Kali-chemie Aktiengesellschaft

Kali-chemie Pharma Gmbh

Werner Stuhmer

Horst Zeugner

Wolfgang Milkowski

Siegfried Funke

Renke Budden

Rolf Huschens

Hans-Gunther Liepmann

Klaus-Wolf Von Eickstedt

Gunter Peschke

Rudolf Kaufung

Hans Hell

Horst Oppermann

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

1,4-Benzodiazepin of the formula ##STR1## wherein R is a low molecular straight or branched alkyl and X is halogen or trifluoromethyl, and pharmaceutically acceptable acid addition salts of these benzodiazepins. The benzodiazepins are made by heating an acyldiamine in the presence of phosphorus oxychloride at the latter's boiling point followed by reacting the resulting mixture of 7-member and 8-member compounds with an alkali metal alkoxide.

Benzodiazepine derivatives and process of making them

1,2,3,4-Tetrahydro-1,5-benzodiazocines having the following formula ##STR1## in which R.sup.1 is a hydrogen, alkyl radical having at most 6 carbon atoms, methoxyethyl, or benzyl radical,

Bendodiazocine derivatives and process of making the same

A 1,3 diaminopropane derivative having the formula I ##STR1## in which R.sub.1 is hydrogen, methoxyethyl, benzyl or alkyl of at most 6 carbon atoms or is cycloalkyl of 3 to 6 carbon atoms,

1,3 Diaminopropane derivatives

1,4-benzodiazepin of the formula ##STR1## wherein R is a low molecular straight or branched alkyl and X is halogen or trifluoromethyl, and pharmaceutically acceptable acid addition salts of these benzodiazepins. The benzodiazepins are made by heating an acyldiamine in the presence of phosphorus oxychloride at the latter's boiling point followed by reacting the resulting mixture of 7-member and 8-member compounds with an alkali metal alkoxide.

Benzodiazepin derivatives

A benzodiazepine derivative of the formula ##STR1## wherein R.sub.1 is hydrogen, lower alkyl which may be a straight chain, branched chain or cyclic group and may also be substituted,

Process for making benzodiazepine derivatives

N.sub.1 -[3-(4'-fluorobenzoyl)-propyl]-N.sub.2 -[2-(2'-chloro-5'-methylphenoxy)ethyl]-piperazine of the formula ##STR1## or a pharmaceutically acceptable salt thereof. The compounds are sedatives of low toxicity.

N,[3-(4'-fluorobenzoyl)propyl]-N.sub.2 -(2'-chloro-5'-methylphenoxy)ethyl]p

A freely flowable pancreatin of high amylolytic, lipolytic, and proteolytic activity, of a low germ content and substantially free of pathogenic germs and fibrous tissue material, of a high bulk weight between about 500 g./liter and about 700 g./liter and a very fine particulate size is produced according to the continuous process of extracting finely comminuted pancreas glands with a mixture of chlorinated hydrocarbons and fluoro-chloro-carbons and, if required, water, separating the fat-containing solvent phase, and recovering pancreatin from the enzyme phase.

Continuous process of producing pancreatin and product thereof

Benzodiazepine derivatives

1,4-diazacycloalkane derivatives of the formula ##SPC1## Wherein R is hydrogen, halogen, lower alkoxy, nitro or lower secondary amine, R.sub.1 is lower alkoxyphenyl, nitrophenyl or trifluoromethylphenyl or wherein R.sub.1 is phenyl, that is disubstituted by two halogen, by two lower alkyl, by halogen and nitro, by halogen and lower alkyl, by halogen and lower alkoxy or by lower alkoxy and lower alkoyl, lower in these definitions meaning from 1 to 4 carbon atoms and wherein n, n' and m are 2 or 3; And pharmaceutically acceptable acid addition products of these compounds. The compounds are sedatives with an analgesic and anti-histaminic effect and possess a low toxicity.

N-[3-(p-f-benzoyl)-propyl]-N'-[2.(nitro,nitro-el, or methoxyphenyl)-ethyl]-

Piperazine derivatives having the following general formula ##EQU1## in which n is 2 or 3, X is an oxy or thio radical, and A and B are each a radical of the group consisting of phenyl radicals containing at most three substituents of the group consisting of nitro, trifluoromethyl, halogen, cyano, and alkyl, alkoxy, alkylthio, acyl, and alkylsulfonyl radicals containing at most 6 carbon atoms, and similar cycloalkyl and cycloalkylalkyl radicals, their acid addition salts, processes for their production, and pharmaceutical compositions containing the same. The compounds have a very favorable action on the central nervous system and are effective agents for the treatment of anxiety states, psychoses, emotional disturbances, aggressive tendencies, and can be used generally for the treatment of psychiatrically disturbed and psychoneurotic patients.

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Eldagsen, Germany

Werner Stuhmer