Discovery, total synthesis, and bioactivity of doscadenamides

Patent metadata

Field	Value
Publication number	US-12565474-B2
Application number	US-202017630138-A
Country	US
Kind code	B2
Filing date	Jul 24, 2020
Priority date	Jul 26, 2019
Publication date	Mar 3, 2026
Grant date	Mar 3, 2026

Abstract

The invention is directed towards compounds (e.g., Formulae (I)-(IX)), their mechanism of action, processes to prepare the compounds, methods of activating quorum sensing signaling activity, and methods of treating diseases and disorders using the compounds described herein (e.g., Formulae (I)-(IX)).

First claim

What is claimed:

1 . A compound of Formula (IX):

or a pharmaceutically acceptable salt, solvate, or hydrate thereof;
wherein R 13 is H, Boc, acetyl, Fmoc,

each R 14 is independently H or C 1 -C 6 alkyl;
R 15 is H or C 1 -C 6 alkyl;
each R 6 is independently H, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, or C 2 -C 6 alkynyl;
R 8 is H, Boc, acetyl, Fmoc, or

R 7 is H, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, or C 2 -C 6 alkynyl;
R 9 is H or C 1 -C 6 alkyl; and
R 10 is H or C 1 -C 6 alkyl, wherein the compound is not:

2 . The compound of claim 1 , or pharmaceutically acceptable salt thereof, wherein the compound is a compound according to Formula (I):

or a pharmaceutically acceptable salt thereof;
wherein R 1 is H, Boc, acetyl, Fmoc, or

R 2 is H or C 1 -C 6 alkyl;
R 3 is H;
R 4 is H or C 1 -C 6 alkyl;
R 5 is H or C 1 -C 6 alkyl;
R 6 is H, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, or C 2 -C 6 alkynyl; and
R 7 is H, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, or C 2 -C 6 alkynyl.

3 . The compound of claim 2 , or a pharmaceutically acceptable salt thereof, wherein the compound is a compound according to Formula (II):

or a pharmaceutically acceptable salt thereof.

4 . The compound of claim 2 , or a pharmaceutically acceptable salt thereof, according to Formula (III):

or a pharmaceutically acceptable salt thereof.

5 . The compound of claim 2 , or a pharmaceutically acceptable salt thereof, according to Formula (IV):

or a pharmaceutically acceptable salt thereof.

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

or a pharmaceutically acceptable salt thereof.

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

or a pharmaceutically acceptable salt thereof.

8 . The compound of claim 1 , or pharmaceutically acceptable salt thereof, wherein the compound is a compound according to Formula (VIII):

or a pharmaceutically acceptable salt thereof;
wherein:
R 16 is H, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, or C 2 -C 6 alkynyl; and R 17 is H or C 1 -C 6 alkyl; or
R 16 is H or C 1 -C 6 alkyl; and R 17 is H, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, or C 2 -C 6 alkynyl.

9 . The compound of claim 8 , or a pharmaceutically acceptable salt thereof, wherein the compound is:

(doscadenamide S4),
or a pharmaceutically acceptable salt thereof.

10 . The compound of claim 1 , or pharmaceutically acceptable salt thereof, wherein the compound is a compound according to Formula (V):

or a pharmaceutically acceptable salt thereof;
wherein R 4 is H or C 1 -C 6 alkyl;
R 5 is H or C 1 -C 6 alkyl;
R 6 is H, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, or C 2 -C 6 alkynyl;
R 8 is H, Boc, acetyl, Fmoc, or

R 7 is H, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, or C 2 -C 6 alkynyl;
R 9 is H or C 1 -C 6 alkyl; and
R 10 is H or C 1 -C 6 alkyl.

11 . The compound of claim 10 , or a pharmaceutically acceptable salt thereof, wherein the compound is:

or a pharmaceutically acceptable salt thereof.

12 . The compound of claim 11 , or pharmaceutically acceptable salt thereof, wherein the compound is a compound according to Formula (VI):

or a pharmaceutically acceptable salt thereof;
wherein R 12 is H, Boc, acetyl, Fmoc, or

R 11 is C 1 -C 6 alkyl;
R 6 is H, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, or C 2 -C 6 alkynyl;
R 8 is H, Boc, acetyl, Fmoc, or

R 7 is H, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, or C 2 -C 6 alkynyl;
R 9 is H or C 1 -C 6 alkyl; and
R 10 is H or C 1 -C 6 alkyl.

13 . The compound of claim 12 , or a pharmaceutically acceptable salt thereof, wherein the compound is:

or a pharmaceutically acceptable salt thereof.

14 . A pharmaceutical composition comprising a compound of claim 1 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

15 . A method of activating quorum sensing signaling, the method comprising administering an effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof.

16 . A method of inhibiting bacterial growth, the method comprising administering an effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof.

17 . A method of treating a bacterial infection in a subject, the method comprising administering an effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof.

18 . A method of treating cancer in a subject, the method comprising administering an effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof.

19 . A method of increasing the effectiveness of anti-cancer therapy in a subject currently being administered one or more anti-cancer therapies, the method comprising administering an effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof.

20 . A method of increasing the e

Assignees

• Univ Florida
• Smithsonian Inst

Inventors

• Luesch Hendrik
• Liang Xiao
• Matthew Susan
• Kwan Jason C
• Chen Qi-Yin
• Paul Valerie J

Classifications

• A61P31/04

  Antibacterial agents · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A01N43/36

  five-membered rings · CPC title

• C07D207/38 Primary

  2-Pyrrolones · CPC title