# US 10,766,890 B2 · Hepatitis B core protein modulators

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- Number: US 10,766,890 B2
- Document ID: US10766890B2
- Status: Granted
- Kind: B2
- Application number: 15/760,387
- Filed: 2016-09-15
- Published: 2018-09-20
- Granted: 2020-09-08
- Earliest claimed: 2015-09-15
- Assignees: Assembly Biosciences, Inc.; Indiana University Research and Technology Corporation
- Applicants: Assembly Biosciences, Inc.; Indiana University Research and Technology Corporation
- Inventors: William Turner; Hans Maag; Samson Francis
- Web page: https://patentgrep.com/patent/US10766890B2

## CPC

- C07D 417/12: linked by a chain containing hetero atoms as chain links
- A61K 31/554: having at least one nitrogen and one sulfur as ring hetero atoms, e.g. clothiapine, diltiazem
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61P 31/20: for DNA viruses
- C07D 243/38: [b, e]- or [b, f]-condensed with six-membered rings
- C07D 267/20: [b, f]-condensed
- C07D 281/16: [b, f]-condensed
- C07D 401/12: linked by a chain containing hetero atoms as chain links
- C07D 403/12: linked by a chain containing hetero atoms as chain links
- C07D 413/12: linked by a chain containing hetero atoms as chain links
- C07D 417/14: containing three or more hetero rings
- C07D 453/02: containing not further condensed quinuclidine ring systems
- C07D 471/04: Ortho-condensed systems
- 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 present disclosure provides, in part, compounds having allosteric effector properties against Hepatitis B virus Cp. Also provided herein are methods of treating viral infections, such as hepatitis B, comprising administering to a patient in need thereof a disclosed compound.

## Claims

### Claim 1

A compound represented by:
wherein
Y is S(O)y, wherein y is 2;
Rz is H;
Rm′ and Rm are each H;
R21 is selected for each occurrence from the group consisting of H, and C1-6alkyl;
q is 0, 1, or 2;
R22 is selected from the group consisting of hydroxyl, nitro, cyano, carboxy, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, NR′R″, —C(O)—C1-6alkyl, —C(O)—C1-6alkoxy, —C(O)—NR′R″, —C(═NH)—NR′R″, X2-phenyl (optionally substituted by one, two or three substituents represented by R63), phenyl (optionally substituted by one, two or three substituents represented by R63), 5-6 membered monocyclic heteroaryl (optionally substituted by one, two or three substituents represented by R63), 9-10 membered bicyclic heteroaryl (optionally substituted by one, two or three substituents represented by R73), C3-6cycloalkyl, —S(O)w-C1-6alkyl (where w is 0, 1 or 2), —S(O)w—NR′R″ (where w is 0, 1 or 2), and —NR′—S(O)w, (where w is 0, 1 or 2);
R′ is selected, independently for each occurrence, from H, methyl, ethyl, and propyl;
R″ is selected, independently for each occurrence, from H, methyl, ethyl, propyl, butyl, —C(O)-methyl and —C(O)-ethyl, or R′ and R″ taken together with the nitrogen to which they are attached may form a 4-7 membered heterocycle;
each of moieties R4, R5, R6, R7, R8, R9, and R10 is independently selected for each occurrence from the group consisting of hydrogen, C1-6alkyl, C2-6alkynyl, C2-6alkenyl, halogen, hydroxyl, nitro, cyano, and NR′R″;
R63 is selected independently at each occurrence from the group consisting of H, halogen, hydroxyl, nitro, cyano, carboxy, C1-6alkyl, —C(O)—O—C1-6alkyl, heterocycle (optionally substituted by halogen or NR′R′), —C(O)—NR′R″, —C(═NH)—NR′R″, heteroaryl, phenyl, benzyl, C2-6alkenyl, C2-6alkynyl, C1-6alkoxy, carboxy, NR′R″, —C(O)—C1-6alkyl, —C(O)—C1-6alkoxy, C3-6cycloalkyl, —S(O)w—C1-6alkyl (where w is 0, 1 or 2), —S(O)w—NR′R″ (where w is 0, 1 or 2), —NR′—S(O)w—C1-6alkyl (where w is 0, 1 or 2), X2—R69;
R69 is selected from the group consisting of H, halogen, hydroxyl, nitro, cyano, C1-6alkyl, —C(O)—O—C1-6alkyl, heterocycle (optionally substituted by halogen or NR′R′),), —C(O)—NR′R″, —C(═NH)—NR′R″, heteroaryl, phenyl, C2-6alkenyl, C2-6alkynyl, C1-6alkoxy, carboxy, NR′R″, —C(O)—C1-6alkyl, —C(O)—C1-6alkoxy, C3-6cycloalkyl, —S(O)w—C1-6alkyl (where w is 0, 1 or 2), —S(O)w—NR′R″ (where w is 0, 1 or 2), and —NR′—S(O)w— C1-6alkyl (where w is 0, 1 or 2),
X2 is selected from S(O)w (wherein w is 0, 1, or 2), O, CH2, or NR′;
wherein for each occurrence, C1-6alkyl may be optionally substituted with one, two, three or more substituents selected from the group consisting of halogen, hydroxyl, nitro, cyano, carboxy, C2-6alkenyl, C2-6alkynyl, NR′R″, —NR′—S(O)w—C1-6alkyl (where w is 0, 1 or 2), and S(O)w—NR′R″(where w is 0, 1 or 2); C1-6alkoxy may be optionally substituted with one, two, three or more substituents selected from the group consisting of halogen, hydroxyl, nitro, cyano, carboxy, C1-6alkyl, NR′R″, —NR′—S(O)w— C1-6alkyl (where w is 0,1 or 2), and S(0)w—NR′R″ (where w is 0, 1 or 2);
and pharmaceutically acceptable salts thereof.

### Claim 2 (depends on 1)

The compound of claim 1, wherein R22 is selected from the group consisting of NR′R″, —C(O)—C1-6alkyl, —C(O)—C1-6alkoxy, —C(O)—NR′R″, —C(═NH)—NR′R″, X2-phenyl (optionally substituted by one, two or three substituents represented by R63), phenyl (optionally substituted by one, two or three substituents represented by R63), C3-6cycloalkyl, —S(O)w—C1-6alkyl (where w is 0, 1 or 2), —S(O)w—NR′R″ (where w is 0, 1 or 2), and —NR′—S(O)w, (where w is 0, 1 or 2).

### Claim 3 (depends on 1)

The compound of claim 1, wherein R22 is selected from the group consisting of X2-phenyl (optionally substituted by one, two or three substituents represented by R63), phenyl (optionally substituted by one, two or three substituents represented by R63), 5-6 membered monocyclic heteroaryl (optionally substituted by one, two or three substituents represented by R63), and 9-10 membered bicyclic heteroaryl (optionally substituted by one, two or three substituents represented by R73).

### Claim 4 (depends on 1)

The compound of claim 1, wherein R22 is —X2-phenyl (optionally substituted by one, two or three substituents represented by R63).

### Claim 5 (depends on 1)

The compound of claim 1, wherein R22 is phenyl (optionally substituted by one, two or three substituents represented by R63).

### Claim 6 (depends on 1)

The compound of claim 1, wherein R22 is a 5-6 membered monocyclic heteroaryl (optionally substituted by one, two or three substituents represented by R63) or a 9-10 membered bicyclic heteroaryl (optionally substituted by one, two or three substituents represented by R73).

### Claim 7 (depends on 1)

The compound of claim 1, wherein q is 0.

### Claim 8 (depends on 1)

The compound of claim 1, represented by:
wherein R21 is selected from the group consisting of H and C1-6alkyl.

### Claim 9 (depends on 1)

The compound of claim 1, wherein the compound is represented by:
wherein R21 is selected from the group consisting of H and CH3.

### Claim 10 (depends on 1)

The compound of claim 1, wherein the compound is represented by:
wherein X2 is selected from the group consisting of O, CH2, and S, and R21 is selected from the group consisting of H and CH3.

### Claim 11 (depends on 1)

The compound of claim 1, wherein R22 is represented by a substituent selected from the group consisting of:
wherein each R22 is optionally substituted by one, two or three substituents represented by R63.

### Claim 12 (depends on 1)

The compound of claim 1, wherein
R63 is selected independently at each occurrence from the group consisting of H, halogen, hydroxyl, nitro, cyano, C1-6alkyl, C1-6haloalkyl, —C1-6alkyl-OH, —C(O)—O—C1-6alkyl, —C(O)—NR′R″, —C(═NH)—NR′R″, C2-6alkenyl, C2-6alkynyl, C1-6alkoxy, carboxy, NR′R″, —C(O)—C1-6alkyl, —C(O)—C1-6alkoxy, C3-6cycloalkyl, —S(O)w—C1-6alkyl (where w is 0,1 or 2), —S(O)w—NR′R″ (where w is 0, 1 or 2), —NR′—S(O)w— C1-6alkyl (where w is 0, 1 or 2) and —NR′—S(O)w, (where w is 0, 1 or 2) and X2—C1-6alkylene-R69.

### Claim 13 (depends on 1)

The compound of claim 1, wherein
R63 is selected independently at each occurrence from the group consisting of H, halogen, hydroxyl, cyano, C1-6alkyl, C1-6haloalkyl, C1-6alkyl-OH, C1-6alkyl-NR′R″, —O—C1-6alkyl-NR′R″, —C1-6alkyl-OH, —C(O)—NR′R″, C1-6alkoxy, carboxy, NR′R″, and benzyl.

### Claim 14 (depends on 1)

A pharmaceutically acceptable composition comprising a compound of claim 1, and a pharmaceutically acceptable excipient.

### Claim 15 (depends on 1)

A method of treating a hepatitis B infection in a patient in need thereof, comprising administering an effective amount of a compound of claim 1.