# US 11,999,717 B2 · Triazole carbamate pyridyl sulfonamides as LPA receptor antagonists and uses thereof

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- Number: US 11,999,717 B2
- Document ID: US11999717B2
- Status: Granted
- Kind: B2
- Application number: 18/061,822
- Filed: 2022-12-05
- Published: 2023-07-06
- Granted: 2024-06-04
- Earliest claimed: 2019-11-15
- Assignees: Gilead Sciences, Inc.
- Applicants: Gilead Sciences, Inc.
- Inventors: Brian P. Bestvater; Zhimin Du; Julie Farand; Gregory Notte; Barton W. Phillips; Doris T. Tang; Chandrasekar Venkataramani; Peiyuan Wang; Kin S. Yang; Anna Zagorska
- Web page: https://patentgrep.com/patent/US11999717B2

## CPC

- C07D 401/14: containing three or more hetero rings
- A61P 25/00: Drugs for disorders of the nervous system
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P 35/00: Antineoplastic agents
- A61P 37/00: Drugs for immunological or allergic disorders
- C07D 401/04: directly linked by a ring-member-to-ring-member bond
- C07D 405/14: containing three or more hetero rings
- C07D 409/14: containing three or more hetero rings
- C07D 413/14: containing three or more hetero rings
- C07D 417/14: containing three or more hetero rings
- C07B 2200/05: Isotopically modified compounds, e.g. labelled
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C07B: GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR (preparation of carboxylic acid esters by telomerisation C07C67/47; telomerisation C08F)

## Abstract

The present disclosure relates generally to compounds that bind to Lysophosphatidic Acid Receptor 1 (LPAR1) and act as antagonists of LPAR1. The disclosure further relates to the use of the compounds for the preparation of a medicament for the treatment of diseases and/or conditions through binding of LPAR1, including fibrosis and liver diseases such as non-alcoholic steatohepatitis (NASH).

## Claims

### Claim 1

A compound of Formula (II),
or a pharmaceutically acceptable salt thereof,
wherein:
R1 is C1-6 alkyl optionally substituted with 1 to 3 substituents independently selected from halogen, cyano, and C1-3 alkoxy;
R3 is hydrogen, halogen, C1-6 alkyl, C3-6 cycloalkyl, —O—R3A, or —N(R3A)2, wherein the C1-6 alkyl is optionally substituted with 1 to 3 substituents independently selected from C1-3 alkoxy and halogen, and wherein each R3A is independently C1-3 alkyl optionally substituted with 1 to 3 halogens;
each R4 is independently deuterium, halogen, C1-6 alkyl, C3-10 cycloalkyl, or C1-3 alkoxy, wherein the C1.6 alkyl or C3-10 cycloalkyl, is optionally substituted with 1 to 3 halogens;
n is 0, 1 or 2;
R5 is C1-6 alkyl optionally substituted with 1 to 3 substituents independently selected from halogen, cyano, C1-3 alkoxy, —C(O)N(R1A), and —N(R1A)2, wherein each R1A is independently —H, C1-6 alkyl, or C3-10 cycloalkyl; or
R5 is C3-6 cycloalkyl or 3 to 6 membered heterocyclyl having 1 or 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, wherein the cycloalkyl or heterocyclyl are optionally substituted with 1 to 3 substituents independently selected from halogen, cyano, C1-3 alkyl and C1-3 alkoxy;
Y is hydrogen or C1-6 alkyl optionally substituted with 1 to 3 substituents independently selected from halogen, cyano, C1-3 alkynyl, C1-3 alkoxy, and —C(O)NH—Ry, wherein Ry is C1-3 alkyl; and
Z is 5 to 12 membered heteroaryl having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, wherein the heteroaryl is optionally substituted with 1 to 3 substituents independently selected from halogen, cyano, C1-3 alkyl, C1-3 alkenyl, C1-3 alkoxy, and C3-6 cycloalkyl, wherein the C1-3 alkyl is optionally substituted with 1 to 3 substituents selected from C1-3 alkoxy and halogen.

### Claim 2 (depends on 1)

The compound or pharmaceutically acceptable salt thereof of claim 1, wherein the compound is of Formula (IIa):

### Claim 3 (depends on 1)

The compound or pharmaceutically acceptable salt thereof of claim 1, wherein R1 is C1-3 alkyl optionally substituted with 1 to 3 substituents independently selected from —F and cyano.

### Claim 4 (depends on 1)

The compound or pharmaceutically acceptable salt thereof of claim 1, wherein R1 is methyl.

### Claim 5 (depends on 1)

The compound or pharmaceutically acceptable salt thereof of claim 1, wherein R3 is hydrogen.

### Claim 6 (depends on 1)

The compound or pharmaceutically acceptable salt thereof of claim 1, wherein R3 is halogen, C1-6 alkyl, C3-6 cycloalkyl, —O—R3A, or —N(R3A)2, wherein the C1-6 alkyl is optionally substituted with 1 to 3 substituents independently selected from halogen and C1-3 alkoxy, and wherein each R3A is independently —H or C1-3 alkyl optionally substituted with 1 to 3 halogens.

### Claim 7 (depends on 1)

The compound or pharmaceutically acceptable salt thereof of claim 1, wherein R3 is —F, —Cl, —CH3, —C2H5, —CH2—OCH3, —O—CH3, —NH—CH3, or

### Claim 8 (depends on 1)

The compound or pharmaceutically acceptable salt thereof of claim 1, wherein n is 0 or 1.

### Claim 9 (depends on 1)

The compound or pharmaceutically acceptable salt thereof of claim 1, wherein n is 0.

### Claim 10 (depends on 1)

The compound or pharmaceutically acceptable salt thereof of claim 1, wherein R4 is halogen or C1-3 alkyl optionally substituted with 1 to 3 halogens.

### Claim 11 (depends on 1)

The compound or pharmaceutically acceptable salt thereof of claim 1, wherein R5 is C1-3 alkyl optionally substituted with 1 to 3 substituents independently selected from cyano and —F.

### Claim 12 (depends on 1)

The compound or pharmaceutically acceptable salt thereof of claim 1, wherein R5 is —CH3.

### Claim 13 (depends on 1)

The compound or pharmaceutically acceptable salt thereof of claim 1, wherein Y is methyl optionally substituted with 1 to 3 substituents independently selected from —F, —Cl, cyano, and methoxy.

### Claim 14 (depends on 1)

The compound or pharmaceutically acceptable salt thereof of claim 1, wherein Y is —CH3, or —CHF2.

### Claim 15 (depends on 1)

The compound or pharmaceutically acceptable salt thereof of claim 1, wherein Z is 5 or 6 membered heteroaryl having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, wherein the heteroaryl is optionally substituted with 1 to 3 substituents independently selected from halogen and C1-3 alkyl.

### Claim 16 (depends on 1)

The compound or pharmaceutically acceptable salt thereof of claim 1, wherein Z is thiophenyl, thiazolyl, isothiazolyl, pyrazolyl or oxazolyl, each optionally substituted with 1 or 2 substituents independently selected from —CH3, —F and —Cl.

### Claim 17 (depends on 1)

The compound or pharmaceutically acceptable salt thereof of claim 1, wherein Z is

### Claim 18 (depends on 1)

The compound or pharmaceutically acceptable salt thereof of claim 1, wherein Z is

### Claim 19 (depends on 1)

The compound or pharmaceutically acceptable salt thereof of claim 1, wherein Z is pyridyl, pyrimidyl, pyridazinyl, optionally substituted with 1 to 3 substituents independently selected from cyano, halogen, C1-3 alkyl, C1-3 alkenyl, or C1-3 alkoxy, wherein the C1-3 alkyl, C1-3 alkenyl, or C1-3 alkoxy is optionally substituted with 1 to 3 halogens.

### Claim 20 (depends on 1)

The compound or pharmaceutically acceptable salt thereof of claim 1,
wherein Z is

### Claim 21 (depends on 1)

The compound or pharmaceutically acceptable salt thereof of claim 1, wherein the compound is selected from the group consisting of:

### Claim 22 (depends on 1)

The compound or pharmaceutically acceptable salt thereof of claim 1, wherein the compound is selected from the group consisting of:

### Claim 23 (depends on 1)

A pharmaceutical composition comprising a therapeutically effective amount of a compound, or pharmaceutically acceptable salt thereof, of claim 1, and a pharmaceutically acceptable excipient.