Disclosed herein are new O-biphenyl- and O-phenylheteroarylmannoside compounds and compositions and their application as pharmaceuticals for use in the treatment of human disease. Methods of inhibition of FimH activity in human subjects are also provided for the treatment of diseases such as urinary tract infection.

Disclosed herein are new O-biphenyl- and O-phenylheteroarylmannoside compounds and compositions and their application as pharmaceuticals for use in the treatment of human disease. Methods of inhibition of FimH activity in human subjects are also provided for the treatment of diseases such as urinary tract infection.

Synthetic pathways for preparing pseudo-trisaccharide aminoglycoside compounds represented by Formula I or Ia as defined in the specification and donor and acceptor compounds useful for preparing such compounds are provided. A process of stereoselectively preparing compounds represented by Formula III as defined in the specification, while avoiding chromatographic separation of stereoisomers are also provided. Compounds prepared by the described processes and uses thereof are also provided.

Synthetic pathways for preparing pseudo-trisaccharide aminoglycoside compounds represented by Formula I or Ia as defined in the specification and donor and acceptor compounds useful for preparing such compounds are provided. A process of stereoselectively preparing compounds represented by Formula III as defined in the specification, while avoiding chromatographic separation of stereoisomers are also provided. Compounds prepared by the described processes and uses thereof are also provided.

Novel aminoglycosides, represented by Formulae Ia and Ib, as defined in the instant specification, designed to exhibit stop codon mutation readthrough activity, are provided. Also provided are pharmaceutical compositions containing the same, and uses thereof in the treatment of genetic diseases and disorders, such as diseases and disorders associated with stop codon mutations.

Novel aminoglycosides, represented by Formulae Ia and Ib, as defined in the instant specification, designed to exhibit stop codon mutation readthrough activity, are provided. Also provided are pharmaceutical compositions containing the same, and uses thereof in the treatment of genetic diseases and disorders, such as diseases and disorders associated with stop codon mutations.

A new class of pseudo-trisaccharide aminoglycosides having an alkyl group at the 5″ position, exhibiting efficient stop codon mutation readthrough activity, low cytotoxicity and high selectivity towards eukaryotic translation systems are provided. Also provided are pharmaceutical compositions containing the same, and uses thereof in the treatment of genetic disorders, as well as processes of preparing these aminoglycosides. The disclosed aminoglycosides can be represented by the general formula I:

##STR00001##

or a pharmaceutically acceptable salt thereof, wherein R.sub.1 is selected from the group consisting of alkyl, cycloalkyl and aryl; and all other variables and features are as described in the specification.

A new class of pseudo-trisaccharide aminoglycosides having an alkyl group at the 5″ position, exhibiting efficient stop codon mutation readthrough activity, low cytotoxicity and high selectivity towards eukaryotic translation systems are provided. Also provided are pharmaceutical compositions containing the same, and uses thereof in the treatment of genetic disorders, as well as processes of preparing these aminoglycosides. The disclosed aminoglycosides can be represented by the general formula I:

##STR00001##

or a pharmaceutically acceptable salt thereof, wherein R.sub.1 is selected from the group consisting of alkyl, cycloalkyl and aryl; and all other variables and features are as described in the specification.

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.