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JP2526128B2 - Quinolonecarboxylic acid derivative - Google Patents

Quinolonecarboxylic acid derivative

Info

Publication number
JP2526128B2
JP2526128B2 JP1189214A JP18921489A JP2526128B2 JP 2526128 B2 JP2526128 B2 JP 2526128B2 JP 1189214 A JP1189214 A JP 1189214A JP 18921489 A JP18921489 A JP 18921489A JP 2526128 B2 JP2526128 B2 JP 2526128B2
Authority
JP
Japan
Prior art keywords
reaction
solvent
compound
acid derivative
chloroform
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.)
Expired - Fee Related
Application number
JP1189214A
Other languages
Japanese (ja)
Other versions
JPH02138261A (en
Inventor
晶弘 柴田
秀明 松田
健光 浅岡
勝 松本
隆一 川原
達彦 香取
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
SSP Co Ltd
Original Assignee
SSP Co Ltd
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by SSP Co Ltd filed Critical SSP Co Ltd
Priority to US07/807,856 priority Critical patent/US5324735A/en
Priority to CA002058424A priority patent/CA2058424A1/en
Priority to EP19900905660 priority patent/EP0486687A4/en
Priority to KR1019910701725A priority patent/KR920701163A/en
Priority to PCT/JP1990/000425 priority patent/WO1991001308A1/en
Publication of JPH02138261A publication Critical patent/JPH02138261A/en
Application granted granted Critical
Publication of JP2526128B2 publication Critical patent/JP2526128B2/en
Anticipated expiration legal-status Critical
Expired - Fee Related legal-status Critical Current

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
    • C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
    • C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D215/48—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
    • C07D215/54—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen attached in position 3
    • C07D215/56—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen attached in position 3 with oxygen atoms in position 4

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Quinoline Compounds (AREA)

Description

【発明の詳細な説明】 〔産業上の利用分野〕 本発明は優れた抗菌作用を有する新規なキノロンカル
ボン酸誘導体又はその塩に関する。DETAILED DESCRIPTION OF THE INVENTION [Field of Industrial Application] The present invention relates to a novel quinolonecarboxylic acid derivative having an excellent antibacterial activity or a salt thereof.

〔従来の技術〕 従来、グラム陰性菌による感染症の治療薬としては、
ナリジクス酸、ピロミド酸等の合成抗菌剤知られてい
る。しかし、これらは緑膿菌感染等の難治性疾患に対し
て効果が低いという欠点があった。また一方、ノルフロ
キサシン、シプロフロキサシン等の抗菌活性の強い抗菌
剤が開発され、臨床において使用されている。[Prior Art] Conventionally, as a therapeutic agent for infectious diseases caused by Gram-negative bacteria,
Synthetic antibacterial agents such as nalidixic acid and pyromidic acid are known. However, they have a drawback that they are less effective against intractable diseases such as Pseudomonas aeruginosa infection. On the other hand, antibacterial agents with strong antibacterial activity such as norfloxacin and ciprofloxacin have been developed and used clinically.

〔発明が解決しようとする課題〕[Problems to be Solved by the Invention]

合成抗菌剤が生体で有効に作用するには、抗菌活性が
強いことと、利用率がよいことが必要であるが、上記の
従来の合成抗菌剤は、吸収が悪く、生体利用率が低いと
いう欠点があった。In order for a synthetic antibacterial agent to act effectively in a living body, it must have a strong antibacterial activity and a high utilization rate. However, the above-mentioned conventional synthetic antibacterial agents have poor absorption and low bioavailability. There was a flaw.

〔課題を解決するための手段〕 斯かる実情において、本発明者は、数多くのキノリン
誘導体を合成し、その抗菌活性及び生体への吸収を検討
したところ、後記式（Ｉ）で表わされるキノロンカルボ
ン酸誘導体及びその塩が優れた抗菌活性と吸収性を有す
ることを見出し、本発明を完成した。[Means for Solving the Problems] In such circumstances, the present inventor synthesized a large number of quinoline derivatives and studied their antibacterial activity and absorption into the living body. As a result, the quinolone carvone represented by the following formula (I) was obtained. The present invention was completed by finding that the acid derivative and its salt have excellent antibacterial activity and absorbability.

すなわち、本発明は、次の式（Ｉ） で表わされるキノロンカルボン酸誘導体又はその塩を提
供するものである。That is, the present invention provides the following formula (I): The present invention provides a quinolonecarboxylic acid derivative represented by or a salt thereof.

本発明化合物（Ｉ）は、例えば次の方法によって製造
される。The compound (I) of the present invention is produced, for example, by the following method.

製法1: （式中、R1は低級アルキル基、Ｘはハロゲン原子を示
す） 原料化合物（II）は、例えば西独特許DE3,522,406号
に記載の方法によって製造される。Process 1: (In the formula, R 1 represents a lower alkyl group and X represents a halogen atom.) The starting compound (II) is produced, for example, by the method described in West German Patent DE 3,522,406.

化合物（II）から（III）を製造するには、（II）１
モルに対しハロゲン化剤１〜５モルを使用し、溶媒中、
室温ないし還流下、１〜20時間反応させる。ここでハロ
ゲン化剤としては、塩化チオニル、臭化チオニル、オキ
シ塩化リン、三塩化リン、三臭化リン、五塩化リン等が
使用され、また溶媒としては、塩化メチレン、クロロホ
ルム、四塩化炭素、1,2−ジクロルエタン、トリクロル
エタン等が使用される。反応終了後、反応物を濃縮し、
残渣をシリカゲルカラムクロマトグラフィー等で精製す
れば、（III）が得られる。To produce (III) from compound (II), (II) 1
Using 1 to 5 moles of the halogenating agent per mole, in a solvent,
The reaction is carried out at room temperature or under reflux for 1 to 20 hours. Here, as the halogenating agent, thionyl chloride, thionyl bromide, phosphorus oxychloride, phosphorus trichloride, phosphorus tribromide, phosphorus pentachloride, etc. are used, and as the solvent, methylene chloride, chloroform, carbon tetrachloride, 1,2-dichloroethane, trichloroethane, etc. are used. After the reaction is completed, the reaction product is concentrated,
By purifying the residue by silica gel column chromatography or the like, (III) can be obtained.

化合物（III）から（Ｖ）を製造するには、（III）１
モルに対して（IV）を１〜５モル使用し、ジメチルスル
ホキシド、アセトニトリル等の溶媒中、室温ないし100
℃で、１〜15時間加温して反応させる。反応終了後、反
応物を冷水に注加し、酸で中和した後クロロホルム等の
溶媒で抽出し、次いで溶媒を留去するか、あるいは反応
物を濃縮し、残渣を水洗して粗生成物を得、更にこれを
シリカゲルカラムクロマトグラフィー又は再結晶等で精
製して（Ｖ）を得る。To produce (V) from compound (III), (III) 1
1 to 5 mol of (IV) is used per mol, in a solvent such as dimethylsulfoxide or acetonitrile at room temperature to 100
Allow to react by heating at ℃ for 1 to 15 hours. After completion of the reaction, the reaction product is poured into cold water, neutralized with an acid and then extracted with a solvent such as chloroform, and then the solvent is distilled off, or the reaction product is concentrated and the residue is washed with water to obtain a crude product. And further purify it by silica gel column chromatography or recrystallization to obtain (V).

化合物（Ｖ）から（Ｉ）を製造するには、（Ｖ）１モ
ルに対しアルカリを２〜４モル使用し、エタノール等の
溶媒中５〜60時間加熱反応させ、次いで水を加え１〜20
時間加熱して反応させる。ここでアルカリとしては水酸
化ナトリウム、水酸化カリウムが好ましい。反応終了
後、反応物を冷水に注加し、酸で中和酸、クロロホルム
等の溶媒で抽出し、溶媒を留去後、残渣を適当な溶媒で
再結晶すれば（Ｉ）の純品が得られる。To produce (I) from compound (V), 2 to 4 mol of alkali is used per 1 mol of (V), the mixture is heated and reacted in a solvent such as ethanol for 5 to 60 hours, and then water is added to 1 to 20 mol.
Heat for a reaction to react. Here, sodium hydroxide and potassium hydroxide are preferable as the alkali. After completion of the reaction, the reaction product is poured into cold water, neutralized with an acid, extracted with a solvent such as chloroform, the solvent is distilled off, and the residue is recrystallized with an appropriate solvent to obtain a pure product of (I). can get.

製法2: （式中、Ｐは保護基、Ｌは脱離基を示し、R1及びＸは前
記と同じ） 原料化合物（VI）は公知の化合物であり、例えばジャ
ーナル・オブ・メディシナル・ケミストリー、23,1358
（1980）に記載の方法によって製造される。Process 2: (In the formula, P represents a protecting group, L represents a leaving group, and R 1 and X are the same as above.) The starting compound (VI) is a known compound, for example, Journal of Medicinal Chemistry, 23 , 1358.
It is manufactured by the method described in (1980).

化合物（VI）から（VIII）を製造するには、（VI）１
モルと炭酸アルカリ２〜４モルをジメチルホルムアミド
等の溶媒に溶かし、これに室温ないし還流下、（VII）
を２〜４モル添加し、１〜20時間反応させる。反応終了
後、反応物を濃縮し、酢酸等で酸性とした後、40〜80℃
で１〜５時間加温し、濃縮後、クロロホルム等の溶媒で
抽出し、シリカゲルカラムクロマトグラフィー等で精製
し、更に必要ならば、再結晶を行えば（VIII）が得られ
る。To produce (VIII) from compound (VI), (VI) 1
Mol and 2 to 4 mol of alkali carbonate are dissolved in a solvent such as dimethylformamide, and the mixture is allowed to stand at room temperature or under reflux (VII).
2 to 4 mol is added and the reaction is carried out for 1 to 20 hours. After the reaction is complete, concentrate the reaction product, acidify it with acetic acid, etc., and then cool it at 40-80 ℃.
After heating for 1 to 5 hours, the solution is concentrated, extracted with a solvent such as chloroform, purified by silica gel column chromatography and recrystallized, if necessary, to obtain (VIII).

化合物（VIII）から（IX）を得る反応は、製法１の
（II）から（III）を得る反応と同様にして行われる。The reaction for obtaining (IX) from compound (VIII) is carried out in the same manner as the reaction for obtaining (III) from (II) in production method 1.

化合物（IX）から（Ｘ）を製造するには、（IX）１モ
ルに対して（IV）を１〜５モル使用し、ジメチルスルホ
キシド、アセトニトリル等の溶媒中、室温ないし100℃
で、１〜60時間反応させる。反応終了後、反応物を冷水
に注加し、クロロホルム等の溶媒で抽出し、更にクロロ
ホルム層を酸で逆抽出し、水層をアルカリ性とし、再度
クロロホルム等で抽出し、溶媒を留去後、残渣をシリカ
ゲルカラムクロマトグラフィー等で精製すれば（Ｘ）が
得られる。In order to produce (X) from compound (IX), 1 to 5 mol of (IV) is used per 1 mol of (IX), and the mixture is used in a solvent such as dimethyl sulfoxide or acetonitrile at room temperature to 100 ° C.
And react for 1 to 60 hours. After completion of the reaction, the reaction product was poured into cold water and extracted with a solvent such as chloroform, the chloroform layer was back-extracted with an acid, the aqueous layer was made alkaline, and the solution was extracted again with chloroform and the solvent was distilled off. The residue is purified by silica gel column chromatography or the like to obtain (X).

化合物（Ｘ）から（Ｉ）を製造する反応は、（Ｘ）を
水酸化ナトリウム、水酸化カリウム等のアルカリの存在
下、含水アルコール中、１〜５時間加熱することにより
行われる。反応終了後、反応物を酸で中和し、濃縮後、
アルコール等で抽出し、溶媒を留去し、残渣を再結晶等
で精製すれば（Ｉ）が得られる。The reaction for producing (I) from compound (X) is carried out by heating (X) in a hydrous alcohol for 1 to 5 hours in the presence of an alkali such as sodium hydroxide or potassium hydroxide. After the reaction is completed, the reaction product is neutralized with an acid, and after concentration,
Extraction with alcohol or the like, removal of the solvent by distillation, and purification of the residue by recrystallization or the like give (I).

斯くて得られた本発明化合物（Ｉ）は、更に必要に応
じて、常法により、アルカリ金属、無機酸、有機酸等の
塩とすることができる。例えば、アルカリ金属塩として
は、リチウム塩、ナトリウム塩、カリウム塩等；無機酸
塩としては、塩酸塩、硫酸塩、硝酸塩、臭化水素酸塩、
リン酸塩等；有機酸塩としては、酢酸塩、フマル酸塩、
マレイン酸塩、乳酸塩、酒石酸塩、クエン酸塩、リンゴ
酸塩、シュウ酸塩、メタンスルホン酸塩、ベンゼンスル
ホン酸塩等が挙げられる。The compound (I) of the present invention thus obtained can be converted into a salt of an alkali metal, an inorganic acid, an organic acid or the like by a conventional method, if necessary. For example, as the alkali metal salt, lithium salt, sodium salt, potassium salt, etc .; as the inorganic acid salt, hydrochloride, sulfate, nitrate, hydrobromide,
Phosphate, etc .; as organic acid salts, acetate, fumarate,
Examples thereof include maleate, lactate, tartrate, citrate, malate, oxalate, methanesulfonate, benzenesulfonate and the like.

〔発明の効果〕〔The invention's effect〕

本発明化合物（Ｉ）は優れた抗菌活性及び吸収性を示
す、生体利用率の高い抗菌剤である。The compound (I) of the present invention is an antibacterial agent exhibiting excellent antibacterial activity and absorbability and having high bioavailability.

〔実施例〕〔Example〕

次に参考例及び実施例を挙げて説明する。 Next, reference examples and examples will be described.

参考例１ １−（１−クロロプロプ−２−イル）−6,7,8−トリ
フルオロ−1,4−ジヒドロ−４−オキソキノリン−３−
カルボン酸エチルエステル： 6,7,8−トリフルオロ−1,4−ジヒドロ−１−（１−ヒ
ドロキシプロプ−２−イル）−４−オキソキノリン−３
−カルボン酸エチルエステル0.988g（3.0mmole）をクロ
ロホルム50mlに溶解し、塩化チオニル0.714g（6.0mmol
e）を加え、加熱還流下10時間反応させる。反応混合物
を減圧濃縮し、残留物をシリカゲルカラムクロマトグラ
フィー（クロロホルム：メタノール＝100:1）により精
製し、無色針状晶の１−（１−クロロプロプ−２−イ
ル）−6,7,8−トリフルオロ−1,4−ジヒドロ−４−オキ
ソキノリン−３−カルボン酸エチルエステル1.001gを得
る。融点190〜191℃。Reference Example 1 1- (1-chloroprop-2-yl) -6,7,8-trifluoro-1,4-dihydro-4-oxoquinoline-3-
Carboxylic acid ethyl ester: 6,7,8-trifluoro-1,4-dihydro-1- (1-hydroxyprop-2-yl) -4-oxoquinoline-3
-Carboxylic acid ethyl ester 0.988g (3.0mmole) is dissolved in chloroform 50ml, thionyl chloride 0.714g (6.0mmol)
e) is added, and the mixture is reacted under heating under reflux for 10 hours. The reaction mixture was concentrated under reduced pressure and the residue was purified by silica gel column chromatography (chloroform: methanol = 100: 1) to give colorless needle crystals of 1- (1-chloroprop-2-yl) -6,7,8-. 1.001 g of trifluoro-1,4-dihydro-4-oxoquinoline-3-carboxylic acid ethyl ester is obtained. Melting point 190-191 ° C.

IR（KBr）:1730,1618cm-1 1 H−NMR（CDCl3）ppm: 1.40（3H,t,J＝7.2Hz）,1.77（3H,d,d,J＝6.5,1.8Hz）,
3.89（2H,d,d,J＝5.5,1.8Hz）,4.31（2H,q,J＝7.2Hz）,
5.2−5.7（1H,m）,7.9−8.3（1H,m）,8.58（1H,s） 参考例２ ７−（３−アミノ−１−ピロリジニル）−１−（１−ク
ロロプロプ−２−イル）−6,8−ジフルオロ−1,4−ジヒ
ドロ−４−オキソキノリン−３−カルボン酸エチルエス
テル： １−（１−クロロプロプ−２−イル）−6,7,8−トリ
フルオロ−1,4−ジヒドロ−４−オキソキノリン−３−
カルボン酸エチルエステル174mg（0.5mmole）をアセト
ニトリル20mlに溶解し、３−アミノピロリジン215mg
（2.5mmole）を加え、加熱還流下７時間反応させる。反
応混合物を減圧濃縮し、残留物をシリカゲルカラムクロ
マトグラフィー（クロロホルム：メタノール＝100:1〜2
0:1）により精製し、淡黄色結晶の７−（３−アミノ−
１−ピロリジニル）−１−（１−クロロプロプ−２−イ
ル）−6,8−ジフルオロ−1,4−ジヒドロ−４−オキソキ
ノリン−３−カルボン酸エチルエステル172mgを得る。IR (KBr): 1730,1618 cm -1 1 H-NMR (CDCl 3 ) ppm: 1.40 (3H, t, J = 7.2Hz), 1.77 (3H, d, d, J = 6.5,1.8Hz),
3.89 (2H, d, d, J = 5.5,1.8Hz), 4.31 (2H, q, J = 7.2Hz),
5.2-5.7 (1H, m), 7.9-8.3 (1H, m), 8.58 (1H, s) Reference Example 2 7- (3-Amino-1-pyrrolidinyl) -1- (1-chloroprop-2-yl) -6,8-Difluoro-1,4-dihydro-4-oxoquinoline-3-carboxylic acid ethyl ester: 1- (1-chloroprop-2-yl) -6,7,8-trifluoro-1,4- Dihydro-4-oxoquinoline-3-
Carboxylic acid ethyl ester 174mg (0.5mmole) is dissolved in acetonitrile 20ml, 3-aminopyrrolidine 215mg
(2.5 mmole) is added, and the mixture is reacted under heating under reflux for 7 hours. The reaction mixture was concentrated under reduced pressure, and the residue was subjected to silica gel column chromatography (chloroform: methanol = 100: 1 to 2).
0: 1) to give 7- (3-amino-
172 mg of 1-pyrrolidinyl) -1- (1-chloroprop-2-yl) -6,8-difluoro-1,4-dihydro-4-oxoquinoline-3-carboxylic acid ethyl ester are obtained.

融点:106〜108℃ IRcm-1（KBr）:3420、3340、1720、16801 H−NMR ppm（CDCl3）： 1.41（3H,t,J＝7.2Hz）,1.70（2H,s）,1.73（2H,d,d,J
＝6.6,1.5Hz）,1.8〜2.3（2H,m）,3.2〜4.1（7H,m）,4.
39（2H,q,J＝7.1Hz）,5.0〜5.5（1H,m）,7.89（1H,d,d,
J＝14.1,2.OHz）,8.47（1H,s） 参考例３ ７−（３−アミノ−１−ピロリジニル）−6,8−ジフル
オロ−1,4−ジヒドロ−４−オキソ−１−（プロプ−１
−エン−２−イル）−キノリン−３−カルボン酸： 参考例２で得られた７−（３−アミノ−１−ピロリジ
ニル）−１−（１−クロロプロプ−２−イル）−6,8−
ジフルオロ−1,4−ジヒドロ−４−オキソキノリン−３
−カルボン酸エチルエステル（化合物１）159mg（0.38m
mole）をエタノール20mlに溶解し、粉砕した水酸化カリ
ウム65mg（1.15mmole）を加え、加熱還流下14時間反応
させ、更に水3mlを添加し、３時間加熱還流する。冷後
反応物を減圧濃縮し、残渣を水洗後、乾燥し、粗生成物
を得、更にシリカゲルカラムクロマトグラフィー（クロ
ロホルム：メタノール＝5:1）で精製し、淡黄色結晶の
７−（３−アミノ−１−ピロリジニル）−6,8−ジフル
オロ−1,4−ジヒドロ−４−オキソ−１−（プロプ−１
−エン−２−イル）−キノリン−３−カルボン酸52mgを
得る。Melting point: 106-108 ° C IRcm -1 (KBr): 3420, 3340, 1720, 1680 1 H-NMR ppm (CDCl 3 ): 1.41 (3H, t, J = 7.2Hz), 1.70 (2H, s), 1.73 (2H, d, d, J
= 6.6,1.5Hz), 1.8 to 2.3 (2H, m), 3.2 to 4.1 (7H, m), 4.
39 (2H, q, J = 7.1Hz), 5.0 to 5.5 (1H, m), 7.89 (1H, d, d,
J = 14.1,2.OHz), 8.47 (1H, s) Reference Example 3 7- (3-amino-1-pyrrolidinyl) -6,8-difluoro-1,4-dihydro-4-oxo-1- (prop -1
-En-2-yl) -quinolin-3-carboxylic acid: 7- (3-amino-1-pyrrolidinyl) -1- (1-chloroprop-2-yl) -6,8- obtained in Reference Example 2.
Difluoro-1,4-dihydro-4-oxoquinoline-3
-Carboxylic acid ethyl ester (Compound 1) 159 mg (0.38 m
65 mg (1.15mmole) of crushed potassium hydroxide is added, reacted for 14 hours under heating under reflux, 3 ml of water is added, and the mixture is heated under reflux for 3 hours. After cooling, the reaction product was concentrated under reduced pressure, the residue was washed with water and dried to obtain a crude product, which was further purified by silica gel column chromatography (chloroform: methanol = 5: 1) to give 7- (3- Amino-1-pyrrolidinyl) -6,8-difluoro-1,4-dihydro-4-oxo-1- (prop-1
52 mg of -en-2-yl) -quinoline-3-carboxylic acid are obtained.

融点:174〜178℃（分解） IRcm-1（KBr）:3400、1720、16101 H−NMR ppm（CDCl3）： 1.5〜2.2（2H,m）,2.20（3H,s）,3.0〜4.0（7H,m）,5.4
0（2H,br）,7.60（1H,br.d）,8.41（1H,s） 実施例１ 参考例３と同様にして、本願発明のキノロンカルボン
酸誘導体（Ｉ）を得た。このデータを以下に示す。Melting point: 174 to 178 ° C (decomposition) IRcm -1 (KBr): 3400, 1720, 1610 1 H-NMR ppm (CDCl 3 ): 1.5 to 2.2 (2H, m), 2.20 (3H, s), 3.0 to 4.0 (7H, m), 5.4
0 (2H, br), 7.60 (1H, br.d), 8.41 (1H, s) Example 1 In the same manner as in Reference Example 3, a quinolonecarboxylic acid derivative (I) of the present invention was obtained. This data is shown below.

性状：淡褐色粉末状結晶 融点:221〜225℃（分解） IRcm-1（KBr）:3420、1690、16321 H−NMR ppm（DMSO−d6）： 1.6〜2.4（2H,m）,2.24（3H,s）,3.0〜4.1（5H,m）,5.5
4（1H,s）,5.74（1H,s）,6.47（1H,d,J＝5Hz）,7.85（1
H,d,J＝14.1Hz）,8.57（3H,s,D2Oで2H分消失）Property: Light brown powder crystal Melting point: 221-225 ° C (decomposition) IRcm -1 (KBr): 3420, 1690, 1632 1 H-NMR ppm (DMSO-d 6 ): 1.6-2.4 (2H, m), 2.24 (3H, s), 3.0 ~ 4.1 (5H, m), 5.5
4 (1H, s), 5.74 (1H, s), 6.47 (1H, d, J = 5Hz), 7.85 (1
H, d, J = 14.1Hz), 8.57 (2H loss at 3H, s, D 2 O)

───────────────────────────────────────────────────── フロントページの続き (72)発明者 香取 達彦 茨城県北相馬郡利根町布川3081―11 (56)参考文献 特開 昭56−30964（ＪＰ，Ａ) 特開 昭62−30776（ＪＰ，Ａ) 特開 昭62−207258（ＪＰ，Ａ) ─────────────────────────────────────────────────── ─── Continuation of the front page (72) Inventor Tatsuhiko Katori 3081-11 Nunokawa, Tone-cho, Kitasoma-gun, Ibaraki (56) References JP-A-56-30964 (JP, A) JP-A-62-30776 (JP, A) JP-A-62-207258 (JP, A)

Claims (1)

(57)【特許請求の範囲】(57) [Claims] 【請求項１】次の式（Ｉ） で表わされるキノロンカルボン酸誘導体又はその塩。1. The following formula (I): A quinolonecarboxylic acid derivative represented by or a salt thereof.
JP1189214A 1988-08-08 1989-07-21 Quinolonecarboxylic acid derivative Expired - Fee Related JP2526128B2 (en)

Priority Applications (5)

Application Number Priority Date Filing Date Title
US07/807,856 US5324735A (en) 1989-07-21 1990-03-29 Quinoline carboxylic acid derivatives
CA002058424A CA2058424A1 (en) 1989-07-21 1990-03-29 Quinoline carboxylic acid derivatives
EP19900905660 EP0486687A4 (en) 1989-07-21 1990-03-29 Quinolonecarboxylic acid derivatives
KR1019910701725A KR920701163A (en) 1988-08-08 1990-03-29 Quinolone Carboxylic Acid Derivatives
PCT/JP1990/000425 WO1991001308A1 (en) 1989-07-21 1990-03-29 Quinolonecarboxylic acid derivatives

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JP63-197735 1988-08-08
JP19773588 1988-08-08

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JPS5630964A (en) * 1979-08-22 1981-03-28 Kyorin Pharmaceut Co Ltd Novel substituted quinolinecarboxylic acid and its preparation
JPH0674260B2 (en) * 1985-08-01 1994-09-21 大日本製薬株式会社 Quinoline derivatives, their esters and their salts
JPH0811749B2 (en) * 1986-03-06 1996-02-07 富山化学工業株式会社 Novel quinoline derivative and its salt

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