WO2001034595A1 - Sels de metaux alcalins de derives de l'acide quinolinecarboxylique et procede de purification de ces derives au moyen de ces sels - Google Patents

Sels de metaux alcalins de derives de l'acide quinolinecarboxylique et procede de purification de ces derives au moyen de ces sels Download PDF

Info

Publication number
WO2001034595A1
WO2001034595A1 PCT/JP2000/007906 JP0007906W WO0134595A1 WO 2001034595 A1 WO2001034595 A1 WO 2001034595A1 JP 0007906 W JP0007906 W JP 0007906W WO 0134595 A1 WO0134595 A1 WO 0134595A1
Authority
WO
WIPO (PCT)
Prior art keywords
carboxylic acid
alkali metal
quinoline carboxylic
acid derivative
metal salt
Prior art date
Application number
PCT/JP2000/007906
Other languages
English (en)
Japanese (ja)
Inventor
Akira Yazaki
Shizuka Aoki
Original Assignee
Wakunaga Pharmaceutical 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 Wakunaga Pharmaceutical Co., Ltd. filed Critical Wakunaga Pharmaceutical Co., Ltd.
Priority to AU13047/01A priority Critical patent/AU1304701A/en
Publication of WO2001034595A1 publication Critical patent/WO2001034595A1/fr

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents

Definitions

  • the present invention relates to a novel quinoline carboxylic acid derivative metal salt suitable for purification of a quinoline carboxylic acid derivative and a method for purifying a quinoline carboxylic acid derivative using the same.
  • a quinoline carboxylic acid derivative having a nitrogen-containing heteroaromatic group substituted at the 1-position with an amino group has strong antibacterial activity and low toxicity. It has been found that it retains excellent properties and has extremely high photostability (WOZ97Z11068), and further has a 3-hydroxyazetidine-1-yl group at the 7-position.
  • the compound has a very strong antibacterial activity against Gram-positive bacteria and is characterized by a marked enhancement of this activity, especially under acidic conditions.
  • quinoline carboxylic acid compounds generally have low solubility in various solvents, which limits the solvent used to recrystallize the compound, and also restricts solvents due to restrictions on residual solvents that are acceptable for pharmaceuticals.
  • problems such as the final step of compound purification becoming complicated and insufficient purification are left. Disclosure of the invention
  • An object of the present invention is to provide a simple and efficient purification method for obtaining a high-purity quinoline carboxylic acid derivative.
  • the present inventors examined various purification methods other than recrystallization of the quinoline carboxylic acid derivative, and found that the quinoline carboxylic acid salt was almost always an acid addition salt, and was isolated as an alkali metal salt. Although no examples have been found, it is possible to convert the quinoline carboxylic acid derivative represented by the following formula (I) to an alkali metal salt very easily by reacting it with various alkali metal compounds. A high-purity purified quinoline carboxylic acid derivative can be obtained by subjecting the alkali metal salt to acid treatment and desalting, and further, it is not necessary to use a special solvent in the purification means via the alkali metal salt. This led to the completion of the present invention. That is, the present invention provides the following formula ( ⁇ )
  • the present invention provides an alkali metal salt of a quinoline carboxylic acid derivative represented by the following formula:
  • the present invention also provides an antibacterial agent containing an alkali metal salt of compound (II) as an active ingredient.
  • the present invention also provides an antibacterial agent composition
  • an antibacterial agent composition comprising the metal salt of Compound II and a pharmaceutically acceptable carrier.
  • the present invention also provides the use of an alkaline metal salt of Compound II as an antibacterial agent.
  • the present invention also provides a method for treating infectious diseases, comprising administering a metal salt of Compound III.
  • R represents a halogen atom or a methyl group
  • the purification method of the present invention uses an alkali metal salt of quinoline carboxylic acid as an intermediate thereof.
  • the quinoline carboxylic acid derivative represented by the formula (I) is very easily converted to an alkali metal salt by reacting with various alkali metal compounds in various solvents that hardly dissolve the compound. Surprisingly, it could not be predicted at all that the treatment of the alkali metal salt with various acids produced purified quinoline carboxylic acid of high purity.
  • the alkali metal salt of the quinoline carboxylic acid derivative represented by the formula (II) of the present invention can exist not only in an unsolvated form but also as a hydrate or a solvate. Accordingly, the compounds of the present invention include all crystal forms and hydrates or solvates thereof.
  • the alkali metal salt is useful as an intermediate in the purification operation, but the alkali metal salt itself exhibits an excellent antibacterial action as shown in the test examples described later, Needless to say, it is useful as an agent.
  • the alkali metal salt of the quinoline carboxylic acid derivative represented by the formula ( ⁇ ) according to the present invention is obtained by, for example, adding a quinoline carboxylic acid represented by the formula (I) to various solvents together with a base containing various alkali metals. It can be obtained by separating the precipitate deposited by stirring at an appropriate temperature for an appropriate time.
  • the solvent used here is not limited to a special solvent as described above, and may be any solvent that does not react with a base containing an alkali metal.
  • a base containing an alkali metal for example, water; methanol, ethanol, propanol, etc. Alcohols; ethers such as getyl ether, tetrahydrofuran, dioxane, monoglyme, diglyme and the like; aprotic polar solvents such as dimethylformamide, dimethylsulfoxide and the like; and mixed solvents thereof.
  • solvents ordinary quinoline carboxylic acid is hardly dissolved in water, alcohols (methanol, ethanol, propanol, etc.) and ethers (getyl ether, tetrahydrofuran, etc.), and the solvent for recrystallization is used.
  • a solvent particularly water, ethanol, or the like can be used as a suitable solvent.
  • alkali metal compound examples include hydroxides such as lithium hydroxide, sodium hydroxide and potassium hydroxide, carbonates such as sodium carbonate and potassium carbonate, lithium methoxide, lithium ethoxide, sodium methoxide, sodium methoxide, and the like.
  • Alkoxides such as sodium propoxide, potassium methoxide, and potassium tert-butoxide, and the like, particularly lithium hydroxide, sodium hydroxide, potassium hydroxide, sodium methoxide, and sodium methoxide are preferred. Better.
  • the amount of the base containing an alkali metal is preferably at least equimolar to the quinoline carboxylic acid represented by the formula (I), particularly preferably about 1 to 10 moles.
  • This reaction is carried out usually at 0 to 150 ° C, preferably at 0 to 100 ° C, and the reaction time is usually 10 minutes to 48 hours.
  • a usual solid-liquid separation method for example, a method such as filtration or centrifugal separation may be used, and if necessary, treatment such as washing and dehydration, recrystallization operation, etc. Purification can be performed by commonly used purification means.
  • Examples of the solvent used here include the same solvents as those used in the above steps, for example, water; alcohols such as methanol, ethanol, propanol, etc .; ethyl ether, tetrahydrofuran, dioxane, monoglyme, Ethers such as diglyme; aprotic polar solvents such as dimethylformamide, dimethylsulfoxide and the like and mixed solvents thereof can be used, and water and alcohols (methanol, ethanol, propanol, etc.) which hardly dissolve alkali metal compounds ) Can also be used as a suitable solvent.
  • Examples of the acid used here include mineral acids such as hydrochloric acid, hydrobromic acid and sulfuric acid; organic carboxylic acids such as formic acid, acetic acid, propionic acid, citric acid, trichloroacetic acid, trifluoroacetic acid, fumaric acid and maleic acid; Examples thereof include sulfonic acids such as methanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, mesitylenesulfonic acid, and naphthalenesulfonic acid, and particularly preferred are hydrochloric acid, formic acid, and acetic acid.
  • mineral acids such as hydrochloric acid, hydrobromic acid and sulfuric acid
  • organic carboxylic acids such as formic acid, acetic acid, propionic acid, citric acid, trichloroacetic acid, trifluoroacetic acid, fumaric acid and maleic acid
  • sulfonic acids such as methanesulfonic acid
  • the amount of the acid to be used is preferably at least equimolar, particularly preferably about 1 to 10 moles per mole of the alkali metal salt of the quinoline carboxylic acid represented by the formula (II).
  • This reaction is usually carried out at 0 to 120 ° (preferably 0 to 80 ° C), and the reaction time is usually 10 minutes to 10 hours.
  • the resulting free quinoline carboxylic acid (I) can be separated and obtained by a conventional solid-liquid separation method, for example, a method such as filtration or centrifugation. If necessary, washing and dehydration are performed. be able to.
  • a conventional solid-liquid separation method for example, a method such as filtration or centrifugation. If necessary, washing and dehydration are performed. be able to.
  • the isolated quinoline carboxylic acid is sufficiently pure as it is, it can be used as a usual purification means such as recrystallization if necessary. It can be further purified.
  • the thus obtained purified quinoline carboxylic acid derivative represented by the formula (I) has a high purity of 98% or more by HPLC without recrystallization, as shown in Examples described later.
  • the quinoline carboxylic acid represented by the formula (I) is a known compound, and can be produced by an arbitrary method in addition to the method already reported (WOZ97 / 11068). It is as follows.
  • R 1 R 2 represents a lower alkyl group
  • R 3 represents a hydrogen atom or an amino-protecting group removable by acid treatment or hydrogenation (eg, tert-butyl group, 1,1,3,3-tetratol) Methylbutyl, benzyl, p-methoxybenzyl, 1-phenyletyl, etc., and R is the same as above.)
  • the compound (A) is reacted with an orthoformate such as ethyl orthoformate or methyl orthoformate to form an acrylate derivative (B), and then reacted with the amino compound (C) to obtain a compound (D).
  • the compound is subjected to a cyclization reaction, and when R 3 is an amino protecting group, the compound is further deprotected to obtain a compound (E), and then reacted with 3-hydroxyazetidine to obtain (F).
  • the reaction of the compound (A) with the orthoformates is usually carried out at 0 to 160 ° C, preferably at 50 to 150 ° C, and the reaction time is usually 10 minutes to 48 hours, preferably 1 to 10 hours.
  • the amount of orthoformate to be used is preferably at least equimolar to compound (A), particularly preferably about 1 to 10 moles.
  • a carboxylic anhydride such as anhydrous acetic acid
  • the amount of the reaction aid is preferably at least equimolar to compound (A), particularly preferably about 1 to 10 moles.
  • the reaction between compound (B) and amino compound (C) is carried out without a solvent or in a suitable solvent. Any solvent may be used as long as it does not affect the reaction.
  • Examples thereof include aromatic hydrocarbons such as benzene, toluene, and xylene; getyl ether, tetrahydrofuran, dioxane, monoglyme, and the like.
  • Ethers such as jiglime; aliphatic hydrocarbons such as pentane, hexane, heptane, rigoin; halogenated hydrocarbons such as methylene chloride, chloroform, carbon tetrachloride, etc .; dimethyl Aprotic polar solvents such as formamide and dimethyl sulfoxide; alcohols such as methanol, ethanol and propanol;
  • This reaction is carried out usually at 0 to 150 ° C, preferably 0 to 100 ° C, and the reaction time is usually 10 minutes to 48 hours.
  • Amino compounds The amount of (C) used is preferably close to equimolar to the compound (A).
  • compound (A) is reacted with acetal compounds such as N, N-dimethylformamide dimethyl acetal and N, N-dimethylformamide decyl acetal, and then with an amino compound (C). It can also lead to compound (D).
  • acetal compounds such as N, N-dimethylformamide dimethyl acetal and N, N-dimethylformamide decyl acetal
  • an amino compound (C) It can also lead to compound (D).
  • any solvent may be used as long as it does not affect the reaction, and examples thereof include those described above. This reaction is carried out usually at 0 to 150 ° C, preferably at room temperature to 100 ° C, and the reaction time is 10 minutes to 48 hours, preferably 1 to 10 hours.
  • reaction of subjecting compound (D) to a cyclization reaction to give compound (E) is carried out in a suitable solvent in the presence or absence of a basic compound.
  • a suitable solvent any solvent can be used as long as it does not affect the reaction.
  • Examples thereof include aromatic hydrocarbons such as benzene, toluene, xylene, etc .; Ethers such as lahydrofuran, dioxane, monoglyme, diglyme, etc .; halogenated hydrocarbons such as methylene chloride, chloroform, carbon tetrachloride, etc .; aprotic polar solvents such as dimethylformamide, dimethylsulfoxide, etc .; methanol And alcohols such as ethanol, propanol and the like.
  • Examples of the basic compound used include alkali metals such as sodium metal and potassium metal; metal hydrides such as sodium hydride and calcium hydride; lithium hydroxide, sodium hydroxide, and potassium hydroxide.
  • Inorganic salts such as sodium carbonate, sodium carbonate and potassium carbonate; alkoxides such as sodium methoxide, sodium ethoxide, potassium tert-butoxide and the like; metal fluorides such as sodium fluoride and potassium fluoride; Organic bases such as triethylamine, 1,8-diazabicyclo [5.4.0] indene (DBU) and the like.
  • a reaction auxiliary such as lithium chloride can be added as a reaction auxiliary.
  • the amount of the reaction aid is at least equimolar to the compound (A), and In particular, about 1 to 10 moles is preferable.
  • the temperature of this reaction is usually 0 to 200 ° C, preferably room temperature to 180 ° C, and the reaction is usually completed in 5 minutes to 24 hours.
  • the amount of the basic compound to be used is 1 mol or more, preferably 1 mol to 2 mol, per 1 mol of compound (D).
  • R 3 When R 3 is an amino-protecting group, it is deprotected by a conventional method.
  • R 3 when R 3 is a protecting group that can be removed with an acid, tetrahydrofuran, dioxane, and the like in the presence of an acid such as trifluoroacetic acid, methanesulfonic acid, or hydrochloric acid And the like, ketones such as acetone, methyl ethyl ketone and the like, a solvent such as acetic acid and the like, or in the presence or absence of a mixed solvent thereof.
  • This reaction is carried out usually at room temperature to 150 ° C, preferably at room temperature to 80 ° C, and the reaction time is usually 1 to 24 hours.
  • R 3 is a protecting group that can be removed by hydrogenation, an alcohol such as methanol or ethanol, an ether such as tetrahydrofuran or dioxane, acetone, or methyl ester in a hydrogen atmosphere in the presence of a palladium catalyst or a platinum catalyst.
  • the reaction is performed in the presence or absence of a solvent such as ketones such as tyl ketone, acetic acid, or a mixed solvent thereof.
  • This reaction is carried out usually at room temperature to 150 ° C., preferably at room temperature to 80 ° C.
  • the hydrogen pressure is from normal pressure to 10 atm
  • the reaction time is usually from 1 to 24 hours.
  • the compound (F) is obtained by reacting the compound (E) with 3-hydroxyazetidine.
  • alcohols such as methanol, ethanol, etc .; ethers, such as tetrahydrofuran, dioxane, monoglyme, etc .; halogenated hydrocarbons, such as methylene chloride, chloroform, carbon tetrachloride, etc .; dimethylformamide Aprotic polar solvents such as dimethylsulfoxide, N-methylpyrrolidone, etc .; solvents such as acetonitrile, pyridine, etc., which do not affect the reaction; if necessary, a deoxidizing agent, for example, sodium carbonate, calcium carbonate, triethylamine , N-methylpyrrolidine, 1,8-diazabicyclo [5.4.0] indene (DBU), potassium carbonate, etc., at room temperature to 160 ° C. reaction The time is several minutes to 48 hours, preferably 10 minutes to 24 hours.
  • the amount of 3-hydroxyazetidine to be used is 1 mol or more, preferably 1 mol to
  • Compound (I) can be obtained by hydrolyzing compound (F) and removing the carboxy protecting group of R 1 .
  • a generally known reaction is used, and examples thereof include hydrolysis, and basic compounds such as lithium hydroxide, sodium hydroxide, potassium hydroxide, sodium carbonate, and lithium carbonate; hydrochloric acid, sulfuric acid, Mineral acids such as hydrobromic acid; or! 1) In the presence of an organic acid such as toluenesulfonic acid, water, alcohols such as methanol, ethanol, propanol, etc., ethers such as tetrahydrofuran, dioxane, etc., ketones such as acetone, methylethylketone, etc. And acetic acid or a mixed solvent thereof.
  • This reaction is carried out usually at room temperature to 180 ° C, preferably at room temperature to 140 ° C, and the reaction time is usually 1 to 24 hours.
  • Ethyl 1 _ (6-amino-1,3,5-difluoropyridine-12-yl) 1,6,7-difluoro-8 _methyl-4-oxo-1 1,4-dihydroquinoline-3 -force
  • Rupoxylate 910 mg, 3 —Hydroxyazetidine (240 mg), N-methylpyrrolidine (410 mg), and lithium chloride (23 Omg) were added to 161 Omg of dimethyl sulfoxide, and the mixture was stirred at 60 ° C. for 22 hours.
  • the reaction solution was added to 6 mL of a 10% aqueous solution of citric acid with stirring. The precipitate was collected by filtration and washed with water.
  • the obtained solid was added to a mixture of 3 mL of water and 3 mL of ethanol together with 20 Omg of sodium hydroxide, and the mixture was stirred at 60 ° C for 2 hours under a nitrogen atmosphere. After returning to room temperature, concentrated hydrochloric acid was added to adjust the pH to 1. After stirring at room temperature for one day, the precipitate was collected by filtration and washed with water.
  • the obtained solid was dispersed in 1.5 mL of ethanol and stirred at room temperature for 19 hours. The precipitate was collected by filtration and washed with ethanol. The title compound (65 Omg) was obtained as a yellow powder.
  • the purity of the compound was determined by high-performance liquid chromatography using a reversed-phase column under the following conditions and the area ratio of the target substance to the sum of all detected peak areas (hereinafter referred to as Examples). The same applies to 13 to 17).
  • UV detection 254 nm or 290 nm
  • CPFX is 1-cyclopropyl-6-fluoro-7 _ (1-pirazinyl) — 1,4-dihydro-14-oxoquinoline-3 —capillonic acid
  • LVF X is S (-) One 9-Fluoro-2,3-dihydro-1-methyl_10— (4-Methyl_1-piperazinyl) —7-oxo-1H-pyrido [1,2,3-de] [1,4] Benzoxazine-1 6 —Indicates liponic acid.
  • the quinoline carboxylic acid derivative represented by the formula (I) hardly dissolves, and the compound can be prepared in a short time even from a solvent that could not be used as a recrystallization solvent. It can be purified with sufficiently high purity and high recovery. Therefore, the purification method of the present invention is industrially useful as a simple and efficient method for purifying the quinolinecarbonic acid derivative represented by the formula (I).
  • the alkali metal salt of the quinoline carboxylic acid derivative represented by the formula ( ⁇ ) is useful as an intermediate for purifying the quinoline carboxylic acid derivative represented by the formula (I) and an antibacterial agent.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Communicable Diseases (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Oncology (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

L'invention porte sur un procédé de purification de dérivés de l'acide quinolinecarboxylique de la formule générale (I) (dans laquelle R est halogéno ou méthyle). Ce procédé consiste à faire réagir un dérivé d'acide quinolinecarboxylique de la formule générale (I) avec un composé de métal alcalin afin de former un sel métallique alcalin à partir du dérivé, isoler le sel et traiter le sel obtenu avec un acide. L'invention porte également sur les sels de métaux alcalins des dérivés (I) de l'acide quinolinecarboxylique et sur des agents antimicrobiens contenant les sels et constituant l'ingrédient actif. Ce procédé permet de purifier des dérivés (I) de l'acide quinolinecarboxylique sur une courte durée et à un niveau de pureté et de récupération suffisamment élevé, celui-ci étant utilisé dans l'industrie comme procédé de purification de dérivés (I) simple et efficace. De plus, les sels métalliques alcalins des dérivés (I) sont utiles comme intermédiaires pour la purification et comme agents antimicrobiens.
PCT/JP2000/007906 1999-11-11 2000-11-10 Sels de metaux alcalins de derives de l'acide quinolinecarboxylique et procede de purification de ces derives au moyen de ces sels WO2001034595A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU13047/01A AU1304701A (en) 1999-11-11 2000-11-10 Alkali metal salts of quinolinecarboxylic acid derivatives and process for purifying quinoline-carboxylic acid derivatives by using the salts

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP11/321107 1999-11-11
JP32110799A JP2005097116A (ja) 1999-11-11 1999-11-11 キノリンカルボン酸誘導体アルカリ金属塩及びこれを用いたキノリンカルボン酸誘導体の精製法

Publications (1)

Publication Number Publication Date
WO2001034595A1 true WO2001034595A1 (fr) 2001-05-17

Family

ID=18128909

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP2000/007906 WO2001034595A1 (fr) 1999-11-11 2000-11-10 Sels de metaux alcalins de derives de l'acide quinolinecarboxylique et procede de purification de ces derives au moyen de ces sels

Country Status (3)

Country Link
JP (1) JP2005097116A (fr)
AU (1) AU1304701A (fr)
WO (1) WO2001034595A1 (fr)

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2008515910A (ja) * 2004-10-08 2008-05-15 アボット・ラボラトリーズ 薬物の塩およびその結晶形
WO2010036329A2 (fr) 2008-09-24 2010-04-01 Rib-X Pharmaceuticals, Inc. Procédé de préparation de composés de quinolone
WO2010056872A2 (fr) 2008-11-15 2010-05-20 Rib-X Pharmaceuticals, Inc. Compositions antimicrobiennes
CN103936717A (zh) * 2013-01-22 2014-07-23 上海医药工业研究院 一种delafloxacin中间体及其制备方法
CN103936718A (zh) * 2013-01-22 2014-07-23 上海医药工业研究院 一种高纯度delafloxacin的制备方法
CN106831723A (zh) * 2017-02-15 2017-06-13 鲁南制药集团股份有限公司 一种改进的德拉沙星的精制方法
EP3581180A1 (fr) 2014-06-20 2019-12-18 Melinta Subsidiary Corp. Compositions antimicrobiennes ayant des agents effervescents

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104876911A (zh) * 2014-02-27 2015-09-02 南京工业大学 一种简易的方法合成德拉沙星

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0324298A1 (fr) * 1987-12-29 1989-07-19 Laboratorios Del Dr. Esteve, S.A. Dérivés des acides 7-(1-azétidinyl)-1,4-dihydro-4-oxoquinoléine-3-carboxyliques, leur préparation et leur application en tant que médicaments
WO1997011068A1 (fr) * 1995-09-22 1997-03-27 Wakunaga Pharmaceutical Co., Ltd. Nouveaux derives de l'acide pyridone-carboxylique ou leurs sels et agent antibacterien les contenant comme ingredient actif

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0324298A1 (fr) * 1987-12-29 1989-07-19 Laboratorios Del Dr. Esteve, S.A. Dérivés des acides 7-(1-azétidinyl)-1,4-dihydro-4-oxoquinoléine-3-carboxyliques, leur préparation et leur application en tant que médicaments
WO1997011068A1 (fr) * 1995-09-22 1997-03-27 Wakunaga Pharmaceutical Co., Ltd. Nouveaux derives de l'acide pyridone-carboxylique ou leurs sels et agent antibacterien les contenant comme ingredient actif

Cited By (18)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8969569B2 (en) 2004-10-08 2015-03-03 Abbvie Inc. Salt and crystalline forms thereof of a drug
US10329276B2 (en) 2004-10-08 2019-06-25 Abbvie Inc. Salt and crystalline forms thereof of a drug
US9539250B2 (en) 2004-10-08 2017-01-10 Abbvie Inc. Salt and crystalline forms thereof of a drug
JP2008515910A (ja) * 2004-10-08 2008-05-15 アボット・ラボラトリーズ 薬物の塩およびその結晶形
US8273892B2 (en) 2004-10-08 2012-09-25 Abbott Laboratories Salt and crystalline forms thereof of a drug
US8648093B2 (en) 2004-10-08 2014-02-11 Abbvie Inc. Salt and crystalline forms thereof of a drug
US9873681B2 (en) 2004-10-08 2018-01-23 Abbvie Inc. Salt and crystalline forms thereof of a drug
US8252813B2 (en) 2004-10-08 2012-08-28 Abbott Laboratories Salt and crystalline forms thereof of a drug
EP3214083A1 (fr) 2008-09-24 2017-09-06 Melinta Therapeutics, Inc. Procédé de préparation de composés de quinolone
WO2010036329A2 (fr) 2008-09-24 2010-04-01 Rib-X Pharmaceuticals, Inc. Procédé de préparation de composés de quinolone
EP3766876A1 (fr) 2008-09-24 2021-01-20 Melinta Subsidiary Corp. Formulation pharmaceutique comprenant des composés de quinolone
WO2010056872A2 (fr) 2008-11-15 2010-05-20 Rib-X Pharmaceuticals, Inc. Compositions antimicrobiennes
CN103936718A (zh) * 2013-01-22 2014-07-23 上海医药工业研究院 一种高纯度delafloxacin的制备方法
CN103936717A (zh) * 2013-01-22 2014-07-23 上海医药工业研究院 一种delafloxacin中间体及其制备方法
EP3919057A1 (fr) 2014-06-20 2021-12-08 Melinta Subsidiary Corp. Compositions antimicrobiennes ayant des agents effervescents
EP3581180A1 (fr) 2014-06-20 2019-12-18 Melinta Subsidiary Corp. Compositions antimicrobiennes ayant des agents effervescents
CN106831723B (zh) * 2017-02-15 2020-07-28 鲁南制药集团股份有限公司 一种改进的德拉沙星的精制方法
CN106831723A (zh) * 2017-02-15 2017-06-13 鲁南制药集团股份有限公司 一种改进的德拉沙星的精制方法

Also Published As

Publication number Publication date
AU1304701A (en) 2001-06-06
JP2005097116A (ja) 2005-04-14

Similar Documents

Publication Publication Date Title
US5424311A (en) Azaquinoxalines and their use
KR870001693B1 (ko) 1,4-디하이드로-4-옥소나프티리딘 유도체의 제조방법
KR910009330B1 (ko) 항균작용을 갖는 퀴놀린계 화합물과 그의 제조방법
EP2280954A1 (fr) Dérivés de 6-pyridin-3-yl-3,4-dihydro-1h-quinolin-2-one et composés apparentés en tant qu inhibiteurs de l'aldostérone synthase cyp11b2 humaine
JP3448305B2 (ja) 新規ピリドンカルボン酸誘導体又はその塩及びこれを有効成分とする医薬
JPH05239051A (ja) ７−イソインドリニル−キノロン−および−ナフチリドンカルボン酸誘導体
JP3014001B2 (ja) 興奮性アミノ酸拮抗剤
JPH0566945B2 (fr)
JP2948660B2 (ja) 新規なピリドンカルボン酸誘導体
JPH02279672A (ja) ２―アルキル―４―アリールメチルアミノキノリン
WO2001034595A1 (fr) Sels de metaux alcalins de derives de l'acide quinolinecarboxylique et procede de purification de ces derives au moyen de ces sels
HU187356B (en) Process for producing quinoline-carboxylic acid derivatives
JPH07103123B2 (ja) 新規４‐ピリドン誘導体、その製造方法及びこれを含有する薬学的調製物
US5498615A (en) Quinolone carboxylic acid derivatives and process for preparing the same
JP2003508517A (ja) キノロンカルボン酸誘導体の製造に関する中間体
JP2848538B2 (ja) ２環性アミノ基で置換されたピリドンカルボン酸誘導体、そのエステルおよびその塩ならびにこれらの中間体たる２環性アミン
KR920001135B1 (ko) 퀴놀론카르복실산 유도체
JP2865761B2 (ja) ベンゾ［ｂ］［１，８］ナフチリジン誘導体類およびそれらの調製
JP2704428B2 (ja) キノロンカルボン酸誘導体またはその塩
FI105400B (fi) Uudet 3-karboksyylihappo-fluorikinoliinijohdannaiset, niiden valmistus ja niiden käyttö bentsonaftyridiinijohdannaisten valmistukseen
JPH05345777A (ja) ７−（４，４−ジアルキル−３−アミノ置換ピロリジニル）キノロン−３−カルボン酸誘導体
JP2631854B2 (ja) 新規な１，８−ナフチリジン誘導体
JPS6270370A (ja) キノロンカルボン酸誘導体およびその製造方法
JP2990903B2 (ja) ４−オキソキノリン−３−カルボン酸類の製造方法
WO2001012608A1 (fr) Composes de quinoline et procede de preparation desdits composes

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A1

Designated state(s): AE AG AL AM AT AU AZ BA BB BG BR BY BZ CA CH CN CR CU CZ DE DK DM DZ EE ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX MZ NO NZ PL PT RO RU SD SE SG SI SK SL TJ TM TR TT TZ UA UG US UZ VN YU ZA ZW

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): GH GM KE LS MW MZ SD SL SZ TZ UG ZW AM AZ BY KG KZ MD RU TJ TM AT BE CH CY DE DK ES FI FR GB GR IE IT LU MC NL PT SE TR BF BJ CF CG CI CM GA GN GW ML MR NE SN TD TG

DFPE Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101)
121 Ep: the epo has been informed by wipo that ep was designated in this application
REG Reference to national code

Ref country code: DE

Ref legal event code: 8642

122 Ep: pct application non-entry in european phase
NENP Non-entry into the national phase

Ref country code: JP