Hoffmann-la Roche Inc.

Peter S Ringrose

Cedric H Hassall

Robert W Lambert

Michael J Hall

Frank R Atherton

Peptide derivatives provided by the present invention are compounds of the general formula ##STR1## wherein R.sup.1 represents a hydrogen atom or the methyl or hydroxymethyl group or a mono-, di- or trihalomethyl mgroup; R.sup.2 represents the characterizing group of an .alpha.-amino acid of the type normally found in proteins or a lower alkyl or hydroxy- (lower alkyl) group other than the characterising group of an .alpha.-amino acid of the type normally found in proteins; R.sup.3 represents a lower alkyl, lower cycloalkyl, lower alkenyl, aryl or aryl-(lower alkyl) group; R.sup.4 represents a hydrogen atom or a lower alkyl group; n stands for 1,2 or 3; the configuration at the carbon atom designated as (a) is (R) when R.sup.1 represents other than a hydrogen atom and the configuration at the carbon atom designated as (b) is (L) when R.sup.2 represents other than a hydrogen atom, and pharmaceutically acceptable salts thereof. The compounds exhibit activity as antibacterial agents against a range of gram-positive and gram-negative bacteria. Also disclosed are intermediates and a process for the production of the end product.

Acyl derivatives

The present disclosure relates to halo-phosphonopeptides. The subject compounds are antibacterial agents and also potentiate the activity of antibiotics.

Halo-phosphonopeptides

Compositions having antibiotic properties containing as antibiotic potentiators peptides of the formula ##STR1## wherein R.sup.1 represents a hydrogen atom or a lower alkyl, lower cycloalkyl, (lower cycloalkyl)-(lower alkyl), aryl or aryl(lower alkyl) group (said group being optionally substituted as the case may require by one or more amino, hydroxy, thio, methylthio, carboxy or guanidino groups so as to form the characterizing group of a naturally occurring L .alpha.-amino acid);

Compositions having antibiotic properties

There is provided peptide derivatives of the general formula ##STR1## wherein R.sup.1, R.sup.2 and R.sup.3 each represent the characterizing group of an .alpha.-amino acid of the type normally found in proteins; R.sup.4 represents a hydroxy or methyl group; n stands for zero, 1, 2 or 3; the configuration at the carbon atoms designated as (a), (b) and (c) is L (when R.sup.1 or R.sup.2 .noteq. H); and the configuration at the carbon atom designated as (d) is (R) (when R.sup.3 .noteq. H) and pharmaceutically acceptable salts thereof. The above compounds exhibit antibacterial activity against various microorganisms.

Peptide derivatives

Compositions having antibiotic properties containing as antibiotic potentiators peptides of the formula ##STR1## wherein R.sup.1 represents a hydrogen atom or a lower alkyl, lower cycloalkyl, (lower cycloalkyl)-(lower alkyl), aryl or aryl-(lower alkyl) group (said group being optionally substituted as the case may require by one or more amino, hydroxy, thio, methylthio, carboxy or guanidino groups so as to form the characterizing group of a naturally occurring L .alpha.-amino acid);

Compositions having antibiotic properties containing as antibiotic potentiators peptides of the formula ##STR1## wherein R.sup.1 represents a hydrogen atom or a lower alkyl, lower cycloalkyl, (lower cycloalkyl)-(lower alkyl), aryl or aryl(lower alkyl) group (said group being optionally substituted as the case may require by one or more amino, hydroxy, thio, methylthio, carboxy or guanidino groups so as to form the characterizing group of a naturally occurring L .alpha.-amino acid); R.sup.2 and R.sup.3 each represent the characterizing group of an .alpha.-amino acid of the type normally found in proteins with the proviso that R.sup.3 cannot represent a hydrogen atom when n is zero and R.sup.1 is a hydrogen atom or the phenyl group; R.sup.4 represents a hydroxy or methyl group; n stands for zero, 1, 2 or 3; and single asterisks denote that the configuration at the carbon atom so-marked is L when R.sup.2 or R.sup.3 as the case may be represents other than a hydrogen atom; and the double asterisk denotes that, when R.sup.1 represents other than a hydrogen atom, the configuration at the carbon atom so-marked is (R) (as hereinafter defined), And an antibiotic are disclosed.

The present disclosure relates to peptide derivatives. More particularly, the disclosure is concerned with peptide derivatives of phosphonic and phosphinic acids, a process for the manufacture thereof and pharmaceutical preparations containing same.

Growing community of inventors

Harston, United Kingdom

Peter S Ringrose