# US 2023/0054782 A1 · Bicyclic heterocycle compounds methods of use thereof for the treatment of herpes viruses

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- Number: US 2023/0054782 A1
- Document ID: US20230054782A1
- Status: Published application
- Kind: A1
- Application number: 17/783,810
- Filed: 2020-12-17
- Published: 2023-02-23
- Earliest claimed: 2019-12-18
- Assignees: Merck Sharp & Dohme Corp.
- Applicants: Merck Sharp & Dohme LLC
- Inventors: Andrew John Cooke; Brendan M. Crowley; Marc A. Labroli; Michael Aaron Plotkin; Izzat T. Raheem; Ling Tong; Deyou Sha
- Web page: https://patentgrep.com/patent/US20230054782A1

## CPC

- C07D 491/04: Ortho-condensed systems
- C07D 498/04: Ortho-condensed systems
- A61P 31/22: for herpes viruses
- C07D 217/24: Oxygen atoms
- C07D 401/12: linked by a chain containing hetero atoms as chain links
- C07D 403/04: directly linked by a ring-member-to-ring-member bond
- C07D 403/14: containing three or more hetero rings
- C07D 405/14: containing three or more hetero rings
- C07D 471/04: Ortho-condensed systems
- C07D 519/00: Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

The present invention relates to novel Bicyclic Heterocycle Compounds of Formula (I) and pharmaceutically acceptable salts thereof, wherein A, X, Y, Z, R1 R5, R6, and R7 are as defined herein. The present invention also relates to compositions comprising at least one Bicyclic Heterocycle Compound, and methods of using the Bicyclic Heterocycle Compounds for treating or preventing a herpesvirus infection in a patient.

## Claims

### Claim 1

A compound of structural formula (I):
or a pharmaceutically acceptable salt thereof,
wherein:
A is a bond or —O—;
X is —N— or —C(R2)—;
Y is —N— or —C(R3)—, such that only one of X and Y can be —N—;
Z is —N— or —C(R4)—;
R1 is 5 to 7-membered monocyclic heterocycloalkyl or 9 or 10-membered bicyclic heterocycloalkyl, wherein said 5 to 7-membered monocyclic heterocycloalkyl group, and said 9 or 10-membered bicyclic heterocycloalkyl group can be optionally substituted with up to three RA groups, which can be the same or different, and wherein said 5 to 7-membered monocyclic heterocycloalkyl group, and said 9 or 10-membered bicyclic heterocycloalkyl group can optionally have a ring carbon atom functionalized as a carbonyl group;
R2 is selected from H, C1-C6 alkyl, —O—(C1-C6 alkyl), C1-C6 hydroxyalkyl, C1-C6 aminoalkyl, —CN, —NH2, —C(O)O—(C1-C6 alkyl), C3-C7 cycloalkyl, C4-C7 heterocycloalkyl, C6-C10 aryl, 5 to 7-membered monocyclic heteroaryl, and 9 or 10-membered bicyclic heteroaryl, wherein said C3-C7 cycloalkyl group, said C6-C10 aryl group, said 5 to 7-membered monocyclic heteroaryl group, and said 9 or 10-membered bicyclic heteroaryl group can be optionally substituted with up to three RB groups, which can be the same or different, or where R2 and R3, together with atoms to which they are attached, are joined to form a 5-membered heteroaryl group;
R3 is selected from H, C1-C6 alkyl, C1-C6 hydroxyalkyl, 5 to 7-membered monocyclic heteroaryl, —O-(5 to 7-membered monocyclic heteroaryl), C3-C7 cycloalkyl, wherein said C3-C7 cycloalkyl group, and any of said 5 to 7-membered monocyclic heteroaryl groups, can be optionally substituted with up to three RC groups, which can be the same or different;
R4 is selected from H, C1-C6 alkyl, C1-C6 hydroxyalkyl, and C3-C7 cycloalkyl;
R5 is selected from H, C1-C6 alkyl, —OR7, —CN, —NH2, C1-C6 hydroxyalkyl, C1-C6 haloalkyl, —O—(C1-C6 hydroxyalkyl), —(C1-C6 alkylene)-NH—(C1-C6 haloalkyl), —O—(C1-C6 alkylene)m-(C3-C7 cycloalkyl), —O—(C1-C6 alkylene)m-(5 to 7-membered monocyclic heterocycloalkyl), and —(C1-C6 alkylene)m-(5 to 7-membered monocyclic heterocycloalkyl), wherein said C1-C6 alkyl group, said C3-C7 cycloalkyl group, and said 5 to 7-membered monocyclic heterocycloalkyl group can each be optionally substituted with one or more substituents, each independently selected from —OH, C1-C6 alkyl, and C3-C7 cycloalkyl, and wherein said C1-C6 haloalkyl can be optionally substituted with one —NH2 group;
R6 represents up to 3 phenyl ring substituents, which can be the same or different, and are each independently selected from C1-C6 haloalkyl, C1-C6 hydroxyalkyl, —CN, —NO2, —OR7, and halo;
each occurrence of R7 is independently selected from H, C1-C6 alkyl, and C3-C7 cycloalkyl;
each occurrence of RA is independently selected from C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxyalkyl, 5 to 7-membered monocyclic heterocycloalkyl, —C(O)—(C1-C6 alkyl), and halo, wherein said 5 to 7-membered monocyclic heterocycloalkyl group can be optionally substituted with up to 3 substituents, which can be the same or different, and are each independently selected from C1-C6 alkyl, 5 to 7-membered monocyclic heterocycloalkyl, and halo;
each occurrence of RB is independently selected from C1-C6 alkyl, C3-C7 cycloalkyl, —O—(C3-C7 cycloalkyl), —OR7, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, —O—(C1-C6 alkylene)m-(5 to 7-membered monocyclic heterocycloalkyl), and —(C1-C6 alkylene)m-(5 to 7-membered monocyclic heterocycloalkyl), and —NH2;
each occurrence of RC is independently selected from C1-C6 alkyl, —OR7, C1-C6 haloalkyl, and 5 to 7-membered monocyclic heterocycloalkyl; and
each occurrence of m is independently 0 or 1.

### Claim 2 (depends on 1)

The compound of claim 1, wherein -A-R1 is:

### Claim 3 (depends on 1)

The compound of claim 1, wherein X is N.

### Claim 4 (depends on 1)

The compound of claim 1, wherein Y is N.

### Claim 5 (depends on 1)

The compound of claim 1, wherein Z is N.

### Claim 6 (depends on 1)

The compound of claim 1, wherein none of X, Y and Z is N.

### Claim 7 (depends on 1)

The compound of claim 1, wherein R2 is selected from H, —CN, cyclobutyl, pyrazolyl, pyridyl, trizolyl, oxazolyl, —CH2C(CH3)2NH2, —CH2C(CH3)2OH, —CH2CH(CH3)OH,
wherein said pyrazolyl group, said triazolyl group, said pyridyl group, and said cyclobutyl group can be optionally substituted with up to 2 groups, which are independently selected from —CHF2, —CF3, piperdinyl, —OCH3, —OH, and methyl.

### Claim 8 (depends on 1)

The compound of any of claim 1, wherein Y is —C(R3)— and R3 is selected from H, —O-pyrazolyl, oxazolyl, —CH2OH, —CH2C(CH3)2OH, and —CH2CH(CH3)OH.

### Claim 9 (depends on 1)

The compound of claim 1, wherein Z is —C(R4)— and R4 is selected from H, —CH2OH, and cyclopropyl.

### Claim 10 (depends on 1)

The compound of claim 1, wherein R5 is selected from H, —OH, —OCH3, methyl, ethyl, and cyclopropyl.

### Claim 11 (depends on 1)

The compound of claim 1, wherein X and Y are each —CH—.

### Claim 12 (depends on 1)

The compound of claim 1, wherein R6 is 4-Cl or 4-CN.

### Claim 13 (depends on 1)

The compound of claim 1, wherein R7 is H or methyl.

### Claim 14

A compound being any of the compounds numbered 1-157 in the above specification, or a pharmaceutically acceptable salt thereof.

### Claim 15 (depends on 1)

A pharmaceutical composition comprising an effective amount of the compound of claim 1, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

### Claim 16 (depends on 15)

The pharmaceutical composition according to claim 15, further comprising one or more additional therapeutic agents, wherein said additional therapeutic agents are selected from anti-herpes agents, and immunomodulators.

### Claim 17 (depends on 1)

A method of treating a patient infected with a herpesvirus, comprising the step of administering an amount of the compound according to claim 1, or a pharmaceutically acceptable salt thereof, effective to treat infection by said herpesvirus in said patient.

### Claim 18 (depends on 17)

The method according to claim 17, further comprising administering one or more additional therapeutic agents, wherein said additional therapeutic agents are selected from anti-herpes agents, and immunomodulators.