# US 2019/0375781 A1 · Cyclic dinucleotides as sting agonists

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- Number: US 2019/0375781 A1
- Document ID: US20190375781A1
- Status: Published application
- Kind: A1
- Application number: 16/478,864
- Filed: 2018-01-26
- Published: 2019-12-12
- Earliest claimed: 2017-01-27
- Assignees: Janssen Biotech, Inc.
- Applicants: Janssen Biotech, Inc.
- Inventors: Stuart Emanuel; Mark Richter; Peter J. Connolly; James Patrick Edwards; Guangyi Wang; Santhosh Kumar Thatikonda; Leonid Beigelman; Minghong Zhong; Gilles Bignan
- Web page: https://patentgrep.com/patent/US20190375781A1

## CPC

- C07H 21/00: Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
- A61P 31/12: Antivirals
- A61P 35/00: Antineoplastic agents
- A61K 31/7076: containing purines, e.g. adenosine, adenylic acid
- A61K 31/708: having oxo groups directly attached to the purine ring system, e.g. guanosine, guanylic acid
- A61K 31/7084: Compounds having two nucleosides or nucleotides, e.g. nicotinamide-adenine dinucleotide, flavine-adenine dinucleotide
- C07H: SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS (derivatives of aldonic or saccharic acids C07C, C07D; aldonic acids, saccharic acids C07C59/105, C07C59/285; cyanohydrins C07C255/16; glycals C07D; compounds of unknown constitution C07G; polysaccharides, derivatives thereof C08B; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification C12N15/00; sugar industry C13)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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)

## Abstract

Disclosed are compounds, compositions and methods for treating of diseases, syndromes, or disorders that are affected by the modulation of STING. Such compounds are represented by Formula (I) as follows: wherein R1A, R1B, R1C, R1D, B1, R2A, R2B, R2C, R2D, and R2E are defined herein and Formula (II) wherein R1H, R1K, R1J, and R2L are defined herein.

## Claims

### Claim 1

A compound of Formula (I)
wherein
R1A, R2A, R1D, R2D, and R2E are each independently selected from hydrogen or methyl; such that one of said R1A, R2A, R1D, R2D, and R2E is methyl;
R1B is hydrogen, hydroxy or fluoro;
or, R1B is —O—, and R1D is CH2, wherein R1B, R1D and the atoms to which they are attached form a 5-membered ring;
R1C is selected from the group consisting of hydroxy, thiol, and BH3−;
B1 is selected from the group consisting of rings b1 and b2
R2B is selected from the group consisting of hydroxy, fluoro and methoxy;
R2C is selected from the group consisting of hydroxy, thiol, and BH3−;
or an enantiomer, diastereomer, or pharmaceutically acceptable salt form thereof.

### Claim 2 (depends on 1)

The compound of claim 1 wherein R1B is hydrogen or fluoro.

### Claim 3 (depends on 1)

The compound of claim 1 wherein R1B is —O—, and R1D is CH2, wherein R1B, R1D and the atoms to which they are attached form a 5-membered ring.

### Claim 4 (depends on 1)

The compound of claim 1 wherein R1C is selected from the group consisting of hydroxy and thiol.

### Claim 5 (depends on 1)

The compound of claim 1 wherein R1D is hydrogen.

### Claim 6 (depends on 1)

The compound of claim 1 wherein B1 is ring b2

### Claim 7 (depends on 1)

The compound of claim 1 wherein R2A is hydrogen.

### Claim 8 (depends on 1)

The compound of claim 1 wherein R2C is selected from the group consisting of hydroxy and thiol.

### Claim 9 (depends on 1)

The compound of claim 1 wherein R2D is hydrogen.

### Claim 10

A compound of Formula (I)
wherein
R1A, R2A, R1D, R2D, and R2E are each independently selected from hydrogen or methyl; such that one of said R1A, R2A, R1D, R2D, and R2E is methyl;
R1B is hydrogen, hydroxy or fluoro;
or, R1B is —O—, and R1D is CH2, wherein R1B, R1D and the atoms to which they are attached form a 5-membered ring;
R1C is selected from the group consisting of hydroxy and thiol;
B1 is ring b2
R2B is selected from the group consisting of hydroxy, fluoro and methoxy;
R2C is selected from the group consisting of hydroxy and thiol;
or an enantiomer, diastereomer, or pharmaceutically acceptable salt form thereof.

### Claim 11 (depends on 1)

A compound of Formula (I) of claim 1 selected from the group consisting of compounds 1 to 3
or a pharmaceutically acceptable salt form thereof.

### Claim 12 (depends on 1)

A pharmaceutical composition comprising a compound of claim 1 and at least one of a pharmaceutically acceptable carrier, a pharmaceutically acceptable excipient, and a pharmaceutically acceptable diluent.

### Claim 13 (depends on 12)

The pharmaceutical composition of claim 12, wherein the composition is a solid oral dosage form.

### Claim 14 (depends on 12)

The pharmaceutical composition of claim 12, wherein the composition is a syrup, an elixir or a suspension.

### Claim 15

A compound of Formula (II)
wherein
R1H is fluoro; or, R1H is —O—, and R1J is CH2, wherein R1H, R1J and the atoms to which they are attached form a 5-membered ring;
R1J is hydrogen or methyl;
R1K is selected from the group consisting of hydroxy or thiol;
R2L is selected from the group consisting of hydroxy and thiol;
or an enantiomer, diastereomer, or pharmaceutically acceptable salt form thereof.

### Claim 16 (depends on 15)

A compound of Formula (II) of claim 15 selected from the group consisting of compounds 4 to 6
or a pharmaceutically acceptable salt form thereof.

### Claim 17 (depends on 15)

A pharmaceutical composition comprising a compound of claim 15 and at least one of a pharmaceutically acceptable carrier, a pharmaceutically acceptable excipient, and a pharmaceutically acceptable diluent.

### Claim 18 (depends on 17)

The pharmaceutical composition of claim 17, wherein the composition is a solid oral dosage form.

### Claim 19 (depends on 17)

The pharmaceutical composition of claim 17, wherein the composition is a syrup, an elixir or a suspension.

### Claim 20 (depends on 1)

A method of treating a disease, syndrome, or condition modulated by STING, comprising administering to a subject in need thereof a therapeutically effective amount of the compound of claim 1.

### Claim 21 (depends on 1)

A method of treating a disease, syndrome, or condition, wherein said disease, syndrome, or condition is affected by the agonism of STING, comprising administering to a subject in need thereof a therapeutically effective amount of the compound of claim 1.

### Claim 22 (depends on 21)

The method of claim 21 wherein said disease, syndrome, or condition is cancer.

### Claim 23 (depends on 22)

The method of claim 22 wherein said cancer is selected from the group consisting of melanoma, colon cancer, breast cancer, prostate cancer, lung cancer, and fibrosarcoma.

### Claim 24 (depends on 21)

The method of claim 21, wherein said disease, syndrome, or condition is a viral infection.

### Claim 25 (depends on 24)

The method of claim 24, wherein the viral infection is hepatitis B.

### Claim 26 (depends on 12)

A method of treating a disease, syndrome, or condition selected from the group consisting of viral infection, melanoma, colon cancer, breast cancer, prostate cancer, lung cancer, and fibrosarcoma, comprising administering to a subject in need thereof a therapeutically effective amount of the composition of claim 12.

### Claim 27 (depends on 26)

The method of claim 26, wherein the viral infection is hepatitis B.

### Claim 28

(canceled)

### Claim 29

(canceled)