N-phenyl-3-mercaptopropanamide derivatives as metallo-beta-lactamase inhibitors for the treatment of bacterial infections
AssigneeHelmholtz-Zentrum FüR Infektionsforschung GmbH
InventorsRolf W. Hartmann, Jelena Konstantinovic, Jörg Haupenthal, Anna K. Hirsch, Andreas M. Kany, Cansu Kaya, Samir Yahiaoui, Thomas Wichelhaus, Eugen Proschak
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Abstract
The present invention related to novel inhibitors of metallo-β-lactamases of formula (I) wherein R1 is an optionally substituted aryl group of an optionally substituted heteroaryl group, and the use thereof in the treatment of bacterial infections, especially in combination with β-lactam antibiotics.
Claims20
A compound of formula (I):
- wherein
- R1 is a substituted phenyl group or a substituted heteroaryl group containing 5 or 6 ring atoms selected from C, O, N and S,
- wherein the substituents are independently selected from groups of formula —O—C1-6 alkyl, —NHC1-6 alkyl, —N(C1-6 alkyl)2, —COOH, —COOMe, —COMe, —NHSO2Me, —SO2NMe2, —SO2NCNH2NH2, —CH2N(CH2CH3)2, —SO2NHCONH2, —SO2NHC(NH)NH2, —CH2N(CH2CH2)2NCH3, —SO3H, —SO2NH2, —CONH2, —CH2NH2, —CN, —S—C1-6 alkyl, NHAc, —SO2—N(CH2CH2)2O, —NHCONH2, —SO2Me and cyclopropyl,
- or a pharmaceutically acceptable salt thereof.
A compound selected from the following compounds, or a salt thereof:
- wherein R2 is —COOH, —NHSO2Me, —OH or —COOMe;
- R3 is —OH, —COOH, —NHSO2Me, —CH2NH2, —NO2, —SO3H or —CH2N(CH2CH3)2;
- and R4 is —OH, —NH2, —COOH, —COOMe, —COMe, —SO2NMe2, —SO2—N(CH2CH2)2O, —SO2NHCONH2, —SO2NHC(NH)NH2 or —CH2N(CH2CH2)2NCH3.
A method for treating a bacterial infection which comprises administering to a subject in need of such treatment a therapeutically effective amount of a compound of formula (I), or a pharmaceutically acceptable salt thereof, in combination with a β-lactam antibiotic:
- wherein
- R1 is an optionally substituted phenyl group or an optionally substituted heteroaryl group containing 5 or 6 ring atoms selected from C, O, N and S,
- wherein the optional substituents are independently selected from fluorine, chlorine, bromine and iodine and groups of formula —OH, —O—C1-6 alkyl, —NH2, —NHC1-6 alkyl, —N(C1-6 alkyl)2, —COOH, —COOMe, —COMe, —NHSO2Me, —SO2NMe2, —SO2NCNH2NH2, —CH2N(CH2CH3)2, —SO2NHCONH2, —SO2NHC(NH)NH2, —CH2N(CH2CH2)2NCH3, —SO3H, —SO2NH2, —CONH2, —CH2NH2, —CN, —C1-6 alkyl, —SH, —S—C1-6 alkyl, NHAc, —SO2—N(CH2CH2)2O, —NO2, —C≡CH, —NHCONH2, —SO2Me and cyclopropyl.
Dependencies are inferred from the claim text.