family C, oculocutaneous albinism II resected in esophageal cancer 1, melan-A, SRY-box 10, ATPase, class V, type 10C, matrix metalloproteinase 1, latent transforming growth factor beta b, ATP-binding cassette, subfamily C, hydroxyprostaglandin dehydrogenase 15, transmembrane 7 superfamily member 1, glutaminyl-peptide cyclotransferase, and one or more other genes identified by Lee and collaborators (Lee, et al., 2013).

[0694] Melanocytes, like many other cell types, undergo programmed cell death, or apoptosis. The melanocyte apoptotic pathway is known to those skilled in the art (Wang, et al.). (al., 2014), the apoptotic pathway has been generally outlined by Elmore (Elmore, 2007). The compounds or compositions of the present invention, for example, in melanocytes, The compounds or compositions of the present invention "induce" melanocyte apoptosis by causing activation of a specific pro-apoptotic signaling pathway or by causing inhibition of a specific anti-apoptotic pathway. The compounds or compositions of the present invention are conceived to be able to directly activate / inhibit apoptosis-related pathways by directly interacting with the signaling molecules of the pathway or by indirectly interacting with the molecules of the pathway through direct interaction with one or more intermediate molecules that do not normally function within the pathway.

[0695] Melanocyte activity can be modulated in several ways as intended by the present invention, including but not limited to inducing melanocyte apoptosis or altering melanocyte gene expression, cell motility, cell growth, melanin production, melanosome biodevelopment, or melanosome transport.

[0696] As used herein, the terms “modulate,” “modulate,” and their grammatical variations refer to adjusting a biological activity or phenomenon to a desired level. In this invention, “modulate” is conceived to include adjustments that increase or decrease the level of biological activity or phenomenon.

[0697] As used herein, the terms “agonist,” “activate,” and their grammatical variations refer to molecules that trigger (e.g., initiate or promote), partially or completely enhance, stimulate, or activate one or more biological activities. The agonists of the present invention can interact with receptors to activate them, thereby initiating a physiological or pharmacological response characteristic of that receptor. The agonists of the present invention include natural and synthetic substances.

[0698] As used herein, the terms “antagonist,” “antagonist,” and their grammatical variations refer to molecules that partially or completely suppress, inhibit, or inactivate one or more biological activities. The antagonists of the present invention can competitively bind to receptors at the same site as agonists, but do not activate the intracellular response initiated by the active form of the receptor. The antagonists of the present invention can inhibit the intracellular response of agonists or partial agonists.

[0699] The aromatic hydrocarbon receptor (AhR) of the present invention is any naturally occurring aromatic hydrocarbon receptor in the subjects described herein. Aromatic hydrocarbon receptors are known to those skilled in the art (Noakes, 2015). Agonists of aromatic hydrocarbon receptors are not limited to the following. Although not listed, tryptophan-related compounds such as kynurenine, kynurenic acid, cinnavalinic acid, and 6-formylindoro[3,2-b]carbazole (FICZ) are included. Malasedin is also known as an aromatic hydrocarbon receptor agonist (Wille, et al., 2001).

[0700] When used herein, the compounds, compositions, and methods of the present invention may be used to improve hyperpigmentation caused by hyperpigmentation disorders, for example, by reducing the level of hyperpigmentation in areas affected by hyperpigmentation disorders, by slowing further hyperpigmentation, or by preventing further hyperpigmentation from occurring. However, not all subjects may respond to a particular dosing protocol, regimen, or method, so hyperpigmentation disorders can be a contributing factor. Improvement of hyperpigmentation does not require achieving the desired physiological response or outcome in every subject or population. Therefore, a given subject or population may not respond to administration, or may respond inappropriately, while other subjects or populations may respond and thus experience improvement in their hyperpigmentation disorder.

[0701] As used herein, the term “hyperpigmentation” refers to an actual or perceived skin disorder that is excessively dark in color. The skin disorder may be actual, for example, due to age, excessive sun exposure, or a disease or condition that causes darkening of skin areas. Darkened skin areas may take the form of spots, blemishes, or relatively large areas of darkness. This skin disorder may also be perceived as a perceived condition, for example, an individual’s perception that their skin tone is too dark. Individuals may have a cosmetic desire to lighten their skin tone.

[0702] Hyperpigmentation disorders are disorders in which hyperpigmentation is the primary symptom, and disorders in which hyperpigmentation occurs as a secondary symptom. The hyperpigmentation disorders of the present invention include, but are not limited to, congenital hyperpigmentation disorders and acquired hyperpigmentation disorders. The congenital hyperpigmentation disorders of the present invention include, but are not limited to, those with epidermal hyperpigmentation (nevus cell nevi, Spitz nevus, and flat nevi), dermal hyperpigmentation (blue nevus, nevus of Ota, cutaneous melanosis, nevus of Ito, and Mongolian spot), freckles, acroretic pigmentation, acropigmentation / acral pigmentation, and lentigo (lentigo generalis, leopard syndrome, hereditary patterned lentigo, Carney complex, Peutz-Jeggers syndrome, Laugier-Hunziker-Baran syndrome, and Cronchite-Canada syndrome). (Yamaguchi, (et al., 2014). The acquired hyperpigmentation disorders of the present invention include, but are not limited to, senile lentigine / lentiformis, melasma / melasma, Riehl's melanosis, melanosis of the lips, penile / vulvovaginal melanosis, facial follicular erythema melanosis (Kitamura), UV-induced pigmentation (sunburn and actinic lentigines), post-inflammatory pigmentation (friction melanosis and achydermatosis), chemical / drug-induced pigmentation (polychlorinated biphenyls, arsenic, 5-FU, bleomycin, cyclophosphamide, methotrexate, chlorpromazine, phenytoin, tetracycline, and chloroquine), pigmented borders, and foreign body deposits (carotene, silver, gold, mercury, bismuth, and tattoos). Hyperpigmentation associated with systemic disorders includes metabolic / enzyme disorders (hemochromatosis, Wilson's disease, Gaucher disease, Niemann-Pick disease, amyloidosis, histological porphyria, acanthosis nigricans, and porphyria porphyria), endocrine disorders (Addison's disease, Cushing's syndrome, and hyperthyroidism), nutritional deficiencies (pellagra, vitamin B12 deficiency, folic acid deficiency, vagabond's disease, and pruritic pigmented lesions), mastocytosis, collagen diseases, hepatic and renal dysfunction. Hyperpigmentation may also be associated with infections (measles, syphilis, and Malassezia furfur) and syndromes (von Recklinghausen's disease, Sotos syndrome, POEMS syndrome, Naegheli syndrome, Cantu syndrome, McCune-Albright syndrome, Watson syndrome, and Bloom syndrome) (Yamaguchi, et al., 2014).

[0703] Melanin is a naturally produced pigment that gives color to the skin and hair. A schematic diagram of skin is shown in Figure 1A. Melanin is produced by melanocytes in organelles known as melanosomes by a process known as melanogenesis. The compounds or compositions of the present invention modulate melanin production (also known as melanogenesis) in subjects, for example, by modulating melanosome biogenesis and by directly or indirectly inhibiting melanin synthesis at the enzymatic level.

[0704] Melanosome biogenesis occurs in four stages: Stage I is characterized by premelanosomes, which are essentially non-pigmented vacuoles. In Stage II, the premelanosomes develop striae, into which melanin is deposited in Stage III. Stage IV is the maturation stage, which is rich in melanin. These become melanosomes. The compounds and compositions of the present invention modulate melanosome biogenesis by inhibiting or attenuating the biological processes that normally promote any or all of these steps (Wasmeier, et al., 2008).

[0705] Melanin synthesis primarily involves three enzymes: tyrosinase, tyrosinase-related protein-1, and dopachrome tautomerase. Additional factors that influence the intracellular transport of these enzymes include, but are not limited to, BLOC-1, OA1, and SLC45A2. The compounds and compositions of the present invention can modulate melanin production, for example, by inhibiting or attenuating the activity of any of these enzymes or factors. (Yamaguchi, et al., 2014).

[0706] Once melanosomes are formed and melanin is synthesized, they need to be transported from epidermal melanocytes to keratinocytes in skin and hair. Melanosomes originate near the nucleus of melanocytes and are transported along microtubules and actin filaments to the periphery of the melanocyte. The compounds and compositions of the present invention modulate melanosome transport by interfering with either of the biological processes that result in the transport of melanosomes from the perinuclear region to the periphery of the melanocyte and into the interior of adjacent keratinocytes. Schematic diagrams of melanin synthesis, melanin transport, and melanocyte apoptosis are shown in Figure 1B.

[0707] Melanin concentration can be modulated, for example, in a subject by increasing or decreasing melanin formation, by promoting melanin degradation, or by eliminating melanin from the subject.

[0708] The compounds isolated from Malassezia yeast in this invention are either always present in Malassezia yeast or produced by Malassezia yeast prior to isolation. Therefore, the compounds isolated from Malassezia yeast originate from actual yeast cells. Standard protocols for extracting compounds from cellular material are known to those skilled in the art.

[0709] Compounds that can be isolated from Malassezia yeast do not necessarily need to originate from actual yeast cells. Instead, synthetic reactions can be used to produce compounds that would otherwise be produced in yeast, without the involvement of actual yeast cells. Organic synthesis reactions are well known to those skilled in the art and can be used in this regard.

[0710] As used herein, the term “epidermal melanin” means melanin produced in the epidermis, transported to the epidermis, or otherwise found in the epidermis.

[0711] As used herein, the term “reduce” and its grammatical variations mean causing a reduction in a given biological phenomenon or species. For example, the compounds and compositions of the present invention reduce epidermal melanin in a subject, which means that the compounds and compositions of the present invention induce a reduction in the level of epidermal melanin in a subject. The term “reduce” and its grammatical variations can mean, for example, reducing a given phenomenon or species by at least 5%, 10%, 25%, 50%, 75%, or 100%.

[0712] As used herein, the term “to bring into contact” and its grammatical variations refer to bringing two or more substances into close enough proximity to interact with each other. Therefore, for illustrative purposes only, the compounds of the present invention can come into contact with melanocytes, for example, by interacting with receptors on the surface of melanocytes. Thus, the compositions of the present invention can come into contact with human subjects, for example, by being applied directly to the skin of a subject.

[0713] As used herein, “subject” means mammalian cells, tissues, organisms, or populations thereof. The subject of the present invention includes human cells, tissues, and organisms, preferably humans, but also includes primates, livestock, domesticated animals, laboratory animals, etc. Some examples of agricultural animals include cattle, pigs, horses, and goats. Some examples of domesticated animals include dogs and cats. Some examples of laboratory animals include primates, rats, mice, rabbits, and guinea pigs.

[0714] As used herein, subjects who “need” improvement of hyperpigmentation caused by hyperpigmentation disorder include subjects who actually need improvement or who perceive it as necessary.

[0715] As used herein, the terms “to treat,” “to treat,” “treatment,” and their grammatical variations mean administering a protocol, regimen, method, or treatment to an individual subject, with the expectation of obtaining a physiological response or outcome in that subject, e.g., a patient. In particular, the methods and compositions of the present invention may be used to slow the onset of disease symptoms, delay the onset of a disease or condition, or halt the progression of disease development. However, treating does not require achieving a desired physiological response or outcome in every subject or subject group, e.g., a patient group, since not all subjects being treated may respond to a particular treatment protocol, regimen, method, or treatment. Therefore, a given subject or subject group, e.g., a patient group, may not respond to a treatment, or may respond inappropriately.

[0716] As used herein, the terms “prevent,” “prevention,” “prevention,” and their grammatical variations mean that the compounds of the present invention are useful when administered to patients who, at the time of administration, have not been diagnosed as potentially having a disorder or disease, but who are typically expected to develop a disorder or disease, or who are in a state of increased risk of developing a disorder or disease. The compounds and compositions of the present invention, for example, slow the onset of symptoms of a disorder or disease, delay the onset of a disorder or disease, or completely prevent an individual from developing a disorder or disease. Prevention also includes administering the compounds of the present invention to such individuals who are considered susceptible to a disorder or disease due to age, family history, genetic or chromosomal abnormalities, and / or the presence of one or more biological markers for a disorder or disease.

[0717] As used herein, the term “promote” and its grammatical variations mean to enable, enhance, permit, facilitate, encourage, boost, induce, or otherwise help to bring about.

[0718] As used herein, the term “to produce” and its grammatical variations mean to cause, bring about, or result a particular outcome. In non-limiting examples, the compounds and compositions of the present invention produce a photoprotective or UV-protective effect in a subject.

[0719] As used herein, the term “erythema” refers to redness of the skin. Erythema may be caused by dilation and / or irritation of surface capillaries. The term “UV-induced erythema” refers to redness of the skin that develops as a result of UV exposure. As used herein, “sunburn” and its grammatical variations refer to UV-induced erythema caused by exposure to sunlight or to an artificial UV source (e.g., a tanning bed).

[0720] As used herein, the term “hyperpigmentation” generally refers to an area of ​​skin where the pigmentation is larger than the pigmentation in adjacent areas of skin (e.g., lentigines, age spots, moles, etc.). Hyperpigmentation in the present invention includes, but is not limited to, localized hyperpigmentation due to melanocyte hyperactivity, other localized hyperpigmentation due to benign melanocyte hyperactivity and proliferation, and disease-related hyperpigmentation, as well as incidental hyperpigmentation such as that due to photosensitivity, genetic structure, chemical ingestion or other exposure (e.g., UV exposure), age, and post-lesion scarring. As used herein, “UV-induced hyperpigmentation” refers to any hyperpigmentation caused by exposure to natural or artificial UV.

[0721] As used herein, the term "hypopigmentation" generally refers to an area of ​​skin in which the pigmentation is less than that of adjacent areas of skin. Hypopigmentation in the present invention includes, but is not limited to, vitiligo, depigmentation, pityriasis white, localized hypopigmentation, post-inflammatory hypopigmentation, mottled plaque, albinism, tinea versicolor, photosensitivity, congenital pigment deficiency, hypomelanosis, atopic dermatitis, and psoriasis.

[0722] As used herein, “UV-induced skin damage” means skin damage resulting from exposure to UV rays, including UVA, UVB, and UVC. UV-induced skin damage according to the present invention includes, but is not limited to, wrinkles, hyperpigmentation, dysplasia, actinic keratosis, and skin cancer.

[0723] As used herein, “UV-induced skin aging” means skin aging resulting from exposure to UV rays, including UVA, UVB, and UVC. The UV-induced skin aging of the present invention manifests, for example, as wrinkles, fine lines, age spots, moles, dryness, thinning, or loss of skin elasticity, uneven skin tone, and other declines in skin radiance, texture, elasticity, firmness, sagging, and clarity caused in whole or in part by UV exposure.

[0724] As used herein, the term “photoprotective” and its grammatical variations, when used to describe the effects of the compounds and compositions of the present invention, mean that the compounds and compositions described herein prevent and / or mitigate damage caused by light, particularly sunlight. Similarly, “photoprotective agents” of the present invention are the compounds and compositions described herein that prevent and / or mitigate damage caused by light, particularly sunlight.

[0725] As used herein, the term “UV protective” and its grammatical variations, when used to describe the effects of the compounds and compositions of the present invention, mean that the compounds and compositions described herein prevent and / or mitigate damage caused by ultraviolet ("UV") light. Similarly, “UV protective agents” of the present invention are the compounds and compositions described herein that prevent and / or mitigate damage caused by UV. The ultraviolet light of the present invention includes, for example, UVA (320-240 nm), UVB (290-320 nm), and UVC (200-290 nm).

[0726] As used herein, the term “filter” and its grammatical variations mean blocking, reflecting, absorbing, or scattering UV rays. The “Sunscreens” of the present invention include all of the compounds and compositions of the present invention that block, reflect, absorb, or scatter UV rays.

[0727] As used herein, the term “absorb” and its grammatical variations mean to take in UV light or to convert UV light into thermal energy. In non-limiting examples, the compounds and compositions of the present invention may absorb UV light, and as a result, release thermal energy into their surroundings. It can emit ghee.

[0728] As used herein, the term “reflect” and its grammatical variations, when used in the context of UV, mean to emit or reflect UV without absorbing it.

[0729] As used herein, the term “composition” means an entity comprising one or more of the compounds of the present invention, and any entity directly or indirectly derived from a combination of one or more of the compounds of the present invention with other components. The compositions of the present invention can be used, for example, as research reagents in vitro or in vivo. The compositions of the present invention can also be applied directly to the skin of a human or non-human subject for cosmetic or pharmaceutical effects. Furthermore, the compositions of the present invention may include one or more of the compounds listed in Table 5 or Figure 130, or their chemical analogs, crystalline forms, hydrates, or pharmaceutically or cosmetically acceptable salts.

[0730] The compositions of the present invention are for both in vitro and in vivo use: they may be administered orally or parenterally, or by any suitable method of administration, such as intraperitoneal, subcutaneous, topical, intradermal, inhalation, intrapulmonary, rectal, vaginal, sublingual, intramuscular, intravenous, intraarterial, intrasacral, or lymphatic, in any desired effective manner. Furthermore, the compositions of the present invention may be administered in conjunction with other compositions. The compositions of the present invention may be encapsulated, or otherwise, if desired, protected from gastric or other secretions.

[0731] The compositions of the present invention comprise one or more cosmetic or pharmaceutically acceptable carriers, and, optionally, one or more active ingredients mixed with one or more other compounds, components, and / or substances. Regardless of the selected route of administration, the compounds and compositions of the present invention are formulated into cosmetic or pharmaceutically acceptable dosage forms by conventional methods known to those skilled in the art.

[0732] Cosmetic or pharmaceutically acceptable vehicles, diluents, and carriers are well known in the art and include substances suitable for contact with human and non-human tissues without excessive toxicity, incompatibility, instability, irritation, allergic reactions, etc. Cosmetic or pharmaceutically acceptable vehicles, diluents, and carriers include, for example, any substantially non-toxic substances conventionally usable for topical, oral, intraperitoneal, or subcutaneous administration of cosmetics or pharmaceuticals, and the compounds and compositions of the present invention remain stable and bioavailable whether applied to human or non-human subjects, ingested, injected, or otherwise administered. Cosmetic or pharmaceutically acceptable carriers suitable for topical application are well known to those skilled in the art and include conventional cosmetic or pharmaceutically acceptable liquids, creams, oils, lotions, ointments, gels, or solids such as cosmetic night creams, foundation creams, sunscreens, sunscreens, hand lotions, makeup and makeup bases, and masks. Suitable carriers for the selected dosage form and intended route of administration are well known in the art, and carriers acceptable for the selected dosage form and method of administration can be determined using the usual art.

[0733] The compositions of the present invention may contain other ingredients commonly used in cosmetics, including fragrances, estrogens, vitamins A, C, and E, alpha-hydroxy acids or alpha-keto acids such as pyruvic acid, lactic acid, or glycolic acid, lanolin, petrolatum, aloe, methylparaben or propylparaben, and pigments. Non-limiting cosmetic or pharmaceutically acceptable vehicles, diluents, and carriers of the present invention may include sugars (e.g., lactose, sucrose, mannitol, and sorbitol), starches, cellulose preparations, calcium phosphates (e.g., dicalcium phosphate, tricalcium phosphate, and calcium hydrogen phosphate). These include sodium citrate, water, aqueous solutions (e.g., physiological saline, sodium chloride injection, Ringer's injection, dextrose injection, dextrose and sodium chloride injection, Ringer's lactate injection), alcohols (e.g., ethyl alcohol, propyl alcohol, and benzyl alcohol), polyols (e.g., glycerol, propylene glycol, and polyethylene glycol), organic esters (e.g., ethyl oleate and triglycerides), biodegradable polymers (e.g., polylactide-polyglycolide, poly(orthoester), and poly(anhydrous)), elastomer matrices, liposomes, microspheres, oils (e.g., corn, germ, olive, castor, sesame, cottonseed, and peanut), cocoa butter, waxes (e.g., suppository wax), paraffin, silicone, talc, salicylate, etc.

[0734] The compositions of the present invention may optionally contain additional components and / or substances commonly used in cosmetic compositions. These components and substances are well known in the art and include, for example, (1) fillers or bulking agents such as starch, lactose, sucrose, glucose, mannitol and silicic acid; (2) binders such as carboxymethylcellulose, alginate, gelatin, polyvinylpyrrolidone, hydroxypropyl methylcellulose, sucrose and acacia; (3) humectants such as glycerol; (4) agar, calcium carbonate, potato or tapioca starch, alginic acid, certain silicates, sodium starch glycolate, (5) Disintegrants such as cross-linked carboxymethylcellulose sodium and sodium carbonate, (6) Dissolution retarders such as paraffin, (7) Absorption enhancers such as quaternary ammonium compounds, (8) Wetting agents such as cetyl alcohol and glycerol monostearate, (9) Absorbents such as kaolin and bentonite clay, (10) Lubricants such as talc, calcium stearate, magnesium stearate, solid polyethylene glycol and sodium lauryl sulfate, (11) Suspensioning agents such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol and sorbitan esters, microcrystalline cellulose, aluminum metahydroxyoxide, bentonite, agar and tragacanth, (12) Buffering agents, (13) Lactose, polyethylene glycol, animal and vegetable fats, oils, waxes, paraffin, cocoa butter, starch, tragacanth, cellulose derivatives, polyethylene glycol, silicone, bentonite, silicic acid, talc, salicylate, zinc oxide, aluminum hydroxide, calcium silicate, and polyamide powder (13) Excipients such as water or other solvents, (14) Preservatives, (15) Surfactants, (16) Dispersants, (17) Controlled release agents or absorption retarders such as hydroxypropyl methylcellulose, other polymer matrices, biodegradable polymers, liposomes, microspheres, aluminum monostearate, gelatin and wax, (18) Emulsifiers, (19) Adjuvants, (20) Wetting agents, (21) Emulsifiers and suspending agents, (22) Ethyl alcohol, isopropyl alcohol, ethyl carbonate, ethyl acetate,(23) Propellantants such as benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butylene glycol, oils (especially cottonseed oil, peanut oil, corn oil, germ oil, olive oil, castor oil, and sesame oil), glycerol, tetrahydrofuryl alcohol, polyethylene glycol, and fatty acid esters of sorbitan; (24) Antioxidants such as chlorofluoro hydrocarbons and volatile unsubstituted hydrocarbons (such as butane and propane); (25) Agents that make the preparation isotonic with the blood of the intended recipient, such as sugars and sodium chloride; (26) Thickeners; (27) Coating materials such as lecithin; and (28) Sweeteners, flavorings, colorants, fragrances, and preservatives. Each such component or substance must be “acceptable” in the sense that it is compatible with the other components of the preparation and is not harmful to the subject. Suitable ingredients and substances for the selected dosage form and intended route of administration are well known in the art, and acceptable ingredients and substances for the selected dosage form and method of administration can be determined using ordinary art practice.

[0735] The compositions of the present invention, suita...

Claims

[Claim 1] The invention as shown in the drawings.

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