New cephem compounds, processes for their preparation, pharmaceutical compositions containing them and their starting compounds

Claim 2

A new cephem compound of the formula : wherein R 1 is amino or a protected amino group; R 2 is lower aliphatic hydrocarbon group which may be substituted with suitable substituent(s), or cyclo(lower)alkenyl; and a group of the formula : is a heterocyclic cation group containing more than one nitrogen atom, which may be substituted with suitable substituent(s); and pharmaceutically acceptable salts thereof.

Claim 3

Syn isomer of a compound of claim 1, wherein group is

Claim 4

A compound of claim 2, wherein R 1 is amino; R 2 is lower aliphatic hydrocarbon group which may be substituted with lower alkylthio or carboxy, or cyclo(lower)-alkenyl; and a group of the formula : is unsaturated 5 to 6-membered heteromonocyclic cation group containing more than one nitrogen atom, which may be substituted with lower alkyl, amino, lower alkenyl, halogen, hydroxy or hydroxy(lower)-alkyl.

Claim 5

A compound of claim 3, wherein R 2 is lower alkyl, lower alkenyl or lower alkynyl, each of which may be substituted with one lower alkylthio or carboxy, or cyclo(lower)alkenyl; and a group of the formula : is triazolio, imidazolio, pyrimidinio, pyrazolio, pyridazinio or pyrazinio, each of which may be substituted with one lower alkyl, amino, lower alkenyl, halogen, hydroxy or hydroxy(lower)alkyl.

Claim 6

A compound of claim 4, wherein R 2 is methyl, ethyl, allyl, 2-propynyl, carboxymethyl, methylthiomethyl or 2-cyclopenten r l-yl; and a group of the gormula : is triazolio substituted with one methyl, imidazolio substituted with one methyl, pyrimidinio substituted with one methyl or amino, pyrazolio substituted with one methyl, ethyl, 2-hydroxyethyl or allyl, pyridazinio which may be substituted with one hydroxy or chlorine, or pyrazinio.

Claim 7

A compound of claim 4, wherein R 2 is lower alkyl and a group of the formula : is triazolio substituted with one lower alkyl.

Claim 8

A compound of claim 4, wherein R 2 is lower alkyl and a group of the formula : is imidazolio substituted with one lower alkyl.

Claim 9

A compound of claim 4, wherein R 2 is lower alkyl and a group of the formula : is pyrimidinio substituted with one lower alkyl or amino.

Claim 10

A compound of claim 4, wherein R 2 is lower alkyl, lower alkenyl, lower alkynyl, carboxy(lower)alkyl, lower alkylthio(lower)alkyl or cyclo(lower)alkenyl and a group of the formula : is pyrazolio substituted with one lower alkyl, hydroxy(lower)alkyl or lower alkenyl.

Claim 11

A compound of claim 4, wherein R 2 is lower alkyl or lower alkynyl and a group of the formula : is pyridazinio which may be substituted with one hydroxy or halogen.

Claim 12

A compound of claim 4, wherein R 2 is lower alkyl and a group of the formula : is pyrazinio.

Claim 13

A compound of claim 5, which is selected from the group consisting of : 7-[2-ethoxyimino-2-(5-amino-l,2,4-thiadiazol-3-yl)-acetamido]-3-(3-methyl-l-imidazoliomethyl)-3-cephem-4-carboxylate (syn isomer), 7-[2-ethoxyimino-2-(5-amino-1,2,4-thiadiazol-3-yl)-acetamido]-3-[3-methyl-1-(1,2,3-triazolio)methyl]-3-cephem-4-carboxylate (syn isomer), 7-[2-ethoxyimino-2-(5-amino-1,2,4-thiadiazol-3-yl)-acetamido]-3-(S-methyl-l-pyrimidiniomethyl)-3-cephem-4-carboxylate (syn isomer), 7-[2-ethoxyimino-2-(S-amino-1,2,4-thiadiazol-3-yl)-acetamido]-3-(2-methyl-l-pyrazoliomethyl)-3-cephem-4-carboxylate (syn isomer), 7-[2-ethoxyimino-2-(5-amino-1,2,4-thiadiazol-3-yl)-acetamido]-3-(1-pyridaziniomethyl)-3-cephem-4-carboxylate (syn isomer), 7-[2-ethoxyimino-2-(5-amino-l,2,4-thiadiazol-3-yl)-acetamido]-3-(1-pyraziniomethyl)-3-cephem-4-carboxylate (syn isomer), 7- [2-methoxyimino-2-(5-amino-1,2,4-thiadiazol-3-yl)-acetamido]-3-(1-pyridaziniomethyl)-3-cephem-4-carboxylate (syn isomer), 7-[2-methoxyimino-2-(5-amino-1,2,4-thiadiazol-3-yl)acetamido]-3-(2-methyl-l-pyrazoliomethyl)-3-cephem-4-carboxylate (syn isomer), 7-[2-ethoxyimino-2-(5-amino-1,2,4-thiadiazol-3-yl)acetamido]-3-(2-ethyl-l-pyrazoliomethyl)-3-cephem-4-carboxylate (syn isomer), 7-[2-allyloxyimino-2-(5-amino-1,2,4-thiadiazol-3-yl)acetamido]-3-(2-methyl-l-pyrazoliomethyl)-3-cephem-4-carboxylate (syn isomer), 7-[2-(2-propynyloxyimino)-2-(5-amino-l,2,4-thiadiazol-3-yl)acetamido]-3-(1-pyridaziniomethyl)-3-cephem-4-carboxylate (syn isomer), 7-[2-(2-propynyloxyimino)-2-(S-amino-1,2,4-thiadiazol-3-yl)acetamido]-3-(2-methyl-l-pyrazoliomethyl)-3-cephem-4-carboxylate (syn isomer), 7-[2-methylthiomethoxyimino-2-(S-amino-1,2,4-thiadiazol-3-yl)acetamido]-3-(2-methyl-l-pyrazoliomethyp-3-cephem-4-carboxylate (syn isomer), 7-[2-carboxymethoxyimino-2-(5-amino-1,2,4-thiadiazol-3-yl)acetamido]-3-(2-methyl-l-pyrazoliomethyl)-3-cephem-4-carboxylate (syn isomer), 7-[2-(2-cyclopenten-1-yloxyimino)-2-(5-amino-1,2,4-thiadiazol-3-yl)acetamido]-3-(2-methyl-1-pyrazoliomethyl)-3-cephem-4-carboxylate (syn isomer), 7-[2-ethoxyimino-2-(5-amino-1,2,4-thiadiazol-3-yl)acetamido]-3-(2-allyl-l-pyrazoliomethyl)-3-cephem-4-carboxylate (syn isomer), 7-[2-ethoxyimino-2-(5-amino-1,2,4-thiadiazol-3-yl)acetamido]-3-(3-chloro-l-pyridaziniomethyl)-3-cephem-4-carboxylate (syn isomer), 7-[2-ethoxyimino-2-(5-amino-1,2,4-thiadiazol-3-yl)-acetamido]-3-[3-methyl-1-(1,3,4-triazoliomethyl)]-3-cephem-4-carboxylate (syn isomer), 7-[2-ethoxyimino-2-(5-amino-1,2,4-thiadiazol-3-yl)acetamido]-3-[4-methyl-1-(1,2,4-tziazoliomethyl)]-3-cephem-4-carboxylate (syn isomer), 7-[2-ethoxyimino-2-(5-amino-l,2,4-thiadiazol-3-yl)acetamido]-3-(3-hydroxy-l-pyridaziniomethyl)-3-cephem-4-carboxylate (syn isomer), 7-[2-ethoxyimino-2-(5-amino-1,2,4-thiadiazol-3-yl)-acetamido]-3-[2-(2-hydroxyethyl)-l-pyrazoliomethyl]-3-cephem-4-carboxylate (syn isomer), and 7-[2-ethoxyimino-2-(5-amino-1,2,4-thiadiazol-3-yl)acetamido]-3-(2-amino-l-pyrimidiniomethyl)-3-cephem-4-carboxylate (syn isomer).

Claim 14

A process for preparing a new cephem compound of the formula : wherein R 1 is amino or a protected amino group; R 2 is lower aliphatic hydrocarbon group which may be substituted with suitable substituent(s), or cyclo(lower)alkenyl; and a group of the formula : is a heterocyclic cation group containing more than one nitrogen atom, which may be substituted with suitable substituent(s); or a salt thereof, which comprises (a) reacting a compound of the formula : wherein R 1 and R 2 are each as defined above; and R 3 is a group which can be substituted with a group of the formula : or a salt thereof, with a compound of the formula : wherein the compound of the formula : is a heterocyclic compound containing more than one nitrogen atom, which may be substituted with suitable substituent(s), or (b) subjecting a compound of the formula : wherein R l , R 2 and a group of the formula : are each as defined above, R 4 is a protected carboxy group and X is an acid residue, to elimination reaction of carboxy-protective group.

Claim 15

A process for preparing a new cephem compound of the formula : wherein R 1 is amino or a protected amino group; R 2 is lower aliphatic hydrocarbon group which may be substituted with suitable substituent(s), or cyclo(lower)alkenyl; and a group of the formula : is a heterocyclic cation group containing more than one nitrogen atom, which may be substituted with suitable substituent(s); or a salt thereof, which comprises (a) reacting a compound of the formula : wherein R 1 and R 2 are each as defined above; and R 3 is a group which can be substituted with a group of the formula : or a salt thereof, with a compound of the formula : wherein the compound of the formula : is a heterocyclic compound containing more than one nitrogen atom, which may be substituted with suitable substituent(s), or (b) subjecting a compound of the formula : wherein R l , R 2 and a group of the formula : are each as defined above, R 4 is a protected carboxy group and X is an acid residue, to elimination reaction of carboxy-protective group.

Claim 16

A compound of the formula : wherein R 1 is amino or a protected amino group; R 2 is lower aliphatic hydrocarbon group which may be substituted with suitable substituent(s), or cyclo(lower)alkenyl; R 4 is a protected carboxy group, X is an acid residue, Y is -S- or and a group of the formula : is a heterocyclic cation group containing more than one nitrogen atom, which may be substituted with suitable substituent(s); and salts thereof.

Claim 17

A compound of the formula : wherein R 1 is amino or a protected amino group; R 2 is lower aliphatic hydrocarbon group which may be substituted with suitable substituent(s), or cyclo(lower)alkenyl; R 4 is a protected carboxy group, X is an acid residue, Y is -S- or and a group of the formula : is a heterocyclic cation group containing more than one nitrogen atom, which may be substituted with suitable substituent(s); and salts thereof.

Claim 18

A process for preparing a compound of the formula : wherein R 1 is amino or a protected amino group; R 2 is lower aliphatic hydrocarbon group which may be substituted with suitable substituent(s), or cyclo(lower)alkenyl; R 4 is a protected carboxy group; X is an acid residue and a group of the formula : is a heterocyclic cation group containing more than one nitrogen atom, which may be substituted with suitable substituent(s); which comprises reducing a compound of the formula : wherein R 1 , R 2 . R 4 , X and a group of the formula : are each as defined above.

Claim 19

A process for preparing a compound of the formula : wherein R 1 is amino or a protected amino group; R 2 is lower aliphatic hydrocarbon group which may be substituted with suitable substituent(s), or cyclo(lower)alkenyl; R 4 is a protected carboxy group; X is an acid residue and a group of the formula : is a heterocyclic cation group containing more than one nitrogen atom, which may be substituted with suitable substituent(s); which comprises reducing a compound of the formula : wherein R 1 , R 2 . R 4 , X and a group of the formula : are each as defined above.

Claim 20

A pharmaceutical antibacterial composition comprising a compound of claim 1 in association with a pharmaceutically acceptable, substantially non-toxic carrier or excipient.

Claim 21

A compound as defined in any of claims 1 to 12 for use as a pharmaceutical.

Claim 22

A compound as defined in any of claims 1 to 12 for use in the treatment of infectious diseases.