Metallo-beta-lactamase inhibitors
AssigneeMeiji Seika Kaisha, Ltd.
InventorsKen Chikauchi, Mizuyo Ida, Takao Abe, Yukiko Hiraiwa, Akihiro Morinaka, Toshiaki Kudo
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Abstract
A new metallo-β-lactamase inhibitor which acts as a medicament for inhibiting the inactivation of β-lactam antibiotics and recovering anti-bacterial activities is disclosed. The maleic acid derivatives having the general formula (I) have metallo-β-lactamase inhibiting activities. It is possible to recover the anti-bacterial activities of β-lactam antibiotics against metallo-β-lactamase producing bacteria by combining the compound of the general formula (I) with β-lactam antibiotics.
Claims11
1-20. (canceled)
A pharmaceutical composition comprising at least a compound represented by the following formula (I), or a salt thereof:
- wherein:
- R1 represents a C2-6 alkyl group, a C3-7 cycloalkyl group, a hydroxymethyl group, a —C1-3 alkylene-phenyl group, a —C0-1 alkylene-heterocycle, a —O—C1-6 alkyl group, or a —S—C1-6 alkyl group, all of which may be substituted;
- R2 represents a C1-6 alkyl group, a C3-7 cycloalkyl group, a hydroxymethyl group, —C1-3 alkylene-phenyl group, a —C0-1 alkylene-heterocycle, a —O—C1-6 alkyl group, or a —S—C1-6 alkyl group, all of which may be substituted;
- and
- each M1 independently represents a hydrogen atom, a pharmaceutically acceptable cation, or a pharmaceutically acceptable group which can be hydrolyzed in vivo,
- a β-lactam antibiotic,
- and a pharmaceutically acceptable carrier.
A compound represented by the following formula (II), or a salt thereof:
- in which
- R3 represents a C2-6 alkyl group, a C3-7 cycloalkyl group, or a hydroxymethyl group, all of which may be substituted;
- R4 represents a C1-6 alkyl group or a C3-7 cycloalkyl group, all of which may be substituted;
- and
- each M2 independently represents a hydrogen atom, a pharmaceutically acceptable cation, or a pharmaceutically acceptable group which may be hydrolyzed in vivo.
A compound represented by the following formula (III), or a salt thereof:
- in which
- R5 represents an ethyl group;
- R6 represents a C1-3 linear alkyl group;
- and
- each M3 independently represents a pharmaceutically acceptable cation, or a pharmaceutically acceptable group which can be hydrolyzed in vivo.
A compound represented by the following formula (IV), or a salt thereof:
- in which
- R7 represents a C1-6 alkyl group, a C3-7 cycloalkyl group, a —C1-3 alkylene-phenyl group, a —C1 alkylene-ring A, a —O—C1-6 alkyl group, or a alkyl group, all of which may be substituted;
- R8 represents a —C1-3 alkylene-phenyl group, a —C0-1 alkylene-ring A, a —O—C1-6 alkyl group, or a —S—C1-6 alkyl group, all of which may be substituted;
- the ring A represents a five- to ten-membered mono- or bi-cyclic heterocyclic ring having 1-4 hetero atoms selected from nitrogen, oxygen and sulfur atoms;
- and
- each M4 independently represents a hydrogen atom, a pharmaceutically acceptable cation, or a pharmaceutically acceptable group which can be hydrolyzed in vivo;
- provided that when R7 is a C1-6 alkyl group, R8 excludes dihydrofuran.
A compound represented by the following formula (V), or a salt thereof:
- in which
- R9 represents a C1-6 alkyl group, a C3-7 cycloalkyl group, a —C1-3 alkylene-phenyl group, a —C0-1 alkylene-ring B, a —O—C1-6 alkyl group, or, a —S—C1-6 alkyl group, all of which may be substituted;
- R10 represents a —C1-3 alkylene-phenyl group, a —C0-1alkylene-ring B, a —O—C1-6 alkyl group, or a —S—C1-6 alkyl group, all of which may be substituted;
- ring B represents pyridine, piperidine, or tetrahydropyran;
- and
- each M5 independently represents a hydrogen atom, a pharmaceutically acceptable cation or a pharmaceutically acceptable group which may be hydrolyzed in vivo;
- provided that the case when R9 and R10 represent pyridinium is excluded.
Dependencies are inferred from the claim text.