Pfizer Corporation

Braham Shroot

Charles A Baxter

Barry C Ross

David A Cox

A series of novel 7-(D-.alpha.-acylaminoarylacetamido)-.DELTA..sup.3 -cephem derivatives have been prepared wherein the acyl moiety contains an epoxy group immediately adjacent to the carbonyl carbon atom. These compounds are useful as antibacterial agents for the treatment of diseases caused by Gram-negative and Gram-positive bacteria. Preferred members include 7-[D-.alpha.-(cis-2-carboxyoxiran-3-carboxamido)phenylacetamido]-3-(1-meth yl-1,2,3,4-tetrazol-5-ylthiomethyl)-.DELTA..sup.3 -cephem-4-carboxylic acid and 7-[D-.alpha.-(cis-2-carboxyoxiran-3-carboxamido)phenylacetamido]cephalospo ranic acid. Alternate methods of preparation are provided for these compounds and the principal synthetic route is described in detail.

7[(Furanyl-2-acetamido)-2-acetamido]cephalosporin derivatives

A series of novel 7-(D-.alpha.-aminophenylacetamido)- and 7-(D-.alpha.-hydroxyphenylacetamido)-.DELTA..sup.3 -cephem derivatives have been prepared wherein a heterocyclic thiomethyl moiety is located at the 3-position of the molecule. These compounds are useful as antibacterial agents for the treatment of diseases caused by Gram-positive and Gram-negative bacteria. Preferred members include 7-(D-.alpha.-hydroxyphenylacetamido)-3-(3-carbamoyl-1,2,4-triazol-5-yl)thi omethylceph-3-em-4-carboxylic acid and 7-(D-.alpha.-hydroxyphenylacetamido)-3-(2-carboxymethoxy-methyl-1,3,4-thia diazol-5-yl)thiomethylceph-3-em-4-carboxylic acid. Alternative methods of preparation are provided for these compounds, including various synthetic routes leading to the required novel heterocyclic thiol intermediates.

7-Aminophenylacetamido-.DELTA..sup.3 -cephem antibacterial agents and

Substituted mercaptothiadiazole compounds

A series of novel 7-(D-.alpha.-acylaminoarylacetamido)-.DELTA..sup.3 -cephem derivatives have been prepared wherein the acyl moiety contains an epoxy group immediately adjacent to the carbonyl carbon atom. These compounds are useful as antibacterial agents for the treatment of diseases caused by Gram-negative and Gram-positive bacteria. Preferred members include 7-[D-.alpha.-(cis-2-carboxyoxiran-3-carboxamido)phenylacetamido]-3-(1-meth yl-1,2,3,4-tetrazol-5-ylthiomethyl)-.alpha..sup.3 -cephem-4-carboxylic acid and 7-[D-.alpha.-(cis-2-carboxyoxiran-3-carboxamido)phenylacetamido]cephalospo ranic acid. Alternate methods of preparation are provided for these compounds and the principal synthetic route is described in detail.

Epoxy substituted cephalosporin derivatives

A series of novel 7-(D.alpha.-aminophenylacetamido)- and 7-(D-.alpha.-hydroxyphenylacetamido)- .DELTA..sup.3 -cephem derivatives have been prepared wherein a heterocyclic thiomethyl moiety is located at the 3-position of the molecule. These compounds are useful as antibacterial agents for the treatment of diseases caused by Gram-positive and Gram-negative bacteria. Preferred members include 7-(D-.alpha.-hydroxyphenylacetamido)-3-(3-carbamoyl-1,2,4-triazol-5-yl)thi omethylceph-3-em-4-carboxylic acid and 7-(D-.alpha.-hydroxyphenylacetamido)-3-(2-carboxymethoxy-methyl-1,3,4-thia diazol-5-yl)thiomethylceph-3-em-4-carboxylic acid. Alternative methods of preparation are provided for these compounds, including various synthetic routes leading to the required novel heterocyclic thiol intermediates.

Cephalosporin derivatives

A series of novel 7-(D-.alpha.-acylaminoarylacetamido)-.DELTA..sup.3 -cephem derivatives have been prepared wherein the acyl moiety contains an epoxy group immediately adjacent to the carbonyl carbon atom. These compounds are useful as antibacterial agents for the treatment of diseases caused by Gram-negative and Gram-positive bacteria. Preferred members include 7-[D-.alpha.-(cis-2-carboxyoxiran-3-carboxamido)phenylacetamido]-3-(1-meth yl-1,2,3,4-tetrazol-5-ylthiomethyl)-.DELTA..sup.3 -cephem-4-carboxylic acid and 7-[D.alpha.-(cis-2-carboxyoxiran-3-carboxamido)phenylacetamido]cephalospor anic acid. Alternate methods of preparation are provided for these compounds and the principal synthetic route is described in detail.

7[(Carboxyoxiran-3-carboxamido)phenylacetamido]cephalosporin derivatives

Novel antibacterial agents; namely, 7-(.alpha.-acylamino-arylacetamido)-cephalosporanic acid derivatives having the formula: ##STR1## wherein R.sup.1 is thienyl, 2-furyl, phenyl, substituted thienyl or substituted phenyl; R is hydroxyl; R.sup.2 is hydrogen, hydroxy, acetoxy, carbamoyloxy, N-pyridyl, azido or heterocyclic thio group; R and R.sup.2 when taken together represent an oxygen atom; R.sup.3 is sulpho or COOR.sup.4' wherein R.sup.4' is hydrogen or R.sup.4 wherein R.sup.4 is lower alkyl, 5-indanyl, naphthyl, phenyl, or substituted phenyl, CONR.sup.5 R.sup.6, wherein each of R.sup.5 and R.sup.6 is hydrogen, lower alkyl or cycloalkyl; or R.sup.5 and R.sup.6 together with the nitrogen atom to which they are attached form a saturated heterocyclic group; X is oxygen or sulphur, a direct link, carbonyl, methylene, hydroxymethylene, sulphinyl, sulphonyl or an imino group of the formula --NR.sup.7 --, wherein R.sup.7 is hydrogen, lower alkyl, lower alkenyl, or benzyl; and each of alk.sup.1 and alk.sup.2 is a divalent saturated aliphatic hydrocarbon group containing from 1 to 3 carbon atoms; the pharmaceutically acceptable salts thereof, and methods for their preparation.

7-D-(.alpha.-Acylamino-arylacetamido)-cephalosporanic acid derivatives

Novel antibacterial agents; namely, 7-(.alpha.-acylamino-arylacetamido)-cephalosporanic acid derivatives having the formula: ##STR1## wherein R.sup.1 is thienyl, 2-furyl, phenyl, substituted thienyl or substituted phenyl; R is hydroxyl; R.sup.2 is hydrogen, hydroxy, acetoxy, carbamoyloxy, N-pyridyl, azido or heterocyclic thio group; R and R.sup.2 when taken together represent an oxygen atom; R.sup.3 is sulpho or COOR.sup.4.sup.' wherein R.sup.4.sup.' is hydrogen or R.sup.4 wherein R.sup.4 is lower alkyl, 5-indanyl, naphthyl, phenyl, or substituted phenyl, CONR.sup.5 R.sup.6, wherein each of R.sup.5 and R.sup.6 is hydrogen, lower alkyl or cycloalkyl; or R.sup.5 and R.sup.6 together with the nitrogen atom to which they are attached form a saturated heterocyclic group; X is oxygen or sulphur, a direct link, carbonyl, methylene, hydroxymethylene, sulphinyl, sulphonyl or an imino group of the formula --NR.sup.7 --, wherein R.sup.7 is hydrogen, lower alkyl, lower alkenyl, or benzyl; and each of alk.sup.1 and alk.sup.2 is a divalent saturated aliphatic hydrocarbon group containing from 1 to 3 carbon atoms; the pharmaceutically acceptable salts thereof, and methods for their preparation.

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Canterbury, United Kingdom

Braham Shroot