Hoffmann-la Roche Inc.

Basilea Pharmaceutica Ag

Basilea Parmaceutica Ag

Peter Angehrn

Ingrid Heinze-Krauss

Malcolm Page

Paul Hebeisen

Gottfried Alber

Hans G F Richter

Hans G Richter

Daniel Hunziker

Helmut Link

Werner Hofheinz

Chung-Chen Wei

Roland Reiner

Andre Furlenmeier

Urs Weiss

Pierre-Charles Wyss

Erwin G&ouml;tschi

Valerie Runtz

Macrolides with antibacterial activity

Propenyl cephalosporin derivatives and process for the manufacture thereof

The present invention relates to cephalosporin derivatives of the general formula

Vinylpyrrolidinone cephalosporin derivatives

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;

Cephalosporin pyridinium derivatives

The present invention is directed to products containing G-CSF and a TNF binding protein and compositions of G-CSF and TNF-BP, and methods of treating and/or preventing septic shock by administering the products and compositions of the invention.

Compositions of G-CSF and TNF-BP for prophylaxis and treatment of septic

The present invention relates to compounds of the formula ##STR1## wherein R.sup.1 is an acyl group derived from a carboxylic acid, hydrogen, or an amino protecting group;

Cephalosporin antibiotics

Cephalosporin derivatives have the formula ##STR1## wherein Z.sup.1, Z.sup.2, X, Y, P, Q, m, n and p are as defined in the following text. Also described are the readily hydrolyzable esters and pharmaceutically compatible salts of these compounds, and hydrates of compounds of formula I, their esters and salts. Processes are provided for manufacture and pharmaceutical preparations which contain these compounds. Intermediates from the manufacture of these compounds are described, as is the use of the compounds in the control of illnesses and for the manufacture of the aforementioned preparations.

Cephalosporin derivatives

The antibacterially-active substance composition consisting of mecillinam and (2S,3S)-3-((Z)-2-(2-amino-4-thiazolyl)-2-((carboxymethoxy)imino)acetamido) -2-((carbamoyloxy)methyl-4-oxo-1-azetidinesulphonic acid (compound A), or pro-drugs and/or pharmaceutically usable salts thereof, has a pronounced synergism against Enterobacter strains which are resistant to mecillinam and which are only moderately sensitive to compound A.

Antibacterial composition

There is provided cephalosporin derivatives of the formula ##STR1## in which R.sup.1 is carboxy-lower alkyl and

Growing community of inventors

Bockten, Switzerland

Peter Angehrn