Beecham Group Plc

Robert Southgate

Roger J Ponsford

Terence C Smale

Michael J Pearson

John Herbert Nayler

Andrew J Baxter

Patricia M Roberts

David F Corbett

Kay H Dickinson Nee Berryman

Kay H Dickinson

Steven Coulton

Alfred J Eglington

Pamela Brown

Colin H Frydrych

Antibacterial agents have the formula (I) or are pharmaceutically acceptable salts or in vivo hydrolysable esters thereof: ##STR1## wherein R.sup.3 is phenyl, substituted phenyl, cyclohexenyl, cyclohexadienyl or an optionally substituted 5- or 6-membered heterocyclic ring containing up to three hetero atoms selected from oxygen, sulphur or nitrogen, R.sup.4 is hydrogen or formamido, R.sup.5 is hydrogen, C.sub.1-6 alkyl, substituted alkyl, aryl or aralkyl, R.sup.6 and R.sup.7 are the same or different and represent hydrogen, C.sub.1-6 alkyl, substituted alkyl, halogen, amino, phenyl, substituted phenyl, hydroxyl or C.sub.1-6 alkoxy or R.sup.6 and R.sup.7 form the residue of an optionally substituted 5- or 6-membered carbocyclic ring or a 5- or 6- membered heterocyclic ring containing up to three hetero atoms selected from oxygen, sulphr or nitrogen, and X represents ##STR2## or tautomers thereof wherein R.sup.8 and R.sup.9 are the same or different and each represents hydroxy, or protected hydroxy.

Penam derivatives

A process for the preparation of a compound of the formulae (Ia) and/or (Ib): ##STR1## wherein R.sup.1 and R.sup.2 are independently substituted or unsubstituted hydrocarbon groups or are joined together so as to form a carbocyclic or heterocyclic ring, and R.sup.3 is a substituted or unsubstituted hydrocarbon group; which process comprises the ring-closing cyclization of a compound of the formula (II): ##STR2## wherein R.sup.1, R.sup.2 and R.sup.3 are as defined in relation to formulae (Ia) and (Ib).

Chemical process

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 present invention provides a process for inversion of the absolute stereochemistry at the .alpha.-carbon atom of a C-6 substituent of a bicyclic carbapenem antibiotic via a phosphorus - azodicarboxylate mediated reaction. Novel azides, amines and formates are described as useful intermediates and as antibacterial agents.

.beta.-Lactam antibiotics their preparation and their use

Compounds are described of the formula (II): ##STR1## wherein R.sub.1 is a group such that CO.sub.2 R.sub.1 is an ester group; A.sub.1 is a hydrogen atom; and A.sub.2 is a group CR.sub.2 R.sub.3 R.sub.4 wherein R.sub.2 is a hydrogen atom or a hydroxyl group; R.sub.3 is a hydrogen atom or a lower alkyl group; and R.sub.4 is a hydrogen atom or a lower alkyl group, a benzyl group, a phenyl group or is joined to R.sub.3 to form part of a C.sub.5-7 carboxylic ring or is a group of the formula CH(OH)R.sub.5 or CHX wherein R.sub.5 is a hydrogen atom or lower alkyl group and X is an oxygen atom or a CR.sub.6 R.sub.7 group where R.sub.6 is a hydrogen atom or a lower alkyl, phenyl, CN, CO.sub.2 R.sub.8 where R.sub.8 is a lower alkyl, phenyl or benzyl group and R.sub.7 is a hydrogen atom or a lower alkyl group or is joined to R.sub.6 to form part of a C.sub.5-7 carbocyclic ring. These compounds have been found to possess antibacterial properties. The preparation of these compounds is described.

Beta-lactam antibacterial agents

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;

.beta.-Lactam antibacterial agents

Compounds are provided of the formula (II): ##STR1## wherein R.sub.1 is a group such that CO.sub.2 R.sub.1 is an ester group and A.sub.1 is a hydrogen atom or a methyl group. These compounds possess antibacterial activity. The preparation of these compounds is described.

4-Allyl azetidinone intermediate for .beta.-lactam antibacterial agents

The present invention provides the compounds of the formula (II): ##STR1## and pharmaceutically acceptable salts and esters thereof wherein R.sup.3 is a hydrogen atom, a group HO.sub.3 S-- or a group R.sup.5 CO wherein R.sup.5 is C.sub.1-6 alkyl, C.sub.2-6 alkenyl, aryl, aryl(C.sub.1-6)alkyl or aryloxy(C.sub.1-6)alkyl; and R.sup.4 is an organic group other than methyl bonded to the --CO--NH-- moiety via a carbon atom; with the proviso that when R.sup.3 is a hydrogen atom or a group R.sup.5 CO the stereochemical configuration at the .alpha.-carbon atom of the C-6 substituent is S, and with the further proviso that when R.sup.3 is a group HO.sub.3 S-- the hydrogen atoms at C-5 and C-6 are cis. Their use is described as are processes for their preparation. Compounds wherein the R.sup.4 CO-- moiety is replaced by a hydrogen atom are also prepared.

.beta.-Lactam antibiotics, their preparation and their use in

The present invention relates to sodium, thallium, silver or lithium salts of the compound

.beta.-Lactam antibiotics, a process for their preparation and their use

The present invention provides the antibacterial agents 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 thereof or is a group of the formula CO.sub.2 R.sub.1.sup.1 wherein R.sub.1.sup.1 is a group such that CO.sub.2 R.sub.1.sup.1 is an ester group, R.sub.2 is a hydrogen atom or a lower alkyl group; R.sub.3 is a hydrogen atom or a lower alkyl group; and R.sub.4 is a phenyl group or a phenyl group substituted by one or two groups selected from fluorine, chlorine, OR.sub.5, NH.CO.R.sub.5, NH.CO.sub.2 R.sub.5 or CO.sub.2 R.sub.5 where R.sub.5 is a lower alkyl or benzyl group. A process for their preparation and their use in pharmaceutical compositions is also described.

The present invention provides the antibacterial agents 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 thereof or is a group of the formula CO.sub.2 R.sub.1.sup.1 wherein R.sub.1.sup.1 is a group such that CO.sub.2 R.sub.1.sup.1 is an ester group, R.sub.2 is a hydrogen atom or a lower alkyl group; R.sub.3 is a hydrogen atom or a lower alkyl group; and R.sub.4 is a NH. CO.sub.n R.sub.6 group where R.sub.6 is a lower alkyl group, a phenyl group or a phenyl group substituted by one or two halogen atoms, lower alkyl or lower alkoxyl groups; and n is 1 or 2. A process for their preparation and their use in pharmaceutical compositions is also described.

.beta.-Lactam antibiotics, a process for their prepaeration and their

Compounds of the formula (III): ##STR1## wherein R.sub.1 is alkyl of up to 3 carbon atoms and R.sub.2 is alkyl of up to 3 carbon atoms optionally joined to R.sub.1 so that R.sub.1 and R.sub.2 and the carbon atom to which they are attached form a spiro-cyclopentyl or spiro-cyclohexyl ring, and wherein the configuration about the .beta.-lactam ring is trans, are useful in the preparation of antibacterial .beta.-lactam compounds. A process for the preparation of the compounds of the formula (III), is also desired.

Novel intermediates for .beta.-lactams

This invention provides synthetic .beta.-lactam antibacterial compounds, a process for their preparation and pharmaceutical compositions containing them. The compounds are those 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; and R.sub.2 is a phenyl group or a phenyl group substituted by one to four groups selected from lower alkyl, fluorine, chlorine, bromine, CN, NO.sub.2, COR.sub.3, OR.sub.3, SR.sub.3, NH.sub.2, NHCOR.sub.3, NHCO.sub.2 R.sub.3, CO.sub.2 R.sub.3 or CO.sub.2 R.sub.10 where R.sub.3 is lower alkyl, benzyl, fluorobenzyl, chlorobenzyl, bromobenzyl or nitrobenzyl and CO.sub.2 R.sub.10 is carboxyl or a salt thereof, not more than three such groups being selected from fluorine, chlorine, bromine, CN, NO.sub.2, NH.sub.2, COR.sub.3 or CO.sub.2 R.sub.3 and not more than two such groups being selected from CN, NO.sub.2 and NH.sub.2.

Growing community of inventors

Warnham, United Kingdom

Robert Southgate