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WO1993015072A1 - Cetones de thiazolyle 1-normon-2-yl - Google Patents

Cetones de thiazolyle 1-normon-2-yl Download PDF

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Publication number
WO1993015072A1
WO1993015072A1 PCT/GB1993/000126 GB9300126W WO9315072A1 WO 1993015072 A1 WO1993015072 A1 WO 1993015072A1 GB 9300126 W GB9300126 W GB 9300126W WO 9315072 A1 WO9315072 A1 WO 9315072A1
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WO
WIPO (PCT)
Prior art keywords
formula
compound
ketone
thiazol
normon
Prior art date
Application number
PCT/GB1993/000126
Other languages
English (en)
Inventor
Andrew Keith Forrest
Jean Esther Pons
Peter John O'hanlon
Original Assignee
Smithkline Beecham Plc
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
Priority claimed from GB929201506A external-priority patent/GB9201506D0/en
Priority claimed from GB929215889A external-priority patent/GB9215889D0/en
Application filed by Smithkline Beecham Plc filed Critical Smithkline Beecham Plc
Priority to JP5513016A priority Critical patent/JPH07503244A/ja
Priority to EP93902425A priority patent/EP0623130A1/fr
Publication of WO1993015072A1 publication Critical patent/WO1993015072A1/fr

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 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

Definitions

  • This invention relates to a novel class of compounds having antibacterial and antimycoplasmal activity, to processes for their preparation and to their use in human and veterinary medicine.
  • Rl is a 2-(optionally substituted (C ⁇ . ⁇ o)alkoxy)thiazol-5-yl group, that is a group of the formula:
  • R is optionally substituted (C ⁇ .i Q )aIkoxy.
  • Suitable optional substituents for the Qi.iQ)aikoxy group include, for example, halogen, cyano, azido, nitro, carboxy, (C ⁇ _g)alkoxycarbonyl, carbamoyl, mono- and di-(C ⁇ _g)alkylcarbamoyl, sulpho, sulphamoyl, mono- or di-(C ⁇ _g)alkylsulphamoyl, amino, mono-and di-(C ⁇ _ g)alkylamino, acylamino, ureido, (C ⁇ _g)alkoxycarbonylamino, 2,2,2- trichloroethoxycarbonylamino, trialkylthiomethyl, optionally substituted aryl, optionally substituted heterocyclyl, hydroxy, (C ⁇ _g)alkoxy, acyloxy, oxo, acyl, 2-thenoyl, (C ⁇ _g)alkylthio, (C ⁇ _
  • R is optionally substituted (C ⁇ _g)alkoxy, preferably optionally substituted methoxy, ethoxy or hexoxy, more preferably methoxy, most preferably unsubstituted methoxy.
  • Rl is 2- methoxythiazol-5-yl
  • the term 'aryl' includes, unless otherwise defined, phenyl or naphthyl.
  • the aryl ring may be optionally substituted with up to five, preferably up to three substituents.
  • Suitable substituents include, for example, halogen, cyano, (C ⁇ .g)alkyl, phenyl, (C ⁇ .g)alkoxy, halo(C ⁇ .g)alkyl, hydroxy, amino, mono- or di-(C ⁇ _g)alkylamino, acylamino, nitro, carboxy, (C ⁇ _g)alkoxycarbonyl, (C ⁇ .g)- alkoxycarbonyl(C ⁇ _g)alkyl, (C ⁇ _g)alkylcarbonyloxy, (C ⁇ .g)al ⁇ lthio, (C ⁇ _ g)alkylsulphinyl, (C ⁇ _g)alkylsulphonyl, sulphamoyl, mono- or di-(C ⁇
  • heterocyclyl' includes aromatic and non-aromatic single or fused rings comprising up to four hetero-atoms in the ring selected from oxygen, nitrogen and sulphur.
  • the heterocyclic ring comprises from 4 to 7, preferably 5 to 6, ring atoms.
  • a fused heterocyclic ring system may include carbocyclic rings and need only include one heterocyclic ring.
  • the heterocyclyl ring may be optionally substituted with up to three substituents.
  • Suitable substituents include, for example, halogen, (C ⁇ _g)alkyl, (C ⁇ _g)alkoxy, halo(C ⁇ _g)alkyl, hydroxy, amino, mono- or di-(C ⁇ _g)alkylamino, carboxy, (C ⁇ .g)alkoxycarbonyl, (C ⁇ _ g)alkoxycarbonyl(C ⁇ _g)alkyl, aryl and oxo.
  • 'halogen' refers to fluorine, chlorine, bromine or iodine.
  • Compounds of formula (I) may conveniently be named '(l-normon-2- yl ketones'.
  • Normonyl is the trivial name for the 3-[(2S,3R,4R,5S)-5-
  • the compounds of formula (I) of the present invention are intended for use in pharmaceutical compositions, it will be understood that they are each provided in substantially pure form, for example at least 50% pure, more suitably at least 75% pure and preferably at least 95% pure (% are on a wt/wt basis). Impure preparations of the compounds of formula (I) may be used for preparing the more pure forms used in the pharmaceutical compositions. Although the purity of intermediate compounds of the present invention is less critical, it will be readily understood that the substantially pure form is preferred as for the compounds of formula (I). Preferably, whenever possible, the compounds of the present invention are obtained in crystalline form.
  • solvent of crystallisation may be present in the crystalline product.
  • This invention includes within its scope such solvates.
  • some of the compounds of this invention may be crystallised or recrystallised from solvents containing water. In such cases water of hydration may be formed.
  • This invention includes within its scope stoichiometric hydrates as well as compounds containing variable amounts of water that may be produced by processes such as lyophilisation.
  • a preferred example of a compound within this invention is 2- methoxy-(thiazol-5-yl)- l-(normon-2-yl) ketone.
  • compounds of the present invention may be prepared by methods known for the preparation of ⁇ , ⁇ -unsaturated ketones. Some of these processes will be more appropriate than others.
  • compounds of formula (I) may be prepared by a process which comprises treating an arid of formula (IH):
  • Z 2 and 2s- are the same or different and each is hydrogen or a hydroxyl-protecting group, or an activated derivative thereof, with an organometallic reagent; and thereafter, and if necessary, removing any hydroxyl-protecting groups.
  • Suitable organometallic reagents include:
  • the reaction with the organometallic reagent may be conveniently carried out in an ethereal or hydrocarbon solvent, the choice of which is dependent upon the specific requirements of the organometallic reagent.
  • the Grignard reagent is generated and used in diethyl ether or tetrahydrofuran.
  • the reaction is generally carried out in an inert atmosphere such as argon or nitrogen and at ambient temperature or below.
  • the period for which the reaction is allowed to proceed depends upon the particular starting materials employed.
  • the course of the reaction may be followed by conventional methods such as thin layer chromatography and the reaction may be terminated when an optimum quantity of product is present in the reaction mixture.
  • the compound of formula (III) in which 7 , Z ⁇ and Z ⁇ is each hydrogen is monic acid, the preparation of which is described in GB 1 587 058 (Beecham Group).
  • Suitable activated derivatives of the acid of formula (III) include thio-esters of formula (IV):
  • thio-esters are of formula (IVa):
  • a compound of formula (IVa) may be prepared by treating of a compound of formula (III) with 2,2'-dipyridyl disulphide in the presence of triphenylphosphine, by analogy with the metiiod described by E.J. Corey and D.A Clark in Tetrahedron Letters, 1979, 31, 2875.
  • Other suitable activated derivatives of the acid of formula (III) include mixed anhydrides of the formula (V):
  • a compound of formula (V) may be obtained by treating a compound of formula (III) with, for instance, a suitable derivative of the formula
  • a compound of formula (VT) may be obtained by treating a compound of formula (m) with C1POR3R4 ⁇ using the metiiod described by Baxter A.J.G. et al., Tetrahedron Letters, 1980, 21, 5071.
  • Z--, Z 2 and Z ⁇ are as hereinbefore defined and B and R ⁇ , together with the nitrogen atom to which they are bonded, form an imidazolyl or triazolyl ring.
  • a preferred compound of formula (VII) is the N-methoxy-N- methylamide (i.e. R ⁇ and R ⁇ is each methyl) as described in WO 91/09855 (Beecham Group).
  • the reaction of an N-methoxy-N-methylamide with an organolithium or a Grignard reagent to form a ketone is described by Nahm and Weinreb in Tetrahedron Letters, 1981, 3815.
  • a preferred amide of formula (VIII) is the imidazol-1-yl derivative.
  • the reaction of an ⁇ , ⁇ -unsaturated acid or its imidazolyl derivative with a Grignard reagent is described in Chem. Ber., 1965, 95 1284.
  • Amides of formulae (VII) and (VIII) may suitably be obtained from monic acid acid by treatment thereof with iso-butyl chloroformate in tetrahydrofuran, in the presence of triethylamine, at a temperature of from -5 to 20°C, for about 30 min, to form an intermediate mixed anhydride (monic acid iso-butyl carbonic anhydride).
  • This intermediate may then be reacted with an amine HN(OR5)R6 in dichloromethane at about 20°C for about 2h or an amine HNR ⁇ R8.HC1 in the presence of triethylamine and 4-dimethylaminopyridine, in THF, at about 20°C, to form the compound of formula (VII) in which Z--, Z 2 and Z ⁇ is each hydrogen (with Rl, R ⁇ , R6, R7 and R ⁇ as hereinbefore defined).
  • the hydroxyl groups thereof may then be protected by treatment with a suitable hydroxyl protecting agent such as chlorotrimethylsilane, in a solvent such as THF in the presence of triethylamine and 4-dimethyl- amino pyridine as a catalyst.
  • a thio-ester of formula (IV) is preferably treated with an organomanganous reagent of formula R ⁇ MnCl, as hereinbefore defined whilst an amide of formula (VII) or (VIII) is preferably treated with an organolithium reagent of formula R ⁇ -Li as hereinbefore defined.
  • a compound of formula (I) is prepared by a process which comprises treating a compound of formula (VH), as hereinbefore defined, with an organolithium reagent of formula R ⁇ Li as hereinbefore defined.
  • Suitable organometallic reagents may be prepared according to conventional procedures.
  • suitable organomanganous reagents of the formula RlMnCl may be conveniently prepared by adding an organolithium reagent R ⁇ Li to a solution of manganous chloride and lithium chloride in dry THF, or a suspension of anhydrous manganous chloride in dry THF. An excess of R ⁇ MnCl is preferably employed.
  • a Grignard reagent may be used in place of the organolithium reagent, to generate the organomanganous reagent
  • organomanganous reagents which may be used instead of iMnCl include:
  • Organocerium reagents may be generated in situ by treating an organolithium compound of the formula R ⁇ -Li, in which R ⁇ is as hereinbefore defined, with cerium (III) halide, by analogy with the procedure described by Imamoto et al; J Chem Soc, Chem Commun, 1982,
  • B,--, Z--, Z 2 and Z ⁇ are as hereinbefore defined, with an oxidising agent which converts allylic alcohols into ⁇ , ⁇ -unsaturated ketones, and thereafter, and if necessary, removing any hydroxyl-protecting groups.
  • Suitable such oxidising agents include activated manganese dioxide, pyridinium dichromate and pyridinium chlorochromate.
  • the oxidation reaction is carried out in a non-polar organic solvent such as, for example, benzene or toluene.
  • An aldehyde of formula (X) may be treated with a Grignard reagent of formula R ⁇ MgX or, more preferably, with an organocerium reagent RlLi-CeX3, as hereinbefore defined.
  • An aldehyde of formula (X) may be prepared by treating an amide of formula (V ⁇ ), as hereinbefore defined, with a suitable reducing agent such as di-iso-butyl-aluminium hydride, and thereafter, and if necessary, removing any hydroxyl-protecting group.
  • a suitable reducing agent such as di-iso-butyl-aluminium hydride
  • Other suitable methods of preparation of an aldehyde of formula (X) are described in EP-A-0 029 665 (Beecham Group).
  • a compound of formula (I) may also be prepared by treating a ketone of formula (XI):
  • a compound of formula (XI) is described in GB 1 587 060 (Beecham Group).
  • the term 'hydroxyl-protecting group' refers to any such group known in the art which may be removed without disruption of the remainder of the molecule. Suitable hydroxyl-protecting groups include those described in 'Protective Groups in Organic Synthesis', T.W. Greene, Wiley-Interscience, New York 1981.
  • the hydroxyl groups of the compounds of formulae (IEI) to (XT) may be protected at any stage of the above processes, using conventional methods.
  • the hydroxyl-protecting group may be removed by methods known in the art, including enzymatic methods.
  • Particularly suitable hydroxyl protecting groups are silyl groups since these are readily removed under mild conditions.
  • Such groups are introduced using conventional silylating agents, including halosilanes and silazanes, of the formulae:
  • Me 3 Si- V N wherein Me denotes methyl and *Bu denotes t-butyl, Y is halogen and each group L is independently selected from hydrogen, (C ⁇ _g)alkyl, (C ⁇ . g)alkoxy, aryl or aryl(C ⁇ _4)alkyl.
  • a preferred silyating agent is trimethylsilyl chloride.
  • Particularly suitable protecting groups are trimethylsilyl, t-butyldimethylsilyl and t-butyldiphenylsilyl groups. Preferred protecting groups are trimethylsilyl groups because of their ease of removal.
  • glycol function of the compounds of formulae (HI) to (XI) may be protected by forming a cyclic derivative using a compound of formula ⁇ ):
  • R ⁇ is hydrogen, methyl, ethyl, n- or iso- propyl; most suitably it is hydrogen.
  • the groups R*0, R ⁇ and R* 2 are suitably methyl, ethyl, n- or zso-propyl, or n-, iso-, sec- or if-butyl; most suitably methyl.
  • hydroxyl groups of a compound of formula (I) may be protected prior to conversion to a further compound of formula (I) as described above.
  • the hydroxyl protecting groups described above may be removed by mild acid hydrolysis followed by alkaline hydrolysis, for instance, as described by Clayton et al, JCS Perkin Trans 1, 1979, 308.
  • compositions which comprise a compound of formula (I) (hereinafter referred to as the 'drug') together with a pharmaceutically or veterinarily acceptable carrier or excipient.
  • the compositions may be formulated for administration by any route, and would depend on the disease being treated.
  • the compositions may be in the form of tablets, capsules, powders, granules, lozenges, liquid or gel preparations, such as oral, topical or sterile parenteral suspensions.
  • Tablets and capsules for oral administration may be in unit dose presentation form, and may contain conventional excipients such as binding agents, for example syrup, acacia, gelatin, sorbitol, tragacanth, or polyvinylpyrollidone; 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, or acceptable wetting agents such as 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 other suitable vehicle before use.
  • Such liquid preparations may contain conventional additives such as suspending agents, for example sorbitol, syrup, methyl cellulose, glucose syrup, gelatin, hydrogenated edible fats; emulsifying agents, for example lecithin, sorbitan monooleate, or acacia; non-aqueous vehicles (which may include edible oils), for example almond oil, fractionated coconut oil, oily esters such as glycerine, propylene glycol, or ethyl alcohol; preservatives, for example methyl or propyl p-hydroxy- benzoate or sorbic acid, and if desired conventional flavouring or colouring agents.
  • suspending agents for example sorbitol, syrup, methyl cellulose, glucose syrup, gelatin, hydrogenated edible fats
  • emulsifying agents for example lecithin, sorbitan monooleate, or acacia
  • non-aqueous vehicles which may include edible oils
  • almond oil fractionated coconut oil
  • oily esters such as glycerine,
  • Cream or ointment formulations that may be used for the drug are conventional formulations well known in the art, for example, as described in standard text books of pharmaceutics and cosmetics, such as 'Harry's Cosmeticology 1 7th Ed., ed Wilkinson J.B. and Moore R. J., George Goodwin, London, 1982, and the British
  • the drug may be made up into a suspension in a suitable liquid carrier, such as water, glycerol, diluted ethanol, propylene glycol, polyethylene glycol or fixed oils.
  • a suitable liquid carrier such as water, glycerol, diluted ethanol, propylene glycol, polyethylene glycol or fixed oils.
  • the drug is formulated as a suspension in a suitable, sterile aqueous or non-aqueous vehicle.
  • Additives for instance buffers such as sodium metabisulphite or disodium edetate; preservatives including bactericidal and fungicidal agents, such as phenylmercuric acetate or nitrate, benzalkonium chloride or chlorhexidine, and thickening agents such as hypromellose may also be included.
  • the dosage employed for compositions administered topically will, of course, depend on the size of the area being treated. For the ears and eyes each dose will typically be in the range from 10 to 100 mg of the drug.
  • Suppositories will contain conventional suppository bases, e.g. cocoa-butters or other glyceride.
  • fluid unit dosage forms are prepared utilizing the drug and a sterile vehicle.
  • the drug depending on the vehicle and concentration used, can be suspended in the vehicle.
  • adjuvants such as a local anaesthetic, preservative and buffering agents can be dissolved in the vehicle.
  • the composition can be frozen after filling into the vial and water removed under vacuum. The dry lypophilized powder is then sealed in the vial.
  • the drug can be sterilised by exposure to ethylene oxide before suspending in the sterile vehicle.
  • a surfactant or wetting agent is included in the composition to facilitate uniform distribution of the drug.
  • compositions for intramammary treatment of mammary disorders in animals will generally contain a suspension of the drug in an oily vehicle.
  • the compositions may contain from 0.1% to 99% by weight, preferably from 10-60% by weight, of the drug, depending on the method of administration. Where the compositions are in unit dose form, each dosage unit will preferably contain from 50-500 mg, of the drug.
  • the dosage as employed for treating an adult human will preferably range from 100 mg to 3 g, per day, for instance 250 mg to 2 g of the drug per day, depending on the route and frequency of administration.
  • the drug may be administered to non- human animals as part of the total dietary intake.
  • the amount of drug employed may be less than 1% by weight of the diet and in preferably no more than 0.5% by weight.
  • the diet for animals may consist of normal foodstuffs to which the drug may be added or the drug may be included in a premix for admixture with the foodstuff.
  • a suitable method of administration of the drug to a non-human animal is to add it to the non-human animal's drinking water. In this case a concentration of the drug in the drinking water of about 5-500 ⁇ g/ml, for example 5-200 ⁇ g/ml, is suitable.
  • the compounds of this invention are useful for treating bacterial and mycoplasma-induced infections in non-human and human animals, such as the treatment of respiratory tract infections, otitis, meningitis, skin and soft tissue infections in human animals, mastitis in cattle, and respiratory infections in non-human animals such as pigs and cattle.
  • the present invention provides a method for treating a human or non-human animal which method comprises administering an effective amount of a compound of formula (I) as hereinbefore defined, to a human or non-human animal in need of such therapy.
  • a pharmaceutical composition as hereinbefore described may be employed in the treatment.
  • the compounds of this invention are active against both Gram negative and Gram positive organisms, including Haemophilus, for instance H.influenzae Ql; Branhamella,fo ⁇ instance B.Catarrhalis 1502; Streptococci, for instance S.pyogenes CN10 and S.pneumonia PU7; and Staphylococci, for instance S.aureus Oxford; Legionella, for instance L. pneumophila.
  • compounds of this invention are active against Staphylococci organisms such as S. aureus and S.
  • the present invention provides a metiiod of treating humans infected with M. fermentans, in particular humans also infected with HIV, which method comprises treating humans in need of such therapy with an anti- mycoplasmal effective amount of a compound of formula (I).
  • the present invention provides a compound of formula (I) for use in the manufacture of a medicament for antibacterial and/or antimycoplasmal therapy in human and nonhuman animals. No adverse toxicological effects are expected from the administration of a compound of formula (I).
  • Example 1 2-Methoxy-(tl ⁇ azol-5-yl)-l-(normon-2-yl) ketone -
  • N-methoxy-N-methyl-6,7,13-0-i - (trimethylsilyl) monamide (15.4g, l.OOmmolXWO 92/02518, Beecham Group pic) in dry THF (160ml) was added dropwise, whilst maintaining the temperature below -65°C (addition time lh).
  • acetic acid 7.7ml was added.
  • THF trimethylsilyl
  • N-methoxy-N-methyl-6,7,13-0-£ris(trimethylsilyl) monamide (2mmol, 1.206g) in THF (10ml) was added dropwise. After 2 ⁇ hours and warming to -50°C glacial acetic acid (4mm ol, 0.2ml) was added followed by water (10ml).
  • TCM Eagle's Minimal Essential Midium + Earles' salts supplemented with 10% foetal calf serum, 2mM L-glutamine and 1% non-essential amino acids
  • the suspension was further diluted 1:100 in TCM to yield a final inoculum of l ⁇ 4.83 x l ⁇ 6 cfu ml.
  • Human foetal lung fibroblast (MRC- ⁇ ) cells were then inoculated. Thes cells had been previously grown to 80% confluency in 6- well plates, the medium removed and the monolayers washed twice with Dulbecco's PBS. Sixteen hours after inoculation(time 0 h), the medium was removed and the inoculated monolayers washed twice to remove any
  • Test compound prepared to the required concentrations in TCM, was added to the cells.
  • the compound of Example 1 was tested at O. ⁇ , 2 and 8 ⁇ g/ml whilst erythromycin at O. ⁇ and 2 ⁇ g ml was used as a control.
  • O. ⁇ , 2 and 8 ⁇ g/ml whilst erythromycin at O. ⁇ and 2 ⁇ g ml was used as a control.
  • the medium was removed from one well/treatment, and the

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  • 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)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Steroid Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)

Abstract

Cétones de normonyle 2-(C1-10)alkoxythiazol-5-yl éventuellement substituées de formule (I): dans laquelle R1 représente un groupe 2-((C¿1-10?)alkoxy éventuellement substitué) thiazole-5-yl. Les cétones sont destinées à être utilisées en thérapie anti-bactérienne ou anti-mycoplasmique.
PCT/GB1993/000126 1992-01-24 1993-01-20 Cetones de thiazolyle 1-normon-2-yl WO1993015072A1 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
JP5513016A JPH07503244A (ja) 1992-01-24 1993-01-20 抗菌性１−ノルモン−２−イルチアゾリルケトン類
EP93902425A EP0623130A1 (fr) 1992-01-24 1993-01-20 Cetones de thiazolyle 1-normon-2-yl

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
GB929201506A GB9201506D0 (en) 1992-01-24 1992-01-24 Novel compounds
GB9201506.4 1992-01-24
GB9215889.8 1992-07-25
GB929215889A GB9215889D0 (en) 1992-07-25 1992-07-25 Novel compounds

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WO1993015072A1 true WO1993015072A1 (fr) 1993-08-05

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EP (1) EP0623130A1 (fr)
JP (1) JPH07503244A (fr)
CN (1) CN1088926A (fr)
AU (1) AU3361393A (fr)
IL (1) IL104486A0 (fr)
MX (1) MX9300325A (fr)
SI (1) SI9300036A (fr)
WO (1) WO1993015072A1 (fr)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1995005384A1 (fr) * 1993-08-13 1995-02-23 Smithkline Beecham Plc Derives d'acides moniques a et c a activite antibacterienne, antimycoplasmique, antifongique et herbicide
GB2282537A (en) * 1993-10-06 1995-04-12 Zeneca Ltd Herbicidal compositions containing ketones derived from monic acid

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0029665A1 (fr) * 1979-11-10 1981-06-03 Beecham Group Plc Dérivés antibactériens de l'acide monique, procédés pour leur préparation et compositions les contenant
WO1992002518A1 (fr) * 1990-08-01 1992-02-20 Beecham Group Plc Derives de mupirocine

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0029665A1 (fr) * 1979-11-10 1981-06-03 Beecham Group Plc Dérivés antibactériens de l'acide monique, procédés pour leur préparation et compositions les contenant
WO1992002518A1 (fr) * 1990-08-01 1992-02-20 Beecham Group Plc Derives de mupirocine

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
JOURNAL OF THE CHEMICAL SOCIETY, PERKIN TRANSACTIONS 1, no. 11, November 1989, Letchworth, GB, pages 2047 - 2057 M.J. CRIMMIN, ET AL.: 'The chemistry of pseudomonic acid. Part 10. Preparation of heterocyclic derivatives' *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1995005384A1 (fr) * 1993-08-13 1995-02-23 Smithkline Beecham Plc Derives d'acides moniques a et c a activite antibacterienne, antimycoplasmique, antifongique et herbicide
GB2282537A (en) * 1993-10-06 1995-04-12 Zeneca Ltd Herbicidal compositions containing ketones derived from monic acid

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Publication number Publication date
EP0623130A1 (fr) 1994-11-09
SI9300036A (en) 1993-09-30
IL104486A0 (en) 1993-05-13
MX9300325A (es) 1993-07-01
JPH07503244A (ja) 1995-04-06
CN1088926A (zh) 1994-07-06
AU3361393A (en) 1993-09-01

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