US3769295A - Nitrofuryl derivatives of 5-substituted isoxazolines - Google Patents

Nitrofuryl derivatives of 5-substituted isoxazolines Download PDF

Info

Publication number
US3769295A
US3769295A US00752479A US75247968A US3769295A US 3769295 A US3769295 A US 3769295A US 00752479 A US00752479 A US 00752479A US 75247968 A US75247968 A US 75247968A US 3769295 A US3769295 A US 3769295A
Authority
US
United States
Prior art keywords
nitro
furyl
isoxazoline
product
allyl
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.)
Expired - Lifetime
Application number
US00752479A
Other languages
English (en)
Inventor
W Hoyle
G Howarth
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.)
Novartis Corp
Original Assignee
Ciba Geigy Corp
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 Ciba Geigy Corp filed Critical Ciba Geigy Corp
Application granted granted Critical
Publication of US3769295A publication Critical patent/US3769295A/en
Anticipated expiration legal-status Critical
Expired - Lifetime legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • 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

Definitions

  • the invention relates to nitrofuryl derivatives having valuable pharmacological properties and in particular to S-nitro-Z-furyl-Z isoxazolines exhibiting antimicrobial activity. It further relates to pharmaceutical compositions containing these compounds as well as to methods for the treatment of mammals sufiering from microbial infections, particularly urinary tract infections, by administering to said mammals an effective amount of a compound according to the invention.
  • the invention also provides methods for protecting organic material susceptible to microbial attack by treating said material with an eiiective amount of a compound according to the invention.
  • R represents chlorine or bromine; cyano, amino, 2,3- epoxypropoxy, morpholino, piperidino or pyrrolidino; the grouping -SR -OR --O.CO.R CH .CO.R or N(R ).R wherein R represents alkyl having from 1 to 3 carbon atoms; the grouping NH.CO.R wherein R represents alkoxy having from 1 to 3 carbon atoms, cycloalkyl having from 5 to 7 carbon atoms in the carbocyclic ring, alkyl having from 1 to 6 carbon atoms or alkyl having from 1 to 6 carbon atoms substituted by one or two chlorine atoms, bromine atoms, alkoxy groups having from 1 to 6 carbon atoms, alkoxycarbonyl groups having from 2 to 7 carbon atoms, or cyano groups; ureido or ureido N-substituted by one to three al
  • R represents hydrogen or alkyl having from 1 to 3 carbon atoms have not been known up to now.
  • Representative compounds of this scope which have been found to possess antimicrobial properties, especially antibacterial properties to a favourable degree are:
  • the subject S-nitro-2-furyl-2-isoxazolines of the Formula I, given above may be prepared by reacting a 5-nitro-2-furyl nitrile oxide having the Formula II with an ethene derivative having the Formula III RzCHzR (III)
  • the reaction is conveniently effected by generating the nitrile oxide of Formula II as required during the course of the reaction from the corresponding 5-nitro-2-furohydroxamoyl halide having the Formula IV wherein X represents halogen.
  • the 5-nitro-2-furohydroxamoyl halide of Formula IV and the ethene derivative of Formula III are preferably contacted in the presence of a basic condensation promotor, for example sodium methoxide.
  • the compound of Formula IV may be directly reacted with the compound of 'Formula III, preferably by heating together in the presence of toluene or other inert solvent.
  • the S-nitro-2-furohydroxamoyl halide of Formula IV is preferably the chloride or bromide.
  • the halides may be prepared by conventional methods: the chloride may be obtained, for instance, by the method described by Doyle, Hanson, Long and Nayler in the Journal of the Chemical Society (1963) at page 5845 or by that described in Helvetica Chimica Acta (1963) volume 46 at page 1067.
  • the halide used as starting material in the process of the invention may be a purified product or it may be the crude product as prepared, if desired after partial purification.
  • the compounds of the invention have useful pharmacological and, in particular, antimicrobial properties, being valuable antibacterial, antifungal, antiviral, antihelminthic and coccidiostatic agents.
  • the compounds are thus suitable for internal or external veterinary and medicinal use and are particularly valuable in the treatment of infections of the intestinal and, more especially, the urinary tract.
  • the present invention further provides a method for the treatment of a mammal suffering from a microbial infection, which method comprises administering to said mammal a therapeutically effective amount of a compound of the Formula I as hereinbefore defined, and in a particular aspect the invention provides a method for the treatment of a mammal suffering from a urinary tract, microbial infection, which method comprises administering to said mammal a therapeutically etfective amount of a compound of the Formula I as hereinbefore defined.
  • the specific compounds listed above are of special interest.
  • compositions according to the invention contain at least one compound of General Formula I as active substance together with a conventional pharmaceutical carrier.
  • a conventional pharmaceutical carrier for external use, for example in disinfecting healthy skin, disinfecting wounds and in treating dermatoses and affections of the mucous membranes caused by bacteria, ointments, powders and tinctures are used in particular.
  • the ointment bases may be anhydrous, for instance, they can consist of mixtures of wool fat and soft paraifin, or they can consist of aqueous emulsions in which the active substance is suspended.
  • Suitable carriers for powders are, for instance, rice starch and other starches; the bulk weight of the carriers may be made lighter, if desired, for example by adding highly dispersed silicic acid, or may be made heavier by adding talcum.
  • the tinctures may contain at least one active ingredient of the Formula I in aqueous ethanol, in particular 45% to 75% by weight ethanol, to which to 20% by weight of glycerol may be added, if desired. Solutions prepared from polyethyleue glycol and other conventional solubility promoters, and also optionally, from emulsifying agents, may be used with particular advantage in disinfecting healthy skin.
  • the content of active ingredient in pharmaceutical compositions for external application is preferably in the range of from 0.1% to 5% by weight.
  • Gargles or concentrates for their preparation, and tablets for slow dissolution in the mouth are suitable for the disinfection of the mouth and throat.
  • the former are preferably prepared from alcoholic solutions containing 1% to 5% by weight of active substance to which glycerol or fiavourings may be added.
  • Lozenges that is solid dosage units, preferably have a relatively high content of sugar or similar substances and a relatively low content of active substance, for instance 0.2% to 20% by weight, as well as the usual conventional additives such as binding agents and fiavourings.
  • Solid dosage units in particular tablets, drages (sugar coated tablets) and capsules, are convenient for use in intestinal disinfection and for the oral treatment of urinary tract infections. These units preferably contain from 10% to 90% by weight of the comp of the general Formula I to enable the administration of daily doses of from 0.1 to 2.5 grams to adult mammals, or of suitably reduced doses to children, to be made.
  • Tablets and drage cores are produced by combining the compounds of the general Formula I with solid, pulverulent carriers such as lactose, saccharose, sorbitol, maize starch, potato starch or amylopectin, cellulose derivatives or gelatines, preferably with the addition of lubricants such as magnesium or calcium stearate or polyethylene glycols of suitable molecular weight.
  • Drage cores may then be coated, for example with concentrated sugar solutions which can also contain gum arabic, talcum and/0r titanium dioxide, or they may be coated with a lacquer dissolved in volatile organic solvents or mixture of solvents.
  • Dyestuffs can be added to these coatings, for instance to differentiate between varying dosages.
  • Soft gelatine capsules and other closed capsules consist, for example, of a mixture of gelatines and glycerol and may contain, for example mixtures of a compound of Formula I with polyethylene glycol.
  • Hard gelatine capsules contain, for example, granulates of an active substance with solid pulverulent carriers, for instance lactose, saccharose, sorbitol, mannitol, starches (such as potato starch, maize starch or amylopectin), cellulose derivatives of gelatine, and magnesium stearate or stearic acid.
  • compounds of the General Formula I can be present as sole active ingredients or they can also be combined with other known pharmacologically active, and especially antibacterial and/ or antimycotically or other antimicrobially active substances, for example, to broaden the range of application.
  • Daily dosages for example for the treatment of urinary tract infections, are preferably of the order of from about 1 to 100, or more preferably from about 1 to 40 mg./kg. administered orally.
  • the compounds of the invention have been shown to exhibit valuable antimicrobial and notably anti-bacterial properties in vitro and are thus suitable for use in the protection of organic materials susceptible to microbial attack.
  • organic material include synthetic polymeric materails, proteinaceous or carbohydrate substances or natural or synthetic fibres or textile materials produced therefrom.
  • the present invention further provides a method for protecting organic material susceptible to microbial attack, which process comprises treating said material with an effective amount of a compound of the Formula I as hereinbefore defined.
  • a compound of the Formula I as hereinbefore defined.
  • EXAMPLE 1 A solution of 2.3 grams of metallic sodium dissolved in 50 millilitres of anhydrous methanol was added slowly to a mixture of 19.1 grams of 5-nitro-2-furohydroxamoyl chloride and 6.7 grams of allyl cyanide dissolved in 150 millilitres of anhydrous methanol at to After allowing to stand, the crystalline precipitate which formed was collected, washed with water and recrystallised from a mixture of water and ethanol.
  • the product was 5-cyanomethyl-3-(5-nitro-2-furyl)-2- isoxazoline, having melting point 165.
  • the product was 5-methyhnercaptomethyl-3-(S-nitro- 2-furyl)-2-isoxazoline, having melting point 130".
  • the product was 5-(2,3-epoxy-1-propoxymethyl)-3- (S-nitro-Z-furyl)-2-isoxazo1ine, having melting point 81.
  • the product was 5-acetoxymethyl-3-(5-nitro-2-furyl)- 2-isoxazoline, having melting point 136.
  • the product was 5 acetamidomethyl 3 (5-nitro-2- furyl)-2-isoxazoline, having melting point 164.
  • the product was 5-(but-3-one-l-yl)-3-(5-nitro-2-furyl)- 2-isoxazoline, having melting point 110".
  • the product was 5-cyanoacetamidomethyl-3-(5-nitro-2- furyl)-2-isoxazoline, having melting point 156.
  • the product was 3 (5 nitro 2 furyl) 5 ureidomethyl-2-isoxazoline, having melting point 218 with decomposition.
  • Example 10 The procedure described in Example 1 was carried out using the molecular equivalent of N-allylmorpholine as starting material instead of allyl cyanide, the reaction conditions being otherwise essentially the same.
  • Example 11 The procedure described in Example 1 was carried out using the molecular equivalent of allyl bromide as starting material instead of allyl cyanide, the reaction conditions being otherwise essentially the same.
  • the product was 5-bromomethyl-3-(5-nitro-2-furyl)-2- isoxazoline having melting point 105.
  • the product was 5-chloromethyl-5-methyl-3-(5-nitro-2- furyl)-2-isoxazoline, having melting point 113.
  • EXAMPLE 13 A solution of 2.3 grams of metallic sodium dissolved in 50 millilitres of anhydrous methanol was added slowly to a solution of 19.1 grams of 5-nitro-2-furohydroxamoyl chloride dissolved in millilitres of anhydrous methanol through which was passed a continuous stream of propylene gas and which was maintained at 10 to 15. After allowing to stand the crystalline precipitate which formed was collected, Washed with water and recrystallised from a mixture of water and ethanol.
  • the product was S-methyl-S-(5-nitro-2-furyl)-2-isoxazoline, having melting point 137.
  • the product was 3-(5-nitro-2-furyl)-5-pyrrolidin-1-ylmethyl-Z-isoxazoline.
  • Example 17 The procedure described in Example 1 was carried out using the molecular equivalent of N,N-diethylallylamine as starting material instead of allyl cyanide, the reaction conditions being otherwise essentially the same.
  • the product was 5-(N,N-diethylaminomethyl)-3-(5- nitro-2-furyl)-2-isoxazoline.
  • the molecular equivalent of any of the following reactants instead of N,N-diethylallylamine, N,N-dimethylallylamine, N,N-di-propylallylamine, the following products are obtained, respectively: 5-(N,N dimethylaminomethyl) -3-(5-nitro-2-furyl)-2-isoxazoline, 5 (N,N-di-npropylaminomethyl)-3-(5-nitro-2-furyl)-2-isoxazoline.
  • Example 1 The procedure described in Example 1 was carried out using the molecular equivalent of N-allylisobutyramide as starting material instead of allyl cyanide, the reaction conditions being otherwise essentially the same.
  • the product was 5-(isobutyramidomethyl)-3-(5-nitro- 2-furyl)-2-isoxazoline, having melting point 161.
  • the product was S-(hexanamidomethyl)-3-(5-nitro-2- furyl)-2-isoxazoline.
  • the product was 5-chloroacetamidomethyl-3-(S-nitro- 2-furyl)-2-isoxazoline, having melting point 148.
  • the product was 5-dichloroacetamidomethyl3-(5-nitro- 2-furyl)-2-isoxazo1ine, having melting point 187.
  • the product was 5-bromoacetamidomethyl-3-(5-nitro- 2-furyl)-2-isoxazoline.
  • the product was 5-methoxyacetamidomethyl-3-(5- nitro-2-furyl)-2-isoxazoline, having melting point 144.
  • EXAM'PLE 24 A solution of grams of 5-cyanoacetamidomethyl-3- (5-nitro-2-furyl)-2-isoxazoline dissolved in 200 millilitres of anhydrous ethanol was saturated with anhydrous hydrogen chloride gas at 20 to 30. After allowing to stand, 100 millilitres of water was added and the mixture was heated to 60 and then cooled. The crystalline precipitate which formed was collected, washed with water and recrystallised from a mixture of water and ethanol.
  • the product was 5-(ethoxycarbonyl-acetamidomethyl)- 3-(5-nitro-2-furyl)-2-isoxazoline.
  • EXAMPLE 25 The procedure described in Example 1 was carried out using the molecular equivalent of N-allyl-cyclohexanecarboxamide as starting material instead of allyl cyanide, the reaction conditions being otherwise essentially the same.
  • the product was 5-(N-cyclohexanecarbox-amidomethyl)-3-(5-nitro-2-furyl)-2-isoxazoline, having melting point 158.
  • Example 8 The procedure described in Example 1 was carried out using the molecular equivalent of 1-allyl-3-methylurea as starting material instead of allyl cyanide, the reaction conditions being otherwise essentially the same.
  • the product was 5-(3-methylureidomethyD-3-(S-nitro- 2-furyl)-2-isoxazoline, having melting point 216.
  • the product was 5-isopropoxymethyl-3-(S-nitro-Z- furyl)-2-isoxazolir1e, having melting point 79.
  • EXAMPLE 28 The procedure described in Example 1 was carried out using the molecular equivalent of allyl-chloride as starting material instead of allyl cyanide, the reaction conditions being otherwise essentially the same.
  • the product was 5-chloromethyl-3-(5-nitro-2-furyl)-2- isoxazoline having melting point 102.
  • EXAMPLE 29 Preparation of tablets g. of active substance, e.g., of S-cyanoacetamidomethyl-3-(5-nitro-2-furyl)-2-isoxazoline are mixed with 60.0 g. of maize starch and 35.0 g. of lactose, the mixture is moistened with a solution of 5.0 g. of gelatin and 3.0 g. of glycerol in 70.0 g. of Water and granulated through a sieve. The granulate is mixed with a' mixture of 15.0 g. of talcum, 10.0 g. of maize starch and 2.0 g. of magnesium stearate. The resulting mixture is pressed into 1,000 tablets each containing 100 mg. of active substance. If desired the tablets can be grooved for better adaptation of the dosage.
  • active substance e.g., of S-cyanoacetamidomethyl-3-(5-nitro-2-furyl)-2-isoxazoline are mixed with 60.0 g
  • Active substance e.g. 5-chloracetamidomethyl- 3-(5-nitro-2-furyl)-2-isoxazoline 100.0 Maize starch 27.0 Gelatin 8.0
  • Composition I is granulated in the heat with composition (II) through a sieve of 1.2 mm. mesh diameter. The dried granulate is mixed with composition (HI) and the resulting mixture is pressed into 1,000 dragee cores. These are then coated with composition (IV) and dried. The dragees obtained weigh 255.0 mg. and contain 100 mg. of active substance.
  • Active substance e.g. S-methoxyacetamido-
  • the active substance and the colloidal silicon dioxide are passed through a sieve of 1.2 mm. mesh diameter (I).
  • the p-hydroxybenzoic acid esters, the citric acid and the sodium cyclamate are dissolved in the given amount of boiling distilled water; the glycerol is then added to this solution (II).
  • the sodium carboxymethyl cellulose and the sugar are thoroughly mixed (III).
  • composition (III) is then added at 75 C. to Solution (II) under stirring until complete dissolution of (III).
  • the viscous, slightly turbid liquid is cooled to room temperature, filtered, if necessary, and mixed with composition (I). Water is added to the resulting mixture up to the prescribed weight of 1,155.0 g. and the syrup obtained is homogenised.
  • R represents the grouping NH.CO.R wherein R represents alkoxy having from 1 to 3 carbon atoms, the group alkyl having from 1 to 6 carbon atoms or alkyl having from 1 to 6 carbon atoms substituted by 1 or 2 chlorine atoms, bromine atoms, alkoxy groups having from 1 to 6 carbon atoms, alkoxycarbonyl groups having from 2 to 7 carbon atoms, or cyano groups, ureido or ureido N-substituted by one to three alkyl groups, which alkyl groups may be the same or different and may each have from 1 to 3 carbon atoms; and R represents hydrogen or methyl.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
US00752479A 1967-08-26 1968-08-14 Nitrofuryl derivatives of 5-substituted isoxazolines Expired - Lifetime US3769295A (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
GB3935167 1967-08-26

Publications (1)

Publication Number Publication Date
US3769295A true US3769295A (en) 1973-10-30

Family

ID=10409082

Family Applications (1)

Application Number Title Priority Date Filing Date
US00752479A Expired - Lifetime US3769295A (en) 1967-08-26 1968-08-14 Nitrofuryl derivatives of 5-substituted isoxazolines

Country Status (18)

Country Link
US (1) US3769295A (is")
JP (1) JPS4827310B1 (is")
AT (1) AT277221B (is")
BE (1) BE719891A (is")
CA (1) CA933926A (is")
CH (1) CH502372A (is")
CS (1) CS157037B2 (is")
DE (1) DE1795208A1 (is")
DK (1) DK118820B (is")
ES (1) ES357511A1 (is")
FI (1) FI48930C (is")
FR (2) FR1589115A (is")
GB (1) GB1234213A (is")
IE (1) IE32300B1 (is")
NL (2) NL6811722A (is")
NO (1) NO125931B (is")
SE (1) SE330540B (is")
YU (1) YU199068A (is")

Cited By (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3915978A (en) * 1970-01-07 1975-10-28 Merck & Co Inc Nitroimidazoles
US4010176A (en) * 1972-10-27 1977-03-01 Merck & Co., Inc. Isoxazole substituted nitroimidazoles
US4109002A (en) * 1976-06-14 1978-08-22 Eli Lilly And Company Fungicidal 3-phenyl-5-(substituted methyl) isoxaxoles
US4203994A (en) * 1976-06-14 1980-05-20 Eli Lilly And Company Fungicidal 3-phenyl-5-(substituted methyl)isoxazoles
EP0287819A1 (en) * 1987-04-10 1988-10-26 Fisons Corporation 5-(phenyl or phenoxyalkyl)-3-(2-furanyl or 2-thienyl)-3-(1H-imidazol-1-ylmethyl)-2-methylisoxazolidines
WO1998007708A1 (en) * 1996-08-21 1998-02-26 Pharmacia & Upjohn Company Isoxazoline derivatives useful as antimicrobials
WO1999043671A1 (en) * 1998-02-25 1999-09-02 Pharmacia & Upjohn Company Substituted aminomethyl isoxazoline derivatives useful as antimicrobials
US6069141A (en) * 1998-02-13 2000-05-30 Pharmacia & Upjohn Company Substituted aminophenyl isoxazoline derivatives useful as antimicrobials
US6689769B2 (en) 2000-12-21 2004-02-10 Pharmacia & Upjohn Company Antimicrobial quinolone derivatives and use of the same to treat bacterial infections
US20050043374A1 (en) * 2001-10-25 2005-02-24 Gravestock Michael Barry Aryl substituted oxazolidinones with antibacterial activity
US20050119317A1 (en) * 2001-10-25 2005-06-02 Astrazeneca Ab Isoxazoline derivatives useful as antimicrobials
CN101781294A (zh) * 2010-03-10 2010-07-21 天津药物研究院 一类咪唑的衍生物、其制备方法和用途
CN101774976B (zh) * 2010-01-26 2012-05-09 天津药物研究院 磺酰基异噁唑啉衍生物及抗肿瘤用途
CN115160248A (zh) * 2015-02-27 2022-10-11 海洋规划生物工厂株式会社 Kakeromycin及其衍生物的制造方法

Cited By (20)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3915978A (en) * 1970-01-07 1975-10-28 Merck & Co Inc Nitroimidazoles
US4010176A (en) * 1972-10-27 1977-03-01 Merck & Co., Inc. Isoxazole substituted nitroimidazoles
US4109002A (en) * 1976-06-14 1978-08-22 Eli Lilly And Company Fungicidal 3-phenyl-5-(substituted methyl) isoxaxoles
US4203994A (en) * 1976-06-14 1980-05-20 Eli Lilly And Company Fungicidal 3-phenyl-5-(substituted methyl)isoxazoles
EP0287819A1 (en) * 1987-04-10 1988-10-26 Fisons Corporation 5-(phenyl or phenoxyalkyl)-3-(2-furanyl or 2-thienyl)-3-(1H-imidazol-1-ylmethyl)-2-methylisoxazolidines
WO1998007708A1 (en) * 1996-08-21 1998-02-26 Pharmacia & Upjohn Company Isoxazoline derivatives useful as antimicrobials
US5990136A (en) * 1996-08-21 1999-11-23 Pharmacia & Upjohn Company Isoxazoline derivatives useful as antimicrobials
US6093736A (en) * 1996-08-21 2000-07-25 Pharmacia & Upjohn Company Isoxazoline derivatives useful as antimicrobials
US6069141A (en) * 1998-02-13 2000-05-30 Pharmacia & Upjohn Company Substituted aminophenyl isoxazoline derivatives useful as antimicrobials
WO1999043671A1 (en) * 1998-02-25 1999-09-02 Pharmacia & Upjohn Company Substituted aminomethyl isoxazoline derivatives useful as antimicrobials
US6689769B2 (en) 2000-12-21 2004-02-10 Pharmacia & Upjohn Company Antimicrobial quinolone derivatives and use of the same to treat bacterial infections
US20040215017A1 (en) * 2000-12-21 2004-10-28 Pharmacia & Upjohn Company Antimicrobial quinolone derivatives and use of the same to treat bacterial infections
US6869965B2 (en) 2000-12-21 2005-03-22 Pharmacia & Upjohn Company Antimicrobial quinolone derivatives and use of the same to treat bacterial infections
US20050043374A1 (en) * 2001-10-25 2005-02-24 Gravestock Michael Barry Aryl substituted oxazolidinones with antibacterial activity
US20050119317A1 (en) * 2001-10-25 2005-06-02 Astrazeneca Ab Isoxazoline derivatives useful as antimicrobials
US20060035895A1 (en) * 2001-10-25 2006-02-16 Astrazeneca Ab Isoxazoline derivatives useful as antimicrobials
US7022705B2 (en) 2001-10-25 2006-04-04 Astrazeneca Ab Isoxazoline derivatives useful as antimicrobials
CN101774976B (zh) * 2010-01-26 2012-05-09 天津药物研究院 磺酰基异噁唑啉衍生物及抗肿瘤用途
CN101781294A (zh) * 2010-03-10 2010-07-21 天津药物研究院 一类咪唑的衍生物、其制备方法和用途
CN115160248A (zh) * 2015-02-27 2022-10-11 海洋规划生物工厂株式会社 Kakeromycin及其衍生物的制造方法

Also Published As

Publication number Publication date
IE32300L (en) 1969-02-26
SE330540B (is") 1970-11-23
ES357511A1 (es) 1970-03-16
GB1234213A (is") 1971-06-03
YU199068A (en) 1978-05-15
FR1589115A (is") 1970-03-23
IE32300B1 (en) 1973-06-13
DE1795208A1 (de) 1972-03-16
BE719891A (is") 1969-02-24
FR8102M (is") 1970-07-27
CS157037B2 (is") 1974-08-23
FI48930B (is") 1974-10-31
JPS4827310B1 (is") 1973-08-21
NL137326C (is")
CH502372A (de) 1971-01-31
NL6811722A (is") 1969-02-28
AT277221B (de) 1969-12-10
FI48930C (fi) 1975-02-10
NO125931B (is") 1972-11-27
DK118820B (da) 1970-10-12
CA933926A (en) 1973-09-18

Similar Documents

Publication Publication Date Title
US3769295A (en) Nitrofuryl derivatives of 5-substituted isoxazolines
JPS62161728A (ja) 抗菌剤
JP5897566B2 (ja) 環式ｎ，ｎ’−ジアリールチオ尿素及びｎ，ｎ’−ジアリール尿素−アンドロゲン受容体アンタゴニスト、抗癌剤、その調製のための方法及び使用
US3228833A (en) Anticoccidial compositions and methods of using same
US3716555A (en) New 5-nitrofuryl derivatives
US3948913A (en) New 5-nitrofuryl derivatives
US4044130A (en) Compositions for the control of microorganisms
US3632577A (en) 5-nitrofuryl derivatives
US2847416A (en) Nu-[1-(5-nitro-2-furyl) ethylidene]-3-amino-2-oxazolidone
US3562267A (en) Derivatives of 3-(5-nitrofur-2-yl)-5-aminoisoxazoles
US3598812A (en) 5-nitrofuryl derivatives
US3830926A (en) Anti-microbial compositions and methods with 3-(5-nitro-2-furyl)-pyrazoles
US3793316A (en) 5-nitrofuryl derivatives
US3821382A (en) 5-nitrofuryl derivatives as antibacterial agents
US3491190A (en) Pharmaceutical composition containing phenylbutazone derivative
US3562286A (en) Nitrofuryl isoxazole derivatives
US3318772A (en) Compositions and methods of treating convulsant seizures
US3906101A (en) Pharmaceutical compositions containing substituted 5-nitrofurfurylideneamino-oxazolidinones
US3835165A (en) Nitrofuryl-alpha-halo-hydrazones
US3639614A (en) Arylthiete-1 1-dioxides as antiinflammatory agents
US3682953A (en) Substituted 5-nitrofuryl-pyrazoles
US3686408A (en) Compositions with 5-nitro-2-furyl-isoxazoles and their use as antibacterial and antifungal agents
US3686170A (en) Novel substituted t-nitrofurfurylideneamino-oxazolidinones
EP1233963A2 (de) Sulfonyloxazolamine und deren verwendung als 5-ht6 rezeptorliganden
TW201744B (is")