WO2002062337A1 - Thiazolidinediones - Google Patents

Thiazolidinediones Download PDF

Info

Publication number
WO2002062337A1
WO2002062337A1 PCT/US2001/049118 US0149118W WO02062337A1 WO 2002062337 A1 WO2002062337 A1 WO 2002062337A1 US 0149118 W US0149118 W US 0149118W WO 02062337 A1 WO02062337 A1 WO 02062337A1
Authority
WO
WIPO (PCT)
Prior art keywords
benzylidene
thiazolidine
dione
thiazolidin
thioxo
Prior art date
Application number
PCT/US2001/049118
Other languages
English (en)
Inventor
Dirk A. Heerding
Original Assignee
Smithkline Beecham Corporation
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 Corporation filed Critical Smithkline Beecham Corporation
Priority to JP2002562344A priority Critical patent/JP2004518697A/ja
Publication of WO2002062337A1 publication Critical patent/WO2002062337A1/fr

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
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/02—Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system

Definitions

  • This invention relates to the use of thiazolidinediones as anti-bacterials.
  • the object of this invention is to identify novel compounds having antibiotic activity.
  • compounds of the present invention have antibacterial activity and, therefore, may be useful for the treatment of bacterial infections in mammals, particularly in man.
  • This invention comprises the use of thiazolidinedione derivatives as antibacterials for the treatment of Gram positive and Gram negative bacterial infections such as respiratory tract infections, urinary tract infections, systemic and soft tissue infections , bone and joint infections, meningitis, endocarditis and sexually transmitted diseases.
  • Gram positive and Gram negative bacterial infections such as respiratory tract infections, urinary tract infections, systemic and soft tissue infections , bone and joint infections, meningitis, endocarditis and sexually transmitted diseases.
  • the present invention provides for a method of treatment of Gram positive and Gram negative bacterial infections such as respiratory tract infections, urinary tract infections, systemic and soft tissue infections , bone and joint infections, meningitis, endocarditis and sexually transmitted diseases which comprises administering to a patient in need thereof, a compound of Formula (I):
  • R 1 is independently hydrogen or C 1.3 alkyl
  • R.2 is methyl, benzyl, phenyl, napthyl, C2.4 alkenyl, or C2.4 alkynyl, wherein the benzyl, phenyl, and napthyl may be substituted or unsubstituted by one or two halogens or CF 3 ;
  • X is O or S; or a pharmaceutically acceptable salt thereof.
  • alkyl includes all straight chain and branched isomers. Representative examples thereof include methyl, ethyl, n-propyl, or wo-propyl.
  • halogen' and lialo' include fluorine, chlorine, bromine and iodine.
  • the compounds of this invention may contain one or more asymmetric carbon atoms and may exist in racemic and optically active forms. All of these compounds and diastereomers are contemplated to be within the scope of the present invention.
  • solvates may be formed.
  • This invention includes within its scope stoichiometric solvates including hydrates as well as compounds containing variable amounts of water that may be produced by processes such as lyophilisation.
  • the antibiotic compounds of the invention are intended for use in pharmaceutical compositions it will readily be understood that they are each provided in substantially pure form, for example at least 60% pure, more suitably at least 75% pure and preferably at least 85%, especially at least 95% pure, particularly at least 98% pure (% are on a weight for weight basis).
  • Impure preparations of the compounds may be used for preparing the more pure forms used in the pharmaceutical compositions; these less pure preparations of the compounds should contain at least 1%, more suitably at least 5% and preferably from 10 to 49% of a compound of the formula (I) or salt thereof.
  • R 1 is hydrogen or methyl.
  • R 2 is phenyl, (2-propenyl-4-ethoxy)phenyl, 3-(trifluoromethyl)phenyl, 2-,ethoxy- 4-chlorophenyl, 3-chloro-4-methylphenyl, 4-chloronapthyl, 3-trifluoromethyl, 3,4- dichlorophenyl, 3,5-dichlorophenyl or 4-t-butyl-phenyl.
  • X is O.
  • Preferred compounds are:
  • a suitable aldehyde such as 1-Scheme 1 is condensed with thiazolidine-2,4-dione (2-Scheme 1) in an aldol reaction.
  • the condensation is catalyzed using piperidine and benzoic acid and heated in a suitable solvent such as toluene.
  • Other catalysts such as piperidine or sodium acetate, and other solvents, such as glacial acetic acid, can also be used to carry out this reaction.
  • a representative range of conditions to carry out aldol condensations are listed by March (Advanced Organic Chemistry, Third Edition; Wiley-Interscience: New York, 1985; p 829- 834) and references cited therein.
  • the compound of this invention may be used as antibacterials for the treatment of Gram positive and Gram negative bacterial infections such as respiratory tract infections, urinary tract infections, systemic and soft tissue infections, bone and joint infections, meningitis, endocarditis and sexually transmitted diseases. Evidence of their activity is demonstrated by the following assay.
  • Biological Assay Whole-cell antimicrobial activity was determined by broth microdilution. Test compounds were dissolved in DMSO and diluted 1:10 in water to produce a 256 ug/mL stock solution. Using a 96 well microtitre plate, a Microlab AT Plus 2 (Hamilton Co., Reno, NV) serially diluted 50uL of the stock solution into cation adjusted Mueller Hinton broth.
  • test isolate ⁇ 1 x 10" cfu/ L
  • Organisms were selected from the following laboratory strains: S. aureus Oxford, S. aureus WCUH29, E. faecalis 1, E. faecalis 7, H. influenzae, Ql, H. influenzae NEMCl, M. catarrhalis 1502, S. pneumoniae 1629, S. pneumoniae N1387, S. pneumoniae ERY2, E. coli 7623 AcrABEFD + and E. coli 120 AcrAB " .
  • the minimum inhibitory concentration (MIC) was determined as the lowest concentration of compound that inhibited visible growth.
  • Compounds of this invention had at least one MIC of 64ug/mL or less.
  • the compound of Example 9 had the following MICs:
  • the present invention also provides a pharmaceutical composition that comprises a compound of formula (I) or a pharmaceutically acceptable salt or in vivo hydrolysable ester thereof and a pharmaceutically acceptable carrier.
  • the compositions of the invention include those in a form adapted for oral, topical or parenteral use and may be used for the treatment of bacterial infection in mammals including humans.
  • the antibiotic compounds according to the invention may be formulated for administration in any convenient way for use in human or veterinary medicine, by analogy with other antibiotics.
  • compositions may be formulated for administration by any route, such as oral, topical or parenteral, especially oral.
  • the compositions may be in the form of tablets, capsules, powders, granules, lozenges, creams or liquid preparations, such as oral or sterile parenteral solutions or suspensions.
  • the topical formulations of the present invention may be presented as, for instance, ointments, creams or lotions, eye ointments and eye or ear drops, impregnated dressings and aerosols, and may contain appropriate conventional additives such as preservatives, solvents to assist drug penetration and emollients in ointments and creams.
  • the formulations may also contain compatible conventional carriers, such as cream or ointment bases and ethanol or oleyl alcohol for lotions. Such carriers may be present as from about 1 % up to about 98% of the formulation. More usually they will form up to about 80% of the formulation.
  • 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, 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 such as glycerine, propylene glycol, or ethyl alcohol; preservatives, for example methyl or propyl p-hydroxybenzoate or sorbic acid, and, if desired, conventional flavoring or coloring 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, or
  • Suppositories will contain conventional suppository bases, e.g. cocoa butter or other glyceride.
  • fluid unit dosage forms are prepared utilizing the compound and a sterile vehicle, water being preferred.
  • the compound depending on the vehicle and concentration used, can be either suspended or dissolved in the vehicle.
  • the compound can be dissolved in water for injection and filter sterilized before filling into a suitable vial or ampoule and sealing.
  • the solution preferably contains a buffer (such as phosphate) to keep the pH in the range of about 3.5 to 7.
  • DMSO or alcoholic solvents may also be present (at concentrations such as 0.01 to 10 mL/liter) to aid solubility and penetration of the compound of Formula (I).
  • agents 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 the water removed under vacuum.
  • the dry lyophilized powder is then sealed in the vial and an accompanying vial of water for injection may be supplied to reconstitute the liquid prior to use.
  • Parenteral suspensions are prepared in substantially the same manner except that the compound is suspended in the vehicle instead of being dissolved and sterilization cannot be accomplished by filtration.
  • the compound can be sterilized 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 compound.
  • the compositions may contain from 0.1% by weight, preferably from 10-60% by weight, of the active material, depending on the method of administration. Where the compositions comprise dosage units, each unit will preferably contain from 50-500 mg of the active ingredient.
  • the dosage as employed for adult human treatment will preferably range from 1 to 140 mg kg of body weight, depending on the route and frequency of administration.
  • the compounds of formula (I) may be the sole therapeutic agent in the compositions of the invention or a combination with other antibiotics or compounds which enhance the antibacterial activity of a compound of formula (I) may be employed.
  • the antibiotic compounds of the present invention are active against a wide range of organisms including both Gram-negative organisms such as Escherichia coli, Haemophilus influenzae and Moraxella catarrhalis and Gram-positive organisms such as Staphylococcus aureus, Streptococcus pneumoniae and Enterococcus faecalis, including isolates resistant to existing antibiotics.
  • Gram-negative organisms such as Escherichia coli, Haemophilus influenzae and Moraxella catarrhalis
  • Gram-positive organisms such as Staphylococcus aureus, Streptococcus pneumoniae and Enterococcus faecalis, including isolates resistant to existing antibiotics.
  • Example 1 is illustrative but not limiting embodiments of the present invention.
  • Example 4 The following examples were prepared in a manner analogous to the preparation of Example 4.
  • Example 35 Formulations for pharmaceutical use incorporating compounds of the present invention can be prepared in various forms and with numerous excipients. Examples of such formulations are given below.
  • Step 1 Blend ingredients No. 1, No. 2, No. 3 and No. 4 in a suitable mixer/blender.
  • Step 2 Add sufficient water portion-wise to the blend from Step 1 with careful mixing after each addition. Such additions of water and mixing until the mass is of a consistency to permit its conversion to wet granules.
  • Step 3 The wet mass is converted to granules by passing it through an oscillating granulator using a No. 8 mesh (2.38 mm) screen.
  • Step 4 The wet granules are then dried in an oven at 140°F (60°C) until dry.
  • Step 5 The dry granules are lubricated with ingredient No. 5.
  • Step 6 The lubricated granules are compressed on a suitable tablet press.
  • Inhalant Formulation A compound of Formula I, (1 mg to 100 mg) is aerosolized from a metered dose inhaler to deliver the desired amount of drug per use.
  • a pharmaceutical composition for parenteral administration is prepared by dissolving an appropriate amount of a compound of Formula I in polyethylene glycol with heating. This solution is then diluted with water for injections Ph Eur. (to 100 ml). The solution is then sterilized by filtration through a 0.22 micron membrane filter and sealed in sterile containers.

Landscapes

  • Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Oncology (AREA)
  • Communicable Diseases (AREA)
  • Rheumatology (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Reproductive Health (AREA)
  • Endocrinology (AREA)
  • Pulmonology (AREA)
  • Epidemiology (AREA)
  • Urology & Nephrology (AREA)
  • Immunology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Cardiology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Thiazole And Isothizaole Compounds (AREA)

Abstract

L'invention concerne de nouveaux thiazolidinédiones et leur utilisation en tant qu'agents antibactériens.
PCT/US2001/049118 2000-12-18 2001-12-17 Thiazolidinediones WO2002062337A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
JP2002562344A JP2004518697A (ja) 2000-12-18 2001-12-17 チアゾリジンジオン類

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US25630000P 2000-12-18 2000-12-18
US60/256,300 2000-12-18

Publications (1)

Publication Number Publication Date
WO2002062337A1 true WO2002062337A1 (fr) 2002-08-15

Family

ID=22971724

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2001/049118 WO2002062337A1 (fr) 2000-12-18 2001-12-17 Thiazolidinediones

Country Status (2)

Country Link
JP (1) JP2004518697A (fr)
WO (1) WO2002062337A1 (fr)

Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB2387172A (en) * 2002-03-28 2003-10-08 Pantherix Ltd [(Aryl-/arylthio-)aryl]methylene substituted azole & azine derivatives and their therapeutic use as antibacterials
WO2004024061A2 (fr) * 2002-04-30 2004-03-25 Merck & Co., Inc. Thiazolidine-dione et oxazolidine-dione a substitution aryle-liaison-aryle utiles en tant que bloqueurs des canaux sodiques
WO2005007141A2 (fr) * 2003-07-11 2005-01-27 Proteologics, Inc. Inhibiteurs de l'ubiquitine ligase et methodes associees
EP1739083A1 (fr) * 2005-06-28 2007-01-03 L'Oréal Composés benzylidène-1,3-thiazolidine-2,4-diones, leurs utilisations et compositions pour stimuler ou induire la pousse des fibres kératiniques et/ou freiner leur chute et/ou augmenter leur densité.
EP2296476A1 (fr) * 2008-05-19 2011-03-23 Microbiotix, Inc. Inhibiteurs de la formation de biofilm bactérien
US20120122877A1 (en) * 2009-07-01 2012-05-17 Trustees Of Dartmouth College Compositions for Treating Bacterial Infections
KR101782618B1 (ko) * 2015-04-24 2017-10-23 조선대학교 산학협력단 미세조류 파괴용 조성물
CN112521382A (zh) * 2020-12-14 2021-03-19 西南大学 芦荟大黄素噻唑烷二酮类化合物及其制备方法和应用

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5202341A (en) * 1987-03-11 1993-04-13 Kanegafuchi Kagaku Kogyo Kabushiki Kaisha Hydroxystyrene compounds having tyrosine kinase inhibiting activity

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5202341A (en) * 1987-03-11 1993-04-13 Kanegafuchi Kagaku Kogyo Kabushiki Kaisha Hydroxystyrene compounds having tyrosine kinase inhibiting activity

Cited By (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB2387172A (en) * 2002-03-28 2003-10-08 Pantherix Ltd [(Aryl-/arylthio-)aryl]methylene substituted azole & azine derivatives and their therapeutic use as antibacterials
US7348348B2 (en) 2002-04-30 2008-03-25 Merck & Co. Inc. Aryl-link-aryl substituted thiazolidine-dione and oxazolidine-dione as sodium channel blockers
WO2004024061A2 (fr) * 2002-04-30 2004-03-25 Merck & Co., Inc. Thiazolidine-dione et oxazolidine-dione a substitution aryle-liaison-aryle utiles en tant que bloqueurs des canaux sodiques
WO2004024061A3 (fr) * 2002-04-30 2004-06-10 Merck & Co Inc Thiazolidine-dione et oxazolidine-dione a substitution aryle-liaison-aryle utiles en tant que bloqueurs des canaux sodiques
WO2005007141A2 (fr) * 2003-07-11 2005-01-27 Proteologics, Inc. Inhibiteurs de l'ubiquitine ligase et methodes associees
WO2005007141A3 (fr) * 2003-07-11 2005-03-24 Proteologics Inc Inhibiteurs de l'ubiquitine ligase et methodes associees
US7659277B2 (en) 2003-07-11 2010-02-09 Proteologies, Ltd. Ubiquitin ligase inhibitors and methods related thereto
EP1739083A1 (fr) * 2005-06-28 2007-01-03 L'Oréal Composés benzylidène-1,3-thiazolidine-2,4-diones, leurs utilisations et compositions pour stimuler ou induire la pousse des fibres kératiniques et/ou freiner leur chute et/ou augmenter leur densité.
EP2296476A1 (fr) * 2008-05-19 2011-03-23 Microbiotix, Inc. Inhibiteurs de la formation de biofilm bactérien
EP2296476A4 (fr) * 2008-05-19 2013-11-06 Microbiotix Inc Inhibiteurs de la formation de biofilm bactérien
US20120122877A1 (en) * 2009-07-01 2012-05-17 Trustees Of Dartmouth College Compositions for Treating Bacterial Infections
US9999617B2 (en) * 2009-07-01 2018-06-19 Trustees Of Dartmouth College Compositions for treating bacterial infections
KR101782618B1 (ko) * 2015-04-24 2017-10-23 조선대학교 산학협력단 미세조류 파괴용 조성물
CN112521382A (zh) * 2020-12-14 2021-03-19 西南大学 芦荟大黄素噻唑烷二酮类化合物及其制备方法和应用

Also Published As

Publication number Publication date
JP2004518697A (ja) 2004-06-24

Similar Documents

Publication Publication Date Title
CN101277695A (zh) 作为抗菌剂的喹啉衍生物
WO2005060936A1 (fr) Suspension orale de cefdinir
WO2002062337A1 (fr) Thiazolidinediones
CN113975396B (zh) 包含β-内酰胺类化合物的药物组合物及其用途
TWI387457B (zh) 作為抗細菌劑之喹啉衍生物（二）
WO2010136804A1 (fr) Dérivés de pyrimidine à utiliser en tant qu'antibiotiques
JP2005527575A (ja) 糖尿病性足病変感染を治療するためのオキサゾリジノンの非経口、静脈内および経口投与
CN106146558A (zh) 新的噁唑烷酮类化合物及其制备方法
ZA200507179B (en) Crystalline N-formyl hydroxylamine compounds
CN101541752B (zh) 抗菌的喹啉衍生物
WO2002060443A1 (fr) Thiazolidinediones
AU664767B2 (en) Composition for accelerating healing of wound
WO2002050024A2 (fr) Thiazolidinediones
JP2008534444A (ja) 新規な方法
CN101418015A (zh) 头孢曲松磷酰化衍生物
CN1321997C (zh) 一种稳定的噻丁啶喹啉羧酸盐在制备抗感染药物中的应用
CN1261439C (zh) 头孢克肟钠药物化合物及其制备方法和应用
WO2006099196A1 (fr) Nouvelle methode
CA2497410A1 (fr) Hydrazides pyrazole acide carboxylique antibacteriennes
JPH0692970A (ja) トリアゾリルチオメチルチオセファロスポリン塩酸塩およびその水和物結晶ならびにそれらの製法
JP2009519269A (ja) ジフェニル尿素誘導体
WO2009055677A1 (fr) Disulfures s-hétérosubstitués antibactériens
JP2001511451A (ja) 家畜乳房炎の治療のためのリファマイシン誘導体の使用
JP2004137185A (ja) チオフェン骨格を有する抗菌剤
WO1996006825A1 (fr) Derive ester de l'acide guanidinomethylcyclohexanecarboxylique

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A1

Designated state(s): AE AG AL AM AT AU AZ BA BB BG BR BY BZ CA CH CN CO CR CU CZ DE DK DM DZ EC EE ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX MZ NO NZ PH PL PT RO RU SD SE SG SI SK SL TJ TM TR TT TZ UA UG US UZ VN YU ZA ZW

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): GH GM KE LS MW MZ SD SL SZ TZ UG ZM ZW AM AZ BY KG KZ MD RU TJ TM AT BE CH CY DE DK ES FI FR GB GR IE IT LU MC NL PT SE TR BF BJ CF CG CI CM GA GN GQ GW ML MR NE SN TD TG

121 Ep: the epo has been informed by wipo that ep was designated in this application
DFPE Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101)
WWE Wipo information: entry into national phase

Ref document number: 2002562344

Country of ref document: JP

REG Reference to national code

Ref country code: DE

Ref legal event code: 8642

122 Ep: pct application non-entry in european phase