Cephem compounds, their production and use

Claim 2

A compound of the formula: wherein Q is nitrogen or CH; R 1 is hydrogen or a lower alkyl group which may be substituted; and ring A is a pyridine or pyridazine ring which is substituted at the ring-constituting carbon atom by a group of the formula: in which E is sulfur or NH; R2 is an amino, carbamoylamino, formylamino, acetylamino, N-formimidoylamino, N-acetimidoylamino, lower alkylamino, hydroxyl or carbamoyloxy group; and n is an integer of 2 to 4, or a pharmaceutically acceptable salt thereof.

Claim 3

The compound as claimed in claim 1, wherein ring A is a pyridazine ring which is substituted at the ring-constituting carbon atom by a group of the formula: in which the symbols have the same meanings as defined in claim 1.

Claim 4

The compound as claimed in claim 1, wherein ring A is a pyridine ring which is substituted at the ring-constituting carbon atom by a group of the formula: in which the symbols have the same meanings as defined in claim 1.

Claim 5

The compound as claimed in claim 1, wherein E is NH.

Claim 6

The compound as claimed in claim 2, wherein R2 is a formylamino or carbamoyloxy group.

Claim 7

The compound as claimed in claim 3, wherein R2 is a formylamino or carbamoyloxy group.

Claim 8

The compound as claimed in claim 4, wherein R 2 is a formylamino or carbamoyloxy group.

Claim 9

The compound as claimed in claim 1, wherein Rl is a C 1-6 alkyl group which may be substituted by an amino or vinyl group, the number of the substituent being one.

Claim 10

The compound as claimed in claim 3, namely 7β-[2-(2-aminothiazol-4-yl)-(Z)-2-ethoxyiminoacetamido]-3-C[5-(2-aminoethylthio)imidazo[1,2-a]pyridinium-l-yl]methyl]-3-cephem-4-carboxylate or a pharmaceutically acceptable salt thereof.

Claim 11

The compound as claimed in claim 4, namely 7β-[2-(2-aminothiazol-4-yl)-(Z)-2-ethoxyiminoacetamido]-3-[[6-(2-aminoethylamino)imidazo[1,2-b]pyridazinium-l-yl]methyl]-3-cephem-4-carboxylate or a pharmaceutically acceptable salt thereof.

Claim 12

The compound as claimed in claim 2, namely 7β-[2-(2-aminothiazol-4-yl)-(Z)-2-ethoxyiminoacetamido]-3-[[6-(2-aminoethylthio)imidazo[1,2-b]pyridazinium-1-yl]methyl]-3-cephem-4-carboxylate or a pharmaceutically acceptable salt thereof.

Claim 13

The compound as claimed in claim 3, namely 7β-[2-(2-aminothiazol-4-yl)-(Z)-2-ethoxyiminoacetamido]-3-[[5-(Z-carbamoyloxyethylthio)imidazo[1,2-a]pyridinium-1-yl]methyl]-3-cephem-4-carboxylate or a pharmaceutically acceptable salt thereof.

Claim 14

The compound as claimed in claim 3, namely 7p-[2-(2-aminothiazol-4-yl)-(Z)-2-ethoxyiminoacetamido]-3-[[5-(2-formylaminoethylthio)imidazo[1,2-a]pyridinium-1-yl]methyl]-3-cephem-4-carboxylate or a pharmaceutically acceptable salt thereof.

Claim 15

A process of producing a compound of the formula: wherein Q is nitrogen or CH; Rl is hydrogen or a lower alkyl group which may be substituted; and ring A is a pyridine or pyridazine ring which is substituted at the ring-constituting carbon atom by a group of the formula: -E-(CH 2 ) n -R 2 in which E is sulfur or NH; R2 is an amino, carbamoylamino, formylamino, acetylamino, N-formimidoylamino, N-acetimidoylamino, lower alkylamino, hydroxyl or carbamoyloxy group; and n is an integer of 2 to 4, or a pharmaceutically acceptable salt thereof, which comprises (1) reacting a compound of the formula: wherein R3 is an amino group which may be protected; R 4 is a hydroxyl, acyloxy, carbamoyloxy, substituted carbamoyloxy group or a halogen; and the other symbols have the same meanings as defined above or a salt thereof with a compound of the formula: wherein ring A' is a pyridine or pyridazine ring which is substituted at the ring-constituting carbon atom by a group of the formula: wherein R 2 ' is an amino or lower alkyl amino group which is protected; a hydroxyl, carbamoylamino or carbamoyloxy group which may be protected; or a formylamino or acetylamino group; and the other symbols have the same meanings as defined above, or a salt thereof, or (2) reacting a compound of the formula: wherein the symbols have the same meanings as defined above or a salt thereof with a compound of the formula: wherein the symbols have the same meanings as defined above, or a salt or reactive derivative thereof, or (3) reacting a compound of the formula: wherein the symbols have the same meanings as defined above or a salt thereof with a compound of the formula: wherein Rl'is a lower alkyl group which may be substituted or a salt or reactive derivative thereof, or (4) reacting a compound of the formula: wherein X is a halogen; and the symbols have the same meanings defined above or a salt thereof with thiourea, and if desired, followed by imidation reaction or deprotecting reaction.

Claim 16

A process of producing a compound of the formula: wherein Q is nitrogen or CH; Rl is hydrogen or a lower alkyl group which may be substituted; and ring A is a pyridine or pyridazine ring which is substituted at the ring-constituting carbon atom by a group of the formula: -E-(CH 2 ) n -R 2 in which E is sulfur or NH; R2 is an amino, carbamoylamino, formylamino, acetylamino, N-formimidoylamino, N-acetimidoylamino, lower alkylamino, hydroxyl or carbamoyloxy group; and n is an integer of 2 to 4, or a pharmaceutically acceptable salt thereof, which comprises (1) reacting a compound of the formula: wherein R3 is an amino group which may be protected; R 4 is a hydroxyl, acyloxy, carbamoyloxy, substituted carbamoyloxy group or a halogen; and the other symbols have the same meanings as defined above or a salt thereof with a compound of the formula: wherein ring A' is a pyridine or pyridazine ring which is substituted at the ring-constituting carbon atom by a group of the formula: wherein R 2 ' is an amino or lower alkyl amino group which is protected; a hydroxyl, carbamoylamino or carbamoyloxy group which may be protected; or a formylamino or acetylamino group; and the other symbols have the same meanings as defined above, or a salt thereof, or (2) reacting a compound of the formula: wherein the symbols have the same meanings as defined above or a salt thereof with a compound of the formula: wherein the symbols have the same meanings as defined above, or a salt or reactive derivative thereof, or (3) reacting a compound of the formula: wherein the symbols have the same meanings as defined above or a salt thereof with a compound of the formula: wherein Rl'is a lower alkyl group which may be substituted or a salt or reactive derivative thereof, or (4) reacting a compound of the formula: wherein X is a halogen; and the symbols have the same meanings defined above or a salt thereof with thiourea, and if desired, followed by imidation reaction or deprotecting reaction.

Claim 17

A pharmaceutical composition containing at least one of the compounds of the formula: wherein Q is nitrogen or CH; Rl is hydrogen or a lower alkyl group which may be substituted; and ring A is a pyridine or pyridazine ring which is substituted at the ring-constituting carbon atom by a group of the formula: in which E is sulfur or NH; R2 is an amino, carbamoylamino, formylamino, acetylamino, N-formimidoylamino, N-acetimidoylamino, lower alkylamino, hydroxyl or carbamoyloxy group; and n is an integer of 2 to 4, or a pharmaceutically acceptable salt thereof.

Claim 18

A pharmaceutical composition containing at least one of the compounds of the formula: wherein Q is nitrogen or CH; Rl is hydrogen or a lower alkyl group which may be substituted; and ring A is a pyridine or pyridazine ring which is substituted at the ring-constituting carbon atom by a group of the formula: in which E is sulfur or NH; R2 is an amino, carbamoylamino, formylamino, acetylamino, N-formimidoylamino, N-acetimidoylamino, lower alkylamino, hydroxyl or carbamoyloxy group; and n is an integer of 2 to 4, or a pharmaceutically acceptable salt thereof.