JPH0733769A - Pyrazolopyridine derivative and its production - Google Patents
Pyrazolopyridine derivative and its productionInfo
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- JPH0733769A JPH0733769A JP20356693A JP20356693A JPH0733769A JP H0733769 A JPH0733769 A JP H0733769A JP 20356693 A JP20356693 A JP 20356693A JP 20356693 A JP20356693 A JP 20356693A JP H0733769 A JPH0733769 A JP H0733769A
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Abstract
Description
【０００１】[0001]
【産業上の利用分野】本発明は強力な抗アレルギー作用
と、気道過敏抑制作用を併せ持つ、新規なピラゾロピリ
ジン誘導体及びそれらの製造法に関する。BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a novel pyrazolopyridine derivative having both a strong antiallergic action and an airway hyperresponsiveness inhibiting action, and a process for producing them.
【０００２】[0002]
【従来の技術】抗アレルギー作用を有するピラゾロピリ
ジン誘導体としては、本出願人らによる特開昭59-16751
6 号公報記載の化合物が知られており、その構造はピラ
ゾロピリジン骨格の３位置換基がアシル誘導体である。BACKGROUND OF THE INVENTION As a pyrazolopyridine derivative having an antiallergic action, the applicants of the present invention have disclosed JP-A-59-16751.
The compound described in Japanese Patent No. 6 is known, and its structure is such that the 3-position substituent of the pyrazolopyridine skeleton is an acyl derivative.
【０００３】また、アデノシン拮抗作用を有し、多様な
用途が示されているピラゾロピリジン誘導体としては、
特開昭64-45385号公報、特開平3-141222号公報及び特開
平4-244084号公報記載の化合物群（Ａ群）、並びに特開
平2-243689号公報及び特開平4-253978号公報記載の化合
物群（Ｂ群）が知られているが本発明化合物とは作用を
異にし、また構造的にも異なるものである。In addition, pyrazolopyridine derivatives having an adenosine antagonistic action and showing various uses include:
Compound groups (group A) described in JP-A-64-45385, JP-A-3-141222, and JP-A-4-24084, and JP-A-2-243689 and JP-A-4-253978 Although the compound group (B group) is known, it has a different action from the compound of the present invention and is structurally different.
【０００４】即ち、Ａ群はピラゾロピリジン骨格の３位
置換基はアクリル酸誘導体であり、有用性ある化合物で
の２位置換基はアリール基、特にフェニル基であること
を特徴としている。一方、Ｂ群での３位置換基は不飽和
含窒素複素環、特に３−オキソ−２，３−ジヒドロピリ
ダジン誘導体であり、２位置換基はアリール基に限定さ
れている。That is, Group A is characterized in that the 3-position substituent of the pyrazolopyridine skeleton is an acrylic acid derivative, and the 2-position substituent in useful compounds is an aryl group, especially a phenyl group. On the other hand, the 3-position substituent in Group B is an unsaturated nitrogen-containing heterocycle, especially a 3-oxo-2,3-dihydropyridazine derivative, and the 2-position substituent is limited to an aryl group.
【０００５】[0005]
【発明が解決しようとする課題及び課題を解決する手
段】従来、気管支喘息等のアレルギー疾患は、抗原−抗
体反応に伴うケミカルメディエーターの仲介によるもの
と考えられ、抗アレルギー剤の研究はケミカルメディエ
ーターの放出を抑制するもの、又はその作用に拮抗する
ものの開発に向けられてきている。本発明者らは、抗ア
レルギー作用を有する化合物について鋭意研究を重ねた
結果、これまでに知られている抗アレルギー剤とは構造
を異にした新規なシクロアルケニルピラゾロピリジン誘
導体が強力な抗アレルギー作用を持つことを見い出し、
発明を完成した。Problems to be Solved by the Invention and Means for Solving the Problems Conventionally, allergic diseases such as bronchial asthma are considered to be mediated by chemical mediators associated with antigen-antibody reaction, and research on antiallergic agents is based on chemical mediators. It has been directed to the development of substances that suppress release or antagonize its action. As a result of intensive studies on compounds having an antiallergic action, the present inventors have found that a novel cycloalkenylpyrazolopyridine derivative having a structure different from that of known antiallergic agents has a strong antiallergic effect. Found to have an effect,
Completed the invention.
【０００６】即ち本発明は、一般式（１） （式中、Ｒは水素原子、炭素数１〜４の低級アルキル
基、炭素数３〜６のシクロアルキル基を示し、ｍは０〜
２の整数を示し、ｎは０又は１の整数を示す）で表され
るピラゾロピリジン誘導体に関するものである。That is, the present invention is based on the general formula (1) (In the formula, R represents a hydrogen atom, a lower alkyl group having 1 to 4 carbon atoms, or a cycloalkyl group having 3 to 6 carbon atoms, and m is 0 to
It represents an integer of 2 and n represents an integer of 0 or 1).
【０００７】本発明の一般式（１）において、「低級ア
ルキル基」とはメチル、エチル、プロピル等、直鎖もし
くは分岐した炭素数１〜４のものが挙げられる。In the general formula (1) of the present invention, examples of the "lower alkyl group" include linear or branched ones having 1 to 4 carbon atoms such as methyl, ethyl and propyl.
【０００８】本発明によれば上記一般式（１）である化
合物は以下の方法により製造することができる。According to the present invention, the compound represented by the general formula (1) can be produced by the following method.
【０００９】一般式（１）のうち下記の一般式（１−
ａ）である化合物は、下記一般式（２）の化合物に下記
一般式（３）の化合物を作用させることにより製造する
ことができる。Of the general formula (1), the following general formula (1-
The compound a) can be produced by reacting the compound of the following general formula (2) with the compound of the following general formula (3).
【００１０】 （式中、Ｒは水素原子、炭素数１〜４の低級アルキル
基、炭素数３〜６のシクロアルキル基を示し、ｎは０又
は１の整数を示す）[0010] (In the formula, R represents a hydrogen atom, a lower alkyl group having 1 to 4 carbon atoms, a cycloalkyl group having 3 to 6 carbon atoms, and n represents an integer of 0 or 1)
【００１１】 （式中、Ｒは前述の通り）[0011] (In the formula, R is as described above)
【００１２】 （式中、ｎは前述の通り）[0012] (In the formula, n is as described above)
【００１３】反応は、酢酸溶媒中、反応温度としては、
室温〜溶媒還流温度で行うことができるが、加温が好ま
しい。また触媒として、濃硫酸、リン酸等の酸触媒又は
それらの希釈したものの添加が好適である。また、無水
酢酸の添加も好ましい。The reaction is carried out in acetic acid solvent at a reaction temperature of
The reaction can be carried out at room temperature to the solvent reflux temperature, but warming is preferable. Further, as the catalyst, it is preferable to add an acid catalyst such as concentrated sulfuric acid or phosphoric acid or a diluted one thereof. It is also preferable to add acetic anhydride.
【００１４】一般式（１）のうちｍが１又は２である下
記の一般式（１−ｂ）の化合物は、下記一般式（１−
ａ）の化合物を酸化することにより製造することができ
る。The compound of the following general formula (1-b) in which m is 1 or 2 in the general formula (1) is represented by the following general formula (1-
It can be produced by oxidizing the compound of a).
【００１５】 （式中、Ｒは水素原子、炭素数１〜４の低級アルキル
基、炭素数３〜６のシクロアルキル基を示し、ｎは０又
は１の整数を示し、ｍ′は１又は２の整数を示す）[0015] (In the formula, R represents a hydrogen atom, a lower alkyl group having 1 to 4 carbon atoms, a cycloalkyl group having 3 to 6 carbon atoms, n represents an integer of 0 or 1, and m ′ represents an integer of 1 or 2. Show)
【００１６】 （式中、Ｒ、ｎは前述の通り）[0016] (In the formula, R and n are as described above)
【００１７】反応は、無機過酸あるいは有機過酸により
行うことができる。例えば、含水メタノール、含水ジオ
キサン等中、ｍ−過ヨウ素酸ナトリウムにより行うこと
ができる。反応温度としては特に限定されないが、室温
〜加温が好ましい。あるいは、有機溶媒、例えば塩化メ
チレン等中、ｍ−クロロ過安息香酸により行うことがで
きる。この場合、メタクロロ過安息香酸の添加量によ
り、硫黄原子の酸化状態を調節することができる。反応
温度は特に限定されないが、氷冷下〜加温が好ましい。The reaction can be carried out with an inorganic or organic peracid. For example, m-sodium periodate can be used in water-containing methanol or water-containing dioxane. The reaction temperature is not particularly limited, but room temperature to heating is preferable. Alternatively, it can be carried out with m-chloroperbenzoic acid in an organic solvent such as methylene chloride. In this case, the oxidation state of the sulfur atom can be adjusted by the addition amount of metachloroperbenzoic acid. The reaction temperature is not particularly limited, but is preferably under ice cooling to warming.
【００１８】本発明における一般式（２）の化合物のう
ちＲが炭素数３〜６のシクロアルキル基である化合物は
先に出願の方法（特願平5-86704 号）により製造するこ
とができる。なお、本発明における一般式（１）の化合
物のうち、ｍが１である化合物は硫黄原子に基づく２種
の光学異性体が存在するが、その各々、あるいはそれら
の混合物のいずれも本発明に包含される。The compound of the general formula (2) in the present invention in which R is a cycloalkyl group having 3 to 6 carbon atoms can be produced by the method previously filed (Japanese Patent Application No. 5-86704). . In the compound of the general formula (1) in the present invention, the compound in which m is 1 has two kinds of optical isomers based on a sulfur atom, and each of them or a mixture thereof is included in the present invention. Included.
【００１９】[0019]
【実施例】次に本発明を具体例によって説明するが、こ
れらの例によって本発明が限定されるものではない。EXAMPLES The present invention will be described below with reference to specific examples, but the present invention is not limited to these examples.
【００２０】（実施例１）３−（５，６−ジヒドロ−２
Ｈ−チオピラン−４−イル）−２−メチルピラゾロ
［１，５−ａ］ピリジン(Example 1) 3- (5,6-dihydro-2)
H-thiopyran-4-yl) -2-methylpyrazolo [1,5-a] pyridine
【００２１】２−メチルピラゾロ［１，５−ａ］ピリジ
ン（2.00ｇ）、テトラヒドロチオピラン−４−オン（2.
64ｇ）、２Ｎ−リン酸10ml、酢酸20mlの混合物を80℃に
て６時間攪拌した。反応液を氷水に加え、濃アンモニア
水にてｐＨ９としクロロホルムで抽出した。有機層を飽
和食塩水で洗浄し、無水硫酸ナトリウムで乾燥した。溶
媒を減圧留去後、残渣を減圧蒸留し、淡黄色無晶形の目
的物2.01ｇ（収率58％、沸点 215℃、 0.4mmHg）を得
た。融点76〜78℃（ヘキサン）2-Methylpyrazolo [1,5-a] pyridine (2.00 g), tetrahydrothiopyran-4-one (2.
64 g), a mixture of 10 ml of 2N-phosphoric acid and 20 ml of acetic acid was stirred at 80 ° C. for 6 hours. The reaction solution was added to ice water, adjusted to pH 9 with concentrated ammonia water, and extracted with chloroform. The organic layer was washed with saturated saline and dried over anhydrous sodium sulfate. After the solvent was distilled off under reduced pressure, the residue was distilled under reduced pressure to obtain 2.01 g of a pale yellow amorphous target product (yield 58%, boiling point 215 ° C., 0.4 mmHg). Melting point 76-78 ° C (hexane)
【００２２】元素分析値（％） Ｃ13Ｈ14Ｎ2 Ｓとして 計算値 Ｃ：67.79 Ｈ：6.13 Ｎ：12.16 実測値 Ｃ：67.68 Ｈ：6.08 Ｎ：12.08 ＭＳ（m/z)： 230（Ｍ+ ）Elemental analysis value (%) Calculated value as C 13 H 14 N 2 S C: 67.79 H: 6.13 N: 12.16 Measured value C: 67.68 H: 6.08 N: 12.08 MS (m / z): 230 (M + )
【００２３】（実施例２）２−シクロプロピル−３−
（５，６−ジヒドロ−２Ｈ−チオピラン−４−イル）ピ
ラゾロ［１，５−ａ］ピリジン(Example 2) 2-cyclopropyl-3-
(5,6-Dihydro-2H-thiopyran-4-yl) pyrazolo [1,5-a] pyridine
【００２４】テトラヒドロチオピラン−４−オン（4.41
ｇ）、無水酢酸12.2ml、酢酸26.7mlの混合物を50℃にて
20分間攪拌後、２−シクロプロピルピラゾロ［１，５−
ａ］ピリジン（5.00ｇ）の酢酸10ml溶液を加え、 100℃
で27時間加熱攪拌した。途中18時間後にテトラヒドロチ
オピラン−４−オン(370mg）を追加した。反応液を氷水
に加え、酢酸エチルで抽出した。有機層を飽和炭酸水素
ナトリウム水溶液、水、飽和食塩水にて順次洗浄し、無
水硫酸ナトリウムで乾燥した。溶媒を減圧留去し、残渣
をシリカゲルカラムクロマトグラフィー（展開相：酢酸
エチル−ヘキサン １：４）にて精製後、43％含水エタ
ノールで再結晶し、無色リン片状結晶の目的物1.88ｇ
（収率23％）を得た。融点： 119〜120 ℃Tetrahydrothiopyran-4-one (4.41
g), a mixture of 12.2 ml of acetic anhydride and 26.7 ml of acetic acid at 50 ° C.
After stirring for 20 minutes, 2-cyclopropylpyrazolo [1,5-
a] Add a 10 ml solution of pyridine (5.00 g) in acetic acid, and add 100 ° C.
The mixture was heated and stirred for 27 hours. 18 hours later, tetrahydrothiopyran-4-one (370 mg) was added. The reaction solution was added to ice water and extracted with ethyl acetate. The organic layer was washed successively with saturated aqueous sodium hydrogen carbonate solution, water and saturated brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure, the residue was purified by silica gel column chromatography (developing phase: ethyl acetate-hexane 1: 4), and recrystallized with 43% hydrous ethanol to give 1.88 g of the desired product as colorless flaky crystals.
(Yield 23%) was obtained. Melting point: 119-120 ° C
【００２５】元素分析値（％） Ｃ15Ｈ16Ｎ2 Ｓとして 計算値 Ｃ：70.28 Ｈ：6.29 Ｎ：10.93 実測値 Ｃ：70.13 Ｈ：6.49 Ｎ：10.96 ＭＳ（m/z)： 256（Ｍ+ ）Elemental analysis value (%) Calculated value as C 15 H 16 N 2 S C: 70.28 H: 6.29 N: 10.93 Measured value C: 70.13 H: 6.49 N: 10.96 MS (m / z): 256 (M + )
【００２６】（実施例３）２−シクロペンチル−３−
（５，６−ジヒドロ−２Ｈ−チオピラン−４−イル）ピ
ラゾロ［１，５−ａ］ピリジンExample 3 2-Cyclopentyl-3-
(5,6-Dihydro-2H-thiopyran-4-yl) pyrazolo [1,5-a] pyridine
【００２７】テトラヒドロチオピラン−４−オン(469m
g）、２−シクロペンチルピラゾロ［１，５−ａ］ピリ
ジン(751mg）、酢酸40ml、濃硫酸３滴の混合溶液をディ
ーンスターク装置を付して16時間加熱還流した。反応液
を冷却後、水を加えて酢酸エチルで抽出、得られた有機
層を水、飽和炭酸水素ナトリウム水溶液、水にて順次洗
浄し、無水硫酸ナトリウムで乾燥した。溶媒を減圧留去
し、残渣にヘキサンを加え、結晶を濾取した。得られた
結晶をシリカゲルカラムクロマトグラフィー（展開相：
塩化メチレン）にて精製後、ヘキサンで再結晶し、無色
リン片状結晶の目的物648mg （収率57％）を得た。融
点：91〜92℃Tetrahydrothiopyran-4-one (469m
A mixed solution of g), 2-cyclopentylpyrazolo [1,5-a] pyridine (751 mg), 40 ml of acetic acid and 3 drops of concentrated sulfuric acid was heated under reflux for 16 hours with a Dean Stark apparatus. After cooling the reaction solution, water was added and the mixture was extracted with ethyl acetate. The obtained organic layer was washed successively with water, saturated aqueous sodium hydrogen carbonate solution and water, and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, hexane was added to the residue, and the crystals were collected by filtration. The obtained crystals are subjected to silica gel column chromatography (developing phase:
After purification with methylene chloride), it was recrystallized from hexane to obtain 648 mg (yield 57%) of the desired product as colorless flaky crystals. Melting point: 91-92 ° C
【００２８】元素分析値（％） Ｃ17Ｈ20Ｎ2 Ｓとして 計算値 Ｃ：71.79 Ｈ：7.09 Ｎ：9.85 実測値 Ｃ：71.72 Ｈ：7.00 Ｎ：9.82 ＭＳ（m/z)： 284（Ｍ+ ）Elemental analysis value (%) Calculated value as C 17 H 20 N 2 S C: 71.79 H: 7.09 N: 9.85 Actual value C: 71.72 H: 7.00 N: 9.82 MS (m / z): 284 (M + )
【００２９】（実施例４，５）実施例１と同様にして表
１の化合物を得た。(Examples 4 and 5) In the same manner as in Example 1, the compounds shown in Table 1 were obtained.
【００３０】[0030]
【表１】 [Table 1]
【００３１】（実施例６）３−（４，５−ジヒドロチオ
フェン−３−イル）−２−メチルピラゾロ［１，５−
ａ］ピリジンExample 6 3- (4,5-dihydrothiophen-3-yl) -2-methylpyrazolo [1,5-
a] pyridine
【００３２】２−メチルピラゾロ［１，５−ａ］ピリジ
ン(3.0ｇ）、テトラヒドロチオフェン−３−オン（3.48
ｇ）、２Ｎ−リン酸（15ml）、酢酸（30ml）の混合物を
80℃で 9.5時間加熱攪拌した後、更に９時間加熱還流し
た。反応液を氷水中に加え、濃アンモニア水でｐＨ９と
し、塩化メチレンで抽出した。有機層を飽和食塩水で洗
浄し、無水硫酸ナトリウムで乾燥した。溶媒を減圧留去
し残渣をフラッシュカラムクロマトグラフィー（展開
相：ヘキサン−塩化メチレン−酢酸エチル 20：５：
１）にて精製し、ヘキサンで再結晶した。黄色針状結晶
の目的物 470mg（収率 9.6％）を得た。融点：72〜74℃2-Methylpyrazolo [1,5-a] pyridine (3.0 g), tetrahydrothiophen-3-one (3.48)
g) a mixture of 2N-phosphoric acid (15 ml) and acetic acid (30 ml)
After heating and stirring at 80 ° C. for 9.5 hours, the mixture was heated and refluxed for 9 hours. The reaction solution was added to ice water, adjusted to pH 9 with concentrated ammonia water, and extracted with methylene chloride. The organic layer was washed with saturated saline and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure and the residue was subjected to flash column chromatography (developing phase: hexane-methylene chloride-ethyl acetate 20: 5:
Purified in 1) and recrystallized from hexane. 470 mg (yield: 9.6%) of the desired product of yellow needle crystals was obtained. Melting point: 72-74 ° C
【００３３】元素分析値（％） Ｃ12Ｈ12Ｎ2 Ｓとして 計算値 Ｃ：66.64 Ｈ：5.59 Ｎ：12.95 実測値 Ｃ：66.46 Ｈ：5.43 Ｎ：12.95 ＭＳ（m/z)： 216（Ｍ+ ）Elemental analysis value (%) Calculated value as C 12 H 12 N 2 S C: 66.64 H: 5.59 N: 12.95 Measured value C: 66.46 H: 5.43 N: 12.95 MS (m / z): 216 (M + )
【００３４】（実施例７）３−（５，６−ジヒドロ−２
Ｈ−チオピラン−１−オキシド−４−イル）−２−メチ
ルピラゾロ［１，５−ａ］ピリジン(Example 7) 3- (5,6-dihydro-2)
H-thiopyran-1-oxide-4-yl) -2-methylpyrazolo [1,5-a] pyridine
【００３５】３−（５，６−ジヒドロ−２Ｈ−チオピラ
ン−４−イル）−２−メチルピラゾロ［１，５−ａ］ピ
リジン(1.0ｇ）を10％含水メタノール(200ml）に溶解
し、氷冷下メタ過ヨウ素酸ナトリウム(929mg）を加え、
室温にて８時間攪拌した。反応液を飽和食塩水中に加
え、エーテルで抽出した。有機層を無水硫酸マグネシウ
ムで乾燥し溶媒を減圧留去した。残渣を酢酸エチル−エ
タノール（１：１）混液にて再結晶し、淡褐色プリズム
状結晶の目的物 495mg（収率46％）を得た。融点： 164
〜166 ℃3- (5,6-Dihydro-2H-thiopyran-4-yl) -2-methylpyrazolo [1,5-a] pyridine (1.0 g) was dissolved in 10% hydrous methanol (200 ml) and cooled with ice. Add lower sodium metaperiodate (929 mg),
The mixture was stirred at room temperature for 8 hours. The reaction solution was added to saturated saline and extracted with ether. The organic layer was dried over anhydrous magnesium sulfate and the solvent was distilled off under reduced pressure. The residue was recrystallized from a mixed solution of ethyl acetate-ethanol (1: 1) to obtain 495 mg (yield 46%) of the target product as light brown prismatic crystals. Melting point: 164
~ 166 ℃
【００３６】元素分析値（％） Ｃ13Ｈ14Ｎ2 ＯＳとし
て 計算値 Ｃ：63.39 Ｈ：5.73 Ｎ：11.37 実測値 Ｃ：63.14 Ｈ：5.73 Ｎ：11.31 ＭＳ（m/z)： 246（Ｍ+ ）Elemental analysis value (%) Calculated value as C 13 H 14 N 2 OS C: 63.39 H: 5.73 N: 11.37 Measured value C: 63.14 H: 5.73 N: 11.31 MS (m / z): 246 (M + )
【００３７】（実施例８）３−（５，６−ジヒドロ−２
Ｈ−チオピラン−１−ジオキシド−４−イル）−２−メ
チルピラゾロ［１，５−ａ］ピリジン(Example 8) 3- (5,6-dihydro-2)
H-thiopyran-1-dioxide-4-yl) -2-methylpyrazolo [1,5-a] pyridine
【００３８】３−（５，６−ジヒドロ−２Ｈ−チオピラ
ン−４−イル）−２−メチルピラゾロ［１，５−ａ］ピ
リジン(1.0ｇ）を塩化メチレン30mlに溶解し、氷冷下、
ｍ−クロロ過安息香酸（70％）（2.14ｇ）を加え、同温
で３時間攪拌した。反応液をろ過し、氷水中に加え、塩
化メチレンで抽出した。有機層を10％亜硫酸水素ナトリ
ウム水溶液、飽和炭酸水素ナトリウム水溶液、水、飽和
食塩水にて順次洗浄後、無水硫酸ナトリウムで乾燥し
た。溶媒を減圧留去し、残渣をシリカゲルカラムクロマ
トグラフィー（展開相：ヘキサン−酢酸エチル ２：
３）にて精製し、酢酸エチルで再結晶した。無色プリズ
ム状結晶の目的物 537mg（収率47％）を得た。融点： 1
24〜126 ℃3- (5,6-Dihydro-2H-thiopyran-4-yl) -2-methylpyrazolo [1,5-a] pyridine (1.0 g) was dissolved in 30 ml of methylene chloride and cooled under ice.
m-Chloroperbenzoic acid (70%) (2.14 g) was added, and the mixture was stirred at the same temperature for 3 hours. The reaction solution was filtered, added to ice water, and extracted with methylene chloride. The organic layer was washed successively with 10% aqueous sodium hydrogen sulfite solution, saturated aqueous sodium hydrogen carbonate solution, water and saturated brine, and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the residue was subjected to silica gel column chromatography (developing phase: hexane-ethyl acetate 2:
It was purified in 3) and recrystallized from ethyl acetate. 537 mg (yield 47%) of the target product was obtained as colorless prism crystals. Melting point: 1
24-126 ° C
【００３９】元素分析値（％） Ｃ13Ｈ14Ｎ2 Ｏ2 Ｓと
して 計算値 Ｃ：59.52 Ｈ：5.38 Ｎ：10.68 実測値 Ｃ：59.63 Ｈ：5.30 Ｎ：10.63 ＭＳ（m/z)： 262（Ｍ+ ）Elemental analysis value (%) Calculated value as C 13 H 14 N 2 O 2 S C: 59.52 H: 5.38 N: 10.68 Measured value C: 59.63 H: 5.30 N: 10.63 MS (m / z): 262 ( M + )
【００４０】[0040]
（実験例１） モルモットアナフィラキシー性気道収縮抑制試験 Experimental Example 1 Guinea pig anaphylactic airway contraction suppression test
【００４１】体重 350ｇ前後の雄性ハートレイ(Hartle
y）系モルモットに卵アルブミンを筋肉内及び腹腔内に
それぞれ 100mg／kg投与して感作し、３日後さらに卵ア
ルブミン 100mg／kg（腹腔内）を投与して追加感作し
た。感作動物を初回感作３〜４週間後にペントバルビタ
ールナトリウム30mg／kg（腹腔内）で麻酔し、気道内圧
の変化をコンツェットレスラー変法（J. Harvey, et a
l.; J. Pharmacol. Method,9, 147-155, 1983 ）に従っ
て測定し、最小有効量を求めその結果を表２に示した。
アナフィラキシー性気道収縮は卵アルブミン（５mg／k
g）を左外頸静脈に挿入したカニューレより投与するこ
とにより惹起した。被験化合物はアラビアゴムを用いた
懸濁液とし、卵アルブミン投与１時間前に経口投与し
た。A male Hartle weighing about 350 g
y) Ovalbumin was intramuscularly and intraperitoneally administered to the guinea pigs of 100 mg / kg, respectively, and after 3 days, 100 mg / kg of ovalbumin (intraperitoneal) was further administered for additional sensitization. The sensitized animals were anesthetized with pentobarbital sodium 30 mg / kg (intraperitoneal) 3 to 4 weeks after the first sensitization, and the change in the airway pressure was modified by the kontzett wrestler modified method (J. Harvey, et a.
l .; J. Pharmacol. Method, 9, 147-155, 1983), and the minimum effective dose was determined and the results are shown in Table 2.
Anaphylactic airway constriction is caused by ovalbumin (5 mg / k
It was induced by administering g) from a cannula inserted into the left external jugular vein. The test compound was made into a suspension using gum arabic and orally administered 1 hour before the administration of ovalbumin.
【００４２】[0042]
【表２】 [Table 2]
Claims (4)
基、炭素数３〜６のシクロアルキル基を示し、ｍは０〜
２の整数を示し、ｎは０又は１の整数を示す）で表され
るピラゾロピリジン誘導体。1. The general formula (1) (In the formula, R represents a hydrogen atom, a lower alkyl group having 1 to 4 carbon atoms, or a cycloalkyl group having 3 to 6 carbon atoms, and m is 0 to
A pyrazolopyridine derivative represented by the formula (2) and n represents an integer of 0 or 1.
基、炭素数３〜６のシクロアルキル基を示す）で表され
る化合物に一般式（３） （式中、ｎは０又は１の整数を示す）で表される化合物
を作用させることを特徴とする一般式（１−ａ） （式中、Ｒ、ｎは前述の通り）で表されるピラゾロピリ
ジン誘導体の製造法。2. The general formula (2) (In the formula, R represents a hydrogen atom, a lower alkyl group having 1 to 4 carbon atoms, or a cycloalkyl group having 3 to 6 carbon atoms), and a compound represented by the general formula (3) (In the formula, n represents an integer of 0 or 1) A compound represented by the general formula (1-a) (In the formula, R and n are as described above) A method for producing a pyrazolopyridine derivative.
基、炭素数３〜６のシクロアルキル基を示し、ｎは０又
は１の整数を示す）で表される化合物を、酸化すること
を特徴とする一般式（１−ｂ） （式中、Ｒ、ｎは前述の通り、ｍ′は１又は２の整数を
示す）で表されるピラゾロピリジン誘導体の製造法。3. The general formula (1-a) (In the formula, R represents a hydrogen atom, a lower alkyl group having 1 to 4 carbon atoms, a cycloalkyl group having 3 to 6 carbon atoms, and n represents an integer of 0 or 1) and is oxidized. General formula (1-b) characterized by (In the formula, R and n are as described above, and m ′ is an integer of 1 or 2.) A process for producing a pyrazolopyridine derivative represented by the formula.
基、炭素数３〜６のシクロアルキル基を示し、ｍは０〜
２の整数を示し、ｎは０又は１の整数を示す）で表され
るピラゾロピリジン誘導体の少なくとも一種以上を有効
成分とする抗喘息薬。4. The general formula (1) (In the formula, R represents a hydrogen atom, a lower alkyl group having 1 to 4 carbon atoms, or a cycloalkyl group having 3 to 6 carbon atoms, and m is 0 to
An anti-asthma drug containing at least one or more pyrazolopyridine derivatives represented by the formula (2) and n is an integer of 0 or 1.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP20356693A JPH0733769A (en) | 1993-07-26 | 1993-07-26 | Pyrazolopyridine derivative and its production |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP20356693A JPH0733769A (en) | 1993-07-26 | 1993-07-26 | Pyrazolopyridine derivative and its production |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH0733769A true JPH0733769A (en) | 1995-02-03 |
Family
ID=16476256
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP20356693A Pending JPH0733769A (en) | 1993-07-26 | 1993-07-26 | Pyrazolopyridine derivative and its production |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH0733769A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1997040047A1 (en) * | 1996-04-25 | 1997-10-30 | Fujisawa Pharmaceutical Co., Ltd. | Preventives and remedies for ischemic intestinal lesion and ileus |
| US9504625B2 (en) | 2008-03-31 | 2016-11-29 | Kohler Co. | Vibroacoustic water system |
-
1993
- 1993-07-26 JP JP20356693A patent/JPH0733769A/en active Pending
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1997040047A1 (en) * | 1996-04-25 | 1997-10-30 | Fujisawa Pharmaceutical Co., Ltd. | Preventives and remedies for ischemic intestinal lesion and ileus |
| US6214843B1 (en) * | 1996-04-25 | 2001-04-10 | Fujitsawa Pharmaceutical Co., Ltd. | Preventives and remedies for ischemic intestinal lesion and ileus |
| US9504625B2 (en) | 2008-03-31 | 2016-11-29 | Kohler Co. | Vibroacoustic water system |
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