Kali-Chemie Pharma Gmbh

Kali-Chemie Aktiengesellschaft

Horst Zeugner

Wolfgang Milkowski

Hans Liepmann

Henning Heinemann

Werner Stuhmer

Renke Budden

Siegfried Funke

Hans-Gunther Liepmann

Rolf Huschens

Rolf Hueschens

Klaus-Ullrich Wolf

Insa Hell

Daniel Jasserand

Reinhard Hempel

Michael Ruhland

Dietmar Roemer

Dimitri Yavordios

Werner Benson

Klaus-Wolf Von Eickstedt

Herbert Muesch

Dietmar Romer

Ineke Van Wijngaarden

Klaus-Ulrich Wolf

Peter-Colin Gregory

Jacqueline Bahlsen

Harald Waldeck

Derk Hamminga

Compounds corresponding to the formula I ##STR1## in which R.sup.1 represents hydrogen, lower alkyl or cycloalkylalkyl with 4-7 carbon atoms,

1,7-fused 1H-indole-2-carboxylic acid-N-(1,4-benzodiazepin-3-yl)amides

New 2-acylaminomethyl-1H-2,3-dihydro-1,4-benzodiazepine compounds are described having the general formula I ##STR1## wherein R.sub.1 is a hydrogen atom or a lower alkyl or alkenyl radical or the cyclopropylmethyl radical, R.sub.2 is a hydrogen atom, n is 0, 1 or 2, R.sub.3 is an optionally substituted furyl, thienyl, pyrrolyl, pyridyl or phenyl radical, R.sub.4 is an optionally substituted furyl, thienyl or, pyrrolyl radical, R.sub.5 is a hydrogen or halogen atom, or a lower alkyl, lower alkoxy, hydroxyl, lower alkylthio, nitro, trifuloromethyl, cyano, amino, lower mono- or dialkylamino, lower monoalkanoylamino, lower N-alkyl-N-alkanoylamino or lower alkanoyloxy radical, and R.sub.6 is a hydrogen atom, or a lower alkyl or lower alkoxy radical or R.sub.5 and R.sub.6 together denote a methylenedioxy or ethylenedioxy radical. The compounds have pharmacological, for example, analgesic, properties.

2-acylaminomethyl-1,4-benzodiazepine compounds, the preparation thereof,

Benzodiazocines corresponding to the formula ##STR1## are converted to benzodiazepines corresponding to the formula ##STR2## of claim 1 by subjecting the benzodiazocine (a) if it is halogen-substituted in the 3-position to a thermal treatment which may also take place in the presence of a nucleophilic agent for the reaction or (b) if the 3-position is hydroxy substituted to treatment with a Lewis acid which is a chlorinating or brominating agent. Whenever the diazepine obtained as the final product has a 2-halogenomethyl group it may then be converted to benzodiazepine which is otherwise substituted in the 2-position.

Process of making benzodiazepine derivatives

[1,2]-fused 1,4-benzodiazepine compounds are disclosed corresponding to the general formula I ##STR1## wherein X is an oxygen or sulfur atom or an optionally substituted imino group, R.sub.1 is a hydrogen or halogen atom, lower alkyl radical, a lower alkoxy radical or a nitro group and R.sub.2 is a hydrogen or halogen atom, a lower alkyl radical, a lower alkoxy radical or a nitro group, or if R.sub.1 is a hydrogen atom, R.sub.2 may also be a lower alkylthio radical, or, if R.sub.1 is a hydrogen atom and X is a sulfur atom or an imino group, R.sub.2 may be a trifluoromethyl radical; or R.sub.1 and R.sub.2 are bonded to adjacent carbon atoms and together denote a methylenedioxy or ethylenedioxy radical; R.sub.3 is an optionally substituted furyl, thienyl, pyrrolyl or pyridyl radical and n is zero or, if R.sub.3 is furyl or thienyl, n may be 0 or 1. The compounds may be in the form of their optical isomers or acid addition salts. The compounds exhibit neuroleptic properties. Processes for preparing the compounds and pharmaceutical compositions containing them are also disclosed.

Isomeric 2-chloromethyl-1,4-benzodiazepine or

Compounds corresponding to the formula: ##STR1## wherein R.sub.1 and R.sub.3 each represent hydrogen, halogen, lower alkyl, lower alkoxy or trifluoromethyl; R.sub.2 and R.sub.4 each represent hydrogen, halogen, lower alkyl or lower alkoxy; Z represents an alkylene radical with 2 to 6 carbon atoms and Y' is halogen, hydroxyl, lower alkanesulphonyl, benzenesulphonyl, or lower alkyl or halogen substituted benzenesulphonyl, and acid addition salts thereof, with the proviso the Y' is other than chlorine if R.sub.1, R.sub.2, R.sub.3 and R.sub.4 each are hydrogen and Z is ethylene or propylene. The claimed compounds are useful intermediates in the synthesis of 1-phenyl-2-[(4-substituted piperazinyl) alkyl]-1,2-dihydro-3H-indazol-3-ones which exhibit antiallergic activity.

1-Phenylindazol-3-one compounds

Novel 2-acyl amino methyl-5-phenyl-1H-2,3-dihydro-1,4-benzo diazepine compounds of the following Formula I ##STR1## which have valuable pharmacological properties are provided. In said Formula I the acyl group --CO--R.sub.3 represents a benzoyl group or a phenyl alkanoyl group which may be unsubstituted or mono- or di-substituted in the phenyl ring. The substituent R.sub.1 in said compounds indicates lower alkyl, lower alkenyl, or cyclopropyl methyl, and the substituent R.sub.2 indicates hydrogen, lower alkyl, or lower alkenyl, while the substituent R.sub.6 indicates hydrogen, halogen, lower alkyl, lower alkoxy, hydroxyl, lower alkylthio, nitro, trifluoro methyl, cyano, amino, mono- or di-lower alkyl amino, lower mono-alkanoyl amino, lower N-alkyl-N-alkanoyl amino, or lower alkanoyloxy, and the substituent R.sub.7 indicates hydrogen, halogen, lower alkyl, lower alkoxy, hydroxyl, or lower alkanoyloxy, whereby R.sub.6 and R.sub.7, when attached to adjacent carbon atoms, may form together the methylene dioxy or the ethylene dioxy group. The substituents R.sub.8 and R.sub.9 designate the same substituents as indicated for the substituents R.sub.6 and R.sub.7. The compounds of Formula I have a surprising analgesic activity.

2-Acylaminomethyl-1,4-benzodiazepine compounds and analgesic use

Intermediates of the isomeric formulae II or III ##STR1## wherein R.sub.1 is a hydrogen or halogen atom, or a lower alkyl, lower alkoxy, hydroxyl, trifluoromethyl or lower alkanoyloxy group,

1,5-Diphenyl-2-haloalkylpyrazolin-3-one intermediates

[1,2]-Fused 1,4-benzodiazepine compounds, process for their preparation

Disclosed are 7-bromo-5-(2-halophenyl)-1H-2,3-dihydro-1,4-benzodiazepines of the formula I ##STR1## in which R.sub.1 is a hydrogen atom or a lower alkoxy or alkanoyloxy radical and R.sub.2 is a halogen atom. The compounds possess psychopharmacological, and especially anti-aggressive properties. To manufacture compounds of formula I, corresponding 2-halomethyl-7-bromo-5-(2-halophenyl)-1H-2,3-dihydro-1,4-benzodiazepines are cyclized to corresponding 7-bromo-1,2-methylene-5-(2-halophenyl)-1H-2,3-dihydro-1,4-benzodiazepines and in these the aziridine ring is opened through treatment with a lower alcohol or a lower carboxylic acid in the presence of a Lewis acid.

7-Bromo-5-(2-halophenyl)-1H-2,3-dihydro-1,4-benzodiazepine

New 2-acylaminomethyl-1H-2,3-dihydro-1,4-benzodiazepine compounds are described having the general formula I ##STR1## wherein R.sub.1 is a hydrogen atom or a lower alkyl or alkenyl radical or the cyclopropylmethyl radical, R.sub.2 is a hydrogen atom, or a lower alkyl or alkenyl radical, n is 0, 1 or 2, R.sub.3 is an optionally substituted furyl, thienyl, pyrrolyl, pyridyl or phenyl radical, R.sub.4 is an optionally substituted furyl, thienyl, pyrrolyl or pyridyl radical, R.sub.5 is a hydrogen or halogen atom, or a lower alkyl, lower alkoxy, hydroxyl, lower alkylthio, nitro, trifluoromethyl, cyano, amino, lower mono- or dialkylamino, lower monoalkanoylamino, lower N-alkyl-N-alkanoylamino or lower alkanoyloxy radical, and R.sub.6 is a hydrogen atom, or a lower alkyl or lower alkoxy radical or R.sub.5 and R.sub.6 together denote a methylenedioxy or ethylenedioxy radical. The compounds have pharmacological, for example, analgesic, properties.

2-Azidomethyl-1,4-benzodiazepine compounds

Highly effective analgesic pharmaceutical compositions and methods of using same are described. Said compositions contain, as analgesic agent, a 5-phenyl-1H-2,3-dihydro-1,4-benzodiazepine compound of the formula ##STR1## wherein R.sub.1 indicates a substituent selected from the group consisting of hydrogen and lower alkyl,

Analgesic pharmaceutical compositions containing 5-phenyl-1,4-benzo

New 1-phenylindazol-3-one compounds are described which have the formula I ##STR1## where R.sub.1 is a hydrogen or halogen atom, or a lower alkyl, lower alkoxy or trifluoromethyl radical, R.sub.2 is a hydrogen or halogen atom, or a lower alkyl or lower alkoxy radical, R.sub.3 is a hydrogen or halogen atom, or a lower alkyl, lower alkoxy or trifluoromethyl radical, R.sub.4 is a hydrogen or halogen, atom, or a lower alkyl or lower alkoxy radical, Z is an alkylene radical with 2 to 6 carbon atoms and R.sub.5 is an unsubstituted or substituted pyridyl radical, a thienyl radical or an unsubstituted or substituted phenyl radical. The compounds have pharmacological actions, for example antiallergic actions. Methods of preparing these compounds are described as well as intermediates useful in these methods. Pharmaceutical compositions containing the compounds are also described.

1-Phenylindazole-3-one compounds, process and intermediates for their

New 1,5-diphenylpyrazolin-3-one compounds and a method of preparing them are described. The compounds have the general formula I ##STR1## where R.sub.1 is a hydrogen or halogen atom, or a lower alkyl, lower alkoxy, hydroxy, trifluoromethyl or lower alkanoyloxy radical, R.sub.2 is a hydrogen or halogen atom, or a lower alkyl, or lower alkoxy radical, or R.sub.1 and R.sub.2 are bonded to adjacent carbon atoms and together denote a methylenedioxy or ethylenedioxy radical, R.sub.3 is a hydrogen or halogen atom, or a lower alkyl, lower alkoxy, hydroxy, trifluoromethyl or lower alkanoyloxy radical, R.sub.4 is a hydrogen or halogen atom, or a lower alkyl, lower alkoxy radical, or R.sub.3 and R.sub.4 are bonded to adjacent carbon atoms and together denote a methylenedioxy or ethylenedioxy radical, Z is an alkylene radical with 2 to 6 carbon atoms and R.sub.5 is an optionally substituted pyridyl radical, a thienyl radical or an optionally substituted phenyl radical. The compounds have pharmacological properties, for example antiallergic properties.

1,5-Diphenylpyrazolin-3-one compounds, process and intermediates for

N.sub.1 -acyl-N.sub.2 -phenyl-1,3-diaminopropan-2-ols are disclosed which possess ulcer-inhibiting activities. Further disclosed are pharmaceutical compositions which are effective in the treatment and prophylaxis of ulcers and which comprise as a pharmacologically active ulcus-inhibiting ingredient N.sub.1 -acyl-N.sub.2 -phenyl-1,3-diaminopropan-2-ols, or a pharmaceutically acceptable acid addition salt thereof, and a pharmaceutically acceptable diluent. Further disclosed are processes for the preparation of the N.sub.1 -acyl-N.sub.2 -phenyl-1,3-diaminopropan-2-ols.

N.sub.1 -Acyl-N.sub.2 -phenyl-diaminopropanols and pharmaceutical

Novel 2-acylaminomethyl-1H-2,3-dihydro-1,4-benzodiazepine derivatives are disclosed which possess the Formula I ##STR1## wherein R.sub.1 represents hydrogen, lower alkyl, lower alkenyl or cyclopropylmethyl;

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Hanover, Germany

Horst Zeugner