Amphotericin B derivatives with improved therapeutic index

Patent metadata

Field	Value
Publication number	US-11028114-B2
Application number	US-201916530109-A
Country	US
Kind code	B2
Filing date	Aug 2, 2019
Priority date	Oct 7, 2013
Publication date	Jun 8, 2021
Grant date	Jun 8, 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, or a pharmaceutically acceptable salt thereof, selected from the group consisting of:

2. The compound of claim 1 , wherein the compound is represented by:

3. The compound of claim 1 , wherein the compound is represented by:

4. The compound of claim 1 , wherein the compound is represented by:

5. The compound of claim 1 , wherein the compound is represented by:

6. The compound of claim 1 , wherein the compound is represented by:

7. The compound of claim 1 , wherein the compound is represented by:

8. The compound of claim 1 , wherein the compound is represented by:

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

10. The pharmaceutical composition of claim 9 , wherein the pharmaceutical composition is an oral or intravenous dosage form.

11. The pharmaceutical composition of claim 9 , wherein the pharmaceutical composition is an oral dosage form.

12. The pharmaceutical composition of claim 9 , wherein the pharmaceutical composition is an intravenous dosage form.

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

• A61P31/10

  Antimycotics · CPC title

• A61K31/7042

  Compounds having saccharide radicals and heterocyclic rings · CPC title

• A61K31/7048

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

• 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