Technion Research & Development Foundation Ltd

Tel Aviv University

Alex Martin Szpilman

Itai Benhar

Nir Osherov

Vladimir Dergachev

Michal Amar

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]: wherein R is H, Calkyl or phenyl; Ris (CH)wherein m is between 0 and 4; Rand Rare each independently H or Calkyl, Ris or OH, Ris selected from a group consisting of: amide and alkyl, and Ris a water-soluble polymer, and pharmaceutically acceptable salts, solvates, hydrates, diastereomers, and prodrugs of the compound of Formula [I].

Amphotericin B derivatives

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]: wherein R is H, Calkyl or phenyl; Ris (CH)wherein m is between 0 and 4; Rand Rare each independently H or Calkyl, Ris H or OH, Ris selected from a group consisting of: amide and alkyl, and Ris a water-soluble polymer, and pharmaceutically acceptable salts, solvates, hydrates, diastereomers, and prodrugs of the compound of Formula [I].

Novel alpha-hydrogen substituted nitroxyl compounds and their corresponding oxidized (oxoammonium cations) and reduced (hydroxylamine) forms, and the use of such compounds, inter alia, for oxidation of primary and secondary alcohols to aldehydes and ketones, respectively; resolution of racemic alcohols; desymmetrization of meso-alcohol; as radicals and spin trapping reagents; and as polymerization agents. Processes for preparing the novel nitroxyl/oxoammonium/hydroxylamine compounds from the corresponding amines, and certain novel amine derivatives and their uses. The compounds and amine precursors are useful as ligands for transition metals and as organocatalysts in e.g., aldol reactions.

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Kiryat Tivion, Israel

Alex Martin Szpilman