University of Illinois

Northwestern University

Brice E Uno

Stephen J Davis

Martin D Burke

Kaitlyn C Gray

Stephen Scott Davis

David M Knapp

Justin Robert Struble

Ian Dailey

Pulin Wang

Nagarjuna Palyam

Karl A Scheidt

Souvik Rakshit

Justin Struble

Stephen Davis

Provided are certain derivatives of amphotericin B (AmB) characterized by reduced toxicity and retained anti-fungal activity. Certain of the derivatives are C16 urea derivatives of AmB. Certain of the derivatives are C3, C5, C8, C9, C11, C13, or C15 deoxy derivatives of AmB. Certain of the derivatives include C3′ or C4′ modifications of the mycosamine appendage of AmB. Also provided are methods of making AmB derivatives of the invention, pharmaceutical compositions comprising AmB derivatives of the invention, and methods of use of AmB derivatives of the invention.

Amphotericin B derivatives with improved therapeutic index

Disclosed are complexes and methods of using the complexes as catalysts for addition of amines to unsaturated electrophiles, as well as novel compounds produced by the disclosed complexes and methods. The disclosed methods may utilize the disclosed complexes as catalysts for adding unprotected primary amines and secondary amines to unsaturated electrophiles in an enantioselective manner to produce novel compounds which may include amino substituted succinimide compounds.

Catalysts and methods for enantioselective conjugate addition of amines to unsaturated electrophiles

Provided are certain derivatives of amphotericin B (AmB) characterized by reduced toxicity and retained anti-fungal activity. Certain of the derivatives are C16 urea derivatives of AmB. Certain of the derivatives are C3, C5, C8, C9, C11, C13, or C15 deoxy derivatives of AmB. Certain of the derivatives include C3' or C4&#x2032; modifications of the mycosamine appendage of AmB. Also provided are methods of making AmB derivatives of the invention, pharmaceutical compositions comprising AmB derivatives of the invention, and methods of use of AmB derivatives of the invention.

Catalysts and methods for enantioselective conjugate additions of amines to unsaturated electrophiles

Disclosed is a simplified, readily scalable series of individual methods that collectively constitute a method for the synthesis of C2'epiAmB, an efficacious and reduced-toxicity derivative of amphotericin B (AmB), beginning from AmB. Also provided are various compounds corresponding to intermediates in accordance with the series of methods. 

Scalable synthesis of reduced toxicity derivative of amphotericin B

Disclosed is a simplified, readily scalable series of individual methods that collectively constitute a method for the synthesis of C2'epiAmB, an efficacious and reduced-toxicity derivative of amphotericin B (AmB), beginning from AmB. Also provided are various compounds corresponding to intermediates in accordance with the series of methods.

Disclosed is a derivative of amphotericin B (AmB), denoted C2'epiAmB, with an improved therapeutic index over amphotericin B, pharmaceutical compositions comprising the AmB derivative, methods of making the AmB derivative and the pharmaceutical composition, and their use in methods of inhibiting growth of a yeast or fungus and treating a yeast or fungal infection. C2&#x2032;epiAmB is an epimer of the parent compound. Specifically, C2&#x2032;epiAmB differs from the parent compound at the C2&#x2032; stereogenic center on mycosamine. This difference in structure results in (i) retained capacity to bind ergosterol and inhibit growth of yeast, (ii) greatly reduced capacity to bind cholesterol, and (iii) essentially no toxicity to human cells.

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Highland Park, IL, United States of America

Brice E Uno