Beecham Group Plc

John B Harbridge

Irene Stirling

Thomas T Howarth

Brian P Clarke

George R Fosker

Ronald Hubbard

A compound of formula I ##STR1## or a salt or ester thereof. Processes for the preparation of these compounds and the use of these compounds in the preparation of further bicyclic compounds are also disclosed.

Deadcat reaction for making 9-deoxy-9-isocyanato clavulanates

The compounds of the formula (II): ##STR1## or pharmaceutically acceptable salts or esters thereof wherein A is a hydrogen atom or an esterifying radical; X is an alkyl group of 1-12 carbon atoms optionally substituted by a hydroxy, amino, acylamino of C.sub.1-6 alkoxy group, which substituents are not on the carbon atom adjacent to the nitrogen atom; or a C.sub.5-7 cycloalkyl group; or a phenylalkyl group wherein the carbon atom content of the alkyl part is 1-6 and the phenyl part is optionally substituted with a fluorine, bromine, chlorine, C.sub.1-6 alkyl, or C.sub.1-6 alkoxy; with the proviso that when X represents an optionally substituted phenylalkyl group and A represents C.sub.1-3 alkyl, then the --CO.sub.2 A group is attached to the alkyl part of the phenylalkyl group; have been found to be .beta.-lactamase inhibitors and antibacterial agents. Their preparation and use is described.

A-deoxy-a-aza derivatives of clavulanic acid, a process for their

Tetrazolyl derivatives of clavulanic acid are described, having the formula: ##STR1## wherein X is an optionally substituted tetrazolyl group attached via a nitrogen atom. These compounds are useful as antibiotics and .beta.-lactamase inhibitors.

Derivatives of clavulanic acid their preparation and their use

9-deoxy-9-isocyanato clavulante intermediates

9-deoxy-9-tetrazolyl-derivatives of clavulanic acid, their preparation

A compound of formula (I) or a salt or ester thereof: ##STR1## Pharmaceutical compositions comprising a compound of formula (I) or a pharmaceutically acceptable salt or pharmaceutically acceptable ester thereof are also disclosed.

Compounds containing beta-lactams

Derivatives of clavulanic acid, their preparation and their use

Derivatives of clavulanic acid, a process for their preparation and

The compounds of the formula (II): ##STR1## wherein R.sub.3 and R.sub.4 are as defined in relation to formula (I) and R.sub.7 is a nitro, cyano, amino or aminomethyl group, are antibacterial agents and .beta.-lactamase inhibitors. Their use and a process for their preparation are described.

Clavulanic acid derivatives, a process for their preparation and their

Benzylamino clavulanates and their production

Compounds of the formula (II): ##STR1## wherein X is sulphur or oxygen and R is hydrogen or alkyl of 1 to 3 carbon atoms, are useful for their antibacterial, .beta.-lactamase inhibitory activity and synergistic activity when combined with a penicillin or cephalosporin.

Clavulanic acid derivatives a process for their preparation and their

Methylaminodeoxy-clavulanic acid derivatives, their production and use

Compounds of the formula (II): ##STR1## wherein A is a group such that CO.sub.2 A is carboxylic acid, a non-toxic salt thereof or non-toxic ester thereof; R.sub.1 is COR.sub.4 or OR.sub.5 wherein R.sub.4 is lower alkyl, lower alkenyl, lower alkyl aryl or aryl and R.sub.5 is CO.sub.2 R.sub.6, COR.sub.6 or SO.sub.2 R.sub.6 wherein R.sub.6 is lower alkyl, lower alkenyl, lower alkyl aryl or aryl; and R.sub.2 is COR.sub.8 wherein R.sub.8 is lower alkyl, lower alkenyl, lower alkyl aryl or aryl; when R.sub.1 is COR.sub.4 and R.sub.2 is COR.sub.8, R.sub.4 and R.sub.8 are joined so that the N(COR.sub.4) COR.sub.8 moiety is a 5-,6-, or 7-membered heterocyclic ring or said ring to which is fused a phenyl ring unsubstituted or substituted by one or two lower alkyl, lower alkoxyl, fluorine or chlorine; when R.sub.1 is OR.sub.5 and R.sub.2 is COR.sub.8, R.sub.5 and R.sub.8 are joined so that the N(OR.sub.5) COR.sub.8 moiety is a 5-, 6-, or 7-membered heterocyclic ring, are useful for their antibacterial activity and as synergists for penicillins and cephalosporins.

Antibacterial agents

Compounds of the formula: ##STR1## wherein X is oxygen or sulphur, R is hydrogen or an inert organic group of up to 18 carbon atoms, and A is a group such that CO.sub.2 A represents a carboxylic acid group or a salt or ester thereof useful for their antibacterial activity and may be combined with a penicillin or cephalosporin to produce pharmaceutical compositions having enhanced antibacterial properties.

Clavulanic acid carbamates

Amides of the compound of the formula ##STR1## are useful for their .beta.-lactamase inhibitory activity.

Growing community of inventors

Coulsdon, United Kingdom

John B Harbridge