# US 12,180,165 B2 · Human TLR8-selective agonists

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- Number: US 12,180,165 B2
- Document ID: US12180165B2
- Status: Granted
- Kind: B2
- Application number: 17/472,371
- Filed: 2021-09-10
- Published: 2022-01-06
- Granted: 2024-12-31
- Earliest claimed: 2015-08-21
- Assignees: University of Kansas
- Applicants: University of Kansas
- Inventors: Sunil A. David; Mallesh Beesu; Giuseppe Caruso; Alex Salyer
- Web page: https://patentgrep.com/patent/US12180165B2

## CPC

- C07D 215/38: Nitrogen atoms (nitro radicals C07D215/18)
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61P 37/02: Immunomodulators
- A61K 39/39: characterised by the immunostimulating additives, e.g. chemical adjuvants
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- 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

## Abstract

The disclosure provides human toll-like receptor modulators of general Formula (II), wherein R1, R2, R3, R4, R5, R6, R7, R8 are defined herein.

## Claims

### Claim 1

A compound represented by Formula (II):
or a salt thereof, wherein:
R3 is selected from the group consisting of
R1 is selected from the group consisting of
R2, R4, and R5 are independently selected from the group consisting of H, halogen, —OR10, —N(R10)2, —SR10, —CN, —NO2, —OC(O)R10, —C(O)R10, —C(O)OR10, —C(O)N(R10)2, —S(O)2R10, —S(O)2OR10, optionally substituted C1-20 alkyl, optionally substituted C2-20 alkenyl, optionally substituted C2-20 alkynyl, optionally substituted C3-20 carbocycle, and optionally substituted 3-to 20-membered heterocycle;
R6 is selected from the group consisting of —OR11, —N(R11)2, —SR11, optionally substituted C1-20 alkyl, optionally substituted C2-20 alkenyl, and optionally substituted C2-20 alkynyl;
R7 and R8 are each independently H;
R10 is independently selected at each occurrence from the group consisting of H, optionally substituted C1-10 alkyl, optionally substituted C2-10 alkenyl, optionally substituted C2-10 alkynyl, optionally substituted C3-12 carbocycle and optionally substituted 3-to 12-membered heterocycle; and
R11 is independently selected at each occurrence from the group consisting of optionally substituted C1-10 alkyl, optionally substituted C2-10 alkenyl, and optionally substituted C2-10 alkynyl.

### Claim 2 (depends on 1)

The compound or salt of claim 1, wherein R2, R4, and R5 are independently selected from the group consisting of H, halogen, —OR10, —N(R10)2, —SR10, —CN, —NO2, —OC(O)R10, —C(O)R10, —C(O)OR10, —C(O)N(R10)2, —S(O)2R10, —S(O)2OR10, and substituted C1-20 alkyl.

### Claim 3 (depends on 1)

The compound or salt of claim 1, wherein R10 is independently selected at each occurrence from the group consisting of:
optionally substituted C1-10 alkyl, optionally substituted C2-10 alkenyl, optionally substituted C2-10 alkynyl, optionally substituted C3-12 carbocycle and optionally substituted 3-to 12-membered heterocycle, wherein the C1-10 alkyl, C2-10 alkenyl, and C2-10 alkynyl optional substituents are one or more substituents independently selected from the group consisting of: halogen, —CN, —NO2, —OR50, —SR50, —N(R50)2, —NR50C(N(R50))N(R50)2, —OC(O)R50, —C(O)R50, —C(O)OR50, —C(O)N(R50)2, —S(O)2R50, and —S(O)2OR50, and wherein the C3-12 carbocycle and 3-to 12-membered heterocycle optional substituents are one or more substituents selected from the group consisting of halogen, —CN, —NO2, —OR50, —SR50, —N(R50)2, C1-10 alkyl, C1-10 haloalkyl, —C1-10 alkyl-N(R50)2, —C1-10 alkyl-OR50, and -C1-10 alkyl-C(O)N(R50)2; and
wherein R50 at each occurrence is independently selected from the group consisting of hydrogen, C1-10 alkyl, and C1-10 haloalkyl.

### Claim 4 (depends on 1)

The compound or salt of claim 1, wherein R6 is selected from the group consisting of optionally substituted C1-20 alkyl, optionally substituted C2-20 alkenyl, and optionally substituted C2-20 alkynyl.

### Claim 5

A compound that is represented by
or a salt thereof.

### Claim 6 (depends on 1)

A pharmaceutical composition comprising a compound or salt of claim 1, and a pharmaceutically acceptable excipient, optionally wherein the composition further comprises a vaccine.

### Claim 7 (depends on 1)

A method for modulating activity of a human toll-like receptor, comprising administering to a subject in need thereof a compound of claim 1 or a salt thereof.

### Claim 8 (depends on 7)

The method of claim 7, wherein modulating the activity of the human toll-like receptor comprises agonizing the human toll-like receptor.

### Claim 9 (depends on 7)

The method of claim 7, wherein the human toll-like receptor comprises hTLR8.

### Claim 10 (depends on 7)

The method of claim 7, wherein the method further comprises administering a vaccine to the subject before, in conjunction with, or after administration of the compound or salt thereof.

### Claim 11 (depends on 1)

A method of increasing an immune response to an antigen or vaccine, wherein the method comprises administering to a subject in need thereof a compound of claim 1 or a salt thereof.

### Claim 12 (depends on 11)

The method of claim 11, wherein the method further comprises administering a vaccine to the subject before, in conjunction with, or after administration of the compound or salt thereof.