# US 11,993,600 B2 · Saturated spirocyclics as antiviral agents

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 11,993,600 B2
- Document ID: US11993600B2
- Status: Granted
- Kind: B2
- Application number: 18/075,567
- Filed: 2022-12-06
- Published: 2023-06-08
- Granted: 2024-05-28
- Earliest claimed: 2021-12-08
- Assignees: Enanta Pharmaceuticals, Inc.
- Applicants: Enanta Pharmaceuticals, Inc.
- Inventors: Joseph D. Panarese; Samuel Bartlett; Yat Sun Or
- Web page: https://patentgrep.com/patent/US11993600B2

## CPC

- C07D 471/10: Spiro-condensed systems
- A61P 31/14: for RNA viruses
- C07D 471/04: Ortho-condensed systems
- C07D 487/04: Ortho-condensed systems
- C07D 487/10: Spiro-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 discloses compounds of Formula (I), and pharmaceutically acceptable salts, thereof: which inhibit coronavirus replication activity. The invention further relates to pharmaceutical compositions comprising a compound of Formula (I) or a pharmaceutically acceptable salt thereof, and methods of treating or preventing a coronavirus infection in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a compound of Formula (I) or a pharmaceutically acceptable salt thereof.

## Claims

### Claim 1

A compound represented by Formula (I):
or a pharmaceutically acceptable salt thereof, wherein:
A is selected from:
1) —R11;
2) —OR12;
3) —NR17R18; and
4) —C(R13R14)N(R17R18);
n is 1, 2, or 3;
Q1 is selected from:
1) —CN;
2) —C(O)R15;
3) —CH(OH)SO3R16;
4) —C(O)NR13R14;
5) —C(O)C(O)NR13R14; and
6) Optionally substituted —C2-C8 alkynyl;
R1, R2, R3, Q2, and Q3 are each independently selected from:
1) Hydrogen;
2) Optionally substituted —C1-C8 alkyl;
3) Optionally substituted —C2-C8 alkenyl;
4) Optionally substituted —C2-C8 alkynyl;
5) Optionally substituted —C3-C8 cycloalkyl;
6) Optionally substituted 3- to 8-membered heterocycloalkyl;
7) Optionally substituted aryl;
8) Optionally substituted arylalkyl;
9) Optionally substituted heteroaryl; and
10) Optionally substituted heteroarylalkyl;
alternatively, R1 and R2 are taken together with the carbon atom to which they are attached to form an optionally substituted 3- to 8-membered carbocyclic ring or an optionally substituted 3- to 8-membered heterocyclic ring;
alternatively, Q2 and Q3 are taken together with the carbon atom to which they are attached to form an optionally substituted 3- to 8-membered carbocyclic ring or an optionally substituted 3- to 8-membered heterocyclic ring;
R4 is hydrogen, optionally substituted —C1-C4 alkyl, optionally substituted C2-C4-alkenyl, or optionally substituted —C3-C6 cycloalkyl;
R11 and R12 are each independently selected from:
1) Optionally substituted —C1-C8 alkyl;
2) Optionally substituted —C2-C8 alkenyl;
3) Optionally substituted —C2-C8 alkynyl;
4) Optionally substituted —C3-C8 cycloalkyl;
5) Optionally substituted 3- to 8-membered heterocycloalkyl;
6) Optionally substituted aryl;
7) Optionally substituted arylalkyl;
8) Optionally substituted heteroaryl; and
9) Optionally substituted heteroarylalkyl;
R13, R14, and R17 each independently selected from:
1) Hydrogen;
2) Optionally substituted —C1-C8 alkyl;
3) Optionally substituted —C2-C8 alkenyl;
4) Optionally substituted —C2-C8 alkynyl;
5) Optionally substituted —C3-C8 cycloalkyl;
6) Optionally substituted 3- to 8-membered heterocycloalkyl;
7) Optionally substituted aryl;
8) Optionally substituted arylalkyl;
9) Optionally substituted heteroaryl; and
10) Optionally substituted heteroarylalkyl;
alternatively, R13 and R14 are taken together with the carbon atom to which they are attached to form an optionally substituted 3- to 8-memberedheterocyclic ring;
R15 is hydrogen, hydroxy, or optionally substituted —C1-C8 alkyl;
R16 is hydrogen or Na30; and
R18 is selected from:
—C(O)R11;
—C(O)OR11;
—C(O)NR13R14;
—S(O)2R11;
Hydrogen;
Optionally substituted —C1-C8 alkyl;
Optionally substituted —C2-C8 alkenyl;
Optionally substituted —C2-C8 alkynyl;
Optionally substituted —C3-C8 cycloalkyl;
Optionally substituted 3- to 8-membered heterocycloalkyl;
Optionally substituted aryl;
Optionally substituted arylalkyl;
Optionally substituted heteroaryl; and
Optionally substituted heteroarylalkyl.

### Claim 2 (depends on 1)

The compound of claim 1, wherein Q1 is —CN, and R4 is hydrogen.

### Claim 3 (depends on 1)

The compound of claim 1, wherein A is derived from one of the following by removal of a hydrogen atom and is optionally substituted:

### Claim 4 (depends on 1)

The compound of claim 1 represented by Formulae (IV-1) or Formula (IV-2), or a pharmaceutically acceptable salt thereof:
wherein A, Q1, Q2, Q3, R1, and R3 are as defined in claim 1.

### Claim 5 (depends on 1)

The compound of claim 1, represented by one of Formulae (VII-1) to (VII-9), or a pharmaceutically acceptable salt thereof:
wherein each R21 and R22 are independently selected from:
1) Halogen;
2) —CN;
3) —OR13;
4) —SR13;
5) —NR13R14;
6) —OC(O)NR13R14;
7) Optionally substituted —C1-C6alkyl;
8) Optionally substituted —C3-C8cycloalkyl;
9) Optionally substituted 3- to 8-membered heterocycloalkyl;
10) Optionally substituted aryl; and
11) Optionally substituted heteroaryl;
m is 0, 1, 2, 3, or 4; v is 0, 1, or 2, and R1, R13, and R14 are as defined in claim 1.

### Claim 6 (depends on 1)

The compound of claim 1, represented by one of Formulae (VIII-1) to (VIII-9), or a pharmaceutically acceptable salt thereof:
wherein each R21 and R22 is independently selected from:
1) Halogen;
2) —CN;
3) —OR13;
4) —SR13;
5) —NR13R14;
6) —OC(O)NR13R14;
7) Optionally substituted —C1-C6 alkyl;
8) Optionally substituted —C3-C8 cycloalkyl;
9) Optionally substituted 3- to 8-membered heterocycloalkyl;
10) Optionally substituted aryl; and
11) Optionally substituted heteroaryl;
m is 0, 1, 2, 3, or 4; v is 0, 1, or 2, and R1, R13, and R14 are as defined in claim 1.

### Claim 7 (depends on 1)

The compound of claim 1, represented by Formula (X), or a pharmaceutically acceptable salt thereof:
wherein E is —C(R13R14)—, —N(R13)—, or —O—, t is 0, 1, 2, 3, or 4, and n, A, Q1, R13, R14, R1, and R3 as defined in claim 1.

### Claim 8 (depends on 1)

The compound of claim 1, selected from the compounds set forth below or a pharmaceutically acceptable salt thereof:
Compound
Structure
1
2
3
4

### Claim 9 (depends on 1)

A pharmaceutical composition comprising a compound according to claim 1 and a pharmaceutically acceptable carrier or excipient.

### Claim 10 (depends on 1)

A method of treating or preventing a virus infection in a subject susceptible to or suffering from the virus infection, the method comprising administering to the subject an effective amount of a compound according to claim 1.

### Claim 11 (depends on 1)

A method of treating or preventing a coronavirus infection in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a compound or a combination of compounds according to claim 1.

### Claim 12 (depends on 11)

The method according to claim 11, wherein the coronavirus is a 229E, NL63, OC43, HKU1, SARS-CoV-1, SARS-CoV-2 or a MERS coronavirus.

### Claim 13 (depends on 1)

A method of inhibiting viral 3C protease or viral 3CL protease in a subject, comprising administering to said subject an effective amount of a compound according to claim 1, or a pharmaceutically acceptable salt thereof.

### Claim 14 (depends on 13)

The method according to claim 13, wherein the subject is a human.

### Claim 15 (depends on 1)

A method of treating a respiratory disorder in a subject in need thereof, comprising administering to the subject an effective amount of a compound of claim 1.

### Claim 16 (depends on 15)

The method according to claim 15, wherein the compound or pharmaceutical composition is administered orally, subcutaneously, intravenously or by inhalation.