# US 2021/0277038 A1 · Imidazoquinoline derivatives and their use in therapy

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- Number: US 2021/0277038 A1
- Document ID: US20210277038A1
- Status: Published application
- Kind: A1
- Application number: 16/330,599
- Filed: 2016-09-05
- Published: 2021-09-09
- Earliest claimed: 2016-09-05
- Assignees: Glaxosmithkline Biologicals SA
- Applicants: Glaxosmithkline Biologicals, S.A.
- Inventors: Helene G. BAZIN-LEE; Jay T. EVANS; David BURKHART; Michael COCHRAN; David A. JOHNSON
- Web page: https://patentgrep.com/patent/US20210277038A1

## CPC

- C07F 9/6561: containing systems of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring or ring system, with or without other non-condensed hetero rings
- A61K 31/4745: condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines (yohimbine derivatives, vinblastine A61K31/475; ergoline derivatives A61K31/48)
- A61P 37/04: Immunostimulants
- C07D 471/04: Ortho-condensed systems
- C07D 487/14: Ortho-condensed systems
- C07F: ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM (metal-containing porphyrins C07D487/22)
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)

## Abstract

This invention relates inter alia to novel imidazoquinoline derivatives and their use in therapy, particularly as vaccine adjuvants.

## Claims

### Claim 1

A compound of formula (I):
wherein:
R1 represents —O—Z—(P(═O)—OH)—O—Y-A
R2 represents H, C1-C6 alkyl, C1-C6 alkylamino, C1-C6 alkoxy, C3-C6 cycloalkylC1-C6 alkyl, C3-C6 cycloalkylC1-C6 alkylamino, C3-C6 cycloalkylC1-C6 alkoxy, C1-C6 alkoxyC1-C6 alkyl, C1-C6 alkoxyC1-C6 alkylamino, C1-C6 alkoxyC1-C6 alkoxy; and optionally terminally substituted with a hydroxyl, amino, —NHNH2, N3, —CΞCH, —COOH, or maleimido group;
Z represents (C2-C6 alkyleneO)q;
Y represents (C2-C6 alkyleneO)r;
q represents an integer 1 to 6;
r represents 0 or an integer 1 to 20;
R3 represents C2-C6 alkylene-OH, C2-C6 alkylene-NH2, C2-C5 alkenyl-CH2—OH or C2-C5 alkenyl-CH2—NH2;
A represents
wherein:
R4 represents H, C4-C24 alkyl, C4-C24 alkenyl, —CO—C3-C23 alkyl, or —CO—C3-C23 alkenyl;
R5 represents C4-C24 alkyl, C4-C24 alkenyl, —CO—C3-C23 alkyl, or —CO—C3-C23 alkenyl;
p represents 0 or an integer 1 to 6;
or a pharmaceutically acceptable salt thereof.

### Claim 2 (depends on 1)

The compound according to claim 1 wherein R2 represents H, C1-C6 alkyl or C1-C6 alkoxyC1-C6 alkyl.

### Claim 3 (depends on 1)

The compound according to claim 1 wherein r represents 0 or an integer 1 to 3.

### Claim 4 (depends on 1)

The compound according to claim 1 wherein R3 represents C2-C6 alkylene-OH.

### Claim 5 (depends on 11)

The compound according to claim 11 wherein p represents an integer 1 to 3.

### Claim 6 (depends on 1)

The compound according to claim 1 wherein A represents

### Claim 7 (depends on 1)

The compound according to claim 1 which is a compound of formula (IA):
wherein:
R1 represents —O—Z—O—(P(═O)—OH)—O—Y-A
R2 represents H, C1-C6 alkyl or C1-C3 alkoxyC1-C3 alkyl;
Z represents (C2-C6 alkyleneO)q;
Y represents (C2-C6 alkyleneO)r;
q represents an integer 1 to 6;
r represents 0 or an integer 1 to 20;
R3 represents C2-C6 alkylene-OH;
A represents
wherein:
R4 represents H, —CO—C3-C23 alkyl, or —CO—C3-C23 alkenyl;
R5 represents, —CO—C3-C23 alkyl, or —CO—C3-C23 alkenyl;
or a pharmaceutically acceptable salt thereof.

### Claim 8 (depends on 7)

The compound according to claim 7 wherein R2 represents H, n-butyl or CH3CH2OCH2—

### Claim 9

(canceled)

### Claim 10 (depends on 7)

The compound according to claim 7 wherein Z represents CH2CH2O.

### Claim 11 (depends on 7)

The compound according to claim 7 wherein Y represents ((CH2)2O)r.

### Claim 12 (depends on 7)

The compound according to claim 7 wherein q represents an integer 1 to 3.

### Claim 13 (depends on 7)

The compound according to claim 7 wherein r represents 0 or an integer 1 to 6.

### Claim 14

(canceled)

### Claim 15 (depends on 13)

The compound according to claim 13 wherein R3 represents —CH2CH2OH.

### Claim 16 (depends on 7)

The compound according to claim 7 wherein R4 represents H and R5 represents —CO—C3-C23 alkyl, or —CO—C3-C23 alkenyl.

### Claim 17 (depends on 7)

The compound according to claim 7 wherein R4 and R5 independently represent —CO—C3-C23 alkyl or —CO—C3-C23 alkenyl.

### Claim at position 18

18-19. (canceled)

### Claim 20 (depends on 1)

The compound according to claim 1 selected from:
and pharmaceutically acceptable salts thereof.

### Claim 21 (depends on 20)

The compound according to claim 20 selected from
and pharmaceutically acceptable salts thereof.

### Claim 22

(canceled)

### Claim 23 (depends on 1)

An immunogenic composition comprising a compound according to claim 1 and a vaccine antigen.

### Claim at position 23

24-25. (canceled)

### Claim 26 (depends on 1)

A method of inducing an immune response in a mammal which comprises administering to said mammal in need thereof an immunostimulatory amount of a compound or composition according to claim 1.

### Claim 27

(canceled)

### Claim 28 (depends on 1)

A method of inducing protective immunity against a disease in a mammal which comprises administering to a mammal in need thereof an immunostimulatory amount of a compound according to claim 1 together with a disease antigen.

### Claim 29 (depends on 1)

A method of treatment or prophylaxis of cancer in a mammal which comprises administering to a mammal in need thereof an immunostimulatory amount of a compound according to claim 1 together with a cancer antigen.

### Claim 30 (depends on 1)

A compound of formula (II):
wherein:
R1a represents —O—Z—H;
and Z, R2 and R3 are defined according to claim 1;
or a protected derivative thereof.

### Claim 31 (depends on 1)

A compound of formula (VI)
wherein:
R1a represents —O—Z—H;
and Z, R2 and R3 are defined according to claim 1;
or a protected derivative thereof.

### Claim at position 30

32-33. (canceled)

### Claim 34 (depends on 1)

A method of preparing a choline salt of a compound according to claim 1, comprising:
(a) dissolving the compound in an aqueous vehicle;
(b) adding the choline salt; and
(c) mixing the compound and choline salt;
wherein the method does not include the use of an organic solvent.

### Claim at position 32

35-36. (canceled)

### Claim 37 (depends on 1)

A method of preparing a choline salt of a compound according to claim 1, comprising:
(a) dissolving the compound in an organic solvent;
(b) adding the choline salt;
(c) mixing the compound and choline salt; and
(d) removing the organic solvent,
wherein the method does not include a vacuum drying step.

### Claim at position 34

38-39. (canceled)