US3865832A - Substituted, 6,7 ethylenedioxy 4 hydroxy 3 non oxo carbonylic quinolines - Google Patents

Substituted, 6,7 ethylenedioxy 4 hydroxy 3 non oxo carbonylic quinolines Download PDF

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US3865832A
US3865832A US329692A US32969273A US3865832A US 3865832 A US3865832 A US 3865832A US 329692 A US329692 A US 329692A US 32969273 A US32969273 A US 32969273A US 3865832 A US3865832 A US 3865832A
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Prior art keywords
quinoline
dihydro
hydroxy
carboxylic acid
dioxino
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Theodorus Antonius Co Boschman
Jacob Gerard Korsloot
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US Philips Corp
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US Philips Corp
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Priority claimed from NL7201675A external-priority patent/NL7201675A/xx
Priority claimed from NL7215366A external-priority patent/NL7215366A/xx
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Priority to US05/529,291 priority Critical patent/US3959473A/en
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Publication of US3865832A publication Critical patent/US3865832A/en
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    • 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
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/47—Quinolines; Isoquinolines
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A61P7/10—Antioedematous agents; Diuretics
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
    • C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
    • C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom 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 ring carbon atoms
    • C07D215/48—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
    • C07D215/54—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen attached in position 3
    • C07D215/56—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen attached in position 3 with oxygen atoms in position 4
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D319/00—Heterocyclic compounds containing six-membered rings having two oxygen atoms as the only ring hetero atoms
    • C07D319/10—1,4-Dioxanes; Hydrogenated 1,4-dioxanes
    • C07D319/14—1,4-Dioxanes; Hydrogenated 1,4-dioxanes condensed with carbocyclic rings or ring systems
    • C07D319/16—1,4-Dioxanes; Hydrogenated 1,4-dioxanes condensed with carbocyclic rings or ring systems condensed with one six-membered ring
    • C07D319/20—1,4-Dioxanes; Hydrogenated 1,4-dioxanes condensed with carbocyclic rings or ring systems condensed with one six-membered ring with substituents attached to the hetero ring

Definitions

  • R is either a group where R is an alkoxy or dialkylaminoalkoxy group, an alkoxyalkyloxy, alkenyloxy, cycloalkoxy or cycloalkylalkoxy group containing at most 4 C atoms, but if R denotes a halogen atom or a CF;; group, ,at most 6 C atoms, a hydroxy group, an amino group, a hydrogen atom or an alkyl group containing at most 3 C atoms,
  • R is a hydrogen atom or an acyl group containing from 2 to 4 C atoms and R, is a hydrogen atom or an alkyl group containing at most 3 C atoms,
  • R represents either a group (CH 0R where R, is a hydrogen atom, an alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkoxyalkyl or tetrahydrofuranalkyl group containing at most 6 C atoms, an acyl group containing from 2 to 4 C atoms, a phenylalkyl group containing up to 8 C atoms or a dialkylaminoalkyl group, whilst n is 1 or 2,
  • R is a hydrogen atom or a halogen atom, an alkyl or alkoxy group containing at most 4 C atoms, a trifluoromethyl group, a nitro or amino group, an acylamino group containing up to 4 C atoms, a cyano or a hydroxy group;
  • R represents a hydroxy or mercapto group, an alkoxy or alkylthio group containing at most 3 C atoms or, if R represents a halogen atom or a trifluoromethyl group, a chlorine or bromine atom.
  • the said compounds include the alkali metal salts of the carboxyl group R, and the acid addition salts formed with pharmaceutically acceptable acids.
  • alk(en)yl (oxy) groups denotes both straightchain and branched-chain groups.
  • the formula I denotes both racemates andenantiomers.
  • the compounds in which R represents a hydroxy group or a mercapto group are tautomeric with the compounds of the formula 1a in which X represents an oxygen atom or a sulphur atom.
  • the equilibrium is greatly shifted towards the structure of formula 1a.
  • compounds of the formula la also are considered as falling within the scope of the invention.
  • the compounds of the formula have a strong diuretic effect showing a high ceiling. Unlike the commonly used diuretic furosemide (4-chloro-5-sulfamoyl-N-(furyl-2-methyl) anthranilic acid) the compounds have a dose-effect relation which varies very gradually. As a result, the compounds may readily be used and in spite of individual differences in sensitivity between patients they may be admdinistered without the risk of excessive or insufficient effect of the dose administered.
  • the diuretic effect is accompanied by a saluretic effect which mainly shows itself as a strong increase in the excretion of sodium ions, whereas the increase of the excretion of potassium ions is much smaller.
  • the toxicity of the compounds is very small.
  • the compound of the formula 2a has a LD of 4,080 mg/kg, the compound of formula 2b a [D of 1,000 mg/kg. Even after repeated administration no infulence on the blood sugar content is found.
  • the compounds may be used for treating hypertension, cardiac asthma, decompensation of the heart, pulmonary edema, hepatic edema with ascites, nephrogenous edema, cardiac edema, pregnancy edema, lymphatic, edema, iodopathic edema, edema in adiposis, post-traumatic edema, medicamentous edema, edema in malignant diseases, premenstrual tension, nephrotic syndrome, gestational teoxicosis, barbiturate intoxica' tion, inhibition of lactation and renal and central diabetes insipidus.
  • the doses in which, the frequency at which and the route by which the compounds are administered depend upon the nature and the seriousness of the diseases for the treatment of which they are used. In general a daily dose of from 0.5 mg to 200 mg will be sufficient.
  • R represents a hydroxyl group
  • R an alkoxycarbonyl, alkoxyalkoxycarbonyl, carboxyl, alkylcarbonyl or hydfoxymethyl group
  • R is an alkoxyalkyl or an alkoxyalkoxyalkyl group
  • R is a hydrogen atom, a halogen atom, a trifluoromethyl group or a nitro group
  • R represents a hydroxyl group
  • R an alkoxycarbonyl, alkoxyalkoxycarbonyl, carboxyl, alkylcarbonyl or hydfoxymethyl group
  • R is an alkoxyalkyl or an alkoxyalkoxyalkyl group
  • R is a hydrogen atom, a halogen atom, a trifluoromethyl group or a nitro group
  • the diuretic effect of the compounds was determined in the test arrangement described by Lipschitz, Hadidian and Kerpcsar, J. Pharm. exptl. Therap. 79, 97-l10 (1943), with a few small modifications
  • the compounds to be tested were suspended in an aqueous 1 percent by weight solution of tragacanth in water and orally administered to male rats (weight between 100 g and 200 g) which were fasted for 18 hours.
  • rats weight between 100 g and 200 g
  • mice were orally given 2.5 ml of physiological salt solution per 100 g of body weight.
  • the animals were put in metabolism cages in which urine and faeces could be collected separately.
  • the urine was collected in graduated 'vessels, and readings of the volume were taken 2% hours and hours after administration. The amounts of Na ions, K ions and Cl ions in the urine obtained after 5 hours were determined. The urine volumes and the electrolyte concentrations of the animals treated with the compounds were compared with those of control animals.
  • the compounds of the formula 1 can be obtained by known methods. Accordingly the invention also relates to a method of preparing novel quinoline derivatives which is'characterized in that compounds of the formula l, alkali metal salt, acid addition salts and tautomers thereof are prepared by methods known for the preparation of such compounds and by analogous methods. 4 1
  • R denotes the same group als R, when R, represents a carboxyl group or an esterified carbonyl group, but in all other cases it may also represent a halogencarbonyl group or a group alklol where alk is a lower alkyl group, for example a methyl group or an ethyl group.
  • the reaction is carried out at elevated temperature up to most about 250C.
  • the reaction may proceed in the melt or in a solution.
  • a highboiling-point solvent such as diphenyl, diphenyl ether, mineral oils and the like, may be used, or a condensing agent, such as polyphosphoric acid or an ester thereof, phosphorus oxychloride (POCI phosphorus pentoxide, quinoline, aluminium chloride and the like, and a solvent may be used.
  • the condensing agent may also serve as a solvent.
  • the protected hydroxy and amino groups in R, to R' can be converted into free amino and hydroxy groups by acid or alkaline hydrolysis.
  • Protective benzyl and benzyloxycarbonyl groups may also be removed by hydrogenolysis, for example with Pt or Pd/C and hydrogen under a slightly increased pressure, for example 1.1 atmospheres.
  • reaction product need not be isolated, but may be converted into compounds of the formula 1, for example, by adding a high-boiling-point solvent and raising the temperature.
  • the amines of the formula 5 are usually obtained by reducing the corresponding nitrocompounds, for example with Pd/C and hydrogen.
  • the compounds of the formula 1 in which R represents a hydroxy group may also be obtained by intramolecularly condensing a compound of the formula 7 or a tautomer thereof in which R represents a carboxyl group or an esterified carboxyl group.
  • This reaction may be carried out in an inert solvent such, for example, as diethyl ether and a base such, for example, as an alcoholate at temperatures between room temperature and the boiling point of the mixture.
  • a base such, for example, as an alcoholate at temperatures between room temperature and the boiling point of the mixture.
  • the compounds of the formula 7 may be obtained by reacting a compound of the formula 8 with a compound of the formula 9 in an inert solvent, such as ethanol, with heating.
  • Another method of preparing compounds of the formula l is that in which a compound of the formula 10 or a tautomer thereof is intramolecularly condensed.
  • the reaction is carried out in an inert solvent, such as for example dioxan, in the presence of a catalytic amount of a base, for example NaOH or KOH.
  • a base for example NaOH or KOH.
  • the reaction is performed at temperatures between room temperature and about C.
  • the protected hydroxy groups and amino groups in the substituents R, to R' are converted into free amino groups and hydroxy groups by hydrolysis or hydrogenolysis.
  • the compounds of the formula 10 are obtainable by reacting a compound of the formula 1 l with a compound of the formula 12 or a tautomer thereof, for example in dioxan, using a base as a catalyst.
  • Compounds of the formula 1 l are obtained by reacting the corresponding anthranilic acid derivitative with phosgene.
  • the compounds of the formula I in which R represents a hydroxy group are also obtainable by ring closure of a compound of the formula l3 or a tautomer thereof in which Hal represents a halogen atom.
  • the reaction is carried out in an inert solvent such as, for example, water, alcohols such as ethanol, ketones such as acetone and methylethylketone, preferably in the presence of a base such, for example, as K CO KOl-l or NaOH.
  • a base such, for example, as K CO KOl-l or NaOH.
  • the reaction temperature is between 50C and 100C.
  • the compounds of formula 13 are obtainable, for example, by reacting a compound of the formula 14 with a compound of the formula 15 whilst heating in the presence of a base. Subsequently the group R a benzyl group or a methoxymethyl group, is split off by acid hydrolysis.
  • the compounds of the formula l in which R is a hydroxy group and R is a hydroxymethyl group may also be obtained by ring closure of a compound of the formula 16 or a tautomer thereof, for example in a diluted aqueous solution of a base, at about 50C to 100C.
  • the compounds of the formula 16 are obtainable by condensing a compound of the formula 14 under alkaline conditions with an epihalogenhydrin, subsequent acid hydrolysis to split off the group R and reaction with an aqueous solution of a base.
  • the compounds of the formula l in which R represents a hydroxy group and R represents an esterified carboxyl group may be prepared from compounds of the formula 17 by alcoholysis with the alcohol with which the carboxyl group is to be esterified. This reaction is carried out under acid conditions at temperatures up to the boiling point of the mixture. The intermediately formed imino esters are decomposed with water.
  • the compounds of the formula 1 in which R represents a hydroxy group may also be obtained by hydrolysing a compound of the formula 18 to substitute an oxygenatom for the halogen atom Hal.
  • the reaction is carried out in an inert solvent such, for example, as an alcohol to which a small amount of water has been added. If required the medium may be acidified.
  • the temperature of the mixture is preferably raised to about 100C to increase the reaction velocity.
  • the compounds of the formula 18 are obtained by reacting compounds of the formula 19 with more than 2 equivalents of a phosphorus oxyhalide.
  • the carboxylic acids of the formula 1 in which R represents a hydroxy group may alternatively be obtained in that ina compound of the formula 20 in which Hal is a halogen atom and p 3, hydroxy is substituted for halogen and protected amino and hydroxy groups in R' and R are converted into free hydroxy and amino groups.
  • the reaction may be carried out in an alcoholic or aqueous solution of mixed alkali at temperatures between room temperature and the boiling point of the mixture.
  • aldehydes of the formula 1 in which R represents a hydroxy group are obtainable from compounds of the formula 20 (p 2).
  • the compounds of the formula 20 are obtained by one of the aforementioned cyclization reactions.
  • the compounds according to the invention may be brought into a form suitable for administration to the patient by known methods.
  • the compounds may be worked up with solid and/or liquid excipients commonly used in pharmaceutics to form preparations such as powders, tablets, dragees, pills, suppositories, capsules, injection liquids and the like.
  • the solid substance formed was filtered off, stirred with a mixture of 25 ml of acetone and 25 ml of diethylether and filtered off again.
  • the substance was crystallized from dimethylformamide, washed with diethylether and dried. Melting point 266-268C with decomposition.
  • the superscribed ester was obtained by reacting 1.2 g of the aforementioned compound in a boiling solution of 0.23 g of sodium in 6 ml of methanol for 5 minutes. The substance was isolated by concentrating the reaction mixture by evaporation in a vacuum, diluting the concentrate with water and extracting it with diethylether. The extract was dried, concentrated, chromatographed (silicagel and gradient elution with benzene/acetone) and crystallized from etherpetroleum ether. Melting point 9599C.
  • the water layer was washed with methylene chloride.
  • the solution in. methylene chloride was washed with water, then twice with 2 N solution of caustic soda, and again with water.
  • the alkaline washing liquid was acidified with concentrated hydrochloric acid and then extracted 3 times with methylene chloride.
  • the collected extracts were washed with water and, after being dried and concentrated, chromatographed on a column comprising 25 g of silicagel with the use of methylene chloride with from 10% to of acetone as the eluent (gradient elution). By crystallization of the chromatographed substance from isopropanol the superscribed substance was obtained. Melting point 199C-202C.
  • a solution of 0.17 g of the carboxylic acid obtained by the method described in Example 24a in 2 ml of thionyl chloride was boiled with stirring for half an hour.
  • the obtained suspension was then concentrated in a vacuum, mixed with 4 ml of anhydrous allyl alcohol and then heated to complete solution. After 1 hour 1 drop of water was added.
  • the solution was heated at about 90C for half an hour. Then the liquid was concentrated by evaporation in a vacuum, and the concentrate was mixed with water and diethyl ether.
  • the resulting solid substrate as sucked off and washed with diethyl ether and water to which 2ml of 1.5 N ammonia had been admixed, and again sucked off, washed with 1.5 N ammonia, water and diethyl ether and finally dried in a vacuum. After crystallization from dimethyl formamide the melting point was 263C-265C.
  • the concentrate was chromatographed on a column comprising 200 g of silicagel with the use of methylene chloride containing up to 12% of acetone as the eluent (gradient elution). Melting point 139.5l40.5C.
  • Example 28a 3.5 g of the substance obtained by the method described in Example 28a was mixed with 35 ml of acetic acid and 7.0 g of sodium acetate. The mixture was refluxed for 4 hours. After it had been cooled it was mixed with water; the solid substance produced was sucked off, washed thrice with water, then once with ethanol and finally dried. Melting point about 300C with decomposition.
  • the substance obtained was ethylated to 2-(ethoxymethyl)-5-iodo-7-nitro-1,4- benzodioxane (melting point of the crude product 90-99C), and this was converted with CF J and powdered copper in dimethylformamide into 2- (ethoxymethyl)-7-nitro-5-(trifluoromethyl)-l ,4- benzodioxan by the method described in Tetrahedron Letters 1969 pages 4095-4096.
  • the reaction product was hydrogenated by means of a palladium on active carbon catalyst at room temperature and under a pressure of about 1.1 atmospheres to form 7-amino-2- (ethoxymethyl)-5-(trifluoromethyl)-1,4-benzodioxan, which was immediately converted with 2-(ethoxymethylene)malonlc acid diethyl ester into 2- [2- (ethoxymethyl )-5-(trifluoromethyl l ,4-benzodioxzin 7-ylaminoI-mcthylenc malonic acid dicthyl ester which had a melting point of 96-98C.
  • Example (30a) 1.2 g of the compound obtained by the method described in Example (30a) was dissolved in 12 ml of a mixture of 26.5 percent by weight of diphenyl and 73.5 percent by weight of diphenyl ether. The solution was mixed with 0.12 ml of quinoline and subsequently maintained at a temperature between 245C and 250C whilst stirring in a nitrogen atmosphere for 20 minutes. After the reaction mixture had cooled, it was diluted with 12 ml of petroleum ether, the crude product crystallizing out.
  • a suspension of 0.58 g of 3-(ethoxymethyl)-2,3- dihydro-9-hydroxy-dioxino [2,3-g] quinolinyl-8-methyl l etone in 50 ml of methanol was mixed with 0.12 g of sodium boron hydride and the mixture was stirred at room temperature for 1.5 hours. Subsequently a further amount of 0.05 g of sodiumboron hydride was added, the mixture was stirred for 16 hours, a still further amount of 0.1 g of sodium boron hydride was added, after which stirring was continued at 50C for 0.5 hour.
  • the obtained solution was mixed with 5 ml of water and the mixture was concentrated by evaporation in a vacuum.
  • Example (42c) The concentrate of obtained by the method described in Example (42c) was mixed with 10 ml of 2N solution of caustic soda and an amount of water such as to enable the mixture to be thoroughly stirred. After stirring at room temperature for half an hour another portion of 10 ml of 2N solution of caustic soda was added, and the mixture was heated at 100C with stirring in a nitrogen atmosphere for 2 hours, whilst after about one hour a further portion of 10 ml of 2N solution of caustic soda was added.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
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  • General Health & Medical Sciences (AREA)
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  • Diabetes (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
US329692A 1972-02-09 1973-02-05 Substituted, 6,7 ethylenedioxy 4 hydroxy 3 non oxo carbonylic quinolines Expired - Lifetime US3865832A (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
US05/529,291 US3959473A (en) 1972-02-09 1974-12-04 Quinoline derivatives having pharmacological effects

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
NL7201675A NL7201675A (xx) 1972-02-09 1972-02-09
NL7215366A NL7215366A (en) 1972-11-14 1972-11-14 P-dioxino(2,3-g)quinolines - diuretics, saluretics and hypotensives

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US (1) US3865832A (xx)
JP (1) JPS5727112B2 (xx)
AR (1) AR211510A1 (xx)
AT (1) AT323740B (xx)
BE (1) BE795265A (xx)
CA (1) CA1000279A (xx)
CH (1) CH593285A5 (xx)
DE (1) DE2303496A1 (xx)
DK (1) DK138120B (xx)
ES (1) ES411374A1 (xx)
FI (1) FI55847C (xx)
FR (1) FR2181708B1 (xx)
GB (1) GB1366834A (xx)
IL (1) IL41471A (xx)
PH (1) PH14448A (xx)
SE (1) SE416467B (xx)

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4036962A (en) * 1974-08-12 1977-07-19 E. I. Du Pont De Nemours And Co. 6,7-Methylenedioxy-1-(2,2,2-trifluoroethyl)-4(1H)-quinolone-3-carboxylic acid and its salts and esters
US4179506A (en) * 1978-11-13 1979-12-18 Warner-Lambert Company New pyridobenzodioxin compounds and methods for their production
US20060058372A1 (en) * 2002-10-25 2006-03-16 Herve Dumas N-Benzodioxolyl, n-benzodioxanyl and n-benzodioxepinyl arylcarboxamide derivatives and pharmaceutical compositions comprising them
US20150148539A1 (en) * 2009-03-30 2015-05-28 Transtech Pharma, Llc Substituted Azoanthracene Derivatives and Intermediates for Preparation Thereof
CN113717185A (zh) * 2021-08-19 2021-11-30 云南省烟草农业科学研究院 雪茄烟根茎中一种具有抗菌活性的喹啉生物碱化合物及其制备方法和应用

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3178348A (en) * 1961-02-08 1965-04-13 Norwich Pharma Co Hypotensive quinolines
US3287458A (en) * 1963-12-12 1966-11-22 Warner Lambert Pharmaceutical 1, 4-dihydro-1-lower alkyl-6, 7-methylene-dioxy-4-oxo-3-quinoline-carboxylic acid
US3761482A (en) * 1969-07-09 1973-09-25 Sumitomo Chemical Co Process and intermediates for the preparation of n-substituted 6,7-methylenedioxy-4-quinolone derivatives

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE1908548A1 (de) * 1968-02-29 1970-11-05 Warner Lambert Co Chinolinderivate
DE2030899A1 (de) * 1970-06-18 1971-12-23 Schering Ag, 1000 Berlin Und 4619 Bergkamen Chinolincarbonsäurederivate

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3178348A (en) * 1961-02-08 1965-04-13 Norwich Pharma Co Hypotensive quinolines
US3287458A (en) * 1963-12-12 1966-11-22 Warner Lambert Pharmaceutical 1, 4-dihydro-1-lower alkyl-6, 7-methylene-dioxy-4-oxo-3-quinoline-carboxylic acid
US3761482A (en) * 1969-07-09 1973-09-25 Sumitomo Chemical Co Process and intermediates for the preparation of n-substituted 6,7-methylenedioxy-4-quinolone derivatives

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4036962A (en) * 1974-08-12 1977-07-19 E. I. Du Pont De Nemours And Co. 6,7-Methylenedioxy-1-(2,2,2-trifluoroethyl)-4(1H)-quinolone-3-carboxylic acid and its salts and esters
US4179506A (en) * 1978-11-13 1979-12-18 Warner-Lambert Company New pyridobenzodioxin compounds and methods for their production
US20060058372A1 (en) * 2002-10-25 2006-03-16 Herve Dumas N-Benzodioxolyl, n-benzodioxanyl and n-benzodioxepinyl arylcarboxamide derivatives and pharmaceutical compositions comprising them
US20150148539A1 (en) * 2009-03-30 2015-05-28 Transtech Pharma, Llc Substituted Azoanthracene Derivatives and Intermediates for Preparation Thereof
US9175003B2 (en) * 2009-03-30 2015-11-03 Vtv Therapeutics Llc Substituted azoanthracene derivatives and intermediates for preparation thereof
CN113717185A (zh) * 2021-08-19 2021-11-30 云南省烟草农业科学研究院 雪茄烟根茎中一种具有抗菌活性的喹啉生物碱化合物及其制备方法和应用

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IL41471A0 (en) 1973-04-30
FI55847B (fi) 1979-06-29
GB1366834A (en) 1974-09-11
FR2181708A1 (xx) 1973-12-07
BE795265A (fr) 1973-08-09
DE2303496A1 (de) 1973-08-23
SE416467B (sv) 1981-01-05
JPS4886896A (xx) 1973-11-15
DK138120B (da) 1978-07-17
ES411374A1 (es) 1976-07-01
FR2181708B1 (xx) 1975-10-10
JPS5727112B2 (xx) 1982-06-08
DK138120C (xx) 1978-12-04
FI55847C (fi) 1979-10-10
AT323740B (de) 1975-07-25
CA1000279A (en) 1976-11-23
CH593285A5 (xx) 1977-11-30
AR211510A1 (es) 1978-01-30
IL41471A (en) 1975-12-31
PH14448A (en) 1981-07-23

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