CN1102184A - Novel pyridonecarboxylic acid derivatives and processes for preparing the same - Google Patents
Novel pyridonecarboxylic acid derivatives and processes for preparing the same Download PDFInfo
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- CN1102184A CN1102184A CN93119572A CN93119572A CN1102184A CN 1102184 A CN1102184 A CN 1102184A CN 93119572 A CN93119572 A CN 93119572A CN 93119572 A CN93119572 A CN 93119572A CN 1102184 A CN1102184 A CN 1102184A
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Abstract
The present invention relates to a new type pyridone carboxylic acid derivative and its stereoisomer as shown in its structural formula (I) and its acceptable salt for drugs, in which R1, R2, R3 and R4 can be identical or different, and respectively represents hydrogen or lower alkyl; X represents oxygen or sulphur; Y represents hydrogen or methyl; and n is integer of 0 or 1. The compounds of the structural formula (I) have a broad antibiotic spectrum, so that they have a strong antibacterial activity for gram-positive bacterium and gram-negative bacterium. Said invention also relates to a method for prepairng those compounds.
Description
The present invention relates to have the novel pyridone carboxylic acid derivatives of broad-spectrum antimicrobial, the invention still further relates to the preparation method of these compounds.
Known have many pyridonecarboxylic acid type antiseptic-germicides, and wherein Ofloxacine USP 23 (ofloxacin) is compared with other quinolone antibacterial agent, shows remarkable anti-microbial activity and have good characteristic in bioavailability and usefulness.Yet Ofloxacine USP 23 also has shortcoming, although its anti-Gram-negative bacteria is effective, gram-positive microorganism is shown more weak anti-microbial activity.
Therefore, still be necessary to develop the antiseptic-germicide that can overcome above-mentioned Ofloxacine USP 23 inherent defect.
The inventor has made extensive studies, and finds that above-mentioned shortcoming can be overcome by novel pyridone carboxylic acid derivatives of the present invention.The compounds of this invention has broad spectrum antibiotic activity, and wherein, their show to Gram-negative and gram-positive microorganism and to streptococcus aureus that can anti-methicillinum all remarkable anti-microbial activity.
The object of the invention provide formula I compound and its steric isomer, with and pharmaceutically acceptable salt,
Wherein:
R
1, R
2, R
3And R
4Can be identical or different, they represent hydrogen or low alkyl group respectively;
X represents oxygen or sulphur;
Y represents hydrogen or methyl;
N is 0 or 1 integer.
Another purpose of the present invention is: provide formula (I a) and the Stereoselective compound of formula (I b), or its racemic mixture:
Wherein, R
1, R
2, R
3, R
4, X and n as defined above.
Another object of the present invention provides the preparation method of above-mentioned formula I compound.
Below the present invention is described in detail:
According to the present invention, the formula I compound prepares by illustrated being reacted by formula II compound and formula III compound of following reaction icon:
R in following formula
1, R
2, R
3, R
4, X, Y and n all as defined above.
Here used " low alkyl group " term is meant the C of straight or branched
1-3Alkyl is such as methyl, ethyl, n-propyl or sec.-propyl.
As mentioned above, the formula I compound can and prepare by the reaction of above-mentioned formula II compound and formula III compound.
This method is carried out having in the presence of the solvent.Appropriate solvent has: acetonitrile, dimethyl formamide, methyl-sulphoxide, pyridine, water, alcohol with and composition thereof.
This method has been preferably under the alkali existence carries out, and this alkali can react such as hydrogen fluoride gas with byproduct of reaction.
Used for this purpose suitable bases has such as the mineral alkali of salt of wormwood, lime carbonate with such as triethylamine, pyridine, 1,8-diazabicylo [5.4.0] 11 carbon-7-alkene (DBU) and 1, the organic bases of 5-diazabicylo [4.3.0] ninth of the ten Heavenly Stems-5-alkene (DBN).
Reaction can be arrived between about 200 ℃ of temperature at about 20 ℃, is preferably between 60 ℃ to about 130 ℃ and carries out.Preferably about 1 hour to about 24 hours reaction times.
This paper at length is disclosed among the korean patent application 92-13212 as the synthetic of the used formula III compound of starting material, and its denomination of invention is: " novel diazabicylo alkene derivatives and preparation method thereof ", and by the application of inventor's name.
Following examples are in order to describing the present invention in detail, but do not limit the scope of the invention.
Embodiment 1:9-fluoro-3-(S)-and methyl isophthalic acid 0-[(2,8-diazabicylo [4.3.0] ninth of the ten Heavenly Stems-5-alkene)-the 8-yl]-7-oxygen-2, the preparation of 3-dihydro-7H-pyrido [1.2.3-goes] [1.4]-benzoxazines-6-carboxylic acid
With 2 of 0.2 gram, 9 of 8-diazabicylo [4.3.0] ninth of the ten Heavenly Stems-5-alkene dihydrochloride and 0.28 gram, 10-two fluoro-3-(S)-methyl-7-oxygen-2,3-dihydro-7H-pyrido [1.2.3-goes] [1.4]-benzoxazine-6-carboxylic acid is added in 5 milliliters of anhydrous acetonitriles.The DBU that under agitation adds 0.36 milliliter then again heats this reaction mixture 5 hours under refluxing.After the reaction mixture cooling, such precipitated solid is filtered out, and wash successively and drying under reduced pressure, obtain 0.25 gram title compound with cold acetonitrile and water.
Analyze: calculated value (%) C:62.33 H:5.17 N:10.90
Measured value (%) C:62.28 H:51.8 N:11.21
Embodiment 2:9-fluoro-3-(S)-and methyl isophthalic acid 0-[(2-methyl-2,8-diazabicylo [4.3.0] ninth of the ten Heavenly Stems-5-alkene)-the 8-yl]-7-oxygen-2, the preparation of 3-dihydro-7H-pyrido [1.2.3-goes] [1.4]-benzoxazines-6-carboxylic acid
Under agitation 0.32 milliliter DBN is added in the gram of 0.2 in 5 milliliters of anhydrous acetonitriles 2-methyl-2,8-diazabicylo [4.3.0] ninth of the ten Heavenly Stems-5-alkene dihydrochloride and 0.30 gram 9,10-two fluoro-3-(S)-and methyl-7-oxygen-2, in the suspension of 3-dihydro-7H-pyrido [1.2.3-goes] [1.4]-benzoxazine-6-carboxylic acid.Reaction mixture was heated 5 hours under refluxing.After the reaction mixture cooling, such precipitated solid is filtered out, and wash successively with cold acetonitrile, water and methyl alcohol, dry under vacuum, obtain 0.27 title compound that restrains.
Analyze: calculated value (%) C:63.15 H:5.55 N:10.52
Measured value (%) C:63.21 H:5.58 N:10.49
Embodiment 3:9-fluoro-3-(S)-and methyl isophthalic acid 0-[(5-methyl-2,8-diazabicylo [4.3.0] ninth of the ten Heavenly Stems-5-alkene)-the 8-yl]-7-oxygen-2, the preparation of 3-dihydro-7H-pyrido [1.2.3-goes] [1.4]-benzoxazines-6-carboxylic acid
Under agitation 0.32 milliliter DBN is added in the gram of 0.2 in 5 milliliters of anhydrous acetonitriles 5-methyl-2,8-diazabicylo [4.3.0] ninth of the ten Heavenly Stems-5-alkene dihydrochloride and 0.29 gram 9,10-two fluoro-3-(S)-and methyl-7-oxygen-2, in the suspension of 3-dihydro-7H-pyrido [1.2.3-goes] [1.4]-benzoxazine-6-carboxylic acid.Reaction mixture was heated 5 hours under refluxing.The reaction mixture cool to room temperature filters out such precipitated solid, and washs successively and drying with cold acetonitrile, water and methyl alcohol, obtains 0.3 gram title compound.
Analyze: calculated value (%) C:63.15 H:5.55 N:10.52
Measured value (%) C:63.19 H:5.51 N:10.46
Embodiment 4:9-fluoro-3-(S)-and methyl isophthalic acid 0-[(3-methyl-2,8-diazabicylo [4.3.0] ninth of the ten Heavenly Stems-5-alkene)-the 8-yl]-7-oxygen-2, the preparation of 3-dihydro-7H-pyrido [1.2.3-goes] [1.4]-benzoxazines-6-carboxylic acid
Under agitation 0.32 milliliter DBN is added in the gram of 0.2 in 5 milliliters of anhydrous acetonitriles 3-methyl-2,8-diazabicylo [4.3.0] ninth of the ten Heavenly Stems-5-alkene dihydrochloride and 0.3 gram 9,10-two fluoro-3-(S)-and methyl-7-oxygen-2, in the suspension of 3-dihydro-7H-pyrido [1.2.3-goes] [1.4]-benzoxazine-6-carboxylic acid.Reaction mixture was heated 5 hours under refluxing.After the reaction mixture cooling, the solid filtering that forms is like this come out, wash successively with cold acetonitrile, water and methyl alcohol, drying gets 0.27 gram title compound.
Analyze: calculated value (%) C:63.15 H:5.55 N:10.52
Measured value (%) C:63.19 H:5.50 N:10.49
Embodiment 5:9-fluoro-3-(S)-and methyl isophthalic acid 0-[(4-methyl-2,8-diazabicylo [4.3.0] ninth of the ten Heavenly Stems-5-alkene)-the 8-yl]-7-oxygen-2, the preparation of 3-dihydro-7H-pyrido [1.2.3-goes] [1.4]-benzoxazines-6-carboxylic acid
Under agitation 0.32 milliliter DBN is added in the gram of 0.2 in 5 milliliters of anhydrous acetonitriles 4-methyl-2,8-diazabicylo [4.3.0] ninth of the ten Heavenly Stems-5-alkene dihydrochloride and 0.29 gram 9,10-two fluoro-3-(S)-and methyl-7-oxygen-2, in the suspension of 3-dihydro-7H-pyrido [1.2.3-goes] [1.4]-benzoxazine-6-carboxylic acid.Reaction mixture was heated 5 hours under refluxing.Behind the reaction mixture cool to room temperature, the gained solid is leached and wash successively with cold acetonitrile, water and methyl alcohol, drying under reduced pressure obtains 0.35 gram title compound.
Analyze: calculated value (%) C:63.15 H:5.55 N:10.52
Measured value (%) C:63.10 H:5.55 N:10.48
Embodiment 6:9-fluoro-3-(S)-and methyl isophthalic acid 0-[(2,7-diazabicylo [3.3.0] suffering-4-alkene)-the 7-yl]-7-oxygen-2, the preparation of 3-dihydro-7H-pyrido [1.2.3-goes] [1.4]-benzoxazines-6-carboxylic acid
Under agitation 0.32 milliliter DBN is added in the gram of 0.2 in 5 milliliters of anhydrous acetonitriles 2,7-diazabicylo [3.3.0] suffering-4-alkene dihydrochloride and 0.26 gram 9,10-two fluoro-3-(S)-and methyl-7-oxygen-2, in the suspension of 3-dihydro-7H-pyrido [1.2.3-goes] [1.4]-benzoxazine-6-carboxylic acid.Reaction mixture was heated 10 hours under refluxing.After the reaction mixture cooling, the solid filtering that forms is like this come out, wash successively with cold acetonitrile, water and methyl alcohol, water and carbinol mixture are washed again, and drying under reduced pressure obtains 0.32 gram title compound.
Analyze: calculated value (%) C:61.45 H:4.89 N:11.31
Measured value (%) C:61.51 H:4.83 N:11.27
Embodiment 7:9-fluoro-3-(S)-and methyl isophthalic acid 0-[(4-methyl-2,7-diazabicylo [3.3.0] suffering-4-alkene)-the 7-yl]-7-oxygen-2, the preparation of 3-dihydro-7H-pyrido [1.2.3-goes] [1.4]-benzoxazines-6-carboxylic acid
Under agitation 0.32 milliliter DBU is added in the gram of 0.2 in 5 milliliters of anhydrous acetonitriles 4-methyl-2,7-diazabicylo [3.3.0] suffering-4-alkene dihydrochloride and 0.25 gram 9,10-two fluoro-3-(S)-and methyl-7-oxygen-2, in the suspension of 3-dihydro-7H-pyrido [1.2.3-goes] [1.4]-benzoxazine-6-carboxylic acid.Reaction mixture was heated 7 hours under refluxing.Behind the reaction mixture cool to room temperature, the gained solid is leached, wash successively with cold acetonitrile, water and methyl alcohol, drying under reduced pressure obtains 0.33 gram title compound.
Analyze: calculated value (%) C:62.33 H:5.17 N:10.90
Measured value (%) C:62.30 H:5.13 N:10.81
Embodiment 8:9-fluoro-3-(S)-and methyl isophthalic acid 0-[(3-methyl-2,7-diazabicylo [3.3.0] suffering-4-alkene)-the 7-yl]-7-oxygen-2, the preparation of 3-dihydro-7H-pyrido [1.2.3-goes] [1.4]-benzoxazines-6-carboxylic acid
Under agitation 0.32 milliliter DBU is added in the gram of 0.2 in 5 milliliters of anhydrous acetonitriles 3-methyl-2,7-diazabicylo [3.3.0] suffering-4-alkene dihydrochloride and 0.26 gram 9,10-two fluoro-3-(S)-and methyl-7-oxygen-2, in the suspension of 3-dihydro-7H-pyrido [1.2.3-goes] [1.4]-benzoxazine-6-carboxylic acid.Reaction mixture was heated 10 hours under refluxing.Behind the reaction mixture cool to room temperature, the gained solid is leached, and use cold acetonitrile, water and methyl alcohol to wash successively, drying under reduced pressure obtains 0.35 gram title compound.
Analyze: calculated value (%) C:62.33 H:5.17 N:10.90
Measured value (%) C:62.30 H:5.11 N:10.20
Embodiment 9:9-fluoro-10-[(2,8-diazabicylo [4.3.0] ninth of the ten Heavenly Stems-5-alkene)-the 8-yl]-7-oxygen-2, the preparation of 3-dihydro-7H-pyrido [1.2.3-goes] [1.4]-benzothiazine-6-carboxylic acid
Under agitation 0.32 milliliter DBU is added in the gram of 0.2 in 5 milliliters of anhydrous acetonitriles 2,8-diazabicylo [4.3.0] ninth of the ten Heavenly Stems-5-alkene dihydrochloride and 0.35 gram 9,10-two fluoro-7-oxygen-2 are in the suspension of 3-dihydro-7H-pyrido [1.2.3-goes] [1.4]-benzothiazine-6-carboxylic acid.Reaction mixture was heated 5 hours under refluxing.When reaction mixture is as cold as room temperature, precipitation is leached, and wash successively with cold acetonitrile, water and methyl alcohol, drying under reduced pressure obtains 0.36 gram title compound.
Analyze: calculated value (%) C:58.90 H:4.68 N:10.85
Measured value (%) C:58.81 H:4.59 N:10.27
Embodiment 10:9-fluoro-10-[(2,7-diazabicylo [3.3.0] suffering-4-alkene)-the 7-yl]-7-oxygen-2, the preparation of 3-dihydro-7H-pyrido [1.2.3-goes] [1.4]-benzothiazine-6-carboxylic acid
Under agitation 0.3 milliliter DBU is added in the gram of 0.2 in 5 milliliters of anhydrous acetonitriles 2,7-diazabicylo [3.3.0] suffering-4-alkene dihydrochloride and 0.35 gram 9,10-two fluoro-7-oxygen-2 are in the suspension of 3-dihydro-7H-pyrido [1.2.3-goes] [1.4]-benzothiazine-6-carboxylic acid.Reaction mixture was heated 5 hours under refluxing.After reaction mixture is as cold as room temperature, the gained solid is leached, and use cold acetonitrile, water and methanol wash successively, drying under reduced pressure obtains 0.35 gram title compound.
Analyze: calculated value (%) C:66.44 H:4.96 N:12.91
Measured value (%) C:66.51 H:5.02 N:12.88
Embodiment 11:9-fluoro-3-(R, S)-methyl isophthalic acid 0-[(2,8-diazabicylo [4.3.0] ninth of the ten Heavenly Stems-5-alkene)-the 8-yl]-7-oxygen-2, the preparation of 3-dihydro-7H-pyrido [1.2.3-goes] [1.4]-benzoxazines-6-carboxylic acid
By handling 2 of 0.2 gram with methyl alcohol similar in appearance to embodiment 1 described method, 9 of 8-diazabicylo [4.3.0] ninth of the ten Heavenly Stems-5-alkene dihydrochloride and 0.28 gram, 10-two fluoro-3-(R, S)-methyl-7-oxygen-2,3-dihydro-7H-pyrido [1.2.3-goes] [1.4]-benzoxazines-6-carboxylic acid and obtain 0.27 the gram title compound.
Analyze: calculated value (%) C:62.33 H:5.17 N:10.90
Measured value (%) C:62.28 H:5.19 N:10.11
Embodiment 12:9-fluoro-3-(R, S)-methyl isophthalic acid 0-[(2,7-diazabicylo [3.3.0] suffering-4-alkene)-the 7-yl]-7-oxygen-2, the preparation of 3-dihydro-7H-pyrido [1.2.3-goes] [1.4]-benzoxazines-6-carboxylic acid
Press embodiment 6 described similarity methods and handle 2 of 0.2 gram with methyl alcohol, 9 of 7-diazabicylo [3.3.0] suffering-4-alkene dihydrochloride and 0.26 gram, 10-two fluoro-3-(R, S)-methyl-7-oxygen-2,3-dihydro-7H-pyrido [1.2.3-goes] [1.4]-benzoxazines-6-carboxylic acid and obtain 0.24 the gram title compound.
Analyze: calculated value (%) C:61.45 H:4.89 N:11.31
Measured value (%) C:61.36 H:4.79 N:11.24
Embodiment 13:9-fluoro-3-(R)-and methyl isophthalic acid 0-[(2,8-diazabicylo [4.3.0] ninth of the ten Heavenly Stems-5-alkene)-the 8-yl]-7-oxygen-2, the preparation of 3-dihydro-7H-pyrido [1.2.3-goes] [1.4]-benzoxazines-6-carboxylic acid
Press embodiment 1 described similarity method, handle 2 of 0.2 gram with methyl alcohol, 9 of 8-diazabicylo [4.3.0] ninth of the ten Heavenly Stems-5-alkene dihydrochloride and 0.28 gram, 10-two fluoro-3-(R)-methyl-7-oxygen-2,3-dihydro-7H-pyrido [1.2.3-goes] [1.4]-benzoxazine-6-carboxylic acid and obtain 0.26 the gram title compound.
Embodiment 14:9-fluoro-3-(S)-and methyl isophthalic acid 0-[(2,8-diazabicylo [4.3.0] ninth of the ten Heavenly Stems-5-alkene)-the 8-yl]-7-oxygen-2, the preparation of the hydrochloride of 3-dihydro-7H-pyrido [1.2.3-goes] [1.4]-benzoxazines-6-carboxylic acid
To derive from the 0.30 gram 9-fluoro-3-(S of embodiment 1)-methyl isophthalic acid 0-[2,8-diazabicylo [4.3.0] ninth of the ten Heavenly Stems-5-alkene-8-yl]-7-oxygen-2,3-dihydro-7H-pyrido [1.2.3-goes] [1.4]-benzoxazines-6-carboxylic acid is added in 5 milliliters of 3N hydrochloric acid-methanol solutions of 0 ℃, stirs the gained mixture 2 hours.Under reduced pressure remove and desolvate, with methyl alcohol-ether (1:4) wash residual thing and leach, restrain light yellow title compound and obtain 0.29.
1H-NMR（DMSO-d
6，δ）：1.55（3H，d），1.85（1H，m），2.20（2H，m），
3.05（1H，m），3.56（1H，m），4.00（3H，m），
4.38(2H, m), 4.65(1H, m), 5.90(1H, s(is wide)),
7.60（1H，d），8.30（1H，s），8.25（NH
3，s）
Embodiment 15:9-fluoro-3-(S)-and methyl isophthalic acid 0-[(2,7-diazabicylo [3.3.0] suffering-4-alkene)-the 7-yl]-7-oxygen-2, the preparation of the hydrochloride of 3-dihydro-7H-pyrido [1.2.3-goes] [1.4]-benzoxazines-6-carboxylic acid
To derive from the 0.25 gram 9-fluoro-3-(S of embodiment 6)-methyl isophthalic acid 0-[2,7-diazabicylo [3.3.0] suffering-4-alkene-7-yl]-7-oxygen-2,3-dihydro-7H-pyrido [1.2.3-goes] [1.4]-benzoxazines-6-carboxylic acid is added to and contains in the 0.15 tartaric 10 milliliters of chloroform-methanols of gram (10:1), at room temperature stirs the gained mixture 10 hours.Under reduced pressure remove and desolvate,, obtain the white title compound of 0.16 gram with 5ml acetonitrile treatment residue and stirring, filtered and recycled solid.
1H-NMR（DMSO-d
6，δ）：1.55（3H，d），2.25（2H，m），3.05（1H，m），
3.56（1H，m），4.00（3H，m），4.10（2H，m），
4.38（2H，m），4.62（1H，m），5.90（1H，s），
7.60（1H，d），8.16（NH
3，s），8.30（1H，s）.
According to nutrient agar doubling dilution (Hoechst 345), measure the antibiotic vigor of Carbostyril derivative of the present invention with the Muller-Hinton nutrient agar.The Hoechst reference culture is used as test strain.To have 10
7The inoculation of CFU/ milliliter is on substratum, and in the growth of 37 ℃ of insulations observation bacterial strain after 18 hours, wherein with ring third Ofloxacine USP 23 (ciprofloxacin) and Ofloxacine USP 23 agent in contrast, these test-results are listed in table 1 and table 2.
Table 1 in-vitro antibacterial vitality test (MIC: minimum inhibition concentration, μ g/ml)
Annotate: A: embodiment 1 compound
B: embodiment 6 compounds
C: embodiment 11 compounds
D: embodiment 13 compounds
Streptococcus pyogenes: streptococcus pyogenes
Streptococcus faecium: streptococcus faecium
Streptococcus aureus: golden yellow suis
Escherichia coli: intestinal bacteria
Pseudomonas aeruginose: Pseudomonas aeruginosa
Salmonella Typhimurium: salmonella typhi
Klebsiella aerogenes: aerogenesis Klebsiella pneumoniae
Enterobacter cloacae: enterobacter cloacae
The antibacterial activity in vitro of the streptococcus aureus of table 2 pair Methicillin resistance (MIC: minimum inhibition concentration, μ g/ml)
Annotate: A: embodiment 1 compound
B: embodiment 2 compounds
Staphylococcus aureus: streptococcus aureus
By shown in the last table 1, confirmed that The compounds of this invention to the antibacterial activity in vitro of gram-positive microorganism than Ofloxacine USP 23 and ring third Ofloxacine USP 23 strong 2-3 doubly or more; And also doubly than the strong 2-3 of the latter to the antibacterial activity in vitro of Gram-negative bacteria.As shown in table 2, confirmed that The compounds of this invention is for the antibacterial activity in vitro of the streptococcus aureus (MRSA) of Methicillin resistance than Ofloxacine USP 23 and the strong 2-3 of ring third Ofloxacine USP 23 doubly.
Claims (4)
1, the compound of logical formula I and its steric isomer with and pharmaceutically acceptable salt:
Wherein:
R
1, R
2, R
3And R
4Can be identical or different, and they represent hydrogen or low alkyl group respectively;
X represents oxygen or sulphur;
Y represents hydrogen or methyl;
N is 0 or 1 integer.
2, according to the compound of claim 1, and pharmaceutically acceptable salt, 3-(R)-the picoline keto carboxylic acid derivatives by general formula (I a) is represented:
Wherein,
R
1, R
2, R
3, R
4, n such as top defined.
3, according to the compound of claim 1,3-(S)-the picoline keto carboxylic acid derivatives represented by general formula (I b):
Wherein,
R
1, R
2, R
3, R
4Defined identical with n with claim 1.
4, its steric isomer of formula I compound with and the preparation method of pharmaceutically acceptable salt,
Wherein, R
1, R
2, R
3And R
4Can be identical or different, and represent hydrogen or low alkyl group respectively;
X represents oxygen or sulphur;
Y represents hydrogen or methyl: and
N is integer 0 and 1,
This preparation method comprises makes formula II compound and the reaction of formula III compound,
In the formula II: X and Y such as top defined
In the formula III: R
1, R
2, R
3, R
4As top defined.
Priority Applications (8)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR1019920013213A KR960003616B1 (en) | 1992-07-23 | 1992-07-23 | New pyridone carboxylic acid derivatives having potent antibacterial activities and the preparation process thereof |
| MX9304444A MX9304444A (en) | 1992-07-23 | 1993-07-22 | NEW DERIVATIVES OF PIRIDINECARBOXILICO ACID, PROCESS TO PREPARE THE SAME. |
| PCT/KR1993/000064 WO1994002487A1 (en) | 1992-07-23 | 1993-07-23 | Novel pyridonecarboxylic acid derivatives and processes for preparing the same |
| ZA935345A ZA935345B (en) | 1992-07-23 | 1993-07-23 | Pyridonecarboxylic acid derivatives and processes for preparing same |
| AU45874/93A AU4587493A (en) | 1992-07-23 | 1993-07-23 | Novel pyridonecarboxylic acid derivatives and processes for preparing the same |
| JP6504362A JP2552101B2 (en) | 1992-07-23 | 1993-07-23 | Novel pyridonecarboxylic acid derivative and method for preparing the same |
| EP93916265A EP0651753A1 (en) | 1992-07-23 | 1993-07-23 | Pyridonecarboxylic acid derivatives and processes for preparing the same |
| CN93119572A CN1102184A (en) | 1992-07-23 | 1993-10-25 | Novel pyridonecarboxylic acid derivatives and processes for preparing the same |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR1019920013213A KR960003616B1 (en) | 1992-07-23 | 1992-07-23 | New pyridone carboxylic acid derivatives having potent antibacterial activities and the preparation process thereof |
| CN93119572A CN1102184A (en) | 1992-07-23 | 1993-10-25 | Novel pyridonecarboxylic acid derivatives and processes for preparing the same |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN1102184A true CN1102184A (en) | 1995-05-03 |
Family
ID=36930224
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN93119572A Pending CN1102184A (en) | 1992-07-23 | 1993-10-25 | Novel pyridonecarboxylic acid derivatives and processes for preparing the same |
Country Status (8)
| Country | Link |
|---|---|
| EP (1) | EP0651753A1 (en) |
| JP (1) | JP2552101B2 (en) |
| KR (1) | KR960003616B1 (en) |
| CN (1) | CN1102184A (en) |
| AU (1) | AU4587493A (en) |
| MX (1) | MX9304444A (en) |
| WO (1) | WO1994002487A1 (en) |
| ZA (1) | ZA935345B (en) |
Family Cites Families (6)
| 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 (en) * | 1983-08-24 | 1985-03-13 | 三菱油化株式会社 | Thermoplastic fluoroplastic laminate |
| JPS62275134A (en) * | 1986-02-18 | 1987-11-30 | Tosoh Corp | Bonding |
| DE3906365A1 (en) * | 1988-07-15 | 1990-01-18 | Bayer Ag | 7- (1-PYRROLIDINYL) -3-CHINOLONE AND NAPHTHYRIDONE CARBOXYLIC ACID DERIVATIVES, METHOD AND SUBSTITUTED (OXA) DIAZABICYCLOOCTANES AND NONANESE AS INTERMEDIATE PRODUCTS, AND ANTIBACTERIAL AGENTS AND FOOD ADDITIVES CONTAINING THEM |
| NZ240883A (en) * | 1990-12-05 | 1994-09-27 | Synphar Lab Inc | Antibacterial 7-substituted-6-fluoro-1,4-dihydro-4-oxo- quinoline-3-carboxylic acid derivatives |
-
1992
- 1992-07-23 KR KR1019920013213A patent/KR960003616B1/en not_active IP Right Cessation
-
1993
- 1993-07-22 MX MX9304444A patent/MX9304444A/en unknown
- 1993-07-23 AU AU45874/93A patent/AU4587493A/en not_active Abandoned
- 1993-07-23 ZA ZA935345A patent/ZA935345B/en unknown
- 1993-07-23 JP JP6504362A patent/JP2552101B2/en not_active Expired - Fee Related
- 1993-07-23 EP EP93916265A patent/EP0651753A1/en not_active Ceased
- 1993-07-23 WO PCT/KR1993/000064 patent/WO1994002487A1/en not_active Application Discontinuation
- 1993-10-25 CN CN93119572A patent/CN1102184A/en active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| EP0651753A1 (en) | 1995-05-10 |
| KR960003616B1 (en) | 1996-03-20 |
| MX9304444A (en) | 1994-04-29 |
| AU4587493A (en) | 1994-02-14 |
| WO1994002487A1 (en) | 1994-02-03 |
| KR940002252A (en) | 1994-02-17 |
| JP2552101B2 (en) | 1996-11-06 |
| JPH07509240A (en) | 1995-10-12 |
| ZA935345B (en) | 1994-02-14 |
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| SE01 | Entry into force of request for substantive examination | ||
| C06 | Publication | ||
| PB01 | Publication | ||
| C01 | Deemed withdrawal of patent application (patent law 1993) | ||
| WD01 | Invention patent application deemed withdrawn after publication |