Hoffmann-la Roche Inc.

Malcolm Page

Peter Angehrn

Ingrid Heinze-Krauss

Paul Hebeisen

Hans G Richter

Urs Weiss

Valerie Runtz

The invention relates to antimicrobial compositions comprising a combination of (1) a therapeutically effective amount of a compound of formula I ##STR1## with (2) a second ingredient selected from carbapenem antibiotics or with .beta.-lactamase inhibitors, to the use of the compositions for producing a medicament for the treatment and prophylaxis of infectious diseases, including MRSA infections, and to pharmaceutical compositions containing the combination.

Antimicrobial compositions

The present invention relates to compounds having the formula ##STR1## wherein X, R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6, and R.sup.7 are as defined herein as well as readily hydrolyzable esters thereof, pharmaceutically acceptable salts of said compounds and hydrates of the compounds of formula I and of their esters and salts. These compounds have valuable pharmacological activity for the treatment and prophylaxis of infectious diseases, especially those caused by methicillin resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa.

Vinyl-pyrrolidinone cephalosporins

Compounds of formula I wherein R.sup.1 is hydrogen, lower alkyl which is unsubstituted or substituted by fluoro, aralkyl, cycloalkyl, --COR.sup.4 or --C(R.sup.5 R.sup.6)CO.sub.2 R.sup.7 --C(R.sup.5 R.sup.6)CONHR.sup.7 ; where R.sup.5 and R.sup.6 are each independently hydrogen or lower alkyl, or R.sup.5 and R.sup.6 taken together form a cycloalkyl group; R.sup.4 is hydrogen or lower alkyl and R.sup.7 is hydrogen, lower alkyl, lower alkenyl or a carboxylic acid protecting group; R.sup.2 is hydrogen, hydroxy, lower alkyl-Q.sub.m, cycloalkyl, lower alkoxy, lower alkenyl, cycloalkenyl, lower alkynyl, aralkyl-Q.sub.m, aryl-Q.sub.m, aryloxy, aralkoxy, a heterocyclic ring or heterocyclyl lower alkyl, the lower alkyl, cycloalkyl, lower alkoxy, lower alkenyl, cycloalkenyl, lower alkynyl, aralkyl, aryl, aryloxy, aralkoxy and the heterocyclic ring being unsubstituted or substituted with at least one group selected from carboxy, amino, nitro, cyano, lower alkyl which is unsubstituted or substituted by fluoro, lower alkoxy, hydroxy, halogen, --COR.sup.6, --C(R.sup.5 R.sup.6)CO.sub.2 R.sup.7, --C(R.sup.5 R.sup.6)CONR.sup.5 R.sup.8, --CONR.sup.5 R.sup.6, --N(R.sup.6)COOR.sup.10, R.sup.6 OCO-- or R.sup.6 COO-- where R.sup.5 and R.sup.6 are hydrogen or lower alkyl; R.sup.7 is hydrogen, lower alkyl, lower alkenyl or a carboxylic acid protecting group; R.sup.8 is hydrogen, lower alkyl or phenyl which is unsubstituted or substituted with at least one halogen, hydroxy, amino, lower alkyl, or lower alkoxy; R.sup.10 is lower alkyl, lower alkenyl or a carboxylic acid protecting group; Q is --CHR--, --CO-- or --SO.sub.2 --; R is hydrogen or lower alkyl; R.sup.3 is hydroxy, --O--, lower alkoxy, --OM and M represents an alkali metal; m is 0 or 1; n is 0, 1 or 2; x is CH or N as well as readily hydrolysable esters thereof, pharmaceutically acceptable salts of said compounds and hydrates of the compounds of formula I and of their esters and salts are provided. These compounds have valuable antiinfective properties.

1-carba-(dethia)-cephalosporin derivatives

Compounds of formula I ##STR1## wherein R.sup.1 is hydrogen, lower alkyl, cycloalkyl or acetyl;

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Basel, Switzerland

Malcolm Page