Heteromonocyclic and heterobicyclic derivatives of unsaturated 7-acylamido-3-cephem-4-carboxylic acid

Claim 2

A compound of the formula (I) ##STR68## wherein Z is cyano, carbamoyl or --COOR, wherein R is hydrogen or C 1 -C 6 alkyl; A is --CH═CH--; X is a free carboxy group or esterified carboxy group of the formula --COOM, wherein M is ##STR69## wherein R' 3 is hydrogen or C 1 -C 6 alkyl; Q is --O-- or --NH--; R 4 is C 1 -C 6 alkyl or benzyl, which may be unsubstituted or substituted by at least one --NH 2 group which may itself be substituted by C 1 -C 6 alkyl or phenyl; R 5 is C 1 -C 6 alkyl, phenyl, cycloalkyl selected from the group consisting of cyclopentyl, cyclohexyl and cycloheptyl, pyridyl, indanyl or benzyl; B is (1) a tetrazolyl radical of the formula: ##STR70## wherein Q is --(CH 2 ) n --COOR wherein n is an integer of 1 to 3 and R is as defined above, or --(CH 2 ) n --CONH 2 wherein n is as defined above; or (2) a tetrazolo-pyridazinyl radical of the formula: ##STR71## wherein T 1 and T 2 are the same or different and are H or NH 2 ; and the pharmaceutically or veterinarily acceptable salts thereof.

Claim 3

A compound of claim 1 wherein X is carboxy.

Claim 4

A compound of claim 1 wherein A is cis--CH═CH-- and X is carboxy.

Claim 5

A compound of claim 1 wherein A is cis--CH═CH--, X is carboxy and B is a tetrazolyl radical as defined in claim 1.

Claim 6

A compound of claim 4 wherein n is 2 and R is hydrogen.

Claim 7

A compound of claim 1 wherein A is cis--CH═CH--, X is carboxy and B is tetrazolo-pyridazinyl as defined in claim 1.

Claim 8

A compound of claim 6 wherein R is hydrogen.

Claim 9

A compound selected from the group consisting of: 7-[β-cyano-ethylene(cis)-thio-acetamido]-3-[(1-carboxy-methyl-1,2,3,4-tetrazol-5-yl)-thiomethyl]-3-cephem-4-carboxylic acid; 7-[β-cyano-ethylene(cis)-thio-acetamido]-3-[(1-β-carboxy-ethyl-1,2,3,4-tetrazol-5-yl)-thiomethyl]-3-cephem-4-carboxylic acid; 7-[β-cyano-ethylene(cis)-thio-acetamido]-3-[(1-γ-carboxy-propyl-1,2,3,4-tetrazol-5-yl)-thiomethyl]-3-cephem-4-carboxylic acid; 7-[β-cyano-ethylene(cis)-thio-acetamido]-3-[(1-carboxamido-methyl-1,2,3,4-tetrazol-5-yl)-thiomethyl]-3-cephem-4-carboxylic acid; 7-[β-cyano-ethylene(cis)-thio-acetamido]-3-[(1-β-carboxamidoethyl-1,2,3,4-tetrazol-5-yl)-thiomethyl]-3-cephem-4-carboxylic acid; 7-[β-carboxamido-ethylene(cis)-thio-acetamido]-3-[(1-carboxymethyl-1,2,3,4-tetrazol-5-yl)-thiomethyl]-3-cephem-4-carboxylic acid; 7-[β-carboxamido-ethylene(cis)-thio-acetamido]-3-[(1-β-carboxyethyl-1,2,3,4-tetrazol-5-yl)-thiomethyl]-3-cephem-4-carboxylic acid; and a pharmaceutically or veterinarily acceptable salt thereof.

Claim 10

A compound selected from the group consisting of: 7-[β-cyano-ethylene(cis)-thio-acetamido]-3-[(1-carboxy-methyl-1,2,3,4-tetrazol-5-yl)-thiomethyl]-3-cephem-4-carboxylic acid; 7-[β-cyano-ethylene(cis)-thio-acetamido]-3-[(1-β-carboxy-ethyl-1,2,3,4-tetrazol-5-yl)-thiomethyl]-3-cephem-4-carboxylic acid; 7-[β-cyano-ethylene(cis)-thio-acetamido]-3-[(1-γ-carboxy-propyl-1,2,3,4-tetrazol-5-yl)-thiomethyl]-3-cephem-4-carboxylic acid; 7-[β-cyano-ethylene(cis)-thio-acetamido]-3-[(1-carboxamido-methyl-1,2,3,4-tetrazol-5-yl)-thiomethyl]-3-cephem-4-carboxylic acid; 7-[β-cyano-ethylene(cis)-thio-acetamido]-3-[(1-β-carboxamidoethyl-1,2,3,4-tetrazol-5-yl)-thiomethyl]-3-cephem-4-carboxylic acid; 7-[β-carboxamido-ethylene(cis)-thio-acetamido]-3-[(1-carboxymethyl-1,2,3,4-tetrazol-5-yl)-thiomethyl]-3-cephem-4-carboxylic acid; 7-[β-carboxamido-ethylene(cis)-thio-acetamido]-3-[(1-β-carboxyethyl-1,2,3,4-tetrazol-5-yl)-thiomethyl]-3-cephem-4-carboxylic acid; and a pharmaceutically or veterinarily acceptable salt thereof.

Claim 11

A compound selected from the group consisting of: 7-[β-cyano-ethylene(cis)-thio-acetamido]-3-[(tetrazolo[1,5-b]pyridazin-6-yl)-thiomethyl]-3-cephem-4-carboxylic acid; 7-[β-cyano-ethylene(cis)-thio-acetamido]-3-[(tetrazolo[1,5-b]pyridazin-8-amino-6-yl)-thiomethyl]-3-cephem-4-carboxylic acid; 7-[β-cyano-ethylene(cis)-thio-acetamido]-3-[(tetrazolo[1,5-b]pyridazin-7-amino-8-yl)-thiomethyl]-3-cephem-4-carboxylic acid; 7-[β-carboxamido-ethylene(cis)-thio-acetamido]-3-[(tetrazolo[1,5-b]pyridazin-6-yl)-thiomethyl]-3-cephem-4-carboxylic acid; 7-[β-carboxamido-ethylene(cis)-thio-acetamido]-3-[(tetrazolo[1,5-b]pyridazin-8-amino-6-yl)-thiomethyl]-3-cephem-4-carboxylic acid; 7-[β-carboxamido-ethylene(cis)-thio-acetamido]-3-[(tetrazolo[1,5-b]pyridazin-7-amino-8-yl)-thiomethyl]-3-cephem-4-carboxylic acid; 7-[β-carboxy-ethylene(cis)-thio-acetamido]-3-[(tetrazolo[1,5-b]pyridazin-6-yl)-thiomethyl]-3-cephem-4-carboxylic acid; 7-[β-carboxy-ethylene(cis)-thio-acetamido]-3-[(tetrazolo[1,5-b]pyridazin-8-amino-6-yl)-thiomethyl]-3-cephem-4-carboxylic acid; 7-[β-cyano-ethylene(cis)-thio-acetamido]-3-[(tetrazolo[1,5-b]pyridazin-7,8-diamino-6-yl)-thiomethyl]-3-cephem-4-carboxylic acid; 7-[β-carboxamido-ethylene(cis)-thio-acetamido]-3-[(tetrazolo[1,5-b]pyridazin-7,8-diamino-6-yl)-thiomethyl]-3-cephem-4-carboxylic acid; and the pharmaceutically or veterinarily acceptable salts thereof.

Claim 12

A compound selected from the group consisting of: 7-[β-cyano-ethylene(cis)-thio-acetamido]-3-[(tetrazolo[1,5-b]pyridazin-6-yl)-thiomethyl]-3-cephem-4-carboxylic acid; 7-[β-cyano-ethylene(cis)-thio-acetamido]-3-[(tetrazolo[1,5-b]pyridazin-8-amino-6-yl)-thiomethyl]-3-cephem-4-carboxylic acid; 7-[β-cyano-ethylene(cis)-thio-acetamido]-3-[(tetrazolo[1,5-b]pyridazin-7-amino-8-yl)-thiomethyl]-3-cephem-4-carboxylic acid; 7-[β-carboxamido-ethylene(cis)-thio-acetamido]-3-[(tetrazolo[1,5-b]pyridazin-6-yl)-thiomethyl]-3-cephem-4-carboxylic acid; 7-[β-carboxamido-ethylene(cis)-thio-acetamido]-3-[(tetrazolo[1,5-b]pyridazin-8-amino-6-yl)-thiomethyl]-3-cephem-4-carboxylic acid; 7-[β-carboxamido-ethylene(cis)-thio-acetamido]-3-[(tetrazolo[1,5-b]pyridazin-7-amino-8-yl)-thiomethyl]-3-cephem-4-carboxylic acid; 7-[β-carboxy-ethylene(cis)-thio-acetamido]-3-[(tetrazolo[1,5-b]pyridazin-6-yl)-thiomethyl]-3-cephem-4-carboxylic acid; 7-[β-carboxy-ethylene(cis)-thio-acetamido]-3-[(tetrazolo[1,5-b]pyridazin-8-amino-6-yl)-thiomethyl]-3-cephem-4-carboxylic acid; 7-[β-cyano-ethylene(cis)-thio-acetamido]-3-[(tetrazolo[1,5-b]pyridazin-7,8-diamino-6-yl)-thiomethyl]-3-cephem-4-carboxylic acid; 7-[β-carboxamido-ethylene(cis)-thio-acetamido]-3-[(tetrazolo[1,5-b]pyridazin-7,8-diamino-6-yl)-thiomethyl]-3-cephem-4-carboxylic acid; and the pharmaceutically or veterinarily acceptable salts thereof.

Claim 13

7-[β-cyano-ethylene(cis)-thio-acetamido]-3-[(tetrazolo[1,5-b]pyridazin-8-amino-6-yl)-thiomethyl]-3-cephem-4-carboxylic acid; and the pharmaceutically or veterinarily acceptable salts thereof.

Claim 14

7-[β-cyano-ethylene(cis)-thio-acetamido]-3-[(tetrazolo[1,5-b]pyridazin-8-amino-6-yl)-thiomethyl]-3-cephem-4-carboxylic acid; and the pharmaceutically or veterinarily acceptable salts thereof.

Claim 15

7-[β-carboxy-ethylene(cis)-thio-acetamido]-3-[(tetrazolo[1,5-b]pyridazin-8-amino-6-yl)-thiomethyl]-3-cephem-4-carboxylic acid; and the pharmaceutically or veterinarily acceptable salts thereof.

Claim 16

7-[β-carboxy-ethylene(cis)-thio-acetamido]-3-[(tetrazolo[1,5-b]pyridazin-8-amino-6-yl)-thiomethyl]-3-cephem-4-carboxylic acid; and the pharmaceutically or veterinarily acceptable salts thereof.

Claim 17

A pharmaceutical or veterinary composition suitable for the treatment of infections caused by Gram-positive and Gram-negative microorganisms, said composition consisting essentially of a therapeutically effective amount of a compound according to claim 1, and a pharmaceutically or veterinarily acceptable carrier or diluent.

Claim 18

Method for the treatment of an infection caused by Gram-positive or Gram-negative microorganisms in a patient, said method comprising administering to said patient a therapeutically effective amount of a compound of claim 1.

Claim 19

Method of claim 13 wherein said compound is administered orally or parenterally.