# US 9,751,876 B2 · Bicyclic heterocycle derivatives for the treatment of pulmonary arterial hypertension

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- Number: US 9,751,876 B2
- Document ID: US9751876B2
- Status: Granted
- Kind: B2
- Application number: 14/511,044
- Filed: 2014-10-09
- Published: 2015-01-22
- Granted: 2017-09-05
- Earliest claimed: 2011-09-01
- Assignees: Novartis AG
- Applicants: Novartis AG
- Inventors: Ian Bruce; Sylvie Chamoin; Stephen Paul Collingwood; Pascal Furet; Vikki Furminger; Diana Janus; Sarah Lewis; Jon Christopher Loren; Valentina Molteni; Alex Michael Saunders; Duncan Shaw; Lilya Sviridenko; Christopher Thomson; Ryan West; Vince Yeh
- Web page: https://patentgrep.com/patent/US9751876B2

## CPC

- C07D 471/04: Ortho-condensed systems
- A61K 31/444: containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone
- A61K 31/4545: containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
- A61K 31/4745: condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines (yohimbine derivatives, vinblastine A61K31/475; ergoline derivatives A61K31/48)
- A61K 31/496: Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
- A61K 31/5377: not condensed and containing further heterocyclic rings, e.g. timolol
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61P 9/12: Antihypertensives
- A61P 11/00: Drugs for disorders of the respiratory system
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- 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

Bicyclic heterocyclic derivatives of formula I useful in inhibiting PDGF receptor mediated biological activity. wherein A is and R1, R1a, R2, R3, R4, R5, R6 and X are as defined herein.

## Claims

### Claim 1

A method for treating a disease or disorder mediated by the PDGF receptor, wherein the method comprises administering to a subject in need thereof a compound of Formula (I):
or a pharmaceutically acceptable salt thereof, wherein:
A is
R1 is C1-C4 alkyl; C1-C4 alkoxy optionally substituted by one or more halogen atoms; CN; or halogen;
R1a is H, halogen, C1-C4 alkyl or C1-C4 haloalkyl;
X is N or CH;
R2 is H; C1-C8 alkyl optionally substituted by one or more OH, —NR9R11 or C1-C4 alkoxy; C1-C8 haloalkyl; C2-C8 alkynyl substituted by one or more halogen, OH, —NR9R11 or C1-C4 alkoxy; C3-C10 cycloalkyl; —(C1-C4 alkyl)-C3-C8 cycloalkyl; C1-C8 alkoxy optionally substituted by one or more halogen, —NR9R11 or OH; OH; CN; halogen; —(C0-C4 alkyl)-NR9R11; —(C0-C4 alkyl)-CO2R15; —(C0-C4 alkyl)-C(O)NR9R11; —(C0-C4 alkyl)-C6-C14 aryl; or —(C0-C4 alkyl)-3 to 14 membered heterocyclyl; wherein the cycloalkyl, —(C0-C4 alkyl)-C6-C14 aryl and —(C0-C4 alkyl)-3 to 14 membered heterocyclyl are each optionally substituted by one or more Za substituents;
R3 is H; C1-C8 alkyl optionally substituted by one or more OH, —NR9R11 or C1-C4 alkoxy; C1-C8 haloalkyl; C2-C8 alkynyl substituted by one or more halogen, OH, —NR9R11, or C1-C4 alkoxy; C3-C10 cycloalkyl; —(C1-C4 alkyl)-C3-C8 cycloalkyl; C1-C8 alkoxy optionally substituted by one or more halogen, —NR9R11 or OH; OH; CN; halogen; —(C0-C4 alkyl)-NR9R11; —(C0-C4 alkyl)-CO2R15; —(C0-C4 alkyl)-C(O)NR9R11; —(C0-C4 alkyl)-C6-C14 aryl; or —(C0-C4 alkyl)-3 to 14 membered heterocyclyl; wherein the cycloalkyl, —(C0-C4 alkyl)-C6-C14 aryl and —(C0-C4 alkyl)-3 to 14 heterocyclyl are each optionally substituted by one or more Za substituents;
each Za is independently OH; (C0-C4 alkyl)-C6 aryl; O—C6 aryl; C1-C4 alkyl optionally substituted by one or more OH, CN or —NR19aR21a; C1-C4 haloalkyl; C1-C4 alkoxy optionally substituted by one or more OH, —CO2R19a, —NR19aR21a or C1-C4 alkoxy; —NR18aC(O)R21a; —C(O)NR19aR21a; —NR18aC(O)NR19aR21a; NR19aR21a; —(C0-C4 alkyl)-C(O)OR18a; —(C0-C4 alkyl)-C(O)R19a; oxo; CN; NO2; halogen; —(C0-C4 alkyl)-4 to 6 membered heterocyclyl; or —O-(4 to 6 membered heterocyclyl); wherein the (C0-C4 alkyl)-C6 aryl, O—C6 aryl, —(C0-C4 alkyl)-4 to 6 membered heterocyclyl and —O-(4 to 6 membered heterocyclyl) are each optionally substituted by OH, halogen, C1-C4 alkyl, C1-C4 haloalkyl or C1-C4 alkoxy optionally substituted by one or more halogens;
R4 is H;
R5 is H, C1-C4 alkyl or C1-C4 haloalkyl;
R6 is selected from C1-C8 alkyl optionally substituted by one or more C1-C4 alkoxy or —NR19R21; C1-C8 haloalkyl; —(C0-C4alkyl)-C3-C8cycloalkyl; C1-C8alkoxy optionally substituted by one or more halogen atoms; —NR19R21; —(C0-C4 alkyl)-C6-C14aryl; and —(C0-C4 alkyl)-3 to 14 membered heterocyclyl; wherein the —(C0-C4alkyl)-C3-C8cycloalkyl, —(C0-C4 alkyl)-C6-C14aryl and —(C0-C4 alkyl)-3 to 14 heterocyclyl are each optionally substituted by one or more Z substituents;
each Z is independently selected from (C0-C4 alkyl)-C6 aryl; O—C6 aryl; C1-C6 alkyl optionally substituted by one or more C1-C6 alkoxy, CN or —NR19R21; C1-C6 haloalkyl; C1-C6 alkoxy optionally substituted by one or more —NR19R21 or C1-C4 alkoxy; —NR19R21; (C0-C4 C4 alkyl)-C(O)R19; CN; halogen and (C0-C4 alkyl)-4 to 6 membered heterocyclyl; and wherein the aryl and heterocyclyl are each optionally substituted by one or more halogen, C1-C6 alkyl, C1-C6 haloalkyl and C1-C6 alkoxy optionally substituted by one or more halogens;
R9 and R11 are each independently selected from H; C1-C6 alkyl optionally substituted by one or more C1-C4 alkoxy or OH; C1-C6 haloalkyl; —(C0-C1alkyl)-C3-C6 cycloalkyl; (C0-C4 alkyl)-C6-C14aryl optionally substituted by one or more groups selected from C1-C6 alkyl, C1-C6 alkoxy and halogen; and (C0-C4 alkyl)-3- to 14-membered heterocyclyl optionally substituted by one or more groups selected from halogen, oxo, C1-C6 alkyl and C(O)C1-C6 alkyl; or
R9 and R11 together with the nitrogen atom to which they are attached form a 5- to 10-membered heterocyclyl, which heterocyclyl includes 0 to 3 further heteroatoms selected from N, O and S, the heterocyclyl being optionally substituted by one or more substituents selected from OH; halogen; phenyl, 5- to 10-membered heterocyclyl; C1-C6 alkyl; C1-C6 haloalkyl; C1-C6 alkoxy optionally substituted by one or more OH or C1-C4 alkoxy; and C(O)OC1-C6alkyl; wherein the phenyl and heterocyclyl substituent groups are themselves optionally substituted by C1-C6 alkyl, C1-C6 haloalkyl or C1-C6 alkoxy;
R15 is selected from H; C1-C8 alkyl; C1-C8 haloalkyl; C3-C10 cycloalkyl; (—C1-C4alkyl)-C3-C8 cycloalkyl; —(C0-C4 alkyl)-C6-Ci4aryl and —(C0-C4 alkyl)-3 to 14 membered heterocyclyl group; wherein the C3-C10 cycloalkyl, (—C1-C4alkyl)-C3-C8 cycloalkyl, —(C0-C4 alkyl)-C6-C14aryl and —(C0-C4 alkyl)-3 to 14 membered heterocyclyl groups are each optionally substituted by one or more Z substituents;
R18a is independently H or C1-C6 alkyl;
R19a and R21a are each independently H; C1-C6 alkyl optionally substituted by one or more C1-C4 alkoxy, —NR22R23′, or OH; C1-C6 haloalkyl; —(C0-C1alkyl)-C3-C6cycloalkyl; —(C0-C4 alkyl)- C6-C14aryl optionally substituted by one or more groups selected from C1-C6 alkyl, C1-C6 alkoxy and halogen; or —(C0-C4 alkyl)-3- to 14-membered heterocyclyl optionally substituted by one or more groups selected from halogen, oxo, C1-C6 alkyl and C(O)C1-C6 alkyl; or
R19a and R21a together with the nitrogen atom to which they attached form a 5- to 10-membered heterocyclyl, which heterocyclyl includes 0 to 3 further heteroatoms selected from N, O and S, the heterocyclyl being optionally substituted by one or more substituents selected from OH; halogen; phenyl; 5- to 10-membered heterocyclyl; C1-C6 alkyl; C1-C6 haloalkyl; C1-C6 alkoxy optionally substituted by one or more OH or C1-C4 alkoxy; and C(O)OC1-C6alkyl; wherein the phenyl and heterocyclyl substituent groups are themselves optionally substituted by C1-C6 alkyl, C1-C6 haloalkyl or C1-C6 alkoxy;
R18 is independently H or C1-C6 alkyl;
R19 and R21 are each independently C1-C6 alkyl optionally substituted by one or more C1-C4 alkoxy; C1-C6 haloalkyl; —(C0-C1alkyl)-C3-C6cycloalkyl; —(C0-C4 alkyl)-C6-C14aryl optionally substituted by one or more groups selected from C1-C6 alkyl, C1-C6 alkoxy and halogen; or —(C0-C4 alkyl)-3- to 14-membered heterocyclyl, optionally substituted by one or more groups selected from halogen, C1-C6 alkyl and —C(O)C1-C6 alkyl; or
R19 and R21 together with the nitrogen atom to which they attached form a 5- to 10-membered heterocyclyl, which heterocyclyl includes 0 to 3 further heteroatoms selected from N, O and S, the heterocyclyl being optionally substituted by one or more substituents selected from halogen; phenyl; 5- to 10-membered heterocyclyl; C1-C6 alkyl; C1-C6 haloalkyl; C1-C6 alkoxy optionally substituted by one or more C1-C4 alkoxy and C(O)OC1-C6alkyl; wherein the phenyl and heterocyclyl substituent groups are themselves optionally substituted by a substituent selected from C1-C6 alkyl, C1-C6 haloalkyl and C1-C6 alkoxy; and
R22 and R23 are each independently H or C1-C6 alkyl;
wherein the disease or condition is asthma, allergic rhinitis, irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), pulmonary arterial hypertension (PAH), pulmonary fibrosis, liver fibrosis, cardiac fibrosis, scleroderma, type I diabetes or type II diabetes.

### Claim 2 (depends on 1)

The method of claim 1, wherein the disease or condition is pulmonary arterial hypertension (PAH).

### Claim 3 (depends on 1)

The method of claim 1, wherein
R5 is H;
R6 is C1-C4 alkyl optionally substituted by one or more C1-C4 alkoxy; phenyl; C1-C4 haloalkyl; tetrahydrofuran; pyrrolidine, —CH2-pyrrolidine or —CH2-piperidine; wherein phenyl, tetrahydrofuran, pyrrolidine, —CH2-pyrrolidine and —CH2-piperidine are each optionally substituted by one or more Z substituents; and
each Z is independently C1-C4 alkoxy, halogen, C1-C4 alkyl or C1-C4 haloalkyl.

### Claim 4 (depends on 1)

The method of claim 1, wherein
R2 is H; C1-C8 alkyl optionally substituted by one or more OH, —NR9R11 or C1-C4 alkoxy; C1-C8 haloalkyl; C2-C8 alkynyl substituted by one or more halogen, OH, —NR9R11 or C1-C4 alkoxy; C3-C10 cycloalkyl; —(C1-C4 alkyl)-C3-C8 cycloalkyl; C1-C8 alkoxy optionally substituted by one or more halogen, —NR9R11 or OH; OH; CN; halogen; —(C0-C4 alkyl)-NR9R11; —(C0-C4 alkyl)-CO2R15; —(C0-C4 alkyl)-C(O)NR9R11; —(C0-C4 alkyl)-C6-C14 aryl; or —(C0-C4 alkyl)-3 to 14 membered heterocyclyl; wherein the cycloalkyl, —(C0-C4 alkyl)-C6-C14 aryl and —(C0-C4 alkyl)-3 to 14 membered heterocyclyl are each optionally substituted by one or more Za substituents;
R3 is H;
R9 and R11 are each independently H; C1-C6 alkyl optionally substituted by one or more C1-C4 alkoxy or OH; C1-C6 haloalkyl; —(C0-C1alkyl)-C3-C6cycloalkyl; (C0-C4 alkyl)-C6-C14 aryl optionally substituted by one or more groups selected from C1-C6 alkyl, C1-C6 alkoxy and halogen; or (C0-C4 alkyl)-5- to 6-membered heterocyclyl optionally substituted by one or more groups selected from halogen, oxo, C1-C6 alkyl and C(O)C1-C6 alkyl;
Za is independently OH; (C0-C4 alkyl)-C6 aryl; O—C6 aryl; C1-C4 alkyl optionally substituted by one or more OH, CN or —NR19aR21a; C1-C4 haloalkyl; C1-C4 alkoxy optionally substituted by one or more OH, —CO2R19a, —NR19aR21a or C1-C4 alkoxy; —NR18aC(O)R21a; —C(O)NR19aR21a; —NR18aC(O)NR19aR21a; —NR19aR21a; (C0-C4 alkyl)-C(O)OR18a; (C0-C4 alkyl)-C(O)R19a; oxo; CN; NO2; halogen; or (C0-C4 alkyl)-4 to 6 membered heterocyclyl; wherein the aryl and heterocyclyl are each optionally substituted by halogen, C1-C4 alkyl, C1-C4 haloalkyl or C1-C4 alkoxy optionally substituted by one or more halogens;
R18a is independently H or C1-C6 alkyl;
R19a and R21a are each independently H; C1-C6 alkyl optionally substituted by one or more C1-C4 alkoxy or OH; C1-C6 haloalkyl; —(C0-C1alkyl)-C3-C6cycloalkyl; —(C0-C4 alkyl)-C6-C14 optionally substituted by one or more groups selected from C1-C6 alkyl, C1-C6 alkoxy and halogen; or (C0-C4 alkyl)-5- to 6-membered heterocyclyl optionally substituted by one or more groups selected from halogen, oxo, C1-C6 alkyl and C(O)C1-C6 alkyl; or
R19a and R21a together with the nitrogen atom to which they attached form a 5- to 10-membered heterocyclyl, which heterocyclyl includes 0 to 3 further heteroatoms selected from N, O and S, the heterocyclyl being optionally substituted by one or more substituents selected from OH; halogen; phenyl; 5- to 10-membered heterocyclyl; C1-C6 alkyl; C1-C6 haloalkyl; C1-C6 alkoxy optionally substituted by one or more OH or C1-C4 alkoxy; or C(O)OC1-C6alkyl; wherein the phenyl and heterocyclyl substituent groups are themselves optionally substituted by C1-C6 alkyl, C1-C6 haloalkyl or C1-C6 alkoxy.

### Claim 5 (depends on 1)

The method of claim 1, wherein
R2 is H; C1-C4 alkyl optionally substituted by one or more OH or —NR9R11; C1-C4 haloalkyl; C1-C4 alkoxy optionally substituted by one or more halogen, —NR9R11 or OH; OH; CN; halogen; —(C0-C4 alkyl)-NR9R11; —(C0-C4 alkyl)-C(O)NR9R11; phenyl; or —(C0-C4 alkyl)-5 to 6 membered heterocyclyl; wherein the phenyl and —(C0-C4 alkyl)-5 to 6 membered heterocyclyl are each optionally substituted by one or more Za substituents;
R3 is H;
R9 and R11 are each independently H; C1-C6 alkyl optionally substituted by one or more C1-C4 alkoxy or OH; C1-C6 haloalkyl; —(C0-C1alkyl)-C3-C6cycloalkyl; (C0-C4 alkyl)-C6-C14 optionally substituted by one or more groups selected from C1-C6 alkyl, C1-C6 alkoxy and halogen; or (C0-C4 alkyl)-5- to 6-membered heterocyclyl optionally substituted by one or more groups selected from halogen, oxo, C1-C6 alkyl and C(O)C1-C6 alkyl;
each Za is independently OH; C1-C4 alkyl optionally substituted by one or more OH or —NR19aR21a; C1-C4 haloalkyl; C1-C4 alkoxy optionally substituted by one or more OH, C1-C4 alkoxy or —NR19aR21a; —C(O)NR19aR21a; CN; halogen or —(C0-C4 alkyl)-4 to 6 membered heterocyclyl; wherein the heterocyclyl is optionally substituted by halogen, C1-C4 alkyl, C1-C4 haloalkyl or C1-C4 alkoxy optionally substituted by one or more halogens;
R19a and R21a are each independently H; C1-C4 alkyl optionally substituted by one or more C1-C4 alkoxy or OH; C1-C4 haloalkyl; —(C0-C1alkyl)-C3-C6cycloalkyl; —(C0-C4 alkyl)-C6-C14 optionally substituted by one or more groups selected from C1-C6 alkyl, C1-C6 alkoxy and halogen; or —(C0-C4 alkyl)-5- to 6-membered heterocyclyl optionally substituted by one or more groups selected from halogen, oxo, C1-C6 alkyl and C(O)C1-C6 alkyl.

### Claim 6 (depends on 1)

The method of claim 1, wherein
R1 is fluorine or methyl;
R1a is H;
R2 is H, F, Br,
R3 is H;
R4 is H;
R5 is H; and
R6 is

### Claim 7 (depends on 1)

The method of claim 1, wherein the compound of Formula (I) is selected from:
N-(2-Fluoro-5-(2-(4-methylpiperazin-1-yl)benzylcarbamoyl)phenyl)-7-(1-methyl-1H-pyrazol-5-yl)imidazo[1,2-a]pyridine-3-carboxamide;
7-(3-Fluoro-4-(2-hydroxyethylcarbamoyl)phenyl)-N-(2-fluoro-5-(2-(4-methylpiperazin-1-yl)benzylcarbamoyl)phenyl)imidazo[1,2-a]pyridine-3-carboxamide;
7-Bromo-N-(2-methyl-5-(2-(4-methylpiperazin-1-yl)benzylcarbamoyl)phenyl)imidazo[1,2-a]pyridine-3-carboxamide;
7-(1-Methyl-1H-pyrazol-5-yl)-N-(2-methyl-5-(2-(4-methylpiperazin-1-yl)benzylcarbamoyl)phenyl)imidazo[1,2-a]pyridine-3-carboxamide;
N-(2-Fluoro-5-(2-(4-methylpiperazin-1-yl)benzylcarbamoyl)phenyl)-7-(pyridine-3-yl)imidazo[1,2-a]pyridine-3-carboxamide;
N-(2-Fluoro-5-(2-(4-methylpiperazin-1-yl)benzylcarbamoyl)phenyl)-7-(1-methyl-1H-pyrazol-4-yl)imidazo[1,2-a]pyridine-3-carboxamide;
N-(5-(3,4-difluorobenzylcarbamoyl)-2-fluorophenyl)-7-(1-methyl-1H-pyrazol-5-yl) imidazo[1,2-a]pyridine-3-carboxamide;
N-(5-(benzylcarbamoyl)-2-fluorophenyl)-6-(1-methyl-1H-pyrazol-3-yl)imidazo[1,2-a]pyridine-3-carboxamide;
N-(4-fluoro-2-methyl-5-(2-(4-methyl piperazin-1-yl)benzylcarbamoyl)phenyl)-7-(pyridine-3-yl)imidazo[1,2-a]pyridine-3-carboxamide;
N-(5-(3,4-difluorobenzylcarbamoyl)-2-fluorophenyl)-7-(6-(3-(dimethylamino) propoxy)pyridine-3-yl)imidazo[1,2-a]pyridine-3-carboxamide;
N-(5-(2-(2,6-cis-dimethylpiperidin-1-yl)ethylcarbamoyl)-2-fluorophenyl)-7-(1-methyl-1H-pyrazol-5-yl)imidazo[1,2-a]pyridine-3-carboxamide;
7-(4-(aminomethyl)phenyl)-N-(2-fluoro-5-(2-(4-methylpiperazin-1-yl)benzylcarbamoyl)phenyl)imidazo[1,2-a]pyridine-3-carboxamide;
N-(5-(2-tert-butoxyethylcarbamoyl)-2-fluorophenyl)-7-(1-(2-morpholinoethyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyridine-3-carboxamide;
N-(5-((5,5-dimethyltetrahydrofuran-2-yl)methyl carbamoyl)-2-fluorophenyl)-7-(1-(2-morpholinoethyl)-1H-pyrazol-4-yl)imidazo [1,2-a]pyridine-3-carboxamide;
N-(2-fluoro-5-(2-(4-methylpiperazin-1-yl)benzylcarbamoyl)phenyl)-7-(6-methoxy pyridine-3-yl)imidazo [1,2-a]pyridine-3-carboxamide;
N-(2-fluoro-5-(2-(4-methylpiperazin-1-yl)benzylcarbamoyl)phenyl)-6-(1-methyl-1H-pyrazol-5-yl)pyrazolo[1,5-a]pyridine-3-carboxamide;
1-(2-(4-fluoro-3-(7-(pyridine-3-yl)imidazo [1,2-a]pyridine-3-carboxamido)benzamido)ethyl)-2,6-cis-dimethylpiperidine;
N-(5-(2-tert-butoxyethylcarbamoyl)-2-fluorophenyl)-6-(6-(3-(dimethylamino) propoxy)pyridine-3-yl)pyrazolo[1,5-a]pyridine-3-carboxamide;
N-(2-methyl-5-(2-(4-methylpiperazin-1-yl)benzylcarbamoyl)phenyl)-7-(pyridine-3-yl)imidazo[1,2-a]pyridine-3-carboxamide;
1-methyl-4-(2-((6-methyl-5-(7-(1-methyl-1H-pyrazol-5-yl)imidazo[1,2-a]pyridine-3-carboxamido)nicotinamido)methyl)phenyl)piperazin-1-ium;
7-(1-Methyl-1H-pyrazol-4-yl)-imidazo[1,2-a]pyridine-3-carboxylic acid {5-[2-(2,6-cis-dimethyl-piperidin-1-yl)-ethylcarbamoyl]-2-fluoro-phenyl}-amide;
N-(5-(2-tert-Butoxyethylcarbamoyl)-2-fluorophenyl)-7-(6-(3-(dimethylamino)propoxy)pyridin-3-yl)imidazo[1,2-a]pyridine-3-carboxamide;
N-(5-(3,4-Difluorobenzylcarbamoyl)-2-fluorophenyl)-7-(6-(2-(pyrrolidin-1-yl)ethoxy)pyridin-3-yl)imidazo[1,2-a]pyridine-3-carboxamide;
6-(1-Methyl-1H-pyrazol-5-yl)-N-(2-methyl-5-(2-(4-methylpiperazin-1-yl)benzylcarbamoyl)phenyl)pyrazolo[1,5-a]pyridine-3-carboxamide;
N-(2-Bromo-5-(2-(4-methylpiperazin-1-yl)benzylcarbamoyl)phenyl)imidazo[1,2-a]pyridine-3-carboxamide;
N-(2-Bromo-5-(2-(4-methylpiperazin-1-yl)benzylcarbamoyl)phenyl)pyrazolo[1,5-a]pyridine-3-carboxamide;
N-(5-(3,4-Difluorobenzylcarbamoyl)-2-fluorophenyl)-7-(3-hydroxy-3-methyl butyl)imidazo[1,2-a]pyridine-3-carboxamide;
N-(5-(3,4-Difluorobenzylcarbamoyl)-2-fluorophenyl)-7-(3-fluoro-4-(2-(piperidin-1-yl)ethylcarbamoyl)phenyl)imidazo[1,2-a]pyridine-3-carboxamide;
N-(5-(3,4-Difluorobenzylcarbamoyl)-2-fluorophenyl)-7-(3-fluoro-4-(2-(tetrahydro-2H-pyran-4-yl)ethylcarbamoyl)phenyl)imidazo[1,2-a]pyridine-3-carboxamide;
N-(5-(3,4-Difluorobenzylcarbamoyl)-2-fluorophenyl)-7-(3-fluoro-4-(3-morpholino propylcarbamoyl)phenyl)imidazo[1,2-a]pyridine-3-carboxamide;
N-(5-(3,4-Difluorobenzylcarbamoyl)-2-fluorophenyl)-7-(1-(3-(dimethyl amino)propyl)-1H-pyrazol-4-yl)imidazo[1,2-a]pyridine-3-carboxamide;
N-(5-((5,5-Dimethyltetrahydrofuran-2-yl)methylcarbamoyl)-2-fluorophenyl)-7-(5-((tetrahydro-2H-pyran-4-ylamino)methyl)pyridin-3-yl)imidazo[1,2-a]pyridine-3-carboxamide;
(S)—N-(5-4(5,5-Dimethyltetrahydrofuran-2-yl)methyl) carbamoyl)-2-fluorophenyl)-7-(5-(((2-fluoroethyl)amino)methyl)pyridin-3-yl)imidazo[1,2-a]pyridine-3-carboxamide;
(R)—N-(5-(((5,5-dimethyltetrahydrofuran-2-yl)methyl) carbamoyl)-2-fluorophenyl)-7-(5-(((2-methoxyethyl)(methyl)amino)methyl)pyridin-3-yl) imidazo[1,2-a]pyridine-3-carboxamide;
(R)-7-(5-((tert-butylamino)methyl)pyridin-3-yl)-N-(5-4(5,5-dimethyltetrahydrofuran-2-yl)methyl)carbamoyl)-2-fluorophenyl) imidazo[1,2-a]pyridine-3-carboxamide;
N-(5-(3,4-Difluorobenzylcarbamoyl)-2-fluorophenyl)-7-(6-(2-(pyrrolidin-1-yl)ethoxy)pyridin-3-yl)imidazo[1,2-a]pyridine-3-carboxamide;
N-(5-((2-(tert-Butoxy)ethyl)carbamoyl)-2-fluoro phenyl)-7-(6-(2-(pyrrolidin-1-yl) ethoxy)pyridin-3-yl) imidazo[1,2-a]pyridine-3-carboxamide;
N-(5-(((5,5-dimethyl tetrahydrofuran-2-yl)methyl)carbamoyl)-2-fluorophenyl)-7-(6-((1-methyl piperidin-4-yl)oxy)pyridin-3-yl)imidazo[1,2-a]pyridine-3-carboxamide;
6-(1-Methyl-1H-pyrazol-5-yl)-N-(2-methyl-5-(2-(4-methylpiperazin-1-yl)benzylcarbamoyl)phenyl)pyrazolo[1,5-a]pyridine-3-carboxamide;
N-(2-Bromo-5-(2-(4-methylpiperazin-1-yl)benzylcarbamoyl)phenyl)imidazo[1,2-a]pyridine-3-carboxamide;
N-(2-Bromo-5-(2-(4-methylpiperazin-1-yl)benzylcarbamoyl)phenyl)pyrazolo[1,5-a]pyridine-3-carboxamide;
N-(5-(3,4-Difluorobenzylcarbamoyl)-2-fluorophenyl)-7-(3-hydroxy-3-methyl butyl)imidazo[1,2-a]pyridine-3-carboxamide;
N-(5-(3,4-Difluorobenzylcarbamoyl)-2-fluorophenyl)-7-(3-fluoro-4-(2-(piperidin-1-yl)ethylcarbamoyl)phenyl)imidazo[1,2-a]pyridine-3-carboxamide;
N-(5-(3,4-Difluorobenzylcarbamoyl)-2-fluorophenyl)-7-(3-fluoro-4-(2-(tetrahydro-2H-pyran-4-yl)ethylcarbamoyl)phenyl)imidazo[1,2-a]pyridine-3-carboxamide;
N-(5-((2-(2,2-Dimethylpyrrolidin-1-yl)ethyl)carbamoyl)-2-fluorophenyl)-7-(1-methyl-1H-pyrazol-4-yl)imidazo[1,2-a]pyridine-3-carboxamide;
N-(5-(2-(2,2-Dimethylpyrrolidin-1-yl)ethylcarbamoyl)-2-fluorophenyl)-7-(3-fluoro-4-(1-hydroxy-2-methylpropan-2-ylcarbamoyl)phenyl)imidazo[1,2-a]pyridine-3-carboxamide;
N-(5-(2-(2,2-Dimethylpyrrolidin-1-yl)ethylcarbamoyl)-2-methylpyridin-3-yl)-6-(3-fluoro-4-(1-hydroxy-2-methylpropan-2-ylcarbamoyl)phenyl)pyrazolo[1,5-a]pyridine-3-carboxamide;
N-(5-(3,4-Difluorobenzylcarbamoyl)-2-fluorophenyl)-7-(3-fluoro-4-(3-morpholino propylcarbamoyl)phenyl)imidazo[1,2-a]pyridine-3-carboxamide;
N-(5-(2-(2,6-cis-Dimethylpiperidin-1-yl)ethylcarbamoyl)-2-fluorophenyl)-7-(3-fluoro-4-(1-hydroxy-2-methylpropan-2-ylcarbamoyl)phenyl)imidazo[1,2-a]pyridine-3-carboxamide;
7-(3-Fluoro-4-(2-fluoroethylcarbamoyl)phenyl)-N-(2-fluoro-5-(2-(4-methylpiperazin-1-yl)benzylcarbamoyl)phenyl)imidazo[1,2-a]pyridine-3-carboxamide;
N-(2-Fluoro-5-(2-(4-methylpiperazin-1-yl)benzylcarbamoyl)phenyl)-7-(3-fluoro-5-(2-hydroxy ethylcarbamoyl)phenyl)imidazo[1,2-a]pyridine-3-carboxamide;
N-(5-(2-(2,2-dimethylpyrrolidin-1-yl)ethylcarbamoyl)-2-methylpyridin-3-yl)-6-(1-methyl-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyridine-3-carboxamide;
(S)—N-(2-Fluoro-5-(2-(2-(methoxy methyl) pyrrolidin-1-yl)ethyl carbamoyl)phenyl)-7-(1-methyl-1H-pyrazol-4-yl)imidazo[1,2-a]pyridine-3-carboxamide;
N-(2-Fluoro-5-((2-(3-propylpyrrolidin-1-yl)ethyl)carbamoyl)phenyl)-7-(1-methyl-1H-pyrazol-4-yl)imidazo [1,2-a]pyridine-3-carboxamide;
(R)—N-(2-Fluoro-5-((2-(2-(methoxymethyl) pyrrolidin-1-yl)ethyl) carbamoyl)phenyl)-7-(1-methyl-1H-pyrazol-4-yl)imidazo[1,2-a]pyridine-3-carboxamide;
N-(5-((2-(3,5-Dimethylpiperidin-1-yl)ethyl)carbamoyl)-2-fluorophenyl)-7-(1-methyl-1H-pyrazol-4-yl)imidazo[1,2-a]pyridine-3-carboxamide;
N-(2-fluoro-5-((2-(2,2,6,6-tetra methylpiperidin-1-yl)ethyl)carbamoyl)phenyl)-7-(1-methyl-1H-pyrazol-5-yl)imidazo[1,2-a]pyridine-3-carboxamide;
N-(5-((2-(2,2-dimethylpyrrolidin-1-yl)ethyl)carbamoyl)-2-methylpyridin-3-yl)-6-(1-methyl-1H-pyrazol-5-yl)pyrazolo[1,5-a]pyridine-3-carboxamide;
N-(5-((2-(butyl(ethyl)amino)ethyl)carbamoyl)-2-fluoro phenyl)-7-(3-fluoro-4-((2-hydroxyethyl)carbamoyl)phenyl)imidazo[1,2-a]pyridine-3-carboxamide;
7-(3-fluoro-4-((1-hydroxy-2-methylpropan-2-yl)carbamoyl)phenyl)-N-(2-fluoro-5-((2-(3-propylpyrrolidin-1-yl)ethyl)carbamoyl)phenyl)imidazo[1,2-a]pyridine-3-carboxamide;
N-(5-((2-(3,3-dimethylmorpholino)ethyl)carbamoyl)-2-fluorophenyl)-7-(3-fluoro-4-((1-hydroxy-2-methylpropan-2-yl)carbamoyl)phenyl)imidazo[1,2-a]pyridine-3-carboxamide;
(R)-7-(3-fluoro-4-((1-hydroxy-2-methylpropan-2-yl)carbamoyl)phenyl)-N-(2-fluoro-5-((2-(2-(methoxymethyl)pyrrolidin-1-yl)ethyl) carbamoyl)phenyl)imidazo[1,2-a]pyridine-3-carboxamide;
N-(5-((3,4-Difluorobenzyl)carbamoyl)-2-fluorophenyl)-7-(6-((2-(dimethylamino)ethyl)carbamoyl)pyridin-3-yl)imidazo[1,2-a]pyridine-3-carboxamide;
N-(5-((2-(2,2-Dimethylpiperidin-1-yl)ethyl)carbamoyl)-2-methylpyridin-3-yl)-6-(1-methyl-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyridine-3-carboxamide;
N-(5-((2-(2,6-cis-Dimethylpiperidin-1-yl)ethyl)carbamoyl)-2-methylpyridin-3-yl)-6-(1-methyl-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyridine-3-carboxamide;
N-(5-((2-((2S,3R)-2,3-diethylazetidin-1-yl)ethyl) carbamoyl)-2-fluorophenyl)-7-(1-methyl-1H-pyrazol-4-yl)imidazo[1,2-a]pyridine-3-carboxamide;
N-(5-(3,4-Difluorobenzylcarbamoyl)-2-fluorophenyl)-7-(6-(((2-hydroxyethyl)(methyl)amino)methyl)pyridin-3-yl)imidazo[1,2-a]pyridine-3-carboxamide;
N-(5-((3,4-difluorobenzyl)carbamoyl)-2-fluorophenyl)-7-(6-((methyl(phenethyl)amino)methyl)pyridin-3-yl)imidazo[1,2-a]pyridine-3-carboxamide;
N-(5-((3,4-Difluoro benzyl)carbamoyl)-2-fluorophenyl)-7-(5-((methylamino)methyl)pyridin-3-yl)imidazo[1,2-a]pyridine-3-carboxamide;
7-(5-((Cyclohexyl amino)methyl)pyridin-3-yl)-N-(5-((3,4-difluorobenzyl) carbamoyl)-2-fluoro phenyl) imidazo[1,2-a]pyridine-3-carboxamide; and
N-(5-((3,4-Difluoro benzyl)carbamoyl)-2-fluorophenyl)-7-(5-(((2-methoxyethyl)(methyl)amino)methyl)pyridin-3-yl)imidazo[1,2-a]pyridine-3-carboxamide;
or a pharmaceutically acceptable salt thereof.

### Claim 8 (depends on 1)

The method of claim 1, wherein X is N.

### Claim 9 (depends on 8)

The method of claim 8, wherein R2 is phenyl or 5- or 6-membered heterocyclyl, each optionally substituted by one, two or three Za substituents.

### Claim 10 (depends on 9)

The method of claim 9, wherein R6 is (C0-C2 alkyl)-5 to 6 membered heterocyclyl, optionally substituted by one, two or three Z substituents.

### Claim 11 (depends on 10)

The method of claim 10, wherein each Z is independently C1-C4 alkoxy, halogen, C1-C4 alkyl or C1-C4 haloalkyl.

### Claim 12 (depends on 1)

The method of claim 1, wherein the compound of Formula (I) is N-(5-((2-(2,2-Dimethylpyrrolidin-1-yl)ethyl)carbamoyl)-2-fluorophenyl)-7-(1-methyl-1H-pyrazol-4-yl)imidazo[1,2-a]pyridine-3-carboxamide or a pharmaceutically acceptable salt thereof.

### Claim 13 (depends on 1)

The method of claim 1, wherein the compound of Formula (I) is N-(5-(2-(2,6-cis-Dimethylpiperidin-1-yl)ethylcarbamoyl)-2-fluorophenyl)-7-(1-methyl-1H-pyrazol-5-yl)imidazo[1,2-a]pyridine-3-carboxamide or a pharmaceutically acceptable salt thereof.

### Claim 14 (depends on 1)

The method of claim 1, wherein the compound of Formula (I) is N-(5-(2-(2,2-dimethylpyrrolidin-1-yl)ethylcarbamoyl)-2-methylpyridin-3-yl)-6-(1-methyl-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyridine-3-carboxamide or a pharmaceutically acceptable salt thereof.

### Claim 15 (depends on 1)

The method of claim 1, wherein the compound of Formula (I) is 7-(1-Methyl-1H-pyrazol-4-yl)-imidazo[1,2-a]pyridine-3-carboxylic acid {5-[2-(2,6-cis-dimethyl-piperidin-1-yl)-ethylcarbamoyl]-2-fluoro-phenyl}-amide or a pharmaceutically acceptable salt thereof.

### Claim 16 (depends on 1)

The method of claim 1, wherein the compound of Formula (I) is N-(5-((2-(2,2-dimethylpyrrolidin-1-yl)ethyl)carbamoyl)-2-methylpyridin-3-yl)-6-(1-methyl-1H-pyrazol-5-yl)pyrazolo[1,5-a]pyridine-3-carboxamide or a pharmaceutically acceptable salt thereof.

### Claim 17 (depends on 1)

The method of claim 1, wherein the compound of Formula (I) is N-(5-(2-(2,6-cis-Dimethylpiperidin-1-yl)ethylcarbamoyl)-2-fluorophenyl)-7-(3-fluoro-4-(1-hydroxy-2-methylpropan-2-ylcarbamoyl)phenyl)imidazo [1,2-a]pyridine-3-carboxamide or a pharmaceutically acceptable salt thereof.

### Claim 18

A method of treating pulmonary arterial hypertension in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a compound selected from:
N-(5-((2-(2,2-Dimethylpyrrolidin-1-yl)ethyl)carbamoyl)-2-fluorophenyl)-7-(1-methyl-1H-pyrazol-4-yl)imidazo[1,2-a]pyridine-3-carboxamide;
N-(5-(2-(2,6-cis-Dimethylpiperidin-1-yl)ethylcarbamoyl)-2-fluorophenyl)-7-(1-methyl-1H-pyrazol-5-yl)imidazo[1,2-a]pyridine-3-carboxamide;
N-(5-(2-(2,2-dimethylpyrrolidin-1-yl)ethylcarbamoyl)-2-methylpyridin-3-yl)-6-(1-methyl-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyridine-3-carboxamide;
7-(1-Methyl-1H-pyrazol-4-yl)-imidazo[1,2-a]pyridine-3-carboxylic acid {5-[2-(2,6-cis-dimethyl-piperidin-1-yl)-ethylcarbamoyl]-2-fluoro-phenyl}-amide;
N-(5-((2-(2,2-dimethylpyrrolidin-1-yl)ethyl)carbamoyl)-2-methylpyridin-3-yl)-6-(1-methyl-1H-pyrazol-5-yl)pyrazolo[1,5-a]pyridine-3-carboxamide; and
N-(5-(2-(2,6-cis-Dimethylpiperidin-1-yl)ethylcarbamoyl)-2-fluorophenyl)-7-(3-fluoro-4-(1-hydroxy-2-methylpropan-2-ylcarbamoyl)phenyl)imidazo[1,2-a]pyridine-3-carboxamide;
or a pharmaceutically acceptable salt thereof.