WO1997026261A1 - Pyrido (3,2,1-ij)-1,3,4-benzoxadiazine - Google Patents
Pyrido (3,2,1-ij)-1,3,4-benzoxadiazine Download PDFInfo
- Publication number
- WO1997026261A1 WO1997026261A1 PCT/GB1996/002674 GB9602674W WO9726261A1 WO 1997026261 A1 WO1997026261 A1 WO 1997026261A1 GB 9602674 W GB9602674 W GB 9602674W WO 9726261 A1 WO9726261 A1 WO 9726261A1
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- Prior art keywords
- compound
- formula
- methyl
- treating
- administration
- Prior art date
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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
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23K—FODDER
- A23K20/00—Accessory food factors for animal feeding-stuffs
- A23K20/10—Organic substances
- A23K20/116—Heterocyclic compounds
-
- 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
- the present invention relates to a novel compound, to processes for its production, to pharmaceutical formulations containing it, and to its use in therapy, particularly in the treatment of microbial infections.
- EP-A-0 259 804 describes the compound of formula (A):
- the present invention provides a compound of formula (I):
- R is C ⁇ _g alkyl, such as methyl or ethyl.
- a particular compound of formula (I) is 6-(ethoxycarbonyl)acetyl 9-fluoro-3-methyl-10-(4-methyl-l- piperazinyl)-7-oxo-2,3-diJhydro-7H-pyrido[3,2,l-ij]-l,3,4-benzoxadiazine.
- Compounds of formula (I) have antibacterial activity and are therefore of use in the treatment and prophylaxis of bacterial infections in humans and animals.
- the invention in a second aspect- further provides a process for the production of a compound of formula (I), which comprises treating a compound of formula (II):
- X is a leaving group, such as imidazole or halide, such as chlorine, with a carbanion derivable by treating a dialkyl malonate with a strong base, such as sodium hydride.
- the compound of formula (II) can be obtained by treating the compound of formula (A) with, for example, an excess of carbonyl diimidazole. This reaction is typically carried out in an aprotic solvent such as chloroform at ambient or elevated temperature, eg at reflux, under dry conditions, e.g. in an argon, atmosphere.
- an aprotic solvent such as chloroform at ambient or elevated temperature, eg at reflux, under dry conditions, e.g. in an argon, atmosphere.
- Generation of the carbanion is typically carried out at between-70 and 70° C, for instance at ambient temperature, in an aprotic solvent such as THF.
- an aprotic solvent such as THF.
- a solution of the compound of formula (II) in THF is then added and the mixture is refluxed. After evaporation of solvent the residue is dissolved in water and the reaction quenched by neutralization to pH7.
- the product is extracted and purified by chromatography such as HPLC.
- the compound according to the invention is suitably provided in substantially pure form, for example at least 50% pure, suitable at least 60% pure, advantageously at least 75% pure, preferably at least 85% pure, more preferably at least 95% pure, especially at least 98% pure, all percentages being calculated as weight/weight.
- An impure or less pure form of the compound according to the invention may, for example, be used in the preparation of a more pure form of the same compound.
- the compound of the invention has antibacterial activity and is useful for the prophylactic and therapeutic treatment of bacterial infections in animals, especially mammals, including humans, in particular humans and domesticated animals (including farm animals).
- the compound may be used for the treatment of infections caused by, among other organisms, species of Staphylococcus, Streptococcus, Aerococcus, Enterococcus, Micrococcus, actobacillus, 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.
- a third aspect of the invention provides the compound of formula (I) for use in medical therapy, in particular for use as an antibacterial agent
- the invention further provides a method of treating a human or animal suffering from a bacterial infection by the administration of an effective amount of the compound of the invention.
- a particular method of the invention comprises 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.
- the method comprises administering to the animal via the oral route an antibacterially effective amount of a compound of formula (I):
- a further 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 invention further provides a pharmaceutical composition
- a pharmaceutical composition comprising a compound of the formula (I) together with a pharmaceutically acceptable diluent or carrier.
- the compound of the invention can be administered alone, but will generally be administered in admixture with a pharmaceutical carrier selected with regard to the intended route of administration and standard pharmaceutical practice.
- a pharmaceutical carrier selected with regard to the intended route of administration and standard pharmaceutical practice.
- it may 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.
- It may be injected parenterally, for example, intravenously, intramuscularly or subcutaneously.
- a sterile solution which may contain other substances, for example, enough salts or glucose to make the solution isotonic.
- the daily dosage level of the compound of formula (I) will be from 0.5 to 500, preferably 1 to 300 mg/kg (in divided doses) when administered by either the oral or parenteral route.
- the compounds and compositions according to the invention may be formulated for administration in any convenient way for use in human or veterinary medicine, by analogy with other antibacterial agents.
- 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 polyvinylpyrrollidone; fillers, for example lactose, sugar, maize-starch, calcium phosphate, sorbitol or glycine; 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
- compositions according to the invention intended for topical administration may, for example, be in the form of ointments, creams, lotions, eye ointments, eye drops, ear drops, impregnated dressings, and aerosols, and may contain appropriate conventional additives, including, for example, preservatives, solvents to assist drug penetration, and emollients in ointments and creams.
- Such topical formulations may also contain compatible conventional carriers, for example cream or ointment bases, and ethanol or oleyl alcohol for lotions.
- Such carriers may constitute from about 1% to about 98% by weight of the formulation; more usually they will constitute up to about 80% by weight of the formulation.
- compositions according to the invention may be formulated as suppositories, which may contain conventional suppository bases, for example cocoa-butter or other glycerides.
- compositions according to the invention intended for parenteral administration may conveniently be in fluid unit dosage forms, which may be prepared utilizing the compound and a sterile vehicle, propyleneglycol.
- the compound depending on the vehicle and concentration used, may be either suspended or dissolved in the vehicle.
- Parenteral suspensions may be prepared in substantially the same manner except that the compound is suspended in the vehicle instead of being dissolved and sterilisation cannot be accomplished by filtration.
- the compound may instead be sterilised by exposure to ethylene oxide before being suspended in the sterile vehicle.
- a surfactant or wetting agent is included in such suspensions in order to facilitate uniform distribution of the compound.
- compositions according to the invention may also be administered by inhalation.
- inhalation is meant intranasal and oral inhalation administration.
- Appropriate dosage forms for such administration such as an aerosol formulation or a metered dose inhaler, may be prepared by conventional techniques.
- 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 polyvinylpyrrollidone, 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.
Abstract
Compounds of formula (I) wherein R is C1-6 alkyl, such as methyl or ethyl, have antibacterial activity and are therefore of use in treatment and prophylaxis of bacterial infections in humans and animals
Description
PY IDO (3, 2, 1-IJ)-1, 3,4-BENZ0XADIAZINE
The present invention relates to a novel compound, to processes for its production, to pharmaceutical formulations containing it, and to its use in therapy, particularly in the treatment of microbial infections.
EP-A-0 259 804 describes the compound of formula (A):
(A)
(9-fluoro-3-methyl-10-(4-methyl-l-piperazinyl)-7-oxo-2,3-dihydro-7H- pyrido[3,2,l-ij]-l,3,4-benzadiazine-6-carboxylic acid). The compound of formula (A) is reported to have antibacterial activity.
The present invention provides a compound of formula (I):
Compounds of formula (I) have antibacterial activity and are therefore of use in the treatment and prophylaxis of bacterial infections in humans and animals.
The invention in a second aspect- further provides a process for the production of a compound of formula (I), which comprises treating a compound of formula (II):
(ID
wherein X is a leaving group, such as imidazole or halide, such as chlorine, with a carbanion derivable by treating a dialkyl malonate with a strong base, such as sodium hydride.
The compound of formula (II) can be obtained by treating the compound of formula (A) with, for example, an excess of carbonyl diimidazole. This reaction is typically carried out in an aprotic solvent such as chloroform at ambient or elevated temperature, eg at reflux, under dry conditions, e.g. in an argon, atmosphere.
Generation of the carbanion is typically carried out at between-70 and 70° C, for instance at ambient temperature, in an aprotic solvent such as THF. A solution of the compound of formula (II) in THF is then added and the mixture is refluxed. After evaporation of solvent the residue is dissolved in water and the reaction
quenched by neutralization to pH7. The product is extracted and purified by chromatography such as HPLC.
The compound according to the invention is suitably provided in substantially pure form, for example at least 50% pure, suitable at least 60% pure, advantageously at least 75% pure, preferably at least 85% pure, more preferably at least 95% pure, especially at least 98% pure, all percentages being calculated as weight/weight. An impure or less pure form of the compound according to the invention may, for example, be used in the preparation of a more pure form of the same compound.
The compound of the invention has antibacterial activity and is useful for the prophylactic and therapeutic treatment of bacterial infections in animals, especially mammals, including humans, in particular humans and domesticated animals (including farm animals). The compound may be used for the treatment of infections caused by, among other organisms, species of Staphylococcus, Streptococcus, Aerococcus, Enterococcus, Micrococcus, actobacillus, 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.
Accordingly a third aspect of the invention provides the compound of formula (I) for use in medical therapy, in particular for use as an antibacterial agent
The invention further provides a method of treating a human or animal suffering from a bacterial infection by the administration of an effective amount of the compound of the invention.
A particular method of the invention comprises 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. The method comprises administering to the animal via the oral route an antibacterially effective amount of a compound of formula (I):
A further 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 invention further provides a pharmaceutical composition comprising a compound of the formula (I) together with a pharmaceutically acceptable diluent or carrier.
The compound of the invention can be administered alone, but will generally be administered in admixture with a pharmaceutical carrier selected with regard to the intended route of administration and standard pharmaceutical practice. For example, it may 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. It may be injected parenterally, for example, intravenously, intramuscularly or subcutaneously. For parenteral administration, it is best used in the form of a sterile solution which may contain other substances, for example, enough salts or glucose to make the solution isotonic.
For oral and parenteral administration , it is expected that the daily dosage level of the compound of formula (I) will be from 0.5 to 500, preferably 1 to 300 mg/kg (in divided doses) when administered by either the oral or parenteral route.
No unacceptable toxicological effects are expected when the compound is administered in the above mentioned dosage ranges.
The compounds and compositions according to the invention may be formulated for administration in any convenient way for use in human or veterinary medicine, by analogy with other antibacterial agents.
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 polyvinylpyrrollidone; fillers, for example lactose, sugar, maize-starch, calcium phosphate, sorbitol or glycine; 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.
Compositions according to the invention intended for topical administration may, for example, be in the form of ointments, creams, lotions, eye ointments, eye drops, ear drops, impregnated dressings, and aerosols, and may contain appropriate conventional additives, including, for example, preservatives, solvents to assist drug penetration, and emollients in ointments and creams. Such topical formulations may also contain compatible conventional carriers, for example cream or ointment bases, and ethanol or oleyl alcohol for lotions. Such carriers may constitute from about 1% to about 98% by weight of the formulation; more usually they will constitute up to about 80% by weight of the formulation.
Compositions according to the invention may be formulated as suppositories, which may contain conventional suppository bases, for example cocoa-butter or other glycerides.
Compositions according to the invention intended for parenteral administration may conveniently be in fluid unit dosage forms, which may be prepared utilizing the compound and a sterile vehicle, propyleneglycol. The compound, depending on the vehicle and concentration used, may be either suspended or dissolved in the vehicle. Parenteral suspensions may be prepared in substantially the same manner except that the compound is suspended in the vehicle instead of being dissolved and sterilisation cannot be accomplished by filtration. The compound may instead be sterilised by exposure to ethylene oxide before being suspended in the sterile vehicle. Advantageously, a surfactant or wetting agent is included in such suspensions in order to facilitate uniform distribution of the compound.
Compositions according to the invention may also be administered by inhalation. By "inhalation" is meant intranasal and oral inhalation administration. Appropriate dosage forms for such administration such as an aerosol formulation or a metered dose inhaler, may be prepared by conventional techniques.
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 polyvinylpyrrollidone, 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.
The following example serves to illustrate the present invention.
EXAMPLE 1
6-(Ethoxycarbonyl)acetyl 9 -fluoro- 3-methyl-l 0-(4-methyl-l -piperazinyl)- 7-oxo- 2,3-dihydro-7H-pyrido[3,2, 1 -ijj-l.3.4-benzoxadiazine.
Sodium hydride (0.67g, 16.7mmol of a 60% suspension in oil) was added portionwise to a stirred solution of diethyl malonate (2.67g, 16.7mmol) in dry THF (50ml). The resulting effervescent mixture turned pale yellow after 5min and was allowed to stir at room temperature for 3h (solution A). A solution of carbonyl diimidazole (1.8g, 11.12mmol) and 9-fluoro-3-methyl-10-(4-methyl-l- piperazinyl)-7-oxo-2,3-dihydro-7H-pyrido[3,2,l-ij]-l,3,4-benzoxadiazine-6- carboxylic acid (2.0g, 5.56mmol) in chloroform (50ml) was heated under reflux in an argon atmosphere for 12h. The chloroform was then evaporated in vacuo and the residue was dissolved in anhydrous THF (50ml) (solution B). Solution B was added to solution A in one portion under an argon atmosphere and the resulting mixture was heated under reflux for a period of 16h. The volatiles were then removed by evaporation in vacuo and the residue was dissolved in water (50ml). The aqueous solution was neutralised to pH 7 by careful addition of acetic acid and the resulting mixture was extracted with ethyl acetate (3 x 50ml). The combined organic extracts were dried (MgSO.}) and evaporated in vacuo. The residue was purified by normal phase HPLC using a Dynamax 300A silica column with a flow rate of l.Oml/min and 5% methanol/dichloromethane as eluant to give the title compound, retention time 20.7 min, m/z (FAB) 433 (M + 1).
Claims
1 . A compound of formula (I)
(I) wherein R is C,.6 alkyl.
2. Compound as claimed in claim 1 which is β-(ethoxycarbonyl) acetyl 9-fluoro-3-methyl-10-(4-methyl-1 -piperazinyl)-7-oxo-2,3- dihydro-7H-pyrido[3,2-1 -ij]-1 ,3,4-benzoxadiazine.
3. A process for the production of a compound of formula (I), as defined in claim 1 , which comprises treating a compound of formula (II)
(II) wherein X is a leaving group, with a carbanion derivable by treating a dialkyl malonate with a strong base.
4. A process as claimed in claim 3, wherein X is imidazolyl or halide.
5. Compound of claim 1 or claim 2 for use in medical therapy.
6. A method of treating a human or animal suffering from a bacterial infection comprising the administration of an effective amount of a compound of claim 1 or claim 2.
7. Method as claimed in claim 6 which comprises the administration via the oral route of an antibacterially effective amount of a compound of claim 1 or claim 2.
8. The use of a compound of claim 1 or claim 2 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.
9. A pharmaceutical composition comprising a compound of claim 1 or claim 2 together with a pharmaceutically acceptable diluent or carrier.
1 0. Feedstuff or drinking water for animals comprising a compound of claim 1 or claim 2.
1 1 . Premix comprising a compound of claim 1 or claim 2 together with a veterinarily acceptable carrier.
Priority Applications (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| NZ320483A NZ320483A (en) | 1996-01-17 | 1996-10-31 | Pyrido(3,2,1-ij)-1,3,4-benzoxadiazine |
| EP96935144A EP0935602A1 (en) | 1996-01-17 | 1996-10-31 | Pyrido (3,2,1-ij)-1,3,4-benzoxadiazine |
| AU73221/96A AU7322196A (en) | 1996-01-17 | 1996-10-31 | Pyrido (3,2,1-ij)-1,3,4-benzoxadiazine |
| JP9516887A JP2000501071A (en) | 1996-01-17 | 1996-10-31 | Pyrido (3,2,1-IJ) -1,3,4-benzoxadiazine |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB9600886.7 | 1996-01-17 | ||
| GBGB9600886.7A GB9600886D0 (en) | 1996-01-17 | 1996-01-17 | Novel compound |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO1997026261A1 true WO1997026261A1 (en) | 1997-07-24 |
Family
ID=10787122
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/GB1996/002674 WO1997026261A1 (en) | 1996-01-17 | 1996-10-31 | Pyrido (3,2,1-ij)-1,3,4-benzoxadiazine |
Country Status (7)
| Country | Link |
|---|---|
| EP (1) | EP0935602A1 (en) |
| JP (1) | JP2000501071A (en) |
| AU (1) | AU7322196A (en) |
| CA (1) | CA2242713A1 (en) |
| GB (1) | GB9600886D0 (en) |
| NZ (1) | NZ320483A (en) |
| WO (1) | WO1997026261A1 (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2896416B1 (en) * | 2006-01-24 | 2010-08-13 | Vetoquinol | ANTI-INFECTIOUS COMPOSITION COMPRISING A PYRIDO (3,2,1-IJ) -BENZOXADIAZINE COMPOUND |
Citations (1)
| 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 |
-
1996
- 1996-01-17 GB GBGB9600886.7A patent/GB9600886D0/en active Pending
- 1996-10-31 JP JP9516887A patent/JP2000501071A/en active Pending
- 1996-10-31 CA CA002242713A patent/CA2242713A1/en not_active Abandoned
- 1996-10-31 AU AU73221/96A patent/AU7322196A/en not_active Abandoned
- 1996-10-31 EP EP96935144A patent/EP0935602A1/en not_active Withdrawn
- 1996-10-31 NZ NZ320483A patent/NZ320483A/en unknown
- 1996-10-31 WO PCT/GB1996/002674 patent/WO1997026261A1/en not_active Application Discontinuation
Patent Citations (1)
| 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 |
Also Published As
| Publication number | Publication date |
|---|---|
| CA2242713A1 (en) | 1997-07-24 |
| AU7322196A (en) | 1997-08-11 |
| EP0935602A1 (en) | 1999-08-18 |
| GB9600886D0 (en) | 1996-03-20 |
| NZ320483A (en) | 2000-01-28 |
| JP2000501071A (en) | 2000-02-02 |
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