Cephalosporins, process for their preparation and pharmaceutical compositions containing them

Claim 2

Compounds of formula (I) wherein R 1 represents a hydrogen atom or a C 1-4 alkyl group optionally substituted by one to three halogen atoms: R 2 and R 3 , which may be the same or different, each represents a hydrogen atom or a carboxyl blocking group; R 4 represents a hydrogen atom or an amino protecting group; R 5 and R 6 each represents a hydroxy or substituted hydroxy group or R 5 and R 6 together represent a cyclic protected diol group; Z is -S-or -SO-(α-or β-) and the dotted line bridging the 2-, 3-, and 4-positions indicates that the compound is a ceph-2-em or ceph-3-em compound; and salts and solvates thereof.

Claim 3

Compounds as claimed in claim 1 of formula (la) wherein R 1 is as defined in claim 1; R5 a is a hydroxy or acetoxy group; R 6a is a hydroxy or acetoxy group; and the non-toxic salts and metabolically labile esters thereof.

Claim 4

Compounds of formula (Ia) as claimed in claim 2 in which R 1 is a hydrogen atom or a methyl, ethyl or 2-chloroethyl group.

Claim 5

Compounds of formula (Ia) as claimed in claim 2 in which the oxime etherifying group has the S-configuration.

Claim 6

A compound selected from (6R,7R,2'Z,S)-7-[2-(2-aminothiazol-4-yl)-2-(carboxy) (3,4-dihydroxyphenyl)methoxyimino]acetamido]-3-carbamoyloxymethyl-ceph-3-em-4-carboxylic acid; (6R,7R,2'Z,)-7-[2-(2-aminothiazol-4-yl)-2-(carboxy) (3,4-dihydroxyphenyl)methoxyimino]acetamido]-3-carbamoyloxymethyl-ceph-3-em-4-carboxylic acid; (6R,7R,2'ZL,S)-7-[2-(2-aminothiazol-4-yl)-2-(carboxy) (3,4-dihydroxyphenyl)methoxyimino]acetamido]-3-N-methyl-carbamoyloxymethyl-ceph-3-em-4-carboxylic acid; and the non-toxic salts and metabolically labile esters thereof.

Claim 7

A compound selected from (6R,7R,2'Z,S)-7-[2-(2-aminothiazol-4-yl)-2-(carboxy) (3,4-dihydroxyphenyl)methoxyimino]acetamido]-3-carbamoyloxymethyl-ceph-3-em-4-carboxylic acid; (6R,7R,2'Z,)-7-[2-(2-aminothiazol-4-yl)-2-(carboxy) (3,4-dihydroxyphenyl)methoxyimino]acetamido]-3-carbamoyloxymethyl-ceph-3-em-4-carboxylic acid; (6R,7R,2'ZL,S)-7-[2-(2-aminothiazol-4-yl)-2-(carboxy) (3,4-dihydroxyphenyl)methoxyimino]acetamido]-3-N-methyl-carbamoyloxymethyl-ceph-3-em-4-carboxylic acid; and the non-toxic salts and metabolically labile esters thereof.

Claim 8

A process for the preparation of compounds of formula (I) as defined in claim 1 or salts or solvates thereof which comprises forming a compound of formula (I') (wherein R 1a is as defined in claim 1 for R 1 or is a N-protecting group, and R 2 ,R 3 ,R 4 .R 5 ,R 6 , Z and the dotted line are as defined in claim 1, or a salt thereof), by (A) acylating a compound of formula (II) (wherein R 1a , R 2 , Z and the dotted line are as defined above) or a salt or 7-N-silyl derivative thereof, with an acid of formula (III) (wherein R 3 , R 4 , R 5 and R 6 are as defined above) or a salt thereof, or with an acylating agent corresponding thereto; or (B) reacting a compound of formula (IV) (wherein R 2 ,R 3 ,R 4 ,R 5 ,R 6 , Z and the dotted line are as defined above) or a salt thereof, with an acylating agent serving to form the group -CH 2 0CONHR 1a (wherein R 1a is as defined above) at the 3-position; whereafter, if necessary and/or desired in each instance, any of the following reactions, in any appropriate sequence, are carried out:- i) conversion of a Δ 2 -isomer into the desired AS-isomer, ii) reduction of a compound wherein Z is -SO-to form a compound wherein Z is -S-, iii) conversion of a carboxyl group into a non-toxic metabolically labile ester function, iv) formation of a salt or solvate, v) removal of any carboxy blocking and/or N-protecting groups, and vi) removal of any hydroxy blocking groups.

Claim 9

A pharmaceutical composition comprising as active ingredient a compound of formula (Ia) as defined in claim 2.