JPS60246384A - Chromone-8-carboxamide derivative - Google Patents
Chromone-8-carboxamide derivativeInfo
- Publication number
- JPS60246384A JPS60246384A JP10037684A JP10037684A JPS60246384A JP S60246384 A JPS60246384 A JP S60246384A JP 10037684 A JP10037684 A JP 10037684A JP 10037684 A JP10037684 A JP 10037684A JP S60246384 A JPS60246384 A JP S60246384A
- Authority
- JP
- Japan
- Prior art keywords
- chromone
- formula
- carboxylic acid
- compound
- general formula
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
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- Plural Heterocyclic Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
【発明の詳細な説明】
発明の目的
本発明は優れた抗アレルギー作用及び去痰作用を有する
新規なりロモンー８−カルボキサミド誘導体、及びその
薬理学的に許容しつる塩に関するものである。DETAILED DESCRIPTION OF THE INVENTION OBJECTS OF THE INVENTION The present invention relates to novel lomone-8-carboxamide derivatives having excellent antiallergic and expectorant effects, and pharmacologically acceptable salts thereof.
発明の構成
即ち、本発明は一般式（１）
（式中、Ｒ１はメチル基又はフェニル基を、Ｒ２は水素
原子、メチル基又はエチル基を表わす０）で示される新
規なりロモンー８−カルボキサミド誘導体、及びその薬
理学的に許容しつる塩に関するものである。Components of the Invention Namely, the present invention provides novel lomon-8-carboxamide derivatives represented by the general formula (1) (wherein R1 represents a methyl group or a phenyl group, and R2 represents a hydrogen atom, a methyl group, or an ethyl group). , and its pharmacologically acceptable salts.
本発明の前記一般式（１）で示される化合物の薬理学的
に許容しつる塩としては、たとえばナトリウム、カリウ
ム、カルシウム、アルミニウム等の金属塩等が挙げられ
る。Examples of pharmacologically acceptable salts of the compound represented by the general formula (1) of the present invention include metal salts of sodium, potassium, calcium, aluminum, and the like.
本発明の前記一般式（１）で示される新規なりロモンー
８−カルボキサミド誘導体は種々の方法により製造する
こきができる。The novel lomon-8-carboxamide derivative of the present invention represented by the general formula (1) can be produced by various methods.
本発明に係わる化合物の製造方法の第一の様式によれば
、前記一般式（１）で示される化合物は、次の一般式（
ロ）
（式中、Ｒ１及びＲ２は前述と同意義を、Ｘけハロゲン
原子を表わす。）
で示されるクロモン−８−カルボン酸ハロゲニド誘導体
と、次の式（Ｉｌｌ ）
で示されるテトラゾリルアミンとを、不活性有機溶媒中
で反応させることにより製造することができる。According to the first mode of the method for producing a compound according to the present invention, the compound represented by the general formula (1) is produced by the following general formula (
(b) (In the formula, R1 and R2 have the same meanings as above, and X represents a halogen atom.) A chromone-8-carboxylic acid halide derivative represented by the following formula (Ill); and a tetrazolylamine represented by the following formula (Ill). can be produced by reacting in an inert organic solvent.
本発明の方法において使用される不活性有機溶媒として
は、反応を阻害しない限りいかなるものでもよく、たと
えば、アセトン、エーテル、テトラヒドロ７ラン、ベン
ゼン、トルエン、クロロホルム、ピリジン等が使用され
る。Any inert organic solvent may be used in the method of the present invention as long as it does not inhibit the reaction, and examples thereof include acetone, ether, tetrahydroctane, benzene, toluene, chloroform, and pyridine.
又、反応は室温から加熱還流下において行なわれるが、
特に好ましくは室温下において行なわれることである。In addition, the reaction is carried out at room temperature to reflux, but
Particularly preferably, the reaction is carried out at room temperature.
本発明の製造方法において出発原料となった前記一般式
（ＩＩ）で示されるクロモン−８−カルボン酸ハロゲニ
ド誘導体は、次の一般式（ＩＹ）（式中、Ｒ，及びＲ２
は前述と同意義を表わすＱ）−Ｃ示−ａれるクロモン−
８−カルボン酸誘導体を、常法に従い酸ノ・ロゲニドに
用時変換することにより製造される。The chromone-8-carboxylic acid halide derivative represented by the general formula (II), which is the starting material in the production method of the present invention, has the following general formula (IY) (wherein R, and R2
represents the same meaning as above Q) -C indicates -a chromone -
It is produced by converting an 8-carboxylic acid derivative into an acid norogenide according to a conventional method at the time of use.
本発明に係わる化合物の製造方法の第二の様式によれば
、前記一般式（１）で示される化合物は、次の一般式（
Ｖ）
（式中、Ｒ１及びＲ２は前述と同意義を、Ｒ３１−１低
級アルキル基を表わす。）
で示されるクロモン−８−カルボン酸混合酸無水物誘導
体と、前記式（Ｉｌｌ ）で示されるテトラゾリルアミ
ン七を、不活性有機溶媒中で反応させることにより製造
することができる。According to the second mode of the method for producing a compound according to the present invention, the compound represented by the general formula (1) is prepared by the following general formula (
V) A chromone-8-carboxylic acid mixed acid anhydride derivative represented by the formula (wherein R1 and R2 have the same meanings as above and R31-1 represents a lower alkyl group) and a chromone-8-carboxylic acid mixed acid anhydride derivative represented by the above formula (Ill) Tetrazolylamine 7 can be prepared by reacting in an inert organic solvent.
本発明の方法において使用される不活性有機溶媒きして
は、反応を阻害しない限りいかなるものでもよく、たと
えば、アセトン、エーテル、テトラヒドロ７ラン、クロ
ロホルム、１化メチレン。Any inert organic solvent may be used in the method of the present invention as long as it does not inhibit the reaction, such as acetone, ether, tetrahydro7rane, chloroform, and methylene monide.
ジメチルホルムアミド等が使用される。Dimethylformamide etc. are used.
又、反応は−１００から加熱還流下において行なわれる
が、好ましくは室温下において行なわれることである。Further, the reaction is carried out under heating under reflux from -100 °C, but preferably at room temperature.
本発明の製造方法において出発原料となった前記一般式
（Ｖ）で示されるクロモン−８−カルボン酸混合酸無水
物誘導体は、前記一般式（１ｖ）で示されるクロモン−
８−カルボン酸誘導体を、常法に従いトリエチルアミン
の存在下、次の一般式（）
％式％（）
（式中、Ｒ３及びＸは前述と同意義を表わす。）で示さ
れるハロゲノ炭酸アルキル誘導体と反応きせることによ
り用時製造される。The chromone-8-carboxylic acid mixed acid anhydride derivative represented by the general formula (V), which is the starting material in the production method of the present invention, is the chromone-8-carboxylic acid mixed acid anhydride derivative represented by the general formula (1v).
The 8-carboxylic acid derivative is converted into a halogenoalkyl carbonate derivative represented by the following general formula () % formula % () (wherein R3 and X represent the same meanings as above) in the presence of triethylamine according to a conventional method. It is produced at the time of use by reaction.
発明の効果
この様にして製造される前記一般式（１）で示される新
規なりコモン−８−カルボキサミド誘導体、及びその薬
理学的に許容しうる＃１は、優れた抗アレルギー作用、
去痰作用を有し、気管支喘、＠。Effects of the Invention The novel common-8-carboxamide derivative represented by the general formula (1) and its pharmacologically acceptable #1 produced in this manner have excellent anti-allergic activity,
It has an expectorant effect and causes bronchial asthma.
アレルギー性胃腸障害、枯草熱、じん麻疹、アレルギー
性鼻炎等の治療剤として極めて有用である。It is extremely useful as a therapeutic agent for allergic gastrointestinal disorders, hay fever, hives, allergic rhinitis, etc.
以下、本発明を実施例によって説明する。Hereinafter, the present invention will be explained by examples.
実施例１
２．３−ジメチル−Ｎ−（ＩＨ−５−テトラゾリル）ク
ロモン−８−カルボキサミド
２．８−ジメチルクロモン−８−カルボン酸１゜５０＆
のテトラヒドロ７ラン５０ゴ懸濁液中に、水冷攪拌下、
トリエチルアミン１．０５ｇ／及びクロル炭酸エチル０
．７２＋ｌを加え、３０分間攪拌する。Example 1 2.3-dimethyl-N-(IH-5-tetrazolyl)chromone-8-carboxamide 2.8-dimethylchromone-8-carboxylic acid 1°50&
in a suspension of 50% tetrahydro7ran under water-cooled stirring,
Triethylamine 1.05g/and ethyl chlorocarbonate 0
．． Add 72+l and stir for 30 minutes.
次いで、水冷下、ＩＨ−５−テトラゾリルアミン・１水
和物０．７８．９を加え、室温にて２４時間攪拌する。Next, 0.78.9 of IH-5-tetrazolylamine monohydrate was added under water cooling, and the mixture was stirred at room temperature for 24 hours.
反応後、析出結晶をｐ取し、塩酸水溶液にて洗浄して、
淡褐色結晶１．１５＆を得る。ジメチルクロモンド及び
メタノールの混液より再［＆して、融点８００°以上の
淡黄色結晶を得る。After the reaction, the precipitated crystals were collected and washed with an aqueous hydrochloric acid solution.
Light brown crystals of 1.15% are obtained. Re-mix from a mixture of dimethyl chromone and methanol to obtain pale yellow crystals with a melting point of 800° or higher.
元素分析値 Ｃ１３Ｈ１ｌＮ５０３
理論値 Ｃ，５４，７４；Ｈ，８，８９；Ｎ、 ２４．
５５実験値 Ｃ，５４，８８；Ｈ，４，０６；Ｎ、 ２
４．１９実施例２
Ｎ−（ＩＨ−５−テトラゾリル）７ラボンー８−カルボ
キサミド
フラボン−８−カルボン酸１．５０．Ｌ テトラヒドロ
フラン５０ｇ／、）リエチルアミン０．８６ｍ１゜クロ
ル炭酸エチル０．５９ ｍｌ及び】Ｈ−５−テトラゾリ
ルアミン・１水和物０６４ｇを用いて、実施例１と同様
に処理し、無色結晶０．８６．９を得る０ジメチルスル
ホキシド及びメタノールの混液より再結晶して、融点３
０００以上の無色針状晶を得る。Elemental analysis value C13H11N503 Theoretical value C, 54, 74; H, 8, 89; N, 24.
55 experimental value C, 54,88; H, 4,06; N, 2
4.19 Example 2 N-(IH-5-tetrazolyl)7rabone-8-carboxamide flavone-8-carboxylic acid 1.50. The treatment was carried out in the same manner as in Example 1 using 50 g of L tetrahydrofuran, 0.86 ml of ) ethylamine, 0.59 ml of ethyl chlorocarbonate, and 064 g of H-5-tetrazolylamine monohydrate, resulting in 0 colorless crystals. Recrystallized from a mixture of dimethyl sulfoxide and methanol to obtain .86.9, melting point 3.
000 or more colorless needle crystals are obtained.
元素分析値 Ｃ１７Ｈ１１Ｎ５０３・捗Ｈ２０理論値
Ｃ，５９，６５；Ｈ，ｓ５ａ ：Ｎ、 ２０．４６実験
値 Ｃ，５９，９８；Ｈ，８，６５；Ｎ、 ２０．８２
実施例３
８−メチル−Ｎ−（−１Ｈ−５−テトラゾリル）フラボ
ン−８−カルボキサミド
３−メチルフラボン−８−カルボン酸クロリド（３−メ
チルフラボン−８−カルボン酸２．０ＯＦ及び塩化チオ
ニル１．５６ｇ？より製する）、ＩＨ−５−テトラゾリ
ルアミン・１水和物０６６ｇ及びピリジン２０＊／の混
合物を、室温にて２時間攪拌する０反応混合物に塩酸水
溶液を加えて、析出物をｐ取する。ｐ散物を炭酸水素す
） ＩＪウム水溶液にて洗浄し、無色結晶０．８６．９
を得る０ジメチルホルムアミド及びメタノールの混液よ
り再結晶して、融点２９２〜２９６°（分解）の無色針
状晶を得る。Elemental analysis value C17H11N503, progress H20 theoretical value
C, 59, 65; H, s5a: N, 20.46 Experimental value C, 59, 98; H, 8, 65; N, 20.82
Example 3 8-Methyl-N-(-1H-5-tetrazolyl)flavone-8-carboxamide 3-methylflavone-8-carboxylic acid chloride (2.0OF of 3-methylflavone-8-carboxylic acid and 1.0OF of thionyl chloride). A mixture of 066 g of IH-5-tetrazolylamine monohydrate and 20* of pyridine was stirred at room temperature for 2 hours. An aqueous hydrochloric acid solution was added to the reaction mixture to remove the precipitate. take. Wash the P powder with hydrogen carbonate aqueous solution to give colorless crystals of 0.86.9
Recrystallization from a mixture of dimethylformamide and methanol gives colorless needles with a melting point of 292-296° (decomposition).
元素分析値 Ｃｌ８Ｈ１３Ｎ５０３
理論値 Ｃ，６２，２５ｉＨ，８゜７７；Ｎ、２０．１
６実験値 Ｃ，６２，２２；Ｈ，１９ｇ 、Ｎ、 ２０
．８１実施例４
３−エチル−Ｎ−（ＩＨ−５−テトラゾリル）フラボン
−８−カルボキサミド
８−エチル７ラボンー８−カルボン酸クロリド２．００
ｇ、ＩＨ−５−テトラゾリルアミン・１水和物０６０ｇ
及びピリジン２０ｇｔの混合物を、室温忙て１時間攪拌
する。析出結晶をｐ取し、水。Elemental analysis value Cl8H13N503 Theoretical value C, 62, 25iH, 8° 77; N, 20.1
6 Experimental values C, 62, 22; H, 19g, N, 20
．． 81 Example 4 3-ethyl-N-(IH-5-tetrazolyl)flavone-8-carboxamide 8-ethyl 7ravone-8-carboxylic acid chloride 2.00
g, IH-5-tetrazolylamine monohydrate 060g
and 20 gt of pyridine is stirred at room temperature for 1 hour. Collect the precipitated crystals and add water.
酢酸エチルにて順次洗浄し、無色結晶１．５２９を得る
。ジメチルホルムアミド及びメタノールの混液より再結
晶して、融点２９４〜２９６°（分解）の無色結晶を得
る。After successive washing with ethyl acetate, 1.529 colorless crystals were obtained. Recrystallization from a mixture of dimethylformamide and methanol gives colorless crystals with a melting point of 294-296° (decomposition).
元素分析値 Ｃ１９Ｈｌ ５Ｎ ５０３理論値 Ｃ，６
１１５；Ｈ，４，１８、Ｎ、 １９．８８実験値 Ｃ，
６８，８８；Ｈ，４，０７；Ｎ、 ］、９．５６特許出
願人 北陸製薬株式会社Elemental analysis value C19Hl 5N 503 Theoretical value C,6
115; H, 4, 18, N, 19.88 experimental value C,
68,88; H, 4,07; N, ], 9.56 Patent applicant Hokuriku Pharmaceutical Co., Ltd.
Claims (1)
水０素原子、メチル基又はエチル基を表わす。） で示されるクロモン−８−カルボキサミド誘導体、及び
その薬理学的に許容しうる塩。[Scope of Claims] A chromone-8-carboxamide derivative represented by the general formula (wherein R11-j is a methyl group or a phenyl group, and R2 represents a hydrogen atom, a methyl group, or an ethyl group), and its Pharmacologically acceptable salts.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP10037684A JPS60246384A (en) | 1984-05-21 | 1984-05-21 | Chromone-8-carboxamide derivative |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP10037684A JPS60246384A (en) | 1984-05-21 | 1984-05-21 | Chromone-8-carboxamide derivative |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPS60246384A true JPS60246384A (en) | 1985-12-06 |
Family
ID=14272306
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP10037684A Pending JPS60246384A (en) | 1984-05-21 | 1984-05-21 | Chromone-8-carboxamide derivative |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS60246384A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2005077942A1 (en) * | 2004-02-12 | 2005-08-25 | Sk Chemicals, Co., Ltd. | Process for preparing substituted benzopyran compounds |
| WO2010037127A1 (en) * | 2008-09-29 | 2010-04-01 | Sirtris Pharmaceuticals, Inc. | Chromenone analogs as sirtuin modulators |
-
1984
- 1984-05-21 JP JP10037684A patent/JPS60246384A/en active Pending
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2005077942A1 (en) * | 2004-02-12 | 2005-08-25 | Sk Chemicals, Co., Ltd. | Process for preparing substituted benzopyran compounds |
| WO2010037127A1 (en) * | 2008-09-29 | 2010-04-01 | Sirtris Pharmaceuticals, Inc. | Chromenone analogs as sirtuin modulators |
| JP2012504148A (en) * | 2008-09-29 | 2012-02-16 | サートリス ファーマシューティカルズ， インコーポレイテッド | Chromenone analog as a sirtuin modulator |
| EP2342188A4 (en) * | 2008-09-29 | 2012-06-06 | Sirtris Pharmaceuticals Inc | Chromenone analogs as sirtuin modulators |
| AU2009295946B2 (en) * | 2008-09-29 | 2013-03-21 | Sirtris Pharmaceuticals, Inc. | Chromenone analogs as sirtuin modulators |
| US8987258B2 (en) | 2008-09-29 | 2015-03-24 | Christopher Oalmann | Chromenone analogs as sirtuin modulators |
| JP2015134809A (en) * | 2008-09-29 | 2015-07-27 | サートリス ファーマシューティカルズ， インコーポレイテッド | Chromenone analogs as sirtuin modulators |
| US9326986B2 (en) | 2008-09-29 | 2016-05-03 | Glaxosmithkline Llc | Quinazolinone, quinolone and related analogs as sirtuin modulators |
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