Hoffmann-la Roche Inc.

Robert W Lambert

Cedric H Hassall

Michael J Hall

Peter S Ringrose

Frank R Atherton

Gareth J Thomas

Joseph A Martin

Sally Redshaw

Geoffrey Lawton

Michael Richard Attwood

Compounds of the formula ##STR1## wherein R.sup.1 is halogen, C.sub.1-4 -alkyl, halo-(C.sub.1-4 -alkyl) or C.sub.2-4 -alkanoyl,

Method of treating herpes simplex viral infection employing pyrimidine

Compounds of the formula ##STR1## wherein A is C.sub.1-8 -alkylene, R.sup.1 is halogen, C.sub.1-4 -alkyl or halo-(C.sub.1-4 -alkyl), R.sup.2 is hydrogen, hydroxy or acyloxy, R.sup.3 is hydrogen or C.sub.1-4 -alkyl, R.sup.4 is aryl or aryloxy and X is O or NH,

Pyrimidine derivatives as an antiviral agent

Compounds of the formula ##STR1## wherein A is C.sub.1-8 -alkylene, R.sup.1 is halogen, C.sub.1-4 -alkyl or halo-(C.sub.1-4 -alkyl), R.sup.2 is hydrogen, hydroxy or acyloxy, R.sup.3 is hydrogen or C.sub.1-4 -alkyl, R.sup.4 is aryl or aryloxy and X is O or NH, and tautomers thereof are described. The compounds of formula I and their tautomers possess antiviral activity and can be used in the form of medicaments for the control and prevention of viral infections.

Pyrimidine derivatives, pharmaceutical compositions and method of using

Compounds of the formula ##STR1## wherein R.sup.1 is halogen, C.sub.1-4 -alkyl or halo-(C.sub.1-4 - alkyl), R.sup.2 is hydrogen, hydroxy or acyloxy, R.sup.3 and R.sup.4 each are hydrogen or C.sub.1-4 -alkyl, R.sup.5 is aryl or aryloxy, X is O or NH and Y is --CO--CH.sub.2 --, --CH(OH)--CH.sub.2 --, --CH.sub.2 --CH.sub.2 --, --S--, --SO-- or --SO.sub.2 --, and tautomers thereof are described. Compounds of formula I and their tautomers possess antiviral activity and can be used in the form of medicaments for the control and prevention of viral infections.

Pyrimidine derivatives

Novel compounds of the formula ##STR1## wherein B represents a methylene, ethylene or vinylene group, R.sup.1 represents a hydrogen atom or an alkyl, aralkyl, amino-alkyl, mono-alkylamino-alkyl, dialkylamino-alkyl, acylamino-alkyl, phthalimido-alkyl, alkoxycarbonylamino-alkyl, aryloxycarbonylamino-alkyl, aralkoxycarbonylamino-alkyl, alkylaminocarbonylamino-alkyl, arylaminocarbonylamino-alkyl, aralkylaminocarbonylamino-alkyl, alkylsulphonylamino-alkyl or arylsulphonylamino-alkyl group, R.sup.2 represents a carboxyl, alkoxycarbonyl or aralkoxycarbonyl group or a group of the formula ##STR2## , R.sup.3 represents a carboxyl, alkoxycarbonyl or aralkoxycarbonyl group, R.sup.4 and R.sup.5 each represent a hydrogen atom or R.sup.4 and R.sup.5 together represent an oxo group, R.sup.6 and R.sup.7 each represent a hydrogen atom or an alkyl or aralkyl group or R.sup.6 and R.sup.7 together with the nitrogen atom to which they are attached represent a 5-membered or 6-membered heteromonocyclic ring which may contain a further nitrogen atom or an oxygen or sulphur atom, and n stands for zero, 1 or 2, and pharmaceutically acceptable salts thereof have antihypertensive activity and can be used as medicaments in the form of pharmaceutical preparations.

Anthypertensive pyridazo [1,2-a][1,2]diazepines

Novel compounds of the formula ##STR1## wherein B represents a methylene, ethylene or vinylene group, R.sup.1 represents a hydrogen atom or an alkyl, aralkyl, amino-alkyl, mono-alkylamino-alkyl, dialkylamino-alkyl, acylamino-alkyl, phthalimido-alkyl, alkoxycarbonylamino-alkyl, aryloxycarbonylamino-alkyl, aralkoxycarbonylamino-alkyl, alkylaminocarbonylamino-alkyl, arylaminocarbonylamino-alkyl, aralkylaminocarbonylamino-alkyl, alkylsulphonyl-amino-alkly or arylsulphonylamino-alkyl group, R.sup.2 represents a carboxyl, alkoxycarbonyl or aralkoxycarbonyl carbonyl group or a group of the formula ##STR2## R.sup.3 represents a carboxyl, alkoxycarbonyl or aralykoxycarbonyl group, R.sup.4 and R.sup.5 each represent a hydrogen atom or R.sup.4 and R.sup.5 together represent an oxo group; R.sup.6 and R.sup.7 each represent a hydrogen atom or an alkyl or aralkyl group or R.sup.6 and R.sup.7 together with the nitrogen atom to which they are attached represent a 5-membered or 6-membered heteromonocyclic ring which may contain a further nitrogen atom or an oxygen or sulphur atom, and n stands for zero, 1 or 2, and pharmaceutically acceptable salts thereof have antihypertensive activity and can be used as medicaments in the form of pharmaceutical preparations.

Pyridazo[1,2]pyridazines and pyrazolo[1,2]pyridazines as

Novel compounds of the formula ##STR1## wherein B represents a methylene, ethylene or vinylene group, R.sup.1 represents a hydrogen atom or an alkyl, aralkyl, amino-alkyl, mono-alkylamino-alkyl, dialkylamino-alkyl, acylamino-alkyl, phthalimido-alkyl, alkoxycarbonylamino-alkyl, aryloxycarbonylamino-alkyl, aralkoxycarbonylamino-alkyl, alkylaminocarbonylamino-alkyl, arylaminocarbonylamino-alkyl, aralkylaminocarbonylamino-alkyl, alkylsulphonylamino-alkyl or arylsulphonylamino-alkyl group, R.sup.2 represents a carboxyl, alkoxycarbonyl or aralkoxycarbonyl group or a group of the formula ##STR2## R.sup.3 represents a carboxyl, alkoxycarbonyl or aralkoxycarbonyl group, R.sup.4 and R.sup.5 each represent a hydrogen atom or R.sup.4 and R.sup.5 together represent an oxo group, R.sup.6 and R.sup.7 each represent a hydrogen atom or an alkyl or aralkyl group or R.sup.6 and R.sup.7 together with the nitrogen atom to which they are attached represent a 5-membered or 6-membered heteromonocyclic ring which may contain a further nitrogen atom or an oxygen or sulphur atom, and n stands for zero, 1 or 2, and pharmaceutically acceptable salts thereof have antihypertensive activity and can be used as medicaments in the form of pharmaceutical preparations.

Pyrazolo [1,2-a][1,2]-diazepines useful as antihypertensives

Novel compounds of the formula ##STR1## wherein B represents a methylene, ethylene or vinylene group, R.sup.1 represents a hydrogen atom or an alkyl, aralkyl, amino-alkyl, mono-alkylamino-alkyl, dialkylaminoalkyl, acylamino-alkyl, phthalimido-alkyl, alkoxycarbonylamino-alkyl, aryloxycarbonylamino-alkyl, aralkoxycarbonylamino-alkyl, alkylaminocarbonylamino-alkyl, arylaminocarbonylamino-alkyl, aralkylaminocarbonylamino-alkyl, alkylsulphonylamino-alkyl or arylsulphonylamino-alkyl group, R.sup.2 represents a carboxyl, alkoxycarbonyl or aralkoxycarbonyl group or a group of the formula ##STR2## R.sup.3 represents a carboxyl, alkoxycarbonyl or aralkoxycarbonyl group, R.sup.4 and R.sup.5 each represent a hydrogen atom or R.sup.4 and R.sup.5 together represent an oxo group, R.sup.6 and R.sup.7 each represent a hydrogen atom or an alkyl or aralkyl group or R.sup.6 and R.sup.7 together with the nitrogen atom to which they are attached represent a 5-membered or 6-membered heteromonocyclic ring which may contain a further nitrogen atom or an oxygen or sulphur atom, and n stands for zero, 1 or 2, and pharmaceutically acceptable salts thereof have antihypertensive activity and can be used as medicaments in the form of pharmaceutical preparations.

Pyridazo[1,2-a][1,2]diazepines

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.

Growing community of inventors

Welwyn, United Kingdom

Robert W Lambert