USRE32196E - Aurone derivatives - Google Patents

Aurone derivatives Download PDF

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Publication number
USRE32196E
USRE32196E US06/379,793 US37979382A USRE32196E US RE32196 E USRE32196 E US RE32196E US 37979382 A US37979382 A US 37979382A US RE32196 E USRE32196 E US RE32196E
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carboxyl
iaddend
iadd
formula
chcooh
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Stephen R. Baker
William B. Jamieson
William J. Ross
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Lilly Industries Ltd
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Lilly Industries Ltd
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D257/00—Heterocyclic compounds containing rings having four nitrogen atoms as the only ring hetero atoms
    • C07D257/02—Heterocyclic compounds containing rings having four nitrogen atoms as the only ring hetero atoms not condensed with other rings
    • C07D257/04—Five-membered rings
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
    • C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
    • C07C45/63—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by introduction of halogen; by substitution of halogen atoms by other halogen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C65/00—Compounds having carboxyl groups bound to carbon atoms of six—membered aromatic rings and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups
    • C07C65/32—Compounds having carboxyl groups bound to carbon atoms of six—membered aromatic rings and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups containing keto groups
    • C07C65/40—Compounds having carboxyl groups bound to carbon atoms of six—membered aromatic rings and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups containing keto groups containing singly bound oxygen-containing groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
    • C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
    • C07D307/78—Benzo [b] furans; Hydrogenated benzo [b] furans
    • C07D307/82—Benzo [b] furans; Hydrogenated benzo [b] furans with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the hetero ring
    • C07D307/83—Oxygen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
    • C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
    • C07D307/92—Naphthofurans; Hydrogenated naphthofurans
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
    • C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
    • C07D317/10—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 not condensed with other rings
    • C07D317/14—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 not condensed with other rings with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D317/30—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals

Definitions

  • This invention relates to novel aurone derivatives possessing valuable pharmacological activity, a process for their production and their use as pharmaceuticals.
  • R 1 , R 2 , R 3 , R 4 , R 5 and R 6 are the same or different and can each represent hydrogen, halogen, C 1-6 alkyl, C 1-6 alkoxy, C 3-8 cycloalkyl, optionally substituted phenyl, C 1-6 haloalkyl, amido, amino, cyano, hydroxy, nitro, C 2-4 alkenyl, carboxyl, tetrazol-5-yl or --C ⁇ CHCOOH; or in which R 1 and R 2 taken together respresent a group of formula --CH ⁇ CH--CH ⁇ CH--; provided that at least one of R 1 , R 2 , R 3 , R 4 , R 5 and R 6 is carboxyl, tetrazol-5-yl or --CH ⁇ CHCOOH; or a pharmaceutically-acceptable salt or ester thereof.
  • the compounds of formula I may exist in the (E)-- or (Z)-- form, the (Z)-- form being preferred.
  • a more particular group of compounds is one of formula (I) in which R 1 , R 2 , R 3 , R 4 , R 5 and R 6 have the values defined above provided that when R 1 , R 2 and R 3 are all hydrogen at least one of R 4 , R 5 and R 6 is tetrazol-5-yl or --CH ⁇ CHCOOH. It is preferred that the benzofuranone ring be substituted and thus a preferred group is one of formula (I) in which at least one of R 1 , R 2 and R 3 is other than hydrogen.
  • a further particular group of compounds is one of formula (I) in which R 1 , R 2 , R 3 , R 4 , R 5 and R 6 have the values defined above provided that when one of R 1 , R 2 and R 3 is carboxyl at least one of R 4 , R 5 and R 6 is halogen, C 3-8 cycloalkyl, optionally substituted phenyl, C 1-6 haloalkyl, amido, cyano, nitro, carboxyl, tetrazol-5-yl or --CH ⁇ CHCOOH.
  • At least one of the substituents on the free benzene ring is one such substituent and thus a preferred group is one of formula (I) in which at least one of R 4 , R 5 and R 6 is halogen, C 3-8 cycloalkyl, optionally substituted phenyl, C 1-6 haloalkyl, amido, cyano, nitro, carboxyl, tetrazol-5-yl or --CH ⁇ CHCOOH.
  • An especially preferred group of compounds is one of formula (I) in which at least one of R 1 , R 2 and R 3 is other than hydrogen and at least one of R 4 , R 5 and R 6 is halogen, C 3-8 cycloaklyl, optionally substituted phenyl, C 1-6 haloalkyl, amido, cyano, nitro, carboxyl, tetrazol-5-yl or --CH ⁇ CHCOOH.
  • halogen means especially chlorine, bromine and fluorine.
  • C 1-6 alkyl includes, for example, methyl, ethyl, propyl, isopropyl, butyl, tert butyl, pentyl and hexyl, being preferably methyl, ethyl or tert-butyl.
  • C 1-6 alkoxy includes, for example, methoxy, ethoxy, propoxy, butoxy and is preferably methoxy.
  • C 3-8 cycloalkyl is preferably cyclohexyl.
  • phenyl includes, for example, phenyl optionally substituted with 1 to 3 substituents selected from methyl, methoxy, halogen and nitro.
  • C 1-6 haloalkyl can be, for example, any of the groups listed for "C 1-6 alkyl” substituted with one to three halo atoms such as fluorine or chlorine and is especially trifluoromethyl.
  • C 2-4 alkenyl is preferably allyl.
  • R 1 , R 2 , R 3 , R 4 , R 5 and R 6 be selected from hydrogen, halogen, C 1-4 alkyl, C 1-4 alkoxy, cyclohexyl, trifluoromethyl, N-isopropylcarboxamido, acetamido, dimethylamino, hydroxy, carboxyl, tetrazol-5-yl or --CH ⁇ CHCOOH, or R 1 and R 2 together represent --CH ⁇ CH--CH ⁇ CH--.
  • R 1 is C 1-4 alkyl such as methyl
  • R 1 is C 1-4 alkoxy such as methoxy
  • R 1 is halogen such as chlorine
  • R 1 is C 3-8 cycloalkyl such as cyclohexyl
  • R 1 is carboxyl
  • R 1 is a 5- or 6-substituent
  • a particularly preferred group of compounds is one in which R 1 is C 1-4 alkyl, carboxyl or halogen, R 2 and R 3 are hydrogen, R 4 is carboxyl or --CH ⁇ CHCOOH and R 5 and R 6 are hydrogen.
  • R 1 is alkyl or carboxyl
  • R 2 and R 3 are hydrogen
  • R 4 is carboxyl or --CH ⁇ CHCOOH
  • R 5 and R 6 are hydrogen.
  • the compounds in which R 1 is alkyl or carboxyl, R 2 and R 3 are hydrogen, R 4 is carboxyl or --CH ⁇ CHCOOH and R 5 and R 6 are hydrogen are most preferred.
  • the compounds of formula I can also be in the form of their pharmaceutically-acceptable salts or esters. Such derivatives are encountered, for example, when one or more of the substituents R 1 , R 2 , R 3 , R 4 , R 5 and R 6 are the acid function, carboxyl or --CH ⁇ CHCOOH.
  • Suitable salts include for example those of mineral bases such as alkali metal hydroxides, especially the potassium or sodium salts, or alkaline earth metal hydroxides, especially the calcium salts, or of organic bases such as amines.
  • esters are those derived from C 1-4 alkanols, for example, the methyl, ethyl, propyl, isopropyl, butyl, t-butyl, methoxyethyl or ethoxyethyl esters.
  • the invention also includes a method of preparing aurones of formula (I) which comprises reacting a benzaldehyde of formula (III) ##STR4## with (a) a benzofuranone of formula (IV) ##STR5## or (b) an ⁇ -substituted acetophenone of formula (V) ##STR6## i which X is a leaving group; optionally followed when one or more of R 1 , R 2 , R 3 , R 4 , R 5 or R 6 is cyano by reaction with an azide to give the corresponding tetrazol-5-yl compound.
  • aurones of formula (I) may be prepared by condensing an appropriately substituted benzaldehyde (III) with a benzofuranone derivative (IV) as schematically depicted below: ##STR7##
  • Suitable solvents for this reaction include ethereal solvents such as dioxan and tetrahydrofuran and liquid alkanols such as ethanol.
  • temperature is not critical and is only determinative of the reaction rate.
  • the reaction will proceed at all temperatures between ambient and the reflux temperature of the reaction mixture, for example, between 25° and 150° C.
  • the reaction is preferably acid or base catalysed.
  • Suitable acid catalysts include mineral acids such as hydrochloric acid and strong organic acids such as p-toluene sulphonic acids, whereas suitable inorganic or organic base catalysts incllude alkalies such as caustic soda, caustic potash, sodium carbonate or triethylamine. This type of condensation reaction is well known and those skilled in the art will well appreciate the nature of the reaction conditions and reagents necessary to produce a particular aurone of the formula (I)
  • An alternative process for preparing compounds of formula (I) involves the reaction of an ⁇ -substituted acetophenone (V) with an appropriate benzaldehyde (III) as depicted schematically below: ##STR8## where X is a leaving group, such as for example halogen, especially chloride or bromide, or the tosyl group.
  • Suitable solvents include ethereal solvents such as dioxan and tetrahydrofuran and liquid alkanols such as ethanol.
  • the reaction is preferably base catalysed using a catalyst such as caustic soda, caustic potash or sodium carbonate. Temperatures from 0° to 150° C. can be used to effect the reaction.
  • the reactants of formula (III), (IV) and (V) are in the main known compounds and can be prepared by well known routes described in the literature.
  • compounds of formula (I) in which one of the R groups is tetrazol-5-yl can be derived by preparing the corresponding nitrile and forming the tetrazole therefrom utilising a preferably non-nucleophilic azide, for example trimethylsilyl azide, in a high boiling solvent such as dimethylformamide at temperatures above 100° C.
  • a preferably non-nucleophilic azide for example trimethylsilyl azide
  • the aurones of formula (I) have been shown to be useful in the propylactic treatment of asthma in mammals. This activity has been demonstrated in guinea pigs using either the "Herxheimer” test described in the Journal of Physiology (London) 7, 251 (1952) or the "guinea-pig chopped lung test” described by Mongar and Schild in the Journal of Physiology (London) 3, 207 (1956) or Brocklehurst Journal of Physiology (London) 52, 414 (1960). Compounds are also active in the "rat peritoneal anaphylaxis test” based on allergic reaction in the peritoneal cavity of the rat, as described by Orange, Stechschulte and Austen in Fed. Proc. 28 1710 (1969).
  • the "Herxheimer" test is based on an allergic bronchospasm induced in guinea pigs which closely resembles an asthamatic attack in man.
  • the mediators causing the bronchospasm are very similar to those released when sensitised human lung tissue is challenged with an antigen.
  • Compounds of the invention have exhibited activity in the "Herxheimer” test at dosages ranging from 25 mg/kg to 200 mg/kg.
  • the compounds of formula (I) may be administered by various routes and for this purpose may be formulated in a variety of forms, although it is a special feature of the compounds of the invention that they are effective when administered orally.
  • the compounds of the invention may be administered by the oral and rectal routes, topically, parenterally, e.g.
  • excipients which may be employed in the pharmaceutical formulations of the present invention are lactose, dextrose, sucrose, sorbitol, mannitol, propylene glycol, liquid paraffin, white soft paraffin, kaolin, fumed silicon dioxide, microcrystalline cellulose, calcium silicate, silica, polyvinylpyrrolidone, cetostearyl alcohol, starch, modified starches, gum acacia, calcium phosphate, cocoa butter, ethoxylated esters, oil of theobroma, arachis oil, alginates, tragacanth, gelatin, syrup B.P., methyl cellulose, polyoxyethylene sorbitan monolaurate, ethyl lactate, methyl and propyl hydroxybenzoate, sorbitan trioleate, sorbitan sesquioleate and oleyl alcohol and propellants such as trichloromonofluoromethane, dichlorodifluoromethane and
  • a lubricant may be incorporated to prevent sticking and binding of the powdered ingredients in the dies and on the punch of the tabletting machine.
  • a lubricant may be employed for instance aluminium, magnesium or calcium stearates, talc or mineral oil.
  • the invenion also includes a pharmaceutical formulation which comprises as an active ingredient a compound of formula (I) or a pharmaceutically-acceptable salt or ester thereof, associated with a pharmaceutically-acceptable carrier therefor.
  • Pharmaceutical formulations can be provided in dosage unit form, each dosage unit preferably containing from 5 to 500 mg. (from 5.0 to 50 mg. in the case of parenteral administration, from 5.0 to 50 mg. in the case of inhalation and from 25 to 500 mg. in the case of oral or rectal administration) of a compound of formula (I).
  • unit dosage form refers to physically discrete units suitable as unitary dosages for human subjects and animals, each unit containing a predetermined quantity of active material calculated to produce the desired therapeutic effect in association with the required pharmaceutical diluent, carrier or vehicle.
  • Dosages of from 0.5 to 200 mg/kg per day, preferably 1 to 20 mg/kg of active ingredient may be administered, although it will, of course, be understood that the amount of the aurone of formula (I) actually administered will be determined by a physician, in the light of the revealent circumstances including the condition to be treated, the choice of compound to be administered and the chosen of route of administration and therefore the above preferred dosage range is not intended to limit the scope of the present invention in any way.
  • Finely ground copper (II) bromide (88 g, 0.4 mole) was suspended in a 50:50 mixture of ethyl acetate and chloroform (200 ml). 2,6-Dihydroxyacetophenone (10 g, 0.0657 mole) in chloroform (20 ml) was added to the above suspension which was stirred under reflux for 8 hours, hydrogen bromide being evolved. After cooling the copper (I) bromide formed in the above reaction was filtered off and the solution evaporated to dryness to give 3,5-dibromo-2,6-dihydroxy ⁇ -bromoacetophenone (8.2 g, 0.21 mole) and sodium acetate (20 g) were refluxed in 90% ethanol (100 ml) for 15 minutes.
  • Methyl-3'-acetyl-4-hydroxy benzoate (5.39 g 0.028 mole) was stirred in dioxan (200 ml) at 40° C. and bromine (1.5 ml) added dropwise. After 45 minutes the colourless solution was evaporated to give a straw coloured oil which was dissolved in ethanol/water (75/15 ml.). Sodium acetate (6.0 g) was added and the solution stirred at room temperature for 5 minutes. The red solution was poured on to ice (100 g) and extracted via chloroform. Evaporation of the chloroform extract gave 5-methoxycarbonylbenzofuran-3-(2H)one as an orange red oil (65% pure by NMR).
  • Hard gelatin capsules were prepared using the following ingredients:
  • a tablet formula was prepared using the ingredients below:
  • the components were blended and compressed to form tablets.
  • the active compound was mixed with ethanol and the mixture added to the propellant 22, cooled to -30° C. and transferred to a filling device. The required amount was then fed to a stainless steel container and diluted further with a metered amount of propellant. The valve units were then fitted to the container.
  • a suppository formula was prepared containing 200 mg of the compound using the following ingredients:
  • the active compound was mixed in the molten glycol bases and then the mixture was poured into appropriate suppository moulds, to give the active fill weight.
  • the active compound was added to the molten paraffin and then the mixture was allowed to cool.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Pulmonology (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Furan Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
US06/379,793 1978-09-13 1982-05-19 Aurone derivatives Expired - Lifetime USRE32196E (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GB7836705 1978-09-13
GB36705/78 1978-09-13

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US06/071,515 Reissue US4259340A (en) 1978-09-13 1979-08-31 Aurone derivatives

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JP (1) JPS5540692A (d)
KR (1) KR830001919B1 (d)
AR (2) AR228020A1 (d)
AT (1) AT376968B (d)
AU (1) AU535369B2 (d)
BG (2) BG40315A3 (d)
CA (1) CA1202309A (d)
CH (1) CH644603A5 (d)
CS (1) CS214806B2 (d)
DD (1) DD146046A5 (d)
DK (1) DK382579A (d)
EG (1) EG14105A (d)
ES (1) ES484115A1 (d)
FI (1) FI792850A7 (d)
GR (1) GR71200B (d)
HU (1) HU181450B (d)
IE (1) IE48824B1 (d)
IL (1) IL58229A (d)
IT (1) IT1162395B (d)
MX (1) MX6232E (d)
NZ (1) NZ191556A (d)
PH (1) PH15712A (d)
PL (1) PL124296B1 (d)
PT (1) PT70170A (d)
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SU (1) SU1138027A3 (d)
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ZA (1) ZA794836B (d)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1997026873A1 (en) * 1996-01-26 1997-07-31 Phytera, Inc. Antimicrobial aurone derivatives
WO1999004789A1 (en) * 1997-07-25 1999-02-04 Phytera, Inc. Substituted aurone derivatives
US6307070B1 (en) 1996-01-26 2001-10-23 Phytera, Inc. Substituted aurone derivatives

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WO1999012540A1 (fr) * 1997-09-11 1999-03-18 Snow Brand Milk Products Co., Ltd. Remedes contre des maladies hormonales
DE50104383D1 (de) 2000-01-28 2004-12-09 Merck Patent Gmbh Benzofuranonderivate enthaltende formulierung zum schutz vor oxidativem stress
USD685270S1 (en) 2012-04-04 2013-07-02 Colgate-Palmolive Company Container
USD688951S1 (en) 2012-04-04 2013-09-03 Colgate-Palmolive Company Container
USD685269S1 (en) 2012-04-04 2013-07-02 Colgate-Palmolive Company Container
USD685271S1 (en) 2012-04-04 2013-07-02 Colgate-Palmolive Company Container

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US3716531A (en) * 1967-11-14 1973-02-13 Schering Ag 5-nitro-furfurylidene antimicrobic agents
US3975380A (en) * 1974-06-03 1976-08-17 Smithkline Corporation Substituted aurones
US4067993A (en) * 1975-09-24 1978-01-10 Riker Laboratories, Inc. Antimicrobial 2-nitro-3-phenylbenzofurancarboxylic acids
US4115567A (en) * 1973-12-27 1978-09-19 Carlo Erba S. P. A. 6-Carboxy-2-(2'-pyrazinyl)-chromones and esters thereof
DE2829619A1 (de) * 1977-07-06 1979-01-25 Inst Nat Sante Rech Med Arzneimittel, enthaltend benzyliden- 2-benzofurane
US4143055A (en) * 1978-03-27 1979-03-06 Gruppo Lepetit S.P.A. 2,4,6-trisubstituted-2,3-dihydro-benzofuran derivatives
US4143145A (en) * 1977-01-12 1979-03-06 Carlo Erba S. P. A. Substituted 2-vinyl-chromones and process for their preparation
BE873826A (fr) * 1978-01-31 1979-05-16 Erba Farmitalia Derives de la 2h-benzofuran-3-one et procede de preparation

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US3716531A (en) * 1967-11-14 1973-02-13 Schering Ag 5-nitro-furfurylidene antimicrobic agents
US4115567A (en) * 1973-12-27 1978-09-19 Carlo Erba S. P. A. 6-Carboxy-2-(2'-pyrazinyl)-chromones and esters thereof
US3975380A (en) * 1974-06-03 1976-08-17 Smithkline Corporation Substituted aurones
US4083952A (en) * 1974-06-03 1978-04-11 Smithkline Corporation Substituted aurones
US4067993A (en) * 1975-09-24 1978-01-10 Riker Laboratories, Inc. Antimicrobial 2-nitro-3-phenylbenzofurancarboxylic acids
US4143145A (en) * 1977-01-12 1979-03-06 Carlo Erba S. P. A. Substituted 2-vinyl-chromones and process for their preparation
DE2829619A1 (de) * 1977-07-06 1979-01-25 Inst Nat Sante Rech Med Arzneimittel, enthaltend benzyliden- 2-benzofurane
GB2001631A (en) * 1977-07-06 1979-02-07 Inst Nat Sante Rech Med Physiologically-active benzofuranone derivatives
BE873826A (fr) * 1978-01-31 1979-05-16 Erba Farmitalia Derives de la 2h-benzofuran-3-one et procede de preparation
GB2014566A (en) * 1978-01-31 1979-08-30 Erba Farmitalia 2h benzofuran 3one derivatives
US4143055A (en) * 1978-03-27 1979-03-06 Gruppo Lepetit S.P.A. 2,4,6-trisubstituted-2,3-dihydro-benzofuran derivatives

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Castel et al., Trav. Soc. Pharm. Montpellier, 36 (1976) pp. 239-246.
Derwent Abstract, #29852.
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Flandre, Soc. Biol. Montpellier, 1976, pp. 146 150. *
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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1997026873A1 (en) * 1996-01-26 1997-07-31 Phytera, Inc. Antimicrobial aurone derivatives
US6307070B1 (en) 1996-01-26 2001-10-23 Phytera, Inc. Substituted aurone derivatives
WO1999004789A1 (en) * 1997-07-25 1999-02-04 Phytera, Inc. Substituted aurone derivatives

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PL218277A1 (d) 1980-07-14
AU5078079A (en) 1980-03-20
HU181450B (en) 1983-07-28
ZA794836B (en) 1981-03-25
DK382579A (da) 1980-03-14
CH644603A5 (en) 1984-08-15
SE7907532L (sv) 1980-03-14
YU222079A (en) 1983-02-28
SE447382B (sv) 1986-11-10
MX6232E (es) 1985-01-14
JPS5540692A (en) 1980-03-22
IT1162395B (it) 1987-03-25
CA1202309A (en) 1986-03-25
PL124296B1 (en) 1983-01-31
BG43187A3 (bg) 1988-04-15
FI792850A7 (fi) 1981-01-01
AR226210A1 (es) 1982-06-15
SU1138027A3 (ru) 1985-01-30
KR830001919B1 (ko) 1983-09-23
GR71200B (d) 1983-04-11
IE48824B1 (en) 1985-05-29
IL58229A0 (en) 1979-12-30
IT7950245A0 (it) 1979-09-12
AR228020A1 (es) 1983-01-14
ATA598079A (de) 1984-06-15
PH15712A (en) 1983-03-14
ES484115A1 (es) 1980-04-16
BG40315A3 (bg) 1986-11-14
NZ191556A (en) 1981-03-16
EG14105A (en) 1983-03-31
AU535369B2 (en) 1984-03-15
AT376968B (de) 1985-01-25
CS214806B2 (en) 1982-06-25
DD146046A5 (de) 1981-01-21
IE791729L (en) 1980-03-13
PT70170A (en) 1979-10-01
IL58229A (en) 1984-05-31

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