Hair growth tonic

Abstract

The present invention provides a hair growth stimulant that contains at least one type of compound selected from a group of compounds respectively represented by prescribed chemical structure formulas.

Description

Cross-reference to related applications

[0001] This application claims the priority of Japanese Patent Application No. 2021-008820, and the description of this application is incorporated herein by reference.

Technical Field

[0002] The present invention relates to a hair growth agent.

[0003] Conventionally, various hair growth agents are known. For example, a hair growth agent capable of activating dermal papilla cells at the root of hair is known.

[0004] As this type of hair growth agent, for example, those containing n-(2-(2,3,4’,5’-tetramethoxy chalcone-2-yl)-ethoxyl)-acetamide are known (Patent Document 1).

[0005] When the hair growth agent described in Patent Document 1 is added to dermal papilla cells in culture, the proliferated cells can form cell aggregates to generate spheroids, and hair growth can be promoted by the spheroids. Therefore, it can exert a hair growth effect.

Prior Art Documents

Patent Documents

[0006]

Patent Document 1

Summary of the Invention

Problems to be Solved by the Invention

[0007] However, hair growth agents that can activate dermal papilla cells and exert a good hair growth effect have not yet been fully studied.

[0008] Therefore, an object of the present invention is to provide a hair growth agent that can activate dermal papilla cells and exert a good hair growth effect.

Means for Solving the Problems

[0009] The hair growth agent according to the present invention is characterized by containing at least one compound selected from the group consisting of a compound represented by the following general formula (A), a compound represented by the following general formula (B), a compound represented by the following general formula (C), a compound represented by the following general formula (D), a compound represented by the following formula (E), a compound represented by the following general formula (F), and a compound represented by the following general formula (G). [ka] (However, in general formula (A), stereoisomers are included, the seven * symbols each independently represent a chiral center that forms an enantiomer, and M is either H or CH3.) [ka] (However, in general formula (B), α is one of the following formulas (B'-1) to (B'-17), and β is one of the following formulas (B"-1) to (B"-6).) [ka] [ka] [ka] (However, in general formula (C), γ is one of the following formulas (C'-1) to (C'-10), and X is H or OCH3.) [ka] [ka] (However, in general formula (D), m is 0 or 1, When m is 0, δ is one of the following equations (D'-1) to (D'-9), and Y 1 ,Y 2 ,Y 3 Each of these is independently either H, OH, or OCH3, or Y1 , Y 2 , and Y 3 One of them is H and the other two form a cyclic ether structure, When m is 1, the compound represented by the general formula (D) is represented by either the following general formula (D'-10) or the following general formula (D'-11). In the following general formula (D'-10) or the following general formula (D'-11), Y 1 , Y 2 , Y 3 , Y 4 , Y 5 , and Y 6 are each independently H, OH, or OCH3. In the following general formula (D'-11), Z is H, CH3, C2H5, tert-C4H9, or C(CH3)2-C2H5.)

Chemical formula

Chemical formula

Chemical formula

Chemical formula

Chemical formula

[0010] [Figure 1] Examples of molecular structural formulas for compounds represented by general formula (A). [Figure 2A] Examples of molecular structural formulas for compounds represented by general formula (B). [Figure 2B] Examples of molecular structural formulas for compounds represented by general formula (B). [Figure 2C] Examples of molecular structural formulas for compounds represented by general formula (B). [Figure 2D] Examples of molecular structural formulas for compounds represented by general formula (B). [Figure 3A] Examples of molecular structural formulas for compounds represented by general formula (C). [Figure 3B] Examples of molecular structural formulas for compounds represented by general formula (C). [Figure 4A] The molecular structural formulas of examples of compounds represented by general formula (D). [Figure 4B] The molecular structural formulas of examples of compounds represented by general formula (D). [Figure 4C] The molecular structural formulas of examples of compounds represented by general formula (D). [Figure 5A] Examples of molecular structural formulas for compounds represented by general formula (F). [Figure 5B] Examples of molecular structural formulas for compounds represented by general formula (F). [Figure 6A] Examples of molecular structural formulas for compounds represented by general formula (G). [Figure 6B] Examples of molecular structural formulas for compounds represented by general formula (G). [Figure 6C] Examples of molecular structural formulas for compounds represented by general formula (G). [Figure 6D] Examples of molecular structural formulas for compounds represented by general formula (G). [Figure 6E] Examples of molecular structural formulas for compounds represented by general formula (G). [Figure 6F] Examples of molecular structural formulas for compounds represented by general formula (G). [Figure 6G] Examples of molecular structural formulas for compounds represented by general formula (G). [Figure 6H] Examples of molecular structural formulas for compounds represented by general formula (G). [Figure 6I] Examples of molecular structural formulas for compounds represented by general formula (G). [Figure 6J] Examples of molecular structural formulas for compounds represented by general formula (G). [Figure 7] A graph showing the results of in vitro tests related to the activation of hair papilla cells. [Figure 8] A graph showing the results of in vitro tests related to the activation of hair papilla cells. [Figure 9] A graph showing the results of in vitro tests related to the activation of hair papilla cells. [Figure 10] A graph showing the results of organ culture tests (ex vivo tests) of hair papilla cells. [Figure 11] A graph showing the results of organ culture tests (ex vivo tests) of hair papilla cells. [Figure 12] A graph showing the results of organ culture tests (ex vivo tests) of hair papilla cells. [Modes for carrying out the invention]

[0011] One embodiment of the hair growth agent according to the present invention will be described below.

[0012] The hair growth agent of this embodiment contains at least one compound selected from the group consisting of the compound represented by the above general formula (A), the compound represented by the above general formula (B), the compound represented by the above general formula (C), the compound represented by the above general formula (D), the compound represented by the above formula (E), the compound represented by the above general formula (F), and the compound represented by the above general formula (G). Since the hair growth agent of this embodiment contains at least one of the compounds described above, it can activate hair papilla cells and exhibit a good hair growth effect.

[0013] In the compound represented by general formula (A), M is preferably CH3. In general formula (A), each of the seven asterisks independently represents either the S or R stereoconfiguration of a chiral carbon atom capable of forming enantiomers of the above compound. In other words, each of the seven asterisks independently represents a chiral center.

[0014] Examples of compounds represented by general formula (A) include the compounds having the molecular structure shown in Figure 1. As for compounds represented by general formula (A), the compounds shown in formulas (A1) and (A4) in Figure 1 are preferred because they exhibit better hair growth effects.

[0015] The compound represented by formula (A1) in Figure 1 is called Bardoxolone methyl. The chemical name of such a compound is 2-cyano-3,12-dioxo-oleana-1,9(11)-dien-28-oic acid, methyl ester. The chemical name of general formula (A) that includes the above *S or R is, for example, (4aS,6aR,6bS,8aR,12aS,14aR,14bS)-methyl 11-cyano-2,2,6a,6b,9,9,12a-heptamethyl-10,14-dioxo-1,2,3,4,4a,5,6,6a,6b,7,8,8a,9,10,12a,14,14a,14b-octadecahydropicene-4a-carboxylate.

[0016] In the compound represented by general formula (B), it is preferable that α is of formula (B'-1), formula (B'-2), formula (B'-4), formula (B'-7), or formula (B'-12), and β is of formula (B''-1). This allows for a better hair growth effect.

[0017] Examples of compounds represented by general formula (B) include the compounds with the molecular structures shown in Figures 2A to 2D. As compounds represented by general formula (B), the compounds shown in formulas (B01), (B02), and (B04) in Figure 2A, the compound shown in formula (B07) in Figure 2B, and the compound shown in formula (B12) in Figure 2C are preferred in that they exhibit better hair growth effects.

[0018] The compound represented by formula (B01) in Figure 2A is a compound called necrosulfonamide. The chemical name of this compound is (2E)-N-[4-[[(3-methoxy-2-pyrazinyl)amino]sulfonyl]phenyl]-3-(5-nitro-2-thienyl)-2-propenamide. In Figure 2A, the chemical name of the compound represented by formula (B02) is 3-(furan-2-yl)-N-[[4-[(3-methoxypyrazin-2-yl)sulfamoyl]phenyl]carbamothioyl]prop-2-enamide. In Figure 2A, the chemical name of the compound represented by formula (B04) is N-[4-[(3-methoxypyrazin-2-yl)sulfamoyl]phenyl]-3-(4-nitrophenyl)prop-2-enamide. In Figure 2B, the chemical name of the compound represented by formula (B07) is 4-acetyl-N-[4-[(3-methoxypyrazin-2-yl)sulfamoyl]phenyl]benzamide.

[0019] In the compound represented by general formula (C), γ is preferably formula (C'-1), formula (C'-2), formula (C'-3), formula (C'-7), or formula (C'-10), and X is preferably H or OCH3. This allows for a better hair growth effect.

[0020] Examples of compounds represented by general formula (C) include the compounds with the molecular structures shown in Figures 3A and 3B. As compounds represented by general formula (C), the compounds shown in formulas (C01), (C02), and (C03) in Figure 3A, and the compounds shown in formulas (C07) and (C10) in Figure 3B are preferred in that they exhibit better hair growth effects.

[0021] In Figure 3A, the compound represented by formula (C01) is a compound called SU 9516. The chemical name of this compound is 1,3-dihydro-3Z-(1H-imidazol-5-ylmethylene)-5-methoxy-2H-indol-2-one. In Figure 3B, the chemical name of the compound represented by formula (C07) is (E)-3-benzylidene-5-methoxyindolin-2-one. In Figure 3B, the chemical name of the compound represented by formula (C10) is (E)-5-methoxy-3-(pyridine-2-ylmethylene)indolin-2-one.

[0022] In a compound represented by general formula (D), m is 0, δ is formula (D'-1), formula (D'-2), formula (D'-3), formula (D'-4), or formula (D'-5), and Y 1 , Y 2 , Y 3 However, it is preferable that each component be independently H, OH, or OCH3. This allows for a better hair growth effect. Furthermore, a compound represented by general formula (D) is also represented by general formula (D'-10), and Y 1 , Y 2 , Y 3 , Y 4, Y 5 , Y 6 However, each is preferably independently H or OCH3. Alternatively, the compound represented by general formula (D) is represented by general formula (D'-11), where Z is H and Y 1 , Y 2 , Y 3 , Y 4 , Y 5 , Y 6 However, it is preferable that each component be either H or OCH3 independently. This allows for a better hair growth effect.

[0023] Examples of compounds represented by general formula (D) include the compounds with the molecular structures shown in Figures 4A to 4C. Among the compounds represented by general formula (D), those shown in Figure 4A as (D01), (D02), (D04), and (D08), and those shown in Figure 4B as (D15), (D18), and (D19) are preferred in that they exhibit better hair growth effects. The compound shown in formula (D19) includes stereoisomers.

[0024] In Figure 4A, the compound represented by formula (D01) is a compound called FLLL32. The chemical name of this compound is (2E,2'E)-1,1'-cyclohexylidenebis[3-(3,4-dimethoxyphenyl)]-2-propen-1-one. In Figure 4A, the chemical name of the compound represented by formula (D08) is 2-cyclopentyl-5-[(3,4-dimethoxyphenyl)methylidene]cyclopentan-1-one.

[0025] The compound represented by the above formula (E) is called Vactosertib EW-7197. The chemical name of this compound is N-(2-fluorophenyl)-5-(6-methyl-2-pyridinyl)-4-[1,2,4]triazolo[1,5-a]pyridin-6-yl-1H-imidazole-2-methanamine.

[0026] In the compound represented by general formula (F), it is preferable that n is 1 or 2. Also, T is H, and G 1 and G 2 However, each is independently H, OCH3, or OC2H5, and Q 1 and Q 2 It is preferable that all of these are NH. This allows for a better hair growth effect.

[0027] Examples of compounds represented by general formula (F) include the compounds with the molecular structures shown in Figures 5A and 5B. As for compounds represented by general formula (F), the compounds shown by formula (F1) and (F4) in Figure 5A, and the compound shown by formula (F9) in Figure 5B are preferred in that they exhibit better hair growth effects.

[0028] In Figure 5A, the compound represented by formula (F1) is a compound called ML-346. The chemical name of this compound is 5-[3-(4-methoxyphenyl)-2-propen-1-ylidene]-2,4,6(1H,3H,5H)-pyrimidinetrione. In Figure 5B, the chemical name of the compound represented by formula (F9) is 5-[(4-ethoxyphenyl)methylidene]-1,3-diazinane-2,4,6-trione.

[0029] In the compound represented by general formula (G), preferably A is H, U is C=O, R is NH, and L 1 , L 2 , L 3 , L 4 , L 5 At least three of them are H and the other two are independently H, Cl, F, CH3, or a structure represented by the following formula (G'-1), J 1 , J 2 , J 3 , J 4 , J 5At least three of these are H, and the other two are H, F, or OCH3, or the other two form a five-membered ring represented by (G''-1). This allows for a better hair growth effect.

[0030] Examples of compounds represented by general formula (G) include the compounds with the molecular structures shown in Figures 6A to 6J. As compounds represented by general formula (G), the compounds shown in formulas (G01) and (G05) in Figure 6A, the compound shown in formula (G11) in Figure 6B, the compound shown in formula (G36) in Figure 6D, the compound shown in formula (G70) in Figure 6G, and the compound shown in formula (G82) in Figure 6I are preferred in that they exhibit better hair growth effects.

[0031] The compound represented by formula (G01) in Figure 6A is a compound called CCG-215022. The chemical name of this compound is 4-[4-fluoro-3-[[(2-pyridinylmethyl)amino]carbonyl]phenyl]-1,2,3,4-tetrahydro-N-1H-indazol-5-yl-6-methyl-2-oxo-5-pyrimidinecarboxamide. In Figure 6D, the chemical name of the compound represented by formula (G36) is 6-methyl-4-(3-methylphenyl)-2-oxo-N-phenyl-3,4-dihydro-1H-pyrimidine-5-carboxamide. In Figure 6G, the chemical name of the compound represented by formula (G70) is 4-(4-fluorophenyl)-N-(1H-indazol-5-yl)-6-methyl-2-oxo-3,4-dihydro-1H-pyrimidine-5-carboxamide. In Figure 6I, the chemical name of the compound represented by formula (G82) is N-(2-methoxyphenyl)-6-methyl-4-(3-methylphenyl)-2-oxo-3,4-dihydro-1H-pyrimidine-5-carboxamide.

[0032] As the compounds represented by the above general formulas (A) to (G) and formula (E), commercially available products can be used. For each of the above compounds, products from companies such as Targetmol, Medchemexpress, Cayman Chemical, and Chemscene can be purchased and used.

[0033] In the hair growth agent of this embodiment, the total concentration of the above-mentioned compounds is preferably 0.001% by mass or more and 5% by mass or less, and more preferably 0.01% by mass or more and 1.0% by mass or less. The above-mentioned concentration allows for a more effective hair growth treatment.

[0034] The above hair growth products typically contain water and may also contain thickeners, surfactants, preservatives, and other ingredients in addition to those listed above.

[0035] The properties of the hair growth agent in this embodiment are not particularly limited, but for example, it is liquid. The hair growth agent in this embodiment may also be solid.

[0036] The hair growth agent of this embodiment can be manufactured by a general method. For example, the above hair growth agent can be manufactured by mixing and stirring each of the ingredients. A standard stirring device can be used. If necessary, stirring may be done while heating.

[0037] The hair growth product described above is typically applied to the scalp. It may also be applied to areas where hair growth is desired, such as the eyebrows. Furthermore, it may be used as a patch.

[0038] The hair growth agent of this embodiment is not necessarily bound by the classification of cosmetics, quasi-drugs, pharmaceuticals, etc. as defined by the pharmaceutical laws of various countries around the world.

[0039] The matters disclosed herein include the following: (1) A hair growth agent comprising at least one compound selected from the group consisting of the compound represented by the above general formula (A), the compound represented by the above general formula (B), the compound represented by the above general formula (C), the compound represented by the above general formula (D), the compound represented by the above formula (E), the compound represented by the above general formula (F), and the compound represented by the above general formula (G). (2) The hair growth agent described in (1) above, wherein M is CH3 in the general formula (A) above. (3) The hair growth agent according to (1) or (2) above, wherein in the general formula (B) above, α is the formula (B'-1), (B'-2), (B'-4), or (B'-7) above, and β is the formula (B''-1) above. (4) A hair growth agent according to any one of (1) to (3) above, wherein in the above general formula (C), γ is the above formula (C'-1), (C'-7), or (C'-10), and X is OCH3. (5) In the above general formula (D), m is 0, δ is the above formula (D'-3), and Y 1 , Y 2 , Y 3 However, each is independently either H or OCH3, or m is 1 and the compound represented by the above general formula (D) is the compound represented by the above general formula (D'-10), and Y 1 , Y 2 , Y 3 , Y 4 , Y 5 , Y 6 A hair growth agent according to any of (1) to (4) above, wherein each is independently H or OCH3. (6) In the above general formula (F), n is 1 or 2, T is H, and G 1 and G 2 Each of these is independently H, OCH3, or OC2H5, and Q 1 and Q 2 A hair growth agent according to any of (1) to (5) above, wherein all of the above are NH. (7) In the above general formula (G), A is H, U is C=O, R is NH, and L 1 ,L 2 ,L 3 ,L 4 , and L 5 Each of these is independently a structure represented by H, F, CH3, or the following formula (G'-1), and J 1 ,J 2 ,J 3 ,J 4 , and J 5 All of them are H, or the J 1 ~J 5 A hair growth agent according to any one of (1) to (6) above, wherein two adjacent members of the group form a five-membered ring represented by the above formula (G''-1) and the other three members are H. (8) A hair growth agent according to any one of (1) to (7) above, comprising at least one selected from the group consisting of the compound represented by formula (A1) in Figure 1, the compound represented by formula (B01) in Figure 2A, the compound represented by formula (B02) in Figure 2A, the compound represented by formula (B04) in Figure 2A, the compound represented by formula (B07) in Figure 2B, the compound represented by formula (C01) in Figure 3A, the compound represented by formula (C07) in Figure 3B, the compound represented by formula (C10) in Figure 3B, the compound represented by formula (D01) in Figure 4A, the compound represented by formula (D08) in Figure 4A, the compound represented by the above formula (E), the compound represented by formula (F1) in Figure 5A, the compound represented by formula (F9) in Figure 5B, the compound represented by formula (G01) in Figure 6A, the compound represented by formula (G36) in Figure 6D, the compound represented by formula (G70) in Figure 6G, and the compound represented by formula (G82) in Figure 6I. The chemical structures of each compound are shown in the following paragraph.

[0040] [ka]

[0041] [ka]

[0042] [ka]

[0043] The hair growth agent of the present invention is as illustrated above, but the present invention is not limited to the embodiments described above. Furthermore, the present invention can employ various forms used in general hair growth agents, etc., as long as they do not impair the effects of the present invention. [Examples]

[0044] The present invention will now be described in more detail with reference to examples, but the present invention is not limited to these examples.

[0045] (Test examples 1-7) Each hair growth agent for each test example was prepared by dissolving the following components in water or an organic solvent. Test Example 1 / Compound (a): Compound represented by formula (A1) in Figure 1 Test Example 2 / Compound (b-1): Compound represented by formula (B01) in Figure 2A Test Example 3 / Compound (c-1): Compound represented by formula (C01) in Figure 3A Test Example 4 / Compound (d-1): Compound represented by formula (D01) in Figure 4A Test Example 5 / Compound (e): Compound represented by the above formula (E) Test Example 6 / Compound (f-1): Compound represented by formula (F1) in Figure 5A Test Example 7 / Compound (g-1): Compound represented by formula (G01) in Figure 6A

[0046] <In vitro tests related to the activation of hair papilla cells> Details of the in vitro test are as follows: Hair papilla cells (HFDPC, manufactured by TOYOBO) are divided into 1.2 × 10⁻⁶ units. 5Cells were seeded in 6-well plates and cultured for 24 hours at 37°C and 5% CO2. Culture was performed using dermal papilla cell proliferation medium (TOYOBO). After culture, the medium was removed and replaced with a medium containing each compound. For the replacement medium, Dulbecco's modified MEM medium (GIBCO) supplemented with 1% fetal bovine serum (SIGMA) and 1% penicillin / streptomycin (SIGMA) was used. Subsequently, the cells were cultured for 48 hours at 37°C and 5% CO2. Furthermore, total RNA was purified from the cells using the "PureLink RNA Mini kit" (INVITROGEN) and reverse transcribed into cDNA using "ReverTraAce™ qPCR RT Master Mix" (TOYOBO). The mRNA expression levels of hair growth-related factors were quantitatively evaluated using real-time PCR. ATP5F1 was used as an internal standard. We examined the mRNA expression levels of hair growth-related factors, specifically VEGF, VCAN, FGF7, and ALP. Each compound was dissolved in dimethyl sulfoxide (DMSO) to prepare a solution, and then the prepared solution was added to the culture medium so that each compound was at a concentration of 0.1 to 1.0 μM. At that time, the solution was diluted with DMSO to a concentration that would not cause cytotoxicity (1% or less). The evaluation results are shown in Figure 7.

[0047] (Test examples 8-15) Using the components listed below, hair growth agents for each test example were manufactured in the same manner as the test method described above, and in vitro tests related to the activation of dermal papilla cells were conducted. The evaluation results are shown in Figure 8. Test Example 8 / Compound (b-2): Compound represented by formula (B04) in Figure 2A Test Example 9 / Compound (b-3): Compound represented by formula (B07) in Figure 2B Test Example 10 / Compound (c-2): Compound represented by formula (C07) in Figure 3B Test Example 11 / Compound (c-3): Compound represented by formula (C10) in Figure 3B Test Example 12 / Compound (d-2): Compound represented by formula (D08) in Figure 4A Test Example 13 / Compound (f-2): Compound represented by formula (F9) in Figure 5B Test Example 14 / Compound (g-2): Compound represented by formula (G36) in Figure 6D Test Example 15 / Compound (g-3): Compound represented by formula (G70) in Figure 6G Test Example 16 / Compound (g-4): Compound represented by formula (G82) in Figure 6I

[0048] (Test Example 17) Using the ingredients listed below, a hair growth agent for Test Example 16 was manufactured in the same manner as the test method described above, and an in vitro test related to the activation of dermal papilla cells was conducted. The evaluation results are shown in Figure 9. Test Example 17 / Compound (b-4): Compound represented by formula (B02) in Figure 2A

[0049] <Organ culture test using hair papilla cells (ex. vivo test)> The cheeks of male mice (7 weeks old) were disinfected with 70% ethanol, and cheek tissue was collected. The collected tissue was washed by immersion in phosphate-buffered saline and then immersed in hair follicle culture medium. As the hair follicle culture medium, Dulbecco's modified MEM medium (GIBCO) supplemented with 10% fetal bovine serum (SIGMA) and 1% penicillin / streptomycin (SIGMA) was used. Subsequently, under a stereomicroscope, hair follicle organs were isolated one by one using a microscalpel (the number of hair follicle organs [n] per group per experiment was 8). 2.0 mL of hair follicle culture medium was pre-filled into a 60 mm dish. Dulbecco's modified MEM medium (GIBCO), supplemented with 10% fetal bovine serum (SIGMA) and 1% penicillin / streptomycin (SIGMA), was used as the hair follicle culture medium. A cell culture insert (30 mm, hydrophilic PTFE, 0.4 μm (Millipore)) was then placed in the dish. Isolated hair follicles were placed on the cell culture insert. After 24 hours of pre-culture at 37°C under 5% CO2, the experiment was started by adding one solution containing each compound to each group. Each compound was dissolved in DMSO to achieve a final concentration in the range of 0.1–1.0 μg before being added to the hair follicle culture system. Beard elongation was measured 6 days after addition.

[0050] The results for test examples 1-7 are shown in Figure 10. The results for test examples 9, 12, and 14-16 are shown in Figure 11. The results for test example 17 are shown in Figure 12.

[0051] As can be seen from the results above, the hair growth agent of this embodiment was able to directly activate dermal papilla cells. As a result, the hair growth effect was fully exerted. Furthermore, each compound shown in the diagram has a molecular structure similar to any of the compounds used in the above experiment, and is included in the compounds represented by general formulas (A) to (G). Therefore, it can be said that each compound shown in the diagram can similarly activate hair papilla cells and exert a hair growth effect. [Industrial applicability]

[0052] The hair growth agent of the present invention is used by applying it to the scalp for purposes such as promoting hair growth or regenerating hair. The hair growth agent of the present invention is suitable for use in applications such as quasi-drugs, for example, by applying it directly to the scalp.

Claims

[Claim 1] A hair growth agent comprising at least one selected from the group consisting of a compound represented by the following general formula (B), a compound represented by the following general formula (C), a compound represented by the following general formula (D), a compound represented by the following formula (E), a compound represented by the following general formula (F), and a compound represented by the following general formula (G) (excluding compounds in which γ in general formula (C) is the following formula (C'-1) and X is OCH3). 【Chemistry 1】 (However, in general formula (B), α is one of the following formulas (B'-1) to (B'-17), and β is one of the following formulas (B''-1) to (B''-6).) 【Chemistry 2】 【Transformation 3】 【Chemistry 4】 (However, in general formula (C), γ is one of the following formulas (C'-1) to (C'-10), and X is H or OCH.) ３ (That is the case.) 【Transformation 5】 【Transformation 6】 (However, in general formula (D), m is 0 or 1, When m is 0, δ is one of the following equations (D'-1) to (D'-9), and Y １ , Y ２ , Y ３ These are, independently, H, OH, or OCH. ３ is or Y １ , Y ２ , and Y ３ One of them is H and the other two form a cyclic ether structure, When m is 1, the compound represented by the general formula (D) is represented by either the following general formula (D'-10) or the following general formula (D'-11). In the following general formula (D'-10) or the following general formula (D'-11), Y １ , Y ２ , Y ３ , Y ４ , Y ５ , and Y ６ is, independently of each other, H, OH, or OCH ３ . In the following general formula (D'-11), Z is H, CH ３ , C ２ H ５ , tert-C ４ H ９ , or C(CH ３ ) ２ -C ２ H ５ .) 【Transformation 7】 【Transformation 8】 【Chemistry 9】 【Chemistry 10】 (However, in general formula (F), n is 1 or 2, T is H or OH, and G １ and G ２ These are H and OCH, respectively, independently. ３ , OC ２ H ５ , or OH, Q １ and Q ２ These are N-H and N-CH, respectively, independently. ３ , or N. 【Chemistry 11】 (However, in general formula (G), A is H or CH) ３ U is C=O or C-OH, and R is N-H or N-(cyclo)C ３ H ５ N-CH ２ CH=CH ２ N-CH ３ , N-C ２ H ４ -CH ３ , or N and L １ , L ２ , L ３ , L ４ , and L ５ These are H, F, Cl, CN, OH, NO, each independently. ２ ,CH ３ tert-C ４ H ９ CF ３ , or a structure represented by the following formula (G'-1), J １ , J ２ , J ３ , J ４ , and J ５ These are H, F, Cl, Br, and OCH, respectively, independently. ３ ,CH ３ CF ３ , or NO ２ is or, as stated above, J １ ~J ５ Two of these adjacent atoms form a five-membered ring represented by the following formula (G''-1), and the other three are H atoms. 【Chemistry 12】

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