JP-7856265-B2 - Novel compounds and serotonin reuptake inhibitors

Inventors

• 太田 美里
• 大岩 優貴
• 牧 靖人
• 牧野 利明
• 関口 光広

Assignees

• 九鬼産業株式会社
• 公立大学法人名古屋市立大学
• 石川県公立大学法人

Dates

Publication Date

20260511

Application Date

20240927

Claims (12)

1. A compound represented by formula (1).
2. The compound described in claim 1 , or The compound described in claim 1 and one or more selected from the group consisting of canoconyl acetate and α-kesyl acetate , It contains a serotonin reuptake inhibitor as an active ingredient.
3. A serotonin reuptake inhibitor according to claim 2, comprising the compound described in claim 1, canoconyl acetate, and α-kessyl acetate as active ingredients, and satisfying any of the following conditions. (A) The molar ratio of the canoconyl acetate content to the total amount of the compound described in claim 1 and α-kesyl acetate is 0.5 or more. (B) The canoconyl acetate content relative to the active ingredient content is 3 mol% or more. (C) The α-kesyl acetate content relative to the active ingredient content is 1 mol% or more.
4. The agent according to claim 2 or 3, further comprising kesyl glycol diacetate as an active ingredient.
5. The serotonin reuptake inhibitor according to claim 4, wherein the value calculated by the following formula is 130% or less. Relative serotonin uptake (%) = -440 × log [concentration of canoconyl acetate (μM)] - 327 × log [concentration of kesyl glycol diacetate (μM)] + 122 × log [concentration of canoconyl acetate (μM)] × log [concentration of kesyl glycol diacetate (μM)] + 1259
6. The agent according to claim 4, wherein the ratio of kesyl glycol diacetate to canoconyl acetate (by weight) is 1 to 20:1.
7. The agent according to claim 2 or 3, wherein the active ingredient content is 800 μM or more.
8. The agent according to claim 2 or 3, wherein the active ingredient is derived from at least a part of a plant of the genus Valerian or a processed product thereof.
9. The agent according to claim 8, wherein the plant of the genus Valeriana is one or more species selected from Valeriana fauriei, Valeriana verna, Valeriana japonica, Valeriana sylvestris, and Valeriana lisianthus.
10. The agent according to claim 8, wherein the processed product is an alcohol extract of the plant body or a part thereof of a plant of the genus Valerian.
11. The processed product is the agent according to claim 8, comprising 0.8% by weight or more of kesyl glycol diacetate.
12. A method for producing a serotonin uptake inhibitor, comprising the step of mixing the compound described in claim 1 with a raw material component containing canoconyl acetate and /or α-kessyl acetate.

Description

This invention relates to novel compounds and serotonin reuptake inhibitors. Valeriana fauriei (Briq.) has traditionally been used in Japan as an ingredient in women's medicines. It is included in pharmaceuticals for menopausal symptoms, menstrual cramps, blood-related disorders, menstrual irregularities, and cold sensitivity, due to its expected anti-anxiety effects. It is also used as a flavoring agent in confectionery and other foods. Valeriana officinalis has long been used in Europe as a folk remedy for its sedative properties, and is relatively well-known in Japan as well. Therefore, it is used in herbal teas, bath products, cosmetics, and health supplements. Patent Document 1 describes a composition containing NSAIDs and valerian extract that significantly improves relief from pain and muscle tension caused by stress and trauma. Patent Document 2 describes that combining processed valerian extract with acetaminophen, ethenzamide, and allyl isopropylacetylurea exhibits an effect in improving pain-induced insomnia (sleep maintenance disorder). Patent Document 3 describes that a combination of valerian extract with ascorbic acid, glutamic acid, or Polygala extract can exert an analgesic effect and enhance the sedative effect. Patent Document 4 describes that an oral composition containing an aqueous ethanol extract of valerian root together with cannabidiol can exert a relaxing effect. Special Publication No. 2002-505296Japanese Patent Publication No. 2015-189733Japanese Patent Publication No. 2013-053144Japanese Patent Publication No. 2022-164537 Figure 1 shows the amount of serotonin uptake from valerian ethanol extract.Figure 2 shows the amount of serotonin uptake when (a) kesyl glycol diacetate (KGD) is added alone, or (b) a mixture of KGD and a fraction of valerian ethanol extract is added.Figure 3 shows the serotonin uptake levels of (a) canoconyl acetate (KNA), (b) canocol, or (c) α-kessyl acetate (α-KA).Figure 4 shows the correlation between serotonin uptake levels measured by cell experiments and predicted values for samples 1 to 13 containing KNA, canokol, α-KA, and KGD in various proportions.Figure 5 shows the serotonin reuptake inhibitory effect when KNA, KGD, canocol, and α-KA are mixed. [1. New compound] The novel compound is the compound represented by the following formula (1) (kanokol). Canokol may be either naturally derived or artificially synthesized, but naturally derived is preferred, and preferably derived from plants of the genus Valeriana (using the plant body, a part thereof, or a processed product of a plant of the genus Valeriana as a raw material). Examples of plants of the genus Valeriana include Valeriana fauriei Briq., European valerian (V. officinalis), Indian valerian (V. jatamansi (V. wallichii), climbing valerian (V. flaccidissima), and lisianthus (V. phu (V. edulis)). The plant body of a plant of the genus Valeriana may be a part thereof, for example, a part including the roots, rhizomes, or leaves, preferably a part including the roots and/or rhizomes. Examples of processed products include, Examples include processing treatments (preferably including drying, crushing, and extraction) applied to the plant body or part thereof of a plant of the genus Valerian, such as crushing, drying, heat treatment, extraction, solid-liquid separation, concentration, granulation, and/or powdering. More specifically, for example, a processed product obtained by drying and pulverizing the raw plant body (whole or part) of Valerian (Valerian powder: may be coarse powder or fine powder, the raw plant body or part thereof of a plant of the genus Valerian is dried Examples include chopped processed materials (chopped) and Valerian plant extracts. Examples of Valerian plant extracts include extracts obtained by extracting fresh or a part thereof of Valerian plants, dried materials, dried and crushed materials with a solvent, dried materials (dried extracts), and powdered dried extracts obtained by powdering these. Preferably, processed materials of Valerian roots and rhizomes are used, and more preferably, a dried extract obtained by drying and crushing a part containing the roots and rhizomes of Valerian plants and extracting it with a solvent. Examples of extraction solvents include alcohols such as ethanol, alcohol-water mixtures, and hexane, specifically aqueous alcohol (preferably 30% or more by mass, 40% or more by mass, or 50% or more by mass of alcohol) and hexane. Extraction can be performed by cold maceration or ultrasonic extraction. The extraction time can be determined according to the extraction conditions; for example, 3 to 60 hours for cold maceration and 15 minutes to 3 hours for ultrasonic extraction. Canocol can be isolated from other components in a plant extract of the Valerian genus, for example, by chromatography. Examples of purification methods include those described in the examples below. [2. Serotonin reuptake inhibitors] [Active ingredients (compounds)] Becaus