Merck Patent Gesellschaft MIT Beschrankter Haftung

Merck Patent Gesellschaft MIT Beschraenkter Haftung

E. Merck, Patentabteilung

Werner Rogalski

Helmut Wahlig

Rolf Bergmann

Rudolf Gottschlich

Richard Kirchlechner

Rosmarie Steinigeweg

Walter Hameister

Rolf Gericke

Joachim Gante

Dieter Orth

Elvira Dingeldein

Jurgen Seubert

Juergen Seubert

Flavonoid phosphates of aminoglycoside antibiotics are useful sparingly soluble salts, e.g., for achieving a depot effect.

Flavonoid phosphate salts of aminoglycoside antibiotics

Novel pyridone-acetic acid derivative, viz. 3,5-dichloro-4-pyridone-1-acetic acid (I) is used as an intermediate in the production of certain cephem derivatives having anti-bacterial activity against gram-negative and gram-positive bacteria. The acid (I) is prepared by methods generally known in the art, e.g. by reacting 3,5-dichloro-4-pyridone with chloracetic acid or bromoacetic acid.

Pyridone-acetic acid derivative

Cephem derivatives of the formula ##STR1## wherein Z is 1,4-dihydro-4-oxo-1-pyridyl or the corresponding group substituted by one or more of alkyl of 1-4 carbon atoms, alkoxy of 1-4 carbon atoms, OH, F, Cl, Br, I, NO.sub.2 and NH.sub.2 ; and R is H, --OCOCH.sub.3 or -S-Het, wherein Het is 3-methyl-1,2,4-thiadiazolyl-5, 5-methyl-1,3,4-oxadiazolyl-2, 5-hydroxymethyl-1,3,4-oxadiazolyl-2, 5-methyl-1,3,4-thiadiazolyl-2, 5-hydroxymethyl-1,3,4-thiadiazolyl-2, tetrazolyl-5, 1-methyltetrazolyl-5, 1,2,3-triazolyl-4, 4-methyl-oxazolyl-2 or 1-oxidopyridinio-2, and the readily cleavable esters thereof and the physiologically acceptable salts thereof, possess anti-bacterial activity and can be prepared by reacting a 3-CH.sub.2 R-7-amino-3-cephem-4-carboxylic acid or a functional derivative thereof with a pyridone acetic acid of the formula Z-CH.sub.2 -COOH or a functional derivative thereof.

1,4-Dihydro-4-oxo-pyridylacetamido cephalosporins and their utilization

Carbamic acid lactones of the formula ##STR1## wherein Y is H or alkyl of 1-4 carbon atoms and R.sub.2 and R.sub.3 each are H or collectively with the carbon atoms to which they are attached form a first benzene or pyridine ring which is unsubstituted, substituted by up to two of alkyl, alkoxy of 1-4 carbon atoms, dialkylamino or halogen, wherein alkyl and alkoxy in each instance are of 1-4 carbon atoms, or is fused at two adjacent carbons to a second benzene or pyridine ring, are useful as intermediates for the production of penicillins by reaction with a penicillin of the formula ##STR2##

Penicillins and their preparation

Penicillins of the formula ##STR1## wherein X is O or S; Y is H or alkyl; Z is ##STR2## R.sub.1 is H or OH; and R.sub.2 and R.sub.3 each are H or wherein X is O or S; Y is H or alkyl; R.sub.2 and R.sub.3 each are H or taken together with the carbons to which they are attached form an aromatic six-membered carbocyclic or N-heterocyclic ring and alkyl, alkoxy, dialkylamino or halogen derivatives thereof are active against Gram-positive and Gram-negative bacteria.

Novel penicillins and their preparation

Tetracyclic compounds of the formula ##STR1## wherein R.sup.1, R.sup.2, R.sup.3 and R.sup.4 each are H or alkyl, R.sup.5 is H, F, Cl, Br, CF.sub.3, OH, alkyl, alkoxy, NO.sub.2, NH.sub.2, alkylamino, dialkylamino or acylamino and X is O, S, SO, SO.sub.2, NH, N-alkyl or N-acyl, alkyl and alkoxy in each case being of 1-3 carbon atoms and acyl in each case being of 1-4 carbon atoms, with the proviso that when R.sup.5 is methoxy and X is a sulfur atom, R.sup.5 is in the 8- or 9-position only, and their physiologically acceptable acid addition salts, possess broad spectrum antibacterial activity, including tetracycline-resistant Gram-positive and Gram-negative organisms.

Tetracyclic compounds

7-Methoxy-6-thiatetracyclines of the formula ##SPC1## Wherein R.sup.1, R.sup.2, R.sup.3 and R.sup.4 each are H or alkyl of 1 to 4 carbon atoms, and the physiologically acceptable acid addition salts thereof.

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Darmstadt, Germany

Werner Rogalski