Granted Patent B2

US 12,709,596 · App. 17/622,451 · Granted Aug 18, 2026

Inventors: Ian Holmes (Melbourne, AU); Weiguang Zeng (Melbourne, AU); David Jackson (Melbourne, AU); Christophe Demaison (Melbourne, AU); Grant Mclachlan (Melbourne, AU)

Assignee: ENA Respiratory Pty Ltd

C07C321/14A61K47/60A61K47/64A61P31/12C07K5/081C08G65/3348

Abstract

Claims (96)

1 . A compound of general formula:

A-Y—B

wherein A is represented by:

wherein:

b is 0;

w is 1;

v is an integer from 2 to 5;

z is 1;

X is —S—;

Z 1 and Z 2 are each independently selected from the group consisting of —O—, —NR—, —S—, S(═O), S(═O) 2 —, —C(═O)O—, —OC(═O)—, —C(═O)NR—, —NRC(═O)—, —C(═O)S—, —SC(═O)—, OC(═O)O—, NRC(═O)O—, —OC(═O)NR—, and —NRC(═O)NR—;

R 11 , R 12 , R x , R y , R 14 , R 15 , R 16 , and R 17 are each independently H or C 1 -C 6 aliphatic;

R, R 13 and R 18 are each independently H or C 1 -C 6 aliphatic;

R 19 is H, C 1 -C 6 aliphatic, an amino protecting group, L 3 -C(═O)—, or A 2 ;

L 1 and L 2 are each independently C 5 -C 21 aliphatic or C 4 -C 20 heteroaliphatic;

L 3 is C 1 -C 21 aliphatic or C 2 -C 20 heteroaliphatic;

A 2 is an amino acid or a peptide;

wherein any aliphatic or heteroaliphatic present in any of R, R 11 , R 12 , R 13 , R 14 , R 15 , R 16 , R 17 , R 18 , R 19 , R x , R y , L 1 , L 2 , and L 3 is optionally substituted;

Y is

wherein:

R 1 and R 2 are independently selected from the group consisting of H, —CH 2 OH, —CH 2 CH 2 OH, —CH(CH 3 )OH, —CH 2 OPO(OH)2, —CH 2 C(═O)NH 2 , —CH 2 CH 2 C(═O)OH and —CH 2 CH 2 C(═O)OR 8 , wherein any one of the alkyl hydrogens can be replaced with a halogen;

R 8 is selected from the group consisting of H and a straight or branched C 1 -C 6 alkyl;

and

B represents a Polyethylene Glycol (PEG), wherein the PEG is a substituted PEG according to the following formula:

wherein

n is 3 to 100;

m is 1, 2, 3, or 4;

p is 2, 3, or 4;

q is null or 1;

R 3 is H, —NH 2 , or —OH, wherein when q is null, R 3 is H and when q is 1, R 3 is —NH 2 or —OH;

L is null or consists of 1 to 10 units, wherein each unit has the formula:

wherein

R 4 is H; and

R 5 is a side chain of an amino acid selected from: the 20 naturally occurring amino acids commonly designated by three letter symbols, 4-hydroxyproline, hydroxylysine, demosine, isodemosine, 3-methylhistidine, norvlin, beta-alanine, gamma-aminobutyric acid, citrulline, homocysteine, homoserine, ornithine, and methionine sulfone;

or a pharmaceutically acceptable salt, solvate or prodrug thereof.

2 . The compound of claim 1 , or a pharmaceutically acceptable salt, solvate or prodrug thereof, wherein q is 1.

3 . The compound of claim 1 , or a pharmaceutically acceptable salt, solvate or prodrug thereof, wherein n is from 10 to 14.

4 . The compound of claim 3 , or a pharmaceutically acceptable salt, solvate or prodrug thereof, wherein n is 11.

5 . The compound of claim 1 , or a pharmaceutically acceptable salt, solvate or prodrug thereof, wherein n is from 24 to 30.

6 . The compound of claim 5 , or a pharmaceutically acceptable salt, solvate or prodrug thereof, wherein n is 27.

7 . The compound of claim 1 , or a pharmaceutically acceptable salt, solvate or prodrug thereof, wherein m is from 1 to 3.

8 . The compound of claim 7 , or a pharmaceutically acceptable salt, solvate or prodrug thereof, wherein m is 2.

9 . The compound of claim 1 , or a pharmaceutically acceptable salt, solvate or prodrug thereof, wherein v is 2.

10 . The compound of claim 1 , or a pharmaceutically acceptable salt, solvate or prodrug thereof, wherein R x , R y , R 13 , R 14 , R 15 , R 16 , and R 17 are H.

11 . The compound of claim 1 , or a pharmaceutically acceptable salt, solvate or prodrug thereof, wherein Z 1 and Z 2 are the same and selected from the group consisting of —O—, —NR—, —S—, S(═O), S(═O) 2 —, —C(═O)O—, —OC(═O)—, —C(═O)NR—, —NRC(═O)—, —C(═O)S—, —SC(═O)—, OC(═O)O—, NRC(═O)O—, —OC(═O)NR—, and —NRC(═O)NR—, wherein each R is independently H or C 1 -C 6 aliphatic.

12 . The compound according to claim 1 , or a pharmaceutically acceptable salt, solvate or prodrug thereof, wherein the compound is the R stereoisomer of the compound around the chiral center denoted by *:

and/or

wherein the chiral center denoted by ** in the following formula is in the L-configuration:

wherein the chiral center denoted by *** in the following formula is in the L-configuration:

13 . The compound according to claim 1 selected from any one of the following compounds:

Compound

Compound Structure

name

Compound 1

Compound 2

Compound 3

Compound 4

Compound 5

Compound 6

Compound 7

Compound 8

Compound 9

Compound 10

Compound 11

Compound 12

Compound 13

Compound 14

Compound 15

Compound 16

Compound 17

Compound 18

Compound 19

Compound 20

Compound 21

Compound 22

Compound 23

Compound 24

Compound 25

Compound 26

Compound 27

Compound 28

Compound 29

Compound 30

Compound 31

Compound 32

Compound 33

Compound 34

Compound 35

Compound 36

or a pharmaceutically acceptable salt, solvate or prodrug thereof.

14 . A composition comprising a compound of claim 1 , or a pharmaceutically acceptable salt, solvate or prodrug thereof, and a pharmaceutically acceptable carrier, diluent or excipient.

15 . A method of treating a disease, comprising raising an innate immune response in a subject by administering an effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt, solvate or prodrug thereof to the subject in need thereof.

16 . The method of claim 15 , wherein the disease is selected from one or more of a disease caused by an infectious agent, a respiratory disease or condition associated with a viral or bacterial infection, and a respiratory infection.

17 . The method of claim 15 , which is a method for reducing airway inflammation.

18 . The method of claim 17 , wherein the method further comprises the step of identifying a subject having a respiratory disease or condition.

19 . The method of claim 18 , wherein the respiratory disease or condition is not a rhinovirus infection.

20 . The compound of claim 1 , or a pharmaceutically acceptable salt, solvate or prodrug thereof, wherein R 5 is H.

Assignments (10)

Priority Claims (2)

Continuity (1)

References Cited (240)