WO1997025991A1 - Esters of (9-fluoro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo-2,3-dihydro-7h-pyrido[3,2,1,ij]-1,3,4-benzoaxadiazine-6-carboxylic acid) and their use as antibacterial - Google Patents

Esters of (9-fluoro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo-2,3-dihydro-7h-pyrido[3,2,1,ij]-1,3,4-benzoaxadiazine-6-carboxylic acid) and their use as antibacterial Download PDF

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Publication number
WO1997025991A1
WO1997025991A1 PCT/GB1996/002673 GB9602673W WO9725991A1 WO 1997025991 A1 WO1997025991 A1 WO 1997025991A1 GB 9602673 W GB9602673 W GB 9602673W WO 9725991 A1 WO9725991 A1 WO 9725991A1
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WIPO (PCT)
Prior art keywords
alkyl
methyl
compound
formula
phenyl
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Application number
PCT/GB1996/002673
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French (fr)
Inventor
Roderick John Dorgan
Richard Andrew Bentley Webster
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Pfizer Inc.
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 Pfizer Inc. filed Critical Pfizer Inc.
Priority to EP96935143A priority Critical patent/EP0874633A1/en
Priority to CA002242716A priority patent/CA2242716A1/en
Priority to AU73220/96A priority patent/AU7322096A/en
Priority to JP9525759A priority patent/JP2000501108A/en
Publication of WO1997025991A1 publication Critical patent/WO1997025991A1/en

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
    • A61K31/537—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines spiro-condensed or forming part of bridged ring systems
    • 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
    • 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

  • This invention relates to a method of treating or preventing bacterial infections in non-human animals, more particularly domesticated mammals and birds, such as horses, cattle, swine, sheep, companion animals including dogs and cats, and poultry including chickens.
  • EP-A-0 259 804 describes a compound of formula (A):
  • a disadvantage of the compound of formula (A) is that it is unpalatable and therefore difficult to administer to animals via the oral route.
  • a method of treating or preventing a bacterial infection in a non-human animal comprises administering to the animal via the oral route an antibacterially effective amount of a compound of formula
  • R 1 is a pharmaceutically acceptable in vivo hydrolysable ester group.
  • Suitable pharmaceutically acceptable in vivo hydrolysable ester groups include those which break down readily in the body to leave the parent acid or its salt.
  • Suitable ester groups of this type include those of part formulae (i), (ii), (iii) and (iv):
  • R a is hydrogen, C ⁇ alkyl, C 3 7 cycloalkyl, methyl, or phenyl
  • R b is C,. 6 alkyl, C 1 6 alkoxy, C 3 . 7 cycloalkoxy, phenyl, benzyl, C 3 . 7 cycloalkyl, C,. 6 alkyl, C 3 . 7 cycloalkyl, 1 -amino C ⁇ alkyl, or 1 -(C 1 6 alkyDamino C,. 6 alkyl; or R a and R b together form a 1 ,2-phenylene group optionally substituted by one or two methoxy groups; R c represents C,.
  • Suitable in vivo hydrolysable ester groups include, for example, acyloxyalkyl groups such as acetoxymethyl, pivaloyloxymethyl, ⁇ -acetoxyethyl, ⁇ -pivaloyloxyethyl, 1 - (cyclohexylcarbonyloxy)prop-l -yl, and (1 -aminoethyl) carbonyloxymethyl; alkoxycarbonyloxyalkyl groups, such as ethoxycarbonyloxymethyl and ⁇ -ethoxycarbonyloxyethyl; cycloalkoxycarbonyloxyalkyl groups, such as cyclohexyloxycarbonyloxymethyl; dialkylaminoalkyl especially di- loweralkylamino alkyl groups such as dimethylaminomethyl, dimethylaminoethyl, diethylaminomethyl or diethylaminoethyl; lactone groups such as phthalidyl and dimethoxy
  • a further suitable pharmaceutically acceptable m vivo hydrolysable ester group is that of the formula:
  • R h is hydrogen, C 1 6 alkyl or phenyl.
  • a particularly preferred ester group is pivaloyloxymethyl.
  • a second aspect of the invention provides use of a compound of formula (I) in the manufacture of a medicament for use in the treatment or prevention of bacterial infections in non-human animals by administration via the oral route.
  • the compound of formula (I) is administered in admixture with the animal's feedstuff or drinking water.
  • a further aspect of the invention provides feedstuff or drinking water having a compound of formula (I) mixed therewith, as well as a premix comprising a compound of formula (I) together with a veterinarily acceptable carrier.
  • Suitable carriers include a mixture of a binder, such as polyvinylpyrroilidone, and a filler, such as lactose, which can be extruded, granulated and mixed with or sprinkled on the animals' food.
  • the active is first made up as a concentrate with a liquid carrier, such as gluconolactone.
  • Compounds of the invention may also be administered orally in the form of a tablet containing such excipients as starch or lactose, or in a capsule or ovule either alone or in admixture with excipients, or in the form of an elixir or suspension containing a flavouring or colouring agent.
  • the tablets and capsules for oral administration may be in unit dosage form, and may contain conventional excipients including, for example, binding agents, for example, syrup, acacia, gelatin, sorbitol, tragacanth, or polyvinylpyrroilidone; fillers, for example lactose, sugar, maize-starch, calcium phosphate, sorbitol or giycine; tabletting lubricants, for example magnesium stearate, talc, polyethylene glycol or silica; disintegrants, for example potato starch; and pharmaceutically acceptable wetting agents, for example sodium lauryl sulphate.
  • the tablets may be coated according to methods well known in normal pharmaceutical practice.
  • Oral liquid preparations may be in the form of, for example, aqueous or oily suspensions, solutions, emulsions, syrups or elixirs, or may be presented as a dry product for reconstitution with water or another suitable vehicle before use.
  • Such liquid preparations may contain conventional additives, including, for example, suspending agents, for example sorbitol, methyl cellulose, glucose syrup, gelatin, hydroxyethyl cellulose, carboxymethyl cellulose, aluminium stearate gel or hydrogenated edible fats; emulsifying agents, for example lecithin, sorbitan monooleate or acacia; non-aqueous vehicles (which may include edible oils), for example almond oil, oily esters (for example glycerine), propylene glycol, or ethyl alcohol; preservatives, for example methyl or propyl p-hydroxybenzoate or sorbic acid; and, if desired, conventional flavouring and colour agents.
  • suspending agents for example sorbitol, methyl cellulose, glucose syrup, gelatin, hydroxyethyl cellulose, carboxymethyl cellulose, aluminium stearate gel or hydrogenated edible fats
  • emulsifying agents for example lecithin, sorbitan monooleate
  • the compound of formula (I) is typically provided in an amount sufficient to give from 0.5 to 500 mg/kg of animal body weight, more particularly from 1 to 300 mg/kg.
  • Infections suitable for treatment include infections caused by organisms selected from the group consisting of Staphylococcus, Streptococcus, Aerococcus, Enterococcus, Micrococcus, Kactobacillus, Bifidobacterium, Clostridium, Eubacterium, Peptococcus, Peptostreptococcus, Propionibacterium, Citrobacter, Campylobacter, Enterobacter, Klebsiella, Proteus, Pseudomonas, Serratia, Salmonella, Shigella, Vibrio, Aeromonas, Haemophilus, Neisseria, Acinetobacter, Alcaligenes, Bordetella, Bacteroids, Fusobacterium, Myocoplasma and other microorganisms.
  • Certain compounds of formula (I) are novel and form a further aspect of the invention.
  • An example of such a compound is cyclohexyloxycarbonyloxymethyl 9-fluoro-3-methyl-10-(4-methyl-1 - piperazinyl)-7-oxo-2,3-dihydro-7H-pyrido[3,2, 1 -ij]-1 ,3,4- benzoxadiazine-6-carboxylate.
  • R a to R h are as defined hereinabove and X is a leaving group such as halide, preferably chloride, or hydroxy.
  • the reaction with the compound of formula (A) is typically carried out in a non-aqueous solvent, such as DMF, DMA, DMSO or acetone, in the presence of an acid binding agent such as an organic or inorganic base.
  • a non-aqueous solvent such as DMF, DMA, DMSO or acetone
  • an acid binding agent such as an organic or inorganic base.
  • an inorganic base such as potassium or sodium carbonate, is used.
  • Temperatures are typically between ambient and reflux, for example about 50°C.
  • a suitable activated derivative of the compound of formula (A) can be used.
  • Such a derivative can be prepared by treating the compound of formula (A) with dicyclohexylcarbodiimide.

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

Abstract

Compounds of formula (I) wherein R1 is a pharmaceutically acceptable in vivo hydrolysable ester group, may be used to treat or prevent a bacterial infection in a non-human animal by administration via the oral route.

Description

ESTERS OF (9-FLUORO-3-METHYL-10-(4-METHYL-l-PIPERAZINYL)-7-OXO-2,3-DIHYDRO-7H- PYRIDO[3.2. I.IJJ- l.3,4-BENZOAXADlAZINE-6-CARBOXYLIC ACID) AND THEIR USE AS AN¬ TIBACTERIAL
This invention relates to a method of treating or preventing bacterial infections in non-human animals, more particularly domesticated mammals and birds, such as horses, cattle, swine, sheep, companion animals including dogs and cats, and poultry including chickens.
It is often convenient to administer an antibacterial compound to domesticated animals via the oral route, for example mixed with the animals' feedstuff or drinking water. It is therefore important for such compounds to be palatable to the target animal if the treatment is to be effective.
EP-A-0 259 804 describes a compound of formula (A):
Figure imgf000003_0001
(A)
(9-fluoro-3-methyl-10-(4-methyl-1 -piperazinyl)-7-oxo-2,3-dihydro-7H- pyrido[3,2, 1 -ij]-1 ,3,4-benzadiazine-6-carboxylic acid). This compound is stated to have antibacterial activity.
A disadvantage of the compound of formula (A) is that it is unpalatable and therefore difficult to administer to animals via the oral route. According to the present invention there is provided a method of treating or preventing a bacterial infection in a non-human animal, which method comprises administering to the animal via the oral route an antibacterially effective amount of a compound of formula
Figure imgf000004_0001
wherein R1 is a pharmaceutically acceptable in vivo hydrolysable ester group.
Examples of suitable pharmaceutically acceptable in vivo hydrolysable ester groups include those which break down readily in the body to leave the parent acid or its salt. Suitable ester groups of this type include those of part formulae (i), (ii), (iii) and (iv):
(0
I -C02CH-0 CO.FT
■ Ru
-C02-R -N .
■ Rβ 0
-C02-CH2OR
( in )
Figure imgf000004_0002
NH, wherein Ra is hydrogen, C^ alkyl, C3 7 cycloalkyl, methyl, or phenyl, Rb is C,.6 alkyl, C1 6 alkoxy, C3.7 cycloalkoxy, phenyl, benzyl, C3.7 cycloalkyl, C,.6 alkyl, C3.7 cycloalkyl, 1 -amino C^ alkyl, or 1 -(C1 6 alkyDamino C,.6 alkyl; or Ra and Rb together form a 1 ,2-phenylene group optionally substituted by one or two methoxy groups; Rc represents C,.6 alkylene optionally substituted with a methyl or ethyl group and Rd and Rβ independently represent C1 6 alkyl; Rf represents C1 6 alkyl; R9 represents hydrogen or phenyl optionally substituted by up to three groups selected from halogen, C,.6 alkyl, or C,.6 alkoxy; and Q is oxygen or NH.
Examples of suitable in vivo hydrolysable ester groups include, for example, acyloxyalkyl groups such as acetoxymethyl, pivaloyloxymethyl, α-acetoxyethyl, α-pivaloyloxyethyl, 1 - (cyclohexylcarbonyloxy)prop-l -yl, and (1 -aminoethyl) carbonyloxymethyl; alkoxycarbonyloxyalkyl groups, such as ethoxycarbonyloxymethyl and α-ethoxycarbonyloxyethyl; cycloalkoxycarbonyloxyalkyl groups, such as cyclohexyloxycarbonyloxymethyl; dialkylaminoalkyl especially di- loweralkylamino alkyl groups such as dimethylaminomethyl, dimethylaminoethyl, diethylaminomethyl or diethylaminoethyl; lactone groups such as phthalidyl and dimethoxyphthalidyl; and esters linked to a second antibiotic.
A further suitable pharmaceutically acceptable m vivo hydrolysable ester group is that of the formula:
Figure imgf000005_0001
wherein Rh is hydrogen, C1 6 alkyl or phenyl.
A particularly preferred ester group is pivaloyloxymethyl.
A second aspect of the invention provides use of a compound of formula (I) in the manufacture of a medicament for use in the treatment or prevention of bacterial infections in non-human animals by administration via the oral route.
Preferably, the compound of formula (I) is administered in admixture with the animal's feedstuff or drinking water. Thus, a further aspect of the invention provides feedstuff or drinking water having a compound of formula (I) mixed therewith, as well as a premix comprising a compound of formula (I) together with a veterinarily acceptable carrier. Suitable carriers include a mixture of a binder, such as polyvinylpyrroilidone, and a filler, such as lactose, which can be extruded, granulated and mixed with or sprinkled on the animals' food. For addition to drinking water, the active is first made up as a concentrate with a liquid carrier, such as gluconolactone.
Compounds of the invention may also be administered orally in the form of a tablet containing such excipients as starch or lactose, or in a capsule or ovule either alone or in admixture with excipients, or in the form of an elixir or suspension containing a flavouring or colouring agent. The tablets and capsules for oral administration may be in unit dosage form, and may contain conventional excipients including, for example, binding agents, for example, syrup, acacia, gelatin, sorbitol, tragacanth, or polyvinylpyrroilidone; fillers, for example lactose, sugar, maize-starch, calcium phosphate, sorbitol or giycine; tabletting lubricants, for example magnesium stearate, talc, polyethylene glycol or silica; disintegrants, for example potato starch; and pharmaceutically acceptable wetting agents, for example sodium lauryl sulphate. The tablets may be coated according to methods well known in normal pharmaceutical practice.
Oral liquid preparations may be in the form of, for example, aqueous or oily suspensions, solutions, emulsions, syrups or elixirs, or may be presented as a dry product for reconstitution with water or another suitable vehicle before use. Such liquid preparations may contain conventional additives, including, for example, suspending agents, for example sorbitol, methyl cellulose, glucose syrup, gelatin, hydroxyethyl cellulose, carboxymethyl cellulose, aluminium stearate gel or hydrogenated edible fats; emulsifying agents, for example lecithin, sorbitan monooleate or acacia; non-aqueous vehicles (which may include edible oils), for example almond oil, oily esters (for example glycerine), propylene glycol, or ethyl alcohol; preservatives, for example methyl or propyl p-hydroxybenzoate or sorbic acid; and, if desired, conventional flavouring and colour agents.
The compound of formula (I) is typically provided in an amount sufficient to give from 0.5 to 500 mg/kg of animal body weight, more particularly from 1 to 300 mg/kg.
Infections suitable for treatment include infections caused by organisms selected from the group consisting of Staphylococcus, Streptococcus, Aerococcus, Enterococcus, Micrococcus, Kactobacillus, Bifidobacterium, Clostridium, Eubacterium, Peptococcus, Peptostreptococcus, Propionibacterium, Citrobacter, Campylobacter, Enterobacter, Klebsiella, Proteus, Pseudomonas, Serratia, Salmonella, Shigella, Vibrio, Aeromonas, Haemophilus, Neisseria, Acinetobacter, Alcaligenes, Bordetella, Bacteroids, Fusobacterium, Myocoplasma and other microorganisms.
Certain compounds of formula (I) are novel and form a further aspect of the invention. An example of such a compound is cyclohexyloxycarbonyloxymethyl 9-fluoro-3-methyl-10-(4-methyl-1 - piperazinyl)-7-oxo-2,3-dihydro-7H-pyrido[3,2, 1 -ij]-1 ,3,4- benzoxadiazine-6-carboxylate.
Compounds of formula (I) can be prepared from the compound of formula (A) and its derivatives using techniques which are known in the art. For example, the compound of formula (A) or an activated derivative thereof can be treated with a compound of formula (v), (vi), (vii), (viii), (ix): R"
XCH-O.CO.R" (v)
-Rϋ
(VI)
X-R -N
■ R"
XCH2-OR (VI I )
(„,„)
Figure imgf000008_0001
Figure imgf000009_0001
wherein Ra to Rh are as defined hereinabove and X is a leaving group such as halide, preferably chloride, or hydroxy.
The reaction with the compound of formula (A) is typically carried out in a non-aqueous solvent, such as DMF, DMA, DMSO or acetone, in the presence of an acid binding agent such as an organic or inorganic base. Preferably an inorganic base, such as potassium or sodium carbonate, is used. Temperatures are typically between ambient and reflux, for example about 50°C.
Alternatively, a suitable activated derivative of the compound of formula (A) can be used. Such a derivative can be prepared by treating the compound of formula (A) with dicyclohexylcarbodiimide.
The invention will now be further illustrated by reference to the following examples:
EXAMPLE 1
Pivaloyloxymethyl 9-fluoro-3-methyl-10-(4-methyl-1 -piperazinyl)-7- oxo-2,3-dihydro-7H-pyrido[3,2, 1 -ij]-1 ,3,4-benzoxadiazine-6- carboxylate.
A solution of 9-fluoro-3-methyl-10-(4-methyl-1 -piperazinyl)-7-oxo- 2,3-dihydro-7H-pyrido[3,2, 1 -ij]-1 ,3,4-benzadiazine-6-carboxylic acid - 7/1 -
( 1 .0g, 2.78 mmol), chloromethyl pivalate (0.63g, 4.1 7 mmol) and potassium carbonate (0.77g, 5.56 mmol) in dry DMF (20ml) was stirred at 45°C under an argon atmosphere for 16h. The reaction mixture was poured into DCM (50 ml) and the organic solution was washed with water (30 ml) and then dried over sodium sulfate. The solvent was evaporated in vacuo leaving a white solid contaminated with DMF. The solid was purified by recrystallisation from ethyl acetate to give the pivaloyloxymethyl ester (0.88g, 67%) as a white, microcrystalline solid, m.p. 204-207°C, m/z (FAB) 477 (M + 1 ).
(Found: C, 58.1 , H, 6.0, N, 1 1 .8%. C23H29FN4O6 requires C, 58.2, H, 5.7, N, 1 1 .8%).
Figure imgf000010_0001
EXAMPLE 2
Cyclohexyloxycarbonyloxymethyl 9-fluoro-3-methyl-10-(4-methyl-1 - piperazinyl)-7-oxo-2,3-dihydro-7H-pyrido[3,2, 1 -ij]-1 ,3,4- benzoxadiazine-6-carboxylate.
A solution of 9-fluoro-3-methyl-1 0-(4-methyl-1 -piperazinyl)-7-oxo- 2,3-dihydro-7H-pyrido[3,2, 1 -ij]-1 ,3,4-benzadiazine-6-carboxylic acid (1 .0g, 2.78 mmol), chloromethyl cyclohexyl carbonate (0.80g, 4.1 7 mmol) and potassium carbonate (0.77g, 5.56 mmol) in dry DMF (20 ml) was stirred at 45°C under an argon atmosphere for 1 6h. The reaction mixture was poured into DCM (30ml) and the organic solution was washed with water (30ml) and then dried over sodium - 7/2 - sulfate. The solvent was evaporated in vacuo leaving a white solid which was purified by recrystallisation from ethyl acetate to give the cyclohexyloxycarbonyloxymethyl ester ( 1 .02g, 80%) as a white solid, m.p. 1 80-1 81 °C, m/z (FAB) 51 9 (M + 1 ).
Figure imgf000011_0001

Claims

The use of a compound of formula (I)
Figure imgf000012_0001
α) wherein R1 is a pharmaceutically acceptable in vivo hydrolysable ester group, in the manufacture of a medicament for use in the treatment or prevention of bacterial infections in non-human animals by administration via the oral route.
Use as claimed in claim 1 , wherein R' is selected from the following part formulae (i), (ii), (iii) and (iv)
R* 0)
-CO-CH-O.CO.R0
Figure imgf000012_0002
-C02-CH.OR
(III )
Figure imgf000012_0003
NH, - 9 -
wherein Ra is hydrogen, C, 6 alkyl, C3 7 cycloalkyl, methyl, or phenyl, Rb is C, 6 alkyl, C, 6 alkoxy, C3 7 cycloalkoxy, phenyl, benzyl, C3 7 cycloalkyl, C, 6 alkyl C3 7 cycloalkyl, 1 -amino C, 6 alkyl or 1 -(C, 6 alkyl) ammo C, 6 alkyl; or Ra and Rb together form a 1 ,
2-phenylene group optionally substituted by one or two methoxy groups; Rc represents C, 6 alkylene optionally substituted with a methyl or ethyl group and Rd and Rβ independently represent C, 6 alkyl; R' represents C, 6 alkyl; R9 represents hydrogen or phenyl optionally substituted by up to three groups selected from halogen, C, 6 alkyl or C, 6 alkoxy; and Q is oxygen or NH.
3. Use as claimed in claim 1 , wherein R' is
Figure imgf000013_0001
and wherein Rh is hydrogen, C, 6 alkyl or phenyl.
4. Use as claimed in claim 1 , wherein R' is pivaloyloxymethyl.
5. Compound of formula (I) as defined in claim 1 which is cyclohexyloxycarbonyloxymethyl 9-fluoro-3-methyl-10-(4- methyl- 1 -pιperazιnyl)-7-oxo-2,3-dιhydro-7H-pyrιdo [3,2, 1 -ιj]-
1 ,3,4-benzoxadiazine-6-carboxylate.
6. The compound of claim 5 for use as a medicament.
7. Feedstuff or drinking water for animals comprising a compound of formula (I) as defined in claim 1 . - 10 -
8. Premix comprising a compound of formula (I) as defined in claim 1 together with a veteπnaπly acceptable carrier.
9. A method of treating or preventing a bacterial infection in a non-human animal which comprises administering to the animal via the oral route an antibacterially effective amount of a compound of formula (I) as defined in claim 1 .
PCT/GB1996/002673 1996-01-17 1996-10-31 Esters of (9-fluoro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo-2,3-dihydro-7h-pyrido[3,2,1,ij]-1,3,4-benzoaxadiazine-6-carboxylic acid) and their use as antibacterial WO1997025991A1 (en)

Priority Applications (4)

Application Number Priority Date Filing Date Title
EP96935143A EP0874633A1 (en) 1996-01-17 1996-10-31 Esters of (9-fluoro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo-2,3-dihydro-7h-pyrido[3,2,1,ij]-1,3,4-benzoaxadiazine-6-carboxylic acid) and their use as antibacterial
CA002242716A CA2242716A1 (en) 1996-01-17 1996-10-31 Esters of (9-fluoro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo-2,3-dihydro-7h-pyrido[3,2,1,ij]-1,3,4-benzoaxadiazine-6-carboxylic acid) and their use as antibacterial
AU73220/96A AU7322096A (en) 1996-01-17 1996-10-31 Esters of (9-fluoro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo-2,3-dih ydro-7h-pyrido{3,2,1,ij}-1,3,4-benzoaxadiazine-6-carboxylic acid) and their use as antibacterial
JP9525759A JP2000501108A (en) 1996-01-17 1996-10-31 (9-Fluoro-3-methyl-10- (4-methyl-1-piperazinyl) -7-oxo-2,3-dihydro-7H-pyrido [3,2,1, IJ] -1,3,4- Esters of benzoxadiazine-6-carboxylic acid) and their use as antibacterial agents

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GB9600888.3 1996-01-17
GBGB9600888.3A GB9600888D0 (en) 1996-01-17 1996-01-17 Method of treatment

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WO1997025991A1 true WO1997025991A1 (en) 1997-07-24

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Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0259804A2 (en) * 1986-09-12 1988-03-16 F. Hoffmann-La Roche Ag Pyrido[3,2,1-ij]-1,3,4-benzoxadiazine derivatives, process for their preparation, resulting pharmaceutical preparations and intermediates for use in the process

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0259804A2 (en) * 1986-09-12 1988-03-16 F. Hoffmann-La Roche Ag Pyrido[3,2,1-ij]-1,3,4-benzoxadiazine derivatives, process for their preparation, resulting pharmaceutical preparations and intermediates for use in the process

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JP2000501108A (en) 2000-02-02
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AU7322096A (en) 1997-08-11

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