Cephem compounds and processes for preparation thereof

Claim 2

A compound of the formula : wherein R 1 is amino or a protected amino group, R 2 is an organic group, R 3 is hydrogen, lower alkyl, hydroxy(lower)alkyl, protected hydroxy(lower)alkyi, amino(lower)alkyl, protected amino(lower)alkyl or an imino protective group, R4 is hydrogen, lower alkyl or lower alkylthio, A is lower alkylene which may be substituted with suitable substituent(s) and Z is N or CH, and a pharmaceutically acceptable salt thereof.

Claim 3

A compound of claim 1, wherein R 2 is lower alkyl, lower alkenyl, carboxy(lower)alkyl or protected carboxy(lower)alkyl and A is lower alkylene which may be substituted with an oxo, a hydroxy or a protected hydroxy group.

Claim 4

A compound of Claim 2, wherein R 2 is lower alkyl, lower alkenyl, carboxy(lower)alkyl or esterified carboxy(lower)alkyl, R 3 is hydrogen, lower alkyl, hydroxy(lower)alkyl, acyloxy(lower)alkyl, amino(lower)alkyl, acylamino(lower)-alkyl or an acyl group and A is lower alkylene which may be substituted with an oxo, a hydroxy or an acyloxy group.

Claim 5

A compound of claim 3, wherein R 2 is lower alkyl, lower alkenyl, carboxy(lower)alkyl or lower alkoxycarbonyl(lower)alkyl, R 3 is hydrogen, lower alkyl, hydroxy(lower)alkyl, lower alkanoyloxy(lower)alkyl, amino(lower)alkyl, lower alkanoylamino(lower)alkyl or lower alkanoyl and A is (C 2 -C 3 ) alkylene which may be substituted with an oxo, a hydroxy or an alkanoyloxy group.

Claim 6

A compound of claim 4, wherein R 3 is hydrogen, lower alkyl, hydroxy(lower)alkyl, amino(lower)alkyl, lower alkanoylamino(lower)alkyl or lower alkanoyl and A is (C 2 -C 3 )alkylene which may be substituted with an oxo or a hydroxy group.

Claim 7

A compound of claim 5 wherein R 1 is amino, R 2 is carboxy(lower)alkyl, R 3 is hydrogen, R 4 is hydrogen, A is ethylene, and Z is N.

Claim 8

A compound of claim 6, which is 7β-[2-(5-amino-1,2,4-thiadiazol-3-yl)-2-(1-carboxy-1-methylethoxyimino)acetamido]-3-[2,3-dihydro-5-(1H-imidazo[1,2-b]pyrazolio)]methyl-3-cephem-4-carboxylate (syn isomer).

Claim 9

A compound of claim 6, which is 7β-[2-(5-amino-1,2,4-thiadiazol-3-yl)-2-(1-carboxy-1-methylethoxyimino)acetamido]-3-[2,3-dihydro-5-(1 H-imidazo[1,2-b]pyrazolio)]methyl-3-cephem-4-carboxylate sulfate (syn isomer).

Claim 10

A process for preparing a compound of the formula : wherein R' is amino or a protected amino group, R 2 is an organic group, R 2 is hydrogen, lower alkyl, hydroxy(lower)alkyl, protected hydroxy(lower)alkyl, amino(lower)alkyl, protected amino(lower)alkyl or an imino protective group, R 4 is hydrogen, lower alkyl or lower alkylthio, A is lower alkylene which may be substituted with suitable substituent(s) and Z is N or CH, or a salt thereof, which comprises (1) reacting a compound of the formula: wherein R 3 , R4 and A are each as defined above, or its reactive derivative at the amino group or a salt thereof with a compound of the formula: wherein R 1 , R 2 and Z are each as defined above, or its reactive derivative at the carboxy group or a salt thereof to give a compound of the formula: wherein R 1 , R 2 , R 3 , R 4 , A and Z are each as defined above, or a salt thereof, or (2) subjecting a compound of the formula : wherein R 2 , R 3 , R 4 , A and Z are each as defined above and is a protected amino group, or a salt thereof to elimination reaction of the amino protective group to give a compound of the formula : wherein R 2 , R 3 , R 4 , A and Z are each as defined above, or a salt thereof, or (3) subjecting a compound of the formula : wherein R 1 , R 3 , R 4 , A and Z are each as defined above and is protected carboxy(lower)alkyl, or a salt thereof to elimination reaction of the carboxy protective group to give a compound of the formula : wherein R 1 , R 3 , R 4 , A and Z are each as defined above and is carboxy(lower)alkyl, or a salt thereof, or (4) subjecting a compound of the formula : wherein R 1 , R 2 , R 4 , A and Z are each as defined above and is protected amino(lower)alkyl, or a salt thereof to elimination reaction of the amino protective group to give a compound of the formula : wherein R', R 2 , R 4 , A and Z are each as defined above and is amino(lower)alkyl, or a salt thereof.

Claim 11

A process for preparing a compound of the formula : wherein R' is amino or a protected amino group, R 2 is an organic group, R 2 is hydrogen, lower alkyl, hydroxy(lower)alkyl, protected hydroxy(lower)alkyl, amino(lower)alkyl, protected amino(lower)alkyl or an imino protective group, R 4 is hydrogen, lower alkyl or lower alkylthio, A is lower alkylene which may be substituted with suitable substituent(s) and Z is N or CH, or a salt thereof, which comprises (1) reacting a compound of the formula: wherein R 3 , R4 and A are each as defined above, or its reactive derivative at the amino group or a salt thereof with a compound of the formula: wherein R 1 , R 2 and Z are each as defined above, or its reactive derivative at the carboxy group or a salt thereof to give a compound of the formula: wherein R 1 , R 2 , R 3 , R 4 , A and Z are each as defined above, or a salt thereof, or (2) subjecting a compound of the formula : wherein R 2 , R 3 , R 4 , A and Z are each as defined above and is a protected amino group, or a salt thereof to elimination reaction of the amino protective group to give a compound of the formula : wherein R 2 , R 3 , R 4 , A and Z are each as defined above, or a salt thereof, or (3) subjecting a compound of the formula : wherein R 1 , R 3 , R 4 , A and Z are each as defined above and is protected carboxy(lower)alkyl, or a salt thereof to elimination reaction of the carboxy protective group to give a compound of the formula : wherein R 1 , R 3 , R 4 , A and Z are each as defined above and is carboxy(lower)alkyl, or a salt thereof, or (4) subjecting a compound of the formula : wherein R 1 , R 2 , R 4 , A and Z are each as defined above and is protected amino(lower)alkyl, or a salt thereof to elimination reaction of the amino protective group to give a compound of the formula : wherein R', R 2 , R 4 , A and Z are each as defined above and is amino(lower)alkyl, or a salt thereof.

Claim 12

A compound of the formula : wherein R 3 is hydrogen, lower alkyl, hydroxy(lower)alkyl, protected hydroxy(lower)alkyl, amino(lower)alkyl, protected amino(lower)alkyl or an imino protective group, R 4 is hydrogen, lower alkyl or lower alkylthio and A is lower alkylene which may be substituted with suitable substituent(s), and a salt thereof.

Claim 13

A compound of the formula : wherein R 3 is hydrogen, lower alkyl, hydroxy(lower)alkyl, protected hydroxy(lower)alkyl, amino(lower)alkyl, protected amino(lower)alkyl or an imino protective group, R 4 is hydrogen, lower alkyl or lower alkylthio and A is lower alkylene which may be substituted with suitable substituent(s), and a salt thereof.

Claim 14

A process for preparing a compound of the formula : wherein R 3 is hydrogen, lower alkyl, hydroxy(lower)alkyl, protected hydroxy(lower)alkyl, amino(lower)alkyl, protected amino(lower) alkyl or an imino protective group, R4 is hydrogen, lower alkyl or lower alkylthio and A is lower alkylene which may be substituted with suitable substituent(s), or a salt thereof, which comprises (1) subjecting a compound of the formula : wherein R 3 , R 4 and A are each as defined above, R 5 is a protected amino group, R 6 is a protected carboxy group and Y is an acid residue, or a salt thereof to elimination reaction of the amino protective group in R 5 and the carboxy protective group in R 6 to give a compound of the formula : wherein R 3 , R 4 and A are each as defined above, or a salt thereof, or (2) subjecting a compound of the formula : wherein R4 and A are each as defined above and is an imino protective group, or a salt thereof to elimination reaction of the imino protective group to give a compound of the formula : wherein R4 and A are each as defined above, or a salt thereof.

Claim 15

A process for preparing a compound of the formula : wherein R 3 is hydrogen, lower alkyl, hydroxy(lower)alkyl, protected hydroxy(lower)alkyl, amino(lower)alkyl, protected amino(lower) alkyl or an imino protective group, R4 is hydrogen, lower alkyl or lower alkylthio and A is lower alkylene which may be substituted with suitable substituent(s), or a salt thereof, which comprises (1) subjecting a compound of the formula : wherein R 3 , R 4 and A are each as defined above, R 5 is a protected amino group, R 6 is a protected carboxy group and Y is an acid residue, or a salt thereof to elimination reaction of the amino protective group in R 5 and the carboxy protective group in R 6 to give a compound of the formula : wherein R 3 , R 4 and A are each as defined above, or a salt thereof, or (2) subjecting a compound of the formula : wherein R4 and A are each as defined above and is an imino protective group, or a salt thereof to elimination reaction of the imino protective group to give a compound of the formula : wherein R4 and A are each as defined above, or a salt thereof.

Claim 16

A pharmaceutical composition which comprises, as an active ingredient, a compound of claim 1 or a pharmaceutically acceptable salt thereof in admixture with pharmaceutically acceptable carriers.

Claim 17

Use of a compound of claim 1 or a pharmaceutically acceptable salt thereof for the manufacture of an antimicrobial medicament.

Claim 18

A compound of claim 1 or a pharmaceutically acceptable salt thereof for use as an antimicrobial agent.