Universitetet I Oslo

Universitetet | Oslo

Ørjan Samuelsen

Pål Rongved

Ove Alexander Høgmoen Åstrand

Geir Kildahl-Andersen

Christian Schnaars

Annette Bayer

Zeeshan Muhammad

Hanna-Kirsti Schrøder Leiros

Kine Susann Waade Edvardsen

Ove Alexander Høgmoen ÅStrand

The invention provides compounds for use in a method of treating and/or preventing a bacterial infection in a human or non-human mammal, said method comprising administration of said compound in combination with (either simultaneously, separately, or sequentially) a &#x3b2;-lactam antibiotic, wherein said compound has the general formula I: (wherein:

Compounds

The invention provides compounds for use in a method of treating and/or preventing a bacterial infection in a human or non-human mammal, said method comprising administration of said compound in combination with (either simultaneously, separately, or sequentially) a &#x3b2;-lactam antibiotic, wherein said compound has the general formula I: (I) (wherein: Q is a lipophilic, zinc chelating moiety which is selective for Znions and which comprises at least one, preferably two or more (e.g 2, 3 or 4), optionally substituted, unsaturated heterocyclic rings, e.g. 5 or 6-membered heterocyclic rings (such rings preferably include at least one heteroatom selected from N, S and O, preferably N); wherein any optional substituents may be selected from Calkyl, Calkoxy, halogen, nitro, cyano, amine, and substituted amine; each L, which may be the same or different, is a covalent bond or a linker; each W, which may be the same or different, is a non-peptidic hydrophilic group which comprises one or more hydroxy groups; and x is an integer from 1 to 3) or a stereoisomer, pharmaceutically acceptable salt or prodrug thereof.

Compounds according to formula I are provided:A-L-Bwherein A represents a lipophilic chelating moiety which is selective for Znions; L is a covalent bond or a linker; and B is a vector which is either a moiety capable of interacting with one or more biological structures found in a bacterium (preferably in a bacterial cell wall), for example a penicillin-binding protein such as a metallo-&#x3b2;-lactamase or DD-transferase, or a moiety capable of enhancing transport of the compound across a bacterial cell membrane. A method of treating and/or preventing a bacterial infection in a human or non-human mammal employing such compounds are also provided. In such a method, the compound of formula I may be administered in combination with (either simultaneously, separately, or sequentially) a &#x3b2;-lactam antibiotic.

Inhibitors of metallo-beta-lactamase (MBL) comprising a zinc chelating moiety

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