Rhone-poulenc S.a.

Rhone-poulenc Industries

Rhone-poulenec S.a.

Mayer Naoum Messer

Claude Jeanmart

Daniel Farge

Claude Cotrel

Claude Moutonnier

Christian Berger

Georges Gros

Cornel Crisan

Pierre Le Roy

Jean Bouchaudon

Andre Leger

Gilbert Poiget

Yves Le Goff

Heterocyclic compounds of the formula: ##STR1## wherein the pyrroline ring and the symbols R.sub.1 and R.sub.2 together form an isoindoline, 6,7-dihydro-5H-pyrrolo-[3,4-b]pyrazine, 2,3,6,7-tetrahydro-5H-1,4-oxathiino-[2,3-c]pyrrole or 2,3,6,7-tetrahydro-5H-1,4-dithiino-[2,3-c]pyrrole nucleus, Het represents an optionally substituted pyrid-2-yl, quinol-2-yl or 1,8-naphthyridin-2-yl radical, Z represents oxygen or sulphur and R represents hydrogen, alkyl or halo-substituted alkyl, alkenyl, alkynyl, cycloalkyl, alkoxy, optionally substituted phenyl, phenylalkyl, the phenyl ring of which may optionally be substituted, phenylalkenyl, the phenyl ring of which may optionally be substituted, or R represents a 5- or 6-membered heterocyclic radical containing one or two hetero-atoms selected from nitrogen, oxygen and sulphur, and, when the pyrroline ring and the symbols R.sub.1 and R.sub.2 together form an isoindoline nucleus, the residue of the isoindoline nucleus represented by R.sub.1 and R.sub.2 may optionally be substituted, possess pharmacological properties, and are especially useful as tranquillizers, anti-convulsant agents, decontracturants and agents to produce hypnosis.

Heterocyclic compounds

New oxathiino- and dithiino-aminoacetic acids of the formula: ##STR1## in which A represents oxygen or sulphur, together with their racemic forms, their optically active forms and mixtures thereof, their reactive derivatives and their acid addition salts, are valuable intermediates for the preparation of therapeutically active derivatives, in particular cephalosporin derivatives of the formula: ##STR2## where R is hydrogen or acetoxy.

Oxathiino- and dithiino-aminoacetic acids

Isoindolin-1-one derivatives substituted on the nitrogen atom in the 2-position by an unsubstituted or substituted phenyl radical or a heterocyclic radical having aromatic characteristics, substituted in the 3-position by a 3-amino(or substituted amino)-2-hydroxy-propoxy group, and optionally substituted in the 5- and/or 6-positions by one or two alkoxy radicals or optionally substituted in the 5- and 6-positions by a methylenedioxy radical, possess pharmacodynamic properties, and are especially useful as antiarrhythmic agents.

Isoindolin-1-one derivatives

Compounds of the formula: ##STR1## wherein one of the symbols =X- represents =N- and the other three each represent a group ##STR2## in which Y represents hydrogen, halogen, alkyl, alkoxy, cyano or nitro, =A- and =A.sub.1 - represent a group =CH- or =N-, =A.sub.1 - representing a group =CH- or =N- when =A- represents =CH- and =A.sub.1 - representing =N- when A represents =N-, Z represents hydrogen, halogen, alkyl, alkoxy or nitro, m represents zero or an integer from 1 to 4, and (i) n represents zero and R represents hydrogen, alkyl, alkenyl, alkynyl, hydroxyalkyl or phenyl, or (ii) n represents 1 and R represents alkyl, hydroxyalkyl or phenyl, are new compounds possessing pharmacological properties; they are particularly active as tranquilizers and anticonvulsant agents.

6-(1,8-Naphthyridin-2-yl)-5-piperazino

New cephalosporin derivatives of the formula: ##STR1## in which either (a) R.sub.1 is hydrogen, acetoxy, azido or heterocyclylthio or heterocyclylcarbonylthio which is (1,3,4-thiadiazol-2-yl)-thio which is unsubstituted or substituted by straight or branched chain C.sub.1-4 alkyl or alkoxy, straight or branched chain C.sub.1-4 alkylthio, straight or branched chain C.sub.1-4 alkylsulphonyl, amino or acetylamino; (1,2,3,4-tetrazol-5-yl)-thio which is unsubstituted or substituted in the 1-position by straight or branched chain C.sub.1-4 alkyl, hydroxy straight or branched chain C.sub.1-4 alkyl, phenyl or hydroxyphenyl, or in the 2-position by straight or branched chain C.sub.1-4 alkyl or hydroxy straight or branched chain C.sub.1-4 alkyl; (1,2,4-triazol-3-yl)-thio, (4-methyl-1,3-thiazol-2-yl)-thio, (3-methyl-1,2,4-thiadiazol-5-yl)-thio or (1,2,3-thiadiazol-4-yl)-carbonylthio, and R.sub.2 is carboxy or a radical of the formula: ##STR2## in which the radical: ##STR3## is a radical which can be easily removed enzymatically, and in which R.sub.3 is hydrogen or straight or branched chain C.sub.1-4 alkyl and R.sub.4 is straight or branched chain C.sub.1-4 alkyl or cyclohexyl; or (b) R.sub.1 is a pyridinio ion and R.sub.2 is a carboxylato ion, and pharmaceutically acceptable non-toxic metal salts thereof and addition salts thereof with nitrogen containing bases possess valuable anti-bacterial properties, showing activity against both Gram-positive and Gram-negative bacteria.

Cephalosporin derivatives

New cephalosporin derivatives of the general formula: ##STR1## in which R represents a straight or branched chain C.sub.1-4 alkyl radical, or a phenyl (straight or branched chain C.sub.1-4 alkyl) radical, n is 0, 1 or 2, and either R.sub.1 is a pyridinio ion and R.sub.2 is a carboxylato ion, or R.sub.1 represents a hydrogen atom, or an acetoxy, (5-methyl-1,3,4-thiadiazol-2-yl)-thio or (1-methyl-1,2,3,4-tetrazol-5-yl)-thio radical and R.sub.2 represents a carboxy radical or a radical of the formula; ##STR2## in which the radical: ##STR3## is a radical which can be removed easily by enzymatic means and in which R.sub.3 represents a hydrogen atom or a straight or branched chain C.sub.1-4 alkyl radical, a phenyl radical or a phenyl (C.sub.1-2 alkyl) radical and R.sub.4 represents a straight or branched chain C.sub.1-4 alkyl radical, a straight or branched chain C.sub.1-4 alkoxy radical, a cyclohexyl radical, a phenyl radical or a phenyl (C.sub.1-2 alkyl) radical;

Cephalosporin derivatives, and compositions containing them

New cephalosporin compounds of the formula: ##STR1## in which A is oxygen or sulphur, R.sub.1 is hydrogen or acetoxy and R.sub.2 is carboxy or a radical of the formula: ##STR2## in which the radical ##STR3## is a radical which can be easily removed enzymatically, and in which R.sub.3 is hydrogen or straight or branched chain C.sub.1-4 alkyl and R.sub.4 is straight or branched chain C.sub.1-4, alkyl or cyclohexyl, together with its diastereoisomeric forms and mixtures thereof, its acid addition salts and, where appropriate, its pharmaceutically acceptable non-toxic metal salts and addition salts with nitrogen-containing bases other than ammonia, exhibit valuable anti-bacterial properties, in particular against Gram-positive and Gram-negative bacteria.

1,4-Dithiin (and oxathiin)-yl cephalosporin derivatives, and

Compounds of the formula: ##STR1## wherein one of the symbols =X-- represents =N-- and the other three each represent a group ##STR2## in which Y represents hydrogen, halogen, alkyl, alkoxy, cyano or nitro, at least two of the symbols representing hydrogen, Z represents hydrogen, halogen, alkyl, alkoxy, trifluoromethyl or nitro, and (i) n represents zero and R represents hydrogen, alkyl, alkenyl, alkynyl, hydroxyalkyl or phenyl, or (ii) n represents 1 and R represents alkyl, hydroxyalkyl or phenyl, are new compounds possessing pharmacological properties; they are particularly active as tranquilizers and anti-convulsant agents.

Naphthyridine derivatives

New cephalosporin derivatives of the formula: ##STR1## wherein one of A and A.sub.1 represents oxygen or sulphur and the other represents sulphur, R.sub.1 represents hydrogen, acetoxy, (5-methyl-1,3,4-thiadiazol-2-yl)thio or (1-methyl-1,2,3,4-tetrazol-5-yl)thio and R.sub.2 represents carboxy, or R.sub.1 represents a pyridinio radical and R.sub.2 represents the carboxylate ion, are therapeutically useful compounds possessing antibacterial properties.

Isoindolin-1-one derivatives carrying on the nitrogen atom in the 2-position a phenyl or pyridyl radical, optionally carrying one or two substituents selected from halogen, alkyl (C.sub.1 -C.sub.4), alkoxy (C.sub.1 -C.sub.4), cyano and trifluoromethyl, and in the 3-position a grouping --O--T--NR.sub.1 R.sub.2 wherein T is alkylene (C.sub.2 -C.sub.6), and R.sub.1 and R.sub.2 represent hydrogen or alkyl (C.sub.1 -C.sub.4), are new compounds possessing pharmacodynamic properties and are useful as anti-arrhythmic agents.

3-(Isopropyl amino alkoxy)-2-phenyl-isoindolin-1-ones

Isoindolin-1-one derivatives substituted on the nitrogen atom in the 2-position by an unsubstituted or substituted phenyl radical or a heterocyclic radical having aromatic characteristics, substituted in the 3-position by a 3-amino(or substituted amino)-2-hydroxy-propoxy group, and optionally substituted in the 5-and/or 6-positions by one or two alkoxy radicals or optionally substituted in the 5- and 6-positions by a methylenedioxy radical, possess pharmacodynamic properties, and are especially useful as anti-arrhythmic agents.

Ampicillin is prepared by reacting an inorganic or organic base with a new penicillin G derivative of the formula: ##EQU1## (wherein R.sub.1 represents a group protecting the carboxy radical and R.sub.2 represents a strong electron-attracting group, e.g. a halogenoethyl group) to open the imidazolidine ring and give an intermediate product of the formula: ##EQU2## and removing by methods known per se the groups --R.sub.1 and R.sub.2 O--CS-- which protect the carboxy radical and amine functions respectively.

Process for the preparation of ampicillin

The invention provides 7-trichloroacetamido-3-desacetoxy-cephalosporanic acid derivatives of the formula: ##SPC1## Wherein R is a group which protects the carboxylic acid radical, which can be converted into 7-amino-3-desacetoxycephalosporanic acid by replacing the R-- and Cl.sub.3 C--CO-- radicals by hydrogen atoms.

7-Trichloroacetamido-3-desacetoxy-cephalosporanic acid esters

New compounds of the formula: ##SPC1## Wherein A is a phenyl, pyridyl, pyridazinyl, 2-, 3- or 4-quinolyl or naphthyridinyl radical, or a said radical substituted by one or two atoms or radicals selected from halogen, alkyl, alkoxy cyano and nitro, R is alkyl, alkenyl or hydroxyalkyl, and n is zero or 1, possess pharmacological properties and are, in particular, active as tranquilizers, anti-convulsant agents, decontracturants and agents to produce hypnosis.

1,4-Dithino[2,3-c]pyrrole compositions

New compounds of the formula: ##SPC1## Wherein A is a phenyl, pyridyl, pyridazinyl, 2-, 3- or 4-quinolyl or naphthyridinyl radical, or a said radical substituted by one or two atoms or radicals selected from halogen, alkyl, alkoxy cyano and nitro, R is alkyl, alkenyl or hydroxyalkyl, and n is zero or 1, possess pharmacological properties and are, in particular, active as tranquilisers, anti-convulsant agents, decontracturants and agents to produce hypnosis.

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Bievres, France

Mayer Naoum Messer