METALLO-β-LACTAMASE INHIBITORS Russian patent published in 2012 - IPC C07C51/41 C07C57/42 C07C59/42 C07C69/60 C07C215/74 C07C219/02 C07C279/08 C07D207/02 C07D233/02 C07D241/08 A61K31/194 A61K31/341 A61K31/495 A61K45/08 A61K47/08 A61P31/04 

FIELD: chemistry.

SUBSTANCE: maleic acid derivatives having general formula

have metallo-β-lactamase inhibiting activities. It is possible to recover anti-bacterial activities of β-lactam antibiotics against metallo-β-lactamase producing bacteria by combining the compound of general formula (I) with β-lactam antibiotics. The metallo-β-lactamase inhibitor is a compound of formula (I) or a pharmaceutically acceptable salt thereof, wherein R¹ denotes C_2-6-alkyl; C_3-7-cycloalkyl, where said cycle can be substituted with a hydroxyl group or can be condensed with an aryl; hydroxymethyl; - C_1-3-alkylene phenyl, where said phenyl group can be substituted with a hydroxyl group, C_1-6-alkyl group, hydroxymethyl group, a -COOM group, where M denotes a hydrogen atom or a pharmaceutically acceptable cation, a -CO-NR²²R²³ group, where R²² and R²³, which can be identical or different, denote a hydrogen atom or C_1-6-alkyl, wherein the alkyl can additionally be substituted with an aminocarbonyl, or R²² and R²³, together with a nitrogen atom with which they are bonded, can form a five- or six-member saturated heterocyclic ring containing 1-2 oxygen or nitrogen atoms, and the heterocycle can be substituted with a hydroxyl group or a C_1-6-alkanoyloxy group, a -O-R²⁴ group, where R²⁴ denotes C_1-6-alkyl, wherein the alkyl is optionally substituted with an aminocarbonyl, an amine group, a guanidine group or a five- or six-member saturated heterocycle, having 1-2 nitrogen atoms, -COOM, where M denotes a hydrogen atom, C_1-6-alkyl or a pharmaceutically acceptable cation, or a five- or six-member unsaturated heterocycle, having 1-2 nitrogen atoms; - C_0-1 alkylene heterocycle, where said heterocycle is a five- or six-member saturated or unsaturated heterocycle containing one nitrogen or oxygen atom and can be substituted with a hydroxyl group; - O-C_1-6-alkyl; or - S-C_1-6-alkyl, R² denotes C_1-6-alkyl, C_3-7-cycloalkyl, where said cycle can be substituted with a hydroxyl group or can be condensed with an aryl; or - C_1-3-alkylene phenyl, each M¹ independently denotes a hydrogen atom, a pharmaceutically acceptable cation.

EFFECT: new metallo-β-lactamase inhibitor acts as a medicament for inhibiting inactivation of β-lactam antibiotics and recovering anti-bacterial activities.

18 cl, 3 tbl, 98 ex