Compounds for inducing nicotinamide adenine dinucleotide, composition comprising same, and dermatological topical agent

Abstract

The present disclosure relates to a nicotinic acid riboside derivative compound or a nicotinamide riboside derivative compound. The derivative compound has excellent heat stability and efficiently induces the biosynthesis of nicotinamide adenine dinucleotide (NAD+). The derivative compound, a physiologically acceptable salt thereof and / or a stereoisomer thereof may be utilized as an effective ingredient or an active ingredient of an anti-inflammatory composition, a composition for alleviating or improving inflammation, an anti-aging composition and / or an anti-aging dermatological topical agent.

Description

Compounds for inducing nicotinamide adenine dinucleotide, compositions containing the same, and topical agents for skin use

[0001] This patent application is related to the results of the project “Development of anti-aging (NMN derivative) using skin permeability promotion platform technology” (Main institution: Remi Bio Co., Ltd., Project number: S3223332) as part of the “New product development project with purchase conditions for small and medium-sized enterprises technology development support project” of the Ministry of SMEs and Startups of the Republic of Korea government.

[0002] The present disclosure relates to a compound for inducing nicotinamide adenine nucleotide, and more particularly, to a compound for inducing nicotinamide adenine nucleotide with improved stability and cell permeability, and a functional composition and a skin external preparation containing the compound as an active ingredient.

[0003] Advances in medicine and medical technology are leading to a significant increase in the aging population worldwide. As the proportion of the elderly population rapidly increases, research is being conducted to elucidate the molecular and biological mechanisms associated with aging. Furthermore, interest is growing in drugs, health functional foods, and cosmetics that can delay or inhibit biological aging in living cells and / or tissues.

[0004] It is known that the main mechanism of aging in living tissues and / or living cells, including the skin, is oxidative stress that generates reactive oxygen species (ROS). However, recent studies have reported that aging occurs due to impaired signal transmission within the cell nucleus and mitochondria. One of the substances that has attracted attention in relation to biological aging at the level of living tissues and / or living cells is nicotinamide adenine dinucleotide (NAD). + )am.

[0005] NAD +NAD is a major coenzyme found in cells and is an enzyme that regulates the epigenome. + It plays a variety of roles related to aging, including helping the anti-aging protein sirtuin function properly and supporting the repair of damaged DNA. NAD in living tissues and living cells + Low levels can lead to decreased metabolism, increased risk of metabolic disorders, fatigue, poor vascular health, muscle loss due to aging, cognitive decline, impaired vision and hearing, and a shortened lifespan.

[0006] As aging progresses, NAD within living cells and tissues + It is known that NAD levels decrease and, accordingly, affect the development of various age-related diseases. Therefore, NAD in living tissues and living cells + promotes the synthesis of NAD + By restoring or increasing the level of , biological aging can be delayed or inhibited.

[0007] NAD + It is composed of two nucleotides linked by a phosphate group. Therefore, it is a phosphorylated molecule with a relatively large size compared to the precursor. NAD exists outside the cell. + It is difficult for NAD to pass through cell membranes or mitochondrial membranes. Reduced NAD in living tissues and living cells + By restoring the level of NAD in the body, to delay biological aging + NAD that can be converted to + The precursor is attracting attention.

[0008] Representative NAD +The precursors are nicotinamide riboside (NR), nicotinamide mononucleotide (NMN), nicotinic acid mononucleotide (NAMN), and nicotinic acid adenine dinucleotide (NAAD). Among these, NR is converted to NMN in vivo by the enzyme nicotinamide riboside kinase (NRK), and NMN is converted to NAD by the enzyme nicotinamide mononucleotide adenylyltransferase (NMNAT) in vivo. + can be converted to

[0009] Precursors such as NR and NMN have a mononucleoside structure in which a 5-carbon sugar, ribose, is linked to a base, nicotinamide or nicotinic acid, via an N-glycosidic bond, or a mononucleotide structure in which a phosphate group is further linked to ribose.

[0010] NAD such as NR and NMM + The precursor is NAD, which has a dinucleotide structure. + Because it is a relatively small molecule compared to NAD, + Compared to NAD, it can easily penetrate cell membranes or mitochondrial membranes. Therefore, these NAD + When the precursor is transported from outside the living cell to inside the cell, NAD is produced inside the living cell. + By raising the level, it can effectively prevent and delay the aging process.

[0011] However, NAD known to date +Precursors, such as NR and NMN, are unstable due to heat and other factors, and have the disadvantages of low skin (tissue) penetration and low intracellular delivery. Therefore, NAD in vivo is needed due to its stability, high skin (tissue) penetration and intracellular delivery. + There is growing interest in substances that can induce and promote synthesis.

[0012] The purpose of the present disclosure is to provide a nicotinamide adenine dinucleotide derivative having excellent stability, cell permeability and intracellular delivery properties, a physiologically acceptable salt thereof and / or a stereoisomer thereof.

[0013] Another object of the present disclosure is to provide a composition for inducing the synthesis of nicotinamide adenine dinucleotide in a cell, an anti-inflammatory composition, an anti-aging composition and / or an anti-aging skin topical agent, comprising a compound for inducing nicotinamide adenine dinucleotide, a physiologically acceptable salt thereof and / or a stereoisomer thereof as an active ingredient.

[0014] According to one aspect, the present disclosure provides a compound having a structure represented by the following chemical formula 1.

[0015] [Chemical Formula 1]

[0016]

[0017] In chemical formula 1,

[0018] R 1 , R 2 and R 3 are each independently a hydroxyl group, C1~C 20 An alkoxy group or a structure represented by the following chemical formula 2, R 1 , R 2 and R 3 At least one of them has the structure of the following chemical formula 2,

[0019] R 4 is a hydroxyl group, C1~C 20An alkoxy group or an amino group.

[0020] [Chemical Formula 2]

[0021]

[0022] In chemical formula 2,

[0023] R 11 and R 12 are each independently a hydrogen atom or C1~C 20 Alkyl group, C2~C 20 Alkenyl group, C2~C 20 Alkynyl group and -C(=O)R a An aliphatic substituent selected from the group consisting of,

[0024] R 13 and R 14 are each independently a hydrogen atom, C1~C 20 Alkyl group, C2~C 20 Alkenyl group, C2~C 20 Alkynyl group, C1~C 20 Alkoxy group and -C(=O)R a An aliphatic substituent selected from the group consisting of C4~C 30 Cycloalkyl group, C4~C 30 Heterocycloalkyl group, C4~C 30 Cycloalkenyl group, C4~C 30 Heterocycloalkenyl group, C6~C 30 Aryl group or C2~C 30 When it is a heteroaryl group and m is 2 to 4, each R 14 may be identical or different from each other,

[0025] R a is a hydrogen atom, C1~C 20 Alkyl group, hydroxyl group or C1~C 20 It is an alkoxy group,

[0026] The above R 11 Inland R 14 The above C1~C constituting 20 Alkyl group, C2~C above 20 Alkenyl group, C2~C above 20 Alkynyl group, C1~C above20 Alkoxy group, R above a The above C1~C constituting 20 Alkyl group and the above C1~C 20 Each alkoxy group may have -O(C=O)-, -(C=O)O-, -C(=O)-, -O-, -SC(=O)- or -C(=O)S- in the middle,

[0027] m is an integer from 0 to 4,

[0028] R 11 and R 12 At least one of the above C1~C 20 Alkyl group, C2~C above 20 Alkenyl group, C2~C above 20 Alkynyl group or the above -C(=O)R a or an aliphatic substituent,

[0029] R 13 and R 14 At least one of the above C1~C 20 Alkyl group, C2~C above 20 Alkenyl group, C2~C above 20 Alkynyl group, C1~C above 20 Alkoxy group or the above -C(=O)R a The above aliphatic substituent, the above C4~C 30 Cycloalkyl group, the above C4~C 30 Heterocycloalkyl group, the above C4~C 30 Cycloalkenyl group, C4~C above 30 Heterocycloalkenyl group, the above C6~C 30 Aryl group or the above C2~C 30 It is a heteroaryl group, and R 13 If this is a hydrogen atom, m is an integer from 1 to 4, and at least one R 14 is not a hydrogen atom,

[0030] Asterisks indicate binding sites.

[0031] R of the above chemical formula 2 11 and R 12 At least one of the above C1~C 20Alkyl group, C2~C above 20 Alkenyl group, C2~C above 20 Alkynyl group or the above -C(=O)R a is the aliphatic substituent, and R 13 and R 14 At least one of the above C1~C 20 Alkyl group, C2~C above 20 Alkenyl group, C2~C above 20 Alkynyl group, C1~C above 20 Alkoxy group or the above -C(=O)R a The above aliphatic substituent is or the above C4~C 30 Cycloalkyl group, the above C4~C 30 Heterocycloalkyl group, the above C4~C 30 Cycloalkenyl group, C4~C above 30 Heterocycloalkenyl group, the above C6~C 30 Aryl group or the above C2~C 30 It is a heteroaryl group, and R 13 If this is a hydrogen atom, m is an integer from 1 to 4, and at least one R 14 is not a hydrogen atom, and R a is C1~C 20 It may be an alkyl group.

[0032] R of the above chemical formula 2 11 and R 12 At least one of the above C1~C 20 Alkyl group or the above -C(=O)R a is an aliphatic substituent, and R 13 and R 14 At least one of them is C1~C 20 Alkyl group, C2~C 20 Alkenyl group, C2~C 20 Alkynyl group, C1~C 20 Alkoxy group and -C(=O)R a is selected from the group consisting of, R 13 If this is a hydrogen atom, m is an integer from 1 to 4, and at least one R 14 is not a hydrogen atom, and R a is C1~C10 Alkyl group or C1~C 20 It could be an alkoxy group.

[0033] R of the above chemical formula 2 11 and R 12 At least one of the above -C(=O)R a and R 13 and R 14 At least one of them is C1~C 20 Alkyl group, C2~C 20 Alkenyl group and C2~C 20 Selected from the group consisting of an alkynyl group, R 13 If this is a hydrogen atom, m is an integer from 1 to 4, and at least one R 14 is not a hydrogen atom, and R a is C1~C 10 It may be an alkyl group.

[0034] R of the above chemical formula 1 1 , R 2 and R 3 Among them, one has the structure of the above chemical formula 2, R 1 , R 2 and R 3 The rest of them are each independently a hydroxyl group or C1~C 20 It is an alkoxy group, and R 4 may be a hydroxyl group or an amino group.

[0035] The above compound may have a structure represented by the following chemical formula 3.

[0036] [Chemical Formula 3]

[0037]

[0038] In chemical formula 3, R 21 has the structure of the following chemical formula 4,

[0039] R 22 and R 23 Each independently represents a hydroxyl group or C1~C 20 It is an alkoxy group,

[0040] R 24is a hydroxyl group or an amino group.

[0041] [Chemical Formula 4]

[0042]

[0043] In chemical formula 4,

[0044] R 31 and R 32 One of them is a hydrogen atom, and R 31 and R 32 Another one among them is C1~C 20 Alkyl group or -C(=O)R b is an aliphatic substituent,

[0045] R 33 Inland R 35 are each independently a hydrogen atom or C1~C 20 Alkyl group, C2~C 20 Alkenyl group, C2~C 20 Alkynyl group and -C(=O)R a An aliphatic substituent selected from the group consisting of, and R 33 Inland R 35 At least one of the above C1~C 20 Alkyl group, C2~C above 20 Alkenyl group, C2~C above 20 Alkynyl group or the above -C(=O)R b And,

[0046] The above R 31 Inland R 35 The aliphatic substituents constituting the above may have -O(C=O)-, -(C=O)O-, -C(=O)-, -O-, -SC(=O)- or -C(=O)S- in the middle,

[0047] The above R b is C1~C 20 It is an alkyl group,

[0048] Asterisks indicate binding sites.

[0049] R of the above chemical formula 4 31 and R 32 One of them is a hydrogen atom, and R 31 and R32 Another one among them is -C(=O)R b and R b is C1~C 10 is an alkyl group, and R 33 Inland R 35 At least one of them is C1~C 10 Alkyl group, C2~C 20 Alkenyl group or C2~C 20 It could be an alkynyl group.

[0050] R of the above chemical formula 4 31 and R 32 One of them is a hydrogen atom, and R 31 and R 32 The other one among them is a methyl group, tert-butyl group or -C(=O)R b and R b is a methyl group, tert-butyl group or tert-butoxy group, and R 33 Inland R 35 At least one of them is C1~C 10 It may be an alkyl group.

[0051] In another aspect, the present disclosure provides a method for producing nicotinamide adenine dinucleotide (NAD) in a cell, comprising the above-described compound, a physiologically acceptable salt thereof, or a stereoisomer thereof as an active ingredient. + ) provides a composition that induces the synthesis of.

[0052] In another aspect, the present disclosure provides an anti-inflammatory composition, or a composition for alleviating or improving inflammation, comprising the compound, a physiologically acceptable salt thereof, or a stereoisomer thereof as an active ingredient.

[0053] In another aspect, the present disclosure provides an anti-aging composition comprising the compound, a physiologically acceptable salt thereof, or a stereoisomer thereof as an active ingredient.

[0054] For example, the above NAD +The composition that induces the synthesis of, the anti-inflammatory composition and / or the anti-aging composition may be a pharmaceutical composition, a functional food composition and / or a cosmetic composition, respectively.

[0055] In another aspect, the present disclosure provides an anti-aging skin topical composition comprising the compound, a physiologically acceptable salt thereof, or a stereoisomer thereof as an active ingredient.

[0056] In another aspect, the present disclosure comprises administering to a subject a physiologically effective amount of the compound, a physiologically acceptable salt thereof, or a stereoisomer thereof, thereby producing nicotinamide adenine dinucleotide (NAD) within the subject, for example, within a cell of the subject. + ) provides a method for inducing the synthesis of.

[0057] In another aspect, the present disclosure provides a method of delaying, preventing and / or inhibiting senescence of a subject, e.g., a cell of the subject, comprising administering to the subject a physiologically effective amount of the compound, a physiologically acceptable salt thereof or a stereoisomer thereof.

[0058] Nicotinamide adenine nucleotide (NAD) + ) have excellent stability, cell permeability, and intracellular delivery properties. Nicotinic acid / nicotinamide riboside derivative compounds, physiologically acceptable salts thereof, and / or stereoisomers thereof are administered to a living body to increase NAD in vivo. + can be synthesized efficiently. Accordingly, NAD + It can delay the aging process associated with a decline in the level of iron and can be used to prevent and treat age-related diseases.

[0059] Nicotinic acid / nicotinamide riboside derivative compounds, physiologically acceptable salts thereof, and / or stereoisomers thereof can be used as active ingredients in pharmaceuticals, health functional foods, and / or functional cosmetics. For example, nicotinic acid / nicotinamide riboside derivative compounds, physiologically acceptable salts thereof, and / or stereoisomers thereof can be used as active ingredients or ingredients in compositions that induce the synthesis of nicotinamide adenine dinucleotide in cells, anti-inflammatory compositions, anti-aging compositions, and / or anti-aging skin topical agents.

[0060] FIG. 1 is a graph showing the results of measuring the thermal stability of a nicotinamide adenine dinucleotide derivative compound synthesized according to an exemplary embodiment of the present disclosure.

[0061] Figure 2 is an NAD of a compound for deriving nicotinamide adenine dinucleotide synthesized according to an exemplary embodiment of the present disclosure. + This is a graph showing the results of measuring the inductive effect.

[0062] FIG. 3 is a graph showing the results of measuring the TNF-alpha biosynthesis inhibitory effect of a nicotinamide adenine dinucleotide derivative synthesized according to an exemplary embodiment of the present disclosure.

[0063] Figure 4 shows the NAD induction in inflammation-inducing cells of a compound for inducing nicotinamide adenine dinucleotide synthesized according to an exemplary embodiment of the present disclosure. + This is a graph showing the results of measuring the inductive effect.

[0064] FIG. 5 is a graph measuring the inhibitory effect of a nicotinamide adenine dinucleotide-derived compound synthesized according to an exemplary embodiment of the present disclosure on ROS production in senescence-inducing cells.

[0065] FIG. 6 is a graph showing the results of measuring the SIRT1 induction effect in senescence-inducing cells of a nicotinamide adenine dinucleotide-inducing compound synthesized according to an exemplary embodiment of the present disclosure.

[0066] FIG. 7 is a graph showing the measurement results according to the SA-β-Gal assay of a nicotinamide adenine dinucleotide derivative synthesized according to an exemplary embodiment of the present disclosure.

[0067] FIG. 8 is a graph showing the results of measuring the skin permeability of a compound for deriving nicotinamide adenine dinucleotide synthesized according to an exemplary embodiment of the present disclosure.

[0068] FIG. 9 is a graph showing the results of measuring the thermal stability of a nicotinamide adenine dinucleotide derivative compound synthesized according to an exemplary embodiment of the present disclosure.

[0069] Figure 10 is an NAD of a compound for deriving nicotinamide adenine dinucleotide synthesized according to an exemplary embodiment of the present disclosure. + This is a graph showing the results of measuring the inductive effect.

[0070] Hereinafter, the present disclosure will be described with reference to the attached drawings when necessary.

[0071] [Nicotinic acid / nicotinamide riboside derivative compound]

[0072] In one aspect, the present disclosure provides nicotinamide adenine dinucleotide (NAD), a coenzyme that performs various functions in vivo. + ) to induce the synthesis of NAD in vivo. + The present invention relates to a nicotinic acid / nicotinamide riboside derivative compound capable of increasing the level or content of NAD+. The compound according to the present invention has excellent stability and exhibits good cell permeability and cell delivery properties, as well as increasing NAD+ levels within cells. + is converted to . Therefore, NAD +It can delay the aging phenomenon associated with a decrease in levels, and can be expected to have effects in preventing and treating age-related diseases. The nicotinic acid / nicotinamide riboside derivative compound can have the structure of the following chemical formula 1.

[0073] [Chemical Formula 1]

[0074]

[0075] In chemical formula 1,

[0076] R 1 , R 2 and R 3 are each independently a hydroxyl group, C1~C 20 An alkoxy group or a structure represented by the following chemical formula 2, R 1 , R 2 and R 3 At least one of them has the structure of the following chemical formula 2,

[0077] R 4 is a hydroxyl group, C1~C 20 An alkoxy group or an amino group.

[0078] [Chemical Formula 2]

[0079]

[0080] In chemical formula 2,

[0081] R 11 and R 12 are each independently a hydrogen atom or C1~C 20 Alkyl group, C2~C 20 Alkenyl group, C2~C 20 Alkynyl group and -C(=O)R a An aliphatic substituent selected from the group consisting of,

[0082] R 13 and R 14 are each independently a hydrogen atom, C1~C 20 Alkyl group, C2~C 20 Alkenyl group, C2~C 20 Alkynyl group, C1~C 20 Alkoxy group and -C(=O)R aAn aliphatic substituent selected from the group consisting of C4~C 30 Cycloalkyl group, C4~C 30 Heterocycloalkyl group, C4~C 30 Cycloalkenyl group, C4~C 30 Heterocycloalkenyl group, C6~C 30 Aryl group or C2~C 30 When it is a heteroaryl group and m is 2 to 4, each R 14 may be identical or different from each other,

[0083] R a is a hydrogen atom, C1~C 20 Alkyl group, hydroxyl group or C1~C 20 It is an alkoxy group,

[0084] The above R 11 Inland R 14 The above C1~C constituting 20 Alkyl group, C2~C above 20 Alkenyl group, C2~C above 20 Alkynyl group, C1~C above 20 Alkoxy group, R above a The above C1~C constituting 20 Alkyl group and the above C1~C 20 Each alkoxy group may have -O(C=O)-, -(C=O)O-, -C(=O)-, -O-, -SC(=O)- or -C(=O)S- in the middle,

[0085] m is an integer from 0 to 4,

[0086] R 11 and R 12 At least one of the above C1~C 20 Alkyl group, C2~C above 20 Alkenyl group, C2~C above 20 Alkynyl group or the above -C(=O)R a or an aliphatic substituent,

[0087] R 13 and R 14 At least one of the above C1~C 20 Alkyl group, C2~C above20 Alkenyl group, C2~C above 20 Alkynyl group, C1~C above 20 Alkoxy group or the above -C(=O)R a The above aliphatic substituent, the above C4~C 30 Cycloalkyl group, the above C4~C 30 Heterocycloalkyl group, the above C4~C 30 Cycloalkenyl group, C4~C above 30 Heterocycloalkenyl group, the above C6~C 30 Aryl group or the above C2~C 30 It is a heteroaryl group, and R 13 If this is a hydrogen atom, m is an integer from 1 to 4, and at least one R 14 is not a hydrogen atom,

[0088] Asterisks indicate binding sites.

[0089] In this specification, an alkyl group, an alkenyl group, an alkynyl group, and an alkoxy group are saturated or unsaturated chain-like aliphatic substituents, including both linear and branched groups. A cycloalkyl group, a heterocycloalkyl group, a cycloalkenyl group, and a heterocycloalkenyl group are saturated or unsaturated cyclic aliphatic substituents. An aryl group and a heteroaryl group may correspond to an aromatic substituent or a heteroaromatic substituent, respectively.

[0090] For example, a cycloalkyl group may include a monovalent functional group corresponding to cyclopropane, cyclobutane, cyclopentane, cyclohexane, or cycloheptane, and a heterocycloalkyl group may include a monovalent functional group corresponding to piperazine, piperidine, or homo-piperazine, but is not limited thereto.

[0091] For example, the aryl group can be an unfused or fused aryl group such as, but not limited to, phenyl, biphenyl, terphenyl, naphthyl, anthracenyl, pentanlenyl, indenyl, indenoindenyl, heptalenyl, biphenylenyl, indacenyl, phenalenyl, phenanthrenyl, benzophenanthrenyl, dibenzophenanthrenyl, azulenyl, pyrenyl, fluoranthenyl, triphenylenyl, chrysenyl, tetraphenyl, tetracenyl, plydaenyl, pycenyl, pentaphenyl, pentacenyl, fluorenyl, indenofluorenyl, or fluorenyl having a spiro structure.

[0092] For example, heteroaryl groups include pyrrolyl, pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, triazinyl, tetrazinyl, imidazolyl, pyrazolyl, indolyl, isoindolyl, indazolyl, indolizinyl, pyrrolizinyl, carbazolyl, benzocarbazolyl, dibenzocarbazolyl, indolocarbazolyl, indenocarbazolyl, benzofurocarbazolyl, benzothienocarbazolyl, quinolinyl, isoquinolinyl, phthalazinyl, quinoxalinyl, cinolinyl, quinazolinyl, quinozolinyl, quinolizinyl, purinyl, benzoquinolinyl, benzoisoquinolinyl, benzoquinazolinyl, benzoquinoxalinyl, acridinyl, phenanthrolinyl, perimidinyl, It may be an uncondensed or condensed heteroaryl group such as, but not limited to, phenanthridinyl, pteridinyl, naphtharidinyl, furanyl, pyranyl, oxazinyl, oxazolyl, oxadiazolyl, triazolyl, dioxynyl, benzofuranyl, dibenzofuranyl, thiopyranyl, xanthenyl, chromenyl, isochromenyl, thioazinyl, thiophenyl, benzothiophenyl, dibenzothiophenyl, difuropyrazinyl, benzofurodibenzofuranyl, benzothienothiophenyl, benzothienodibenzothiophenyl, benzothienofuranyl, benzothienodibenzofuranyl or N-substituted spirofluorenyl.

[0093] In an exemplary embodiment, R of formula 2 11 and R 12 At least one of them may not be a hydrogen atom, and / or R 13 and R 14At least one, at least two, or at least three of them may not be hydrogen atoms. In other words, in formula 2, the amino moiety may have at least one substituent, and / or the indole moiety may have at least one, at least two, or at least three substituents.

[0094] For example, R of the above chemical formula 2 11 and R 12 At least one of the above C1~C 20 Alkyl group, C2~C above 20 Alkenyl group, C2~C above 20 Alkynyl group or the above -C(=O)R a is the aliphatic substituent, and R 13 and R 14 At least one of the above C1~C 20 Alkyl group, C2~C above 20 Alkenyl group, C2~C above 20 Alkynyl group, C1~C above 20 Alkoxy group or the above -C(=O)R a The above aliphatic substituent is or the above C4~C 30 Cycloalkyl group, the above C4~C 30 Heterocycloalkyl group, C4~C 30 Cycloalkenyl group, C4~C 30 Heterocycloalkenyl group, the above C6~C 30 Aryl group or the above C2~C 30 It is a heteroaryl group, and R 13 If this is a hydrogen atom, m is an integer from 1 to 4, and at least one R 14 is not a hydrogen atom, and R a is C1~C 20 Alkyl group or C1~C 20 It could be an alkoxy group.

[0095] In another exemplary embodiment, R of formula 2 11 and R 12 At least one of them is an aliphatic substituent, and R 13 and R 14At least one, at least two, or at least three of them may be aliphatic substituents. For example, R of the above chemical formula 2 11 and R 12 At least one of the above C1~C 20 Alkyl group or the above -C(=O)R a is an aliphatic substituent, and R 13 and R 14 At least one of them is C1~C 20 Alkyl group, C2~C 20 Alkenyl group, C2~C 20 Alkynyl group, C1~C 20 Alkoxy group and -C(=O)R a is selected from the group consisting of, R 13 If this is a hydrogen atom, m is an integer from 1 to 4, and at least one R 14 is not a hydrogen atom, and R a is C1~C 10 Alkyl group or C1~C 20 It could be an alkoxy group.

[0096] In another exemplary embodiment, R of formula 2 11 and R 12 At least one of the above -C(=O)R a and R 13 and R 14 At least one of them is C1~C 20 Alkyl group, C2~C 20 Alkenyl group and C2~C 20 Selected from the group consisting of an alkynyl group, R 13 If this is a hydrogen atom, m is an integer from 1 to 4, and at least one R 14 is not a hydrogen atom, and R a is C1~C 10 Alkyl group or C1~C 20 It could be an alkoxy group.

[0097] In another exemplary embodiment, R of formula 1 1 , R 2 and R 3Among them, one has the structure of the above chemical formula 2, R 1 , R 2 and R 3 The rest of them are each independently a hydroxyl group or C1~C 20 It is an alkoxy group, and R 4 may be a hydroxyl group or an amino group.

[0098] In another exemplary embodiment, R of formula 1 1 can have the structure of chemical formula 2, R 2 and R 3 is a hydroxyl group or C1~C 20 It may be an alkoxy group. For example, a nicotinic acid / nicotinamide riboside derivative compound having a structure of Chemical Formula 1 may have a structure of Chemical Formula 3 below.

[0099] [Chemical Formula 3]

[0100]

[0101] In chemical formula 3, R 21 has the structure of the following chemical formula 4,

[0102] R 22 and R 23 Each independently represents a hydroxyl group or C1~C 20 It is an alkoxy group,

[0103] R 24 is a hydroxyl group or an amino group.

[0104] [Chemical Formula 4]

[0105]

[0106] In chemical formula 4,

[0107] R 31 and R 32 One of them is a hydrogen atom, and R 31 and R 32 Another one among them is C1~C 20 Alkyl group or -C(=O)R b is an aliphatic substituent,

[0108] R33 Inland R 35 are each independently a hydrogen atom or C1~C 20 Alkyl group, C2~C 20 Alkenyl group, C2~C 20 Alkynyl group and -C(=O)R a An aliphatic substituent selected from the group consisting of, and R 33 Inland R 35 At least one of the above C1~C 20 Alkyl group, C2~C above 20 Alkenyl group, C2~C above 20 Alkynyl group or the above -C(=O)R b And,

[0109] The above R 31 Inland R 35 The aliphatic substituents constituting the above may have -O(C=O)-, -(C=O)O-, -C(=O)-, -O-, -SC(=O)- or -C(=O)S- in the middle,

[0110] The above R b is C1~C 20 Alkyl group or C1~C 20 It is an alkoxy group,

[0111] Asterisks indicate binding sites.

[0112] In an exemplary embodiment, R of formula 4 31 and R 32 One of them is a hydrogen atom, and R 31 and R 32 Among them, the other one is an alkyl carbonyl group, and R 33 Inland R 35 At least one of them may be a substituent that is an aliphatic hydrocarbon. For example, R of the above chemical formula 4 31 and R 32 One of them is a hydrogen atom, and R 31 and R 32 Another one among them is -C(=O)R b and R b is C1~C 10 Alkyl group or C1~C 20 It is an alkoxy group, and R33 Inland R 35 At least one of them is C1~C 10 Alkyl group, C2~C 20 Alkenyl group or C2~C 20 It could be an alkynyl group.

[0113] In another exemplary embodiment, R of formula 4 31 and R 32 One of them is a hydrogen atom, and R 31 and R 32 Among them, the other one is an alkyl group such as a methyl group or a tert-butyl group, an acetyl group or a tert-butoxycarbonyl group, and R 33 Inland R 35 At least one of them may be an alkyl group (e.g., tert-butyl group). For example, R in chemical formula 4 31 and R 32 One of them is a hydrogen atom, and R 31 and R 32 The other one among them is a methyl group, tert-butyl group or -C(=O)R b and R b is a methyl group, tert-butyl group or tert-butoxy group, and R 33 Inland R 35 At least one of them is C1~C 10 It may be an alkyl group (e.g., tert-butyl group).

[0114] The compound according to the present disclosure is a moiety having a structure of chemical formula 1 or chemical formula 3 having a nucleoside structure in which nicotinic acid / nicotinamide and a pentose sugar, ribose, are linked via an N-glycosidic bond, and a moiety having a structure of chemical formula 2 or chemical formula 4 including a substituted or unsubstituted amino group and a hydrophobic substituted or unsubstituted indole ring, which are conjugated via an ester bond.

[0115] Nicotinic acid / nicotinamide riboside derivative compounds having structures represented by Chemical Formulas 1 to 4 have excellent cell penetration properties. Under physiological conditions, the ester bond, which is a condensed moiety connecting a nicotinic acid / nicotinamide riboside moiety having a structure represented by Chemical Formula 1 or 3 and a moiety having a structure represented by Chemical Formula 2 or 4, is broken. Accordingly, a nicotinic acid / nicotinamide riboside compound in which a riboside having three hydroxy groups is connected to nicotinic acid or nicotinamide, a nicotinamide / nicotinic acid in which the bond between the riboside moiety and nicotinamide / nicotinic acid is further broken, and a compound having an indole ring as represented by Chemical Formula 2 or 4 are generated.

[0116] The generated nicotinamide riboside (NR) can be converted into nicotinamide mononucleotide (NMN) by the enzyme nicotinamide riboside kinase (NRK) in vivo. Alternatively, the nicotinamide (NAM) compound can be converted into NMN by the enzyme nicotinamide phophoribosyltransferase (NAMPT). NMN converted from NR or NAM can be converted into nicotinamide adenine dinucleotide (NAD) by the enzyme nicotinamide mononucleotide adenylyltransferase (NMNAT) in vivo. + ) can be converted to.

[0117] Alternatively, the generated nicotinic acid (NA) can be converted into nicotinic acid mononucleotide (NAMN) by the enzyme nicotinic acid phosphoribosyltransferase (NAPRT). The moiety represented by chemical formula 2 or chemical formula 4 is converted into quinolinic acid (QA) in vivo, and the converted quinolinic acid can be converted into NAMN by quinolinate phosphoribosyl transferase (QPRT). NAMN is converted into nicotinic acid adenine dinucleotide (NAAD), and NAAD is converted into NAD by nicotinamide adenine dinucleotide synthase (NADS). + can be ultimately synthesized.

[0118] Therefore, nicotinic acid / nicotinamide riboside derivative compounds having structures of chemical formulas 1 to 4 can be used to inhibit NAD in aging cells. + Conversion to or NAD + Synthesis can be efficiently induced.

[0119] The nicotinic acid / nicotinamide riboside derivative compound according to the present disclosure is a conventional NAD such as NMN. + Compared to the precursor, it has superior heat stability, cell permeability, skin permeability, and cell delivery characteristics. In cells, the nicotinic acid / nicotinamide riboside derivative compound having a structure of Chemical Formula 1 to Chemical Formula 4 efficiently induces or biosynthesizes NAD+. Compared to NMN, the nicotinic acid / nicotinamide riboside derivative compound according to the present disclosure has superior anti-inflammatory effects and efficiently promotes induction or biosynthesis of NAD+ in cells induced by inflammation and aging.

[0120] In addition, the nicotinic acid / nicotinamide riboside derivative compound having a structure of Chemical Formula 1 to Chemical Formula 4 reduces the level of reactive oxygen species (ROS) that cause cellular aging. The nicotinic acid / nicotinamide riboside derivative compound according to the present disclosure promotes the expression of SIRT1 (silent information regulator transcript-1, NAD-dependent deacetylase sirtuin-1), which is involved in metabolism, aging inhibition, anticancer, neural differentiation, rRNA synthesis, etc., and reduces the expression of senescence-associated-β-galatosidase (SA-β-gal), an enzyme associated with aging.

[0121] [Functional composition and external skin preparation]

[0122] In another aspect, the present disclosure relates to a functional composition and an anti-aging skin external application comprising a compound having a structure of Chemical Formula 1 to Chemical Formula 4, a physiologically acceptable salt thereof and / or a stereoisomer thereof as an active ingredient. The functional composition comprises nicotinamide adenine dinucleotide (NAD) in a cell. + ) or NAD synthesis + promotes the transformation of cells into , and induces anti-inflammatory, anti-inflammatory and / or anti-aging properties of cells.

[0123] The active ingredient and / or physiologically acceptable salt of the functional composition and / or anti-aging skin topical preparation may include any salt that can be converted into the compound according to the present disclosure in vivo. For example, the physiologically acceptable salt may include a pharmaceutically acceptable salt, a food engineering acceptable salt, and / or a cosmetic engineering acceptable salt. Meanwhile, the stereoisomer of the nicotinic acid / nicotinamide riboside derivative compound according to the present disclosure may be an enantiomer or a diastereomer of the compound.

[0124] As used herein, a physiologically acceptable salt is understood to mean any salt that can be converted into the original compound under in vivo conditions and / or ex vivo conditions, or that can exhibit the same or similar performance as the original compound. For example, a physiologically acceptable salt may include a pharmaceutically acceptable salt, a food- and / or cosmetically acceptable salt.

[0125] For example, the physiologically acceptable salt may include, but is not limited to, an acid addition salt or a basic salt formed by a pharmaceutically acceptable free acid, a food-based acceptable free acid, and / or a cosmetically acceptable free acid. For example, the acid addition salt may be prepared by conventional methods, for example, dissolving the active ingredient, a nicotinic acid / nicotinamide riboside derivative compound, in an excess of an aqueous acid solution, and precipitating the salt using a water-miscible organic solvent, for example, methanol, ethanol, acetone, or acetonitrile. Equimolar amounts of the compound and an acid or alcohol (e.g., glycol monomethyl ether) in water may be heated, and the mixture may then be evaporated to dryness, or the precipitated salt may be filtered off with suction.

[0126] Acid addition salts are obtained from inorganic acids such as hydrochloric, nitric, phosphoric, sulfuric, hydrobromic, hydroiodic, nitrous or phosphorous acids and from non-toxic organic acids such as aliphatic mono- and dicarboxylates, phenyl-substituted alkanoates, hydroxyalkanoates and alkanedioates, aromatic acids, aliphatic and aromatic sulfonic acids. Pharmaceutically / food engineeringly and / or cosmetically non-toxic salts include sulfates, pyrosulfates, bisulfates, sulfites, bisulfites, nitrates, phosphates, monohydrogen phosphates, dihydrogen phosphates, metaphosphates, pyrophosphate chlorides, bromides, iodides, fluorides, acetates, propionates, decanoates, caprylates, acrylates, formates, isobutyrates, caprates, heptanoates, propiolates, oxalates, malonates, succinates, suberates, sebacates, fumarates, maleates, butyn-1,4-dioate, hexane-1,6-dioate, benzoates, chlorobenzoates, methylbenzoates, dinitrobenzoates, hydroxybenzoates, Contains methoxybenzoate, phthalate, terephthalate, benzenesulfonate, toluenesulfonate, chlorobenzenesulfonate, xylenesulfonate, phenylacetate, phenylpropionate, phenylbutyrate, citrate, lactate, β-hydroxybutyrate, glycolate, malate, tartrate, methanesulfonate, propanesulfonate, naphthalene-1-sulfonate, naphthalene-2-sulfonate or mandelate.

[0127] Optionally, a base can be used to prepare a pharmaceutically / food engineering- and / or cosmetically acceptable metal salt. The alkali metal or alkaline earth metal salt is obtained, for example, by dissolving the active ingredient, a nicotinic acid / nicotinamide derivative compound, in an excess of an alkali metal hydroxide or alkaline earth metal hydroxide solution, filtering off the undissolved compound salt, and evaporating and drying the filtrate. In this case, sodium, potassium, or calcium salts are pharmaceutically suitable as the metal salt. In addition, the corresponding silver salt is obtained by reacting the alkali metal or alkaline earth metal salt with a suitable silver salt (e.g., silver nitrate).

[0128] In another aspect, the present disclosure comprises administering to a subject a physiologically effective amount of the compound, a physiologically acceptable salt thereof, or a stereoisomer thereof, thereby producing nicotinamide adenine dinucleotide (NAD) within the subject, for example, within a cell of the subject. + ) and / or a method for delaying, preventing and / or inhibiting aging of a subject, for example, a cell of the subject, comprising administering to the subject a physiologically effective amount of the compound, a physiologically acceptable salt thereof or a stereoisomer thereof.

[0129] The term "physiologically effective amount" as used herein refers to a biological and / or biochemical effect or activity (e.g., NAD+ / - within a cell) + It means an amount sufficient to achieve (stimulation and induction of synthesis or conversion, anti-aging and / or anti-inflammatory) effects. For example, a physiologically effective amount may include a 'pharmaceutically effective amount', a 'food engineering effective amount' and / or a 'cosmetic engineering effective amount'.

[0130] For example, nicotinic acid / nicotinamide riboside derivative compounds having structures of chemical formulas 1 to 4, which are active ingredients of pharmaceutical compositions, cosmetic compositions, food compositions and / or external skin preparations, physiologically acceptable salts thereof and / or stereoisomers thereof, may be included in the functional compositions and / or external skin preparations in a concentration of 0.001 to 0.5 mM, for example, 0.001 to 0.1 mM or 0.0075 to 0.06 mM, but are not limited thereto. Functional compositions and external skin preparations in which the derivative compounds according to the present disclosure, physiologically acceptable salts thereof and / or stereoisomers thereof may be included as active ingredients and / or active ingredients will be described in more detail.

[0131] In an exemplary aspect, the present disclosure relates to an anti-inflammatory or anti-inflammatory composition comprising as an active ingredient a nicotinic acid / nicotinamide derivative compound having a structure represented by Formulae 1 to 4, a pharmaceutically acceptable salt thereof, or a stereoisomer thereof.

[0132] For example, a pharmaceutical composition related to anti-inflammation and / or anti-aging may contain, as an active ingredient, a nicotinic acid / nicotinamide riboside derivative compound having a structure of Chemical Formula 1 to Chemical Formula 4, a pharmaceutically acceptable salt thereof and / or a stereoisomer thereof. If necessary, the pharmaceutical composition may further contain, in addition to the active ingredient and / or active component, additional components, i.e., a pharmaceutically acceptable or nutritionally acceptable carrier, excipient, diluent and / or auxiliary component, depending on the formulation, method of use and intended use of the pharmaceutical composition.

[0133] For example, an anti-inflammatory and / or anti-aging pharmaceutical composition comprising a nicotinic acid / nicotinamide riboside derivative compound, a pharmaceutically acceptable salt thereof and / or a stereoisomer thereof can be formulated and used in the form of oral formulations such as powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols, external preparations, suppositories, and sterile injectable solutions according to conventional methods.

[0134] For example, nicotinic acid / nicotinamide riboside derivative compounds, pharmaceutically acceptable salts thereof, and / or stereoisomers thereof can be administered in various oral or parenteral dosage forms for clinical administration. When formulated, they may further include diluents or excipients such as commonly used fillers, bulking agents, binders, humectants, surfactants, anticoagulants, lubricants, wetting agents, flavoring agents, emulsifiers, or preservatives, and can be used either orally or parenterally.

[0135] For example, carriers, excipients and diluents that can be included in a pharmaceutical composition comprising a nicotinic acid / nicotinamide riboside derivative compound, a pharmaceutically acceptable salt thereof and / or a stereoisomer thereof may include, but are not limited to, at least one selected from the group consisting of lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia gum, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil, dextrin, calcium carbonate, propylene glycol, liquid paraffin and saline solution, and any conventional carrier, excipient or diluent may be used. Ingredients other than the active ingredient may be added independently or in combination.

[0136] More specifically, solid preparations for oral administration include tablets, pills, powders, granules, capsules, etc., and these solid preparations are prepared by mixing nicotinic acid / nicotinamide riboside derivative compounds, pharmaceutically acceptable salts thereof, and / or stereoisomers thereof with one or more excipients, such as starch, calcium carbonate, sucrose or lactose, gelatin, etc. In addition to simple excipients, lubricants such as magnesium stearate and talc are also used. Liquid preparations for oral administration include suspensions, oral solutions, emulsions, and syrups, and in addition to commonly used simple diluents such as water and liquid paraffin, various excipients, such as wetting agents, sweeteners, flavoring agents, and preservatives, may be included.

[0137] Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solutions, suspensions, emulsions, lyophilized preparations, and suppositories. Non-aqueous solutions and suspensions may include propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate. Suppository bases may include witepsol, macrogol, Tween 61, cacao butter, laurin butter, glycerol, gelatin, and glycerogelatin. The pharmaceutical composition of the present disclosure may be administered parenterally via subcutaneous injection, intravenous injection, or intramuscular injection.

[0138] Forms for parenteral administration include toothpaste, mouthwash, topical preparations (creams, ointments, dressing solutions, sprays, other applications, etc.). An example of the formulation of the topical preparation may be a pharmaceutical composition containing an active ingredient impregnated into a carrier such as gauze made of natural or synthetic fibers.

[0139] In the case of a cream or ointment, it may be suitable for direct application to a lesion or inflamed area related to dermatitis (e.g., atopic dermatitis). In the case of a spray, it may be manufactured by a conventional spray manufacturing method, except that it contains an active ingredient, and may be filled and packaged in a pressurized container or other spray container and sprayed on a lesion or inflamed area from time to time to prevent or treat inflammatory diseases or diseases caused by bacteria. In the case of a dressing solution, it may be manufactured by a conventional dressing solution manufacturing method, except that it contains an active ingredient, and may be used for dressing a lesion or dressing other bacterially infected areas to prevent or treat inflammatory diseases or diseases caused by bacteria.

[0140] In addition, the dosage form of the pharmaceutical composition of the present disclosure may take various forms depending on the method of use. For example, the pharmaceutical composition may be formulated by adopting a method known in the art so as to provide rapid, sustained, or delayed release of the active ingredient after administration to a mammal. Specific examples of dosage forms include ointments, granules, lotions, liniments, limonades, powders, syrups, eye ointments, solutions, aerosols, extracts, elixirs, ointments, fluid extracts, emulsions, suspensions, emulsions, infusions, eye drops, tablets, suppositories, injections, tablets, capsules, creams, pills, soft or hard gelatin capsules, and the like.

[0141] Optionally, the anti-inflammatory and / or anti-aging pharmaceutical composition may further contain, in addition to the active ingredient, nutrients, vitamins, electrolytes, flavoring agents, coloring agents, thickeners, pectic acid and its salts, alginic acid and its salts, organic acids, protective colloid thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohol, carbonating agents used in carbonated beverages, etc.

[0142] For example, the anti-inflammatory and / or anti-aging pharmaceutical compositions of the present disclosure can be administered to mammals, such as rats, mice, livestock, and humans, via various routes. Any route of administration is contemplated, including oral, rectal, or intravenous, intramuscular, subcutaneous, intrauterine, or intracerebroventricular injection.

[0143] The preferred dosage of the anti-inflammatory and / or anti-aging pharmaceutical composition comprising the nicotinic acid / nicotinamide riboside derivative compound of the present disclosure, a pharmaceutically acceptable salt thereof, and / or a stereoisomer thereof varies depending on the patient's condition and body weight, the extent of the disease, the drug form, the route of administration, and the duration of the administration, but can be appropriately selected by a person skilled in the art. For example, the anti-inflammatory pharmaceutical composition comprising the nicotinic acid / nicotinamide riboside derivative compound, a pharmaceutically acceptable salt thereof, and / or a stereoisomer thereof can be administered at 0.0001 to 100 mg / kg per day, preferably 0.001 to 100 mg / kg. The administration may be administered once a day or divided into several times. The above dosage does not limit the scope of the present disclosure in any way.

[0144] In another exemplary aspect, the present disclosure relates to an anti-inflammatory, anti-inflammatory, and / or anti-aging food composition or health functional food comprising, as an active ingredient, a nicotinic acid / nicotinamide derivative compound having a structure represented by Formulae 1 to 4, a food-technically acceptable salt thereof, and / or a stereoisomer thereof. Examples of the food composition of the present disclosure include a food, a food additive, a beverage, or a beverage additive. As used herein, a food may include all of a food, a food additive, a health functional food, and a beverage.

[0145] For example, foods containing nicotinic acid / nicotinamide riboside derivative compounds, food engineering acceptable salts thereof and / or stereoisomers thereof include dairy products including meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen, other noodles, gum, ice cream, various soups, beverages, tea, drinks, alcoholic beverages and vitamin complexes, and include all health functional foods in the conventional sense. Additionally, in the present disclosure, food includes, but is not limited to, special nutritional foods (e.g., formula milk, infant / toddler food, etc.), processed meat products, fish products, tofu, starch jelly, noodles (e.g., ramen, noodles, etc.), health supplements, seasoned foods (e.g., soy sauce, soybean paste, red pepper paste, mixed paste, etc.), sauces, confectionery (e.g., snacks), dairy products (e.g., fermented milk, cheese, etc.), other processed foods, kimchi, pickled foods (various kimchi, pickled vegetables, etc.), beverages (e.g., fruit and vegetable beverages, soy milk, fermented beverages, ice cream, etc.), natural seasonings (e.g., ramen soup, etc.), vitamin complexes, alcoholic beverages, liquors, and other health supplements. The above foods, beverages, or food additives can be manufactured by a conventional manufacturing method.

[0146] In addition to the active ingredient, the food composition and / or health functional food may contain food additives acceptable in terms of food engineering, and may further contain suitable carriers, excipients, and diluents commonly used in the manufacture of functional foods.

[0147] For example, the food composition or health functional food of the present disclosure may include forms such as tablets, capsules, pills, and liquids, and other than containing a nicotinic acid / nicotinamide riboside derivative compound, a food engineering-acceptable salt thereof, and / or a stereoisomer thereof as an active ingredient, there are no special limitations on other ingredients, and may contain food auxiliary additive ingredients such as flavoring agents or natural carbohydrates as additional ingredients.

[0148] Examples of natural carbohydrates include common sugars such as monosaccharides (single sugars) such as glucose and fructose; disaccharides (disaccharides) such as maltose and sucrose; and polysaccharides (polysaccharides) such as dextrin and cyclodextrin, as well as sugar alcohols such as xylitol, sorbitol, and erythritol. In addition to the flavorings or sweeteners described above, natural flavorings / sweeteners such as thaumatin and stevia extracts (e.g., rebaudioside A, glycyrrhizin); and synthetic flavorings / sweeteners such as saccharin and aspartame can be used.

[0149] In addition, the food composition and / or health functional food may contain various nutrients, vitamins, minerals (electrolytes), flavoring agents such as synthetic flavoring agents and natural flavoring agents, coloring agents and thickening agents (cheese, chocolate, etc.), pectic acid and its salts, alginic acid and its salts, organic acids, protective colloid thickeners, pH adjusters, stabilizers, preservatives, glycerin, carbonating agents used in alcoholic carbonated beverages, etc. In addition, the food composition according to the present disclosure may contain fruit pulp for the production of natural fruit juices, fruit juice drinks, and vegetable drinks. These ingredients may be used independently or in combination.

[0150] For example, the anti-inflammatory composition, anti-inflammatory composition, and / or anti-aging food composition of the present disclosure may include, in addition to the active ingredient, a nicotinic acid / nicotinamide riboside derivative compound, a pharmaceutically and / or food engineering-acceptable salt thereof, and / or a stereoisomer thereof, carbohydrates, proteins, lipids, vitamins, and minerals. The carbohydrates, proteins, lipids, vitamins, or minerals may be appropriately selected depending on the intended use and application thereof.

[0151] For example, the carbohydrate may be honey, dextrin, sucrose, palatinose, glucose, fructose, corn syrup, sugar alcohol, sorbitol, xylitol, and maltitol. The protein may be casein, whey protein, and other milk-derived proteins, soy protein, and hydrolyzates of these proteins by animal-derived enzymes such as trypsin and pepsin, and neutrase and alkalase. The lipid may be various plant-derived oils and fats such as sunflower oil, rapeseed oil, olive oil, safflower oil, corn oil, soybean oil, palm oil, and palm oil, containing primary saturated fatty acids and polyunsaturated fatty acids, middle-chain fatty acids, EPA, DHA, soybean-derived phospholipids, and milk-derived phospholipids. Minerals may include potassium phosphate, potassium carbonate, potassium chloride, sodium chloride, calcium lactate, calcium gluconate, calcium pantothenate, calcium caseinate, magnesium chloride, ferrous sulfate, and sodium bicarbonate. However, carbohydrates, proteins, lipids, vitamins, and minerals are not limited to the specific ingredients mentioned above.

[0152] In another exemplary aspect, the present disclosure relates to an anti-aging cosmetic composition comprising as an active ingredient a nicotinic acid / nicotinamide riboside derivative compound having a structure represented by Formulae 1 to 4, a cosmetically acceptable salt thereof, and / or a stereoisomer thereof.

[0153] The cosmetic composition comprises a cosmetically and / or dermatologically acceptable medium, i.e., a medium suitable for the skin, mucous membranes, hair and scalp. It may be provided in any cosmetic dosage form suitable for topical application, in particular in the form of an aqueous, aqueous / alcoholic or oily solution, or an aqueous, aqueous / alcoholic or oily gel, or a solid or pasty anhydrous product, an emulsion obtained by dispersing an oil phase in an aqueous phase (O / W) or vice versa (W / O), a suspension, a microemulsion, a microcapsule, a microgranule, or an ionic (liposome) and / or non-ionic vesicular dispersion. These compositions may be prepared according to methods conventional in the art. The composition according to the present disclosure may also be used in the form of a foam or in the form of an aerosol composition further containing a compressed propellant.

[0154] In order to manufacture a functional cosmetic composition, at least one selected from among ethanol, glycerin, butylene glycol, propylene glycol, glycereth-26, methyl gluceth-20, isocetyl myristate, isocetyl octanoate, octyldodecyl myristate, octyldodecanol, isostearyl isostearate, cetyl octanoate, and neopentyl glycol dicaprate may be used as a solvent. When the cosmetic composition of the present disclosure is manufactured using such a solvent, the solubility of the compound in the solvent slightly differs depending on the type of the compound and the mixing ratio of the solvent. However, a person skilled in the art to which the present disclosure pertains can appropriately select the type and amount of the solvent according to the characteristics of the product.

[0155] In addition, the cosmetic composition according to the present disclosure may additionally include cosmetic excipients. Known ingredients used in conventional cosmetics, such as moisturizers, powdered ingredients, UV absorbers, antioxidants, cosmetic ingredients, glycolipids, plant extracts, preservatives, fragrances, pH adjusters, pigments, viscosity adjusters, or gelling agents, may be included as auxiliary ingredients, as long as they do not impair the effects of the present disclosure, i.e., anti-inflammatory, antibacterial, skin wrinkle improvement, skin aging prevention, skin whitening, skin antioxidant, or skin moisturizing effects.

[0156] Non-limiting examples of humectants may be propylene glycol, isoprene glycol, 1,2-heptanediol, 1,3-butylene glycol, dipropylene glycol, hexanediol, polyethylene glycol, glycerin, glycerin, diglycerin, triglycerin, polyglycerin, neopentyl glycol, sorbitol, erythritol, pentaerythritol, glycols such as glucose, galactose, fructose, sucrose, maltose, xylose, xylobiose, reduced oligosaccharides, proteins, mucopolysaccharides, collagen, elastin, keratin, or triethanolamine.

[0157] Non-limiting examples of powder components include white inorganic pigments such as titanium oxide, siliconized titanium oxide, zinc oxide, and barium sulfate; colored inorganic pigments such as iron oxide, carbon black, sintered titanium and titanium oxide, and ultramarine; white body powders such as talc, siliconized talc, muscovite, kaolin, silicon carbide, bentonite, smectite, anhydrous silicic acid, aluminum oxide, magnesium oxide, zirconium oxide, diatomaceous earth, calcium silicate, barium silicate, magnesium silicate, calcium carbonate, magnesium carbonate, hydroxyapatite, and boron nitride; organic polymer resin powders such as titanium dioxide-coated mica, iron oxide mica titanium, siliconized mica titanium, young gourd, polyethylene resin, fluorine resin, cellulose resin, and silicone resin; organic low molecular weight powders such as zinc stearate and N-acylysine; natural organic materials such as starch, silk powder, and cellulose powder. It may be an organic pigment powder such as powder, red No. 201, red No. 202, orange No. 203, orange No. 204, blue No. 404 and yellow No. 401, an organic powder pigment such as zirconium, barium or aluminum lake such as red No. 3, red No. 104, red No. 106, orange No. 205, yellow No. 4, yellow No. 5, green No. 3 and blue No. 1, a gold leaf powder such as mica or gold powder, and a composite powder such as titanium dioxide-coated mica titanium.

[0158] Non-limiting examples of UV absorbers include benzophenone derivatives, para-aminobenzoic acid derivatives, methoxycinnamic acid derivatives, urocanic acid, etc. Non-limiting examples of antioxidants include BHT, BHA, vitamin C, vitamin E, derivatives thereof, and salts thereof. Non-limiting examples of cosmetic ingredients include vitamins including the above vitamins, derivatives thereof, and salts thereof, anti-inflammatory agents, and herbal medicines, etc. Non-limiting examples of glycolipids include sphingoglycolipids, etc. Non-limiting examples of plant extracts include extracts of aloe vera, witch hazel, witch hazel, cucumber, lemon, lavender, and rose, etc. Non-limiting examples of preservatives include methyl parahydroxybenzoate, ethyl parahydroxybenzoate, butyl parahydroxybenzoate, propyl parahydroxybenzoate, phenoxyethanol, and ethanol, etc.

[0159] Non-limiting examples of fragrances include camphor oil, tangerine oil, peppermint oil, jasmine absolute, pine oil, lime oil, lavender oil, rose oil, and musk oil. Non-limiting examples of pH adjusters include edetic acid, sodium edetate, sodium chloride, quenched acid, sodium quenched acid, sodium hydroxide, potassium hydroxide, and triethanolamine. Non-limiting examples of colorants include Blue No. 1, Blue No. 204, Red No. 3, and Yellow No. 201.

[0160] Non-limiting examples of viscosity modifiers may include polyvinyl alcohol (PVA), methylcellulose (MC), ethylcellulose, hydroxypropylmethylcellulose, hydroxypropylethylcellulose, other cellulose derivatives, polyvinylpyrrolidone (PVP), carboxymethylcellulose, xanthan gum, alginic acid or a salt thereof, carrageenan, quince seed powder, alkaline polysaccharides, carboxyvinyl polymers, acrylates, acrylic acid polymers (chain-linked, cross-linked), and acrylic acid-alkyl methacrylate copolymers.

[0161] Non-limiting examples of gelling agents include (behenic / eicosane diacid) glyceryl and (behenic / eicosane diacid) polyglyceryl-10, fatty acid metal salts, hydroxystearic acid, dextrin fatty acid esters, inulin fatty acid esters, sugar fatty acid esters, acylated cellobiose, dibenzylidene sorbitol, amino acid gelling agents, silicic anhydride, organo-modified clay minerals, fumed silica, alumina, cross-linked organopolysiloxanes, hydrocarbon waxes such as polyethylene wax or paraffin wax, vegetable waxes such as carnauba wax or candelilla wax, agar, and gelatin.

[0162] The cosmetic composition of the present disclosure may be manufactured in any formulation commonly manufactured in the relevant industry, and may be formulated as, for example, a solution, a suspension, an emulsion, a paste, a gel, a cream, a lotion, a powder, a soap, a surfactant-containing cleansing, an oil, a powder foundation, an emulsion foundation, a wax foundation, and a spray, but is not limited thereto. More specifically, the cosmetic composition of the present disclosure may be manufactured in the form of a flexible toner, a nourishing toner, a cream, a nourishing cream, a massage cream, an essence, an eye cream, a cleansing cream, a cleansing foam, a cleansing water, a pack, a spray, or a powder.

[0163] In addition, the cosmetic composition of the present disclosure may additionally include one or more cosmetically acceptable carriers that are incorporated into cosmetics, and may appropriately incorporate conventional ingredients such as oil, water, surfactants, moisturizers, lower alcohols, thickeners, chelating agents, pigments, preservatives, fragrances, etc., but is not limited thereto. The cosmetically acceptable carriers included in the cosmetic composition of the present disclosure vary depending on the formulation.

[0164] When the formulation of the cosmetic according to the present disclosure is a paste, cream or gel, animal oil, vegetable oil, wax, paraffin, starch, tragacanth, cellulose derivatives, polyethylene glycol, silicone, bentonite, silica, talc or zinc oxide may be used as a carrier component. When the formulation of the cosmetic according to the present disclosure is a powder or spray, lactose, talc, silica, aluminum hydroxide, calcium silicate or polyamide powder may be used as a carrier component, and particularly in the case of a spray, a propellant such as chlorofluorohydrocarbon, propane / butane or dimethyl ether may be additionally included. In addition, when the cosmetic formulation of the present disclosure is a solution or emulsion, a solvent, a solubilizer or an emulsifier is used as a carrier component, and examples thereof include water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butyl glycol oil, and in particular, cottonseed oil, peanut oil, corn germ oil, olive oil, castor oil and sesame oil, glycerol aliphatic ester, polyethylene glycol or fatty acid ester of sorbitan.

[0165] In addition, when the cosmetic formulation of the present disclosure is a suspension, a liquid diluent such as water, ethanol or propylene glycol, a suspending agent such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol ester and polyoxyethylene sorbitan ester, microcrystalline cellulose, aluminum metahydroxide, bentonite, agar or tragacanth, etc. may be used as a carrier component. In addition, when the cosmetic formulation of the present disclosure is a surfactant-containing cleanser, an aliphatic alcohol sulfate, an aliphatic alcohol ether sulfate, a sulfosuccinic acid monoester, an isethionate, an imidazolinium derivative, a methyl taurate, a sarcosinate, a fatty acid amide ether sulfate, an alkyl amidobetaine, an aliphatic alcohol, a fatty acid glyceride, a fatty acid diethanolamide, a vegetable oil, a lanolin derivative or an ethoxylated glycerol fatty acid ester, etc. may be used as a carrier component.

[0166] Meanwhile, the cosmetic according to the present disclosure may be formulated as a skin lotion, skin softener, skin toner, astringent, lotion, milk lotion, moisture lotion, nutrition lotion, massage cream, nutrition cream, moisture cream, hand cream, essence, nutrition essence, pack, soap, shampoo, cleansing foam, cleansing lotion, cleansing cream, body lotion, body cleanser, milky lotion, pressed powder, loose powder, or eye shadow.

[0167] In another aspect, the present disclosure relates to an anti-aging skin topical composition comprising, as an active ingredient, a nicotinic acid / nicotinamide riboside derivative compound having a structure represented by Formulae 1 to 4, a physiologically acceptable salt thereof, and / or a stereoisomer thereof.

[0168] Topical skin preparations can be formulated in a variety of forms. Specific examples of topical skin preparations include: pastes, lotions, liniments, aromatic waters, aerosols, ointments, emulsions, cataplasmas, creams, and pastes.

[0169] For example, the topical skin preparation of the present disclosure may include a pharmaceutically and / or cosmetically acceptable carrier; a carrier; an excipient; a binder including starch, gum tragacanth, gelatin, molasses, polyvinyl alcohol, polyvinyl ether, polyvinyl pyrrolidone, hydroxypropyl cellulose, methylcellulose, ethylcellulose, and carboxymethylcellulose; a grinding agent including agar, starch, gelatin powder, sodium carboxymethylcellulose, calcium carboxymethylcellulose, crystalline cellulose, calcium carbonate, sodium bicarbonate, and sodium alginate; a lubricant including magnesium stearate, talc, and hydrogenated vegetable oil; and a colorant. The carrier and excipient include lactose, glucose, sucrose, mannitol, potato starch, corn starch, calcium carbonate, calcium phosphate, and cellulose. In addition, additives such as stabilizers, solubilizers, percutaneous absorption promoters, fragrances, and preservatives may be added.

[0170] Hereinafter, the present disclosure will be described through exemplary embodiments, but the present disclosure is not limited to the technical ideas described in the following embodiments.

[0171] [Synthesis Example 1] Synthesis of Nicotinamide Riboside Derivative Compounds

[0172] (1) Synthesis of compound 2,3-diol protected NR(2)

[0173] [Reaction Formula 1-1]

[0174]

[0175] Oleum H2SO4 (0.43 mL, 8.00 mmol) was slowly added dropwise to dried acetonitrile (25 mL) at 0°C under a nitrogen atmosphere. After stirring for about 5 minutes, 2,2-dimethoxypropane (14.40 mL, 117.53 mmol) and nicotinamide riboside chloride (NR chloride, 1, 3.00 g, 11.75 mmol) were sequentially added. The temperature of the solution was gradually increased to room temperature and stirred for about 2 hours. After cooling the reaction mixture to 0°C, solid Na2CO3 (0.64 g, 6.00 mmol) was added and stirred for about 1 hour. Water (0.3 mL) was added and stirred for 1 hour, and the solid present in the reaction mixture was removed by filtration. After removing the solvent from the reaction mixture, compound 2 was obtained by purification using silica gel chromatography using a mixed solvent of dichloromethane (DCM) / methanol (MeOH) (9:1) as the mobile phase (yield: 82%).

[0176] (2) Synthesis of compound 2,3-diol protected NRH(3)

[0177] [Reaction Formula 1-2]

[0178]

[0179] After dissolving compound 2 (2 g) in a small amount of water, NaHCO3 (2.77 g, 33.00 mmol) and Na2S2O4 (2.26 g, 13.00 mmol) were sequentially added. After stirring for about 1 minute, ethyl acetate (EtOAc, 20 mL) was added. After stirring the reaction mixture solution at room temperature for about 2 hours, the organic layer was separated using a separatory funnel, and the solvent was removed to obtain the desired yellow compound 3 (yield: 85%).

[0180] (3) Synthesis of compound protected diol Act-Tbt-NRH(4)

[0181] [Reaction Formula 1-3]

[0182]

[0183] Compound 3 (100 mg, 0.34 mmol) and N-acetyl-2,5,7-tri-t-butyl-L-tryptophan (N-Ac-Tbt-OH, 130 mg, 0.32 mmol) were dissolved in methylene chloride (MC, 10 mL). 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC, 100 mg, 0.52 mmol) and 4-(N,N-dimethylamino)pyridine (DMAP, 4 mg, 0.03 mmol) were sequentially added to the solution, and the mixture was stirred at room temperature for about 2 hours. After removing the reaction solvent, the organic layer was separated using ethyl acetate and saturated NaHCO3, and the solvent was removed. Compound 4 was obtained by purification by silica gel chromatography using a mixed solvent of DCM / MeOH (10:1) as the mobile phase (yield: 75%).

[0184] (4) Compound protected diol Ac-Tbt-NR + Cl - (5) Synthesis

[0185] [Reaction Formula 1-4]

[0186]

[0187] Compound 4 (150 mg, 0.22 mmol) was dissolved in ethyl acetate (10 mL), hexachloroacetone (0.16 mL, 1.1 mmol) was added, and the mixture was stirred at room temperature for about 12 hours. The solvent was removed, and the mixture was purified by silica gel chromatography using a mixed solvent of DCM / MeOH (8:2) as the mobile phase to obtain compound 5 (yield: 70%).

[0188] (5) Compound Ac-Tbt-NR + Cl - (6) Synthesis

[0189] [Reaction Formula 1-5]

[0190]

[0191] Compound 5 (100 mg) was dissolved in a mixture of 4M-HCl in Dioxane: H2O (9:1, 5 mL) and stirred at room temperature for 2 hours. Dried diethyl ether (20 mL) was added to the reaction mixture to obtain compound 6 as a white solid (yield: 95%).

[0192] (6) Synthesis of compound Ac-Tbt-NRH

[0193] [Reaction Formula 1-6]

[0194]

[0195] Compound 6 (100 mg) was dissolved in a small amount of water, and then NaHCO3 (122 mg, 1.5 mmol) and Na2S2O4 (160 mg, 0.73 mmol) were sequentially added. The solution was stirred for about 1 minute, and then ethyl acetate (10 mL) was added. The reaction mixture was stirred at room temperature for about 2 hours, and the organic layer was separated using a separatory funnel, and the solvent was removed. The yellow compound Ac-Tbt-NRH was obtained by purification using silica gel chromatography using a mixed solvent of DCM / MeOH (10:1) as the mobile phase (yield: 88%).

[0196] 1 H NMR (400MHz, CDCl3: δ 7.97(s, 1H), 7.53(s, 1H), 7.44(d, 1H), 7.15(d, 2H), 5.86(d, 1H), 5.37(s, 2H), 4.91-4.82(m, 2H), 4.13-3.96(m, 3H), 3.48-3.30(m,4H), 3.16(d, 1H), 3.11(s, 2H), 2.00(s, 3H), 1.49(s, 9H), 1.47(s, 9H), 1.39(s, 9H).

[0197] [Synthesis Example 2] Synthesis of Nicotinamide Riboside Derivative Compounds

[0198] (1) Synthesis of compound protected diol N-methyl-Tbt-NRH(7)

[0199] [Reaction Formula 2-1]

[0200]

[0201] Compound 3 (120 mg, 0.40 mmol) and N-methyl-2,5,7-tri-t-butyl-L-tryptophan (N-Methyl-Tbt-OH, 130 mg, 0.34 mmol) were dissolved in MC (10 mL). EDC (100 mg, 0.52 mmol) and DMAP (4 mg, 0.03 mmol) were sequentially added to the solution, and the mixture was stirred at room temperature for about 2 h. After removing the reaction solvent, the organic layer was separated using ethyl acetate and saturated NaHCO3, and the solvent was removed. Compound 7 was purified by silica gel chromatography using a mixed solvent of DCM / MeOH (10:1) as the mobile phase (yield: 73%).

[0202] (2) Compound Protected diol N-methyl-Tbt-NR + Cl - (8) Synthesis

[0203] [Reaction Formula 2-2]

[0204]

[0205] Compound 7 (150 mg, 0.23 mmol) was dissolved in ethyl acetate (10 mL), hexachloroacetone (0.16 mL, 1.1 mmol) was added, and the mixture was stirred at room temperature for about 12 hours. The solvent was removed, and the mixture was purified by silica gel chromatography using a mixed solvent of DCM / MeOH (8:2) as the mobile phase to obtain compound 8 (yield: 75%).

[0206] (3) Compound N-methyl-Tbt-NR + Cl - Synthesis of (9)

[0207] [Reaction Formula 2-3]

[0208]

[0209] Compound 8 (100 mg) was dissolved in a mixture of 4M-HCl in Dioxane: H2O (9:1, 5 mL) and stirred at room temperature for 2 hours. Dried diethyl ether (20 mL) was added to the reaction mixture to obtain compound 9 as a white solid (yield: 95%).

[0210] (4) Synthesis of compound N-methyl-Tbt-NRH

[0211] [Reaction Formula 2-4]

[0212]

[0213] Compound 9 (100 mg) was dissolved in a small amount of water, and then NaHCO3 (122 mg, 1.5 mmol) and Na2S2O4 (160 mg, 0.73 mmol) were sequentially added, stirred for about 1 minute, and then ethyl acetate (10 mL) was added. The reaction mixture was stirred at room temperature for about 2 hours, and the organic layer was separated using a separatory funnel, and the solvent was removed. The yellow compound N-methyl-Tbt-NRH was obtained by purification using silica gel chromatography using a mixed solvent of DCM / MeOH (10:1) as the mobile phase (yield: 80%).

[0214] 1 H NMR (400MHz, CDCl3: δ 7.97(s, 1H), 7.53(s, 1H), 7.44(d, 1H), 7.15(d, 2H), 5.86(d, 1H), 5.37(s, 2H), 4.91-4.82(m, 2H), 4.13-3.96(m, 3H), 3.48-3.30(m,4H), 3.26(s, 3H), 3.16(d, 1H), 3.11(s, 2H), 1.49(s, 9H), 1.47(s, 9H), 1.39(s, 9H).

[0215] [Synthesis Example 3] Synthesis of Nicotinamide Riboside Derivative Compounds

[0216] (1) Synthesis of compound Protected diol N-Ac-Dbt-NRH(10)

[0217] [Reaction Formula 3-1]

[0218]

[0219] Compound 3 (128 mg, 0.44 mmol) and N-acetyl-5,7-di-t-butyl-L-tryptophan (N-Ac-Dbt-OH, 130 mg, 0.36 mmol) were dissolved in MC (10 mL). EDC (104 mg, 0.54 mmol) and DMAP (4 mg, 0.03 mmol) were sequentially added to the solution, and the mixture was stirred at room temperature for about 2 hours. After removing the reaction solvent, the organic layer was separated using ethyl acetate and saturated NaHCO3, and the solvent was removed. Compound 10 was obtained by purification by silica gel chromatography using a mixed solvent of DCM / MeOH (10:1) as the mobile phase (yield: 75%).

[0220] (2) Compound Protected diol N-Ac-Dbt-NR + Cl - Synthesis of (11)

[0221] [Reaction Formula 3-2]

[0222]

[0223] Compound 10 (150 mg, 0.23 mmol) was dissolved in ethyl acetate (10 mL), hexachloroacetone (0.16 mL, 1.1 mmol) was added, and the mixture was stirred at room temperature for about 12 hours. The solvent was removed, and the mixture was purified by silica gel chromatography using a mixed solvent of DCM / MeOH (8:2) as the mobile phase, obtaining compound 11 (yield: 78%).

[0224] (3) Compound N-Ac-Dbt-NR + Cl- Synthesis of (12)

[0225] [Reaction Formula 3-3]

[0226]

[0227] Compound 11 (100 mg) was dissolved in a mixture of 4M-HCl in Dioxane: H2O (9:1, 5 mL) and stirred at room temperature for 2 hours. Dried diethyl ether (20 mL) was added to the reaction mixture to obtain compound 12 as a white solid (yield: 93%).

[0228] (4) Synthesis of compound N-Ac-Dbt-NRH

[0229] [Reaction Formula 3-4]

[0230]

[0231] Compound 12 (100 mg) was dissolved in a small amount of water, and then NaHCO3 (122 mg, 1.5 mmol) and Na2S2O4 (160 mg, 0.73 mmol) were sequentially added. The mixture was stirred for about 1 minute, and then ethyl acetate (10 mL) was added. The reaction mixture was stirred at room temperature for about 2 hours, and the organic layer was separated using a separatory funnel, and the solvent was removed. The yellow compound N-Ac-Dbt-NRH was obtained by purification using silica gel chromatography using a mixed solvent of DCM / MeOH (10:1) as a mobile phase (yield: 85%).

[0232] 1 H NMR (400MHz, CDCl3: δ 7.97(s, 1H), 7.53(s, 1H), 7.44(d, 1H), 7.18(s, 1H), 7.15(d, 2H), 5.86(d, 1H), 5.37(s, 2H), 4.91-4.82(m, 2H), 4.13-3.96(m, 3H), 3.48-3.30(m,4H), 3.16(d, 1H), 3.11(s, 2H), 2.00(s, 3H), 1.49(s, 9H), 1.47(s, 9H).

[0233] [Synthesis Example 4] Synthesis of Nicotinamide Riboside Derivative Compounds

[0234] (1) Synthesis of compound Protected diol N-Ac-Trp-NRH(13)

[0235] [Reaction Formula 4-1]

[0236]

[0237] Compound 3 (140 mg, 0.49 mmol) and N-acetyl-L-tryptophan (N-Ac-Trp-OH, 100 mg, 0.41 mmol) were dissolved in MC (10 mL). EDC (118 mg, 0.62 mmol) and DMAP (4 mg, 0.03 mmol) were sequentially added to the solution, and the mixture was stirred at room temperature for about 2 hours. After removing the reaction solvent, the organic layer was separated using ethyl acetate and saturated NaHCO3, and the solvent was removed. Compound 13 was obtained by purification by silica gel chromatography using a mixed solvent of DCM / MeOH (10:1) as the mobile phase (yield: 74%).

[0238] (2) Compound Protected diol N-Ac-Trp-NR + Cl - Synthesis of (14)

[0239] [Reaction Formula 4-2]

[0240]

[0241] Compound 13 (150 mg, 0.29 mmol) was dissolved in ethyl acetate (10 mL), hexachloroacetone (0.16 mL, 1.1 mmol) was added, and the mixture was stirred at room temperature for approximately 12 hours. The solvent was removed, and the mixture was purified by silica gel chromatography using a mixed solvent of DCM / MeOH (8:2) as the mobile phase to obtain compound 14 (yield: 77%).

[0242] (3) Compound N-Ac-Trp-NR + Cl - Synthesis of (15)

[0243] [Reaction Formula 4-3]

[0244]

[0245] Compound 14 (100 mg) was dissolved in a mixture of 4M-HCl in Dioxane: H2O (9:1, 5 mL) and stirred at room temperature for 2 hours. Dried diethyl ether (20 mL) was added to the reaction mixture to obtain compound 15 as a white solid (yield: 93%).

[0246] (4) Synthesis of compound N-Ac-Trp-NRH

[0247] [Reaction Formula 4-4]

[0248]

[0249] Compound 15 (100 mg) was dissolved in a small amount of water, and then NaHCO3 (122 mg, 1.5 mmol) and Na2S2O4 (160 mg, 0.73 mmol) were sequentially added, stirred for about 1 minute, and then ethyl acetate (10 mL) was added. The reaction mixture was stirred at room temperature for about 2 hours, and the organic layer was separated using a separatory funnel, and the solvent was removed. The yellow compound N-Ac-Dbt-NRH was obtained by purification using silica gel chromatography using a mixed solvent of DCM / MeOH (9:1) as a mobile phase (yield: 85%).

[0250] 1 H NMR (400MHz, CDCl3: δ 10.1(s, 1H), 8.0(s, 1H), 7.58(d, 1H), 7.33(d, 1H), 7.20(m, 3H), 7.19(t, 1H), 6.98(t, 1H), 5.72(d, 1H), 4.99(m, 1H), 4.88(m, 1H), 4.55(m, 1H), 4.51(m, 1H), 4.42(m, 1H), 4.32-4.07(m, 2H), 3.90(m, 1H), 3.42-3.17(m, 2H), 3.15(d, 2H), 1.98(s, 3H).

[0251] [Synthesis Example 5] Synthesis of Nicotinamide Riboside Derivative Compounds

[0252] (1) Synthesis of the compound Protected diol N-Boc-Tbt-NRH(16)

[0253] [Reaction Formula 5-1]

[0254]

[0255] Compound 3 (75 mg, 0.25 mmol) and N-tert-butyloxycarbonyl-2,5,7-tri-t-butyl-L-tryptophan (Boc-Tbt-OH, 100 mg, 0.21 mmol) were dissolved in MC (10 mL). EDC (60 mg, 0.32 mmol) and DMAP (4 mg, 0.03 mmol) were sequentially added to the solution, and the mixture was stirred at room temperature for about 2 h. After removing the reaction solvent, the organic layer was separated using ethyl acetate and saturated NaHCO3, and the solvent was removed. Compound 16 was purified by silica gel chromatography using a mixed solvent of DCM / MeOH (10:1) as the mobile phase (yield: 74%).

[0256] (2) Compound Protected diol N-Boc-Tbt-NR + Cl - Synthesis of (17)

[0257] [Reaction Formula 5-2]

[0258]

[0259] Compound 16 (150 mg, 0.20 mmol) was dissolved in ethyl acetate (10 mL), hexachloroacetone (0.16 mL, 1.1 mmol) was added, and the mixture was stirred at room temperature for approximately 12 hours. The solvent was removed, and the mixture was purified by silica gel chromatography using a mixed solvent of DCM / MeOH (8:2) as the mobile phase, to obtain compound 17 (yield: 77%).

[0260] (3) Compound H-Tbt-NR + Cl - Synthesis of (18)

[0261] [Reaction Formula 5-3]

[0262]

[0263] Compound 17 (100 mg) was dissolved in a mixture of 4M-HCl in Dioxane: H2O (9:1, 5 mL) and stirred at room temperature for 2 hours. Dried diethyl ether (20 mL) was added to the reaction mixture to obtain compound 18 as a white solid (yield: 93%).

[0264] (4) Synthesis of compound H-Tbt-NRH

[0265] [Reaction Formula 5-4]

[0266]

[0267] Compound 18 (100 mg) was dissolved in a small amount of water, and then NaHCO3 (122 mg, 1.5 mmol) and Na2S2O4 (160 mg, 0.73 mmol) were sequentially added. The mixture was stirred for about 1 minute, and then ethyl acetate (10 mL) was added. The reaction mixture was stirred at room temperature for about 2 hours, and the organic layer was separated using a separatory funnel, and the solvent was removed. The yellow compound H-Tbt-NRH was obtained by purification using silica gel chromatography using a mixed solvent of DCM / MeOH (9:1) as a mobile phase (yield: 85%).

[0268] 1 H NMR (400MHz, CDCl3: δ 7.97(s, 1H), 7.53(s, 1H), 7.44(d, 1H), 7.15(d, 2H), 5.86(d, 1H), 5.37(s, 2H), 4.91-4.82(m, 2H), 4.13-3.96(m, 3H), 3.48-3.30(m, 4H), 3.16(d, 1H), 3.11(s, 2H), 1.49(s, 9H), 1.47(s, 9H), 1.39(s, 9H).

[0269] [Comparative Synthesis Example 1] Synthesis of Nicotinamide Riboside Derivative Compounds

[0270] (1) Synthesis of the compound Protected diol N-Boc-Trp-NRH(19)

[0271] [Comparative Reaction Formula 1-1]

[0272]

[0273] Compound 3 (112 mg, 0.39 mmol) and N-tert-butyloxycarbonyl-L-tryptophan (Boc-Trp-OH, 100 mg, 0.33 mmol) were dissolved in MC (10 mL). EDC (95 mg, 0.5 0 mmol) and DMAP (4 mg, 0.03 mmol) were sequentially added to the solution, and the mixture was stirred at room temperature for approximately 2 h. After removing the reaction solvent, the organic layer was separated using ethyl acetate and saturated NaHCO3, and the solvent was removed. Compound 19 was obtained by purification by silica gel chromatography using a mixed solvent of DCM / MeOH (10:1) as the mobile phase (yield: 74%).

[0274] (2) Compound Protected diol N-Boc-Trp-NR + Cl - Synthesis of (20)

[0275] [Comparative Reaction Formula 1-2]

[0276]

[0277] Compound 19 (100 mg, 0.17 mmol) was dissolved in ethyl acetate (10 mL), hexachloroacetone (0.16 mL, 1.1 mmol) was added, and the mixture was stirred at room temperature for approximately 12 hours. The solvent was removed, and the mixture was purified by silica gel chromatography using a mixed solvent of DCM / MeOH (8:2) as the mobile phase to obtain compound 20 (yield: 75%).

[0278] (3) Compound H-Trp-NR+ Cl - Synthesis of (21)

[0279] [Comparative Reaction Formula 1-3]

[0280]

[0281] Compound 20 (100 mg) was dissolved in a mixture of 4M-HCl in Dioxane: H2O (9:1, 5 mL) and stirred at room temperature for 2 hours. Dried diethyl ether (20 mL) was added to the reaction mixture to obtain compound 21 as a white solid (yield: 95%).

[0282] (4) Synthesis of compound H-Trp-NRH

[0283] [Comparative Reaction Scheme 1-4]

[0284]

[0285] Compound 21 (100 mg) was dissolved in a small amount of water, and then NaHCO3 (122 mg, 1.5 mmol) and Na2S2O4 (160 mg, 0.73 mmol) were sequentially added. The mixture was stirred for about 1 minute, and then ethyl acetate (10 mL) was added. The reaction mixture was stirred at room temperature for about 2 hours, and the organic layer was separated using a separatory funnel, and the solvent was removed. The yellow compound H-Trp-NRH was obtained by purification using silica gel chromatography using a mixed solvent of DCM / MeOH (9:1) as the mobile phase (yield: 88%).

[0286] 1H NMR (400MHz, CDCl3: δ 10.1(s, 1H), 8.0(s, 1H), 7.58(d, 1H), 7.33(d, 1H), 7.20(m, 3H), 7.19(t, 1H), 6.98(t, 1H), 5.72(d, 1H), 4.99(m, 1H), 4.88(m, 1H), 4.55(m, 1H), 4.51(m, 1H), 4.42(m, 1H), 4.32-4.07(m, 2H), 3.90(m, 1H), 3.42-3.17(m, 2H), 3.15(d, 2H).

[0287] [Example 1] Evaluation of the thermal stability of nicotinamide riboside derivative compounds

[0288] Ac-Tbt-NRH (hereinafter referred to as RP-4), a nicotinamide riboside derivative compound synthesized in Synthesis Example 1, and NAD + The thermal stability of the precursor, NMN, was evaluated. Aqueous solutions of the derivative compound were stored in a sealed container in an incubator at 40°C for 10, 20, and 30 days. The chromatograms were compared with those of the NMN compound to determine the possibility of chemical decomposition or denaturation of the derivative compound. The measurement results are shown in Figure 1.

[0289] In the case of NMN, it was completely decomposed from the 10th day, and the target peak could not be confirmed on the chromatogram, but it was confirmed that the nicotinamide riboside derivative compound synthesized in Synthesis Example 1 remained stable at more than 80.5% until the 30th day. Despite the biological usefulness of NMN, its application to various products in the food, cosmetics, and pharmaceutical fields is difficult due to its poor heat stability, but the nicotinamide riboside derivative compound synthesized in Synthesis Example shows relatively excellent heat stability, showing that it can be applied to various products.

[0290] [Example 2] Effect of nicotinamide riboside derivative compound on NAD in senescent cells+ Inductive measurement

[0291] Compound RP-4, a nicotinamide riboside derivative synthesized in Synthesis Example 1, and NAD of NMN + The induction effect was measured. 2x10 HDF (Human Dermal Fibroblast) cells, which are fibroblasts, were seeded in a 48-well plate. 4 After plating at a concentration of 10 cells / well, cell senescence was induced by treating with DOX (doxorubicin) at a concentration of 0.5 μM for 3 days. Subsequently, the derivative compounds RP-4 and NMN were treated to the senescence-induced cells at a concentration of 0.0075–0.06 mM, respectively. After culturing for 24 h (DMEM, 10% FBS), the cell lysate was collected and the NAD / NADH assay kit was used to measure the NAD in the cell lysate. + The content was measured. The measurement results are shown in Fig. 2.

[0292] As shown in Figure 2, NAD in fibroblasts induced to become senescent by treatment with doxorubicin + The level was decreased. On the other hand, when compound RP-4 was treated in senescent cells, the decreased NAD + It was confirmed that the level was recovered in a concentration-dependent manner. On the other hand, NMN, which was used as a positive control substance in the concentration range used in the test (0.0075–0.06 mM), showed a significant NAD + It did not show any inductive effect. Therefore, NAD + As a booster, it was confirmed that the nicotinamide riboside derivative compound synthesized in the synthetic example can be utilized as a biological anti-aging material.

[0293] [Example 3] Anti-inflammatory effect of nicotinamide riboside derivative compound

[0294] The anti-inflammatory effects of the nicotinamide riboside derivative compound RP-4 synthesized in Synthesis Example 1 and NMN were measured. RAW264.7 cells (KCLB No. 40071), a mouse monocyte cell line, were seeded in a 96-well plate at a density of 5x10 4 After plating at a concentration of 10 cells / well, LPS (lipopolysaccharide) was treated at a concentration of 10 ng / mL. The cells, which had induced TNF-α synthesis, a major factor in the inflammatory response, were treated with derivative compounds and NMN at concentrations of 0.0075–0.06 mM. After culturing for 24 hours (DMEM, 10% FBS), TNF-α produced in the conditioned media was quantified using an ELISA kit. The measurement results are shown in Figure 3.

[0295] The nicotinamide riboside derivative compound RP-4 synthesized in Synthesis Example 1 effectively inhibited the biosynthesis of the anti-inflammatory cytokine TNF-α in a concentration-dependent manner at concentrations of 0.0075 to 0.06 mM. In particular, compound RP-4 significantly inhibited the biosynthesis of TNF-α compared to NMN, which was used as a positive control. These results indirectly demonstrate that the nicotinamide riboside derivative compound synthesized in Synthesis Example 1 has much better cell permeability and bioefficiency compared to NMN.

[0296] [Example 4] NAD in an inflammation-inducing model of a nicotinamide riboside derivative compound + Inductive measurement

[0297] Nicotinamide riboside derivative compound RP-4 synthesized in Synthesis Example 1 and NAD in the inflammation-inducing model of NMN + Induction was measured. RAW264.7 cells (KCLB No. 40071) were seeded in 96-well plates at 5x10 4After plating at a concentration of 10 cells / well, an inflammatory response was induced by treating with LPS (lipopolysaccharide) at a concentration of 10 ng / mL. Nicotinamide riboside derivative compound RP-4 and NMN were treated at a concentration of 0.0075–0.06 mM. After culturing for 24 h (DMEM, 10% FBS), cell lysate was collected and NAD / NADH assay kit was used to measure the NAD in the cell lysate. + The content was measured. The measurement results are shown in Fig. 4.

[0298] In the synthetic example, the synthesized nicotinamide riboside derivative compound RP-4 showed a concentration-dependent decrease in NAD in cells induced with an inflammatory response in a concentration-dependent manner in the range of 0.0075 to 0.06 mM. + showed a recovery effect. In particular, compound RP-4 showed an NAD + The inductive activity was excellent. These results indirectly demonstrate that the nicotinamide riboside derivative compound synthesized in the synthetic example has significantly superior cell permeability and bioefficiency compared to NMN.

[0299] [Example 5] Inhibitory effect of nicotinamide derivative compounds on ROS generation

[0300] The inhibition of reactive oxygen species (ROS) production by RP-4, a nicotinamide derivative compound synthesized in Synthesis Example 1, was measured. HDF cells, which are fibroblasts, were seeded in a 24-well plate at a density of 4x10 4After plating at a concentration of 10 cells / well, cell senescence was induced by treating the cells with DOX (doxorubicin) at a concentration of 0.5 μM for 3 days. Subsequently, the derivative compound was treated at a concentration of 0.015–0.06 mM. After culturing for 72 hours (DMEM, 10% FBS), the medium was removed, and the intracellular ROS content was measured using a DCFDA (2',7'-dichlorofluorescin diacetate) ROS assay kit. The measurement results are shown in Fig. 5.

[0301] As shown in Figure 5, ROS levels increased in fibroblasts induced by DOX treatment. However, treatment with the derivative compound resulted in a concentration-dependent recovery and reduction of the increased ROS levels in the senescent cells. These results demonstrate that nicotinamide riboside derivative compounds, acting as ROS scavengers, can function as biological anti-aging agents.

[0302] [Example 6] SIRT1 induction by nicotinamide riboside derivative compounds

[0303] The induction of SIRT1 by RP-4, a nicotinamide riboside derivative compound synthesized in Synthesis Example 1, and NMN was measured. HDF cells, which are fibroblasts, were seeded in a 24-well plate at a density of 4x10 4 After plating at a concentration of 10 cells / well, DOX (doxorubicin) was treated at a concentration of 0.5 μM for 3 days. After inducing cell senescence, the nicotinamide derivative compounds synthesized in the synthesis example were treated at concentrations of 0.0075–0.06 mM, respectively. After culturing for 24 hours (DMEM, 10% FBS), cell lysates were collected, and the level of SIRT1 expression in the cell lysates was measured using a human SIRT1 ELISA kit. The measurement results are shown in Fig. 6.

[0304] As shown in Fig. 6, the SIRT1 level was reduced in fibroblasts induced by DOX treatment, but when the derivative compound was treated in the senescent cells, the reduced SIRT1 expression level was restored in a concentration-dependent manner. Compared to NMN, which was used as a positive control, the SIRT1 expression level was significantly increased when the derivative compound was treated in the concentration range used in the test (0.0075–0.06 mM). These results demonstrate that nicotinamide riboside derivative compounds, as SIRT1 inducers, can function as biological anti-aging materials.

[0305] [Example 7] Anti-aging effect of nicotinamide riboside derivative compound

[0306] In the senescence-induced model, the degree of anti-aging of the nicotinamide riboside derivatives synthesized in Synthesis Examples 1 to 1 and Comparative Synthesis Examples, and NMN, was analyzed using the Senescence-Associated β-Galactosidase (A-β-gal) assay. HDF cells induced to be senescent in Example 6 were used as the fibroblast senescence model. The measurement results are shown in Fig. 7. The level of SA-β-Gal staining increased in fibroblasts aged by DOX treatment, but when the nicotinamide riboside derivative compound was treated to the senescence-induced cells, the increased SA-β-Gal expression level decreased. These results indicate that the nicotinamide riboside derivative compound synthesized in the Synthesis Examples can be utilized as a biological anti-aging material.

[0307] [Example 8] Evaluation of cell permeability of nicotinamide riboside derivative compounds

[0308] In order to evaluate the cell permeability of the nicotinamide riboside derivative compound RP-4 synthesized in Synthesis Example 1 and NMN, an in vitro skin permeation test was conducted using the Franz Diffusion Cell Assay. The measurement results are shown in Fig. 8. While NMN did not show any significant skin permeability for up to 24 hours, RP-4 showed an excellent skin permeability characteristic of approximately 27.6%. Considering these results, despite its biological usefulness, NMN material has had difficulty in application to the cosmetics and pharmaceutical fields due to its poor skin permeability. However, the nicotinamide riboside derivative compound synthesized in Synthesis Example exhibits excellent skin permeability, and therefore is expected to be applicable to various skin-related products.

[0309] [Example 9] Evaluation of the thermal stability of nicotinamide riboside derivative compounds

[0310] The thermal stability of nicotinamide riboside derivative compounds RP-4 (Ac-Tbt-NRH), N-methyl-Tbt-NRH, synthesized in Synthesis Examples 1 and 2, respectively, and nicotinamide riboside derivative compounds H-Trp-NRH, NMN, synthesized in Comparative Synthesis Example 1, was measured using the same method as in Example 1. The measurement results are shown in Fig. 9.

[0311] As in Example 1, NMN was completely decomposed from the 10th day, confirming its vulnerability to heat. In addition, H-Trp-NRH synthesized in Comparative Synthesis Example 1 was also completely decomposed from the 10th day, and no peak could be confirmed on the chromatogram. RP-4 synthesized in Synthesis Example 1 and N-methyl-Tbt-NRH synthesized in Synthesis Example 2 maintained approximately 80% of their compounds in a stable state until the 30th day.

[0312] [Example 10] Effect of nicotinamide riboside derivative compound on NAD in senescent cells + Inductive measurement

[0313] RP-4 (Ac-Tbt-NRH), N-methyl-Tbt-NRH, which are nicotinamide riboside derivative compounds synthesized in Synthesis Example 1 and Synthesis Example 2, respectively, H-Trp-NRH, a nicotinamide riboside derivative compound synthesized in Comparative Synthesis Example 1, NAD of NMN + The inductive effect was measured using the same method as in Example 2. The measurement results are shown in Fig. 10.

[0314] When compounds RP-4 and N-methyl-Tbt-NRH were treated in senescent cells, the decreased NAD + It was confirmed that the level was recovered in a concentration-dependent manner. On the other hand, NMN used as a positive control substance and H-Trp-NRH synthesized in comparative synthesis example 1 showed significant NAD + It did not show any inductive effect. Therefore, NAD + As a booster, it was confirmed again that the nicotinamide riboside derivative compound synthesized in the synthetic example can be utilized as a biological anti-aging material.

[0315] While the present disclosure has been described above based on exemplary embodiments and examples of the present disclosure, the present disclosure is not limited to the technical concepts described in the embodiments and examples. Rather, those skilled in the art to which the present disclosure pertains can readily devise various modifications and variations based on the aforementioned embodiments and examples. However, it is clear from the appended claims that all such modifications and variations fall within the scope of the present disclosure.

Claims

1. A compound having a structure represented by the following chemical formula 1. [Chemical Formula 1] In chemical formula 1, R 1 , R 2 and R 3 are each independently a hydroxyl group, C1~C 20 An alkoxy group or a structure represented by the following chemical formula 2, R 1 , R 2 and R 3 At least one of them has the structure of the following chemical formula 2, R 4 is a hydroxyl group, C1~C 20 An alkoxy group or an amino group. [Chemical Formula 2] In chemical formula 2, R 11 and R 12 are each independently a hydrogen atom or C1~C 20 Alkyl group, C2~C 20 Alkenyl group, C2~C 20 Alkynyl group and -C(=O)R a An aliphatic substituent selected from the group consisting of, R 13 and R 14 are each independently a hydrogen atom, C1~C 20 Alkyl group, C2~C 20 Alkenyl group, C2~C 20 Alkynyl group, C1~C 20 Alkoxy group and -C(=O)R a An aliphatic substituent selected from the group consisting of C4~C 30 Cycloalkyl group, C4~C 30 Heterocycloalkyl group, C4~C 30 Cycloalkenyl group, C4~C 30 Heterocycloalkenyl group, C6~C 30 Aryl group or C2~C 30 When it is a heteroaryl group and m is 2 to 4, each R 14 may be identical or different from each other, R a is a hydrogen atom, C1~C 20 Alkyl group, hydroxyl group or C1~C 20 It is an alkoxy group, The above R 11 Inland R 14 The above C1~C constituting 20 Alkyl group, C2~C above 20 Alkenyl group, C2~C above 20 Alkynyl group, C1~C above 20 Alkoxy group, R above a The above C1~C constituting 20 Alkyl group and the above C1~C 20 Each alkoxy group may have -O(C=O)-, -(C=O)O-, -C(=O)-, -O-, -SC(=O)- or -C(=O)S- in the middle, m is an integer from 0 to 4, R 11 and R 12 At least one of the above C1~C 20 Alkyl group, C2~C above 20 Alkenyl group, C2~C above 20 Alkynyl group or the above -C(=O)R a or an aliphatic substituent, R 13 and R 14 At least one of the above C1~C 20 Alkyl group, C2~C above 20 Alkenyl group, C2~C above 20 Alkynyl group, C1~C above 20 Alkoxy group or the above -C(=O)R a The above aliphatic substituent, the above C4~C 30 Cycloalkyl group, the above C4~C 30 Heterocycloalkyl group, the above C4~C 30 Cycloalkenyl group, C4~C above 30 Heterocycloalkenyl group, the above C6~C 30 Aryl group or the above C2~C 30 It is a heteroaryl group, and R 13 If this is a hydrogen atom, m is an integer from 1 to 4, and at least one R 14 is not a hydrogen atom, Asterisks indicate binding sites.

2. In paragraph 1, R of the above chemical formula 2 11 and R 12 At least one of the above C1~C 20 Alkyl group, C2~C above 20 Alkenyl group, C2~C above 20 Alkynyl group or the above -C(=O)R a The above aliphatic substituent is R 13 and R 14 At least one of the above C1~C 20 Alkyl group, C2~C above 20 Alkenyl group, C2~C above 20 Alkynyl group, C1~C above 20 Alkoxy group or the above -C(=O)R a The above aliphatic substituent is or the above C4~C 30 Cycloalkyl group, the above C4~C 30 Heterocycloalkyl group, the above C4~C 30 Cycloalkenyl group, C4~C above 30 Heterocycloalkenyl group, the above C6~C 30 Aryl group or the above C2~C 30 It is a heteroaryl group, and R 13 If this is a hydrogen atom, m is an integer from 1 to 4, and at least one R 14 is not a hydrogen atom, R a is C1~C 20 Alkyl group or C1~C 20 A compound containing an alkoxy group.

3. In paragraph 1, R of the above chemical formula 2 11 and R 12 At least one of the above C1~C 20 Alkyl group or the above -C(=O)R a is an aliphatic substituent, R 13 and R 14 At least one of them is C1~C 20 Alkyl group, C2~C 20 Alkenyl group, C2~C 20 Alkynyl group, C1~C 20 Alkoxy group and -C(=O)R a is selected from the group consisting of, R 13 If this is a hydrogen atom, m is an integer from 1 to 4, and at least one R 14 is not a hydrogen atom, R a is C1~C 10 Alkyl group or C1~C 20 A compound containing an alkoxy group.

4. In paragraph 1, R of the above chemical formula 2 11 and R 12 At least one of the above -C(=O)R a And, R 13 and R 14 At least one of them is C1~C 20 Alkyl group, C2~C 20 Alkenyl group and C2~C 20 Selected from the group consisting of an alkynyl group, R 13 If this is a hydrogen atom, m is an integer from 1 to 4, and at least one R 14 is not a hydrogen atom, R a is C1~C 10 Alkyl group or C1~C 20 A compound containing an alkoxy group.

5. In paragraph 1, R of the above chemical formula 1 1 , R 2 and R 3 Among them, one has the structure of the above chemical formula 2, R 1 , R 2 and R 3 The rest of them are each independently a hydroxyl group or C1~C 20 It is an alkoxy group, and R 4 A compound containing a hydroxyl group or an amino group.

6. In paragraph 1, The above compound is a compound having a structure represented by the following chemical formula 3. [Chemical Formula 3] In chemical formula 3, R 21 has the structure of the following chemical formula 4, R 22 and R 23 Each independently represents a hydroxyl group or C1~C 20 It is an alkoxy group, R 24 is a hydroxyl group or an amino group. [Chemical Formula 4] In chemical formula 4, R 31 and R 32 One of them is a hydrogen atom, and R 31 and R 32 Another one among them is C1~C 20 Alkyl group or -C(=O)R b is an aliphatic substituent, R 33 Inland R 35 are each independently a hydrogen atom or C1~C 20 Alkyl group, C2~C 20 Alkenyl group, C2~C 20 Alkynyl group and -C(=O)R a An aliphatic substituent selected from the group consisting of, and R 33 Inland R 35 At least one of the above C1~C 20 Alkyl group, C2~C above 20 Alkenyl group, C2~C above 20 Alkynyl group or the above -C(=O)R b And, The above R 31 Inland R 35 The aliphatic substituents constituting the above may have -O(C=O)-, -(C=O)O-, -C(=O)-, -O-, -SC(=O)- or -C(=O)S- in the middle, The above R b is C1~C 20 Alkyl group or C1~C 20 It is an alkoxy group, Asterisks indicate binding sites.

7. In paragraph 6, R of the above chemical formula 4 31 and R 32 One of them is a hydrogen atom, and R 31 and R 32 Another one among them is -C(=O)R b and R b is C1~C 10 Alkyl group or C1~C 20 It is an alkoxy group, and R 33 Inland R 35 At least one of them is C1~C 10 Alkyl group, C2~C 20 Alkenyl group or C2~C 20 A compound containing an alkynyl group.

8. In paragraph 6, R of the above chemical formula 4 31 and R 32 One of them is a hydrogen atom, and R 31 and R 32 Among them, the other one is a methyl group, a tert-butyl group, or -C(=O)R b and R b is a methyl group, tert-butyl group or tert-butoxy group, and R 33 Inland R 35 At least one of them is C1~C 10 Alkyl group compound.

9. A composition for inducing the synthesis of nicotinamide adenine dinucleotide in a cell, comprising as an active ingredient a compound described in any one of claims 1 to 8, a physiologically acceptable salt thereof, or a stereoisomer thereof.

10. An anti-inflammatory composition comprising a compound described in any one of claims 1 to 8, a physiologically acceptable salt thereof, or a stereoisomer thereof as an active ingredient.

11. An anti-aging composition comprising a compound described in any one of claims 1 to 8, a physiologically acceptable salt thereof, or a stereoisomer thereof as an active ingredient.

12. An anti-aging skin topical agent comprising a compound described in any one of claims 1 to 8, a physiologically acceptable salt thereof, or a stereoisomer thereof as an active ingredient.

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