EP0621778A1 - $i(M. FERMENTANS) INFECTION TREATMENT - Google Patents

$i(M. FERMENTANS) INFECTION TREATMENT

Info

Publication number
EP0621778A1
EP0621778A1 EP93902424A EP93902424A EP0621778A1 EP 0621778 A1 EP0621778 A1 EP 0621778A1 EP 93902424 A EP93902424 A EP 93902424A EP 93902424 A EP93902424 A EP 93902424A EP 0621778 A1 EP0621778 A1 EP 0621778A1
Authority
EP
European Patent Office
Prior art keywords
group
denotes
carbon
optionally substituted
sulphur
Prior art date
Legal status (The legal status 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 status listed.)
Withdrawn
Application number
EP93902424A
Other languages
German (de)
French (fr)
Inventor
Peter Charles Thomas Hannan
Peter John O'hanlon
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
SmithKline Beecham Ltd
Original Assignee
SmithKline Beecham Ltd
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 SmithKline Beecham Ltd filed Critical SmithKline Beecham Ltd
Publication of EP0621778A1 publication Critical patent/EP0621778A1/en
Withdrawn legal-status Critical Current

Links

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
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/425—Thiazoles
    • 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
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
    • 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
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/42—Oxazoles
    • 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
    • A61P31/12—Antivirals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A61P37/04—Immunostimulants

Definitions

  • This present application relates to a method for treating Mycoplasma fermentans-ia ⁇ ce ⁇ infections and to compositions for use in such treatment.
  • Mycoplasma fermentans has in the past been suspected of being a human pathogen, having been occasionally isolated from human urogenital tract, from bone marrow of leukaemic patients, from synovial effusions of rheumatoid patients, as well as from tissue cultures. More recently, AIDS researchers have identified a strain of mycoplasma, since identified as M. fermentans, which it is thought may act as co-factor in the pathogenesis of AIDS (Science, vol 248, 11th May 1990). In addition, these same mycoplasma have been implicated in fulminant infections of non-AIDS patients (Amer. J. Trop. Med., Hyg, 42(5), 1990, 399). The provision of a chemotherapeutic agent with activity against M. fermentans would therefore be of assistance in the treatment of such patients.
  • the present invention provides a method 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):
  • a group R which is a 5-membered heterocyclic group having a 6 ⁇ -electron system with up to four heteroatoms which may be selected from oxygen, sulphur and nitrogen, and optionally substituted with two substituents R ⁇ and ⁇ which may be the same or different and is each selected from (C ⁇ _2 ⁇ )alkyl, (C2-8)alkenyl, (C3 tine7)cycloalkyl, aryl(C ⁇ _ g)alkyl, aryl or heterocyclyl, each of which may be optionally substituted; or
  • the invention provides for the use of a compound of formula (I) as hereinbefore defined in the manufacture of a medicament for treating M. fermentans - induced infection.
  • 'aryl' includes for example phenyl and naphthyl optionally substituted with up to five, preferably up to three, groups selected from halogen, optionally substituted (C ⁇ _g)alkyl, phenyl,
  • heterocyclyl' includes for example single or fused rings comprising up to four hetero-atoms in each ring selected from oxygen, nitrogen and sulphur and optionally substituted with up to three groups.
  • the heterocyclic ring comprises from 4 to 7 ring atoms, preferably 5 or 6 atoms.
  • Suitable substituents for 'heterocyclyl' and for heterocyclyl groups specifically named herein are selected from halogen, optionally substituted (C ⁇ _g)alkyl, (C i-.g)alkoxy, halo(C;i-.g)alkyl, hydroxy, amino, mono- or di(C-]_.g)alkylam_no, carboxy, (C ⁇ .g)alkoxycarbonyl, (C _ g)alkoxycarbonyl(C ⁇ _g)alkyl, aryl or oxo.
  • 'halogen' refers to fluorine, chlorine, bromine or iodine.
  • Suitable substituents for alkyl, alkenyl or cycloalkyl include for example halogen, hydroxy, (C ⁇ _g)alkoxy, carboxy and salts thereof, (C- ⁇ . g)alkoxycarbonyl, carbamoyl, mono- or di(C-i L .g)alkylcarbamoyl, sulphamoyl, mono- and di-(C-L_g)alkylsulphamoyl, amino, mono- and di-
  • R* denotes a group:
  • the group R ⁇ denotes a group of the formula:
  • R ⁇ denotes an optionally substituted isoxazol-5-yl, a fur-2-yl, a fur-3-yl or a pyridyl group bonded by a carbon atom thereof to the oxazolyl moiety.
  • Preferred substituents for the isoxazol-5-yl group include (C-j.. g)alkyl, and for the fur-2-yl group include cyano.
  • Example of such compounds are disclosed in EP 0 399 645 and WO 91/09856 (both to Beecham Group pic).
  • Compounds of formula (I) in which R° denotes the group -CO ⁇ are described in WO 91/09855 (Beecham Group pic).
  • compositions which comprises a compound of formula (I) (hereinafter referred to as the 'drug') together with a pharmaceutically 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 polyvinyl-pyrollidone; 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-hydroxybenzoate 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, prop
  • 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 published by Leonard Hill Books, and the British Pharmacopoeia.
  • 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.
  • 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.
  • 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.
  • 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 adult human treatment 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.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Immunology (AREA)
  • Epidemiology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Virology (AREA)
  • Communicable Diseases (AREA)
  • Oncology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)

Abstract

Certains dérivés de normonyle peuvent être utilisés pour traiter des infections induites par M. fermentans.Certain normonyl derivatives can be used to treat infections caused by M. fermentans.

Description

M. fermentans infection treatment.
This present application relates to a method for treating Mycoplasma fermentans-iaά ceά infections and to compositions for use in such treatment.
Mycoplasma fermentans has in the past been suspected of being a human pathogen, having been occasionally isolated from human urogenital tract, from bone marrow of leukaemic patients, from synovial effusions of rheumatoid patients, as well as from tissue cultures. More recently, AIDS researchers have identified a strain of mycoplasma, since identified as M. fermentans, which it is thought may act as co-factor in the pathogenesis of AIDS (Science, vol 248, 11th May 1990). In addition, these same mycoplasma have been implicated in fulminant infections of non-AIDS patients (Amer. J. Trop. Med., Hyg, 42(5), 1990, 399). The provision of a chemotherapeutic agent with activity against M. fermentans would therefore be of assistance in the treatment of such patients.
Accordingly, the present invention provides a method 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):
in which R° denotes:
(a) a group R which is a 5-membered heterocyclic group having a 6π-electron system with up to four heteroatoms which may be selected from oxygen, sulphur and nitrogen, and optionally substituted with two substituents R^ and ^ which may be the same or different and is each selected from (Cι_2θ)alkyl, (C2-8)alkenyl, (C3„7)cycloalkyl, aryl(Cι_ g)alkyl, aryl or heterocyclyl, each of which may be optionally substituted; or
(b) a group -COR^ in which R4 denotes an optionally substituted phenyl group. In a further aspect, the invention provides for the use of a compound of formula (I) as hereinbefore defined in the manufacture of a medicament for treating M. fermentans - induced infection.
When used herein, the term 'aryl' includes for example phenyl and naphthyl optionally substituted with up to five, preferably up to three, groups selected from halogen, optionally substituted (Cι_g)alkyl, phenyl,
(Cι_g)alkoxy, halo(Cι_g)alkyl, hydroxy, amino, mono- or di-(Cι_ g)alkylamino, nitro, carboxy, (Cι_g)alkoxycarbonyl, optionally substituted
(Cι_g)alkoxycarbonyl(C-t_.g)alkyl, (Cι_g)alkylcarbonyloxy, (Cχ_ g)alkylcarbonyl, (Cι_g)alkylthio, (Cι_g)alkanesulphinyl, and (Cj.
6)alkanesulphonyl.
When used herein and unless otherwise defined, the term
'heterocyclyl' includes for example single or fused rings comprising up to four hetero-atoms in each ring selected from oxygen, nitrogen and sulphur and optionally substituted with up to three groups. Suitably the heterocyclic ring comprises from 4 to 7 ring atoms, preferably 5 or 6 atoms.
Suitable substituents for 'heterocyclyl' and for heterocyclyl groups specifically named herein are selected from halogen, optionally substituted (Cι_g)alkyl, (C i-.g)alkoxy, halo(C;i-.g)alkyl, hydroxy, amino, mono- or di(C-]_.g)alkylam_no, carboxy, (Cχ.g)alkoxycarbonyl, (C _ g)alkoxycarbonyl(Cι_g)alkyl, aryl or oxo.
When used herein, the term 'halogen' refers to fluorine, chlorine, bromine or iodine.
Suitable substituents for alkyl, alkenyl or cycloalkyl include for example halogen, hydroxy, (Cι_g)alkoxy, carboxy and salts thereof, (C-χ. g)alkoxycarbonyl, carbamoyl, mono- or di(C-iL.g)alkylcarbamoyl, sulphamoyl, mono- and di-(C-L_g)alkylsulphamoyl, amino, mono- and di-
(Cχ.g)al__ylamino, (Cι.g)acylamino, ureido, (Cι.g)alkoxycarbonylamino,
2,2,2-trichloroethoxy- carbonylamino, aryl, heterocyclyl, oxo, acyl,
2-thenoyl, (Cι.g)alkylthio, arylthio, (Cι.g)alkanesulphinyl, arylsulphinyl,
(Cι.g)alkanesulphonyl, arylsulphonyl, (C-^g)alkoxyimino, hydroxyimino, hydrazono, benzohydroxyimoyl, and 2-thiophenecarbohydroxyimoyl.
Compounds of formula (I) may conveniently be named as
'(l-normon-2-yl)' derivatives. 'Normonyl' is the trivial name for the
3-[(2S,3R,4R,5S)-5-[(2S,4S,5S)-2,3- epoxy-5-hydroxy-4-methylhexyl]-3,4-dihydroxytetrahydro- pyran-2-yl]-2-methylprop-l(E)-enyl radical, as shown in formula (II):
(II)
Suitably R* denotes a group:
in which R^ and R^ are as hereinbefore defined,
X is a divalent group -Y-C=C-, and Y is oxygen or sulphur; for instance an oxazolyl, thiazolyl, isoxazolyl or isothiazolyl, preferably oxazolyl and especially oxazol-2-yl; or a group which is a trivalent, 5-membered heterocyclic group having a 6-π electron system, bonded via carbon, the five ring atoms being either one carbon atom and four atoms selected from carbon and nitrogen, two carbon atoms, two nitrogen atoms and one atom selected from oxygen and sulphur, or four carbon atoms and one atom selected from oxygen and sulphur, and R^ and R^ are as herein before defined and are each substituents on a carbon or nitrogen; for instance, a pyrrolyl, diazolyl, triazolyl, tetrazolyl, oxadiazolyl, thiadiazolyl, furyl and thiophenyl, preferably oxadiazolyl and especially 1,3,4-oxadiazolyl.
Such compounds are disclosed in EP 0 087 953 and EP 0 123 378 (Beecham Group pic).
Preferably, the group R~ denotes a group of the formula:
in which R^ denotes an optionally substituted isoxazol-5-yl, a fur-2-yl, a fur-3-yl or a pyridyl group bonded by a carbon atom thereof to the oxazolyl moiety. Preferred substituents for the isoxazol-5-yl group include (C-j.. g)alkyl, and for the fur-2-yl group include cyano. Example of such compounds are disclosed in EP 0 399 645 and WO 91/09856 (both to Beecham Group pic). Compounds of formula (I) in which R° denotes the group -CO ^ are described in WO 91/09855 (Beecham Group pic).
This invention also provides a pharmaceutical composition which comprises a compound of formula (I) (hereinafter referred to as the 'drug') together with a pharmaceutically 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 polyvinyl-pyrollidone; 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-hydroxybenzoate or sorbic acid, and if desired conventional flavouring or colouring agents.
For topical application to the skin the drug may be made up into a cream, lotion or ointment. 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 published by Leonard Hill Books, and the British Pharmacopoeia.
Suppositories will contain conventional suppository bases, e.g. cocoa-butters or other glyceride. For parenteral administration, 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.
Advantageously, adjuvants such as a local anaesthetic, preservative and buffering agents can be dissolved in the vehicle. To enhance the stability 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. Advantageously, a surfactant or wetting agent is included in the composition to facilitate uniform distribution of the drug.
For topical application to the ear, 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. For topical application to the eye, 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.
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 adult human treatment 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.
Biological Data - Compounds of formula (I) selected from those in which R° denotes an 5-substituted oxazol-2-yl or an aryl ketone were found to have geometric mean values in the range of <0.02 to 0.07μg ιrιl~l when tested against a selection of strains of M. fermentans, where determined after 6 days incubation of the organism on modified Hayflick Agar medium at 37°C.

Claims

Claims
The use of a compound of formula (I):
OH
in which R° denotes:
(a) a group R^* which is a 5-membered heterocyclic group having a 6π-electron system with up to four heteroatoms which may be selected from oxygen, sulphur and nitrogen, and optionally substituted with two substituents R^ and ^ which may be the same or different and each is selected from (Cι_2())alkyl, (C2-8)alkenyl, (C3_7)cycloalkyl, aryl(Cι_ g)alkyl, aryl or heterocyclyl, each of which may be optionally substituted; or
(b) a group -COR^ in which R4- denotes an optionally substituted phenyl group; in the manufacture of a medicament for treating M. fermentans - induced infection in humans.
2. A use as claimed in claim 1 in which the human subject is also infected with HIV.
3. A use as claimed in claim 1 or 2 in which R^ denotes a group:
in which R^ and R^ are as hereinbefore defined,
Xis a divalent group -Y-C=C-, and Y is oxygen or sulphur; for instance an oxazolyl, thiazolyl, isoxazolyl or isothiazolyl, preferably oxazolyl and especially oxazol-2-yl; or a group which is a trivalent, 5-membered heterocyclic group having a 6-π electron system, bonded via carbon, the five ring atoms being either one carbon atom and four atoms selected from carbon and nitrogen, two carbon atoms, two nitrogen atoms and one atom selected from oxygen and sulphur, or four carbon atoms and one atom selected from oxygen and sulphur, and R^ and R^ are as defined in claim 1 and are each substituents on a carbon or nitrogen.
4. A use as claimed in claim 1 or 2 in which the group R* denotes a group of the formula:
in which R > denotes an optionally substituted isoxazol-5-yl, a fur-2-yl, a fur-3-yl or a pyridyl group bonded by a carbon atom thereof to the oxazolyl moiety.
EP93902424A 1992-01-22 1993-01-20 $i(M. FERMENTANS) INFECTION TREATMENT Withdrawn EP0621778A1 (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
GB929201391A GB9201391D0 (en) 1992-01-22 1992-01-22 Method of treatment
GB9201391 1992-01-22
PCT/GB1993/000125 WO1993014752A1 (en) 1992-01-22 1993-01-20 M. fermentans infection treatment

Publications (1)

Publication Number Publication Date
EP0621778A1 true EP0621778A1 (en) 1994-11-02

Family

ID=10709071

Family Applications (1)

Application Number Title Priority Date Filing Date
EP93902424A Withdrawn EP0621778A1 (en) 1992-01-22 1993-01-20 $i(M. FERMENTANS) INFECTION TREATMENT

Country Status (5)

Country Link
EP (1) EP0621778A1 (en)
JP (1) JPH07503243A (en)
AU (1) AU3361293A (en)
GB (1) GB9201391D0 (en)
WO (1) WO1993014752A1 (en)

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7649098B2 (en) 2006-02-24 2010-01-19 Lexicon Pharmaceuticals, Inc. Imidazole-based compounds, compositions comprising them and methods of their use
TW200920355A (en) 2007-09-06 2009-05-16 Lexicon Pharmaceuticals Inc Compositions and methods for treating immunological and inflammatory diseases and disorders

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4812470A (en) * 1982-02-27 1989-03-14 Beecham Group P.L.C. Antibacterial monic acid derivatives
MX9100367A (en) * 1990-08-01 1992-04-01 Beecham Group Plc DERIVATIVES OF HETEROARILCETONE AND PROCEDURE FOR ITS PREPARATION

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO9314752A1 *

Also Published As

Publication number Publication date
GB9201391D0 (en) 1992-03-11
JPH07503243A (en) 1995-04-06
WO1993014752A1 (en) 1993-08-05
AU3361293A (en) 1993-09-01

Similar Documents

Publication Publication Date Title
JP4550417B2 (en) Polyazolidinone compounds as ligands for prostaglandin EP2 and / or EP4 receptors
US7183285B2 (en) Compositions and treatments for inhibiting kinase and/or HMG-CoA reductase
US20040204471A1 (en) Treatment and prevention of otic disorders with Cox-2 inhibitors alone or in combination with otic agents
JPH06505725A (en) Use of 5-fluoro-2&#39;-deoxy-3&#39;-thiacytidine for the treatment of hepatitis B
TNSN04246A1 (en) BENZOCONDENSIC HETEROARYLAMIDE DERIVATIVES OF THIENOPYRIDINES USEFUL AS THERAPEUTIC AGENTS, PHARMACEUTICAL COMPOSITIONS CONTAINING SAME AND METHODS FOR THEIR USE
RO121338B1 (en) Benzenesulphonamide derivatives, process for preparing the same, pharmaceutical composition and use of said derivatives as cox-2 inhibitors
IL275392A (en) Ppar agonists, compounds, pharmaceutical compositions, and methods of use thereof
JP2634202B2 (en) Antiviral compounds
DE69635114T2 (en) PROTEIN FUNGAL SYN-TRANSFERASE INHIBITORS IN COMBINATION WITH HMGCOA REDUCTASE INHIBITORS FOR THE TREATMENT OF AIDS
JPH08505868A (en) Pharmaceutical formulations consisting of clavulanic acid alone or clavulanic acid mixed with other beta-lactam antibiotics
US20190284140A1 (en) Compositions and methods for treating tuberculosis
WO2003015799A1 (en) Compositions for the treatment and prevention of pain and inflammation with a cyclooxygenase-2 selective inhibitor and chondroitin sulfate
AU2002331076A2 (en) Compositions for the treatment and prevention of pain and inflammation with cyclooxygenase-2 selective inhibitor and glucosamine
DE60215042T2 (en) BENZAZOLE DERIVATIVES FOR THE TREATMENT OF SCLERODERMA
FI120403B (en) 4- (2-Amino-6- (cyclopropylamino) -9H-purin-9-yl) -2-cyclopentene-1-methanol succinate as an antiviral agent
JP5254007B2 (en) Substituted β-lactams and their use in medicine
EP0621778A1 (en) $i(M. FERMENTANS) INFECTION TREATMENT
KR20020047329A (en) Isoxazole derivatives to be used as phosphodiesterase vii inhibitors
US11833148B2 (en) Methods for treating or limiting development of cardiovascular disease-related neurological disorders
CA2312021C (en) Use of ketolides for preparing arterial thrombotic complications related to atherosclerosis
JPH0475237B2 (en)
JPS62116555A (en) Anti-glaucoma agent substituted benzenesulfonamide
CN103827100B (en) For reducing [1,2,4] thiadiazine 1,1-dioxide compound of serum uric acid
US3592905A (en) Therapeutic methods
US5068248A (en) N-alkenyl-3-hydroxybenzo[b]thiophene-2-carboxamide derivatives as dual cyclooxygenase and lipoxygenase inhibitors

Legal Events

Date Code Title Description
PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

17P Request for examination filed

Effective date: 19940620

AK Designated contracting states

Kind code of ref document: A1

Designated state(s): BE CH DE FR GB IT LI NL

17Q First examination report despatched

Effective date: 19951222

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: THE APPLICATION IS DEEMED TO BE WITHDRAWN

18D Application deemed to be withdrawn

Effective date: 19960503