US3920633A - New 6-aza-1,4 -benzodiazepine - Google Patents

New 6-aza-1,4 -benzodiazepine Download PDF

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US3920633A
US3920633A US463130A US46313074A US3920633A US 3920633 A US3920633 A US 3920633A US 463130 A US463130 A US 463130A US 46313074 A US46313074 A US 46313074A US 3920633 A US3920633 A US 3920633A
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carbon atoms
aza
hydrogen
alkyl
dihydro
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Walter Vonbebenburg
Heribert Offermanns
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Evonik Operations GmbH
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Degussa GmbH
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/04—Ortho-condensed systems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/20—Hypnotics; Sedatives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]

Definitions

  • NEW 6-AZA-l,4 -BENZODIAZEPINE Inventors: Walter vonBebenburg, Buchscher;
  • R is a halogen
  • R and R are hydrogen, halogen, trifluoromethyl, nitro, nitrile, alkyl of l to 6 carbon atoms or alkoxy of 1 to 6 carbon atoms;
  • R is hydrogen, hydroxy, alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, carbamoyloxy (H NCOO) or carbamoxyloxy substituted with 1) an alkyl group of l to 6 carbon atoms, (2) alkenyl of 2 to 6 carbon atoms, or (3) cycloalkyl of 3 to 6 carbon atoms;
  • Z is nitrogen or the group 5 NO
  • R is carbamoyl, thiocarbamoyl or carbamoyl or thiocarbamoyl substituted with (1) alkyl of 1 to 6 carbon atoms, (2) alkenyl of 2 to 6 carbon atoms, or (3) cycloalkyl of 3 to 6 carbon atoms;
  • the compounds have psychosedative, anxiolytic and antiphlogistic activity.
  • the compounds of the invention have valuable pharmacodynamic properties. For example, they have psychosedative and especially anxiolytic (tranquilizing) properties. Furthermore, an antiphlogistic action is also present.
  • R and R are hydrogen, alkyl of l to 6 carbon atoms, alkenyl of l to 6 carbon atoms or one of R or R is cycloalkyl of 3 to 6 carbon atoms, or
  • this hydroxy group can be alkylated or can be acylated with a compound of formula II wherein X, R, and R have the meanings set forth above.
  • Process (a) can take place for example in solvents or suspension media, especially dioxane, tetrahydrofurane, toluene, benzene, alpha-naphthalene, dimethyl formamide, dimethyl sulfoxide, glacial acetic acid, water, chloroform or methylene chloride at temperatures between 0 and 200 C., especially 20 to [50 C.
  • solvents or suspension media especially dioxane, tetrahydrofurane, toluene, benzene, alpha-naphthalene, dimethyl formamide, dimethyl sulfoxide, glacial acetic acid, water, chloroform or methylene chloride at temperatures between 0 and 200 C., especially 20 to [50 C.
  • basic materials for example organic bases such as pyridine, trialkyl amines such as trimethyl amine and triethyl amine, dimethyl aniline, N-ethyl piperidine or inorganic basic materials such as alkali hydroxides, e.g.,sodium hydroxide and potassium hydroxide, alkali carbonates, e.g., sodium carbonate and potassium carbonate, alkali bicarbonates, e.g., sodium bicarbonate and potassium bicarbonate, etc. It is also possible that is using the compounds of formula II which contain a halogen atom that the corresponding hydrohalide escapes as a gas during the reaction or in a given case forms a salt with the end product.
  • organic bases such as pyridine
  • trialkyl amines such as trimethyl amine and triethyl amine
  • dimethyl aniline N-ethyl piperidine
  • inorganic basic materials such as alkali hydroxides, e.g.,sodium hydroxide and potassium hydro
  • Y is an acyl residue it is preferably a lower aliphatic acyl group, e.g., an alkanoyl group, for example, acetyl, or a substituted aliphatic acyl group, for example, phenyl acetyl.
  • R is an alkyl group or an alkoxy group
  • R is an alkyl group or an alkoxy group
  • the alkylation takes place, for examples, by reaction with esters of the formula l-lalR', SO (OR")'or ArSO OR", where Hal is a halogen atom, especially Cl, Br or I, Ar is an aromatic radical (especially in a given case a phenyl or naphthyl radical with one or more lower alkyl radicals, e.g., methyl or ethyl) and R" is an alkyl group with l to 6 carbon atoms.
  • methyl chloride ethyl bromide, propyl iodide, hexyl chloride, dimethyl sulfate, diethyl sulfate, methyl-p-toluene sulfonate, butyl-p-toluene sulfonate.
  • the alkylation reaction takes place, in a given case, with addition of customary acid binding agents such as alkali carbonates, e.g., sodium carbonate and potassium carbonate, pyridine or other customary tertiary amines, e.g., triethyl amine and N,N-dimethyl aniline, at temperatures between 0 and C.
  • solvents such as alcohols, e.g., methyl alcohol, ethyl alcohol and isopropyl alcohol, dioxane, dimethyl formamide, dimethyl sulfoxide, aromatic hydrocarbons such as benzene, toluene and acetone as well as mixtures of such solvents.
  • the compound of formula I in which R, is H or 0H can first be converted to an alkali compound if it is treated with an alkali metal, alkali hydride or alkali amide (especially sodium or sodium compounds such as sodium hydride and sodamide) in an inert solvent such as dioxane, dimethyl formamide, benzene or toluene at temperatures between and 150 C. and then the alkylating agent added.
  • compounds can be obtained in which R is a hydroxy group by oxidation.
  • compounds of formula I in which R is a hydrogen atom are reacted in inert solvents such as acetic acid, ethyl acetate or acetone with hydrogen peroxide, peracetic acid or other customary organic peroxides.
  • the temperature is preferably between l0 and +l00 C.
  • the oxygen atom can be removed by catalytic hydrogenation, or by chemical deoxygenation.
  • catalysts for the catalytic hydrogenation there are suitable, for example, the customary metallic hydrogenation catalysts, especially noble metal catalysts (palladium/activated carbon, platinum) or Raney-nickel; as solvents there are preferably employed lower alcohols, e.g., methanol, ethanol or isopropanol.
  • the temperatures are between 0 and 200 C., preferably between 0 and 100 C. In a given case the process can be carried out at pressures up to 50 atmospheres absolute.
  • phosphorus trichloride or dimethyl sulfoxide inert solvents such as dioxane, benzene or toluene at temperatures between 0 and 150C., preferably 0 to 100 C.
  • the sulfur atom can be replaced by oxygen.
  • This change of the sulfur atom can take place by treatment of the thiourea at a temperature between 0 and about 250 C., preferably 0 to C. or also 0 to 50 C. with l to 5 moles of potas-' sium ferricyanide, iron (III) chloride, potassium permanganate, potassium chloride, potassium chlorate, potassium hypochlorite, heavy metal oxides such as lead oxide, mercuric oxide, or peroxides such as hydrogen peroxide, sodium peroxide, peracetic acid and similar acting materials, suitably in the presence of a solvent.
  • solvents there can be used water, methanol, ethanol, propanol, tetrahydrofurane, dioxane, dimethyl formamide, acetone or mixtures of these agents (especially with water).
  • compounds of formula I wherein R is the OH group can be reacted with compounds of formula II under the conditions of process (a), or compounds wherein R is H or the OH group can be converted by alkylation as stated above into compounds wherein R is an alkyl radical or an alkoxy radical.
  • the alkylation takes place by reaction with esters of the formula HalR", SO (OR") or ArSO OR", wherein Hal is a halogen atom, especially Cl, Br or 1, Ar is an aromatic radical (especially in a given case a phenyl or naphthyl radical substituted by one or more lower alkyl groups) and R" is an alkyl group with l to 6 carbon atoms.
  • solvents such as alcohols, e.g., methyl alcohol, ethyl alcohol or propyl alcohol, dioxane, dimethyl formamide, dimethyl sulfoxide, aromatic hydrocarbons such as benzene or toluene or acetone as well as mixtures of such solvents.
  • alkylation with alkyl halides for example, iodides
  • alkyl halides for example, iodides
  • the compound of formula I in which R is H or OH can first be converted to an alkali compound if it is treated with an alkali metal, alkali hydride or alkali amide (especially sodium or sodium compounds such as sodium hydride and sodamide) in an inert solvent such as dioxane, dimethyl formamide, benzene or toluene at temperatures between 0 and 150 C. and then the alkylating agent added.
  • an alkali metal, alkali hydride or alkali amide especially sodium or sodium compounds such as sodium hydride and sodamide
  • Basic compounds of Formula I can be converted into their salts by conventional methods.
  • anions for these salts there can be employed the known and therapeutically usable (pharmacologically acceptable) acid residues.
  • acids such as sulfuric acid, phosphoric acid, hydrohalic acids, e.g., hydrochloric acid or hydrobromic acid, ethylenediamine tetraacetic acid, sulfamic acid, benzene sulfonic acid, p-toluene sulfonic acid, camphor sulfonic acid, methane sulfonic acid, guarazulene sulfonic acid, maleic acid, fumaric acid, oxalic acid, tartaric acid, lactic acid, citric acid, ascorbic acid, glycolic acid, salicylic acid, acetic acid, propionic acid, gluconic acid, benzoic acid,
  • acids such as sulfuric acid, phosphoric acid, hydrohalic acids, e.g., hydrochloric acid
  • alcohols e.g., methanol, ethanol or isopropanol
  • soda or soda lye e.g., soda or soda solution
  • an optically active starting material whereby a corre- I
  • dispensing can taken place in the form of tablets, capsules, pills, dragees, plugs, salves, jellies, cremes, powders, liquids, dusts or aerosols.
  • liquids there can be used, for example, oily or aqueous solutions or suspensions, emulsions, injectable aqueous and oily solutions or suspensions.
  • R is chlorine
  • R is chlorine, fluorine, CF or alkyl with l to 3 carbon atoms, e.g., methyl, ethyl, propyl or isopropyl, preferably methyl, preferably in the ortho or para position, and hydrogen.
  • the preferred substituents are hydrogen or fluorine or chlorine in the ortho position;
  • R is hydrogen, fluorine or chlorine with the o-position being preferred
  • R is ethylaminocarbonyl, dimethylaminocarbonyl, diethylaminocarbonyl or dipropylaminocarbonyl or allylaminocarbonyl;
  • A is especially oxygen and also is sulfur or imino or alkylimino with l to 6 carbon atoms, for example, methylimino, ethylimino, propylimino, butylimino, hexylimino; and
  • R is chlorine, R and R are the same or different and are hydrogen, fluorine or chlorine, preferably in the ortho position, A is an oxygen atom and Z is a nitrogen atom, R is hydrogen or hydroxyl and R is an ethylaminocarbonyl or an allylaminocarbonyl.
  • the starting compounds used in process (a) can be prepared for example according to the process of Austrian Application A 10604/71 or von Bebenburg et al U.S. application Ser. No. 313,542, filed Dec. 8, 1972 or in analogous manner to those processes.
  • the entire disclosure of the von Bebenburg et al U.S. Application is hereby incorporated by reference. These starting compounds are claimed as new compounds in said von Bebenburg et al application.
  • HN CH2 CH CH2 CH 2 Cl N N
  • a mixture of 20 grams of 5-(o-fluorophenyl)-6-aza-7- chloro-l ,2-dihydro-3H-l ,4-benzodiazepinone-(2), 40 ml of allyl isocyanate and 100 ml of tetrahydrofurane were heated at reflux for 7 hours. Upon cooling, the reaction product crystallized out. It was washed with ethanol.
  • the compounds of the invention are suited for the production of pharmaceutical compositions and preparations.
  • the pharmaceutical compositions or drugs contain as the active material one or several of the compounds of the invention, in a given case in admixture with other pharmacologically or pharmaceutically effective materials.
  • the production of the medicine can 12 take place with the use of known and customary pharmaceutical assistants, carriers and diluents.
  • Such carriers and assistants as set' forth for example are those recommended in the following literature as adjuvants for pharmacy, cosmetic and related fields such as in Ullmanns Encyklopadie der zur Chemie, Vol. 4 (1953), pages 1 to 39; Journal of Pharmaceutical Sciences, Vol. 52 (1963), pages 918 et seq.; H. v. Czetsch-Lindenwald, Hilfstoffe fur Pharmazie und angrenzende füre; Pharm. Ind. Vol. 2 (1961), pages 72 et seq.; Dr. H. P. Fiedler, Lexicon der Hilfstoffe fur Pharmazie, Kosmetik und angrenzende füre, Cantor Kg. Aulendorf i. Wiirtt, 1971.
  • Such materials include gelatin, natural sugars such as sucrose or lactose, lecithin, pectin, starch (for example corn starch), tylose, talc, lycopodium, silica (for example colloidal silica), glucose, cellulose, cellulose derivatives for example cellulose ethers in which the cellulose hydroxyl groups are partially etherified with lower aliphatic alcohols and/or lower saturated oxyalcohols, (for example, methyl hydroxypropyl cellulose, methyl cellulose, hydroxyethyl cellulose) stearates, e.g., methylstearate, and glyceryl stearate, magnesium and calcium salts of fatty acids with 12 to 22 carbon atoms, especially saturated acids (for example calcium stearate, calcium laurate, magnesium oleates, calcium palmitate, calcium behenate and magnesium stearate), emulsifiers, oils and fats, especially of plant origin (for example, peanut oil, castor
  • water or physiologically compatible organic solvents as for example, ethanol, 1,2-propylene glycol, polyglycols, e.g., diethylene glycol, triethylene glycol and dipropylene glycol and their derivatives, dimethyl sulfoxide, fatty alcohols, e.g., stearyl alcohol, cetyl alcohol, lauryl alcohol and oleyl alcohol, triglycerides, e.g., glyceryl acetate, partial esters of glycerine, e.g., monoacetic diacetin, glyceryl monostearate, glyceryl distearate, glyceryl monopalmitate, paraffins and the like.
  • ethanol 1,2-propylene glycol
  • polyglycols e.g., diethylene glycol, triethylene glycol and dipropylene glycol and their derivatives, dimethyl sulfoxide
  • fatty alcohols e.g., stearyl alcohol, cetyl alcohol
  • solvent aids there can be used known and conventional solvent aids.
  • solvent aids there can be used, for example, polyoxyethylated 13 fats, e.g., polyoxyethylated oleo triglyceride, linolized oleotriglyceride.
  • oleotriglycerides are olive oil, peanut oil, castor oil, sesame oil, cottonseed oil, corn oil (see also Dr. H. P. Fiedler, lexikon der Hilfsstoffe fur Pharmazie, Kosmetik und angrenzende füre, 1971, pages 191 to 195.
  • Polyoxyethylated means that the materials in question contain polyoxyethylene chains whose degree of polymerization is generally between 2 and 40 and especially between 10 and 20. Such materials can be obtained for example by reaction of the corresponding glyceride with ethylene oxide (for example 40 moles of ethylene oxide per mole of glyceride).
  • preservatives for example ethylenediamine tetraacetic acid
  • buffers for example aminoethyl sulfoxide
  • antioxidants for example ethylenediamine tetraacetic acid
  • complex formers for example ethylenediamine tetraacetic acid
  • the pH is adjusted to about 3 to 7 with physiologically compatible acids or buffers.
  • antioxidants there can be used for example sodium meta bisulfite, ascorbic acid, gallic acid, alkyl gallates, e.g., methyl gallate and ethyl gallate, butyl hydroxyanisole, nordihydroguararetic acid, tocopherols such as tocopherol and synergists (materials which bind heavy metals by complex formation, for example, lecithin, ascorbic acid, phosphoric acid). The addition of synergists increases considerably the antioxidant activity of tocopherol.
  • preservatives there can be used for example sorbic acid, p-hydroxybenzoic acid esters (for example, lower alkyl esters such as the methyl ester and the ethyl ester benzoic acid), sodium benzoate, trichloroisobutyl alcohol, phenol cresol, benzethonium chloride and formalin derivatives).
  • p-hydroxybenzoic acid esters for example, lower alkyl esters such as the methyl ester and the ethyl ester benzoic acid
  • sodium benzoate sodium benzoate
  • trichloroisobutyl alcohol phenol cresol
  • benzethonium chloride benzethonium chloride and formalin derivatives
  • the pharmacological and galenical treatment of the compounds of the invention takes place according to the usual standard methods.
  • the active material or materials and assistants or carriers are well mixed by stirring or homogenization (for example by means of a colloid mill or ball mill), wherein the operation is generally carried out at temperatures between 20 and 80 C., preferably 20 to 50 C.
  • the drugs can be used for example orally, parenterally, rectally, vaginally, perlingually or locally.
  • the lowest effective dosage in the above-mentioned animal experiments is for example 5 mg/kg body weight orally, 0.5 mg/kg body weight intravenously and 1 mg/kg sublinqually.
  • the lowest effective dosage in the above-mentioned animal experiments for example is 0.5 mg/kg body weight orally, 0.] mg/kg sublinqually and 0.05 mg/kg intravenously.
  • a general dosage range there can be used, for example, 0.5 to 10 mg/kg body weight orally, 0.1 to 2 mg/kg sublingually and 0.05 to 1 mg/kg intravenously.
  • the compounds of the invention are useful in treating anxiety, stress and restlessness conditions, vegatative dystony, nervousness, irritability, moodiness, footlight fever (of actors), weather feelings, behavior and adaptability problems of children, functional cardiovascular, gastrointestinal and respiratory complaints.
  • the pharmaceutical preparations generally contain 7 between 1 and 10% of the active component .(or components) of the invention.
  • the compounds can be delivered in the form of tablets, capsules, pills, dragees, suppositories, s'alves, gels, creams, powders, liquids, dusts or aerosols.
  • liquids there can be used oily or aqueous solutions or suspensions, emulsions.
  • the preferred forms of use are as tablets which contain between I and 50 mg of active material or. solutions which contain between 0.1 and 5% of active material.
  • the amount of active component of the invention can be used for example in an amount of:
  • parenteral dispensation for example, intravenously, intramuscularly between 0.1 and 5 mg
  • the minimum daily dosage for example is 3 mg; the maximum daily dosage should not be over 200 mg.
  • the oral individual dosage in general is between 0.5 and 50 mg/kg body weight; the parenteral individual dosage is between about 0.1 and 10 mg/kg body weight.
  • the individual dosage orally is generally between 5 and mg/kg; the parenteral individual dosage is between I and 20 mg/kg body weight.
  • the acute toxicity of the compounds of the invention in the mouse is between 500 mg/kg and 10,000 mg/kg (or above 8000 mg/kg).
  • the drugs can be used in human medicine, in veterinary medicine, e.g., to treat cats, dogs, horses, sheep, cattle goats and pigs or in agriculture.
  • the drugs can be used alone or in admixture with other pharmacologically active materials.
  • the salts can also be used as curing agents for melamineformaldehyde resins.
  • R is a halogen
  • R and R are hydrogen, halogen, trifluoromethyl, ni-
  • tro nitrile, alkyl of l to 6 carbon atoms or alkoxy of l to 6 carbon atoms;
  • R is hydrogen, hydroxy, alkyl of l to 6 carbon atoms
  • Z is nitrogen or the group 5 NO
  • R is carbamoyl, thiocarbamoyl or carbamoyl or thiocarbamoyl substituted with (1) alkyl of l to 6 carbon atoms, (2) alkenyl of 2 to 6 carbon atoms, or (3) cycloalkyl of 3 to 6 carbon atoms;
  • -A is oxygen and pharmaceutically acceptable salts thereof.
  • a compound according to claim 1, wherein any halogen present has an atomic weight of 9 to 80.
  • R is hydrogen, chlorine, fluorine, bromine or trifluoromethyl
  • R is hydrogen
  • R is hydrogen or hydroxyl
  • R is carbamoyl or carbamoyl substituted with (l alkyl of l to 6 carbon atoms, (2) alkenyl of 3 to 6 carbon atoms of (3) cycloalkyl of 3 to 6 carbon atoms.
  • R is or carbamoyl orcarbamoyl substituted with alkyl of l to 4 carbon atoms, alkenyl of 3 to 4 carbon atoms or cyclohexyl.
  • R is hydrogen, chlorine or fluorine
  • R is carbamoyl mono substituted with alkyl of 1 to 3 carbon atoms, allyl or cyclohexyl.
  • R is hydrogen, fluorine, CR, or alkyl of l to 3 carbon atoms
  • R is hydrogen, fluorine or chlorine
  • R is hydrogen, alkyl of 1 to 6 carbon atoms or hydroxy
  • R is carbamoyl mono substituted with alkyl of l to 3 carbon atoms, disubstituted with alkyl of l to 3 carbon atoms or mono substituted with allyl
  • Z is nitrogen.
  • R is hydrogen, fluorine, chlorine or methyl
  • R is hydrogen
  • R is hydrogen
  • R is hydrogen
  • R is ethylaminocarbonyl, dimethylaminocarbonyl, dipropylaminocarbonyl or allylaminocarbonyl.
  • a compound according to claim 3 which is (a) -ethylaminocarbonyl-5-phenyl-6-aza-7-chloro-1,2- dihydro-3H-l ,4-benzodiazepinone-(2 (b) ethylaminocarbonyl-3-hydroxy-5- (o-chlorophenyl )-6-aza-7-chloro-l ,Z-dihydro-SH- l ,4- benzodaizepinone-(2); (c) l-allylaminocarbonyl-S- phenyl-6-aza-7-chloro-l ,Z-dihydro- 3H-l ,4-benzodiazepinone-(2); (d) l-ethylaminocarbonyl-5-(o-fluoropheny

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Neurosurgery (AREA)
  • Neurology (AREA)
  • Anesthesiology (AREA)
  • Pain & Pain Management (AREA)
  • Rheumatology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
US463130A 1973-05-08 1974-04-22 New 6-aza-1,4 -benzodiazepine Expired - Lifetime US3920633A (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
AT402973A AT327204B (de) 1973-05-08 1973-05-08 Verfahren zur herstellung von neuen 6-aza-1,4-benzodiazepinen und deren salzen

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US (1) US3920633A (de)
JP (1) JPS5013393A (de)
AR (1) AR201144A1 (de)
AT (1) AT327204B (de)
AU (1) AU6871874A (de)
BE (1) BE814695A (de)
DD (1) DD110876A5 (de)
DE (1) DE2421637A1 (de)
ES (1) ES426023A1 (de)
FR (1) FR2228491A1 (de)
GB (1) GB1407940A (de)
HU (1) HU167441B (de)
IL (1) IL44777A0 (de)
NL (1) NL7406112A (de)
ZA (1) ZA742900B (de)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4009271A (en) * 1973-04-27 1977-02-22 Deutsche Gold- Und Silber-Scheideanstalt Vormals Roessler 6-aza-3h-1,4-benzodiazepines

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3314941A (en) * 1964-06-23 1967-04-18 American Cyanamid Co Novel substituted pyridodiazepins

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3314941A (en) * 1964-06-23 1967-04-18 American Cyanamid Co Novel substituted pyridodiazepins

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4009271A (en) * 1973-04-27 1977-02-22 Deutsche Gold- Und Silber-Scheideanstalt Vormals Roessler 6-aza-3h-1,4-benzodiazepines

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ZA742900B (en) 1975-02-26
NL7406112A (de) 1974-11-12
AU6871874A (en) 1975-11-13
BE814695A (fr) 1974-11-07
IL44777A0 (en) 1974-07-31
ATA402973A (de) 1975-04-15
JPS5013393A (de) 1975-02-12
FR2228491A1 (de) 1974-12-06
AR201144A1 (es) 1975-02-14
HU167441B (de) 1975-10-28
DD110876A5 (de) 1975-01-12
HU167258B (de) 1975-09-27
DE2421637A1 (de) 1974-11-28
ES426023A1 (es) 1976-07-01
GB1407940A (en) 1975-10-01
AT327204B (de) 1976-01-26

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