WO1994002487A1 - Novel pyridonecarboxylic acid derivatives and processes for preparing the same - Google Patents
Novel pyridonecarboxylic acid derivatives and processes for preparing the same Download PDFInfo
- Publication number
- WO1994002487A1 WO1994002487A1 PCT/KR1993/000064 KR9300064W WO9402487A1 WO 1994002487 A1 WO1994002487 A1 WO 1994002487A1 KR 9300064 W KR9300064 W KR 9300064W WO 9402487 A1 WO9402487 A1 WO 9402487A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- methyl
- dihydro
- pyrido
- diazabicyclo
- oxo
- Prior art date
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D498/06—Peri-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
-
- 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 novel pyridonecarboxylic acid derivatives which have a broad antibacterial spectrum.
- the present invention also relates to processes for preparing these compounds.
- the compounds of the present invention have a broad antibacterial activit y.
- the present invention provides compounds of Formula (I);
- R 1 , R 2 , R 3 and R 4 may be the same or different and represent independently hydrogen or lower alkyl
- X represents oxygen or sulfur
- Y represents hydrogen or methyl
- n denotes an integer of 0 or 1, and stereoisomers thereof, and pharmaceutically acceptable salts thereof.
- Another object of the present invention is to provide stereospecific compounds of Formula (la) and Formula (lb):
- R 1 , R 2 , R 3 , R 4 , X and n are as defined above, or a racemic mixture thereof.
- Another object of the present invention is to provide processes for preparing compounds of Formula (I) above.
- compounds of Formula (I) can be prepared by reacting a compound of Formula (II) with a compound (III) as illustrated in the following reaction diagram:
- R 1 , R 2 , R 3 , R 4 , X, Y and n are as defined above, and Z is a leaving group such as fluoro.
- lower alkyl refers to a straight or branched C 1-3 alkyl, such as methyl, ethyl, n-propyl or isopropyl.
- compounds of Formula (I) can be prepared by the reaction of a compound of Formula (II) above and a compound of Formula (III).
- the process may be carried out in the presence of a solvent.
- Suitable solvents include acetonitrile, dimethylformamide, dimethylsulfoxide, pyridine, water, an alcohol and mixtures thereof.
- the process is preferably carried out in the presence of a base that can bind the side product of the reaction, e.g., a hydrogen fluoride gas.
- a base that can bind the side product of the reaction, e.g., a hydrogen fluoride gas.
- Suitable bases for this purpose include inorganic bases such as potassium carbonate and calcium carbonate and organic bases such as triethylamine, pyridine, 1,8-diazabicyclo[5,4,0]undec-7-ene(DBU), and 1,5-diazabiccclo[4,3,0]non-5- ene(DBN).
- inorganic bases such as potassium carbonate and calcium carbonate
- organic bases such as triethylamine, pyridine, 1,8-diazabicyclo[5,4,0]undec-7-ene(DBU), and 1,5-diazabiccclo[4,3,0]non-5- ene(DBN).
- the reaction may be carried out at a temperature between about 20°C and about 200°C, preferably between about 60°C and about 130°C.
- the reaction time is preferably about 1 hour to about 24 hours.
- Example 2 Preparation of 9-fluoro-3-(5)-methyl- 10-[(2-methyl-2, 8- diazabicyclo[4.3.0]non-5-en)-8-yl]-7-oxo-2,3-dihydro-7H-pyrido[1,2,3- de] [1 ,4]-benzoxazine-6-carboxylic acid
- Example 7 Preparation of 9-fluoro-3-(5)-methyl- 10-[(4-methyl-2, 7- diazabicyclo[3.3.0]oct-4-en)-7-yl]-7-oxo-2,3-dihydro-7H-pyrido[1,2,3- de][1 ,4]-benzoxazine-6-carboxylic acid
- Example 8 Preparation of 9-fluoro-3-(S)-methyl- 10-[(3-methyl-2 ,7- diazabicyclo[3.3.0]oct-4-en)-7-yl]-7-oxo-2,3-dihydro-7H-pyrido[1,2,3- de][1,4]-benzoxazine-6-carboxylic acid
- Example 11 Preparation of 9-fluoro-3-(R,5)-methyl-10-[(2,8-diazabicyclo [4.3.0] non-5-en)-8-yl]-7-oxo-2,3-dihydro-7H-pyrido[1 ,2,3-de][ 1 ,4]- benzoxazine-6-carboxylic acid
- Example 15 Preparation of tartaric acid salt of 9-fluoro-3-(5)-methyl-10-[(2,7- diazabicyclo[3.3.0]oct-4-en)-7-yl]-7-oxo-2,3-dihydro-7H-pyrido[1,2,3- de][1.4]-benzoxazine-6-carboxylic acid 0.25G of 9-fluoro-3-(5)-methyl-10-[2,7-diazabicyclo[3,3,0]oct-4-en)-7-yl]-7-oxo-2,3-dihydro-7H-pyrido[1,2,3-de][1,4]-benzoxazine-6-carboxylic acid obtained in Example 6 was added to 10 ml of chloroform-methanol(10: 1) containing 0.15g of tartaric acid and the resulting mixture was stirred for 10 hours at room temperature.
- the antibacterial activity of the quinolone derivatives of the present invention was evaluated in accordance with the agar culture medium two-fold dilution method(Hoechst 345) by using a Muller-Hinton agar medium. Hoechst standard strains were used as the test strains. The strains having 10 7 CFU/ml were inoculated on the culture medium, and the growth of the strains was observed after incubating them at 37°C for 18 hours, in which ciprofloxacin and ofloxacin were used as a control material. The result of these Test are described in Table 1 and 2.
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Priority Applications (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP93916265A EP0651753A1 (en) | 1992-07-23 | 1993-07-23 | Pyridonecarboxylic acid derivatives and processes for preparing the same |
AU45874/93A AU4587493A (en) | 1992-07-23 | 1993-07-23 | Novel pyridonecarboxylic acid derivatives and processes for preparing the same |
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
KR1992-13213 | 1992-07-23 | ||
KR1019920013213A KR960003616B1 (ko) | 1992-07-23 | 1992-07-23 | 우수한 항균작용을 갖는 신규한 피리돈 카르복실산 유도체 및 그의 제조방법 |
CN93119572A CN1102184A (zh) | 1992-07-23 | 1993-10-25 | 新型吡啶酮羧酸衍生物及其制备方法 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO1994002487A1 true WO1994002487A1 (en) | 1994-02-03 |
Family
ID=36930224
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/KR1993/000064 WO1994002487A1 (en) | 1992-07-23 | 1993-07-23 | Novel pyridonecarboxylic acid derivatives and processes for preparing the same |
Country Status (8)
Country | Link |
---|---|
EP (1) | EP0651753A1 (ko) |
JP (1) | JP2552101B2 (ko) |
KR (1) | KR960003616B1 (ko) |
CN (1) | CN1102184A (ko) |
AU (1) | AU4587493A (ko) |
MX (1) | MX9304444A (ko) |
WO (1) | WO1994002487A1 (ko) |
ZA (1) | ZA935345B (ko) |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE3906365A1 (de) * | 1988-07-15 | 1990-01-18 | Bayer Ag | 7-(1-pyrrolidinyl)-3-chinolon- und -naphthyridoncarbonsaeure-derivate, verfahren sowie substituierte (oxa)diazabicyclooctane und -nonane als zwischenprodukte zu ihrer herstellung, und sie enthaltende antibakterielle mittel und futterzusatzstoffe |
WO1992010492A1 (en) * | 1990-12-05 | 1992-06-25 | Synphar Laboratories, Inc. | 7-substituted-6-fluoro-1,4-dihydro-4-oxo-quinoline-3-carboxylic acid compounds useful as antibacterial agents |
Family Cites Families (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS5440112A (en) * | 1977-09-02 | 1979-03-28 | Kubota Ltd | Open culture method for continuous nursery plant for rice transplanter |
JPS5686748A (en) * | 1979-12-18 | 1981-07-14 | Toppan Printing Co Ltd | Multilayer hollow vessel |
JPS6046243A (ja) * | 1983-08-24 | 1985-03-13 | 三菱油化株式会社 | 熱可塑性フツ素樹脂積層体 |
JPS62275134A (ja) * | 1986-02-18 | 1987-11-30 | Tosoh Corp | 接着方法 |
-
1992
- 1992-07-23 KR KR1019920013213A patent/KR960003616B1/ko not_active IP Right Cessation
-
1993
- 1993-07-22 MX MX9304444A patent/MX9304444A/es unknown
- 1993-07-23 JP JP6504362A patent/JP2552101B2/ja not_active Expired - Fee Related
- 1993-07-23 ZA ZA935345A patent/ZA935345B/xx unknown
- 1993-07-23 WO PCT/KR1993/000064 patent/WO1994002487A1/en not_active Application Discontinuation
- 1993-07-23 EP EP93916265A patent/EP0651753A1/en not_active Ceased
- 1993-07-23 AU AU45874/93A patent/AU4587493A/en not_active Abandoned
- 1993-10-25 CN CN93119572A patent/CN1102184A/zh active Pending
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE3906365A1 (de) * | 1988-07-15 | 1990-01-18 | Bayer Ag | 7-(1-pyrrolidinyl)-3-chinolon- und -naphthyridoncarbonsaeure-derivate, verfahren sowie substituierte (oxa)diazabicyclooctane und -nonane als zwischenprodukte zu ihrer herstellung, und sie enthaltende antibakterielle mittel und futterzusatzstoffe |
WO1992010492A1 (en) * | 1990-12-05 | 1992-06-25 | Synphar Laboratories, Inc. | 7-substituted-6-fluoro-1,4-dihydro-4-oxo-quinoline-3-carboxylic acid compounds useful as antibacterial agents |
Also Published As
Publication number | Publication date |
---|---|
JP2552101B2 (ja) | 1996-11-06 |
CN1102184A (zh) | 1995-05-03 |
KR940002252A (ko) | 1994-02-17 |
AU4587493A (en) | 1994-02-14 |
ZA935345B (en) | 1994-02-14 |
JPH07509240A (ja) | 1995-10-12 |
MX9304444A (es) | 1994-04-29 |
EP0651753A1 (en) | 1995-05-10 |
KR960003616B1 (ko) | 1996-03-20 |
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