The present disclosure relates to novel methods for preparing antibacterial aminoglycoside compounds and the compounds used in such preparations.

A chromatographic material including a substrate having a surface and having a polymeric layer covalently bound to the surface; the polymeric layer comprising polymer molecules covalently attached to the surface of the substrate, each polymer molecule being attached to the surface via multiple siloxane bonds and each polymer molecule being connected to one or more functionalizing compounds that each comprise a functional group, wherein the polymeric layer is formed by covalently attaching polymer molecules to the surface of the substrate via multiple siloxane bonds, each polymer molecule containing multiple first reactive groups, and reacting the first reactive groups of the attached polymer molecules with at least one functionalizing compound that comprises a second reactive group that is reactive with the first reactive groups and that further comprises a functional group. Preferred conditions of reacting the polymer with the substrate include elevated temperature and reduced pressure.

A chromatographic material including a substrate having a surface and having a polymeric layer covalently bound to the surface; the polymeric layer comprising polymer molecules covalently attached to the surface of the substrate, each polymer molecule being attached to the surface via multiple siloxane bonds and each polymer molecule being connected to one or more functionalizing compounds that each comprise a functional group, wherein the polymeric layer is formed by covalently attaching polymer molecules to the surface of the substrate via multiple siloxane bonds, each polymer molecule containing multiple first reactive groups, and reacting the first reactive groups of the attached polymer molecules with at least one functionalizing compound that comprises a second reactive group that is reactive with the first reactive groups and that further comprises a functional group. Preferred conditions of reacting the polymer with the substrate include elevated temperature and reduced pressure.

Provided herein are aminoglycoside compounds, such as compounds of formula (I), (II), (III), (IV), (IVa), (V), (VI), (VIIa), or (VIIb) or pharmaceutically acceptable salts, solvates, stereoisomers, or tautomers of any of the foregoing, useful as therapeutic or prophylactic agents. Also provided herein are methods for their preparation. The compounds may be useful in treating a bacterial infection in a subject, for example a Gram-negative bacterial infection.

Provided herein are aminoglycoside compounds, such as compounds of formula (I), (II), (III), (IV), (IVa), (V), (VI), (VIIa), or (VIIb) or pharmaceutically acceptable salts, solvates, stereoisomers, or tautomers of any of the foregoing, useful as therapeutic or prophylactic agents. Also provided herein are methods for their preparation. The compounds may be useful in treating a bacterial infection in a subject, for example a Gram-negative bacterial infection.

A chromatographic material including a substrate having a surface and having a polymeric layer covalently bound to the surface; the polymeric layer comprising polymer molecules covalently attached to the surface of the substrate, each polymer molecule being attached to the surface via multiple siloxane bonds and each polymer molecule being connected to one or more functionalizing compounds that each comprise a functional group, wherein the polymeric layer is formed by covalently attaching polymer molecules to the surface of the substrate via multiple siloxane bonds, each polymer molecule containing multiple first reactive groups, and reacting the first reactive groups of the attached polymer molecules with at least one functionalizing compound that comprises a second reactive group that is reactive with the first reactive groups and that further comprises a functional group. Preferred conditions of reacting the polymer with the substrate include elevated temperature and reduced pressure.

A chromatographic material including a substrate having a surface and having a polymeric layer covalently bound to the surface; the polymeric layer comprising polymer molecules covalently attached to the surface of the substrate, each polymer molecule being attached to the surface via multiple siloxane bonds and each polymer molecule being connected to one or more functionalizing compounds that each comprise a functional group, wherein the polymeric layer is formed by covalently attaching polymer molecules to the surface of the substrate via multiple siloxane bonds, each polymer molecule containing multiple first reactive groups, and reacting the first reactive groups of the attached polymer molecules with at least one functionalizing compound that comprises a second reactive group that is reactive with the first reactive groups and that further comprises a functional group. Preferred conditions of reacting the polymer with the substrate include elevated temperature and reduced pressure.

The present invention relates to conjugates of aminoglycosides and terpenoids, in particular sesquiterpenoids. Furthermore, the present invention relates to nano-assemblies formed by the inventive conjugates and to a method for producing the conjugates and/or the nano-assemblies. The present invention also relates to the inventive conjugates and nano-assemblies for use in therapy, in particular for use in the treatment of infectious diseases. Particularly preferred embodiments of the present invention relate to farnesylated aminoglycosides and nano-assemblies thereof, in which farnesol and its derivatives do not only function as carrier for the aminoglycosides but do themselves have pharmaceutical activity upon cleavage of the conjugate, in particular quorum sensing inhibitory activity.

The present invention relates to conjugates of aminoglycosides and terpenoids, in particular sesquiterpenoids. Furthermore, the present invention relates to nano-assemblies formed by the inventive conjugates and to a method for producing the conjugates and/or the nano-assemblies. The present invention also relates to the inventive conjugates and nano-assemblies for use in therapy, in particular for use in the treatment of infectious diseases. Particularly preferred embodiments of the present invention relate to farnesylated aminoglycosides and nano-assemblies thereof, in which farnesol and its derivatives do not only function as carrier for the aminoglycosides but do themselves have pharmaceutical activity upon cleavage of the conjugate, in particular quorum sensing inhibitory activity.

Modified aminoglycoside compounds represented by Formula I as defined and described in the specification are provided. The modified aminoglycosides feature a diamine-containing functional moiety at one or more of positions 3′, 4′ and 6′. Uses of the modified aminoglycosides as antimicrobial (e.g., antibacterial) agents, and in treating medical conditions associated with microorganisms, are also provided.