Embodiments of the invention provide derivatives of Amphotericin B having increased solubility and reduced toxicity relative to AMB, while retaining antifungal activity against multiple clinical fungal isolates. Derivatives of AMB are provided comprising a polymer group having an amine group, the polymer linked to mycosamine via a relatively stable linker such as an amide linker. The derivatives may be of the general formula [I]: ##STR00001##
wherein R is H, C.sub.1-4 alkyl or phenyl; R.sup.2 is (CH.sub.2).sub.m wherein m is between 0 and 4; R.sup.3 and R.sup.4 are each independently H or C.sub.1-4 alkyl, R.sup.5 is or OH, R.sup.6 is selected from a group consisting of: amide and alkyl, and R.sup.7 is a water-soluble polymer, and pharmaceutically acceptable salts, solvates, hydrates, diastereomers, and prodrugs of the compound of Formula [I].

Provided herein are water-soluble prodrugs, compositions comprising such prodrugs, and related methods of making and administering the same. The prodrugs of the invention comprise a water-soluble polymer having three or more arms, at least three of which are typically covalently attached to an active agent, e.g., a small molecule. The conjugates of the invention provide an optimal balance of polymer size and structure for achieving improved drug loading, since the conjugates of the invention possess three or more active agents releasably attached to a multi-armed water-soluble polymer. The prodrugs of the invention are therapeutically effective, and exhibit improved properties in-vivo when compared to unmodified parent drug.

Embodiments of the invention provide derivatives of Amphotericin B having increased solubility and reduced toxicity relative to AMB, while retaining antifungal activity against multiple clinical fungal isolates. Derivatives of AMB are provided comprising a polymer group having an amine group, the polymer linked to mycosamine via a relatively stable linker such as an amide linker. The derivatives may be of the general formula [I]:

##STR00001##

wherein R is H, C.sub.1-4 alkyl or phenyl; R.sup.2 is (CH.sub.2).sub.m wherein m is between 0 and 4; R.sup.3 and R.sup.4 are each independently H or C.sub.1-4 alkyl, R.sup.5 is or OH, R.sup.6 is selected from a group consisting of: amide and alkyl, and R.sup.7 is a water-soluble polymer, and pharmaceutically acceptable salts, solvates, hydrates, diastereomers, and prodrugs of the compound of Formula [I].

Provided herein are water-soluble prodrugs, compositions comprising such prodrugs, and related methods of making and administering the same. The prodrugs of the invention comprise a water-soluble polymer having three or more arms, at least three of which are typically covalently attached to an active agent, e.g., a small molecule. The conjugates of the invention provide an optimal balance of polymer size and structure for achieving improved drug loading, since the conjugates of the invention possess three or more active agents releasably attached to a multi-armed water-soluble polymer. The prodrugs of the invention are therapeutically effective, and exhibit improved properties in-vivo when compared to unmodified parent drug.

Embodiments of the invention provide derivatives of Amphotericin B having increased solubility and reduced toxicity relative to AMB, while retaining antifungal activity against multiple clinical fungal isolates. Derivatives of AMB are provided comprising a polymer group having an amine group, the polymer linked to mycosamine via a relatively stable linker such as an amide linker. The derivatives may be of the general formula [I]: ##STR00001##
wherein R is H, C.sub.1-4 alkyl or phenyl; R.sup.2 is (CH.sub.2).sub.m wherein m is between 0 and 4; R.sup.3 and R.sup.4 are each independently H or C.sub.1-4 alkyl, R.sup.5 is H or OH, R.sup.6 is selected from a group consisting of: amide and alkyl, and R.sup.7 is a water-soluble polymer, and pharmaceutically acceptable salts, solvates, hydrates, diastereomers, and prodrugs of the compound of Formula [I].

The present invention aims to provide a polyester resin composition capable of producing a molded article having excellent stretchability. The present invention also aims to provide a molded article including the polyester resin composition.

The present invention relates to a polyester resin composition including: a polyester resin; and a polyrotaxane that has a cyclic molecule, a linear molecule threading through a cavity of the cyclic molecule in a skewered manner, and capping groups capping both ends of the linear molecule.

The present disclosure relates to dendrimers composed of a hetero-bifunctional moiety and an aromatic heterocycle and to methods of synthesizing said dendrimers. The present disclosure also relates to dendrimer-bioactive molecule conjugates, the process of synthesizing the conjugates and pharmaceutical compositions comprising said conjugates. The dendrimer in the conjugates acts as a carrier and significantly increases the therapeutic efficacy of the bioactive molecule.

Provided herein are water-soluble prodrugs, compositions comprising such prodrugs, and related methods of making and administering the same. The prodrugs of the invention comprise a water-soluble polymer having three or more arms, at least three of which are typically covalently attached to an active agent, e.g., a small molecule. The conjugates of the invention provide an optimal balance of polymer size and structure for achieving improved drug loading, since the conjugates of the invention possess three or more active agents releasably attached to a multi-armed water-soluble polymer. The prodrugs of the invention are therapeutically effective, and exhibit improved properties in-vivo when compared to unmodified parent drug.

Embodiments of the invention provide derivatives of Amphotericin B having increased solubility and reduced toxicity relative to AMB, while retaining antifungal activity against multiple clinical fungal isolates. Derivatives of AMB are provided comprising a polymer group having an amine group, the polymer linked to mycosamine via a relatively stable linker such as an amide linker. The derivatives may be of the general formula [I]:

##STR00001##

wherein R is H, C.sub.1-4 alkyl or phenyl; R.sup.2 is (CH.sub.2).sub.m wherein m is between 0 and 4; R.sup.3 and R.sup.4 are each independently H or C.sub.1-4 alkyl, R.sup.5 is H or OH, R.sup.6 is selected from a group consisting of: amide and alkyl, and R.sup.7 is a water-soluble polymer, and pharmaceutically acceptable salts, solvates, hydrates, diastereomers, and prodrugs of the compound of Formula [I].

The present disclosure provides conjugates comprising a Factor VIII moiety covalently attached via an oxime-containing linkage to a water-soluble polymer, such as for example, a polyethylene glycol polymer. Methods for preparing and for administering such conjugates, are also provided, as are water-soluble polymer oxyamine reagents useful for preparing the subject conjugates, among other things.