JP6324777B2 - Collagen production promoter - Google Patents

Description

  The present invention relates to a novel collagen production promoter and a skin external preparation suitable for cosmetics. In the description of the present invention, the term cosmetic is defined as including quasi drugs.

  Deterioration of skin symptoms such as wrinkles, spots, dullness and sagging is a qualitative deterioration in the appearance of the skin that is very obvious even as a sign of aging caused by genetic and environmental factors. Such exacerbation of skin symptoms is due to genetic factors that are born, internal factors such as aging, lifestyle, stress, and active oxygen, as well as external environments such as exposure to ultraviolet rays and drying. The effect of factors greatly contributes to the significant deterioration of skin symptoms. In particular, changes in the three-dimensional shape of the skin, such as wrinkles and sagging, are qualitative deteriorations in the appearance of the skin that can be discerned by the naked eyes of themselves and third parties, and protect the skin from such qualitative deterioration of the skin. In particular, middle-aged and elderly people are very interested in this matter, and various means are required to maintain the beauty of the skin.

  Various methods have been used to improve aging symptoms due to changes in the three-dimensional shape of the skin such as wrinkles and sagging (see Non-Patent Document 1, for example). In the conventional cosmetics field, it has been the mainstream to prevent changes in the three-dimensional shape of the skin caused by external environmental factors such as exposure to ultraviolet rays and drying with a cosmetic containing a moisturizing agent (for example, see Patent Document 1). ). Furthermore, attempts have been made to prevent or ameliorate the skin aging phenomenon by including in the cosmetic a component having an antioxidative action such as direct removal of active oxygen, induction of an enzyme having an active oxygen removing function (for example, (See Non-Patent Documents 2 and 3). In addition, the basic research on skin aging phenomena related to wrinkles and sagging has been actively conducted, so that the formation mechanism of wrinkles or sagging has been gradually elucidated, and various anti-aging agents and wrinkle improving agents based on these information. Etc. have been developed.

Collagen is a fibrous protein that has a structure in which three polypeptide chains with a molecular weight of 95,000 are intertwined, and is present in most tissues such as skin, blood vessels, tendons, and teeth, and is a total protein that constitutes the body. About 30% of the total. Collagen in the skin is produced mainly by dermal fibroblasts and then secreted outside the cell, maintaining the structure between cells together with hyaluronic acid as a major extracellular matrix component, and supporting the elasticity of the cells. Involved in biological activities such as proliferation or function maintenance. In addition, due to the influence of external environmental factors such as UV exposure and drying, and genetic factors such as aging, the decrease in the amount of collagen in the skin and the decrease in function due to degeneration proceed, and these factors cause moisture retention of the skin. Functions and elasticity are reduced, skin tension and gloss are lost, and skin aging symptoms such as rough skin, wrinkles and sagging are promoted. In particular, the photoaging phenomenon due to UV exposure is due to a decrease in type I collagen in the dermis, and is caused by the loss of the balance between the formation and degradation of collagen fibers. In order to prevent or improve such a skin aging phenomenon, a collagen production promoter having a collagen production promoting action (for example, refer to Patent Document 2), a collagenase inhibitor (for example, Patent Document 3) for suppressing degradation of collagen. And dermal fibroblast activator (see, for example, Patent Document 4), fibroblast proliferation promoter (see, for example, Patent Document 5), and the like. However, the conventional components that are supposed to prevent or improve the change in skin shape have not always been sufficiently satisfactory for the intended anti-aging effect, particularly the effect of preventing or improving wrinkle formation. In addition, there are some problems in the stability of the anti-aging component and the preparation containing the component, and also in safety such as irritation. For this reason, it is still desired to develop a novel anti-aging agent, particularly a component that prevents or improves wrinkle formation.

In addition to being used as an important building block in organic synthesis, pyridine derivatives are known to have various biological activities. As the biological activity of the pyridine derivative, antimalarial activity (for example, see Patent Document 6), antibacterial activity (for example, see Non-Patent Document 4), and the like have been reported. Further, among the compounds represented by the general formula (1) described below, 2-chloro -N - is attached to the [(4-fluorophenyl) methyl] -5-phenyl-3-pyridinemethanamine, proteases An anti-inflammatory action and an anti-cancer action (for example, see Patent Document 7) due to an inhibitory action of activated receptor 2 (PAR-2: Proteinase activated receptor-2) have been reported.
Furthermore, it has been reported that the amount of collagen production is increased or decreased by the action via the PAR-2 receptor. As such a report, while there is a report that a collagen degradation inhibitory action (for example, see Non-Patent Document 5) is expressed through a PAR-2 receptor inhibitory action, PAR is an action opposite to the above report. - 2 collagen production increasing action by agonism (e.g., see non-Patent Document 6) is reported there that express. In addition to the above reports, there are documents showing the relationship between the PAR-2 receptor and the increase or decrease in the amount of collagen produced, but details of the relationship have not yet been elucidated. Furthermore, the reports regarding the increase / decrease in the production amount of PAR-2 receptor and collagen are all studies on the increase / decrease in the production amount of PAR-2 receptor and collagen in tissues other than skin or tissue-derived cells. Technical contents in a technical field different from cosmetics. Furthermore, as far as the inventor is aware, the role of PAR-2 receptor in the skin, particularly, the relationship with wrinkle formation has not been reported.
In general, substances with a strong pharmacological action that are aimed at development as pharmaceuticals often have a large safety issue as a side effect when used in cosmetics. It is usually difficult to select substances as active ingredients such as cosmetics.

JP 2008-201775 A JP 2009-249366 A JP 2006-241148 A JP 2005-041812 A JP 2006-241034 A Special table 2009-507824 International publication 2007076055 pamphlet

Aging prevention, whitening, moisturizing cosmetic development technology, CM Publishing, supervised by Masato Suzuki Kitani K. et al., Mech Aging. Dev., 111, 211-221 (1999) Mitani H. et al., Eur. J. Pharmacol., 411, 169-174 (2001) Narender P. et al., Bioorg. Med. Chem., 14 (13), 4600-4609 (2006) Milner JM. Et al., Arthritis Rheum., 62 (7), 1955-1966 (2010) Georgy SR. Et al., Clin. Exp. Pharmcol. Physiol., 37 (3), 328-336 (2010)

  The present invention has been made in view of such a situation, and is suitable as a component of an external preparation for skin such as cosmetics. A collagen production promoter having a novel mother nucleus, and an external skin application containing the collagen production promoter. It is an object to provide an agent, a method for producing the same, and a method for screening a collagen production promoter.

In view of such circumstances, the present inventors have made intensive efforts for a collagen production promoter having a novel mother nucleus structure suitable for cosmetics (including quasi drugs). As a result, the inventors have found that the compounds represented by the general formula (1) described below and / or their pharmacologically acceptable salts are excellent in promoting collagen production, and have completed the present invention. The present invention is as follows.
<1> A collagen production promoter comprising a compound represented by the following general formula (1) and / or a pharmacologically acceptable salt thereof.

(1)
[Wherein, R ₁ represents a hydrogen atom, a halogen atom, an aromatic group, or a linear or branched alkyl group having 1 to 3 carbon atoms which may be substituted with an aromatic group. R ₂ represents a hydrogen atom, a halogen atom, a linear or branched alkyl group having 1 to 6 carbon atoms, or a linear or branched alkoxy group having 1 to 6 carbon atoms. R ₃ represents a hydrogen atom, a hydroxyl group, a formyl group, a carboxyl group, a linear or branched alkyl group having 1 to 8 carbon atoms, a linear or branched alkoxy group having 1 to 8 carbon atoms, a straight chain having 1 to 8 carbon atoms. A chain or branched acyl group, an ester group having a linear or branched alkyl chain having 1 to 8 carbon atoms, an alkyl group having 1 to 8 carbon atoms substituted by an aromatic group, or a straight chain having 1 to 4 carbon atoms Represents a chain or branched alkylamino group. The alkylamino group may each independently have a linear or branched alkyl chain having 1 to 4 carbon atoms as a substituent, and the alkyl group further has an aromatic group as a substituent. Also good. ]

<2> The collagen production promoter according to <1>, wherein the compound represented by the general formula (1) is a compound represented by the following general formula (2).

(2)
[Wherein, R ₄ represents a hydrogen atom, a halogen atom, a hydroxyl group, an amino group, a carboxyl group, a linear or branched alkyl group having 1 to 6 carbon atoms, a linear or branched alkoxy group having 1 to 6 carbon atoms, A linear or branched acyl group having 1 to 6 carbon atoms or a linear or branched ester group having 1 to 6 carbon atoms is represented. R ₅ represents a hydrogen atom, a halogen atom, a linear or branched alkyl group having 1 to 6 carbon atoms, or a linear or branched alkoxy group having 1 to 6 carbon atoms. R ₆ represents a hydrogen atom, a hydroxyl group, a formyl group, a carboxyl group, a linear or branched alkyl group having 1 to 8 carbon atoms, a linear or branched alkoxy group having 1 to 8 carbon atoms, a straight chain having 1 to 8 carbon atoms. A chain or branched acyl group, an ester group having a linear or branched alkyl chain having 1 to 8 carbon atoms, an alkyl group having 1 to 8 carbon atoms substituted by an aromatic group, or a straight chain having 1 to 4 carbon atoms Represents a chain or branched alkylamino group. The alkylamino group may each independently have a linear or branched alkyl chain having 1 to 4 carbon atoms as a substituent, and the alkyl group further has an aromatic group as a substituent. Also good. ]

<3> The collagen production promoter according to <1>, wherein the compound represented by the general formula (1) is a compound represented by the following general formula (4).

(4)
[Wherein, R ₁₀ represents a hydrogen atom, a halogen atom, an aromatic group, or a linear or branched alkyl group having 1 to 3 carbon atoms which may be substituted with an aromatic group. R ₁₁ represents a hydrogen atom, a halogen atom, a linear or branched alkyl group having 1 to 6 carbon atoms, or a linear or branched alkoxy group having 1 to 6 carbon atoms. R ₁₂ is a hydrogen atom, a hydroxyl group, a linear or branched alkyl group having 1 to 8 carbon atoms, an alkoxy group having a linear or branched alkyl chain having 1 to 8 carbon atoms, or the number of carbon atoms substituted by an aromatic group. A 1-8 alkyl group or a C1-C4 linear or branched alkylamino group is represented. The alkylamino group may each independently have a linear or branched alkyl chain having 1 to 4 carbon atoms as a substituent, and the alkyl group further has an aromatic group as a substituent. Also good. ]

<4> The compound represented by the general formula (4) is 2-chloro-5-phenylpyridine (compound 2) or 3-methyl-5-phenylpyridine (compound 4). <3> The collagen production promoter according to <3>.

2-Chloro-5-phenylpyridine (Compound 2)

3-methyl-5-phenylpyridine (compound 4)

<5> The collagen production promoter according to <3>, wherein the compound represented by the general formula (4) is a compound represented by the following general formula (5).

(5)
[Wherein, R ₁₃ represents a hydrogen atom, a halogen atom, an aromatic group, or a linear or branched alkyl group having 1 to 3 carbon atoms which may be substituted with an aromatic group. R ₁₄ represents a hydrogen atom, a halogen atom, a linear or branched alkyl group having 1 to 6 carbon atoms, or a linear or branched alkoxy group having 1 to 6 carbon atoms. R ₁₅ and R ₁₆ each independently represent a hydrogen atom, a linear or branched alkyl group having 1 to 4 carbon atoms, or a linear or branched alkyl group having 1 to 4 carbon atoms substituted by an aromatic group. And m represents an integer of 0 to 4. ]

<6> The collagen production promoter according to <5>, wherein the compound represented by the general formula (5) is a compound represented by the following general formula (6).

(6)
[Wherein, R ₁₇ represents a hydrogen atom, a halogen atom, an aromatic group, or a linear or branched alkyl group having 1 to 3 carbon atoms which may be substituted with an aromatic group. R ₁₈ represents a hydrogen atom, a halogen atom, a linear or branched alkyl group having 1 to 6 carbon atoms, or an alkoxy group having a linear or branched alkyl chain having 1 to 6 carbon atoms. R ₁₉ represents a linear or branched alkyl group having 1 to 4 carbon atoms or a linear or branched alkyl group having 1 to 4 carbon atoms substituted by an aromatic group. ]

<7> The compound represented by the general formula (6) is 2-chloro-N-[(4-fluorophenyl) methyl] -5-phenyl-3-pyridinemethanamine (Compound 1). The collagen production promoter according to <6>.

2-Chloro-N-[(4-fluorophenyl) methyl] -5-phenyl-3-pyridinemethanamine (Compound 1)

<8> The collagen production promoter according to <1>, wherein the compound represented by the general formula (1) is a compound represented by the following general formula (3).

(3)
[Wherein, R ₇ represents a hydrogen atom, a halogen atom, an aromatic group, or a linear or branched alkyl group having 1 to 3 carbon atoms which may be substituted with an aromatic group. R ₈ represents a hydrogen atom, a halogen atom, a linear or branched alkyl group having 1 to 6 carbon atoms, or a linear or branched alkoxy group having 1 to 6 carbon atoms. R ₉ represents a hydrogen atom, a hydroxyl group, a linear or branched alkyl group having 1 to 8 carbon atoms, or a linear or branched alkoxy group having 1 to 8 carbon atoms. ]

<9> Collagen production promotion according to <8>, wherein the compound represented by the general formula (3) is 2-chloro-5-phenylpyridine-3-carboxaldehyde (compound 3) Agent.

2-Chloro-5-phenylpyridine-3-carboxaldehyde (Compound 3)

<10> The collagen production promoter according to any one of <1> to <9>, which has an action mechanism that acts on the epidermis and promotes collagen production in the dermis via the epidermis.
<11> A skin external preparation comprising the collagen production promoter according to any one of <1> to <10>.
<12> The skin external preparation according to <11>, wherein the collagen production promoter is contained in an amount of 0.0001 mass% to 10 mass% with respect to the total amount of the external skin preparation.
<13> The skin external preparation described in <11> or <12>, which is for anti-aging.
<14> The external preparation for skin according to any one of <11> to <13>, which is for prevention or improvement against wrinkle formation.
<15> The external preparation for skin according to any one of <11> to <14>, wherein the collagen production promoting action is a procollagen production promoting action.
<16> The external preparation for skin according to any one of <11> to <15>, which is a cosmetic (including quasi-drugs).

  ADVANTAGE OF THE INVENTION According to this invention, the collagen production promoter which has a novel mother nucleus, the skin external preparation containing this component, and the manufacturing method of the skin external preparation containing this component can be provided. Furthermore, a screening method for a collagen production promoter can be provided.

It is a figure which shows the procollagen production promotion effect | action of the collagen production promoter (compound 1) of this invention. It is a figure which shows the procollagen production promotion effect | action of the collagen production promoter (compound 2) of this invention. It is a figure which shows the procollagen production promotion effect | action of the collagen production promoter (compound 3) of this invention. It is a figure which shows the procollagen production promotion effect | action of the collagen production promoter (compound 4) of this invention.

  The collagen production promoter of the present invention is characterized by comprising a compound represented by the following general formula (1) and / or a pharmacologically acceptable salt thereof. Below, it demonstrates about the compound represented by General formula (1) which is a collagen production promoter of this invention.

(1)
[Wherein, R ₁ represents a hydrogen atom, a halogen atom, an aromatic group, or a linear or branched alkyl group having 1 to 3 carbon atoms which may be substituted with an aromatic group. R ₂ represents a hydrogen atom, a halogen atom, a linear or branched alkyl group having 1 to 6 carbon atoms, or a linear or branched alkoxy group having 1 to 6 carbon atoms. R ₃ represents a hydrogen atom, a hydroxyl group, a formyl group, a carboxyl group, a linear or branched alkyl group having 1 to 8 carbon atoms, a linear or branched alkoxy group having 1 to 8 carbon atoms, a straight chain having 1 to 8 carbon atoms. A chain or branched acyl group, an ester group having a linear or branched alkyl chain having 1 to 8 carbon atoms, an alkyl group having 1 to 8 carbon atoms substituted by an aromatic group, or a straight chain having 1 to 4 carbon atoms Represents a chain or branched alkylamino group. The alkylamino group may each independently have a linear or branched alkyl chain having 1 to 4 carbon atoms as a substituent, and the alkyl group further has an aromatic group as a substituent. Also good. ]

<Collagen production promoter comprising the compound represented by the general formula (1) of the present invention>
The collagen production promoter of the present invention comprises the compound represented by the general formula (1) and / or a pharmacologically acceptable salt thereof. Collagen in the skin is mainly produced as procollagen in dermal fibroblasts, then secreted outside the cell, becomes a collagen molecule by cutting both ends with an enzyme, and these are bound to form a collagen fiber bundle . For this reason, in order to prevent or improve wrinkle formation, it is important to increase the amount of procollagen in its precursor as well as increase the amount of collagen production. The collagen production promoter comprising the compound represented by the general formula (1) of the present invention and / or a pharmacologically acceptable salt thereof is reduced in the skin due to external environmental factors and genetic factors. Has the effect of increasing the amount of collagen. Further, it preferably has an action of increasing the amount of collagen in the dermis. The compound represented by the general formula (1) acts directly on the dermis to increase the amount of collagen, and also acts on the epidermis to increase the amount of collagen produced in the dermis by acting on the dermis via the epidermis. In addition, the compound represented by the general formula (1) not only increases the collagen production amount of the final product, but also increases its precursor procollagen. Procollagen synthesized in dermal fibroblasts is an important intermediate in the process of collagen production in vivo, and the increase or decrease in collagen production is greatly affected by the increase or decrease in production of procollagen. Increasing the value leads to an increase in collagen production.
As an evaluation system for evaluating the collagen production promoting action, in addition to a method of directly measuring the amount of collagen produced using a labeled antibody or the like, a method of measuring collagen synthesis or degrading enzyme activity, a method of measuring the expression level of collagen-producing gene Among these evaluation systems, a method for evaluating the production amount of procollagen is particularly preferable. Among the methods for evaluating the production amount of procollagen, a preferable evaluation method can be specifically exemplified. For example, “procollagen production promoting action evaluation” described in the examples below can be suitably exemplified. It is preferable to make a judgment based on whether or not it has a procollagen production promoting action in the “production promoting action evaluation”. In the “evaluation of procollagen production promoting effect” in the examples described later, having collagen production promoting action means that the amount of procollagen production of the test substance is increased compared to the control group, more preferably the control group Compared with (solvent addition group), the component which shows a procollagen production promotion effect 1.5 times or more can be illustrated suitably.

Furthermore, regarding the collagen production promoter comprising the compound represented by the general formula (1) and / or a pharmacologically acceptable salt thereof according to the present invention, the collagen production promoter is summarized in the epidermis. When administered, it acts on the epidermis, releases a stimulating factor from the cells that make up the epidermis, and this factor promotes procollagen production in the dermis, resulting in increased collagen production in the dermis. I can say that. It should be noted here that the release of the stimulating factor itself is due to the collagen production promoter comprising the compound represented by the general formula (1). This increase is due to the collagen production system originally provided in the living body. For this reason, the collagen production promoting action exerted by the collagen production promoting agent of the present invention is an indirect collagen production promoting action that can reflect the influence of an in vivo feedback mechanism that works during collagen overproduction. Collagen overproduction by a conventional collagen production promoter that works directly on the skin can be more accurately suppressed, and side effects due to overproduction of collagen such as scars can be reduced.

Among the compounds represented by the general formula (1) of the present invention, preferred are compounds represented by the general formulas (2) to (4) described later. Furthermore, among the compounds represented by the general formula (4) described later, more preferred are the compounds represented by the general formula (5) described later, and more preferable are the general formula (6) described later. ). Further, among the compounds represented by the general formulas (1) to (6), a particularly preferable compound is specifically exemplified by 2-chloro-N-[(4-fluorophenyl) methyl] -5-phenyl. -3-pyridinemethanamine (compound 1), 2-chloro-5-phenylpyridine (compound 2), 2-chloro-5-phenylpyridine-3-carboxaldehyde (compound 3), 3-methyl-5-phenylpyridine (Compound 4). The compounds represented by the general formulas (1) to (6) and / or pharmacologically acceptable salts thereof promote collagen production, in particular, act on epidermal keratinocytes and promote collagen production in dermal fibroblasts. Excellent in action. Moreover, it has a high procollagen production promoting action, and by containing it in a skin external preparation, it exhibits an excellent anti-aging action, especially, prevention or improvement action against wrinkle formation. The action of the compounds represented by the general formulas (1) to (6) and / or pharmacologically acceptable salts thereof is an indirect action of promoting collagen production, which is easily affected by a biological feedback mechanism. Therefore, excessive collagen production is unlikely to occur. In other words, the collagen production promoter comprising the compound represented by the general formula (1) exerts its effect in a state where the collagen production is low, and it is not necessary to increase the collagen production amount, that is, the amount of collagen production. In the situation, since it does not show much collagen production promoting effect, it rarely exhibits skin symptoms (side effects) in which collagen production such as scars is excessively promoted. The compounds represented by the general formulas (1) to (6) and / or their pharmacologically acceptable salts exhibit high safety in skin irritation and sensitization tests. Moreover, since it is excellent in solubility in a hydrophilic or lipophilic medium and excellent in stability in each medium and in the preparation, it can be easily formulated into a skin external preparation or the like. Furthermore, it has high accumulation at the target site, excellent skin retention, and exhibits an excellent effect in preventing or improving wrinkle formation.

Here, the compound represented by the general formula (1) will be described. In the formula, R ₁ represents a hydrogen atom, a halogen atom, an unsubstituted or substituted aromatic group, and an unsubstituted or substituted aromatic group. It is selected from the group consisting of a linear or branched alkyl group having 1 to 3 carbon atoms which may be substituted by a group. R ₂ is a hydrogen atom, a halogen atom, a straight chain or branched alkyl group having 1 to 6 carbon atoms, more preferably 1 to 4 carbon atoms, and a straight chain having 1 to 6 carbon atoms, more preferably 1 to 4 carbon atoms. Selected from the group consisting of chain or branched alkoxy groups. R ₃ is a hydrogen atom, a hydroxyl group, a formyl group, a carboxyl group, 1 to 8 carbon atoms, more preferably a linear or branched alkyl group having 1 to 4 carbon atoms, 1 to 8 carbon atoms, more preferably 1 carbon atom. -4 linear or branched alkoxy group, 1 to 8 carbon atoms, more preferably 1 to 4 linear or branched acyl group, 1 to 8 carbon atoms, more preferably 1 to 4 carbon atoms. An ester group having a chain or a branched alkyl chain, an alkyl group having 1 to 8 carbon atoms substituted with an unsubstituted or substituted aromatic group, and a linear or branched alkylamino group having 1 to 4 carbon atoms Selected from the group consisting of The alkylamino group may independently have a linear or branched alkyl chain having 1 to 4 carbon atoms as a substituent, and the alkyl group may further be an unsubstituted or substituted aromatic group. You may have as a substituent. Specific examples of R ₁ include hydrogen atom, fluorine atom, chlorine atom, bromine atom, iodine atom, pyridyl group, methylpyridyl group, ethylpyridyl group, methoxypyridyl group, ethoxypyridyl group, phenyl group, methylphenyl group. , Ethylphenyl group, propylphenyl group, butylphenyl group, methoxyphenyl group, ethoxyphenyl group, propyloxyphenyl group, butyloxyphenyl group, hydroxyphenyl group, aminophenyl group, N-methylaminophenyl group, N-ethylamino Phenyl group, N-propylaminophenyl group, N, N-dimethylaminophenyl group, N, N-diethylaminophenyl group, N, N-dipropylaminophenyl group, N, N-diisopropylaminophenyl group, chlorophenyl group, bromo Phenyl group, fluoropheny Group, difluorophenyl group, trifluoromethylphenyl group, naphthyl group, methylnaphthyl group, ethylnaphthyl group, propylnaphthyl group, methoxynaphthyl group, ethoxynaphthyl group, propyloxynaphthyl group, hydroxynaphthyl group, aminonaphthyl group, N -Methylaminonaphthyl group, N-ethylaminonaphthyl group, N-propylaminonaphthyl group, N, N-dimethylaminonaphthyl group, N, N-diethylaminonaphthyl group, N, N-dipropylaminonaphthyl group, chloronaphthyl group , Fluoronaphthyl group, trifluoromethylnaphthyl group, biphenyl group, methylbiphenyl group, ethylbiphenyl group, propylbiphenyl group, methoxybiphenyl group, ethoxybiphenyl group, propyloxybiphenyl group, hydroxybiphenyl group, amino Biphenyl, chlorobiphenyl, bromobiphenyl, fluorobiphenyl, trifluoromethylbiphenyl, benzyl, methylbenzyl, ethylbenzyl, propylbenzyl, butylbenzyl, methoxybenzyl, ethoxybenzyl, propyloxy Benzyl group, butyloxybenzyl group, hydroxybenzyl group, aminobenzyl group, N-methylaminobenzyl group, N-ethylaminobenzyl group, N-propylaminobenzyl group, N, N-dimethylaminobenzyl group, N, N- Diethylaminobenzyl group, N, N-dipropylbenzyl group, chlorobenzyl group, bromobenzyl group, fluorobenzyl group, difluorobenzyl group, trifluoromethylbenzyl group, phenylethyl group, phenylpropyl group, pyridyl group Group, pyridylethyl group, pyridylpropyl group, naphthylmethyl group, naphthylethyl group, naphthylpropyl group, biphenylmethyl group, biphenylethyl group, biphenylpropyl group and the like can be suitably exemplified, more preferably hydrogen atom, bromine atom A methyl group, an ethyl group, a phenyl group, a fluorophenyl group, and the like can be preferably exemplified. Specific examples of R ₂ include hydrogen atom, fluorine atom, chlorine atom, bromine atom, iodine atom, methyl group, ethyl group, propyl group, butyl group, pentyl group, hexyl group, methoxy group, ethoxy group, propyl group. An oxy group, a butyloxy group, a pentyloxy group, a hexyloxy group and the like can be suitably exemplified, and a hydrogen atom, a fluorine atom, a chlorine atom, a bromine atom, a methyl group and an ethyl group can be suitably exemplified. Specific examples of the R ₃ include hydrogen atom, hydroxyl group, formyl group, carboxy group, methyl group, ethyl group, propyl group, butyl group, pentyl group, hexyl group, heptyl group, octyl group, methoxy group, ethoxy group. Propyloxy group, butyloxy group, pentyloxy group, hexyloxy group, heptyloxy group, octyloxy group, acetyl group, propionyl group, butyryl group, valeryl group, hexanoyl group, heptanoyl group, octanoyl group, methoxycarbonyl group, ethoxy Carbonyl, propyloxycarbonyl, butyloxycarbonyl, pentyloxycarbonyl, hexyloxycarbonyl, heptyloxycarbonyl, octyloxycarbonyl, pyridylmethyl, pyridylethyl, pyridylpropyl, pyridyl Butyl, pyridylpentyl, pyridylhexyl, pyridyloctyl, naphthylmethyl, naphthylethyl, naphthylpropyl, naphthylbutyl, naphthylpentyl, naphthylhexyl, naphthylheptyl, naphthyloctyl, biphenylmethyl Group, biphenylethyl group, biphenylpropyl group, biphenylbutyl group, biphenylpentyl group, biphenylhexyl group, biphenylheptyl group, biphenyloctyl group, benzyl group, phenylethyl group, phenylpropyl group, phenylbutyl group, phenylpentyl group, Phenylhexyl group, phenylheptyl group, phenyloctyl group, methylphenylpropyl group, ethylphenylpropyl group, propylphenylpropyl group, methoxyphenylpropyl group, ethoxyphenyl Lopyl group, propyloxyphenylpropyl group, hydroxyphenylpropyl group, aminophenylpropyl group, N-methylaminophenylpropyl group, N-ethylaminophenylpropyl group, N-propylaminophenylpropyl group, N, N-dimethylaminophenylpropylene Group, N, N-diethylaminophenylpropyl group, N, N-diisopropylaminophenylpropyl group, fluorophenylpropyl group, chlorophenylpropyl group, bromophenylpropyl group, trifluoromethylphenylpropyl group, pyridylmethylaminomethyl group, pyridyl Ethylaminomethyl group, pyridylpropylaminomethyl group, pyridylbutylaminomethyl group, pyridylmethylaminoethyl group, pyridylethylaminoethyl group, pyridylpropylamino Til, pyridylbutylaminoethyl, pyridylmethylaminopropyl, pyridylethylaminopropyl, pyridylpropylaminopropyl, pyridylbutylaminopropyl, pyridylmethylaminobutyl, pyridylethylaminobutyl, pyridylpropylaminobutyl , Pyridylbutylaminobutyl group, N-benzylaminomethyl group, N- (methylbenzyl) aminomethyl group, N- (ethylbenzyl) aminomethyl group, N- (propylbenzyl) aminomethyl group, N- (methoxybenzyl) Aminomethyl group, N- (ethoxybenzyl) aminomethyl group, N- (propyloxybenzyl) aminomethyl group, N- (hydroxybenzyl) aminomethyl group, N- (aminobenzyl) aminomethyl group, N- (N ′ -Methylbenzyl Aminomethyl group, N- (N′-ethylbenzyl) aminomethyl group, N- (N ′, N′-dimethylaminobenzyl) aminomethyl group, N- (N ′, N′-diethylbenzyl) aminomethyl group, N- (chlorobenzyl) aminomethyl group, N- (fluorobenzyl) aminomethyl group, N- (trifluoromethylbenzyl) aminomethyl group, N-phenylethylaminomethyl group, N-phenylpropylaminomethyl group, N- Phenylbutylaminomethyl group, N-benzylaminoethyl group, N-phenylethylaminoethyl group, N-phenylpropylaminoethyl group, N-phenylbutylaminoethyl group, N-benzylaminopropyl group, N-phenylethylaminopropyl group Group, N-phenylpropylaminopropyl group, N-phenylbutylaminopropyl group N-benzylaminobutyl group, N-phenylethylaminobutyl group, N-phenylpropylaminobutyl group, N-phenylbutylaminobutyl group, N, N- (diphenylethyl) aminomethyl group, N, N- (diphenylpropyl) ) Aminomethyl group, N, N- (diphenylbutyl) aminomethyl group, N, N- (dibenzyl) aminoethyl group, N, N- (diphenylethyl) aminoethyl group, N, N- (diphenylpropyl) aminoethyl Group, N, N- (diphenylbutyl) aminoethyl group, N, N- (dibenzyl) aminopropyl group, N, N- (diphenylethyl) aminopropyl group, N, N- (diphenylpropyl) aminopropyl group, N , N- (diphenylbutyl) aminopropyl group, N, N- (dibenzyl) aminobutyl group, N, N- Diphenylethyl) aminobutyl group, N, N- (diphenylpropyl) aminobutyl group, N, N- (diphenylbutyl) aminobutyl group, naphthylmethylaminomethyl group, naphthylethylaminomethyl group, naphthylpropylaminomethyl group, naphthyl Butylaminomethyl group, naphthylmethylaminoethyl group, naphthylethylaminoethyl group, naphthylpropylaminoethyl group, naphthylbutylaminoethyl group, naphthylmethylaminopropyl group, naphthylethylaminopropyl group, naphthylpropylaminopropyl group, naphthylbutylamino Propyl group, naphthylmethylaminobutyl group, naphthylethylaminobutyl group, naphthylpropylaminobutyl group, naphthylbutylaminobutyl group, biphenylmethylaminomethyl group, biphenylethyl Ruaminomethyl group, biphenylpropylaminomethyl group, biphenylbutylaminomethyl group, biphenylmethylaminoethyl group, biphenylethylaminoethyl group, biphenylpropylaminoethyl group, biphenylbutylaminoethyl group, biphenylmethylaminopropyl group, biphenylethylaminopropyl group Preferred examples include biphenylpropylaminopropyl group, biphenylbutylaminopropyl group, biphenylmethylaminobutyl group, biphenylethylaminobutyl group, biphenylpropylaminobutyl group, biphenylbutylaminobutyl group and the like. More preferred are a hydrogen atom, a formyl group, a methyl group, an ethyl group, a benzylaminomethyl group, and a fluorobenzylaminomethyl group.

  The compound represented by the general formula (1) is preferably a compound represented by the following general formula (2).

(2)

In the formula, R ₄ is a hydrogen atom, a halogen atom, a hydroxyl group, an amino group, a carboxyl group, a carbon number of 1 to 6, more preferably a linear or branched alkyl group having 1 to 4 carbon atoms, a carbon number of 1 to 6, More preferably, it is a linear or branched alkoxy group having 1 to 4 carbon atoms, 1 to 6 carbon atoms, more preferably a linear or branched acyl group having 1 to 4 carbon atoms, and 1 to 6 carbon atoms, more preferably It is selected from the group consisting of ester groups having a linear or branched alkyl chain having 1 to 4 carbon atoms. R ₅ is a hydrogen atom, a halogen atom, a straight or branched alkyl group having 1 to 6 carbon atoms, more preferably 1 to 4 carbon atoms, and a straight chain having 1 to 6 carbon atoms, more preferably 1 to 4 carbon atoms. Selected from the group consisting of chain or branched alkoxy groups. R ₆ is a hydrogen atom, a hydroxyl group, a formyl group, a carboxyl group, 1 to 8 carbon atoms, more preferably a linear or branched alkyl group having 1 to 4 carbon atoms, 1 to 8 carbon atoms, more preferably 1 carbon atom. -4 linear or branched alkoxy group, 1 to 8 carbon atoms, more preferably 1 to 4 linear or branched acyl group, 1 to 8 carbon atoms, more preferably 1 to 4 carbon atoms. 1 to 8 carbon atoms, more preferably an alkyl group having 1 to 4 carbon atoms, and more preferably 1 to 4 carbon atoms substituted by an ester group having a chain or branched alkyl chain, an unsubstituted or substituted aromatic group Selected from the group consisting of linear or branched alkylamino groups. The alkylamino group may each independently have a linear or branched alkyl chain having 1 to 4 carbon atoms as a substituent, and the alkyl group further has an aromatic group as a substituent. Also good. Specific examples of the compound represented by the general formula (2) include 2-chloro-N-[(4-fluorophenyl) methyl] -5-phenyl-3-pyridinemethanamine (Compound 1), N -Benzyl-2-chloro-5-phenyl-3-pyridinemethanamine, 2-chloro-N-[(methylphenyl) methyl] -5-phenyl-3-pyridinemethanamine, 2-chloro-N-[(ethyl Phenyl) methyl] -5-phenyl-3-pyridinemethanamine, 2-chloro-5-phenyl-N-[(propylphenyl) methyl] -3-pyridinemethanamine, 2-chloro-N-[(methoxyphenyl) Methyl] -5-phenyl-3-pyridinemethanamine, 2-chloro-N-[(ethoxyphenyl) methyl] -5-phenyl-3-pyridinemethanamine, 2-chloro-5-phenyl Cycloalkenyl -N - [(propyloxy) methyl] -3-pyridinemethanamine, 2-chloro -N - [(hydroxyphenyl) methyl]
-5-phenyl-3-pyridinemethanamine, N-[(aminophenyl) methyl] -2-chloro-5-phenyl-3-pyridinemethanamine, 2-chloro-N-[(N'-methylaminophenyl) Methyl] -5-phenyl-3-pyridinemethanamine, 2-chloro-N-[(N′-ethylaminophenyl) methyl] -5-phenyl-3-pyridinemethanamine,
2-chloro-5-phenyl-N-[(N'-propylphenyl) methyl] -3-pyridinemethanamine, 2-chloro-N-[(N ', N'-dimethylphenyl) methyl] -5-phenyl -3-pyridinemethanamine, 2-chloro-N-[(N ′, N′-diethylphenyl)
Methyl] -5-phenyl-3-pyridinemethanamine, 2-chloro-N-[(N ′, N′-dipropylphenyl) methyl] -5-phenyl-3-pyridinemethanamine, N-[(bromophenyl) ) Methyl] -2-chloro-5-phenyl-3-pyridinemethanamine, 2-chloro-N-[(fluorophenyl) methyl] -5-phenyl-3-pyridinemethanamine, 2-chloro-N-[( Difluorophenyl) methyl] -5-phenyl-3-pyridinemethanamine, 2-chloro-5-phenyl-N-[(trifluoromethylphenyl) methyl] -3-pyridinemethanamine, 2-chloro-5-pyridyl- N- (benzyl) -3-pyridinemethanamine, 2-chloro-5-naphthyl-N- (benzyl) -3-pyridinemethanamine, 2-chloro-5-biphenyl-N -(Benzyl) -3-pyridinemethanamine, 5-benzyl-N-benzyl-2-chloro-3-pyridinemethanamine, 5-benzyl-2-
Chloro-N-[(methylphenyl) methyl] -3-pyridinemethanamine, 5-benzyl-2-chloro-N-[(ethylphenyl) methyl] -3-pyridinemethanamine, 5-benzyl-2-chloro- N-[(propylphenyl) methyl] -3-pyridinemethanamine, 5-benzyl-2-chloro-N-[(methoxyphenyl) methyl] -3-pyridinemethanamine, 5-benzyl-2-chloro-N- [(Ethoxyphenyl) methyl] -3-pyridinemethanamine, 5-benzyl-2-chloro-N-[(propyloxyphenyl) methyl] -3-pyridinemethanamine, 5-benzyl-2-chloro-N- [ (Hydroxyphenyl) methyl] -3-pyridinemethanamine, N-[(aminophenyl) methyl] -5-benzyl-2-chloro-3-pyridinemethanamine, 5-Benzyl-2-chloro-N-[(N′-methylaminophenyl) methyl] -3-pyridinemethanamine, 5-benzyl-2-chloro-N-[(N′-ethylaminophenyl) methyl]- 3-pyridinemethanamine, 5-benzyl-
2-chloro-N-[(N′-propylphenyl) methyl] -3-pyridinemethanamine, 5-benzyl-2-chloro-N-[(N ′, N′-dimethylphenyl) methyl] -3-pyridine Methanamine, 5-benzyl-2-chloro-N-[(N ′, N′-diethylphenyl)
Methyl] -3-pyridinemethanamine, 5-benzyl-2-chloro-N-[(N ′, N′-dipropylphenyl) methyl] -3-pyridinemethanamine, 5-benzyl-N-[(bromophenyl) ) Methyl] -2-chloro-3-pyridinemethanamine, 5-benzyl-2-chloro-N-[(fluorophenyl) methyl] -3-pyridinemethanamine, 5-benzyl-2-chloro-N-[( Difluorophenyl) methyl] -3-pyridinemethanamine, 5-benzyl-2-chloro-N-[(trifluoromethylphenyl) methyl] -3-pyridinemethanamine, 2-chloro-5-pyridylmethyl-N- ( Benzyl) -3-pyridinemethanamine, 2-chloro-5-naphthylmethyl-N- (benzyl) -3-pyridinemethanamine, 2-chloro-5-biphenylmethyl -N- (benzyl) -3-pyridinemethanamine, N-benzyl-2-methyl-5-phenyl-3-pyridinemethanamine, 2-methyl-N-[(methylphenyl) methyl] -5-phenyl-3 -Pyridinemethanamine, N-[(ethylphenyl) methyl] -2-methyl-5-phenyl-3-pyridinemethanamine, 2-
Methyl-5-phenyl-N-[(propylphenyl) methyl] -3-pyridinemethanamine, N-[(methoxyphenyl) methyl] -2-methyl-5-phenyl-3-pyridinemethanamine, N-[( Ethoxyphenyl) methyl] -2-methyl-5-phenyl-3-pyridinemethanamine, 2-methyl-5-phenyl-N-[(propyloxyphenyl) methyl] -3-pyridinemethanamine, N-[(hydroxy Phenyl) methyl] -2-methyl-5-phenyl-3-pyridinemethanamine, N-[(aminophenyl) methyl] -2-methyl-5-phenyl-3-pyridinemethanamine, 2-methyl-N- [ (N′-methylaminophenyl) methyl] -5-phenyl-3-pyridinemethanamine, N-[(N′-ethylaminophenyl) methyl] -2-methyl-5 Enyl-3-pyridinemethanamine, 2-methyl-5-phenyl-N-[(N′-propylphenyl) methyl] -3-pyridinemethanamine, N-[(N ′, N′-dimethylphenyl) methyl] 2-methyl-5-phenyl-3-pyridinemethanamine, N-[(N ′, N′-diethylphenyl) methyl] -2-methyl-5-phenyl-3-pyridinemethanamine, N-[(N ', N'-dipropylphenyl)
Methyl] -2-methyl-5-phenyl-3-pyridinemethanamine, N-[(bromophenyl) methyl] -2-methyl-5-phenyl-3-pyridinemethanamine, N-[(fluorophenyl) methyl] 2-methyl-5-phenyl-3-pyridinemethanamine, N-[(difluorophenyl) methyl] -2-methyl-5-phenyl-3-pyridinemethanamine,
2-methyl-5-phenyl-N-[(trifluoromethylphenyl) methyl] -3-pyridinemethanamine, N-benzyl-2-methoxy-5-phenyl-3-pyridinemethanamine, 2-methoxy-N- [(Methylphenyl) methyl] -5-phenyl-3-pyridinemethanamine, N-[(ethylphenyl) methyl] -2-methoxy-5-phenyl-3-pyridinemethanamine, 2-methoxy-5-phenyl- N-[(propylphenyl) methyl] -3-pyridinemethanamine, N-[(methoxyphenyl) methyl] -2-methoxy-5-phenyl-3-pyridinemethanamine, N-[(ethoxyphenyl) methyl]- 2-methoxy-
5-phenyl-3-pyridinemethanamine, 2-methoxy-5-phenyl-N-[(propyloxyphenyl) methyl] -3-pyridinemethanamine, N-[(hydroxyphenyl) methyl] -2-methoxy-5 -Phenyl-3-pyridinemethanamine, N-[(aminophenyl) methyl] -2-methoxy-5-phenyl-3-pyridinemethanamine, 2-methoxy-N-[(N'-methylaminophenyl) methyl] -5-phenyl-3-pyridinemethanamine, N-[(N'-ethylaminophenyl) methyl] -2-methoxy-5-phenyl-3-pyridinemethanamine, 2-methoxy-5-phenyl-N- [ (N′-propylphenyl) methyl] -3-pyridinemethanamine, N-[(N ′, N′-dimethylphenyl) methyl] -2-methoxy-5-phenyl-3- Pyridinemethanamine, N-[(N ′, N′-diethylphenyl) methyl] -2-methoxy-5-phenyl-3-pyridinemethanamine, N-[(N ′, N′-dipropylphenyl) methyl] 2-methoxy-5-phenyl-3-pyridinemethanamine, N-[(bromophenyl) methyl] -2-methoxy-5-phenyl-3-pyridinemethanamine, N-[(fluorophenyl) methyl] -2 -Methoxy-5-phenyl-3-pyridinemethanamine, N-[(difluorophenyl) methyl] -2-methoxy-5-phenyl-3-pyridinemethanamine, 2-methoxy-5-phenyl-N-[(tri Fluoromethylphenyl) methyl] -3-pyridinemethanamine,
2-chloro-5-phenylpyridine (compound 2), 2-chloro-5- (methylphenyl) pyridine, 2-chloro-5- (ethylphenyl) pyridine, 2-chloro-5- (propylphenyl) pyridine, 2 -Chloro-5- (methoxyphenyl) pyridine, 2-chloro-5- (ethoxyphenyl) pyridine, 2-chloro-5- (propyloxyphenyl) pyridine, 2-chloro-5- (hydroxyphenyl) pyridine, 5- (Aminophenyl) -2-chloropyridine, 2-chloro-5- (N-methylphenyl) pyridine, 2-chloro-5- (N-ethylphenyl) pyridine, 2-chloro-5- (N-propylphenyl) Pyridine, 2-chloro-5- (N, N-dimethylphenyl) pyridine, 2-chloro-5- (N, N-diethylphenyl) pyrid 2-chloro-5- (N, N-diisopropylphenyl) pyridine, 2-chloro-5- (chlorophenyl) pyridine, 2-chloro-5- (fluorophenyl) pyridine, 2-chloro-5- (trifluoromethyl) Phenyl) pyridine, 2-chloro-5-phenylpyridine-3-carboxaldehyde (compound 3), 2-chloro-5- (methylphenyl) pyridine-3-carboxaldehyde, 2-chloro-5- (ethylphenyl) pyridine -3-carboxaldehyde, 2-chloro-5- (propylphenyl) pyridine-3-carboxaldehyde, 2-chloro-5- (methoxyphenyl) pyridine-3-carboxaldehyde, 2-chloro-5- (ethoxyphenyl) Pyridine-3-carboxaldehyde, 2-chloro-5- (propylo Cyphenyl) pyridine-3-carboxaldehyde, 2-chloro-5- (hydroxyphenyl) pyridine-3-carboxaldehyde, 5- (aminophenyl) -2-chloropyridine-3-carboxaldehyde, 2-chloro-5- ( N-methylphenyl) pyridine-3-carboxaldehyde, 2-chloro-5- (N-ethylphenyl) pyridine-3-carboxaldehyde, 2-chloro-5- (N-propylphenyl) pyridine-3-carboxaldehyde, 2-chloro-5- (N, N-dimethylphenyl) pyridine-3-carboxaldehyde, 2-chloro-5- (N, N-diethylphenyl) pyridine-3-carboxaldehyde, 2-chloro-5- (N , N-diisopropylphenyl) pyridine-3-carboxaldehyde, 2- Chloro-5- (chlorophenyl) pyridine-3-carboxaldehyde, 2-chloro-5- (fluorophenyl) pyridine-3-carboxaldehyde, 2-chloro-5- (trifluoromethylphenyl) pyridine-3-carboxaldehyde, 3-methyl-5-phenylpyridine (compound 4), 3-methyl-5- (methylphenyl) pyridine, 5- (ethylphenyl) -3-methylpyridine, 3-methyl-5- (propylphenyl) pyridine, 5 -(Methoxyphenyl) -3-methylpyridine, 5- (ethoxyphenyl) -3-methylpyridine, 3-methyl-5- (propyloxyphenyl) pyridine, 5- (hydroxyphenyl) -3-methylpyridine, 5- (Aminophenyl) -3-methylpyridine, 3-methyl-5- (N-methyla) Nophenyl) pyridine, 5- (N-ethylaminophenyl) -3-methylpyridine, 3-methyl-5- (N-propylaminophenyl) pyridine, 5- (N, N-dimethylaminophenyl) -3-methylpyridine 5- (N, N-diethylaminophenyl) -3-methylpyridine, 5- (N, N-diisopropylaminophenyl) -3-methylpyridine, 5- (chlorophenyl) -3-methylpyridine, 5- (fluorophenyl) ) -3-methylpyridine, 5- (bromophenyl) -3-methylpyridine, 3-methyl-5- (trifluoromethylphenyl) pyridine, 2-chloro-3-methyl-5-phenylpyridine, 2-chloro- 3-methyl-5- (methylphenyl) pyridine, 2-chloro-5- (ethylphenyl) -3-methylpyridine 2-chloro-3-methyl-5- (propylphenyl) pyridine, 2-chloro-5- (methoxyphenyl) -3-methylpyridine, 2-chloro-5- (ethoxyphenyl) -3-methylpyridine, 2- Chloro-3-methyl-5- (propyloxyphenyl) pyridine, 2-chloro-5- (hydroxyphenyl) -3-methylpyridine, 2-chloro-5- (aminophenyl) -3-methylpyridine, 2-chloro -3-methyl-5- (N-methylaminophenyl) pyridine, 2-chloro-5- (N-ethylaminophenyl) -3-methylpyridine, 2-chloro-3-methyl-5- (N-propylamino) Phenyl) pyridine, 2-chloro-5- (N, N-dimethylaminophenyl) -3-methylpyridine, 2-chloro-5- (N, N-diethylamino) Enyl) -3-methylpyridine, 2-chloro-5- (N, N-diisopropylaminophenyl) -3-methylpyridine, 2-chloro-5- (chlorophenyl) -3-methylpyridine, 2-chloro-5 (Fluorophenyl) -3-methylpyridine, 2-chloro-5- (bromophenyl) -3-methylpyridine, 2-chloro-3-methyl-5- (trifluoromethylphenyl) pyridine. More preferably, 2-chloro-N-[(4-fluorophenyl) methyl] -5-phenyl-3-pyridinemethanamine (Compound 1), 2-chloro-5-phenylpyridine (Compound 2), 2-chloro -5-phenylpyridine-3-carboxaldehyde (Compound 3) and 3-methyl-5-phenylpyridine (Compound 4).

  The compound represented by the general formula (1) is preferably a compound represented by the following general formula (3).

(3)

In the formula, R ₇ represents a hydrogen atom, a halogen atom, an unsubstituted or substituted aromatic group, and a straight chain having 1 to 3 carbon atoms which may be substituted with an unsubstituted or substituted aromatic group. Or selected from the group consisting of branched alkyl groups. R ₈ is a hydrogen atom, a halogen atom, a straight or branched alkyl group having 1 to 6 carbon atoms, more preferably 1 to 4 carbon atoms, and a straight chain having 1 to 6 carbon atoms, more preferably 1 to 4 carbon atoms. Selected from the group consisting of chain or branched alkoxy groups. R ₉ is a hydrogen atom, a hydroxyl group, a C 1-8, more preferably a C 1-4 straight or branched alkyl group, and a C 1-8, more preferably a C 1-4 straight chain. Alternatively, it is selected from the group consisting of branched alkoxy groups. Specific examples of the compound represented by the general formula (3) and / or a pharmacologically acceptable salt thereof include 3-pyridinecarboxaldehyde, 2-chloro-3-pyridinecarboxaldehyde, 5 -Phenyl-3-pyridinecarboxaldehyde, 5-methylphenyl-3-pyridinecarboxaldehyde, 5-ethylphenyl-3-pyridinecarboxaldehyde, 5-propylphenyl-3-pyridinecarboxaldehyde, 5-methoxyphenyl-3-pyridine Carboxaldehyde, 5-ethoxyphenyl-3-pyridinecarboxaldehyde, 5-propyloxy-3-pyridinecarboxaldehyde, 5-hydroxyphenyl-3-pyridinecarboxaldehyde, 5-aminophenyl-3-pyridinecarboxaldehyde N-methylaminophenyl-3-pyridinecarboxaldehyde, N-ethylaminophenyl-3-pyridinecarboxaldehyde, N, N-dimethylaminophenyl-3-pyridinecarboxaldehyde, N, N-diethylaminophenyl-3-pyridinecarboxaldehyde 5-chlorophenyl-3-pyridinecarboxaldehyde, 5-fluorophenyl-3-pyridinecarboxaldehyde, 5-bromophenyl-3-pyridinecarboxaldehyde, 5-trifluoromethylphenyl-3-pyridinecarboxaldehyde, 2-chloro- 5-phenyl-3-pyridinecarboxaldehyde (compound 3), 2-chloro-5-phenyl-3-pyridinecarboxaldehyde, 2-chloro-5-methylphenyl-3-pyridinecarbox Sialdehyde, 2-chloro-5-ethylphenyl-3-pyridinecarboxaldehyde, 2-chloro-5-propylphenyl-3-pyridinecarboxaldehyde, 2-chloro-5-methoxyphenyl-3-pyridinecarboxaldehyde, 2- Chloro-5-ethoxyphenyl-3-pyridinecarboxaldehyde, 2-chloro-5-propyloxy-3-pyridinecarboxaldehyde, 2-chloro-5-hydroxyphenyl-3-pyridinecarboxaldehyde, 2-chloro-5-amino Phenyl-3-pyridinecarboxaldehyde, 2-chloro- (N-methylaminophenyl) -3-pyridinecarboxaldehyde, 2-chloro- (N-ethylaminophenyl) -3-pyridinecarboxaldehyde, 2-chloro- (N , N-dimethyl Ruaminophenyl) -3-pyridinecarboxaldehyde, 2-chloro- (N, N-diethylaminophenyl) -3-pyridinecarboxaldehyde, 2-chloro-5-chlorophenyl-3-pyridinecarboxaldehyde, 2-chloro-5- Fluorophenyl-3-pyridinecarboxaldehyde, 5-bromophenyl-2-chloro-3-pyridinecarboxaldehyde, 2-chloro-5-trifluoromethylphenyl-3-pyridinecarboxaldehyde, nicotinic acid, 2-chloronicotinic acid, 5-phenylnicotinic acid, 5- (methylphenyl) nicotinic acid, 5- (ethylphenyl) nicotinic acid, 5- (propylphenyl) nicotinic acid, 5- (methoxyphenyl) nicotinic acid, 5- (ethoxyphenyl) nicotinic acid , 5- (propyloxy Phenyl) nicotinic acid, 5- (hydroxyphenyl) nicotinic acid, 5- (aminophenyl) nicotinic acid, 5- (N-methylaminophenyl) nicotinic acid, 5- (N-ethylaminophenyl) nicotinic acid, 5- ( N, N-dimethylaminophenyl) nicotinic acid, 5- (N, N-diethylaminophenyl) nicotinic acid, 5- (chlorophenyl) nicotinic acid, 5- (bromophenyl) nicotinic acid, 5- (fluorophenyl) nicotinic acid, 5- (difluorophenyl) nicotinic acid, 5- (trifluoromethylphenyl) nicotinic acid, 2-chloro-5-phenylnicotinic acid, 5- (methylphenyl) nicotinic acid, 2-chloro-5- (ethylphenyl) nicotine Acid, 2-chloro-5- (propylphenyl) nicotinic acid, 2-chloro-5- (methoxyphene) L) Nicotinic acid, 2-chloro-5- (ethoxyphenyl) nicotinic acid, 2-chloro-5- (propyloxyphenyl) nicotinic acid, 2-chloro-5- (hydroxyphenyl) nicotinic acid, 2-chloro-5 -(Aminophenyl) nicotinic acid, 2-chloro-5- (N-methylaminophenyl) nicotinic acid, 2-chloro-5- (N-ethylaminophenyl) nicotinic acid, 2-chloro-5- (N, N -Dimethylaminophenyl) nicotinic acid, 2-chloro-5- (N, N-diethylaminophenyl) nicotinic acid, 2-chloro-5- (chlorophenyl) nicotinic acid, 5- (bromophenyl) -2-chloronicotinic acid, 2-chloro-5- (fluorophenyl) nicotinic acid, 2-chloro-5- (difluorophenyl) nicotinic acid, 2-chloro-5- (trifluoro) Olomethylphenyl) nicotinic acid. More preferred is 2-chloro-5-phenyl-3-pyridinecarboxaldehyde (Compound 3).

  The compound represented by the general formula (1) is preferably a compound represented by the following general formula (4).

(4)

In the formula, R ₁₀ represents a hydrogen atom, a halogen atom, an unsubstituted or substituted aromatic group, and a straight chain having 1 to 3 carbon atoms which may be substituted with an unsubstituted or substituted aromatic group. Or selected from the group consisting of branched alkyl groups. R ₁₁ is a hydrogen atom, a halogen atom, a straight chain or branched alkyl group having 1 to 6 carbon atoms, more preferably 1 to 4 carbon atoms, and a straight chain having 1 to 6 carbon atoms, more preferably 1 to 4 carbon atoms. Selected from the group consisting of chain or branched alkoxy groups. R ₁₂ is a hydrogen atom, a hydroxyl group, a linear or branched alkyl group having 1 to 8 carbon atoms, a linear or branched alkoxy group having 1 to 8 carbon atoms, more preferably 1 to 4 carbon atoms, unsubstituted or substituted. Selected from the group consisting of an alkyl group having 1 to 8 carbon atoms, more preferably an alkyl group having 1 to 4 carbon atoms, and a linear or branched alkylamino group having 1 to 4 carbon atoms substituted by an aromatic group having a group. . The alkylamino group may each independently have a linear or branched alkyl chain having 1 to 4 carbon atoms as a substituent, and the alkyl group further has an aromatic group as a substituent. Also good. Of the compounds represented by the general formula (4), compounds that are not included in the general formula (5) and the general formula (6) described below are specifically exemplified by 2-chloro-5-phenylpyridine (compound 2), 2-chloro-5- (methylphenyl) pyridine, 2-chloro-5- (ethylphenyl) pyridine, 2-chloro-5- (propylphenyl) pyridine, 2-chloro-5- (methoxyphenyl) pyridine 2-chloro-5- (ethoxyphenyl) pyridine, 2-chloro-5- (propyloxyphenyl) pyridine, 2-chloro-5- (hydroxyphenyl) pyridine, 5- (aminophenyl) -2-chloropyridine, 2-chloro-5- (N-methylphenyl) pyridine, 2-chloro-5- (N-ethylphenyl) pyridine, 2-chloro-5- (N-propylphenyl) Lysine, 2-chloro-5- (N, N-dimethylphenyl) pyridine, 2-chloro-5- (N, N-diethylphenyl) pyridine, 2-chloro-5- (N, N-diisopropylphenyl) pyridine, 2-chloro-5- (chlorophenyl) pyridine, 2-chloro-5- (fluorophenyl) pyridine, 2-chloro-5- (trifluoromethylphenyl) pyridine, 3-methyl-5-phenylpyridine (compound 4), 3-methyl-5- (methylphenyl) pyridine, 5- (ethylphenyl) -3-methylpyridine, 3-methyl-5- (propylphenyl) pyridine, 5- (methoxyphenyl) -3-methylpyridine, 5- (Ethoxyphenyl) -3-methylpyridine, 3-methyl-5- (propyloxyphenyl) pyridine, 5- (hydroxyphenyl) Nyl) -3-methylpyridine, 5- (aminophenyl) -3-methylpyridine, 3-methyl-5- (N-methylaminophenyl) pyridine, 5- (N-ethylaminophenyl) -3-methylpyridine, 3-methyl-5- (N-propylaminophenyl) pyridine, 5- (N, N-dimethylaminophenyl) -3-methylpyridine, 5- (N, N-diethylaminophenyl) -3-methylpyridine, 5- (N, N-diisopropylaminophenyl) -3-methylpyridine, 5- (chlorophenyl) -3-methylpyridine, 5- (fluorophenyl) -3-methylpyridine, 5- (bromophenyl) -3-methylpyridine, 3-methyl-5- (trifluoromethylphenyl) pyridine, 2-chloro-3-methyl-5-phenylpyridine, 2-chloro B-3-Methyl-5- (methylphenyl) pyridine, 2-chloro-5- (ethylphenyl) -3-methylpyridine, 2-chloro-3-methyl-5- (propylphenyl) pyridine, 2-chloro- 5- (methoxyphenyl) -3-methylpyridine, 2-chloro-5- (ethoxyphenyl) -3-methylpyridine, 2-chloro-3-methyl-5-
(Propyloxyphenyl) pyridine, 2-chloro-5- (hydroxyphenyl) -3-methylpyridine, 2-chloro-5- (aminophenyl) -3-methylpyridine, 2-chloro-3-methyl-5- ( N-methylaminophenyl) pyridine, 2-chloro-5- (N-
Ethylaminophenyl) -3-methylpyridine, 2-chloro-3-methyl-5- (N-propylaminophenyl) pyridine, 2-chloro-5- (N, N-dimethylaminophenyl) -3-methylpyridine, 2-chloro-5- (N, N-diethylaminophenyl) -3-methylpyridine, 2-chloro-5- (N, N-diisopropylaminophenyl) -3-methylpyridine, 2-chloro-5- (chlorophenyl) -3-methylpyridine, 2-chloro-5- (fluorophenyl) -3-methylpyridine, 2-chloro-5- (bromophenyl) -3-methylpyridine, 2-chloro-3-methyl-5- (tri Fluoromethylphenyl) pyridine. Among the compounds represented by the general formula (4), more preferred are 2-chloro-N-[(4-fluorophenyl) methyl] -5-phenyl-3-pyridinemethanamine (Compound 1), 2-chloro-5-phenylpyridine (compound 2) and 3-methyl-5-phenylpyridine (compound 4).

  The compound represented by the general formula (1) is preferably a compound represented by the following general formula (5).

(5)

In the formula, R ₁₃ is a hydrogen atom, a halogen atom, an unsubstituted or substituted aromatic group, and a straight chain having 1 to 3 carbon atoms which may be substituted with an unsubstituted or substituted aromatic group. Or selected from the group consisting of branched alkyl groups. R ₁₄ is a hydrogen atom, a halogen atom, a straight chain or branched alkyl group having 1 to 6 carbon atoms, more preferably 1 to 4 carbon atoms, and a straight chain having 1 to 6 carbon atoms, more preferably 1 to 4 carbon atoms. Selected from the group consisting of chain or branched alkoxy groups. R ₁₅ and R ₁₆ are each independently a hydrogen atom, a linear or branched alkyl group having 1 to 4 carbon atoms, and a straight chain having 1 to 4 carbon atoms substituted with an unsubstituted or substituted aromatic group. Selected from the group consisting of chain or branched alkyl groups. m represents an integer of 0 to 4. R ₁₅ and R ₁₆ are each independently present, but one of them is preferably a hydrogen atom. The m represents an integer of 0 to 4, more preferably m = 1.
Of the compounds represented by the general formula (5), regarding a compound not included in the compound represented by the general formula (6), specific examples thereof include 2-chloro-N, N-dibenzyl-5- Phenyl-3-pyridinemethanamine, N, N-bis [(methylphenyl) methyl] -2-chloro-5-phenyl-3-pyridinemethanamine, N, N-bis [(ethylphenyl) methyl] -2- Chloro-5-phenyl-3-pyridinemethanamine, N, N-bis [(propylphenyl) methyl] -2-chloro-5-phenyl-3-pyridinemethanamine, N, N-bis [(methoxyphenyl) methyl ] -2-chloro-5-phenyl-3-pyridinemethanamine, N, N-bis [(ethoxyphenyl) methyl] -2-chloro-5-phenyl-3-pyridinemethanamine, N, N-bis [( The Pyroxyphenyl) methyl] -2-chloro-5-phenyl-3-pyridinemethanamine, N, N-bis [(hydroxyphenyl) methyl] -2-chloro-5-phenyl-3-pyridinemethanamine, N, N-bis [(aminophenyl) methyl] -2-chloro-5-phenyl-3-pyridinemethanamine, N, N-bis [(N′-methylaminophenyl) methyl] -2-chloro-5-phenyl- 3-pyridinemethanamine, N, N-bis [(N′-ethylaminophenyl) methyl] -2-chloro-5-phenyl-3-pyridinemethanamine,
2-chloro-5-phenyl-N, N-bis [(N′-propylphenyl) methyl] -3-pyridinemethanamine, N, N-bis [(N ′, N′-dimethylphenyl) methyl] -2 -Chloro-5-phenyl-3-pyridinemethanamine, N, N-bis [(N ', N'-diethylphenyl) methyl] -2-chloro-5-phenyl-3-pyridinemethanamine, N, N
-Bis [(N ', N'-dipropylphenyl) methyl] -2-chloro-5-phenyl-3-pyridinemethanamine, N, N-bis [(bromophenyl) methyl] -2-chloro-5- Phenyl-3-pyridinemethanamine, N, N-bis [(fluorophenyl) methyl] -2-chloro-5-phenyl-3-pyridinemethanamine, N, N-bis [(difluorophenyl) methyl] -2- Chloro-5-phenyl-3-pyridinemethanamine, N, N-bis [(trifluoromethylphenyl) methyl] -2-chloro - 5-phenyl-3-pyridinemethanamine,
2-chloro-N, N-dibenzyl-5-pyridyl-3-pyridinemethanamine, N, N-dibenzyl-2-chloro-5-naphthyl-3-pyridinemethanamine, 5-biphenyl-2-chloro-N, N-dibenzyl-3-pyridinemethanamine, N-benzyl-2-chloro-5-phenyl-3-pyridineethanamine, 2-chloro-N-[(methylphenyl)
Methyl] -5-phenyl-3-pyridineethanamine, 2-chloro-N-[(ethylphenyl) methyl] -5-phenyl-3-pyridineethanamine, 2-chloro-5-phenyl-
N-[(propylphenyl) methyl] -3-pyridineethanamine, 2-chloro-N-[(
Methoxyphenyl) methyl] -5-phenyl-3-pyridineethanamine, 2-chloro-
N-[(ethoxyphenyl) methyl] -5-phenyl-3-pyridineethanamine, 2-chloro-5-phenyl-N-[(propyloxyphenyl) ethyl] -3-pyridineethanamine, 2-chloro-N -[(Hydroxyphenyl) methyl] -5-phenyl-3-pyridineethanamine, N-[(aminophenyl) methyl] -2-chloro-5-phenyl-3-pyridineethanamine, 2-chloro-N- [ (N′-methylaminophenyl) methyl] -5-phenyl-3-pyridineethanamine, 2-chloro-N-[(N′-ethylaminophenyl) methyl] -5-phenyl-3-pyridineethanamine,
2-chloro-5-phenyl-N-[(N'-propylphenyl) methyl] -3-pyridineethanamine, 2-chloro-N-[(N ', N'-dimethylphenyl) methyl] -5-phenyl -3-pyridineethanamine, 2-chloro-N-[(N ', N'-diethylphenyl)
Methyl] -5-phenyl-3-pyridineethanamine, 2-chloro-N-[(N ′, N′-dipropylphenyl) methyl] -5-phenyl-3-pyridineethanamine, N-[(bromophenyl) ) methyl] -2-chloro-5-phenyl-3-pyridinecarboxylic ethanamine, 2-chloro -N - [(fluorophenyl) methyl] -5-phenyl-3-pyrid N'e Tan'amin, 2-chloro -N - [( difluorophenyl) methyl] -5-phenyl-3-pyridine ethanamine, 2-chloro-5-phenyl -N - [(trifluoromethylphenyl) methyl] -3-pyrid N'e Tan'amin,
2-chloro-5-pyridyl-N- (benzyl) -3-pyridineethanamine, 2-chloro-5-naphthyl-N- (benzyl) -3-pyridineethanamine, 5-biphenyl-2-chloro-N- (Benzyl) -3-pyridineethanamine, N-benzyl-2-methyl-5-phenyl-3-pyridineethanamine, 2-methyl-N-[(methylphenyl) methyl] -5-phenyl-3-pyridineethane Amine, N-[(ethylphenyl) methyl] -2-methyl-5-phenyl-3-pyridineethanamine, 2-methyl-5-phenyl-N-[(
Propylphenyl) methyl] -3-pyridineethanamine, N-[(methoxyphenyl) methyl] -2-methyl-5-phenyl-3-pyridineethanamine, N-[(ethoxyphenyl) methyl] -2-methyl- 5-phenyl-3-pyridineethanamine, 2-methyl-5
-Phenyl-N-[(propyloxyphenyl) ethyl] -3-pyridineethanamine, N-[(hydroxyphenyl) methyl] -2-methyl-5-phenyl-3-pyridineethanamine, N-[(aminophenyl) ) Methyl] -2-methyl-5-phenyl-3-pyridineethanamine, 2-methyl-N-[(N′-methylaminophenyl) methyl] -5-phenyl-3-pyridineethanamine, N-[( N′-ethylaminophenyl) methyl] -2-methyl-5-phenyl-3-pyridineethanamine,
2-methyl-5-phenyl-N-[(N′-propylphenyl) methyl] -3-pyridineethanamine, N-[(N ′, N′-dimethylphenyl) methyl] -2-methyl-5-phenyl -3-pyridineethanamine, N-[(N ', N'-diethylphenyl) methyl] -2-methyl-5-phenyl-3-pyridineethanamine, N-[(N', N'-dipropylphenyl) ) Methyl] -2-methyl-5-phenyl-3-pyridineethanamine, N-[(bromophenyl) methyl] -2-methyl-5-phenyl-3-pyridineethanamine, N-[(fluorophenyl) methyl ] -2-methyl-5-phenyl-3-pyrid N'e Tan'amin,
N - [(difluorophenyl) methyl] -2-methyl-5-phenyl-3-pyridine ethanamine, 2-methyl-5-phenyl -N - [(trifluoromethylphenyl) methyl] -3-pyrid N'e Tan'amin, 2-methyl-5-pyridyl-N- (benzyl) -3-pyridineethanamine, 2-methyl-5-naphthyl-N- (benzyl) -3-pyridineethanamine, 5-biphenyl-2-methyl-N- (Benzyl) -3-pyridineethanamine,
N-benzyl-5-benzyl-2-chloro-3-pyridineethanamine, 5-benzyl-2-chloro-N-[(methylphenyl) methyl] -3-pyridineethanamine, 5-benzyl-2-chloro- N-[(ethylphenyl) methyl] -3-pyridineethanamine, 5-benzyl-2-chloro-N-[(propylphenyl) methyl] -3-pyridineethanamine, 5-benzyl-2-chloro-N- [(Methoxyphenyl) methyl] -3-pyridineethanamine, 5-benzyl-2-chloro-N-[(ethoxyphenyl) methyl] -3-pyridineethanamine, 5-benzyl-2-chloro-N-[( Propyloxyphenyl) ethyl] -3-pyridineethanamine, 5-benzyl-2-chloro-N-[(hydroxyphenyl) methyl] -3-pyridineethanamine N - [(aminophenyl) methyl] -5-benzyl -
2-chloro-3-pyridineethanamine, 5-benzyl-2-chloro-N-[(N′-methylaminophenyl) methyl] -3-pyridineethanamine, 5-benzyl-2-chloro-N-[( N′-ethylaminophenyl) methyl] -3-pyridineethanamine, 5-benzyl-2-chloro-N-[(N′-propylphenyl) methyl] -3-pyridineethanamine, 5-benzyl-2-chloro -N-[(N ', N'-dimethylphenyl) methyl] -3-pyridineethanamine, 5-benzyl-2-chloro-N-[(N', N'-diethylphenyl) methyl] -3-pyridine Ethanamine, 5-benzyl-2-chloro-N-[(N ′, N′-dipropylphenyl) methyl] -3-pyridineethanamine,
5-benzyl -N - [(bromophenyl) methyl] -2-chloro-3-pyridine ethanamine, 5-benzyl-2-chloro -N - [(fluorophenyl) methyl] -3-pyrid N'e Tan'amin, 5- Benzyl-2-chloro-N-[(difluorophenyl) methyl] -3-pyridineethanamine, 5-benzyl-2-chloro-N-[(trifluoromethylphenyl)
Methyl] -3-pyrid N'e Tan'amin, 2-chloro-5-pyridylmethyl -N- (benzyl) -3-pyridine ethanamine, 2-chloro-5-naphthylmethyl -N- (benzyl) -3-pyridin-ethanamine 2-chloro-5-biphenylmethyl-N- (benzyl) -3-pyridineethanamine and / or a pharmacologically acceptable salt thereof can be preferably exemplified.
Among the compounds represented by the general formula (5), 2-chloro-N-[(4-fluorophenyl) methyl] -5-phenyl-3-pyridinemethanamine (Compound 1) is more preferable. is there.

  The compound represented by the general formula (1) is preferably a compound represented by the following general formula (6).

(6)

In the formula, R ₁₇ represents a hydrogen atom, a halogen atom, an unsubstituted or substituted aromatic group, and a straight chain having 1 to 3 carbon atoms which may be substituted with an unsubstituted or substituted aromatic group. Or selected from the group consisting of branched alkyl groups. R ₁₈ is a hydrogen atom, a halogen atom, a straight chain or branched alkyl group having 1 to 6 carbon atoms, more preferably 1 to 4 carbon atoms, and a straight chain having 1 to 6 carbon atoms, more preferably 1 to 4 carbon atoms. Selected from the group consisting of chain or branched alkoxy groups. R ₁₉ is a group consisting of a linear or branched alkyl group having 1 to 4 carbon atoms and a linear or branched alkyl group having 1 to 4 carbon atoms substituted with an unsubstituted or substituted aromatic group. Selected. Specific examples of the compound represented by the general formula (6) and / or a pharmacologically acceptable salt thereof include N-benzyl-2-chloro-5-phenyl-3-pyridinemethanamine. 2-chloro-N-[(methylphenyl) methyl] -5-phenyl-3-pyridinemethanamine, 2-chloro-N-[(ethylphenyl) methyl] -5-phenyl-3-pyridinemethanamine, 2 -Chloro-5-phenyl-N-[(propylphenyl) methyl] -3-pyridinemethanamine, 2-chloro-N-[(methoxyphenyl) methyl] -5-phenyl-3-pyridinemethanamine, 2-chloro -N-[(ethoxyphenyl) methyl] -5-phenyl-3-pyridinemethanamine, 2-chloro-5-phenyl-N-[(propyloxyphenyl) methyl] -3-pyridine 2-chloro-N-[(hydroxyphenyl) methyl] -5-phenyl-3-pyridinemethanamine, N-[(aminophenyl) methyl] -2-chloro-5-phenyl-3-pyridinemethanamine, 2-chloro-N-[(N′-methylaminophenyl) methyl] -5-phenyl-3-pyridinemethanamine,
2-chloro-N-[(N'-ethylaminophenyl) methyl] -5-phenyl-3-pyridinemethanamine, 2-chloro-5-phenyl-N-[(N'-propylphenyl) methyl] -3 -Pyridinemethanamine, 2-chloro-N-[(N ', N'-dimethylphenyl) methyl] -5-phenyl-3-pyridinemethanamine, 2-chloro-N-[(N', N'-diethyl Phenyl) methyl] -5-phenyl-3-pyridinemethanamine, 2-chloro-N
-[(N ', N'-dipropylphenyl) methyl] -5-phenyl-3-pyridinemethanamine, N-[(bromophenyl) methyl] -2-chloro-5-phenyl-3-pyridinemethanamine, 2-chloro-N-[(fluorophenyl) methyl] -5-phenyl-3-pyridinemethanamine, 2-chloro-N-[(difluorophenyl) methyl] -5-phenyl-3-pyridinemethanamine, 2- Chloro-5-phenyl-N-[(trifluoromethylphenyl) methyl] -3-pyridinemethanamine, 2-chloro-5-pyridyl-N- (benzyl) -3-pyridinemethanamine, 2-chloro-5- Naphthyl-N- (benzyl) -3-pyridinemethanamine, 2-chloro-5-biphenyl-N- (benzyl) -3-pyridinemethanamine, 5-benzyl-N-benzene Dil-2-chloro-3-pyridinemethanamine, 5-benzyl-2-chloro-N-[(methylphenyl) methyl] -3-pyridinemethanamine, 5-benzyl-2-chloro-N-[(ethylphenyl) ) Methyl] -3-pyridinemethanamine, 5-benzyl-2-chloro-N-[(propylphenyl) methyl] -3-pyridinemethanamine, 5-benzyl-2-chloro-N-[(methoxyphenyl) methyl ] -3-pyridinemethanamine, 5-benzyl-2-chloro-N-[(ethoxyphenyl) methyl] -3-pyridinemethanamine, 5-benzyl-2-chloro-N-[(propyloxyphenyl) methyl] -3-pyridinemethanamine, 5-benzyl-2-chloro-N-[(hydroxyphenyl) methyl] -3-pyridinemethanamine, N-[(aminopheny ) Methyl] -
5-benzyl-2-chloro-3-pyridinemethanamine, 5-benzyl-2-chloro-N-[(N′-methylaminophenyl) methyl] -3-pyridinemethanamine, 5-benzyl-2-chloro- N-[(N′-ethylaminophenyl) methyl] -3-pyridinemethanamine, 5-benzyl-2-chloro-N-[(N′-propylphenyl) methyl] -3-pyridinemethanamine, 5-benzyl -2-chloro-N-[(N ′, N′-dimethylphenyl)
Methyl] -3-pyridinemethanamine, 5-benzyl-2-chloro-N-[(N ′, N′-diethylphenyl) methyl] -3-pyridinemethanamine, 5-benzyl-2-chloro-
N-[(N ′, N′-dipropylphenyl) methyl] -3-pyridinemethanamine, 5-benzyl-N-[(bromophenyl) methyl] -2-chloro-3-pyridinemethanamine, 5-benzyl 2-chloro-N-[(fluorophenyl) methyl] -3-pyridinemethanamine, 5-benzyl-2-chloro-N-[(difluorophenyl) methyl] -3-pyridinemethanamine, 5-benzyl-2 -Chloro-N-[(trifluoromethylphenyl) methyl] -3-pyridinemethanamine, 2-chloro-5-pyridylmethyl-N- (benzyl) -3-pyridinemethanamine, 2-chloro-5-naphthylmethyl -N- (benzyl) -3-pyridinemethanamine, 2-chloro-5-biphenylmethyl-N- (benzyl) -3-pyridinemethanamine, N-benzyl- -Methyl-5-phenyl-3-pyridinemethanamine, 2-methyl-N-[(methylphenyl) methyl] -5-phenyl-3-pyridinemethanamine, N-[(ethylphenyl) methyl] -2-methyl -5-phenyl-3-pyridinemethanamine, 2-methyl-5-phenyl-N-[(propylphenyl) methyl] -3-pyridinemethanamine, N-[(methoxyphenyl) methyl] -2-methyl-5 -Phenyl-3-pyridinemethanamine, N-[(ethoxyphenyl) methyl] -2-methyl-5-phenyl-3-pyridinemethanamine, 2-methyl-5-phenyl-N-[(propyloxyphenyl) methyl ] -3-pyridinemethanamine, N-[(hydroxyphenyl) methyl]-
2-methyl-5-phenyl-3-pyridinemethanamine, N-[(aminophenyl) methyl] -2-methyl-5-phenyl-3-pyridinemethanamine, 2-methyl-N-[(N′-methyl) Aminophenyl) methyl] -5-phenyl-3-pyridinemethanamine, N-[(N′-ethylaminophenyl) methyl] -2-methyl-5-phenyl-3-pyridinemethanamine, 2-methyl-5- Phenyl-N-[(N′-propylphenyl) methyl] -3-pyridinemethanamine, N-[(N ′, N′-dimethylphenyl) methyl] -2-methyl-5-phenyl-3-pyridinemethanamine N-[(N ′, N′-diethylphenyl) methyl] -2-methyl-5-phenyl-3-pyridinemethanamine, N-[(N ′, N′-dipropylphenyl) methyl] -2- Methyl-5-fu -3- pyridinemethanamine,
N-[(bromophenyl) methyl] -2-methyl-5-phenyl-3-pyridinemethanamine, N-[(fluorophenyl) methyl] -2-methyl-5-phenyl-3-pyridinemethanamine, N- [(Difluorophenyl) methyl] -2-methyl-5-phenyl-3-pyridinemethanamine, 2-methyl-5-phenyl-N-[(trifluoromethylphenyl)
Methyl] -3-pyridinemethanamine, N-benzyl-2-methoxy-5-phenyl-3
-Pyridinemethanamine, 2-methoxy-N-[(methylphenyl) methyl] -5-phenyl-3-pyridinemethanamine, N-[(ethylphenyl) methyl] -2-methoxy-5-phenyl-3-pyridine Methanamine, 2-methoxy-5-phenyl-N-[(propylphenyl) methyl] -3-pyridinemethanamine, N-[(methoxyphenyl) methyl]-
2-methoxy-5-phenyl-3-pyridinemethanamine, N-[(ethoxyphenyl)
Methyl] -2-methoxy-5-phenyl-3-pyridinemethanamine, 2-methoxy-5
-Phenyl-N-[(propyloxyphenyl) methyl] -3-pyridinemethanamine, N-[(hydroxyphenyl) methyl] -2-methoxy-5-phenyl-3-pyridinemethanamine, N-[(aminophenyl) ) Methyl] -2-methoxy-5-phenyl-3-pyridinemethanamine, 2-methoxy-N-[(N′-methylaminophenyl) methyl] -5-phenyl-3-pyridinemethanamine, N-[( N'-ethylaminophenyl) methyl] -2-methoxy-5-phenyl-3-pyridinemethanamine, 2-methoxy-5-phenyl-N-[(N'-propylphenyl) methyl] -3-pyridinemethanamine , N − [(N ′, N
'-Dimethylphenyl) methyl] -2-methoxy-5-phenyl-3-pyridinemethanamine, N-[(N', N'-diethylphenyl) methyl] -2-methoxy-5-phenyl-3-pyridinemethane Amine, N-[(N ′, N′-dipropylphenyl) methyl] -2-methoxy-5-phenyl-3-pyridinemethanamine, N-[(bromophenyl) methyl] -2-methoxy-5-phenyl -3-pyridinemethanamine, N-[(fluorophenyl)
Methyl] -2-methoxy-5-phenyl-3-pyridinemethanamine, N-[(difluorophenyl) methyl] -2-methoxy-5-phenyl-3-pyridinemethanamine, 2-methoxy-5-phenyl-N -[(Trifluoromethylphenyl) methyl] -3-pyridinemethanamine and / or a pharmacologically acceptable salt thereof can be preferably exemplified, and more preferably 2-chloro-N-[(fluorophenyl) Methyl] -5-phenyl-3-pyridinemethanamine and / or pharmacologically acceptable salts thereof are more preferably 2-chloro-N-[(4-fluorophenyl) methyl] -5-phenyl. -3-pyridinemethanamine (Compound 1).

  The compounds represented by the general formulas (1) to (6) and / or pharmacologically acceptable salts thereof are commercially available pyridine derivatives and the like, and the methods described in the examples below. It can also be synthesized according to Moreover, you may use what is marketed and can also purchase from reagent makers, such as Wako Pure Chemicals. Further, such a compound can be used as it is as a collagen production promoter, but it can also be treated with a pharmacologically acceptable acid or base, converted into a salt form, and used as a salt. For example, inorganic acid salts such as hydrochloride, sulfate, nitrate, phosphate, carbonate; maleate, fumarate, oxalate, citrate, lactate, tartrate, methanesulfonate, para Organic acid salts such as toluene sulfonate and benzene sulfonate; alkali metal salts such as sodium salt and potassium salt; alkaline earth metal salts such as calcium salt and magnesium salt; triethylamine salt, triethanolamine salt, ammonium salt, Examples include organic amine salts such as monoethanolamine salts and piperidine salts; basic amino acid salts such as lysine salts and alginates.

  The collagen production promoter of the present invention thus obtained can be used as an active ingredient of an external preparation for skin. Moreover, it has an excellent anti-aging action, in particular, a prevention or improvement effect against wrinkle formation. Furthermore, when using the collagen production promoter of the present invention as an active ingredient of a skin external preparation, the collagen production promoter is 0.0001% by mass to 10% by mass in total with respect to the total amount of the skin external preparation, more preferably It is preferable to contain 0.001 mass%-5 mass%, More preferably, 0.005-3 mass%. When the content relative to the total amount of the external preparation for skin is less than 0.0001% by mass, the effect of preventing or improving wrinkle formation tends to decrease, and even when an amount exceeding 10% by mass is used, the effect tends to peak. Therefore, there is a risk that the degree of freedom of prescription is reduced. Moreover, when making the collagen production promoter of this invention contain in skin external preparations, the collagen production promoter of this invention can also be contained 1 type, and may be contained in combination of 2 or more type.

  The collagen production promoter comprising the compound represented by the general formula (1) and / or a pharmacologically acceptable salt thereof includes external environmental factors such as UV exposure, genetic factors, and the like. There are preventive or ameliorating actions for skin aging caused by various factors, especially, preventing or ameliorating action for skin shape change, specifically, those that have actions other than preventing or ameliorating wrinkle formation. Even if it is an external preparation for skin containing the collagen production promoter of the present invention for the purpose of expressing such an action, if the anti-aging action, especially, the prevention or improvement effect against wrinkle formation is exhibited, this Since the effect of the invention is used, it belongs to the technical scope of the present invention. Actions other than the prevention or improvement action against wrinkle formation include moisturizing action, actinic keratosis or non-actinic keratosis improvement action, skin exfoliation inhibitory action, epidermal renewal stimulating action, pigmentation prevention or improvement action, etc. Is mentioned.

<Skin external preparation of the present invention>
The external preparation for skin of the present invention comprises a collagen production promoter comprising the compound represented by the general formula (1) and / or a pharmacologically acceptable salt thereof. The external preparation for skin of the present invention may contain only one type of collagen production promoter composed of the compound represented by the general formula (1) and / or a pharmacologically acceptable salt thereof. You may contain combining the above. The skin external preparation of this invention exhibits the prevention or improvement effect with respect to the excellent wrinkle formation by containing the collagen production promoter of this invention. In addition, the external preparation for skin of the present invention also has an effect other than the preventive or ameliorating effect on wrinkle formation. Even if it is a skin external preparation containing the collagen production promoter of the present invention for the purpose of expressing such an action, the effect of the present invention is utilized when the effect of improving wrinkles is exhibited, It belongs to the technical scope of the present invention. Examples of actions other than wrinkle improvement include moisturizing action, actinic keratosis or non-actinic keratosis improving action, skin peeling, epidermal renewal stimulation, and aging improving action.

  The external preparation for skin of the present invention can contain optional components that are usually used in external preparations for skin, in addition to the collagen production promoter that is an essential component. Such optional ingredients include hydrocarbons such as squalane, petrolatum, microcrystalline wax, esters such as jojoba oil, carnauba wax, octyldodecyl oleate, triglycerides such as olive oil, beef tallow, coconut oil, stearic acid , Fatty acids such as oleic acid, retinoic acid, higher alcohols such as oleyl alcohol, stearyl alcohol, octyldodecanol, anionic surfactants such as sulfosuccinic acid ester and sodium polyoxyethylene alkylsulfate, and amphoteric surfactants such as alkylbetaine salts Agents, cationic surfactants such as dialkylammonium salts, sorbitan fatty acid esters, fatty acid monoglycerides, polyoxyethylene adducts thereof, polyoxyethylene alkyl ethers, polyoxyethylenes Nonionic surfactants such as fatty acid esters, polyhydric alcohols such as polyethylene glycol, glycerin, 1,3-butanediol, thickening / gelling agents, antioxidants, ultraviolet absorbers, colorants, preservatives , Powder and the like can be contained. Manufacture can be done without difficulty by treating these components according to conventional methods.

  A lotion, emulsion, essence, cream, pack cosmetics, detergents, etc. can be prepared by treating the collagen production promoter and optional components of the present invention according to a conventional method. The external preparation for skin of the present invention can be used in any form as long as it can be applied to the skin. However, since the active ingredient penetrates into the skin and exerts its effect, it is familiar to the skin. A dosage form such as a lotion, milky lotion, cream, or essence is preferred.

<Method for Screening Component Having Collagen Production Promoting Action of the Present Invention>
The method for screening a component having a collagen production promoting action of the present invention is a method capable of accurately and efficiently screening a component having a collagen production promoting action. Examples of the component having a collagen production promoting effect include a component having a collagen production promoting effect in the skin and a component that increases the amount of dermal collagen production. In addition, components that increase the amount of dermal collagen produced include components that directly increase the amount of dermal collagen produced by acting on the epidermis, in addition to components that directly decrease the amount of collagen produced by acting on the dermis. As a screening method for a component that indirectly increases dermal collagen production by acting on the epidermis, the epidermal cells are cultured in the presence of the test substance, and the dermal cells are cultured using the culture supernatant. The amount of procollagen production is measured, and compared with the amount of collagen production of dermal cells cultured in a medium without the test substance, the amount of collagen production is estimated by the amount of increase in collagen production. A method can be illustrated suitably. Further, as a method for evaluating the collagen production promoting action, for example, a method for directly measuring the amount of collagen using a labeled antibody or the like (see, for example, JP-A-2004-108914), collagen producing enzyme Evaluation of collagen production by measuring activity and / or collagenase activity, Reverse Transcription Polymerase Chain Reaction (RT-PCR) method, Real-time PCR
) Method, and further, a method for measuring collagen production gene expression level by a measurement method combining real time PCR and RT-PCR, etc., and evaluating collagen production amount, and further, a collagen precursor using the above method There is a method for measuring the amount of procollagen and evaluating the amount of collagen. In the present invention, a method for directly measuring the production amount of procollagen using a labeling body or the like is preferable from the viewpoints of simplicity of experimental operation, measurement accuracy, and the like. Further, in order to easily measure such procollagen production promoting action, PIP EIA KIT (Takara Bio Inc.) can be used for the amount of procollagen. In addition, as a screening method for a component having a collagen production promoting action of the present invention, a screening method for a component that increases collagen production in the dermis through the epidermis is preferable. A screening method using the amount as an index is preferred. This is because procollagen synthesized in dermal fibroblasts is an important intermediate in the process of collagen production in vivo, and the amount of collagen produced is greatly affected by the increase or decrease in the amount of procollagen. Of the methods for screening for a component having a collagen production promoting action of the present invention, a particularly preferred screening method is specifically exemplified by “evaluation of procollagen production promoting action” described in the examples below. In the “evaluation of procollagen production promoting effect” in the present invention, the component having a procollagen production promoting effect is a component in which the amount of procollagen production of the test substance is increased compared to the control group, more preferably the control. The component which shows the procollagen production promotion effect 1.5 times or more compared with a group can be illustrated suitably.

  The collagen production promoter selected by the method for screening a component having a collagen production promoting action of the present invention includes the compound represented by the general formula (1) and / or a pharmacologically acceptable salt thereof. A preferred collagen production promoter can be exemplified. When administered to the epidermis, the collagen production promoter selected by the method for screening a component having a collagen production promoting action of the present invention acts on the epidermis and releases a stimulating factor from cells constituting the epidermis. Therefore, it can be said that it is a collagen production promoter having an action of promoting procollagen production in the dermis and, as a result, increasing collagen production in the dermis. Further, the collagen production promoter selected by the screening method described above releases a stimulating factor by acting on the epidermis, and increases the collagen production amount (procollagen production amount) in the dermis via the stimulating factor. In addition, the action on the epidermis is due to the collagen production promoter selected by the screening method of the component having the collagen production promoting action of the present invention. Is due to the collagen production system originally provided by the organism. For this reason, the collagen production promoter selected by the screening method of the component having the collagen production promoting action of the present invention is an indirect collagen production promotion capable of reflecting the influence of the feedback mechanism in the living body that works at the time of collagen overproduction. Since it has an action, it can be said that it is a collagen production promoter that can more accurately suppress the overproduction of collagen by the conventional collagen production promoter that works directly on the dermis and has less side effects due to overproduction of collagen such as scars.

  In addition, the component having the collagen production promoting action selected by the screening method described above, when setting it to a plurality of concentrations and evaluating the collagen production promoting action, when it is contained in the external preparation for skin, anti-aging action, especially Therefore, it is possible to produce an external preparation for skin that can surely exert an effect of preventing or improving wrinkle formation.

  In the following, the present invention will be described in more detail with reference to examples, but it goes without saying that the present invention is not limited to such examples.

<Compound represented by the general formula (1) of the present invention>
Among the compounds represented by the general formula (1), compounds 1 to 4 can be purchased as commercially available compounds from Tokyo Chemical Industry Co., Ltd., etc., and are reacted using commercially available raw materials according to the synthesis method described later. It can be synthesized by appropriately changing the conditions. Compound 1 and Compound 2 were synthesized according to the method described below. On the other hand, 2-chloro-5-phenylpyridine-3-carboxaldehyde (compound 3) was purchased from Sigma-Aldrich, and 3-methyl-5-phenylpyridine (compound 4) was purchased from Tokyo Chemical Industry Co., Ltd. did. Of the compounds used in this test, the following production examples are examples of the production method of the compound represented by the general formula (1), and it goes without saying that the present invention is not limited to these examples.

2-Chloro-N-[(4-fluorophenyl) methyl] -5-phenyl-3-pyridinemethanamine (Compound 1)

<Production Example 1: 2-chloro-N-[(4-fluorophenyl) methyl] -5-phenyl-3-
Method for Producing Pyridinemethanamine (Compound 1)>
20 g (91.9 mmol) of 2-chloro-5-phenyl-3-pyridine aldehyde and 1,2-dichloroethane were placed in a 500 mL eggplant-shaped flask and stirred at room temperature under a nitrogen atmosphere. While stirring, 11 mL (96.5 mmol) of 4-fluorobenzylamine was added dropwise. After reacting at room temperature for 2 hours, 35.06 g (165.4 mmol) of sodium triacetoxyborohydride was added. After reacting overnight, a 10% aqueous potassium carbonate solution was added dropwise. After stirring for 3 hours, a liquid separation operation was performed, and a 1,2-dichloroethane layer was recovered. Further, the aqueous layer was re-extracted with chloroform and combined with the aforementioned 1,2-dichloroethane layer. 4 to the combined organic layer
46 mL (92 mmol) of N hydrochloric acid ethyl acetate solution was added dropwise. The precipitated crystals were separated by filtration and washed with 200 mL of ethyl acetate. The crystals were collected by filtration, and again dispersed in 200 mL of ethyl acetate, and a 10% aqueous potassium carbonate solution was added dropwise. After confirming dissolution of the crystals, liquid separation was performed to recover the organic layer. After the organic layer was concentrated, 200 mL of methanol was added to the residue for crystallization. After methanol was once concentrated, 40 mL of methanol and 20 mL of water were added again, and the mixture was cooled in an ice bath. After fully aging, the crystals were collected by filtration. Drying was performed at 60 ° C. to obtain 22.24 g (68.1 mmol) of the desired product as white crystals.

<Physical constant of compound 1>
¹ H-NMR (CDCl ₃ ): 3.84 (2H, s), 3.94 (2H, s), 7.03 (2H
, T), 7.32 (2H, dd), 7.44 (3H, m),
7.54 (2H, dd), 7.98 (1H, d), 8.51 (1H, d)
FAB-MS: 327 (M + H ⁺ )

2-Chloro-5-phenylpyridine (Compound 2)

<Production Example 2: Method for producing 2-chloro-5-phenylpyridine (Compound 2)>
6.65 g (54.56 mmol) of phenylboronic acid, 10 g (51.96 mmol) of 5-bromo-2-chloropyridine, 17.95 g (129.9 mmol) of potassium carbonate, and 100 mL of toluene were sequentially put into a 300 mL eggplant-shaped flask and added with nitrogen. Stir at room temperature under atmosphere. After stirring for 15 minutes, 1.8 g (1.56 mmol) of tetrakistriphenylphosphine palladium was added. The temperature was raised to 90 ° C. in an oil bath and stirred for 4 hours. The progress of the reaction was confirmed by TLC and cooled to room temperature. 100 mL of water was added to the reaction solution to carry out a liquid separation operation, and the toluene layer was recovered. The recovered toluene layer was concentrated, and purified by silica gel column chromatography using a mixed solution of hexane and ethyl acetate as a developing solvent. After the eluate of the target product was concentrated, hexane was added. After removing insolubles by filtration, hexane was distilled off. The crystallized target product was collected and dried to obtain 5.75 g (30.32 mmol) of the target product as slightly yellowish white crystals.

¹ H-NMR (CDCl ₃ ): 7.49 (5H, m), 7.85 (1H, d), 8.60 (1H,
d)
FAB-MS: 190 (M + H ⁺ )

<Test Example 1: Evaluation of procollagen production promoting action>
With respect to Compounds 1 to 4, procollagen production promoting action was evaluated.
1) Using a keratinocyte growth medium (Humedia-KG2, Kurashiki Boseki Co., Ltd.), 1.0
X10 ⁵ cells of human-derived normal keratinocyte cultured cells were seeded in a 24-well plate, and 3
The cells were cultured at 7 ° C. and a carbon dioxide concentration of 5% for 2 hours. Thereafter, compounds 1 to 4 were added to a final concentration of 25 to 100 μM, respectively, and dimethyl was used as a comparative control so that the final concentration was 0.01 × 10 ⁻³ (v / v%) instead of compounds 1 to 4. Sulfoxide was added and cultured for 24 hours.
2) Next, in a keratinocyte basal medium (Humedia-KB2, Kurashiki Boseki Co., Ltd.), DMEM medium (manufactured by SIGMA), and FBS mixed at a ratio of 49/49/2, respectively, to a final concentration similar to the above. Thus, a medium containing compounds 1 to 4 and a medium containing dimethyl sulfoxide were prepared. 3) The cultured keratinocytes were washed with PBS (manufactured by Wako Pure Chemical Industries, Ltd.) and then replaced with a medium containing each of the above compounds and a medium containing dimethyl sulfoxide. The culture was further continued for 24 hours.
4) At the same time, using DMEM medium supplemented with 10% FBS, 1.2 × 10 ⁵ cells of human-derived normal skin fibroblast cultured cells were seeded in a 24-well plate at 37 ° C. in a carbon dioxide concentration of 5%. Cultured.
5) After 24 hours, the culture supernatant of keratinocytes was collected. In addition, the fibroblast 24 hours after seeding was washed with PBS, and then replaced with the recovered keratinocyte culture supernatant.
-Cultured in a carbon dioxide concentration of 5% for 48 hours. 48 hours later, fibroblast is PBS
After washing with DMEM medium, the medium was replaced with DMEM medium, and cultured for 2 hours at 37 ° C. and 5% carbon dioxide concentration, and the culture supernatant was collected. The amount of procollagen in the culture supernatant was measured using PIP EIA KIT (Takara Bio Inc.). Fibroblasts cultured in a dimethyl sulfoxide-added medium were used as controls, and the ratios of procollagen production amounts of compounds 1 to 4 with respect to the controls are shown in FIGS.

  1-4 show that the compounds 1 to 4 have an excellent procollagen production promoting effect.

<Production Example 3: Method 1 for producing skin external preparation of the present invention>
In accordance with the formulation shown below, an essence cosmetic that is an external preparation for skin of the present invention was prepared. That is, the ingredients of a, b and c are heated to 75 ° C., and b is gradually added to emulsify. Further, c is added to neutralize and thicken, and the mixture is cooled with stirring to make an essence emulsion cosmetic (cosmetics). 1) was obtained. Moreover, the comparative example 1 which substituted the collagen production promoter (compound 1) of this invention with water was produced.

<Production Example 4: Production Example 2 of the skin external preparation of the present invention>
In accordance with the formulation shown below, an essence cosmetic that is an external preparation for skin of the present invention was prepared. That is, the ingredients of a, b and c are heated to 75 ° C., and b is gradually added to emulsify. Further, c is added to neutralize and thicken, and the mixture is cooled with stirring to make an essence emulsion cosmetic (cosmetics). 2) was obtained. Moreover, the comparative example 2 which substituted the collagen production promoter (compound 2) of this invention with water was produced.

<Test Example 2: Wrinkle improvement test>
Using the cosmetics 1 and 2 and Comparative Examples 1 and 2, the effect on wrinkle improvement was investigated using 5 people per group and 20 people in total as panelists for people worried about fine wrinkles. That is, before the test, a replica of the target site was taken, and the sample was administered to the target site twice a day for 60 consecutive days, and a replica of the site was taken again 24 hours after the last administration, From the degree of direction of the texture of the replica, score 0: no directionality, score 1: slightly directionality, score 2: directionality, score 3: clearly directionality 4 Judgment was made with a stage score. The results are shown in Table 3. From this, it can also be seen that Cosmetics 1 and 2, which are the external preparation for skin of the present invention, have an excellent wrinkle improving action, which is due to the collagen production promoting action of Compound 1.

  INDUSTRIAL APPLICABILITY The present invention can be applied to skin external preparations such as cosmetics for preventing or improving wrinkle formation and anti-aging.

Claims (10)

A collagen production promoter comprising a compound represented by the following general formula (3), (4) or (5) and / or a pharmacologically acceptable salt thereof.
[Wherein R ₇ represents a phenyl group, a methylphenyl group, an ethylphenyl group, a propylphenyl group, a butylphenyl group, a methoxyphenyl group, an ethoxyphenyl group, a propyloxyphenyl group, a butyloxyphenyl group, or a hydroxyphenyl group. Represent. R ₈ represents a hydrogen atom, a halogen atom, or a linear or branched alkyl group having 1 to 4 carbon atoms. R ₉ represents a hydrogen atom, a hydroxyl group, or a linear or branched alkyl group having 1 to 4 carbon atoms. ]
[Wherein R ₁₀ represents a phenyl group, a methylphenyl group, an ethylphenyl group, a propylphenyl group, a butylphenyl group, a methoxyphenyl group, an ethoxyphenyl group, a propyloxyphenyl group, a butyloxyphenyl group, or a hydroxyphenyl group. Represent. R ₁₁ represents a hydrogen atom, a halogen atom, or a linear or branched alkyl group having 1 to 4 carbon atoms. R ₁₂ represents a hydrogen atom, a hydroxyl group, or a linear or branched alkyl group having 1 to 4 carbon atoms. ]
[Wherein R ₁₃ represents a phenyl group, a methylphenyl group, an ethylphenyl group, a propylphenyl group, a butylphenyl group, a methoxyphenyl group, an ethoxyphenyl group, a propyloxyphenyl group, a butyloxyphenyl group, or a hydroxyphenyl group. Represent. R ₁₄ represents a hydrogen atom, a halogen atom, or a linear or branched alkyl group having 1 to 4 carbon atoms. R ₁₅ and R ₁₆ are each independently substituted with a hydrogen atom, a linear or branched alkyl group having 1 to 4 carbon atoms, or a linear or branched alkyl group having 1 to 4 carbon atoms or a fluoro group. Represents a linear or branched alkyl group having 1 to 4 carbon atoms substituted by an optionally substituted phenyl group, and m represents an integer of 0 to 4. ] The compound represented by the general formula (4), characterized in that 2-chloro-5-phenylpyridine (Compound 2) or a 3-methyl-5-phenylpyridine (Compound 4), according to claim 1 The collagen production promoter described in 1.
The collagen production promoter according to claim 1 , wherein the compound represented by the general formula (5) is a compound represented by the following general formula (6).
[Wherein R ₁₇ represents a phenyl group, a methylphenyl group, an ethylphenyl group, a propylphenyl group, a butylphenyl group, a methoxyphenyl group, an ethoxyphenyl group, a propyloxyphenyl group, a butyloxyphenyl group, or a hydroxyphenyl group . Represent. R ₁₈ represents a hydrogen atom, a halogen atom, or a linear or branched alkyl group having 1 to 4 carbon atoms. R ₁₉ is substituted with a linear or branched alkyl group having 1 to 4 carbon atoms , a linear or branched alkyl group having 1 to 4 carbon atoms , or a phenyl group in which a hydrogen atom may be substituted with a fluoro group. Represents a linear or branched alkyl group having 1 to 4 carbon atoms. ] The compound represented by the general formula (6) is 2-chloro-N-[(4-fluorophenyl) methyl] -5-phenyl-3-pyridinemethanamine (Compound 1),
The collagen production promoter of Claim 3 .
The collagen production promoter according to claim 1 , wherein the compound represented by the general formula (3) is 2-chloro-5-phenylpyridine-3-carboxaldehyde (compound 3).
The collagen production promoter according to any one of claims 1 to 5 , which has an action mechanism that acts on the epidermis and promotes collagen production in the dermis via the epidermis. The collagen production promoter according to claim 6 , wherein the action mechanism for promoting collagen production is an action mechanism for promoting procollagen production. A skin external preparation for anti-aging or prevention or improvement against wrinkle formation , comprising the collagen production promoter according to any one of claims 1 to 7 . The skin external preparation according to claim 8 , wherein the collagen production promoter is contained in an amount of 0.0001 mass% to 10 mass% with respect to the total amount of the external preparation for skin. The skin external preparation according to claim 8 or 9 , which is a cosmetic (however, including quasi-drugs).