US3900466A - 6-aza-3h-1,4-benzodiazepines - Google Patents

6-aza-3h-1,4-benzodiazepines Download PDF

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US3900466A
US3900466A US468088A US46808874A US3900466A US 3900466 A US3900466 A US 3900466A US 468088 A US468088 A US 468088A US 46808874 A US46808874 A US 46808874A US 3900466 A US3900466 A US 3900466A
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group
carbon atoms
phenyl
hydrogen
acid
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Bebenburg Walter Von
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
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen 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
    • C07D213/72—Nitrogen atoms
    • C07D213/75—Amino or imino radicals, acylated by carboxylic or carbonic acids, or by sulfur or nitrogen analogues thereof, e.g. carbamates
    • 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

Definitions

  • n is an integer from 1 to 4.
  • R is alkyl of 1 to 6 carbon atoms, a hydroxy group, an amino group, an alkoxy group having 1 to 6 carbon atoms, a phenyl group or a phenyl group substituted with alkyl of l to 6 carbon atoms, an alkoxy group of l to 6 carbon atoms, trifluoromethyl, fluorine or chlorine;
  • B is oxygen, sulfur, an imino group or an alkylimino group having I to 6 carbon atoms
  • R is hydrogen, a hydroxy group, an alkyl group with 1 to 6 carbon atoms, an alkoxy group with 1 to 6 carbon atoms, or the group N,, is nitrogen or an NO group;
  • R and R are the same or different and are hydrogen, chlorine, fluorine, the trifluoromethyl group, alkyl groups of l to 6 carbon atoms or alkoxy groups with l to 6 carbon atoms, the tautomeric forms thereof and pharmaceutically acceptable salts thereof.
  • the compounds have psychosedative, anxiolytic, spasmolytic, antipsychotic and antiphlogistic activity.
  • R is alkyl of l to 6 carbon atoms, a hydroxy group
  • B is oxygen, sulfur, an imino group or an alkylimino group having 1 to 6 carbon atoms
  • the alkyl group's alkoxy groups and alkylimino groups preferably have] to 4 carbon atoms.
  • R ⁇ is asubstituted' phenyl group it can be mono or di substituted and the substitutents can be the same or different.
  • A is an alkylenedioxy group preferably it is the ethylenedioxy group, i.e., A with the attached carbon atom forms the dioxolane ring.
  • alkyl and ,alkoxy groups which can be present include methyLethyl, propyl, isopropyl, butyl, tert.buty
  • alkylimino groups are methylimino, ethylimino, propylimino, butylimino,
  • R and B are as defined above and Y is a hydroxy group, a halogenatom, an alkoxy group, a mercapto group, an alkyl mercapto group, an amino group or an alkylamino group, in a given case with addition of an acid binding agent, or
  • Process (a') is carried out, in a given case with the addition of customary acid binding agents such as alkali carbonates,'e.g., sodium'carbonate or potassium carbonate, pyridine or other customary tertiary amines, e.g., triethyl amine, at temperatures between 0 and 150C. in inert solvents such as dioxane, dimethyl formamide, dimethyl sulfoxide, aromatic hydrocarbons such as benzene and toluene or acetone.
  • customary acid binding agents such as alkali carbonates,'e.g., sodium'carbonate or potassium carbonate, pyridine or other customary tertiary amines, e.g., triethyl amine, at temperatures between 0 and 150C.
  • inert solvents such as dioxane, dimethyl formamide, dimethyl sulfoxide, aromatic hydrocarbons such as benzene and toluene or acetone.
  • Process (b) takes place in customary solvents or suspension media at temperatures between 0 and 200C., preferably to 150C.
  • polar solvents for example, alcohols, e.g., methyl alcohol, ethylalcohol, propyl alcohol, isopropyl alcohol and butyl alcohol, dioxane, tetrahydrofurane, dimethyl sulfoxide, dimethyl formamide or imidazole, as well as media such as pyridine or quinoline.
  • Y is a halogen atom itcan be advantageous (but otherewise there should not be added) to add basic materials', e.g.,-sodium hydroxide, which facilitate an acid splitting.
  • Y is a hydroxy group it is suitable and,
  • (dehydrating) agents such as dicyelohexylcarbodiimide or l-ethoxy-2-carbethoxy-l.2- dihydroquinoline.
  • Y is alkylmercaptogroup, alkoxy group or alkylamino group these groups are preferably; of lower molecular weight and for example consist of l to 6 carbon atoms, e.g., methyl mcrcato, hexyl mercapto, methoxy, ethoxy, methylamino and hexyl ar'ninoj v
  • protective groups are easily split off.
  • acyl potash,v soda, aqueous alkali solutions, alcoholic alkali solutions, N a
  • Hydrogenizably splittable groups such as the benzyl group or the carbobenzoxy radical are suitably split off by catalytic hydrogenation in the presence of customary hydrogenation catalysts, especially palladium catalysts, in'a solvent or suspension agent, in a given case under elevated pressure.
  • solvents or suspension agent there can be used water, lower aliphatic alcohols such as methyl alcohol, ethyl alcohol, isopropyl alcohol, butyl alcohol, cyclic ethers such as dioxane or tetrahydrofuran, aliphatic ethers, e.g., diethyl ether,
  • protective groups for the amino group there can be used for example, the benzyl group, a-phenylethyl group, benzyl groups substituted in the benzene nucleus as for example, the p-bromo or p.-nitrobenzyl group, the carbobenzoxy group, the carbobenzthio group, the trifluroacetyl, the phthalyl radical, the trityl radical, the p-toluenesulfonyl radical and similar groups as well as simple acyl groups such as the acetyl group, formyl group, tert. butylcarboxy group, etc.
  • Process (b) can also be carried out under some circumstances so that before the true cyclization there is prevously isolated the intermediate product of the formula:
  • azabenzodiazepinc 1 formula I can be reacted further or substituted in a suitable manner.
  • compounds of formulal wherein R is an OH group can be esterified ina suitable manner.
  • lower aliphatie alcohols e.g., of l to 6 carbon .atoms such as methyl alcohol, ethyl alcohol, isopropyl alcohol, propyl alcohol,--butyl alcohol,.sec.
  • butyl alcohol, t-butyl alcohol, amylalcohol, or hexyl alcohol in the presence of-acid catalysts, e.g., hydrochloric acid, sulfuric acid or p-toluene sulfonic acid or there can be reacted diazoalkanes having l to'6 carbon atoms, e.g., diazomethane and .diazohexane, in the conventional manner in ethereal of dioxane solution at temperatures between and 50C.
  • -acid catalysts e.g., hydrochloric acid, sulfuric acid or p-toluene sulfonic acid or there can be reacted diazoalkanes having l to'6 carbon atoms, e.g., diazomethane and .diazohexane
  • the groups Aand B in compounds of formula I can be changed-by various procedures.
  • a and B are oxygen
  • theseatoms can be-replaced by a sulfur atom by means of phosphorus pentasulfide.
  • This reaction takes place in inert solventssuch as-benzene, toluene, dioxane, pyridine,v of chlorohydrocarbons,.-e.g,, chloroform, at temperatures between 0 and 150C.
  • Compounds in whichA and/or B- isoxygen; or sulfur can in turn be reacted in polar mediatsuch as those mentioned above, for example).
  • alkylamines with' l to 6 carbon .atoms,- e.g,, methylamine, ethyl amine, propyl amine, isopropyl amine, butyl amine, amyl amine or hexyl amine to form compounds in which A and/or'B are imi'no or. alkylimno groups.
  • the reactions are carried out for example in polar.solventssuch as methanol, ethanolor excess amine at temperatures. between 0-and 150 C. lg
  • A is two alkoxy s or an alkylenedioxy group (inwhichR, isphenyl min a given case substituted phenyl) there can be obtained therefrom the ketone where A is 0 in a manner known in itself using acid conditions.
  • This reaction is carried out for example in polar solvents or suspension media which contain some water, as well as in aqueous methanol, ethanol, dioxane or tetrahydrofurane with the addition of some aqueous hydrochloric acid, sulfuric acid, p-toluene sulfonic acid, etc., or it can also be carried out in aqueous media.
  • the temperature is between 0 and 100C, prefer- :ably at 0 to C.
  • the temperatue employed are between 0 and 160C, preferably 50 to C.
  • alkyl group with l to 6 carbon atoms or the groups --.(CH C A) R
  • examples are p-toluenesulfonic ac d ethyl, esters. e.g., methyLp-tolucnesulfonate', ethyl-p-toluenesulfonate, lower dialkyl sulfates, e.g., dimethyl sulfate and diethyl sulfate and the like.
  • the alkylation reaction takes place, in a given case, with addition of customary acid potassium carbonate, pyridine or other customary tertiary amines at temperatures between 0 and C.
  • inert solvents such as alcohols, e.g., methyl alcohol, ethyl alcohol or. propyl, alcohol, dioxane, dimethyl formamide, dimethyl sufloxide, aromtiehydrocarbons such as benzene or toluene or acetone as well as mixtures of such solvents, I I
  • alkylation with alkyl halides- for example, iodides
  • alkyl halides- for example, iodides
  • the c0mpound of'formula -l.-in w hi ch R is H or OH.,can firstbe converted to an alkalicompound if it is treated with an alkali metal, alkali'hydride or, alkali amide (especially sodiumorsodium compounds such as sodiumhydride and sodamide) in an inert solvent such as dioxane, dimethylformamide, benzene or toluene at temperatures between 0 and-1509C. ,and then the alkylating agent added.
  • g y I Compunds; of formula'l'wherein N is a nitrogen atom cambe convertedinto the corresponding N -oxide, For
  • catalysts especially nob'le metal, catalysts (palladium/activated .carbom, platinum) or Raneynickel; as solvents there are preferably, employed lower alcohols, e,g., methanol, ethanol and isopropanol.
  • temperatures employed. are between 0.and 200 C apreferablybetween 0 andJQOfC.
  • process . can be carried outat pressures up to 5 0;atmospheres absolute.
  • acids such as sulfuric,;acid,,phosphoric acid, hydrohalic'v acids, e.g., hy-
  • drochloric acid or hydrobromic acid ethylenediamine tetraacetic acid, sulfamic,acid,.benzene sulfonic acid, p-toluene, sulfonic acid, ,camphor sulfonic ,acid, emthane sulfonic acid, guarazulenesulfonic acid, maleic 'acid, furnaric acid, oxalic, acid, tartaric acid, lactic acid,
  • the compoupds of formula l contain acid groups they can be converted in customary manner into their alkali (e.g., sodium or potassium ammonium or subtreating a solution in an organic agent such as alcohols,
  • the compounds of the invention are suitable for the production of pharmaceutical compositions.
  • the pharmaceutical compositions or medicaments can contain one or more of the compounds of the invention or mixtures of the same with other pharmaceutically active materials.
  • the customary pharmaceutical carriers and assistants can be used for the production of pharmaceutical preparations there can be used the customary pharmaceutical carriers and assistants.
  • the medicines can be employed entcrally, parenterally, orally or perlingually.
  • dispensing can take place in the form of tablets, capsules, pills, dragees, plugs, salves, jellies, cremes, powders, liquids, dusts or aerosols.
  • n l to 3 A is oxygen;
  • N is nitrogen
  • R1 is methoxy, ethoxy, propoxy, phenyl, fluorophenyl or chlorophenyl; v
  • R is hydrogen orhydroxy
  • R is hydrogen, fluorine,,or chlorine, preferably ,in
  • R is hydrogen. 3
  • the starting compounds used in process (a) can' be prepared for example according to the process of German published Application No. 2,259,471 or von Bebenburg et al. U.S. application Ser.-No. 313,542, filed Dec. 8, l972 orin analogousmanner 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.
  • EXAMPLE 6 l-acetylmethyl-5-phenyl-6-aza-7-chloro-1,2-dihydro- 3H- l ,4-benzodiazepinone-( 2) CO CH To a mixture of 27 grams (0.1 mole) of -phenyl-6- aza-7-chlorol ,2-dihydro-3H- l benzodiazepinone- (Mi- 400 ml of dioxane and 40 ml of dimethyl formamide thcre were added under nitrogen with Stirring at EXAMPLE 7 l'-( 2-p-chlorophenyl-2-oxo-ethy l )-5 -phenyl-6-aza- 7- chlorol .Z-dihydrq-SH-l ',4-benzodiazepinone-( 2) To amixture of 27.2 grams (0.
  • the crystals that formed were filtered off with suction and recrystallized from dimethyl formamid e/methanol.
  • EXAMPLE 8 l-cyanom'ethyl-5-phenyl-6-aza-7-chlorol ,2-dihydro- 3H- 1 ,4-benzodiazepinonc-( 2) e11 CN v l3.5 grams (0.05 mole) of 5-phenyl-6-aza-7-chlorol,2-dihydro-3H-1,4-benzodiazepin0ne-(2) and 6 grams of chloroacetonitrile were reacted in a manner analogous to- Example 7. The reaction product was recrystal- Iize-d twice from acetone. Yield 6 grams; .M.P.
  • Example 9 The starting'material in Example 9 was produced as follows.
  • the precipitating crystals of the acid were filtc with suction and washed with water. Yield of 11,11 46 grams.
  • the acid was esterified without further purification.
  • the 46 -grams of'acid were dissolved in 500 m1 of ethanol and there was introduced with stirring at 60C hydrogen chloride until saturation occurred. Next the solution was concentrated to 200 ml and cooled while stirring.
  • Theprecipitated crystals of the Z-benzoyl-3 carbethoxymethylamino-ochloropyridine were filtered off with suction and washed with'ethanol. Yield 35 grams; M.P. 88to 90C.
  • compositions or drugs contain as the aetive material one or several of the compounds of the invention, in a given case in admixture with other" pharmacologicalllyor pharmaceutically effective materials.
  • the production of the medicine can take place with the use of known and customary pharmaceutical assistants,carriers and diluents.
  • Such carriers and assistants as set forth for example are thos recommended in the following literature as adjuvants for pharmacy, cosmetic and relatedfields su'ch as in Ullmans Encyklopadie' der intor Chemie,
  • gelatin examples include gelatin, natural sugars such as sucrose or lactose, lecithin, pectin,
  • l off starch for example corn starch
  • tylose, talc, lycopocially of plant origin forexamplc. peanut oil, castor oil, olive oil, sesameoil, cottonseed oil, corn oil, monodiand triglycerides of saturated fatty acids (C H OL to C H O arid their mixtues, e.g., glyceryl 'monostearate, glyceryl distear'atej'glyceryl tristear'ate'; glyceryl trilaurate), pharmaceutically' compatible 'monoor polyvalent alcohols and polyglycols such as glycerine, mannitol, sorbitol, pentaeryth'ritol, ethyl 'alcohoL'diethylene glycol, triethylene glycol, ethylene glycol, ,pr'opy lene glycol.dipropylene'glycol, polyethylene glycol;- proylene
  • unsaturated fatty acids (2 to 22 carbon atoms, especially lOto l8 carbon atoms),i'with monol to 20 carbon atoms alkanol s
  • polyhydric alcohols such as glycols, glycerine, diethylene glycol, pentaerythritol, sorbitol, mannitol, eth
  • esters of polyvalent alcohols can be gi en case also be etherified, benzyl benzoate, dioxolanedglycerine formal, glycol furfural, dimethyl ac'etamide, lactimide, lactates, e.g., ethyl lactate, ethyl carbonate, silicones (especially middle viscosity dimethyl polysioloane) and the like:
  • water or physiologically compatible'organi 'solvents as for example, ethanol, l ,Z-prop yIene glycol, poly glycols, e.g., diethylene glycol, triethylene glycol and dipropylene glycol and their derivatives, dimethyl sulfox ide, fatty alcohols, e.g., stearyl alcohol, cetyl alcohol, lauryl alcohol and oleyl alcohol, triglycerides, e.g., glycoeryl acetate, partial estes of glycerine, e.g., monoacetic diacetin, glyceryl mo'nostearate, glyceryl distearate, glyceryl monopalrnitate, paraffins and the 1 i l '11.
  • ethanol, l ,Z-prop yIene glycol poly glycols, e.g., diethylene glycol, triethylene glycol and dipropylene glycol and their derivatives, dimethyl s
  • the productipn of th'epfepa'rations' thefe canbe used known and conventional solvent-aids.
  • solvent aids there can bej used, for example, polyoxyethy'lated fats, e.g'., polyoxyethylated ol eotriglyceride;linoliaed oleotriglyceride.
  • Examples 'of"oleotriglycerides olive oil, peanut oil, ca'stor oil, sesame oil, cottonseed oil,c'or n oil see @1186 Dr. H.
  • materials qiues tion contain polyxyethylene chains whose degree of polymerization is generally between 2 and 40 and especially between lO and 20. Such materials can be obtained for example by reactionof thecorresponding glyceride with ethylene oxide (for example 40 moles of ethylene oxide per mole of glyceride).
  • preservatives for example ethylenediamine tetraacetic acid
  • buffers for example aqueous sulfate, EDTA, EDTA, EDTA, EDTA, EDTA, EDTA, EDTA, EDTA, EDTA, EDTA, EDTA, EDTA, EDTA, EDTA, EDTA, EDTA, EDTA, EDTA, EDTA, EDTA, EDTA, EDTA, EDTA, EDTA, EDTA, EDTA, EDTA, arate, sulfate, EDTA, EDTA, EDTA, EDTA, EDTA, EDTA, EDTA, EDTA, EDTA, EDTA, EDTA, EDTA, EDTA, EDTA, EDTA, EDTA, EDTA, EDTA, EDTA, EDTA, EDTA, EDTA, EDTA, EDTA, EDTA, ED
  • alkyl gallates e.g., methyl gallate and ethyl gallate, butyl hydroxyanisole, nordihydroguararetic acid
  • tocopherols such as tocopherol and 17 synergists (material which bind heavy metals by com plex formation. for example, lecithin, ascorbicv acid,
  • preservatives there can be used for example sorbic acid, p-hydroxybenzoie acid esters (for example lower alkyl esters such as the methyl ester and the ethyl ester benzoic acid), sodium benzoate, trichloroisobutyl alco-
  • sorbic acid for example lower alkyl esters such as the methyl ester and the ethyl ester benzoic acid
  • sodium benzoate sodium benzoate
  • the lowest effective dosage in the above-mentioned animal experiments for example is 0.5 mg/kg body weight orally, 0.1 mg/kg sublingually and 0.05 mg/kg intravenously.
  • a general dosage range there can be used, for example, 0.5 to l 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, vegetative dystony, nervousness, irritability, moodiness, footlight fever (of actors), weather feelings, behaviour and adaptability problems of children, functional cardiovascular, gastrointestinal and respiratory complaints. They are also useful in' menstrual and climatic disturbances, aiding before operation and in assisting birth.
  • the pharmaceutical preparations generally contain between 1 and I07: of the active component (or components) of the invention.
  • the compounds can be delivered in the form of tablets, capsules, pills, dragees, suppositories, salves, 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 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;
  • r 18 For example, there is recommended the use of l to 3 tablets containing 1 to 50 mg of active ingredient 3 times dailyor for example intravenouslythe injection 1 to 3- times daily or for example intravenously the injection l to 3 times daily of a l to 2 ml ampoule con taining 01 to 10 mg of active substances.
  • 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 ing/kg body weight.
  • the individual dosage orally is generally between 5 and I00 mg/kg; the parenteral individualdosge is between l and ZOmg/kg body weight.
  • the acute toxicity of the co ounds ofthe invention inthe mouse is between 500 mg/kg 10,000fmg/kg (or .above 8000 mg/kg).
  • the drugs can be used in human medicine in veterinary medicine ⁇ elgf, to treat cats, dogs,- horses, sheep, cattlegoats and pigs of in agriculture:
  • the drugs can be used alone or'in admixture with otherpharmacologically active materials.
  • the salts can also be usedias curing agents for melamine-formaldehyde resins.
  • n is an integer from 1 to 4.
  • R is alkyl of l to 6 carbon atoms, a hydroxy group
  • B is oxygen, sulfur, an imino group or an alkylimino group having 1 to 6 carbon atoms
  • R and R are hydrogen, chlorine, fluorine, the trifluoromethyl group, alkyl groups of l to 6 carbon atoms or alkoxy groups with l to 6 carbon atoms, the tautomeric forms thereof and pharmaceutically acceptable salts thereof.
  • R is a hydroxy group, an amino group, an alkoxy group having 1 to 6 carbon atoms, a phenyl group or a phenyl group substituted with alkyl of l to 6 carbon atoms, an alkoxy group of l to 6 carbon atoms, trifluoromethyl, fluorine or chlorine.
  • a compound according to claim 1 wherein the group C(R ) A is cyano, B is oxygen, R is hydrogen, hydroxy or alkoxy with l to 4 carbon atoms, R is hydrogen, chlorine or fluorine, and R is hydrogen.
  • R2 is hydrogen, hydroxy, methoxy, ethoxy or propoxy.
  • n is an integer from 1 to 3
  • R is methyl, hydroxy, ethoxy, phenyl 'or chlorophenyl
  • R2 is hydrogen
  • R is hydrogen or chloro

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Plural Heterocyclic Compounds (AREA)
US468088A 1973-05-25 1974-05-08 6-aza-3h-1,4-benzodiazepines Expired - Lifetime US3900466A (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
US05/576,112 US3972873A (en) 1973-05-25 1975-05-09 Certain pyrido[3,2-e]1,4-diazepinones and derivatives

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AT462873A AT331251B (de) 1973-05-25 1973-05-25 Verfahren zur herstellung von neuen 6-aza-7-chlor-1,2-dihydro-3h-1,4-benzodiazepinen und deren salzen

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AR (1) AR200928A1 (es)
AT (1) AT331251B (es)
BE (1) BE815467A (es)
CA (1) CA1035771A (es)
CH (1) CH605942A5 (es)
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DE (1) DE2425282A1 (es)
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ES (3) ES426617A1 (es)
FR (1) FR2230367B1 (es)
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DE19710449A1 (de) * 1997-03-13 1998-09-17 Basf Ag Verfahren zur Aufreinigung von Natronlauge

Citations (1)

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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

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CH605942A5 (es) 1978-10-13
DD111206A5 (es) 1975-02-05
ATA462873A (de) 1975-11-15
FR2230367A1 (es) 1974-12-20
JPS5019767A (es) 1975-03-01
ES426619A1 (es) 1977-01-01
AR200928A1 (es) 1974-12-27
GB1410319A (en) 1975-10-15
DE2425282A1 (de) 1974-12-19
ZA743348B (en) 1975-05-28
BE815467A (fr) 1974-11-22
ES426618A1 (es) 1976-07-01
ES426617A1 (es) 1976-12-16
FR2230367B1 (es) 1978-03-24
RO63559A (fr) 1978-07-15
HU174561B (hu) 1980-02-28
AT331251B (de) 1976-08-10
AU6932574A (en) 1975-11-27
NL7407015A (es) 1974-11-27
CA1035771A (en) 1978-08-01

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