Cephem derivative

摘要

Provided is a cephem compound which has a wide antimicrobial spectrum, and in particular exhibits potent antimicrobial activity against beta-lactamase producing Gram negative bacteria, and a pharmaceutical composition comprising the same. The cephem compound has the formula (I):;
where W and U are as defined in the specification; R1 is as defined in the specification; R2A and R2B are as defined in the specification, provided that R2A and R2B are not taken together to form an optionally substituted oxime group when R1 is aminothiazole or aminothiadiazole optionally protected at the amino group; ring A is a benzene ring or a 6-membered aromatic heterocyclic group having 1-3 nitrogen atoms; R3 is a hydrogen atom, —OCH3 or —NH—CH(═O); k is an integer from 0 to 2; R4 is as defined in the specification; and D and E are as defined in accordance with a) or b) described in the specification.

主权项

1. A compound of the formula:or an ester, a protected compound at the amino on the ring in the 7-side chain, a pharmaceutically acceptable salt, or a solvate thereof,wherein
W is —CH2—, —S—, or —O—; provided thata) when W is —CH2—, then U is —CH2—, —S—, or —O—, andb) when W is —S— or —O—, then U is —CH2—;
R1 is an optionally substituted carbocyclic group, or optionally substituted heterocyclic group; with regard to R2A and R2B,a) R2A is an optionally substituted amino group, —SO3H, optionally substituted aminosulfonyl group, carboxyl group, optionally substituted (lower alkyl)oxycarbonyl group, optionally substituted carbamoyl group, hydroxyl group, or a substituted carbonyloxy group; and R2B is a hydrogen atom, orb) R2A and R2B are taken together to form an optionally substituted alkenyl group, or optionally substituted oxime group,
provided that when R1 is an aminothiazole of which the amino group is optionally protected, or an aminothiadiazole of which the amino group is optionally protected, R2A and R2B are not taken together to form an optionally substituted oxime group; ring A is a benzene ring, or 6-membered aromatic heterocyclic group having 1-3 nitrogen atoms; R3 is a hydrogen atom, —OCH3, or —NH—CH(═O); k is an integer from 0 to 2; each R4 is independently a hydrogen atom, halogen, hydroxyl group, —CN, —C(═O)—R6, —C(═O)—OH, —C(═O)—OR6, or —OR6; R6 is a lower alkyl or halo(lower)alkyl; and with regard to D and E,a) D is a single bond, —N(R8)—, or —R7—N(R8)— wherein R7 is an optionally substituted lower alkylene, and R8 is a hydrogen or lower alkyl; and E is an optionally substituted quaternary ammonium group of the formula selected from the following formula (1) to (40) and (42) to (53), orb) D has the formula:wherein q is an integer of 0 or 1, and E has the formula of a quaternary ammonium group represented by the following formula (10) or (41);wherein p is an integer from 1 to 3; n is an integer of 1 or 2; RX is an optionally substituted lower alkyl; the left side of attachment binds to methylene; and the right side of attachment binds to D, provided that the case where R1 is a phenyl and E has the formula (53) is excluded.