Roussel Uclaf

Hoechst Aktiengesellschaft

Other

Rene Heymes

Andre Lutz

Jacques Martel

Walter Durckheimer

Elmar Schrinner

Dieter Bormann

Eberhard Ehlers

Alain Bonnet

Michel Vignau

Didier Pronine

Jean Jolly

Primo Rizzi

Andrr Lutz

Michael Vignau

Cephem derivatives of the general formula ##STR1## in which the R.sub.2 O group is in the syn-position, a process for their manufacture and pharmaceutical formulations which are active against bacterial infections and contain these compounds.

Cephem derivatives and processes for their manufacture

Thiazole intermediates for Cephalosporing are prepared.

3-acetoxymethyl-7-(iminoacetamideo)-cephalosporanic acid

Cephalosporins

A novel process for the preparation of syn isomers of cephalosporanic acid derivatives of the formula ##STR1## comprising reacting first in a solvent and optionally in the presence of a base, a compound of the formula ##STR2## with a compound of the formula

Process for the preparation of derivative of

Compounds of the formula ##STR1## wherein R is selected from the group consisting of hydrogen and groups easily removable by acid hydrolysis or hydrogenolysis, R' is selected from the group consisting of hydrogen, alkyl of 1 to 4 carbon atoms, alkenyl and alkynyl of 2 to 4 carbon atoms and groups easily removable by acid hydrolysis or hydrogenolysis, A is selected from the group consisting of hydrogen, alkali metal and equivalents of an alkaline earth metal or magnesium and an organic amine base with the proviso that when R' is a group easily removable by acid hydrolysis or hydrogenolysis, R is also and when R' is hydrogen, R also is hydrogen and the wavy line means the OR' group may be in either one of the two possible syn or anti positions having antibiotic activity and process for their preparation.

3-acetoxymethyl-7-(iminoacetamino)-cephalosporanic acid derivatives

Cephem derivatives

Novel syn isomers of reacemates and optical isomers of 3-amino-2-oxo-azetidine-1-sulfonic acids of the formula ##STR1## wherein R is difluoromethyl, R.sub.1 is --(CH.sub.2).sub.n --X, n is an integer from 1 to 4, X is selected from the group consisting of halogen, --CN, --OR.sub.1 ', --SR.sub.1 ', azido, thiocyanate, isothiocyanate, and ##STR2## R.sub.1 ' is selected from the group consisting of hydrogen and alkyl of 1 to 4 carbon atoms, R.sub.1 ' is selected from the group consisting of hydrogen, alkyl of 1 to 4 carbon atoms and a heterocycle and R' and R' are individually selected from the group consisting of hydrogen and alkyl of 1 to 4 carbon atoms and taken together with the nitrogen to which they are attached form a heterocycle and A.sup.1 is selected from the group consisting of hydrogen, and metal cations and their nontoxic, pharmaceutically acceptable acid addition salts, the wavy line indicating the cis form, trans form or cis trans forms having antibiotic properties.

3-amino-2-oxo-azetidine-1-sulfonic acids

Novel syn isomers of 3-alkoxymethyl or 3-alkylthiomethyl-7-[2-(2-amino-4-thiazolyl)-2-oximino-acetamido]-cephalos poranic acid compounds of the formula ##STR1## wherein R is selected from the group consisting of hydrogen, alkyl of 1 to 6 carbon atoms, alkenyl and alkynyl of 2 to 6 carbon atoms, cycloalkyl of 3 to 6 carbon atoms, acyl of an organic carboxylic acid of 1 to 18 carbon atoms and alkoxy carbonyl of 2 to 6 carbon atoms, A is selected from the group consisting of hydrogen, alkali metal, alkaline earth metal, --NH.sub.4, magnesium, non-toxic, pharmaceutically acceptable organic amine and an easily cleavable ester group, Ra' is selected from the group consisting of alkyl of 1 to 6 carbon atoms optionally interrupted with a heteroatom, alkenyl and alkynyl of 2 to 6 carbon atoms and optionally substituted aralkyl of 7 to 12 carbon atoms, n is 0, 1 or 2, X' is selected from the group consisting of oxygen and sulfur optionally oxidized to sulfoxide or sulfone and their non-toxic, pharmaceutically acceptable acid addition salts having antibiotic activity and their preparation.

Compounds of the formula ##STR1## wherein R is selected from the group consisting of hydrogen and groups easily removable by acid hydrolysis of hydrogenolysis, R' is selected from the group consisting of hydrogen, alkyl of 1 to 4 carbon atoms, alkenyl and alkynyl of 2 to 4 carbon atoms and groups easily removable by acid hydrolysis or hydrogenolysis. A is selected from the group consisting of hydrogen, alkali metal and equivalents of an alkaline earth metal or magnesium and an organic amine base with the proviso that when R' is a group easily removable by acid hydrolysis of hydrogenolysis, R is also and when R' is hydrogen, R also is hydrogen and the wavy line means the OR' group may be in either one of the two possible syn or anti positions having antibiotic activity and process for their preparation.

Novel 3-acetoxymethyl-7-(iminoacetamido)-cephalosporanic acid derivatives

Novel syn isomers of racemates and optical isomers of 3-amino-2-oxo-azetidine-1-sulfonic acids of the formula ##STR1## wherein R is selected from the group consisting of hydrogen linear or branched optionally substituted alkyl of 1 to 12 carbon atoms and optionally substituted alkenyl and alkynyl of 2 to 12 carbon atoms, R.sub.1 is --(CH.sub.2).sub.n --X, n is an integer from 1 to 4, X is selected from the group consisting of halogen, --CN, --OR', --SR.sub.1 ', azido, thiocyanate, isothiocyanate, and ##STR2## is selected from the group consisting of hydrogen and alkyl of 1 to 4 carbon atoms, R' is selected from the group consisting of hydrogen, alkyl of 1 to 4 carbon atoms and a heterocycle and R' and R' are individiually selected from the group consisting of hydrogen and alkyl of 1 to 4 carbon atoms and taken together with the nitrogen to which they are attached form a heterocycle and A.sup.1 is selected from the group consisting of hydrogen, and metal cations and their nontoxic, pharmaceutically acceptable acid addition salts, the wavy line indicating the cis form, trans form or cis trans forms having antibiotic properties.

Novel 3-amino-2-oxo-azetidine-1-sulfonic acids

Aminothiazolyl acetic acid derivatives

Novel syn isomers of 7-amino-thiazolyl-acetamido-3-acetoxymethyl-cephalosporanic acid derivatives of the formula ##STR1## wherein R.sub.1 is selected from the group consisting of --CN, --CONH.sub.2 and --COOR.sub.1 ', R.sub.1 ' is selected from the group consisting of alkyl of 1 to 3 carbon atoms, hydrogen, alkali metal, alkaline earth metal, ammonium, magnesium and a non-toxic, pharmaceutically acceptable organic amine, A is selected from the group consisting of hydrogen, alkali metal, alkaline earth metal, ammonium, magnesium and a non-toxic, pharmaceutically acceptable organic amine, R' and R' are individually selected from the group consisting of hydrogen and alkyl of 1 to 3 carbon atoms with the ##STR2## group in the syn position with the proviso that when R.sub.1 is --COOR.sub.1 ' and R.sub.1 ' is hydrogen, A is hydrogen and when R.sub.1 is --COOR.sub.1 ' and R.sub.1 ' is an alkali metal alkaline earth metal, magnesium, ammonium or an organic amine, A is an alkali metal, alkaline earth metal, magnesium, ammonium or an organic amine having antibiotic properties and novel intermediates and processes.

2-(2-Substitutedamino-4-thiazolyl)-2-(1-methoxy-isopropoxyimino)-acetic

Novel syn isomers of 7-amino-thiazolyl-acetamido-3-acetoxymethyl-cephalosporanic acid derivatives of the formula ##STR1## wherein R.sub.1 is selected from the group consisting of --CN, --CONH.sub.2 and --COOR.sub.1 ', R.sub.1 ' is selected from the group consisting of alkyl of 1 to 3 carbon atoms, hydrogen, alkali metal, alkaline earth metal, ammonium, magnesium and a non-toxic, pharmaceutically acceptable organic amine, A is selected from the group consisting of hydrogen, alkali metal, alkaline earth metal, ammonium, magnesium and a non-toxic, pharmaceutically acceptable organic amine, R' and R' are individually selected from the group consisting of hydrogen and alkyl of 1 to 3 carbon atoms with the ##STR2## in the syn position with the proviso that when R.sub.1 is --COOR.sub.1 ' and R.sub.1 ' is hydrogen, A is hydrogen and when R.sub.1 is --COOR.sub.1 ' and R.sub.1 ' is an alkali metal, alkaline earth metal, magnesium, ammonium or an organic amine, A is an alkali metal, alkaline earth metal, magnesium, ammonium or an organic amine having antibiotic properties and novel intermediates and processes.

Cephalosporanic acid derivatives

Novel syn isomers of optically active isomers and racemates of 7-[2-(2-amino-4-thiazolyl)-2-oxyimino-acetamido]-bicyclooctene-carboxylic acid derivatives of the formula ##STR1## wherein R is selected from the group consisting of hydrogen, optionally substituted alkyl of 1 to 6 carbon atoms and optionally substituted alkenyl and alkynyl of 2 to 6 carbon atoms, R.sub.1 is selected from the group consisting of hydrogen, methyl, halomethyl, hydroxymethyl and acyloxymethyl, X is selected from the group consisting of oxygen and optionally oxidized sulfur, A is selected from the group consisting of hydrogen, an alkali metal, --NH.sub.4, alkaline earth metal equivalent, a non-toxic, pharmaceutically acceptable organic amine and an easily cleavable ester group and their non-toxic, pharmaceutically acceptable acid addition salts having antibiotic activity and their preparation.

Growing community of inventors

Romainville, France

Rene Heymes