JP2022102931A - Anti-inflammatory agent - Google Patents
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Abstract
Description
本発明は、抗炎症剤に関する。 The present invention relates to an anti-inflammatory agent.
従来、非ステロイド系抗炎症薬などを含む、様々な抗炎症剤が知られている(例えば、非特許文献1参照)。 Conventionally, various anti-inflammatory agents including non-steroidal anti-inflammatory drugs are known (see, for example, Non-Patent Document 1).
本発明は、新規な抗炎症剤を提供することを目的とする。 An object of the present invention is to provide a novel anti-inflammatory agent.
本発明の一実施態様は、一般式(I)を有する化合物、またはその薬学的に許容される塩を有効成分として含有する抗炎症剤である。
(I)
One embodiment of the present invention is an anti-inflammatory agent containing a compound having the general formula (I) or a pharmaceutically acceptable salt thereof as an active ingredient.
(I)
(式中、R1及びR2は、独立に、水素、ハロゲン、及び-OR8から選択され、R3及びR4は、一方が水素、ハロゲン、及び-OR8から選択され、他方が
(In the equation, R 1 and R 2 are independently selected from hydrogen, halogen, and -OR 8 , and R 3 and R 4 are independently selected from hydrogen, halogen, and -OR 8 and the other.
であって、R5、R6、及びR7は、独立に、水素、ハロゲン、-OR8、及び-NR9から選択され、R8及びR9は、独立に水素、およびC1~C6のアルキルから選択され、Xは、>O、>S、及び>NR10から選択され、R10は水素およびC1~C6のアルキルまたはシクロアルキルから選択される。) Thus, R 5 , R 6 and R 7 are independently selected from hydrogen, halogen, -OR 8 and -NR 9 , and R 8 and R 9 are independently hydrogen and C1 to C6. Selected from alkyl, X is selected from>O,> S, and> NR 10 , and R 10 is selected from hydrogen and C1-C6 alkyl or cycloalkyl. )
上記一般式(I)において、R1及びR2は、独立に、水素、または-OMeであって、R3は、水素であって、R4は、
In the above general formula (I), R 1 and R 2 are independently hydrogen or -OMe, R 3 is hydrogen, and R 4 is.
であって、R5は、水素、-OH、または-OMeであって、R6は、水素、ハロゲン、-N(CH3)2、-OH、または-OMeであって、R7は、水素、または-OMeであってもよい。また、上記一般式(I)において、R1及びR2は、独立に、水素、または-OMeであって、R3は、
R 5 is hydrogen, -OH, or -OMe, R 6 is hydrogen, halogen, -N (CH 3 ) 2 , -OH, or -OMe, and R 7 is. It may be hydrogen or -OMe. Further, in the above general formula (I), R 1 and R 2 are independently hydrogen or -OMe, and R 3 is.
であって、R5は、水素であって、R6は、水素、ハロゲン、または-OMeであって、R7は、水素、または-OMeであってR4は、水素であってもよい。Xは、>O、>S、及び>NHであることが好ましい。上記抗炎症剤は、以下のいずれかの化合物、またはその薬学的に許容される塩を有効成分として含有してもよい
R 5 may be hydrogen, R 6 may be hydrogen, halogen, or -OMe, R 7 may be hydrogen, or -OMe, and R 4 may be hydrogen. .. X is preferably>O,> S, and> NH. The anti-inflammatory agent may contain any of the following compounds or pharmaceutically acceptable salts thereof as an active ingredient.
上記抗炎症剤は、腫瘍促進性炎症tumor-promoting inflammation)に対するものでもよい。 The anti-inflammatory agent may be for tumor-promoting inflammation).
本発明の他の実施態様は、in vitroで、一般式(I)を有する化合物、またはその薬学的に許容される塩の抗炎症効果を評価する評価方法である。
(I)
Another embodiment of the present invention is an evaluation method for evaluating the anti-inflammatory effect of a compound having the general formula (I) or a pharmaceutically acceptable salt thereof in vitro.
(I)
(式中、R1及びR2は、独立に、水素、ハロゲン、及び-OR8から選択され、R3及びR4は、一方が水素、ハロゲン、及び-OR8から選択され、他方が
(In the equation, R 1 and R 2 are independently selected from hydrogen, halogen, and -OR 8 , and R 3 and R 4 are independently selected from hydrogen, halogen, and -OR 8 and the other.
であって、R5、R6、及びR7は、独立に、水素、ハロゲン、-OR8、及び-NR9から選択され、R8及びR9は、独立に水素、およびC1~C6のアルキルから選択され、Xは、>O、>S、>NR10、>SO、および>SO2から選択され、R10は水素、C1~C6のアルキルまたはシクロアルキル、および置換または無置換のフェニルから選択される。) Thus, R 5 , R 6 and R 7 are independently selected from hydrogen, halogen, -OR 8 and -NR 9 , and R 8 and R 9 are independently hydrogen and C1 to C6. Selected from alkyl, X is selected from>O,>S,> NR 10 ,> SO, and> SO 2 , R 10 is hydrogen, alkyl or cycloalkyl of C1-C6, and substituted or unsubstituted phenyl. Is selected from. )
上記評価方法において、前記化合物、またはその薬学的に許容される塩の存在下で、培養細胞を刺激し、生産される炎症性因子の量を測定することによって、前記化合物、またはその薬学的に許容される塩の抗炎症効果を評価してもよい。前記培養細胞にLPSまたはHMGB1を投与することによって、前記培養細胞を刺激してもよい。前記炎症性因子が、炎症性サイトカインまたはケモカインであってもよい。前記炎症性因子が、TNF-α、IL-1α、IL-1β、IL-6、IL-8、IFR-γ、G-CSF、IL-17、IL33、GM-CSF、CCL2、およびCXCL2から選択される1以上の因子であってもよい。 In the above evaluation method, by stimulating cultured cells and measuring the amount of inflammatory factor produced in the presence of the compound or a pharmaceutically acceptable salt thereof, the compound or its pharmaceutically acceptable salt thereof. The anti-inflammatory effect of the acceptable salt may be evaluated. The cultured cells may be stimulated by administering LPS or HMGB1 to the cultured cells. The inflammatory factor may be an inflammatory cytokine or a chemokine. The inflammatory factor is selected from TNF-α, IL-1α, IL-1β, IL-6, IL-8, IFR-γ, G-CSF, IL-17, IL33, GM-CSF, CCL2, and CXCL2. It may be one or more factors to be used.
本発明によって、新規な抗炎症剤を提供することができるようになった。 The present invention has made it possible to provide a novel anti-inflammatory agent.
本発明の目的、特徴、利点、およびそのアイデアは、本明細書の記載により、当業者には明らかであり、本明細書の記載から、当業者であれば、容易に本発明を再現できる。以下に記載された発明の実施の形態および具体的な実施例などは、本発明の好ましい実施態様を示すものであり、例示または説明のために示されているのであって、本発明をそれらに限定するものではない。本明細書で開示されている本発明の意図並びに範囲内で、本明細書の記載に基づき、様々な改変並びに修飾ができることは、当業者にとって明らかである。 The objects, features, advantages, and ideas thereof of the present invention will be apparent to those skilled in the art by the description of the present specification, and those skilled in the art can easily reproduce the present invention from the description of the present specification. The embodiments and specific examples of the invention described below show preferred embodiments of the present invention and are shown for illustration or illustration purposes, and the present invention is described in them. It is not limited. It will be apparent to those skilled in the art that various modifications and modifications can be made based on the description herein within the intent and scope of the invention disclosed herein.
==化合物==
一般式(I)を有する化合物、またはその薬学的に許容される塩は、本開示の抗炎症剤に、有効成分として含有されている
(I)
== Compound ==
The compound having the general formula (I), or a pharmaceutically acceptable salt thereof, is contained as an active ingredient in the anti-inflammatory agent of the present disclosure.
(I)
(式中、R1及びR2は、独立に、水素、ハロゲン、及び-OR8から選択され、R3及びR4は、一方が水素、ハロゲン、及び-OR8から選択され、他方が
(In the equation, R 1 and R 2 are independently selected from hydrogen, halogen, and -OR 8 , and R 3 and R 4 are independently selected from hydrogen, halogen, and -OR 8 and the other.
であって、R5、R6、及びR7は、独立に、水素、ハロゲン、-OR8、及び-NR9から選択され、R8及びR9は、独立に水素、およびC1~C6のアルキルから選択され、Xは、>O、>S、及び>NR10から選択され、R10は水素およびC1~C6(好ましくは、C1~C3)のアルキルまたはシクロアルキルから選択される。) Thus, R 5 , R 6 and R 7 are independently selected from hydrogen, halogen, -OR 8 and -NR 9 , and R 8 and R 9 are independently hydrogen and C1 to C6. Selected from alkyl, X is selected from>O,> S, and> NR 10 , and R 10 is selected from hydrogen and alkyl or cycloalkyl of C1-C6 (preferably C1-C3). )
本明細書において、上記化合物のうち、R3は、水素であって、R4は、
In the present specification, among the above compounds, R 3 is hydrogen and R 4 is.
である化合物をA群とし、R4は、水素であって、R3は、
である化合物をB群とする。
Group A is a compound that is, R 4 is hydrogen, and R 3 is.
Let the compound be B group.
A群の化合物のうち、R1及びR2は、独立に、水素、または-OMeであって、R5は、水素、-OH、または-OMeであって、R6は、水素、ハロゲン、-N(CH3)2、-OH、または-OMeであって、R7は、水素、または-OMeであって、XはO、S、またはNHであるものが好ましい。特に、以下の化合物が好ましい。
Of the compounds in Group A, R 1 and R 2 are independently hydrogen or -OMe, R 5 is hydrogen, -OH, or -OME, and R 6 is hydrogen, halogen. It is preferably -N (CH 3 ) 2 , -OH, or -OMe, where R 7 is hydrogen, or -OMe, and X is O, S, or NH. In particular, the following compounds are preferred.
また、B群の化合物のうち、R1及びR2は、独立に、水素、または-OMeであって、R5は、水素であって、R6は、水素、ハロゲン、または-OMeであって、R7は、水素、または-OMeであって、XはO、S、またはNHであるものが好ましい。特に、以下の化合物が好ましい。
Further, among the compounds of Group B, R 1 and R 2 are independently hydrogen or -OMe, R 5 is hydrogen, and R 6 is hydrogen, halogen, or -OMe. It is preferable that R 7 is hydrogen or —OMe and X is O, S, or NH. In particular, the following compounds are preferred.
これらの化合物は、公知の製造方法で合成してもよく、市販の化合物を購入して用いてもよい(例えば、A群については、Koichi Takaoらの論文(Chem. Pharm. Bull., vol.62, pp.810-815 (2014);Anticancer Res., vol.40. pp.87-95 (2020))、B群については、Koichi Takaoらの論文(Bioorg. Chem., 92, 103285 (2019)を参照のこと)。
These compounds may be synthesized by a known production method, or commercially available compounds may be purchased and used (for example, for Group A, a paper by Koichi Takao et al. (Chem. Pharm. Bull., Vol.). 62, pp.810-815 (2014); Anticancer Res., Vol.40. Pp.87-95 (2020)), for group B, Koichi Takao et al. (Bioorg. Chem., 92, 103285 (2019) )checking).
==抗炎症剤==
本開示の抗炎症剤は、上記いずれかの化合物、またはその薬学的に許容される塩、またはその組み合わせを有効成分として含有する。
== Anti-inflammatory agent ==
The anti-inflammatory agent of the present disclosure contains any of the above compounds, or a pharmaceutically acceptable salt thereof, or a combination thereof as an active ingredient.
炎症とは、感染あるいは細胞損傷などに対する生体防御反応の一つであるが、本開示の抗炎症剤の対象となる炎症は特に限定されず、例えば慢性炎症であっても急性炎症であってもよいが、花粉症、アレルギー性鼻炎、アレルギー性結膜炎、アトピー性皮膚炎、遅延型アレルギー等のアレルギーからくる炎症、胃炎および潰瘍性大腸炎等の内臓の炎症性疾患、関節リウマチおよび変性性骨関節炎等の関節炎等の炎症だけでなく、動脈硬化、子宮内膜症、急性呼吸急迫症候群、気管支炎、腎臓移植による障害、急性心筋梗塞、糖尿病、全身性エリテマトーデス、クローン病、腎炎、肝炎、肺炎、IgA腎症、エンドトキシンショック、感染症による敗血症、外科的傷害からくる炎症等、様々な炎症性疾患を含むが、特に腫瘍前段階にある新生細胞(neoplasia)を腫瘍に発達させる腫瘍促進性炎症(tumor-promoting inflammation)が好ましい。 Inflammation is one of the biological defense reactions against infection or cell damage, but the inflammation targeted by the anti-inflammatory agent of the present disclosure is not particularly limited, and may be chronic inflammation or acute inflammation, for example. Good, but inflammation from allergies such as pollinosis, allergic rhinitis, allergic conjunctivitis, atopic dermatitis, delayed allergies, visceral inflammatory diseases such as gastric inflammation and ulcerative colitis, rheumatoid arthritis and degenerative osteoarthritis Inflammation such as arthritis, arteriosclerosis, endometriosis, acute respiratory urgency syndrome, bronchitis, disorders due to kidney transplantation, acute myocardial infarction, diabetes, systemic erythematosus, Crohn's disease, nephritis, hepatitis, pneumonia, etc. Tumor-promoting inflammation (neoplasia) that develops neoplastic cells (neoplasia) in the pretumor stage into the tumor, including various inflammatory diseases such as IgA nephropathy, endotoxin shock, septicemia due to infectious disease, and inflammation caused by surgical injury. Tumor-promoting inflammation) is preferred.
抗炎症際の剤形は、特に限定されず、種々の剤形、例えば、経口投与のためには、錠剤、カプセル剤、散剤、顆粒剤、丸剤、液剤、乳剤などとすることができる。非経口剤としては、注射剤、貼付剤、軟膏またはローション、舌下剤、エアゾール剤、坐剤などとすることができる。これらの製剤は、製剤工程において通常用いられる公知の方法により製造することができる。また本発明に係る薬剤は、持続性または徐放性剤形であってもよい。 The dosage form for anti-inflammatory is not particularly limited, and various dosage forms, for example, tablets, capsules, powders, granules, pills, liquids, emulsions and the like can be used for oral administration. Parenteral preparations can be injections, patches, ointments or lotions, sublinguals, aerosols, suppositories and the like. These preparations can be produced by a known method usually used in the preparation process. Further, the agent according to the present invention may be in a long-acting or sustained-release dosage form.
薬剤に含有される有効成分の量は、用量範囲や投薬の回数などにより適宜決定できる。用量範囲は特に限定されず、含有される成分の有効性、投与形態、投与経路、疾患の種類、患者の特質(体重、年齢、病状および他の医薬の使用の有無など)、および担当医師の判断など応じて適宜選択される。上記投与量は1日1回~数回に分けて投与することができる。 The amount of the active ingredient contained in the drug can be appropriately determined depending on the dose range, the number of doses, and the like. The dose range is not particularly limited, and the efficacy of the contained ingredients, the mode of administration, the route of administration, the type of disease, the characteristics of the patient (weight, age, medical condition and the use of other drugs, etc.), and the doctor in charge It is appropriately selected according to the judgment. The above dose can be administered once to several times a day.
一般的には適当な用量は、例えば患者の体重1kgあたり約0.01μg~100mg程度、好ましくは約0.1μg~1mg程度である。しかしながら、医学分野において広く知られたルーティンな試験によって、これらの用量を最適化できる。 Generally, the appropriate dose is, for example, about 0.01 μg to 100 mg, preferably about 0.1 μg to 1 mg per 1 kg of the patient's body weight. However, routine trials well known in the medical field can optimize these doses.
本開示の抗炎症剤を抗炎症用食品(飲料品を含む)として用いてもよく、特定保健用食品や機能性表示食品だけでなく、一般食品や補助食品(サプリメントなど)として用いることもできる。 The anti-inflammatory agent of the present disclosure may be used as an anti-inflammatory food (including beverages), and may be used not only as a food for specified health use and a food with a functional claim, but also as a general food or a supplement (supplement, etc.). ..
==評価方法==
本開示の評価方法は、in vitroで、一般式(II)を有する化合物、またはその薬学的に許容される塩の抗炎症効果を評価する評価方法である。
(II)
== Evaluation method ==
The evaluation method of the present disclosure is an evaluation method for evaluating the anti-inflammatory effect of a compound having the general formula (II) or a pharmaceutically acceptable salt thereof in vitro.
(II)
(式中、
R1及びR2は、独立に、水素、ハロゲン、及び-OR8から選択され、
(During the ceremony,
R 1 and R 2 are independently selected from hydrogen, halogen, and -OR 8 .
R3及びR4は、一方が水素、ハロゲン、及び-OR8から選択され、他方が
R 3 and R 4 are selected from hydrogen, halogen, and -OR 8 on the one hand and the other on the other.
であって、R5、R6、及びR7は、独立に、水素、ハロゲン、-OR8、及び-NR9から選択され、R8及びR9は、独立に水素、およびC1~C6のアルキルから選択され、Xは、>O、>S、>NR10、>SO、および>SO2から選択され、R10は水素、C1~C6のアルキルまたはシクロアルキル、および置換または無置換のフェニルから選択される。)ここで、フェニルの置換基は、それぞれ独立に、ハロゲン、C1~C6のアルキル、および-OHから選択される。これらの化合物は、公知の製造方法で合成してもよく、市販の化合物を購入して用いてもよい Thus, R 5 , R 6 and R 7 are independently selected from hydrogen, halogen, -OR 8 and -NR 9 , and R 8 and R 9 are independently hydrogen and C1 to C6. Selected from alkyl, X is selected from>O,>S,> NR 10 ,> SO, and> SO 2 , R 10 is hydrogen, alkyl or cycloalkyl of C1-C6, and substituted or unsubstituted phenyl. Is selected from. Here, the substituent of phenyl is independently selected from halogen, C1 to C6 alkyl, and -OH. These compounds may be synthesized by a known production method, or commercially available compounds may be purchased and used.
具体的には、例えば、上記化合物、またはその薬学的に許容される塩の存在下で、培養細胞を刺激し、生産される炎症性因子の量を測定することによって、その化合物、またはその薬学的に許容される塩の抗炎症効果を評価することができる。具体的には、周知の方法で培養細胞を培養し、培地に上記化合物、またはその薬学的に許容される塩、および細胞の刺激に用いる刺激剤を添加し、細胞内及び/又は培地中に生産される炎症性因子の量を測定し、その化合物、またはその薬学的に許容される塩を加えない場合(ネガティブコントロール)の量と比較する。そして、炎症性因子の量がネガティブコントロールよりも有意に減少していれば、添加した化合物、またはその薬学的に許容される塩は炎症抑制効果を有すると判定できる。 Specifically, for example, by stimulating cultured cells and measuring the amount of inflammatory factor produced in the presence of the above compound, or a pharmaceutically acceptable salt thereof, the compound, or the pharmaceutical thereof. The anti-inflammatory effect of the acceptable salt can be evaluated. Specifically, cultured cells are cultured by a well-known method, and the above compound, or a pharmaceutically acceptable salt thereof, and a stimulant used for stimulating the cells are added to the medium, and the cells are intracellularly and / or in the medium. The amount of inflammatory factor produced is measured and compared to the amount without the compound or pharmaceutically acceptable salt thereof (negative control). Then, if the amount of the inflammatory factor is significantly lower than that of the negative control, it can be determined that the added compound or the pharmaceutically acceptable salt thereof has an anti-inflammatory effect.
培養細胞には、周知の細胞(例えば、組織中の細胞、初代培養細胞、樹立された培養細胞などを含む)を用いればよいが、特にRAW264.7などのマクロファージ由来の細胞が好ましい。刺激剤は周知のものを用いればよく、例えば、LPSまたはHMGB1が挙げられる。炎症性因子も周知のものを検出すればよく、例えば、TNF-α、IL-1α、IL-1β、IL-6、IL-8、IFR-γ、G-CSF、IL-17、IL33、GM-CSF、CCL2、およびCXCL2などから選択される1以上の炎症性サイトカインまたはケモカインであってもよい。
As the cultured cells, well-known cells (including, for example, cells in tissues, primary cultured cells, established cultured cells, etc.) may be used, but macrophage-derived cells such as RAW264.7 are particularly preferable. Well-known stimulants may be used, and examples thereof include LPS and HMGB1. Well-known inflammatory factors may be detected, for example, TNF-α, IL-1α, IL-1β, IL-6, IL-8, IFR-γ, G-CSF, IL-17, IL33, GM. -It may be one or more inflammatory cytokines or chemokines selected from CSF, CCL2, CXCL2 and the like.
(方法)
まず、DMEM(10%FCS含有)を用いてRAW264.7細胞を96穴細胞培養用ディッシュ(住友ベークライト社)に6×104細胞/wellの密度で播種し、37℃、5%CO2の条件下で、細胞をインキュベートした。22時間後、培地を除去し、Opti-MEM(登録商標)(ThermoFischerSCIENTIFIC社)に交換し2時間培養した。表1及び表2に示した各化合物0.001、0.01、0.03、0.1、0.3、1、3,10、30μMを含有した培地を加え、同条件でインキュベートした。2時間後、LPSまたはHMGB1それぞれ0.1μg/mLまたは5μg/mLをディッシュに添加し、同条件でインキュベートした。18時間後、マウスIL-6 ELISAキット(ThermoFischerSCIENTIFIC社)を用い、培地中に分泌されたIL-6を測定した。なお、ネガティブコントロールとして、化合物を添加しないサンプルで同様に処理した。すべてのサンプルについて、3連で実験を行い、結果として平均値を算出した。
(Method)
First, RAW264.7 cells were seeded in a 96-well cell culture dish (Sumitomo Bakelite) at a density of 6 × 10 4 cells / well using DMEM (containing 10% FCS) at 37 ° C. and 5% CO 2 . Under the conditions, the cells were incubated. After 22 hours, the medium was removed, replaced with Opti-MEM (registered trademark) (ThermoFischer SCIENTIFIC), and cultured for 2 hours. A medium containing 0.001, 0.01, 0.03, 0.1, 0.3, 1, 3, 10, and 30 μM of each compound shown in Tables 1 and 2 was added, and the mixture was incubated under the same conditions. After 2 hours, LPS or HMGB1 was added to the dish at 0.1 μg / mL or 5 μg / mL, respectively, and incubated under the same conditions. After 18 hours, IL-6 secreted into the medium was measured using a mouse IL-6 ELISA kit (ThermoFischer SCIENTIFIC). As a negative control, the same treatment was performed with a sample to which no compound was added. Experiments were carried out in triplets for all samples, and the average value was calculated as a result.
得られた結果について、サンプルごとに、IL-6の分泌量が半分になる化合物の濃度(μM)を求めた(表ではEC50と記載)。EC50が30μMを超えるものについては、化合物が30μMのときの、ネガティブコントロールに対するIL-6の分泌量の減少量の割合(%)を求めた(表ではΔと記載)。表3及び表4に結果を示す。
以上より、A1~A23、B1~B18の全ての化合物について、LPS刺激によるIL-6の分泌抑制が観察された。さらに、A1~A23の全ての化合物については、HMGB1刺激によるIL-6の分泌抑制が観察された。このように、本開示の化合物は、炎症抑制剤として有効である。 From the above, suppression of IL-6 secretion by LPS stimulation was observed for all the compounds A1 to A23 and B1 to B18. Furthermore, for all the compounds A1 to A23, suppression of IL-6 secretion by HMGB1 stimulation was observed. As described above, the compounds of the present disclosure are effective as anti-inflammatory agents.
Claims (10)
(I)
(式中、
R1及びR2は、独立に、水素、ハロゲン、及び-OR8から選択され、
R3及びR4は、一方が水素、ハロゲン、及び-OR8から選択され、他方が
であって、R5、R6、及びR7は、独立に、水素、ハロゲン、-OR8、及び-NR9から選択され、R8及びR9は、独立に水素、およびC1~C6のアルキルから選択され、Xは、>O、>S、及び>NR10から選択され、R10は水素およびC1~C6のアルキルまたはシクロアルキルから選択される。) An anti-inflammatory agent containing a compound having the general formula (I) or a pharmaceutically acceptable salt thereof as an active ingredient.
(I)
(During the ceremony,
R 1 and R 2 are independently selected from hydrogen, halogen, and -OR 8 .
R 3 and R 4 are selected from hydrogen, halogen, and -OR 8 on the one hand and the other on the other.
Thus, R 5 , R 6 and R 7 are independently selected from hydrogen, halogen, -OR 8 and -NR 9 , and R 8 and R 9 are independently hydrogen and C1 to C6. Selected from alkyl, X is selected from>O,> S, and> NR 10 , and R 10 is selected from hydrogen and C1-C6 alkyl or cycloalkyl. )
R3は、水素であって、
R4は、
であって、
R5は、水素、-OH、または-OMeであって、
R6は、水素、ハロゲン、-N(CH3)2、-OH、または-OMeであって、
R7は、水素、または-OMeであり、
Xは、O、S、またはNHである、請求項1に記載の抗炎症剤。 R 1 and R 2 are independently hydrogen, or -OMe, and
R 3 is hydrogen,
R4 is
And
R5 is hydrogen, -OH, or -OMe,
R 6 is hydrogen, halogen, -N (CH 3 ) 2 , -OH, or -OMe.
R 7 is hydrogen, or -OMe,
The anti-inflammatory agent according to claim 1, wherein X is O, S, or NH.
R3は、
であって、
R5は、水素であって、
R6は、水素、ハロゲン、または-OMeであって、
R7は、水素、または-OMeであって、
R4は、水素であり、
Xは、O、S、またはNHである、請求項1に記載の抗炎症剤。 R 1 and R 2 are independently hydrogen, or -OMe, and
R 3 is
And
R5 is hydrogen,
R6 is hydrogen, halogen, or -OMe,
R 7 is hydrogen, or -OMe,
R4 is hydrogen,
The anti-inflammatory agent according to claim 1, wherein X is O, S, or NH.
The anti-inflammatory agent according to claim 1, which contains any of the following compounds or a pharmaceutically acceptable salt thereof as an active ingredient.
(II)
(式中、
R1及びR2は、独立に、水素、ハロゲン、及び-OR8から選択され、
R3及びR4は、一方が水素、ハロゲン、及び-OR8から選択され、他方が
であって、R5、R6、及びR7は、独立に、水素、ハロゲン、-OR8、及び-NR9から選択され、R8及びR9は、独立に水素、およびC1~C6のアルキルから選択され、Xは、>O、>S、>NR10、>SO、および>SO2から選択され、R10は水素、C1~C6のアルキルまたはシクロアルキル、および置換または無置換のフェニルから選択される。) An evaluation method for evaluating the anti-inflammatory effect of a compound having the general formula (II) or a pharmaceutically acceptable salt thereof in vitro.
(II)
(During the ceremony,
R 1 and R 2 are independently selected from hydrogen, halogen, and -OR 8 .
R 3 and R 4 are selected from hydrogen, halogen, and −OR 8 on the one hand and the other on the other.
Thus, R 5 , R 6 and R 7 are independently selected from hydrogen, halogen, -OR 8 and -NR 9 , and R 8 and R 9 are independently hydrogen and C1 to C6. Selected from alkyl, X is selected from>O,>S,> NR 10 ,> SO, and> SO 2 , R 10 is hydrogen, alkyl or cycloalkyl of C1-C6, and substituted or unsubstituted phenyl. Is selected from. )
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