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 compound of Formula (I):

##STR00001##

or a pharmaceutically acceptable salt thereof, in which Ring X is a 3 to 7 membered monocyclic ring, at least one of R.sub.1, R.sub.2, R.sub.3, and R.sub.4 is OR.sub.5 or CH.sub.2OR.sub.5 and the other R.sub.1, R.sub.2, R.sub.3, and R.sub.4 each independently are halogen, OH, OR.sub.5, CH.sub.2OR.sub.5, CO.sub.2H, OC═OR.sub.6, (C═O)R.sub.6, R.sub.6, C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, H, or absent. Also provided herein are therapeutic uses of the compound of Formula (I).

A compound of Formula (I):

##STR00001##

or a pharmaceutically acceptable salt thereof, in which Ring X is a 3 to 7 membered monocyclic ring, at least one of R.sub.1, R.sub.2, R.sub.3, and R.sub.4 is OR.sub.5 or CH.sub.2OR.sub.5 and the other R.sub.1, R.sub.2, R.sub.3, and R.sub.4 each independently are halogen, OH, OR.sub.5, CH.sub.2OR.sub.5, CO.sub.2H, OC═OR.sub.6, (C═O)R.sub.6, R.sub.6, C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, H, or absent. Also provided herein are therapeutic uses of the compound of Formula (I).

Compounds, compositions, and methods for treatment and/or prevention of at least one disease, disorder, and/or condition by inhibiting binding of an E-selectin, galectin-3, or E-selectin and galectin-3 to ligands a disclosed. For example, heterobifunctional inhibitors of E-selectin and galectin-3 are described and pharmaceutical compositions comprising at least one such agent is described.

##STR00001##

Compounds, compositions, and methods for treatment and/or prevention of at least one disease, disorder, and/or condition by inhibiting binding of an E-selectin to an E-selectin ligand are disclosed. For example, haloalkyl fucose-containing E-selectin antagonists and compositions comprising at least one such agent are described.

Disclosed are oligonucleotides that binds specifically to HIV neutralizing monoclonal antibody 2G12 with a K.sub.4 value lower than 20 nM, the oligonucleotide comprising a predicted structure, at 37 C., having exactly one stem-loop whereby the loop comprises the nucleotide sequence of AACCNACGGANAAA (SEQ ID NO: 1), where N is a modified nucleoside base, and the stem includes at least 3 nucleotide base-pairs and one of the nucleotides in the stem includes a modified nucleoside base, wherein the modified nucleoside base has the structure -B-L-A where A is a branched-chain Man.sub.9 oligosaccharide, L is a linker molecule, and B is independently a pyrimidine or pyridine base linked to the sugar-phosphate backbone of the oligonucleotide. Immunogenic conjugates that include the oligonucleotide, and pharmaceutical compositions that include the oligonucleotide or the immunogenic conjugate are also disclosed. Various method of using the oligonucleotides, immunogenic conjugates, and pharmaceutical compositions are also disclosed.

Disclosed are oligonucleotides that binds specifically to HIV neutralizing monoclonal antibody 2G12 with a K.sub.4 value lower than 20 nM, the oligonucleotide comprising a predicted structure, at 37 C., having exactly one stem-loop whereby the loop comprises the nucleotide sequence of AACCNACGGANAAA (SEQ ID NO: 1), where N is a modified nucleoside base, and the stem includes at least 3 nucleotide base-pairs and one of the nucleotides in the stem includes a modified nucleoside base, wherein the modified nucleoside base has the structure -B-L-A where A is a branched-chain Man.sub.9 oligosaccharide, L is a linker molecule, and B is independently a pyrimidine or pyridine base linked to the sugar-phosphate backbone of the oligonucleotide. Immunogenic conjugates that include the oligonucleotide, and pharmaceutical compositions that include the oligonucleotide or the immunogenic conjugate are also disclosed. Various method of using the oligonucleotides, immunogenic conjugates, and pharmaceutical compositions are also disclosed.

The present invention provides improved processes for the preparation of drug-linkers with a -glucuronide cleavable unit, as well as intermediates thereof.

The present disclosure provides, inter alia, antibody-drug conjugates that are useful in treating various diseases such as cancer.

The present disclosure provides, inter alia, antibody-drug conjugates that are useful in treating various diseases such as cancer.