Amphotericin B derivatives with improved therapeutic index

Patent metadata

Field	Value
Publication number	US-11117920-B2
Application number	US-201916443728-A
Country	US
Kind code	B2
Filing date	Jun 17, 2019
Priority date	Oct 7, 2013
Publication date	Sep 14, 2021
Grant date	Sep 14, 2021

Abstract

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.

First claim

We claim:

1. A compound selected from the group consisting of AmBMU, AmBAU, and AmBCU, or a pharmaceutically acceptable salt thereof:

2. The compound of claim 1 , wherein the compound is AmBAU or a pharmaceutically acceptable salt thereof:

3. The compound of claim 1 , wherein the compound is AmBCU or a pharmaceutically acceptable salt thereof:

4. The compound of claim 1 , wherein the compound is AmBMU or a pharmaceutically acceptable salt thereof:

5. A pharmaceutical composition, comprising a compound of claim 1 ; and a pharmaceutically acceptable carrier.

6. The pharmaceutical composition of claim 5 , wherein the pharmaceutical composition is an oral or intravenous dosage form.

7. The pharmaceutical composition of claim 5 , wherein the pharmaceutical composition is an oral dosage form.

8. The pharmaceutical composition of claim 5 , wherein the pharmaceutical composition is an intravenous dosage form.

9. A method of inhibiting growth of a fungus, comprising contacting a fungus with an effective amount of a compound of claim 1 .

10. A method of treating a fungal infection, comprising administering to a subject in need thereof a therapeutically effective amount of a compound of claim 1 .

11. The method of claim 10 , wherein the compound is administered orally or intravenously.

12. The method of claim 10 , wherein the compound is administered orally.

13. The method of claim 10 , wherein the compound is administered intravenously.

Assignees

• Univ Illinois

Inventors

• Burke Martin D
• Davis Stephen
• Uno Brice E
• Struble Justin
• Dailey Ian
• Gray Kaitlyn C
• Knapp David M
• Wang Pulin
• Palyam Nagarjuna

Classifications

• C07H17/08 Primary

  Hetero rings containing eight or more ring members, e.g. erythromycins · CPC title

• A01N43/90

  having two or more relevant hetero rings, condensed among themselves or with a common carbocyclic ring system · CPC title

• A61K31/7048

  having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin {, digitoxin or digoxin} · CPC title

• A61K31/7042

  Compounds having saccharide radicals and heterocyclic rings · CPC title

• A61P31/10

  Antimycotics · CPC title