# US 12,595,245 B2 · Inhibitors of MET kinase

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- Number: US 12,595,245 B2
- Document ID: US12595245B2
- Status: Granted
- Kind: B2
- Application number: 18/341,503
- Filed: 2023-06-26
- Published: 2024-02-29
- Granted: 2026-04-07
- Earliest claimed: 2021-12-16
- Assignees: Celyn Therapeutics, Inc.
- Applicants: Celyn Therapeutics, Inc.
- Inventors: Xiaohu S. Ouyang; Toufike Kanouni; John S. Tyhonas; Jason M. Cox; Robert S. Kania
- Web page: https://patentgrep.com/patent/US12595245B2

## CPC

- C07D 401/12: linked by a chain containing hetero atoms as chain links
- A61P 35/00: Antineoplastic agents
- C07D 215/22: attached in position 2 or 4
- C07D 405/14: containing three or more hetero rings
- C07D 471/04: Ortho-condensed systems
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

Provided herein are inhibitors of MET receptor tyrosine kinase, pharmaceutical compositions comprising said inhibitory compounds, and methods for using said MET kinase inhibitory compounds for the treatment of disease.

## Claims

### Claim 1

A compound, or pharmaceutically acceptable salt or solvate thereof, selected from the group consisting of:
N-[3,5-difluoro-4-({6-methoxy-7-[2-(methylamino)ethoxy]quinolin-4-yl}oxy)phenyl]-4-methoxypyridine-3-carboxamide;
6-chloro-N-[3,5-difluoro-4-({6-methoxy-7-[2-(methylamino)ethoxy]quinolin-4-yl}oxy)phenyl]-4-methoxypyridine-3-carboxamide;
N-(3,5-difluoro-4-((6-methoxy-7-(2-(methylamino)ethoxy)quinolin-4-yl)oxy)phenyl)-2-fluoro-4-methoxypyridine-3-carboxamide formate;
N-[3,5-difluoro-4-({6-methoxy-7-[2-(methylamino)ethoxy]quinolin-4-yl}oxy)phenyl]-4-ethoxypyridine-3-carboxamide;
N-(3-chloro-5-fluoro-4-((6-methoxy-7-(2-(methylamino)ethoxy)quinolin-4-yl)oxy)phenyl)-4-methoxypyridine-3-carboxamide;
N-(3,5-difluoro-4-((6-methoxy-7-(2-(methylamino)ethoxy)quinazolin-4-yl)oxy)phenyl)-2-fluoro-4-methoxypyridine-3-carboxamide;
N-(3,5-difluoro-4-((6-methoxy-7-(2-(methylamino)ethoxy)quinazolin-4-yl)oxy)phenyl)-4-methoxypyridine-3-carboxamide;
N-[2,3-difluoro-4-({6-methoxy-7-[2-(methylamino)ethoxy]quinolin-4-yl}oxy)phenyl]-4-methoxypyridine-3-carboxamide;
N-[2,3-difluoro-4-({6-methoxy-7-[2-(methylamino)ethoxy]quinolin-4-yl}oxy)phenyl]-2-fluoro-4-methoxypyridine-3-carboxamide;
N-[2,3-difluoro-4-({6-methoxy-7-[2-(methylamino)ethoxy]quinolin-4-yl}oxy)phenyl]-4-ethoxypyridine-3-carboxamide;
N-(2,3-difluoro-4-((6-methoxy-7-(3-(methylamino)propoxy)quinolin-4-yl)oxy)phenyl)-4-ethoxypyridine-3-carboxamide;
N-(2,3-difluoro-4-((6-methoxy-7-(3-(methylamino)propoxy)quinolin-4-yl)oxy)phenyl)-4-methoxypyridine-3-carboxamide;
N-(3,5-difluoro-4-((6-methoxy-7-(3-(methylamino)propoxy)quinolin-4-yl)oxy)phenyl)-4-methoxypyridine-3-carboxamide;
N-(3,5-difluoro-4-((6-methoxy-7-(3-(methylamino)propoxy)quinolin-4-yl)oxy)phenyl)-2-fluoro-4-methoxypyridine-3-carboxamide;
N-(3,5-difluoro-4-((6-methoxy-7-(3-(methylamino)propoxy)quinolin-4-yl)oxy)phenyl)-4-ethoxypyridine-3-carboxamide;
N-(2,5-difluoro-4-((6-methoxy-7-(3-(methylamino)propoxy)quinolin-4-yl)oxy)phenyl)-4-methoxypyridine-3-carboxamide;
N-(4-((7-(3-(dimethylamino)propoxy)-6-methoxyquinolin-4-yl)oxy)-2,5-difluorophenyl)-4-ethoxypyridine-3-carboxamide;
N-[2,5-difluoro-4-({6-methoxy-7-[2-(methylamino)ethoxy]quinolin-4-yl}oxy)phenyl]-4-methoxypyridine-3-carboxamide;
N-(2,5-difluoro-4-((6-methoxy-7-(2-(methylamino)ethoxy)quinolin-4-yl)oxy)phenyl)-2-fluoro-4-methoxypyridine-3-carboxamide;
6-chloro-N-[2,5-difluoro-4-({6-methoxy-7-[2-(methylamino)ethoxy]quinolin-4-yl}oxy)phenyl]-4-methoxypyridine-3-carboxamide;
N-[2,5-difluoro-4-({6-methoxy-7-[3-(morpholin-4-yl)propoxy]quinolin-4-yl}oxy)phenyl]-4-methoxypyridine-3-carboxamide;
N-(3,5-difluoro-4-((6-methoxy-7-(3-morpholinopropoxy)quinolin-4-yl)oxy)phenyl)-4-ethoxypyridine-3-carboxamide;
N-[3,5-difluoro-4-({6-methoxy-7-[2-(morpholin-4-yl)ethoxy]quinolin-4-yl}oxy)phenyl]-4-methoxypyridine-3-carboxamide;
N-(3,5-difluoro-4-((6-methoxy-7-(3-morpholinopropoxy)quinolin-4-yl)oxy)phenyl)-4-methoxypyridine-3-carboxamide;
6-amino-N-(2,5-difluoro-4-((6-methoxy-7-(3-morpholinopropoxy)quinolin-4-yl)oxy)phenyl)-4-methoxypyridine-3-carboxamide;
6-amino-N-[2,5-difluoro-4-({6-methoxy-7-[3-(morpholin-4-yl)propoxy]quinolin-4-yl}oxy)phenyl]-4-ethoxypyridine-3-carboxamide;
6-amino-N-[2,3-difluoro-4-({6-methoxy-7-[2-(methylamino)ethoxy]quinolin-4-yl}oxy)phenyl]-4-methoxypyridine-3-carboxamide;
N-(4-((6,7-dimethoxyquinolin-4-yl)oxy)-3,5-difluorophenyl)-4-methoxypyridine-3-carboxamide;
N-(3,5-difluoro-4-((6-methoxy-7-(trifluoromethoxy)quinolin-4-yl)oxy)phenyl)-4-methoxypyridine-3-carboxamide;
N-(4-((7-(difluoromethoxy)-6-methoxyquinolin-4-yl)oxy)-3,5-difluorophenyl)-4-methoxypyridine-3-carboxamide;
N-(3,5-difluoro-4-((7-(2-hydroxy-2-methylpropoxy)-6-methoxyquinolin-4-yl)oxy)phenyl)-4-methoxypyridine-3-carboxamide;
N-(4-((6,7-bis(2-methoxyethoxy)quinolin-4-yl)oxy)-3,5-difluorophenyl)-4-methoxypyridine-3-carboxamide;
N-(3,5-difluoro-4-((6-methoxy-7-(2-(methylamino)ethoxy)quinolin-4-yl)oxy)phenyl)-6-fluoro-4-methoxypyridine-3-carboxamide;
N-(3,5-difluoro-4-((6-methoxy-7-(2-(methylamino)ethoxy)quinolin-4-yl)oxy)phenyl)-4-methoxy-6-methylpyridine-3-carboxamide;
N-(3,5-difluoro-4-((6-methoxy-7-(2-(methylamino)ethoxy)quinolin-4-yl)oxy)phenyl)-4-methoxy-6-((2-methoxyethyl)amino)pyridine-3-carboxamide;
N-[3,5-difluoro-4-({6-methoxy-7-[2-(methylamino)ethoxy]quinolin-4-yl}oxy)phenyl]-4-(difluoromethoxy)pyridine-3-carboxamide;
N-(2,3-difluoro-4-((6-methoxy-7-(2-(methylamino)ethoxy)quinolin-4-yl)oxy)phenyl)-4-(difluoromethoxy)pyridine-3-carboxamide;
4-methoxy-N-[2,3,5-trifluoro-4-({6-methoxy-7-[2-(methylamino)ethoxy]quinolin-4-yl}oxy)phenyl]pyridine-3-carboxamide;
4-ethoxy-N-(2,3,5-trifluoro-4-((6-methoxy-7-(2-(methylamino)ethoxy)quinolin-4-yl)oxy)phenyl)pyridine-3-carboxamide;
N-[2,5-difluoro-4-({6-methoxy-7-[2-(methylamino)ethoxy]quinolin-4-yl}oxy)phenyl]-4-propoxypyridine-3-carboxamide;
4-cyclopropoxy-N-(3,5-difluoro-4-((6-methoxy-7-(3-morpholinopropoxy)quinolin-4-yl)oxy)phenyl)pyridine-3-carboxamide;
4-cyclopropoxy-N-[3,5-difluoro-4-({6-methoxy-7-[2-(methylamino)ethoxy]quinolin-4-yl}oxy)phenyl]pyridine-3-carboxamide;
4-cyclobutoxy-N-(3,5-difluoro-4-((6-methoxy-7-(2-(methylamino)ethoxy)quinolin-4-yl)oxy)phenyl)pyridine-3-carboxamide;
N-[3,5-difluoro-4-({6-methoxy-7-[2-(methylamino)ethoxy]quinolin-4-yl}oxy)phenyl]-4-propoxypyridine-3-carboxamide;
N-(3,5-difluoro-4-((6-methoxy-7-(2-(methylamino)ethoxy)quinolin-4-yl)oxy)phenyl)-4-(3, 3-difluorocyclobutoxy)pyridine-3-carboxamide;
N-(3,5-difluoro-4-((6-methoxy-7-(2-(methylamino)ethoxy)quinolin-4-yl)oxy)phenyl)-4-(3-fluoropropoxy)pyridine-3-carboxamide;
N-(3,5-difluoro-4-((6-methoxy-7-(2-(methylamino)ethoxy)quinolin-4-yl)oxy)phenyl)-4-isopropoxypyridine-3-carboxamide;
N-(3,5-difluoro-4-((6-methoxy-7-(2-(methylamino)ethoxy)quinolin-4-yl)oxy)phenyl)-4-(2,2-difluoroethoxy)pyridine-3-carboxamide;
(R)-N-(3,5-difluoro-4-((6-methoxy-7-(2-(methylamino)ethoxy)quinolin-4-yl)oxy)phenyl)-4-(2-fluoropropoxy)pyridine-3-carboxamide;
(S)-N-(3,5-difluoro-4-((6-methoxy-7-(2-(methylamino)ethoxy)quinolin-4-yl)oxy)phenyl)-4-(2-fluoropropoxy)pyridine-3-carboxamide;
N-(3,5-difluoro-4-((6-methoxy-7-(2-(methylamino)ethoxy)quinolin-4-yl)oxy)phenyl)-4-(2-hydroxyethoxy)pyridine-3-carboxamide;
(S)-N-(3,5-difluoro-4-((6-methoxy-7-(2-(methylamino)ethoxy)quinolin-4-yl)oxy)phenyl)-4-(2-hydroxypropoxy)pyridine-3-carboxamide;
(R)-N-(3,5-difluoro-4-((6-methoxy-7-(2-(methylamino)ethoxy)quinolin-4-yl)oxy)phenyl)-4-(2-hydroxypropoxy)pyridine-3-carboxamide;
N-(3,5-difluoro-4-((6-methoxy-7-(2-(methylamino)ethoxy)quinolin-4-yl)oxy)phenyl)-4-(2-hydroxy-2-methylpropoxy)pyridine-3-carboxamide;
N-(3,5-difluoro-4-((6-methoxy-7-(2-(methylamino)ethoxy)quinolin-4-yl)oxy)phenyl)-4-(2-methoxyethoxy)pyridine-3-carboxamide;
4-butoxy-N-(3,5-difluoro-4-((6-methoxy-7-(2-(methylamino)ethoxy)quinolin-4-yl)oxy)phenyl)pyridine-3-carboxamide;
4-(cyclopropylmethoxy)-N-(3,5-difluoro-4-((6-methoxy-7-(2-(methylamino)ethoxy)quinolin-4-yl)oxy)phenyl)pyridine-3-carboxamide;
N-(3,5-difluoro-4-((6-methoxy-7-(2-(methylamino)ethoxy)quinolin-4-yl)oxy)phenyl)-4-(prop-2-yn-1-yloxy)pyridine-3-carboxamide;
N-(4-((7-(azetidin-3-yloxy)-6-methoxyquinolin-4-yl)oxy)-3,5-difluorophenyl)-4-cyclopropoxypyridine-3-carboxamide;
4-cyclopropoxy-N-(4-((7-(2-(ethylamino)ethoxy)-6-methoxyquinolin-4-yl)oxy)-3,5-difluorophenyl)pyridine-3-carboxamide;
N-[2,3-difluoro-4-({6-methoxy-7-[2-(methylamino)ethoxy]quinolin-4-yl}oxy)phenyl]-4-propoxypyridine-3-carboxamide;
4-cyclopropoxy-N-(2,3-difluoro-4-((6-methoxy-7-(2-(methylamino)ethoxy)quinolin-4-yl)oxy)phenyl)pyridine-3-carboxamide;
4-cyclopropoxy-N-(3,5-difluoro-4-((6-methoxy-7-(3-(methylamino)propoxy)quinolin-4-yl)oxy)phenyl)pyridine-3-carboxamide;
4-cyclobutoxy-N-(3,5-difluoro-4-((6-methoxy-7-(3-(methylamino)propoxy)quinolin-4-yl)oxy)phenyl)pyridine-3-carboxamide;
4-cyclopropoxy-N-(4-((6,7-dimethoxyquinolin-4-yl)oxy)-3,5-difluorophenyl)pyridine-3-carboxamide;
4-cyclopropoxy-N-(4-((6,7-dimethoxyquinolin-4-yl)oxy)-2,3,5-trifluorophenyl)pyridine-3-carboxamide;
4-cyclopropoxy-N-(2,3,5-trifluoro-4-((6-methoxy-7-(2-(methylamino)ethoxy)quinolin-4-yl)oxy)phenyl)pyridine-3-carboxamide;
N-(4-((6,7-dimethoxyquinolin-4-yl)oxy)-3,5-difluorophenyl)-4-(2-hydroxyethoxy)pyridine-3-carboxamide;
4-cyclopropoxy-N-(3,5-difluoro-4-((7-(2-hydroxyethoxy)-6-methoxyquinolin-4-yl)oxy)phenyl)pyridine-3-carboxamide;
(S)-4-cyclopropoxy-N-(3,5-difluoro-4-((7-(2-hydroxypropoxy)-6-methoxyquinolin-4-yl)oxy)phenyl)pyridine-3-carboxamide;
(R)-4-cyclopropoxy-N-(3,5-difluoro-4-((7-(2-hydroxypropoxy)-6-methoxyquinolin-4-yl)oxy)phenyl)pyridine-3-carboxamide;
(R)-4-cyclopropoxy-N-(3,5-difluoro-4-((7-(3-hydroxybutoxy)-6-methoxyquinolin-4-yl)oxy)phenyl)pyridine-3-carboxamide;
4-cyclopropoxy-N-(3,5-difluoro-4-((6-methoxy-7-(2-methoxyethoxy)quinolin-4-yl)oxy)phenyl)pyridine-3-carboxamide;
4-cyclopropoxy-N-(3,5-difluoro-4-((6-(2-hydroxyethoxy)-7-methoxyquinolin-4-yl)oxy)phenyl)pyridine-3-carboxamide;
4-cyclopropoxy-N-(3,5-difluoro-4-((6-methoxy-7-(2-(methylamino)ethoxy)quinolin-4-yl)oxy)phenyl)-6-fluoropyridine-3-carboxamide;
4-cyclopropoxy-N-(3,5-difluoro-4-((7-(2-hydroxyethoxy)-6-methoxyquinolin-4-yl)oxy)phenyl)-6-methoxypyridine-3-carboxamide;
6-chloro-4-cyclopropoxy-N-(3,5-difluoro-4-((6-methoxy-7-(2-(methylamino)ethoxy)quinolin-4-yl)oxy)phenyl)pyridine-3-carboxamide;
4-cyclopropoxy-N-(3,5-difluoro-4-((7-(2-hydroxyethoxy)-6-methoxyquinolin-4-yl)oxy)phenyl)-6-methylpyridine-3-carboxamide;
4-cyclopropoxy-N-(3,5-difluoro-4-((6-methoxy-7-(2-(methylamino)ethoxy)quinolin-4-yl)oxy)phenyl)-6-methylpyridine-3-carboxamide;
4-cyclopropoxy-N-(3,5-difluoro-4-((7-(2-hydroxyethoxy)-6-methoxyquinolin-4-yl)oxy)phenyl)-2-fluoropyridine-3-carboxamide;
N-(3,5-difluoro-4-((6-methoxy-7-(3-(methylamino)propoxy)quinolin-4-yl)oxy)phenyl)-4-ethoxy-2-fluoropyridine-3-carboxamide;
N-(3,5-difluoro-4-((7-(2-hydroxyethoxy)-6-methoxyquinolin-4-yl)oxy)phenyl)-4-methoxypyridine-3-carboxamide;
N-(3,5-difluoro-4-{[6-(2-hydroxyethoxy)-7-methoxyquinolin-4-yl]oxy}phenyl)-4-methoxypyridine-3-carboxamide;
(S)-N-(3,5-difluoro-4-{[6-(2-hydroxypropoxy)-7-methoxyquinolin-4-yl]oxy}phenyl)-4-methoxypyridine-3-carboxamide;
(R)-N-(3,5-difluoro-4-{[6-(2-hydroxypropoxy)-7-methoxyquinolin-4-yl]oxy}phenyl)-4-methoxypyridine-3-carboxamide;
N-(3,5-difluoro-4-{[6-(2-hydroxy-2-methylpropoxy)-7-methoxyquinolin-4-yl]oxy}phenyl)-4-methoxypyridine-3-carboxamide;
(S)-N-(3,5-difluoro-4-{[6-((1-hydroxypropan-2-yl)oxy)-7-methoxyquinolin-4-yl]oxy}phenyl)-4-methoxypyridine-3-carboxamide;
(S)-N-(3,5-difluoro-4-((7-methoxy-6-((1-methoxypropan-2-yl)oxy)quinolin-4-yl)oxy)phenyl)-4-methoxynicotinamide;
(S)-4-cyclopropoxy-N-(3,5-difluoro-4-((6-((1-hydroxypropan-2-yl)oxy)-7-methoxyquinolin-4-yl)oxy)phenyl)nicotinamide;
(R)-N-(3,5-difluoro-4-{[6-((1-hydroxypropan-2-yl)oxy)-7-methoxyquinolin-4-yl]oxy}phenyl)-4-methoxypyridine-3-carboxamide;
N-(3,5-difluoro-4-((6-(1-(hydroxymethyl)cyclopropoxy)-7-methoxyquinolin-4-yl)oxy)phenyl)-4-methoxynicotinamide;
(S)-4-methoxy-N-(2,3,5-trifluoro-4-((6-((1-hydroxypropan-2-yl)oxy)-7-methoxyquinolin-4-yl)oxy)phenyl)nicotinamide;
N-(3,5-difluoro-4-((7-(2-hydroxyethoxy)-6-methoxyquinolin-4-yl)oxy)phenyl)-4-(2,2-difluoroethoxy)pyridine-3-carboxamide;
N-(3,5-difluoro-4-((7-(2-hydroxyethoxy)-6-methoxyquinolin-4-yl)oxy)phenyl)-4-(2,2-difluoroethoxy)-2-fluoropyridine-3-carboxamide;
N-(3,5-difluoro-4-((6-(2-hydroxyethoxy)-7-methoxyquinolin-4-yl)oxy)phenyl)-4-(2,2-difluoroethoxy)-2-fluoropyridine-3-carboxamide; and
N-(3,5-difluoro-4-((6-(2-hydroxyethoxy)-7-methoxyquinolin-4-yl)oxy)phenyl)-4-(2,2-difluoroethoxy)pyridine-3-carboxamide.

### Claim 2 (depends on 1)

The compound of claim 1, or pharmaceutically acceptable salt or solvate thereof, wherein the compound is selected from the group consisting of:
N-[3,5-difluoro-4-({6-methoxy-7-[2-(methylamino)ethoxy]quinolin-4-yl}oxy)phenyl]-4-methoxypyridine-3-carboxamide;
N-(3,5-difluoro-4-{[6-(2-hydroxyethoxy)-7-methoxyquinolin-4-yl]oxy}phenyl)-4-methoxypyridine-3-carboxamide;
4-cyclopropoxy-N-(3,5-difluoro-4-((7-(2-hydroxyethoxy)-6-methoxyquinolin-4-yl)oxy)phenyl)pyridine-3-carboxamide;
(S)-N-(3,5-difluoro-4-{[6-((1-hydroxypropan-2-yl)oxy)-7-methoxyquinolin-4-yl]oxy}phenyl)-4-methoxypyridine-3-carboxamide;
4-cyclopropoxy-N-(4-((6,7-dimethoxyquinolin-4-yl)oxy)-3,5-difluorophenyl)pyridine-3-carboxamide;
N-(3,5-difluoro-4-((6-(1-(hydroxymethyl)cyclopropoxy)-7-methoxyquinolin-4-yl)oxy)phenyl)-4-methoxynicotinamide; and
N-(3,5-difluoro-4-((7-(2-hydroxyethoxy)-6-methoxyquinolin-4-yl)oxy)phenyl)-4-3 methoxypyridine-3-carboxamide.

### Claim 3 (depends on 1)

The compound of claim 1, or pharmaceutically acceptable salt or solvate thereof, wherein the compound is N-[3,5-difluoro-4-({6-methoxy-7-[2-(methylamino)ethoxy]quinolin-4-yl}oxy)phenyl]-4-methoxypyridine-3-carboxamide.

### Claim 4 (depends on 1)

The compound of claim 1, or pharmaceutically acceptable salt or solvate thereof, wherein the compound is N-(3,5-difluoro-4-{[6-(2-hydroxyethoxy)-7-methoxyquinolin-4-yl]oxy}phenyl)-4-methoxypyridine-3-carboxamide.

### Claim 5 (depends on 1)

The compound of claim 1, or pharmaceutically acceptable salt or solvate thereof, wherein the compound is 4-cyclopropoxy-N-(3,5-difluoro-4-((7-(2-hydroxyethoxy)-6-methoxyquinolin-4-yl)oxy)phenyl)pyridine-3-carboxamide.

### Claim 6 (depends on 1)

The compound of claim 1, or pharmaceutically acceptable salt or solvate thereof, wherein the compound is (S)-N-(3,5-difluoro-4-{[6-((1-hydroxypropan-2-yl)oxy)-7-methoxyquinolin-4-yl]oxy}phenyl)-4-methoxypyridine-3-carboxamide.

### Claim 7 (depends on 1)

The compound of claim 1, or pharmaceutically acceptable salt or solvate thereof, wherein the compound is 4-cyclopropoxy-N-(4-((6,7-dimethoxyquinolin-4-yl)oxy)-3,5-difluorophenyl)pyridine-3-carboxamide.

### Claim 8 (depends on 1)

The compound of claim 1, or pharmaceutically acceptable salt or solvate thereof, wherein the compound is N-(3,5-difluoro-4-((6-(1-(hydroxymethyl)cyclopropoxy)-7-methoxyquinolin-4-yl)oxy)phenyl)-4-methoxynicotinamide.

### Claim 9 (depends on 1)

The compound of claim 1, or pharmaceutically acceptable salt or solvate thereof, wherein the compound is N-(3,5-difluoro-4-((7-(2-hydroxyethoxy)-6-methoxyquinolin-4-yl)oxy)phenyl)-4-methoxypyridine-3-carboxamide.

### Claim 10

A pharmaceutical composition comprising a compound, or pharmaceutically acceptable salt or solvate thereof, selected from the group consisting of:
N-[3,5-difluoro-4-({6-methoxy-7-[2-(methylamino)ethoxy]quinolin-4-yl}oxy)phenyl]-4-methoxypyridine-3-carboxamide;
6-chloro-N-[3,5-difluoro-4-({6-methoxy-7-[2-(methylamino)ethoxy]quinolin-4-yl}oxy)phenyl]-4-methoxypyridine-3-carboxamide;
N-(3,5-difluoro-4-((6-methoxy-7-(2-(methylamino)ethoxy)quinolin-4-yl)oxy)phenyl)-2-fluoro-4-methoxypyridine-3-carboxamide formate;
N-[3,5-difluoro-4-({6-methoxy-7-[2-(methylamino)ethoxy]quinolin-4-yl}oxy)phenyl]-4-ethoxypyridine-3-carboxamide;
N-(3-chloro-5-fluoro-4-((6-methoxy-7-(2-(methylamino)ethoxy)quinolin-4-yl)oxy)phenyl)-4-methoxypyridine-3-carboxamide;
N-(3,5-difluoro-4-((6-methoxy-7-(2-(methylamino)ethoxy)quinazolin-4-yl)oxy)phenyl)-2-fluoro-4-methoxypyridine-3-carboxamide;
N-(3,5-difluoro-4-((6-methoxy-7-(2-(methylamino)ethoxy)quinazolin-4-yl)oxy)phenyl)-4-methoxypyridine-3-carboxamide;
N-[2,3-difluoro-4-({6-methoxy-7-[2-(methylamino)ethoxy]quinolin-4-yl}oxy)phenyl]-4-methoxypyridine-3-carboxamide;
N-[2,3-difluoro-4-({6-methoxy-7-[2-(methylamino)ethoxy]quinolin-4-yl}oxy)phenyl]-2-fluoro-4-methoxypyridine-3-carboxamide;
N-[2,3-difluoro-4-({6-methoxy-7-[2-(methylamino)ethoxy]quinolin-4-yl}oxy)phenyl]-4-ethoxypyridine-3-carboxamide;
N-(2,3-difluoro-4-((6-methoxy-7-(3-(methylamino)propoxy)quinolin-4-yl)oxy)phenyl)-4-ethoxypyridine-3-carboxamide;
N-(2,3-difluoro-4-((6-methoxy-7-(3-(methylamino)propoxy)quinolin-4-yl)oxy)phenyl)-4-methoxypyridine-3-carboxamide;
N-(3,5-difluoro-4-((6-methoxy-7-(3-(methylamino)propoxy)quinolin-4-yl)oxy)phenyl)-4-methoxypyridine-3-carboxamide;
N-(3,5-difluoro-4-((6-methoxy-7-(3-(methylamino)propoxy)quinolin-4-yl)oxy)phenyl)-2-fluoro-4-methoxypyridine-3-carboxamide;
N-(3,5-difluoro-4-((6-methoxy-7-(3-(methylamino)propoxy)quinolin-4-yl)oxy)phenyl)-4-ethoxypyridine-3-carboxamide;
N-(2,5-difluoro-4-((6-methoxy-7-(3-(methylamino)propoxy)quinolin-4-yl)oxy)phenyl)-4-methoxypyridine-3-carboxamide;
N-(4-((7-(3-(dimethylamino)propoxy)-6-methoxyquinolin-4-yl)oxy)-2,5-difluorophenyl)-4-ethoxypyridine-3-carboxamide;
N-[2,5-difluoro-4-({6-methoxy-7-[2-(methylamino)ethoxy]quinolin-4-yl}oxy)phenyl]-4-methoxypyridine-3-carboxamide;
N-(2,5-difluoro-4-((6-methoxy-7-(2-(methylamino)ethoxy)quinolin-4-yl)oxy)phenyl)-2-fluoro-4-methoxypyridine-3-carboxamide;
6-chloro-N-[2,5-difluoro-4-({6-methoxy-7-[2-(methylamino)ethoxy]quinolin-4-yl}oxy)phenyl]-4-methoxypyridine-3-carboxamide;
N-[2,5-difluoro-4-({6-methoxy-7-[3-(morpholin-4-yl)propoxy]quinolin-4-yl}oxy)phenyl]-4-methoxypyridine-3-carboxamide;
N-(3,5-difluoro-4-((6-methoxy-7-(3-morpholinopropoxy)quinolin-4-yl)oxy)phenyl)-4-ethoxypyridine-3-carboxamide;
N-[3,5-difluoro-4-({6-methoxy-7-[2-(morpholin-4-yl)ethoxy]quinolin-4-yl}oxy)phenyl]-4-methoxypyridine-3-carboxamide;
N-(3,5-difluoro-4-((6-methoxy-7-(3-morpholinopropoxy)quinolin-4-yl)oxy)phenyl)-4-methoxypyridine-3-carboxamide;
6-amino-N-(2,5-difluoro-4-((6-methoxy-7-(3-morpholinopropoxy)quinolin-4-yl)oxy)phenyl)-4-methoxypyridine-3-carboxamide;
6-amino-N-[2,5-difluoro-4-({6-methoxy-7-[3-(morpholin-4-yl)propoxy]quinolin-4-yl}oxy)phenyl]-4-ethoxypyridine-3-carboxamide;
6-amino-N-[2,3-difluoro-4-({6-methoxy-7-[2-(methylamino)ethoxy]quinolin-4-yl}oxy)phenyl]-4-methoxypyridine-3-carboxamide;
N-(4-((6,7-dimethoxyquinolin-4-yl)oxy)-3,5-difluorophenyl)-4-methoxypyridine-3-carboxamide;
N-(3,5-difluoro-4-((6-methoxy-7-(trifluoromethoxy)quinolin-4-yl)oxy)phenyl)-4-methoxypyridine-3-carboxamide;
N-(4-((7-(difluoromethoxy)-6-methoxyquinolin-4-yl)oxy)-3,5-difluorophenyl)-4-methoxypyridine-3-carboxamide;
N-(3,5-difluoro-4-((7-(2-hydroxy-2-methylpropoxy)-6-methoxyquinolin-4-yl)oxy)phenyl)-4-methoxypyridine-3-carboxamide;
N-(4-((6,7-bis(2-methoxyethoxy)quinolin-4-yl)oxy)-3,5-difluorophenyl)-4-methoxypyridine-3-carboxamide;
N-(3,5-difluoro-4-((6-methoxy-7-(2-(methylamino)ethoxy)quinolin-4-yl)oxy)phenyl)-6-fluoro-4-methoxypyridine-3-carboxamide;
N-(3,5-difluoro-4-((6-methoxy-7-(2-(methylamino)ethoxy)quinolin-4-yl)oxy)phenyl)-4-methoxy-6-methylpyridine-3-carboxamide;
N-(3,5-difluoro-4-((6-methoxy-7-(2-(methylamino)ethoxy)quinolin-4-yl)oxy)phenyl)-4-methoxy-6-((2-methoxyethyl)amino)pyridine-3-carboxamide;
N-[3,5-difluoro-4-({6-methoxy-7-[2-(methylamino)ethoxy]quinolin-4-yl}oxy)phenyl]-4-(difluoromethoxy)pyridine-3-carboxamide;
N-(2,3-difluoro-4-((6-methoxy-7-(2-(methylamino)ethoxy)quinolin-4-yl)oxy)phenyl)-4-(difluoromethoxy)pyridine-3-carboxamide;
4-methoxy-N-[2,3,5-trifluoro-4-({6-methoxy-7-[2-(methylamino)ethoxy]quinolin-4-yl}oxy)phenyl]pyridine-3-carboxamide;
4-ethoxy-N-(2,3,5-trifluoro-4-((6-methoxy-7-(2-(methylamino)ethoxy)quinolin-4-yl)oxy)phenyl)pyridine-3-carboxamide;
N-[2,5-difluoro-4-({6-methoxy-7-[2-(methylamino)ethoxy]quinolin-4-yl}oxy)phenyl]-4-propoxypyridine-3-carboxamide;
4-cyclopropoxy-N-(3,5-difluoro-4-((6-methoxy-7-(3-morpholinopropoxy)quinolin-4-yl)oxy)phenyl)pyridine-3-carboxamide;
4-cyclopropoxy-N-[3,5-difluoro-4-({6-methoxy-7-[2-(methylamino)ethoxy]quinolin-4-yl}oxy)phenyl]pyridine-3-carboxamide;
4-cyclobutoxy-N-(3,5-difluoro-4-((6-methoxy-7-(2-(methylamino)ethoxy)quinolin-4-yl)oxy)phenyl)pyridine-3-carboxamide;
N-[3,5-difluoro-4-({6-methoxy-7-[2-(methylamino)ethoxy]quinolin-4-yl}oxy)phenyl]-4-propoxypyridine-3-carboxamide;
N-(3,5-difluoro-4-((6-methoxy-7-(2-(methylamino)ethoxy)quinolin-4-yl)oxy)phenyl)-4-(3, 3-difluorocyclobutoxy)pyridine-3-carboxamide;
N-(3,5-difluoro-4-((6-methoxy-7-(2-(methylamino)ethoxy)quinolin-4-yl)oxy)phenyl)-4-(3-fluoropropoxy)pyridine-3-carboxamide;
N-(3,5-difluoro-4-((6-methoxy-7-(2-(methylamino)ethoxy)quinolin-4-yl)oxy)phenyl)-4-isopropoxypyridine-3-carboxamide;
N-(3,5-difluoro-4-((6-methoxy-7-(2-(methylamino)ethoxy)quinolin-4-yl)oxy)phenyl)-4-(2,2-difluoroethoxy)pyridine-3-carboxamide;
(R)-N-(3,5-difluoro-4-((6-methoxy-7-(2-(methylamino)ethoxy)quinolin-4-yl)oxy)phenyl)-4-(2-fluoropropoxy)pyridine-3-carboxamide;
(S)-N-(3,5-difluoro-4-((6-methoxy-7-(2-(methylamino)ethoxy)quinolin-4-yl)oxy)phenyl)-4-(2-fluoropropoxy)pyridine-3-carboxamide;
N-(3,5-difluoro-4-((6-methoxy-7-(2-(methylamino)ethoxy)quinolin-4-yl)oxy)phenyl)-4-(2-hydroxyethoxy)pyridine-3-carboxamide;
(S)-N-(3,5-difluoro-4-((6-methoxy-7-(2-(methylamino)ethoxy)quinolin-4-yl)oxy)phenyl)-4-(2-hydroxypropoxy)pyridine-3-carboxamide;
(R)-N-(3,5-difluoro-4-((6-methoxy-7-(2-(methylamino)ethoxy)quinolin-4-yl)oxy)phenyl)-4-(2-hydroxypropoxy)pyridine-3-carboxamide;
N-(3,5-difluoro-4-((6-methoxy-7-(2-(methylamino)ethoxy)quinolin-4-yl)oxy)phenyl)-4-(2-hydroxy-2-methylpropoxy)pyridine-3-carboxamide;
N-(3,5-difluoro-4-((6-methoxy-7-(2-(methylamino)ethoxy)quinolin-4-yl)oxy)phenyl)-4-(2-methoxyethoxy)pyridine-3-carboxamide;
4-butoxy-N-(3,5-difluoro-4-((6-methoxy-7-(2-(methylamino)ethoxy)quinolin-4-yl)oxy)phenyl)pyridine-3-carboxamide;
4-(cyclopropylmethoxy)-N-(3,5-difluoro-4-((6-methoxy-7-(2-(methylamino)ethoxy)quinolin-4-yl)oxy)phenyl)pyridine-3-carboxamide;
N-(3,5-difluoro-4-((6-methoxy-7-(2-(methylamino)ethoxy)quinolin-4-yl)oxy)phenyl)-4-(prop-2-yn-1-yloxy)pyridine-3-carboxamide;
N-(4-((7-(azetidin-3-yloxy)-6-methoxyquinolin-4-yl)oxy)-3,5-difluorophenyl)-4-cyclopropoxypyridine-3-carboxamide;
4-cyclopropoxy-N-(4-((7-(2-(ethylamino)ethoxy)-6-methoxyquinolin-4-yl)oxy)-3,5-difluorophenyl)pyridine-3-carboxamide;
N-[2,3-difluoro-4-({6-methoxy-7-[2-(methylamino)ethoxy]quinolin-4-yl}oxy)phenyl]-4-propoxypyridine-3-carboxamide;
4-cyclopropoxy-N-(2,3-difluoro-4-((6-methoxy-7-(2-(methylamino)ethoxy)quinolin-4-yl)oxy)phenyl)pyridine-3-carboxamide;
4-cyclopropoxy-N-(3,5-difluoro-4-((6-methoxy-7-(3-(methylamino)propoxy)quinolin-4-yl)oxy)phenyl)pyridine-3-carboxamide;
4-cyclobutoxy-N-(3,5-difluoro-4-((6-methoxy-7-(3-(methylamino)propoxy)quinolin-4-yl)oxy)phenyl)pyridine-3-carboxamide;
4-cyclopropoxy-N-(4-((6,7-dimethoxyquinolin-4-yl)oxy)-3,5-difluorophenyl)pyridine-3-carboxamide;
4-cyclopropoxy-N-(4-((6,7-dimethoxyquinolin-4-yl)oxy)-2,3,5-trifluorophenyl)pyridine-3-carboxamide;
4-cyclopropoxy-N-(2,3,5-trifluoro-4-((6-methoxy-7-(2-(methylamino)ethoxy)quinolin-4-yl)oxy)phenyl)pyridine-3-carboxamide;
N-(4-((6,7-dimethoxyquinolin-4-yl)oxy)-3,5-difluorophenyl)-4-(2-hydroxyethoxy)pyridine-3-carboxamide;
4-cyclopropoxy-N-(3,5-difluoro-4-((7-(2-hydroxyethoxy)-6-methoxyquinolin-4-yl)oxy)phenyl)pyridine-3-carboxamide;
(S)-4-cyclopropoxy-N-(3,5-difluoro-4-((7-(2-hydroxypropoxy)-6-methoxyquinolin-4-yl)oxy)phenyl)pyridine-3-carboxamide;
(R)-4-cyclopropoxy-N-(3,5-difluoro-4-((7-(2-hydroxypropoxy)-6-methoxyquinolin-4-yl)oxy)phenyl)pyridine-3-carboxamide;
(R)-4-cyclopropoxy-N-(3,5-difluoro-4-((7-(3-hydroxybutoxy)-6-methoxyquinolin-4-yl)oxy)phenyl)pyridine-3-carboxamide;
4-cyclopropoxy-N-(3,5-difluoro-4-((6-methoxy-7-(2-methoxyethoxy)quinolin-4-yl)oxy)phenyl)pyridine-3-carboxamide;
4-cyclopropoxy-N-(3,5-difluoro-4-((6-(2-hydroxyethoxy)-7-methoxyquinolin-4-yl)oxy)phenyl)pyridine-3-carboxamide;
4-cyclopropoxy-N-(3,5-difluoro-4-((6-methoxy-7-(2-(methylamino)ethoxy)quinolin-4-yl)oxy)phenyl)-6-fluoropyridine-3-carboxamide;
4-cyclopropoxy-N-(3,5-difluoro-4-((7-(2-hydroxyethoxy)-6-methoxyquinolin-4-yl)oxy)phenyl)-6-methoxypyridine-3-carboxamide;
6-chloro-4-cyclopropoxy-N-(3,5-difluoro-4-((6-methoxy-7-(2-(methylamino)ethoxy)quinolin-4-yl)oxy)phenyl)pyridine-3-carboxamide;
4-cyclopropoxy-N-(3,5-difluoro-4-((7-(2-hydroxyethoxy)-6-methoxyquinolin-4-yl)oxy)phenyl)-6-methylpyridine-3-carboxamide;
4-cyclopropoxy-N-(3,5-difluoro-4-((6-methoxy-7-(2-(methylamino)ethoxy)quinolin-4-yl)oxy)phenyl)-6-methylpyridine-3-carboxamide;
4-cyclopropoxy-N-(3,5-difluoro-4-((7-(2-hydroxyethoxy)-6-methoxyquinolin-4-yl)oxy)phenyl)-2-fluoropyridine-3-carboxamide;
N-(3,5-difluoro-4-((6-methoxy-7-(3-(methylamino)propoxy)quinolin-4-yl)oxy)phenyl)-4-ethoxy-2-fluoropyridine-3-carboxamide;
N-(3,5-difluoro-4-((7-(2-hydroxyethoxy)-6-methoxyquinolin-4-yl)oxy)phenyl)-4-methoxypyridine-3-carboxamide;
N-(3,5-difluoro-4-{[6-(2-hydroxyethoxy)-7-methoxyquinolin-4-yl]oxy}phenyl)-4-methoxypyridine-3-carboxamide;
(S)-N-(3,5-difluoro-4-{[6-(2-hydroxypropoxy)-7-methoxyquinolin-4-yl]oxy}phenyl)-4-methoxypyridine-3-carboxamide;
(R)-N-(3,5-difluoro-4-{[6-(2-hydroxypropoxy)-7-methoxyquinolin-4-yl]oxy}phenyl)-4-methoxypyridine-3-carboxamide;
N-(3,5-difluoro-4-{[6-(2-hydroxy-2-methylpropoxy)-7-methoxyquinolin-4-yl]oxy}phenyl)-4-methoxypyridine-3-carboxamide;
(S)-N-(3,5-difluoro-4-{[6-((1-hydroxypropan-2-yl)oxy)-7-methoxyquinolin-4-yl]oxy}phenyl)-4-methoxypyridine-3-carboxamide;
(S)-N-(3,5-difluoro-4-((7-methoxy-6-((1-methoxypropan-2-yl)oxy)quinolin-4-yl)oxy)phenyl)-4-methoxynicotinamide;
(S)-4-cyclopropoxy-N-(3,5-difluoro-4-((6-((1-hydroxypropan-2-yl)oxy)-7-methoxyquinolin-4-yl)oxy)phenyl)nicotinamide;
(R)-N-(3,5-difluoro-4-{[6-((1-hydroxypropan-2-yl)oxy)-7-methoxyquinolin-4-yl]oxy}phenyl)-4-methoxypyridine-3-carboxamide;
N-(3,5-difluoro-4-((6-(1-(hydroxymethyl)cyclopropoxy)-7-methoxyquinolin-4-yl)oxy)phenyl)-4-methoxynicotinamide;
(S)-4-methoxy-N-(2,3,5-trifluoro-4-((6-((1-hydroxypropan-2-yl)oxy)-7-methoxyquinolin-4-yl)oxy)phenyl)nicotinamide;
N-(3,5-difluoro-4-((7-(2-hydroxyethoxy)-6-methoxyquinolin-4-yl)oxy)phenyl)-4-(2,2-difluoroethoxy)pyridine-3-carboxamide;
N-(3,5-difluoro-4-((7-(2-hydroxyethoxy)-6-methoxyquinolin-4-yl)oxy)phenyl)-4-(2,2-difluoroethoxy)-2-fluoropyridine-3-carboxamide;
N-(3,5-difluoro-4-((6-(2-hydroxyethoxy)-7-methoxyquinolin-4-yl)oxy)phenyl)-4-(2,2-difluoroethoxy)-2-fluoropyridine-3-carboxamide; and
N-(3,5-difluoro-4-((6-(2-hydroxyethoxy)-7-methoxyquinolin-4-yl)oxy)phenyl)-4-(2,2-difluoroethoxy)pyridine-3-carboxamide;
and at least one pharmaceutically acceptable excipient.

### Claim 11 (depends on 10)

The pharmaceutical composition of claim 10, wherein the compound is selected from the group consisting of:
N-[3,5-difluoro-4-({6-methoxy-7-[2-(methylamino)ethoxy]quinolin-4-yl}oxy)phenyl]-4-methoxypyridine-3-carboxamide;
N-(3,5-difluoro-4-{[6-(2-hydroxyethoxy)-7-methoxyquinolin-4-yl]oxy}phenyl)-4-methoxypyridine-3-carboxamide;
4-cyclopropoxy-N-(3,5-difluoro-4-((7-(2-hydroxyethoxy)-6-methoxyquinolin-4-yl)oxy)phenyl)pyridine-3-carboxamide;
(S)-N-(3,5-difluoro-4-{[6-((1-hydroxypropan-2-yl)oxy)-7-methoxyquinolin-4-yl]oxy}phenyl)-4-methoxypyridine-3-carboxamide;
4-cyclopropoxy-N-(4-((6,7-dimethoxyquinolin-4-yl)oxy)-3,5-difluorophenyl)pyridine-3-carboxamide;
N-(3,5-difluoro-4-((6-(1-(hydroxymethyl)cyclopropoxy)-7-methoxyquinolin-4-yl)oxy)phenyl)-4-methoxynicotinamide; and
N-(3,5-difluoro-4-((7-(2-hydroxyethoxy)-6-methoxyquinolin-4-yl)oxy)phenyl)-4-methoxypyridine-3-carboxamide.

### Claim 12 (depends on 10)

The pharmaceutical composition of claim 10, or pharmaceutically acceptable salt or solvate thereof, wherein the compound is N-[3,5-difluoro-4-({6-methoxy-7-[2-(methylamino)ethoxy]quinolin-4-yl}oxy)phenyl]-4-methoxypyridine-3-carboxamide.

### Claim 13 (depends on 10)

The pharmaceutical composition of claim 10, or pharmaceutically acceptable salt or solvate thereof, wherein the compound is N-(3,5-difluoro-4-{[6-(2-hydroxyethoxy)-7-methoxyquinolin-4-yl]oxy}phenyl)-4-methoxypyridine-3-carboxamide.

### Claim 14 (depends on 10)

The pharmaceutical composition of claim 10, or pharmaceutically acceptable salt or solvate thereof, wherein the compound is 4-cyclopropoxy-N-(3,5-difluoro-4-((7-(2-hydroxyethoxy)-6-methoxyquinolin-4-yl)oxy)phenyl)pyridine-3-carboxamide.

### Claim 15 (depends on 10)

The pharmaceutical composition of claim 10, or pharmaceutically acceptable salt or solvate thereof, wherein the compound is (S)-N-(3,5-difluoro-4-{[6-((1-hydroxypropan-2-yl)oxy)-7-methoxyquinolin-4-yl]oxy}phenyl)-4-methoxypyridine-3-carboxamide.

### Claim 16 (depends on 10)

The pharmaceutical composition of claim 10, or pharmaceutically acceptable salt or solvate thereof, wherein the compound is 4-cyclopropoxy-N-(4-((6,7-dimethoxyquinolin-4-yl)oxy)-3,5-difluorophenyl)pyridine-3-carboxamide.

### Claim 17 (depends on 10)

The pharmaceutical composition of claim 10, or pharmaceutically acceptable salt or solvate thereof, wherein the compound is N-(3,5-difluoro-4-((6-(1-(hydroxymethyl)cyclopropoxy)-7-methoxyquinolin-4-yl)oxy)phenyl)-4-methoxynicotinamide.

### Claim 18 (depends on 10)

The pharmaceutical composition of claim 10, or pharmaceutically acceptable salt or solvate thereof, wherein the compound is N-(3,5-difluoro-4-((7-(2-hydroxyethoxy)-6-methoxyquinolin-4-yl)oxy)phenyl)-4-methoxypyridine-3-carboxamide.