JPS6176433A - Novel chalcone derivative - Google Patents
Novel chalcone derivativeInfo
- Publication number
- JPS6176433A JPS6176433A JP19926284A JP19926284A JPS6176433A JP S6176433 A JPS6176433 A JP S6176433A JP 19926284 A JP19926284 A JP 19926284A JP 19926284 A JP19926284 A JP 19926284A JP S6176433 A JPS6176433 A JP S6176433A
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- group
- compound
- methoxy
- hydrogen atom
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- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
Description
【発明の詳細な説明】
本発明は、すぐれた抗アレルギー作用を有し抗アレルギ
ー剤として有用な新規なカルコン誘導体に関する。DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a novel chalcone derivative that has excellent antiallergic activity and is useful as an antiallergic agent.
従来技術
従来より各種アレルギー症状の予防、治療剤の研究、開
発が行なわれており、すでに種々の薬物が市販に供され
ている。それらのアレルギー症状のうち、気管支喘息、
じん麻疹、アレルギー性鼻炎などはタイプ■に分類され
る即時型アレルギーである。BACKGROUND OF THE INVENTION Research and development of preventive and therapeutic agents for various allergic symptoms has been carried out, and various drugs are already on the market. Among these allergic symptoms, bronchial asthma,
Urticaria, allergic rhinitis, etc. are immediate allergies classified as type ■.
このタイプ■のアレルギ〜は、そのアレルギー反応の機
序および抗アレルギー剤の作用点から一般に3段階に大
別されている。ずなわら、まず体内に侵入した外来性抗
原に対してマクロファージ、T細胞およびB細胞の相互
作用によってIgE抗体か産生され、このTgE抗体が
組織の肥満細胞や好塩基球のIgE レセプターに固
着して感作が成立するものであって、この過程を第1段
階という。つぎに、これに再び外来性抗原が体内に侵入
すると細胞のIgE レセプターに固着したIgEと外
来性抗原が結合し、その抗原抗体反応が引き金となって
細胞膜酵素の活性化、細胞内へのカルシラ11イオンの
流入などが起り、それによって酵素反応などの生化学的
変化、脱顆粒などの組織学的変化がひき起される。その
結果、ヒスタミンやS RS −A (slow r
eacting 5ubstance ofana
phylaxis )などのケミカルメディエータ−が
細胞外に遊離する。この過程を第2段階という。This type (1) allergy is generally classified into three stages based on the mechanism of the allergic reaction and the point of action of the antiallergic agent. First, IgE antibodies are produced by interactions between macrophages, T cells, and B cells in response to foreign antigens that invade the body, and these TgE antibodies adhere to IgE receptors on mast cells and basophils in tissues. This process is called the first stage. Next, when a foreign antigen enters the body again, the foreign antigen binds to the IgE fixed to the cell's IgE receptor, triggering an antigen-antibody reaction that activates cell membrane enzymes and releases calcila into the cell. The influx of 11 ions occurs, which causes biochemical changes such as enzyme reactions and histological changes such as degranulation. As a result, histamine and SRS-A (slow r
acting 5ubstance ofana
chemical mediators such as phylaxis) are released outside the cell. This process is called the second stage.
」二記第2段階で細胞外に遊離したケミカルメディエー
タ−は平滑筋のれん縮、毛細血管の透過性の光道あるい
は分泌促進作用を生せしめ、種々のアレルギー症状を惹
起する。この過程を第3段階という。Chemical mediators liberated outside the cells in the second step cause smooth muscle spasms, capillary permeability light channels, and secretion promoting effects, causing various allergic symptoms. This process is called the third stage.
従来知られている抗アレルギー剤のうし、抗体産生抑制
剤は第1段階に作用する薬物であり、抗ヒスタミン剤は
第3段階に作用する薬物である。Among the conventionally known antiallergic agents, antibody production inhibitors are drugs that act in the first step, and antihistamines are drugs that act in the third step.
また第2段階に作用する抗アレルギー剤としてはり、S
CG、トラニラストなとが知られている。In addition, as an antiallergic agent that acts in the second stage, S
CG and Toranirasuto are known.
光脚Δ旦的一
本発明者らは、」−記第2段階のアレルギー症状に対し
てずぐれた抗アレルギー作用を示す薬物を得るべく研究
を重ねた結果、特定のカルコン誘導体が、ヒスタミンや
5R9−Aなどのケミカルメディエータ−の遊離抑制活
性にすぐれていることを知り、本発明を完成するに至っ
た。すなわち、本発明は、ケミカルメディエータ−に起
因する各種アレルギー性疾患の予防、治療に有用な新規
なカルコン誘導体を提供するものである。The inventors of the present invention have conducted extensive research to obtain a drug that exhibits excellent anti-allergic effects against the second stage of allergic symptoms. It was discovered that the present invention has excellent activity in inhibiting the release of chemical mediators such as 5R9-A, and the present invention was completed. That is, the present invention provides novel chalcone derivatives useful for the prevention and treatment of various allergic diseases caused by chemical mediators.
発明の構成
本発明の化合物は、式:
[式中、R1およびR2は一方が水素原子、他方がメト
キシ基、R3およびR4は同一または異なって、それぞ
れ水素原子、ヒドロキシ基、メトキシ基、ニトロ基、ア
ミノ基またはRCON H−(Rはフェニル、トリル、
ナフチルなどのアリール=3−
基)で示される基、R5は水素原子またはRC0−(R
は前記と同じ)で示される基を意味する]で表4つされ
るカルコン誘導体である。Constituent Structure of the Invention The compound of the present invention has the formula: [In the formula, one of R1 and R2 is a hydrogen atom and the other is a methoxy group, and R3 and R4 are the same or different and each is a hydrogen atom, a hydroxy group, a methoxy group, or a nitro group. , amino group or RCON H- (R is phenyl, tolyl,
aryl=3- group such as naphthyl, R5 is a hydrogen atom or RC0-(R
means a group represented by (same as above)] These are chalcone derivatives shown in Table 4.
」−記(1)式で示される化合物のうち、R3および/
またはR4がアミノ基である化合物は、薬学的に許容さ
れる酸との酸付加塩を形成することもあり、またR5が
水素原子である化合物は、薬学的に許される塩基との塩
を形成することもあり、本発明はそれらの塩も包含する
。” - Among the compounds represented by formula (1), R3 and /
Alternatively, compounds where R4 is an amino group may form acid addition salts with pharmaceutically acceptable acids, and compounds where R5 is a hydrogen atom may form salts with pharmaceutically acceptable bases. The present invention also includes salts thereof.
酸付加塩としては、塩酸塩、臭化水素酸塩、ヨウ化水素
酸塩、硫酸塩、リン酸塩、硝酸塩などの無機酸塩、およ
び酢酸塩、乳酸塩、酒石酸塩、クエン酸塩、メタンスル
ホン酸塩、エタンスルポン酸塩、ベンゼンスルホン酸塩
、トルエンスルホン酸塩、イセチオン酸塩などの有機酸
塩が挙げられる。また塩基との塩としては、ナトリウム
塩、カリウム塩、カルシウム塩、マグネシウム塩、アン
モニウム塩などが挙げられる。Acid addition salts include inorganic acid salts such as hydrochloride, hydrobromide, hydroiodide, sulfate, phosphate, nitrate, and acetate, lactate, tartrate, citrate, methane. Examples include organic acid salts such as sulfonate, ethanesulfonate, benzenesulfonate, toluenesulfonate, and isethionate. Examples of salts with bases include sodium salts, potassium salts, calcium salts, magnesium salts, and ammonium salts.
本発明のカルコン誘導体は種々の方法で製造され得るが
、基本的には、例えば下記反応式で示さ=4−
れる方法で製造される。Although the chalcone derivative of the present invention can be produced by various methods, it is basically produced, for example, by the method shown in the following reaction formula.
(工I) (エエエ)[式中、R1お
よびR2は前記に同じ、R3°およびR4は同一または
異なって、それぞれ水素原子、ヒドロキシ基、メトキシ
基またはニトロ基を意味する]
すなわち、式(11)のアセトフェノン誘導体と式(I
II)のベンズアルデヒド誘導体とを酸またはアルカリ
触媒の存在下に、室温または加温下で数十分〜数時間縮
合反応に付すことにより製造される。(Engineering I) (EEE) [In the formula, R1 and R2 are the same as above, R3° and R4 are the same or different and each means a hydrogen atom, a hydroxy group, a methoxy group or a nitro group] That is, the formula (11 ) and the acetophenone derivative of formula (I
It is produced by subjecting the benzaldehyde derivative of II) to a condensation reaction in the presence of an acid or alkali catalyst at room temperature or under heating for several tens of minutes to several hours.
用いられる酸またはアルカリ触媒としては、塩化水素酸
、臭化水素酸、硫酸などの無機酸類、水酸化ナトリウム
、水酸化カリウムなどのアルカリ金属水酸化物などが挙
げられる。上記の反応はメタノール、エタノールなどの
アルコール類、水などの適当な有機溶媒を用いて行なう
のが好ましい。Examples of the acid or alkali catalyst used include inorganic acids such as hydrochloric acid, hydrobromic acid, and sulfuric acid, and alkali metal hydroxides such as sodium hydroxide and potassium hydroxide. The above reaction is preferably carried out using an alcohol such as methanol or ethanol, or a suitable organic solvent such as water.
本発明のカルコン誘導体(1)のうち、R3および/ま
たはR4がアミノ基である化合物は、対応するR3およ
び/またはR′がニトロ基である化合物を常法により第
一級アミンに還元することにより製造される。この還元
は、例えば、白金、パラジウム炭素などの接触還元触媒
の存在下に水素ガスに」;る接触還元を行なうか、ある
いは鉄、亜鉛、スズ、または塩化第一スズと塩酸、ある
いはベンゼンの存在下に三塩化チタンを用い、あるいは
水または含水アルコール中硫化すl・リウム、硫化アン
モン、アンモニア水とハイドロザルファイトなどを用い
て還元する方法が採用される。Among the chalcone derivatives (1) of the present invention, compounds in which R3 and/or R4 are amino groups can be obtained by reducing the corresponding compounds in which R3 and/or R' are nitro groups to primary amines by a conventional method. Manufactured by. This reduction can be carried out, for example, by catalytic reduction to hydrogen gas in the presence of a catalytic reduction catalyst such as platinum, palladium on carbon, or in the presence of iron, zinc, tin, or stannous chloride with hydrochloric acid or benzene. A reduction method using titanium trichloride, sulfur sulfide, ammonium sulfide, aqueous ammonia and hydrozulfite in water or hydrous alcohol is employed.
またカルコン誘導体(I)中、R3および/またはR′
がRCON tr−で示される基である化合物は、対応
するR3および/またはR4がアミノ基である化合物を
ピリジン、トリエチルアミンなどの塩基の存在下に、式
RCOOH(式中Rは前記と同じ)で示されるカルボン
酸またはその反応性誘導体、例えば酸塩化物、酸無水物
または混合酸無水物などと反応させることにより製造さ
れる。In addition, in the chalcone derivative (I), R3 and/or R'
is a group represented by RCON tr-, a compound in which the corresponding R3 and/or R4 are an amino group is reacted with the formula RCOOH (wherein R is the same as above) in the presence of a base such as pyridine or triethylamine. They are produced by reacting with the indicated carboxylic acids or reactive derivatives thereof, such as acid chlorides, acid anhydrides or mixed acid anhydrides.
さらに、カルコン誘導体(1)中、R5がRC〇−で示
される基である化合物は、対応するR5が水素原子であ
るフェノール化合物を、ピリジン、トリエチルアミンな
どの塩基の存在下に、」1記と同様の式RCOOHで示
されるカルボン酸またはその反応性誘導体と反応させる
ことにより製造される。Furthermore, in the chalcone derivative (1), the compound in which R5 is a group represented by RC-- is obtained by converting the corresponding phenol compound in which R5 is a hydrogen atom in the presence of a base such as pyridine or triethylamine as described in "1. It is produced by reaction with a carboxylic acid of the similar formula RCOOH or a reactive derivative thereof.
なお、本発明のカルコン誘導体の塩類は対応する遊離化
合物から常法により容易に得ることができ、例えばR3
がアミノ基である化合物を、適当な溶媒中、所望の酸の
理論量と反応さ仕れば対応する酸付加塩が得られ、また
R5が水素原子である化合物を、適当な溶媒中、所望の
塩基の理論量と反応させれば対応する塩基塩が得られる
。In addition, the salts of the chalcone derivatives of the present invention can be easily obtained from the corresponding free compounds by conventional methods, for example, R3
The corresponding acid addition salt can be obtained by reacting a compound in which is an amino group with a theoretical amount of the desired acid in a suitable solvent, and a compound in which R5 is a hydrogen atom can be reacted with a theoretical amount of the desired acid in a suitable solvent. The corresponding base salt is obtained by reacting with a theoretical amount of base.
本発明の化合物は、下記試験例で示すように、すぐれた
ケミカルメディエータ−遊離阻害活性を持っている。The compounds of the present invention have excellent chemical mediator release inhibiting activity, as shown in the following test examples.
試験例I
T−Tartley系モルモット(雄1体重約400g
)に抗卵白アルブミンモルモット血清を静脈内投与して
受動的に感作し、48時間後肺を摘出、細切して肺浮遊
液を調製した。これに被験化合物および卵白アルブミン
を添加して37℃にてインキクベートし、反応終了後、
肺切片を濾去して濾液中のヒスタミンおよび5r(S−
Afiを測定した。ヒスタミン量はMayらの方法[J
、 Allerg、 、 40巻、12頁(1970年
)]に準じて蛍光法で測定した。ST’(S−A量はモ
ルモット回腸を用いたバイオアッセイで測定した。すな
わちマグヌス槽に懸垂したモルモット回腸に抗ヒスタミ
ン剤、抗アセチルコリン剤および被験液を添加し、モル
モット回腸の収縮の程度からSl’(S’−A量を算出
した。Test Example I T-Tartley guinea pigs (one male weighs approximately 400 g)
) were passively sensitized by intravenously administering anti-ovalbumin guinea pig serum, and 48 hours later, the lungs were removed and cut into small pieces to prepare a lung suspension. The test compound and ovalbumin were added to this and incubated at 37°C. After the reaction was completed,
The lung sections were filtered to remove histamine and 5r(S-
Afi was measured. The amount of histamine was determined by the method of May et al. [J
, Allerg, Vol. 40, p. 12 (1970)]. ST' (S-A amount was measured by bioassay using guinea pig ileum. In other words, antihistamines, antiacetylcholine agents, and test solution were added to the guinea pig ileum suspended in a Magnus bath, and Sl' ( The amount of S'-A was calculated.
本発明化合物のヒスタミンおよび5R9−Aの遊離に対
する抑制率を第1表に示す。Table 1 shows the inhibition rates of the compounds of the present invention on the release of histamine and 5R9-A.
=8− 第1表 *)被験化合物は下記のとおりである。=8- Table 1 *) The test compounds are as follows.
1:3−(4−ヒドロキシフェニル)−1−(2,3,
4−トリメトキシフェニル)−2−プロペン−1−オン
2:3−(4−ヒドロキシフェニル)−1−(3,4,
5−トリメトキシフェニル)−2−プロペン−■−オン
3・ 1−(3,4−ジヒドロキシフェニル)−1−(
2,3,4−トリメトキシフェニル)−2−プロペンー
1−オン
4:3−(4−ヒドロキシ−3−メトキシフェニル)−
1(2,3,4−)リメトギノフェニル)−2−プロペ
ン−1−オン
5: 3−(3,5−ノメトキソー4−ヒドロキシフェ
ニル)l−(2,3,4−1,リメトキンフェニル)−
2−プロペン−1−オン6:3−(4−ヒドロキシ−3
−二トロフェニル)−1−(3,4,5−トリメトギン
フェニル)−2−プロペン−1−オン
7: 3−(3−アミノ−4−ヒドロギンフェニル)−
1−(3,4,5−1,リメトギノフェニル)−2−プ
〔Jペン−1−オン
本発明の化合物は、経口または非経口的に投すされるが
、経[]投り、か好ましい。また使用に際しては通常の
医薬担体を用いて常法により各種製剤形に調製される。1:3-(4-hydroxyphenyl)-1-(2,3,
4-trimethoxyphenyl)-2-propen-1-one 2:3-(4-hydroxyphenyl)-1-(3,4,
5-Trimethoxyphenyl)-2-propene-■-one 3.1-(3,4-dihydroxyphenyl)-1-(
2,3,4-trimethoxyphenyl)-2-propen-1-one 4:3-(4-hydroxy-3-methoxyphenyl)-
1(2,3,4-)rimethoginophenyl)-2-propen-1-one 5: 3-(3,5-nomethoxo-4-hydroxyphenyl)l-(2,3,4-1,rimetquin phenyl)−
2-propen-1-one 6:3-(4-hydroxy-3
-nitrophenyl)-1-(3,4,5-trimethogynphenyl)-2-propen-1-one 7: 3-(3-amino-4-hydroginphenyl)-
1-(3,4,5-1,rimetogynophenyl)-2-[Jpen-1-one] The compounds of the present invention may be administered orally or parenterally; Or preferable. For use, they are prepared into various formulations by conventional methods using conventional pharmaceutical carriers.
例えば、経「1投与用には錠剤、カプセル剤、顆粒剤、
細粒剤、ノロツブ剤、粉剤などが挙げられる。For example, tablets, capsules, granules,
Examples include fine granules, powders, and powders.
実施例1
3−(4−ヒドロキシフェニル)−1−(2,3゜4−
トリメトギンフェニル)−2−プロペン−1−オンの製
造。Example 1 3-(4-hydroxyphenyl)-1-(2,3°4-
Preparation of trimethogyne phenyl)-2-propen-1-one.
2°、3°、4° −トリメトキシアセトフェノン1.
0gと4−ヒドロキン−ベンズアルデヒド06gを4
Jのエタノールに溶解し、これに70%水酸化カリウ
ム水溶液7 m、l、を滴下し、室温で4時間かくはん
する。反応溶液を塩酸で酸性にしたのち、酢酸エチルで
3回抽出する。有機層を合せて水洗後、無水硫酸ナトリ
ウムで乾燥して減圧濃縮する。残留物をエタノールより
再結晶し、次の物理的性質を有する表記化合物670m
gを得る。2°, 3°, 4° -trimethoxyacetophenone 1.
0g and 06g of 4-hydroquine-benzaldehyde in 4
J in ethanol, 7 m, l of a 70% aqueous potassium hydroxide solution was added dropwise thereto, and the mixture was stirred at room temperature for 4 hours. The reaction solution was made acidic with hydrochloric acid, and then extracted three times with ethyl acetate. The organic layers are combined, washed with water, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was recrystallized from ethanol to give the title compound 670m having the following physical properties.
get g.
融点: 130〜13+’C
IR(KBr): ν= 3360.1645゜15
90.1550.+520.1440゜14.10.+
345.1290,1275゜+245.+225.1
170.1+00゜1005.830cm ’
NMR(アセトン−d6): δ−8,82(IH。Melting point: 130~13+'C IR (KBr): ν=3360.1645°15
90.1550. +520.1440°14.10. +
345.1290,1275°+245. +225.1
170.1+00°1005.830cm' NMR (acetone-d6): δ-8,82 (IH.
s )、 7. 71〜6.75(81−1,m )、
3.871l−
(6LI、 s )、 3. 78(31−L s
)元素分析値
計算値: C,68,78,I−1,5,77(%)実
測値: C,68,65; H,5,70(%)実施例
2
3−(4−ヒドロギンフェニル)−1−(3,4゜5−
トリメトキノフェニル)−2−プロペン−1−オンの製
造;
実施例1と同様にして、3°、4°、5″ −トリメト
キシアセトフェノンと4−ヒドロギンベンズアルデヒド
から次の物理的性質を有する表記化合物420mgを得
る。s), 7. 71-6.75 (81-1, m),
3.871l- (6LI, s), 3. 78 (31-Ls
) Elemental analysis calculated value: C, 68,78, I-1,5,77 (%) Actual value: C, 68,65; H, 5,70 (%) Example 2 3-(4-hydrogine phenyl)-1-(3,4゜5-
Production of (trimethoquinophenyl)-2-propen-1-one; In the same manner as in Example 1, from 3°, 4°, 5″-trimethoxyacetophenone and 4-hydrogine benzaldehyde, a notation having the following physical properties 420 mg of compound is obtained.
融点: 196〜198°C
IR(KBr): v−3450,3170゜164
0.1555.+505.’1440゜1350.13
10.1280.+235゜1170、I 130cm
’
NMR(DMSO−d6): δ−10,1(I )
■、 s)、7.78(211,d )、7.73(2
H,S )。Melting point: 196-198°C IR (KBr): v-3450, 3170°164
0.1555. +505. '1440°1350.13
10.1280. +235°1170, I 130cm
'NMR (DMSO-d6): δ-10,1(I)
■, s), 7.78 (211, d), 7.73 (2
H,S).
7、 43(21−1,s )、 6. 87(21
(、d )、 3゜93(6H,s )、3.78(
3H,s )元素分析値
計算値:C,68,78; I−I、5.77(%)実
測値: C,68,63,H,5,73(%)実施例3
3−(3,4−ジヒドロキシフェニル)−1−(2,3
,4−1リメトキシフエニル)−2−プロペン−I−オ
ンの製造:
2°、3’、4’ −トリメトキシアセトフェノン4
.2gと3,4−ジヒドロキシベンズアルデヒド2.8
gを80n+4のエタノールに懸濁し、0℃で塩化水素
ガスを3時間導入する。この反応液に水600m4を加
え、−晩4°Cにて静置すると結晶が析出する。これを
枦取し、粗結晶5.2gを得、さらにエタノール/水の
混合溶媒より再結晶を行ない、表記化合物4.3gを得
る。7, 43(21-1,s), 6. 87 (21
(,d), 3゜93(6H,s), 3.78(
3H,s) Elemental analysis value Calculated value: C, 68,78; I-I, 5.77 (%) Actual value: C, 68,63, H, 5,73 (%) Example 3 3-(3 ,4-dihydroxyphenyl)-1-(2,3
,4-1rimethoxyphenyl)-2-propen-I-one: 2°,3',4'-trimethoxyacetophenone 4
.. 2g and 3,4-dihydroxybenzaldehyde 2.8
g was suspended in 80n+4 ethanol, and hydrogen chloride gas was introduced at 0° C. for 3 hours. 600 m4 of water was added to this reaction solution, and the mixture was allowed to stand overnight at 4°C to precipitate crystals. This was collected to obtain 5.2 g of crude crystals, which was further recrystallized from a mixed solvent of ethanol/water to obtain 4.3 g of the title compound.
融点: 170〜172℃(分解)
IR(KBr): v= 3460.1640゜159
0.1550,1530,1,450゜1410、+2
80.1250.1200゜1100.1010.98
0,810cm’NMR(アセトン−d8) δ−8
,33(21+。Melting point: 170-172°C (decomposition) IR (KBr): v = 3460.1640°159
0.1550, 1530, 1,450°1410, +2
80.1250.1200゜1100.1010.98
0,810cm'NMR (acetone-d8) δ-8
,33(21+.
s)、7.50−6.80(7(1,m)、3.92(
611,s )、 3. 83(311,s )元素
分析値
計算値: C,65,45,II、5./19(%)実
測値 C,65,27; 11,5.56(%)実施例
4
3−(4−ヒドロキシ−3−メトギンフエニル)−1−
(2,3,4−)リメトギンフェニル)−2−プロペン
−1−オンの製造。s), 7.50-6.80 (7 (1, m), 3.92 (
611,s), 3. 83 (311, s) Elemental analysis value calculation value: C, 65, 45, II, 5. /19 (%) Actual value C, 65,27; 11,5.56 (%) Example 4 3-(4-hydroxy-3-methogynphenyl)-1-
Preparation of (2,3,4-)rimetogynephenyl)-2-propen-1-one.
2°、 3’、 4°−トリメトキソアセトフエノン
3.0gとバニリン2.1gをエタノール15m4に溶
解し、これに0℃で70%水酸化カリウム溶液25mj
uを滴下する。滴下終了後、室温で48時間かくはんす
る。反応溶液を0℃に冷却し、これに塩酸を徐々に加え
酸性にする。析出した結晶をシ戸取し、さらにn−ヘキ
サン/酢酸エチルの混合溶媒より再結晶を行い、表記化
合物1.2gを得る。Dissolve 3.0 g of 2°, 3', 4°-trimethoxoacetophenone and 2.1 g of vanillin in 15 m4 of ethanol, and add 25 mj of 70% potassium hydroxide solution at 0°C.
Drop u. After the addition is complete, stir at room temperature for 48 hours. The reaction solution is cooled to 0° C., and hydrochloric acid is gradually added thereto to make it acidic. The precipitated crystals were collected and recrystallized from a mixed solvent of n-hexane/ethyl acetate to obtain 1.2 g of the title compound.
融点:99〜1006C
IR(KBr): v−3600〜3100゜164
0.1600,1510,1460゜14’30.+3
90.1370.1200゜1020.800cm−’
NMR(CDC!。):δ−7,7〜6.2(7H,m
)、3.90(+ 20.s )元素分析値
計算値: C,66,27; I(,5,85(%)実
測値・C,66,28; IT、5.80(%)実施例
5
3−(3,5−ジメ)・ギン−4−ヒドロギシフエニル
)−1−(2,3,4−1−リメトギンフェニル)−2
−プロペン−1−オンの製造。Melting point: 99~1006C IR (KBr): v-3600~3100°164
0.1600, 1510, 1460°14'30. +3
90.1370.1200゜1020.800cm-' NMR (CDC!.): δ-7,7~6.2 (7H, m
), 3.90 (+ 20.s) Elemental analysis calculated value: C, 66,27; Example 5 3-(3,5-dime)gin-4-hydroxyphenyl)-1-(2,3,4-1-rimethogynphenyl)-2
-Production of propen-1-one.
2°、3°、4° −1−リメトギンアセトフエノン4
.2gとシリンガアルデヒド3.6gより実施例3と同
様にして表記化合物3,5gを得る。2°, 3°, 4° -1-rimetogine acetophenone 4
.. 2 g and 3.6 g of syringaldehyde to obtain 3.5 g of the title compound in the same manner as in Example 3.
融点134〜136℃
IR(KBr): v−3430,1590゜1515
.1465,1430.14+5゜+305.1270
.1210. 1110゜1105、 1005,81
5c111’NMR(アセトン−d8): δ−7,
72(III。Melting point 134-136°C IR (KBr): v-3430, 1590°1515
.. 1465,1430.14+5゜+305.1270
.. 1210. 1110°1105, 1005,81
5c111'NMR (acetone-d8): δ-7,
72 (III.
s )、7.45〜6.78(6J(、m )、3.8
8(15LT、 br、 s )
元素分析値
計算値: C,64,16; II、5.92(%)実
測値 C,64,34,H,5,88(%)実施例6
3−(4−ヒドロキシ−3−ニトロフェニル)−1−(
3,4,5−トリメトギンフェニル)−2−プロペン−
1−オンの製造:
3゛、4′、5° −トリメトギンアセトフエノン42
gと4−ヒドロキン−3−二トロヘンズアルデヒド33
gを80m児のエタノールに溶解し、0℃で塩化水素ガ
スを3時間導入オろ。この反応液に水500Jを加え、
−晩4℃にて静置すると結晶が析出する。これをシ戸取
し、エタノール/酢酸エチルより再結晶を行い、表記化
合物5゜2gを得る。s), 7.45-6.78 (6J(,m), 3.8
8 (15LT, br, s) Elemental analysis value calculation value: C, 64, 16; II, 5.92 (%) Actual value C, 64, 34, H, 5, 88 (%) Example 6 3-( 4-hydroxy-3-nitrophenyl)-1-(
3,4,5-trimethogynephenyl)-2-propene-
Preparation of 1-one: 3', 4', 5'-trimethogine acetophenone 42
g and 4-hydroquine-3-nitrohenzaldehyde 33
Dissolve g in 80ml of ethanol, and introduce hydrogen chloride gas at 0°C for 3 hours. Add 500 J of water to this reaction solution,
-Crystals precipitate when left at 4°C overnight. This was collected and recrystallized from ethanol/ethyl acetate to obtain 5.2 g of the title compound.
融点:205〜207°C(分解)
IR(KBr): v−3450,1660゜160
0.1575,1535.14+5゜1350.133
0.+310.1285゜1245.1185.115
5.1145゜l 125.1005,985,935
,835゜820.770cm’
NMR(DMSO−do): δ−8、4,3(I
I−T。Melting point: 205-207°C (decomposition) IR (KBr): v-3450, 1660°160
0.1575, 1535.14+5゜1350.133
0. +310.1285°1245.1185.115
5.1145゜l 125.1005,985,935
,835°820.770cm' NMR (DMSO-do): δ-8,4,3(I
I-T.
d )、 8.15(11(、d(1)、7. 82
(2H,(1)。d), 8.15(11(, d(1), 7.82
(2H, (1).
7.45(2H,s )、7.23(I H,d )、
3゜92(6H9s )、3.78(3H,s )元素
分析値
計算値:C,60、I 6.I(、/1.7?、N。7.45 (2H,s), 7.23 (IH,d),
3°92 (6H9s), 3.78 (3H,s) Elemental analysis calculated value: C,60,I 6. I(, /1.7?, N.
3.90(%) 実測値 C,60,15’、I(,4,70,N。3.90(%) Actual measurement value C, 60, 15', I (, 4, 70, N.
3.96(%)
実施例7
3−(3−アミノ−4−ヒドロキソフェニル)−+−(
3,4,5−トリメトギノフェニル)−2−プロペン−
1−オンの製造:
3−(4−ヒドロキシ−3−二i・〔1フエニル)−1
−(3,4,5−トリメトキンフェニル)−2−プロペ
ン−1−オン3.6gに水80m!、テ)・ラヒドロフ
ランI00+Jおよび濃アンモニア水26.5 Jを加
えて溶解させる。これに亜二ヂオン酸ナトリウム18.
5gを水80m!に溶かした溶液を水冷下に加え、40
分間かくはんする。3.96 (%) Example 7 3-(3-amino-4-hydroxophenyl)-+-(
3,4,5-trimethogynophenyl)-2-propene-
Production of 1-one: 3-(4-hydroxy-3-di[1 phenyl)-1
-(3,4,5-trimethquinphenyl)-2-propen-1-one 3.6g and 80ml of water! , TE), add and dissolve 100+J of lahydrofuran and 26.5 J of concentrated aqueous ammonia. Add to this sodium didionite 18.
5g in 80m of water! Add the solution dissolved in water under water cooling and add 40
Stir for a minute.
反応溶液を酢酸エチルで抽出し、抽出液を飽和食塩水で
洗浄後、無水硫酸ナトリウムで乾燥し、溶媒を留去する
。得られた粗結晶を酢酸エチルより再結晶して表記化合
物1.3gを得る。The reaction solution is extracted with ethyl acetate, the extract is washed with saturated brine, dried over anhydrous sodium sulfate, and the solvent is distilled off. The obtained crude crystals were recrystallized from ethyl acetate to obtain 1.3 g of the title compound.
融点: 182〜184℃(分解)
IR(KBr): v−3470,3400゜1640
、+610.1585,1545゜+505.1445
.1415’、+385゜1355.1320,130
5.+285゜+270; 12/10.+220.
.1160゜1140.1125.1080,1000
゜985、 835. 805cm−’
N M R(D M S Odo /アセトンーd6)
: δ−7,71〜6.80(7H,m )、3.95
(6LI。Melting point: 182-184°C (decomposition) IR (KBr): v-3470, 3400°1640
, +610.1585,1545°+505.1445
.. 1415', +385°1355.1320,130
5. +285°+270; 12/10. +220.
.. 1160°1140.1125.1080,1000
゜985, 835. 805cm-' NMR (DMS Odo/Acetone-d6)
: δ-7,71~6.80 (7H,m), 3.95
(6LI.
s )、 3. 80(31−I、 s )元素分
析値
計算値: C,65,64; II、5.82; N。s), 3. 80 (31-I, s) Elemental analysis calculated: C, 65, 64; II, 5.82; N.
425(%) 実測値: C,65,78,r”L 5.91; N。425 (%) Actual value: C, 65,78, r"L 5.91; N.
4.12(%)
実施例8
3−(3−ベンゾイルアミノ−4−ベンゾイルオキシフ
ェニル)−1−(3,4,5−)リメトキシフェニル)
−2−プロペン−1−オンの製造3−(3−アミノ−4
−ヒドロキシフェニル)−1−(3,4,5−1−リメ
トキンフェニル)−2=プロペン−1−オン0.9gを
無水ピリジン15m!に溶解し、水冷下塩化ベンゾイル
0.35Jを滴下する。これを室温で2時間かくはんし
たのち、水を加え、−夜4℃で放置する。析出した結晶
を?取し、エタノールより再結晶して表記化合物0.4
gを得る。4.12 (%) Example 8 3-(3-benzoylamino-4-benzoyloxyphenyl)-1-(3,4,5-)rimethoxyphenyl)
-Production of 2-propen-1-one 3-(3-amino-4
-Hydroxyphenyl)-1-(3,4,5-1-rimethquinphenyl)-2=0.9 g of propen-1-one and 15 m of anhydrous pyridine! 0.35 J of benzoyl chloride was added dropwise while cooling with water. After stirring this at room temperature for 2 hours, water was added and the mixture was left at -4°C overnight. The precipitated crystals? and recrystallized from ethanol to obtain the title compound 0.4
get g.
融点 178〜+ 81 ’C
TR(K13r) : ν −1740,I
660.i 580.1345,1330.1245
,116(1゜1130.710cm’
NMR(1)MSO−d、 ): δ−10,20(I
N、s )、8.10〜7.46(1711,m)、、
390(6Ir、s )、 3. 79(3H,s
)元素分析値
計算値: C,71,50,IJ、5.06; N。Melting point 178~+81'C TR (K13r): ν -1740,I
660. i 580.1345, 1330.1245
,116(1°1130.710cm' NMR(1)MSO-d, ): δ-10,20(I
N, s), 8.10-7.46 (1711, m),
390 (6Ir,s), 3. 79(3H,s
) Calculated elemental analysis value: C, 71,50, IJ, 5.06; N.
2.61(%) 実測値: C,71,72,H,5,00; N。2.61 (%) Actual measurement value: C, 71,72, H, 5,00; N.
2.79(%)2.79 (%)
Claims (1)
メトキシ基、R^3およびR^4は同一または異なって
、それぞれ水素原子、ヒドロキシ基、メトキシ基、ニト
ロ基、アミノ基またはRCONH−(Rはアリール基)
で示される基、R^5は水素原子またはRCO−(Rは
前記と同じ)で示される基を意味する]で表わされるカ
ルコン誘導体またはその薬学的に許容される塩。(1) Formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (I) [In the formula, one of R^1 and R^2 is a hydrogen atom, the other is a methoxy group, and R^3 and R^4 are the same or different. each a hydrogen atom, hydroxy group, methoxy group, nitro group, amino group or RCONH- (R is an aryl group)
A chalcone derivative or a pharmaceutically acceptable salt thereof, represented by the group represented by the following formula, R^5 means a hydrogen atom or a group represented by RCO- (R is the same as above).
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP19926284A JPS6176433A (en) | 1984-09-21 | 1984-09-21 | Novel chalcone derivative |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP19926284A JPS6176433A (en) | 1984-09-21 | 1984-09-21 | Novel chalcone derivative |
Publications (1)
Publication Number | Publication Date |
---|---|
JPS6176433A true JPS6176433A (en) | 1986-04-18 |
Family
ID=16404862
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP19926284A Pending JPS6176433A (en) | 1984-09-21 | 1984-09-21 | Novel chalcone derivative |
Country Status (1)
Country | Link |
---|---|
JP (1) | JPS6176433A (en) |
Cited By (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4952564A (en) * | 1986-03-08 | 1990-08-28 | Dainippon Ink And Chemicals, Inc. | Antiallergic agent |
US5276058A (en) * | 1993-06-09 | 1994-01-04 | Nippon Hypox Laboratories Incorporated | 3,4-dihydroxychalcone derivatives |
WO1999040056A1 (en) * | 1998-02-06 | 1999-08-12 | De Montfort University | Hydroxylation activated prodrugs |
EP0994093A1 (en) * | 1996-05-14 | 2000-04-19 | Hoechst Marion Roussel, Ltd. | Polyhydroxyphenol derivatives and preventive and therapeutic agents for bone and cartilage diseases containing the same |
US6214886B1 (en) | 1998-02-06 | 2001-04-10 | Demontfort University, The Gateway | Hydroxylation activated prodrugs |
US6787672B2 (en) | 2000-03-27 | 2004-09-07 | Cancer Research Technology Limited | Substituted chalcones as therapeutic compounds |
US6794384B1 (en) | 1998-02-12 | 2004-09-21 | De Montfort University | Hydroxylation activated drug release |
US7112698B2 (en) | 2001-10-03 | 2006-09-26 | Spear Therapeutics Limited | 4-(c2-6alkoxy)-substituted chalcones as therapeutic agents |
US7598294B2 (en) | 2001-10-03 | 2009-10-06 | Spear Therapeutics Limited | 3,4-methylenedioxy-substituted chalcones as therapeutic agents |
WO2016159280A1 (en) * | 2015-03-31 | 2016-10-06 | 国立大学法人東北大学 | Antiallergic agent |
-
1984
- 1984-09-21 JP JP19926284A patent/JPS6176433A/en active Pending
Cited By (13)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4952564A (en) * | 1986-03-08 | 1990-08-28 | Dainippon Ink And Chemicals, Inc. | Antiallergic agent |
US5276058A (en) * | 1993-06-09 | 1994-01-04 | Nippon Hypox Laboratories Incorporated | 3,4-dihydroxychalcone derivatives |
EP0629602A1 (en) * | 1993-06-09 | 1994-12-21 | Nippon Hypox Laboratories Incorporated | 3,4-Dihydroxychalcone derivatives |
EP0994093A4 (en) * | 1996-05-14 | 2000-05-17 | Hoechst Marion Roussel Ltd | Polyhydroxyphenol derivatives and preventive and therapeutic agents for bone and cartilage diseases containing the same |
EP0994093A1 (en) * | 1996-05-14 | 2000-04-19 | Hoechst Marion Roussel, Ltd. | Polyhydroxyphenol derivatives and preventive and therapeutic agents for bone and cartilage diseases containing the same |
US6214886B1 (en) | 1998-02-06 | 2001-04-10 | Demontfort University, The Gateway | Hydroxylation activated prodrugs |
WO1999040056A1 (en) * | 1998-02-06 | 1999-08-12 | De Montfort University | Hydroxylation activated prodrugs |
US6346550B2 (en) | 1998-02-06 | 2002-02-12 | Gerald Andrew Potter | Hydroxylation activated prodrugs |
US6794384B1 (en) | 1998-02-12 | 2004-09-21 | De Montfort University | Hydroxylation activated drug release |
US6787672B2 (en) | 2000-03-27 | 2004-09-07 | Cancer Research Technology Limited | Substituted chalcones as therapeutic compounds |
US7112698B2 (en) | 2001-10-03 | 2006-09-26 | Spear Therapeutics Limited | 4-(c2-6alkoxy)-substituted chalcones as therapeutic agents |
US7598294B2 (en) | 2001-10-03 | 2009-10-06 | Spear Therapeutics Limited | 3,4-methylenedioxy-substituted chalcones as therapeutic agents |
WO2016159280A1 (en) * | 2015-03-31 | 2016-10-06 | 国立大学法人東北大学 | Antiallergic agent |
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