Beecham Group Plc

Roger J Ponsford

Thomas T Howarth

Robert Southgate

Michael J Pearson

Stephen C Finch

David F Corbett

Terence C Smale

Andrew J Baxter

Patricia M Roberts

Andrew V Stachulski

Steven Coulton

Allan Guildford Brown

Pamela Brown

Pamela Brown Nee Davis

Compounds of formula (I) and pharmaceutically acceptable salts and in-vivo hydrolysable esters thereof: ##STR1## wherein X is hydrogen or a group NHR.sup.1, wherein R.sup.1 is hydrogen or an amino protecting group, and R is an optionally substituted 5-membered or 6-membered saturated heterocyclic group containing 1 or 2 heteroatoms selected from oxygen, sulphur or nitrogen, are useful in the treatment of bacterial infections in humans and animals.

Penicillins containing an acrylamide side chain

Compounds of formula (I) and their salts and esters: ##STR1## wherein X is hydrogen or a group NHR.sup.1, wherein R.sup.1 is hydrogen or an amino protecting group, and R is optionally substituted C.sub.5-8 cycloalkyl or cycloalkenyl, are useful in the treatment of bacterial infections.

Penicillins having a substituted acrylamido side chain

A monocyclic .beta.-lactam antibiotic having a formamido substituent at the 3S-position, including compounds of the formula (I): ##STR1## and salts thereof wherein R is --SO.sub.3 H; --PO(OH)Y wherein Y is C.sub.1-6 alkoxy, hydroxy, aryloxy, C.sub.1-6 alkyl or aryl; ##STR2## wherein Z represents C.sub.1-6 alkyl or aryl; ##STR3## wherein Z.sup.1 and Z.sup.2 may be the same or different and each represents hydrogen, C.sub.1-6 alkyl, aryl, amino or C.sub.1-6 alkoxy, or Z.sup.1 and Z.sup.2 together form the residue of a heterocyclic ring; --OSO.sub.3 H; or ##STR4## where X is hydrogen or hydroxy; R.sup.1 is an amino, protected amino or carboxylic acylamino group, and R.sup.2 and R.sup.3 are independently selected from hydrogen or a hydrocarbon group of 1 to 18 carbon atoms.

3-formamido azetidinone antibacterial agents, their preparation and use

A monocyclic .beta.-lactam antibiotic having a formamido substitutent at the 3S-position, including compounds of the formula (I): ##STR1## and salts thereof wherein R is --SO.sub.3 H; --PO(OH)Y wherein Y is C.sub.1-6 alkoxy, hydroxy, aryloxy, C.sub.1-6 alkyl or aryl; ##STR2## wherein Z represents C.sub.1-6 alkyl or aryl; ##STR3## wherein Z.sup.1 and Z.sup.2 may be the same or different and each represents hydrogen, C.sub.1-6 alkyl, aryl, amino or C.sub.1-6 alkoxy, or Z.sup.1 and Z.sup.2 together form the residue of a heterocyclic ring; --OSO.sub.3 H; or ##STR4## where X is hydrogen or hydroxy; R.sup.1 is an amino, protected amino or carboxylic acylamino group, and R.sup.2 and R.sup.3 are independently selected from hydrogen or a hydrocarbon group of 1 to 18 carbon atoms.

3S-formamido azetidinone antibacterial agents, their preparation and use

Antibacterial agents, their preparation and use

The compounds of the formula (II): ##STR1## and salts and esters thereof wherein R is an inert organic group of up to 18 carbon atoms and are able to inhibit the action of various bacterial .beta.-lactamases. Thus when a compound of the formula (II) or its salt or ester is used together with a penicillin or cephalosporin, the effectiveness of that penicillin or cephalosporin can be considerably enhanced. These novel synergysts can be prepared by etherification of an ester of clavulanic acid followed if desired by deesterification. The novel synergysts also possess antibacterial activity.

Clavulanic acid ethers as antibacterial agents

The compounds of the formula (II): ##STR1## and salts and esters thereof wherein R is an inert ogranic group of up to 18 carbon atoms and are able to inhibit the action of various bacterial .beta.-lactamases. Thus when a compound of the formula (II) or its salt or ester is used together with a penicillin or cephalosporin, the effectiveness of that penicillin or cephalosporin can be considerably enhanced. These novel synergysts can be prepared by etherification of an ester of clavulanic acid followed if desired by deesterification. The novel synergysts also possess antibacterial activity.

Antibacterial agents

Compounds of the formula ##STR1## wherein X is S, SO or SO.sub.2 and R is an inert hydrocarbon of up to 20 carbon atoms which will not lead to rapid degradation of the above compound unsubstituted or substituted and A is a group such and CO.sub.2 A represents a carboxylic acid group or a salt or ester thereof, are useful for their antibacterial activity and for their .beta.-lactamase inhibitory activity.

Therapeutic compounds containing .beta.-lactams

A process for the preparation of an antibacterially active compound of the formula (I): ##STR1## and salts and esters thereof wherein R.sup.1 and R.sup.2 independently are hydrogen or an organic group, and R.sup.3 is an organic group bonded via a carbon atom to the sulphur atom, which comprises reacting a compound of the formula (II): ##STR2## wherein R.sup.4 is an organic group different to R.sup.3 and R.sup.a is hydrogen or a carboxy-blocking group, with a thiol R.sup.3 SH or reactive derivative thereof. In addition certain compounds within the formula (II) are novel and useful antibacterial agents in their own right.

2-Substituted thio carbapenem derivatives

The compounds of the formula (II): ##STR1## wherein R.sub.1 is a group such that CO.sub.2 R.sub.1 is a carboxylic acid group or a salt or ester thereof; R.sub.2 is a group of the sub-formula (a) or (b):

.beta.-Lactam containing compounds, their preparation and use

The compounds of the formula (II): ##STR1## and salts and esters thereof wherein R.sub.1 is an inert organic group of up to 14 carbon atoms and R.sub.2 is an inert organic group of up to 16 carbon atoms, the group NR.sub.1 R.sub.2 containing up to 22 carbon atoms, are antibacterial agents able to enhance the effectiveness of penicillins and cephalosporins against certain .beta.-lactamase producing bacteria.

Antibiotics

The present invention provides a compound of formula (I): ##STR1## wherein R.sup.1 is a group such that COOR.sup.1 is a carboxyic acid group or a salt or ester thereof;

Compounds of the formula ##STR1## wherein X is S, SO or SO.sub.2 and R is an organic group of up to 20 carbon atoms and A is a group such that CO.sub.2 A represents a carboxylic acid group or a salt or ester thereof, are useful for their antibacterial activity and for their .beta.-lactamase inhibitory activity.

The present invention provides a compound of the formula (I): ##STR1## or a pharmaceutically acceptable salt or in-vivo hydrolyzable ester thereof wherein R.sup.1 is a hydrogen atom, an .alpha.-sulphonato-oxyethyl group, an .alpha.-sulphonato-oxypropyl group or is a group CR.sup.3 R.sup.4 R.sup.5 wherein R.sup.3 is a hydrogen atom or a hydroxy group; R.sup.4 is a hydrogen atom or a C.sub.1-6 alkyl group; and R.sup.5 is a hydrogen atom or a C.sub.1-6 alkyl group, a benzyl group, a phenyl group or is joined to R.sup.4 to form together with the carbon atom to which they are joined a carbocyclic ring of 5 to 7 carbon atoms; R.sup.2 is a pyrimidinyl group substituted by one two or three groups selected from nitro, halo, amino or substituted amino, and in addition may be optionally substituted by one or two C.sub.1-6 alkyl groups as the degree of substitution permits; and x is zero or one. These compounds are antibacterial agents. Their preparation and use are described.

.beta.-Lactam antibiotics, their preparation and use

The compounds of the formula (II): ##STR1## and salts and esters theereof wherein R.sub.1 is an inert organic group of up to 14 carbon atoms and R.sub.2 is an inert organic group of up to 16 carbon atoms, the group NR.sub.1 R.sub.2 containing up to 22 carbon atoms, are antibacterial agents able to enhance the effectiveness of penicillins and cephalosporins against certain .beta.-lactamase producing bacteria.

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Horsham, United Kingdom

Roger J Ponsford