COMPOUNDS AND COMPOSITIONS AS C-KIT KINASE INHIBITORS

• US 20130059846A1
• Filed: 08/27/2012
• Published: 03/07/2013
• Est. Priority Date: 09/01/2011
• Status: Active Grant

• Current Assignee: Novartis Ag
• Original Assignee: IRM LLC
• Inventors: YEH, Vince, LIU, Xiaodong, LOREN, Jon, MOLTENI, Valentina, NABAKKA, Juliet, NGUYEN, Bao, LI, Xiaolin, PETRASSI, Hank Michael James
• Granted Patent: US 9,199,981 B2
• Time in Patent Office: Days
• US Class Current: 514/233.2
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 11/02 Nasal agents, e.g. decongestants
• CPC Class Codes: A61P 11/04 for throat disorders
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 19/04 for non-specific disorders of the connective tissue
• CPC Class Codes: A61P 21/00 Drugs for disorders of the muscular or neuromuscular system
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 3/00 Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• CPC Class Codes: A61P 3/04 Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 37/02 Immunomodulators
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 37/08 Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/12 Antihypertensives
• CPC Class Codes: C07D 471/04 Ortho-condensed systems

Abstract

The invention provides compounds and pharmaceutical compositions thereof, which are useful as protein kinase inhibitors, as well as methods for using such compounds to treat, ameliorate or prevent a condition associated with abnormal or deregulated kinase activity. In some embodiments, the invention provides methods for using such compounds to treat, ameliorate or prevent diseases or disorders that involve abnormal activation of c-kit or c-kit and PDGFR (PDGFRα, PDGFRβ) kinases.

Claims

1. A compound of Formula (I) or Formula (II), or pharmaceutically acceptable salt thereof:

2. The compound of claim 1, wherein the compound is a compound of Formula (Ia), Formula (IIa), Formula (Ib) or Formula (IIb):

3. The compound of claim 1, wherein R¹ is selected from —

CH₃ and F.

4. The compound of claim 3, wherein R¹ is —

CH₃.

5. The compound of claim 1, wherein each R¹ is independently selected from H, F and —

CH₃.

6. The compound of claim 5, wherein each R¹ is H.

7. The compound of claim 1, wherein R³ is selected from an unsubstituted C₃-C₈cycloalkyl, a cyclobutanone, a cyclopentanone and a substituted C₃-C₈cycloalkyl,

wherein the substituted C₃-C₈cycloalkyl of R³ is substituted with 1-4 substituents independently selected from C₁-C₆alkyl, halo, C₁-C₆haloalkyl, —

OR⁴, —

(CR⁹₂)_nOR⁴, —

O(CR⁹₂)_nOR⁴, —

N(R⁴)₂, ═

N—

OR⁴, ═

N—

O—

(CR⁹₂)_nR⁵, —

NR⁴C(═

O)OR⁴, —

NR⁴C(═

O)(CR⁹₂)_nOR⁴, —

NR⁴(CR⁹₂)_nOR⁴, —

NR⁴S(═

O)₂R⁴, —

N(C(═

O)OR⁴)₂, ═

CH₂, ═

CH(CR⁹₂)_nOR⁴, R⁸, deuterated C₁-C₆alkoxy, a spiro attached dioxolane, a spiro attached dioxolane which is substituted with C₁-C₆alkyl, a spiro attached dioxane, a spiro attached tetrahyrofuranly, a spiro attached cyclobutanone, a spiro attached cyclobutanol, an unsubstituted 5-6 membered heterocycloalkyl with 1-2 heteroatoms independently selected from N and O and a 5-6 membered heterocycloalkyl with 1-2 heteroatoms independently selected from N and O substituted with 1-3 substituents independently selected from C₁-C₆alkyl.

8. The compound of claim 7, wherein each R⁴ is independently selected from H, methyl, ethyl, propyl, butyl, i-propyl and t-butyl.

9. The compound of claim 7, wherein R⁵ is independently selected from cyclopropyl or morpholinyl.

10. The compound of claim 7, wherein each R⁷ is independently selected from CH₂F, —

CHF₂, —

CH₂CHF₂, —

CH₂CF₃ and —

CF₃.

11. The compound of claim 7, wherein each R⁹ is independently selected from H, methyl and ethyl.

12. The compound of claim 7, wherein R⁸ is selected from an unsubstituted C₃-C₈cycloalkyl and an unsubstituted 5 membered heteroaryl with 1-4 heteroatoms selected from N.

13. The compound of claim 7, wherein

R³ is selected from cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl, each of which is unsubstituted or each of which is substituted with 1-4 substituents independently selected from —

F, —

CH₃, —

CH₂CH₃, —

CF₃, —

OH, —

OCH₃, —

CH₂OCH₃, —

NH₂, —

N(CH₃)₂, —

OCH₂CH₂OCH₃, ═

N—

OCH₃, ═

N-OCH₂ CH₃, ═

N—

OCH(CH₃)₂, ═

N—

OH, ═

N—

O—

CH₂R⁵, ═

N—

O—

CH₂CH₂R⁵, —

NHC(═

O)OC(CH₃)₃, —

NHC(═

O)OCH₃, —

NHC(═

O)CH₂OCH₃, —

NHCH₂CH₂OCH₃, —

NHCH₂CH₂OH, —

NHS(═

O)₂CH₃, —

N(C(═

O)OCH₃)₂, ═

CH₂, ═

CHCH₂CH₂OH, —

OCD₃, cyclopropyl, triazolyl, pyrazolyl, a spiro attached dioxolane, a spiro attached dioxolane which is substituted with a —

CH₃, a spiro attached dioxane, a spiro attached tetrahyrofuranly, a spiro attached cyclobutanone, a spiro attached cyclobutanol, piperidinyl and piperazinyl substituted with a —

CH₃,

or R³ is a cyclobutanone or a cyclopentanone.

14. The compound of claim 13, wherein:

R³ is cyclopropyl substituted with 1 or 2 F,

or

R³ is cyclobutyl substituted with 2 F.

15. The compound of claim 13, wherein m is 1 and R²⁰ is selected from H, halo, C₁-C₆alkyl, C₁-C₆haloalkyl, C₁-C₆haloalkoxy, deuterated C₁-C₆alkyl, —

CN, —

(CR⁹₂)_nOR⁴, —

(CR⁹₂)_nC(═

O)OR⁴, R¹⁰, —

(CR⁹₂)_nR¹⁰, —

((CR⁹₂)_nO)_tR⁴, —

(CR⁹₂)_nO(CR⁹₂)_nR⁷, (CR⁹₂)_nC(═

O)R⁴, and —

C(═

O)N(R⁴)₂.

16. The compound of claim 15, wherein m is 1 and R²⁰ is selected from H, —

F, —

CH₃, —

CF₃, —

CD₃, —

CN, —

OCHF₂, —

C(CH₃)OH, —

CH₂CH₂C(═

O)OC(CH₃)₃, —

CH₂OCH₂CH₂OH, —

CH₂OCH₂CF₃, —

C(═

O)NH₂, —

CH₂CH₂C(CH₃)₂OH, —

CH₂OCH₂CH₂OCH₃, —

CH₂OCH₂CH₂F, —

CH₂CH₂C(═

O)CH₃, —

CH₂OCH and —

CH₂OCH₃.

17. The compound of claim 16, wherein m is 1 and R²⁰ is —

CH₃.

18. The compound of claim 16, wherein m is 1 and R²⁰ is H.

19. The compound of claim 15, wherein:

R¹⁰ is selected from morpholinyl, piperidinyl, piperidin-1-yl, piperidin-2-yl, piperidin-3-yl, piperidin-4-yl, piperazinyl, piperazin-1-yl, pyrazolyl, pyrazol-1-yl, pyrazol-3-yl, pyrazol-4-yl, triazolyl, 1H-1,2,3-triazol-4-yl, 4H-1,2,4-triazol-3-yl, 1H-1,2,4-triazol-5-yl, thiazolyl, thiazol-4-yl, thiazol-5-yl, imidazolyl, imidazol-1-yl, imidazol-2-yl, each of which is unsubstituted or each of which is substituted with 1-3 substituents independently selected from C₁-C₆alkyl, —

(CR⁹₂)_nOR⁴, —

(C(R⁹)₂)_nC(O)OR⁴, —

(C(R⁹)₂)_nR⁵ and —

S(═

O)₂R⁴

or R¹⁰ is selected from a oxazolidin-2-one and a pyrrolidin-2-one.

20. The compound of claim 19, wherein:

R¹⁰ is selected from morpholinyl, piperidinyl, piperidin-1-yl, piperidin-2-yl, piperidin-3-yl, piperidin-4-yl, piperazinyl, piperazin-1-yl, pyrazolyl, pyrazol-1-yl, pyrazol-3-yl, pyrazol-4-yl, triazolyl, 1H-1,2,3-triazol-4-yl, 4H-1,2,4-triazol-3-yl, 1H-1,2,4-triazol-5-yl, thiazolyl, thiazol-4-yl, thiazol-5-yl, imidazolyl, imidazol-1-yl, imidazol-2-yl, each of which is unsubstituted or each of which is substituted with 1-3 substituents independently selected from —

CH₃, —

CH₂CH₂OH, —

CH₂C(O)OH, —

CH₂CH₂OH, —

CH₂C(CH₃)₂OH, —

S(O)₂CH₃ and —

CH₂CH₂—

R₅.

21. The compound of claim 13, wherein m is 4 and R²⁰ is deuterium.

22. The compound of claim 1 selected from:

N-{5-[3-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-5-yl]-2-methylphenyl}imidazo[1,2-a]pyridine-3-carboxamide;

N-{2-methyl-5-[5-(3-oxocyclopentyl)-1,2,4-oxadiazol-3-yl]phenyl}imidazo[1,2-a]pyridine-3-carboxamide;

N-{5-[5-(3-hydroxy-3-methylcyclobutyl)-1,2,4-oxadiazol-3-yl]-2-methylphenyl}imidazo[1,2-a]pyridine-3-carboxamide;

N-(5-{5-[3-(hydroxyimino)cyclobutyl]-1,2,4-oxadiazol-3-yl}-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide;

N-{5-[5-(4,4-difluorocyclohexyl)-1,2,4-oxadiazol-3-yl]-2-methylphenyl}imidazo[1,2-a]pyridine-3-carboxamide;

N-{5-[5-(3-hydroxy-3-methylcyclobutyl)-1,2,4-oxadiazol-3-yl]-2-methylphenyl}imidazo[1,2-a]pyridine-3-carboxamide;

N-(5-{5-[3-(methoxyimino)cyclobutyl]-1,2,4-oxadiazol-3-yl}-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide;

N-[5-(5-{5,8-dioxaspiro[3.4]octan-2-yl}-1,2,4-oxadiazol-3-yl)-2-methylphenyl]imidazo[1,2-a]pyridine-3-carboxamide;

N-(2-methyl-5-{5-[(6R)-6-methyl-5,8-dioxaspiro[3.4]octan-2-yl]-1,2,4-oxadiazol-3-yl}phenyl)imidazo[1,2-a]pyridine-3-carboxamide;

N-[5-(5-{5,9-dioxaspiro[3.5]nonan-2-yl}-1,2,4-oxadiazol-3-yl)-2-methylphenyl]imidazo[1,2-a]pyridine-3-carboxamide;

N-{2-methyl-5-[5-(3-oxocyclobutyl)-1,2,4-oxadiazol-3-yl]phenyl}imidazo[1,2-a]pyridine-3-carboxamide;

N-(2-methyl-5-{5-[(6S)-6-methyl-5,8-dioxaspiro[3.4]octan-2-yl]-1,2,4-oxadiazol-3-yl}phenyl)imidazo[1,2-a]pyridine-3-carboxamide;

N-{5-[5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-3-yl]-2-methylphenyl}imidazo[1,2-a]pyridine-3-carboxamide;

N-(5-{5-[3-(ethoxyimino)cyclobutyl]-1,2,4-oxadiazol-3-yl}-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide;

N-[5-(5-{3-[(cyclopropylmethoxy)imino]cyclobutyl}-1,2,4-oxadiazol-3-yl)-2-methylphenyl]imidazo[1,2-a]pyridine-3-carboxamide;

N-[2-methyl-5-(5-{3-[(propan-2-yloxy)imino]cyclobutyl}-1,2,4-oxadiazol-3-yl)phenyl]imidazo[1,2-a]pyridine-3-carboxamide;

N-{5-[5-(3-aminocyclobutyl)-1,2,4-oxadiazol-3-yl]-2-methylphenyl}imidazo[1,2-a]pyridine-3-carboxamide;

N-(5-{5-[3-(2-methoxyethoxy)cyclobutyl]-1,2,4-oxadiazol-3-yl}-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide;

N-{5-[5-(3-methoxycyclobutyl)-1,2,4-oxadiazol-3-yl]-2-methylphenyl}imidazo[1,2-a]pyridine-3-carboxamide;

N-(5-{5-[1-(methoxymethyl)cyclopropyl]-1,2,4-oxadiazol-3-yl}-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide;

tert-butyl N-{1-[3-(3-{imidazo[1,2-a]pyridine-3-amido}-4-methylphenyl)-1,2,4-oxadiazol-5-yl]cyclopropyl}carbamate;

N-{5-[5-(1-methanesulfonamidocyclopropyl)-1,2,4-oxadiazol-3-yl]-2-methylphenyl}imidazo[1,2-a]pyridine-3-carboxamide;

methyl N-{1-[3-(3-{imidazo[1,2-a]pyridine-3-amido}-4-methylphenyl)-1,2,4-oxadiazol-5-yl]cyclopropyl}-N-(methoxycarbonyl)carbamate;

methyl N-{1-[3-(3-{imidazo[1,2-a]pyridine-3-amido}-4-methylphenyl)-1,2,4-oxadiazol-5-yl]cyclopropyl}carbamate;

N-(5-{5-[3-hydroxy-3-(trifluoromethyl)cyclobutyl]-1,2,4-oxadiazol-3-yl}-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide;

1-methylcyclopropyl N-{[3-(3-{imidazo[1,2-a]pyridine-3-amido}-4-methylphenyl)-1,2,4-oxadiazol-5-yl]methyl}carbamate;

methyl N-{1-[3-(3-{imidazo[1,2-a]pyridine-3-amido}-4-methylphenyl)-1,2,4-oxadiazol-5-yl]cyclobutyl}carbamate;

N-{5-[5-(1-methanesulfonamidocyclobutyl)-1,2,4-oxadiazol-3-yl]-2-methylphenyl}imidazo[1,2-a]pyridine-3-carboxamide;

N-(5-{5-[1-(dimethylamino)cyclopropyl]-1,2,4-oxadiazol-3-yl}-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide;

N-{2-methyl-5-[5-(3-methylidenecyclobutyl)-1,2,4-oxadiazol-3-yl]phenyl}imidazo[1,2-a]pyridine-3-carboxamide;

N-{5-[5-(3-cyclopropyl-3-hydroxycyclobutyl)-1,2,4-oxadiazol-3-yl]-2-methylphenyl}imidazo[1,2-a]pyridine-3-carboxamide;

N-(5-{5-[3-(3-hydroxypropylidene)cyclobutyl]-1,2,4-oxadiazol-3-yl}-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide;

N-[2-methyl-5-(5-{5-oxaspiro[3.4]octan-2-yl}-1,2,4-oxadiazol-3-yl)phenyl]imidazo[1,2-a]pyridine-3-carboxamide;

N-[5-(5-{[(3,3-difluorocyclobutyl)amino]methyl}-1,2,4-oxadiazol-3-yl)-2-methylphenyl]imidazo[1,2-a]pyridine-3-carboxamide;

N-(2-methyl-5-{5-[(2,2,3,3-tetrafluorocyclobutoxy)methyl]-1,2,4-oxadiazol-3-yl}phenyl)imidazo[1,2-a]pyridine-3-carboxamide;

N-{5-[5-(3-fluorocyclobutyl)-1,2,4-oxadiazol-3-yl]-2-methylphenyl}imidazo[1,2-a]pyridine-3-carboxamide;

N-{5-[5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-3-yl]-2-methylphenyl}-6-(hydroxymethyl)imidazo[1,2-a]pyridine-3-carboxamide;

N-{5-[5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-3-yl]-2-methylphenyl}-6-[(2-hydroxyethoxy)methyl]imidazo[1,2-a]pyridine-3-carboxamide;

N-{5-[5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-3-yl]-2-methylphenyl}-6-(methoxymethyl)imidazo[1,2-a]pyridine-3-carboxamide;

N-{5-[5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-3-yl]-2-methylphenyl}-6-(1H-pyrazol-4-yl)imidazo[1,2-a]pyridine-3-carboxamide;

N-{5-[5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-3-yl]-2-methylphenyl}-6-[1-(2-hydroxyethyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyridine-3-carboxamide;

N-{5-[5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-3-yl]-2-methylphenyl}-6-(1-methyl-1H-pyrazol-4-yl)imidazo[1,2-a]pyridine-3-carboxamide;

N-{5-[5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-3-yl]-2-methylphenyl}-6-(1-methyl-1H-pyrazol-3-yl)imidazo[1,2-a]pyridine-3-carboxamide;

N-{5-[5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-3-yl]-2-methylphenyl}-6-[1-(2-hydroxy-2-methylpropyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyridine-3-carboxamide;

N-(2-methyl-5-{5-[3-(1H-pyrazol-1-yl)cyclobutyl]-1,2,4-oxadiazol-3-yl}phenyl)imidazo[1,2-a]pyridine-3-carboxamide;

N-{5-[5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-3-yl]-2-methylphenyl}-6-(1,3-thiazol-4-yl)imidazo[1,2-a]pyridine-3-carboxamide;

N-{5-[5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-3-yl]-2-fluorophenyl}-6-(1-methyl-1H-pyrazol-4-yl)imidazo[1,2-a]pyridine-3-carboxamide;

N-{5-[5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-3-yl]-2-fluorophenyl}-6-[1-(2-hydroxy-2-methylpropyl)-1H-pyrazol-4-yl]imidazo[1,2-a]pyridine-3-carboxamide;

N-{5-[5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-3-yl]-2-methylphenyl}-7-(1-methanesulfonylpiperidin-4-yl)imidazo[1,2-a]pyridine-3-carboxamide;

N-{5-[5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-3-yl]-2-methylphenyl}-6-{1-[2-(morpholin-4-yl)ethyl]-1H-pyrazol-4-yl}imidazo[1,2-a]pyridine-3-carboxamide;

N-{5-[5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-3-yl]-2-fluorophenyl}-6-{1-[2-(morpholin-4-yl)ethyl]-1H-pyrazol-4-yl}imidazo[1,2-a]pyridine-3-carboxamide;

N-{5-[5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-3-yl]-2-methylphenyl}-6-[(2,2,2-trifluoroethoxy)methyl]imidazo[1,2-a]pyridine-3-carboxamide;

N-{5-[5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-3-yl]-2-methylphenyl}-6-(3-oxobutyl)imidazo[1,2-a]pyridine-3-carboxamide;

N-{5-[5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-3-yl]-2-methylphenyl}-6-(3-hydroxy-3-methylbutyl)imidazo[1,2-a]pyridine-3-carboxamide;

N-(5-{5-[2-(1-hydroxycyclopropyl)ethyl]-1,2,4-oxadiazol-3-yl}-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide;

N-{5-[5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-3-yl]-2-methylphenyl}-6-[2-(morpholin-4-yl)ethyl]imidazo[1,2-a]pyridine-3-carboxamide;

N-[5-(5-cyclobutyl-1,2,4-oxadiazol-3-yl)-2-methylphenyl]imidazo[1,2-a]pyridine-3-carboxamide;

N-{5-[5-(3,3-dimethylcyclobutyl)-1,2,4-oxadiazol-3-yl]-2-methylphenyl}imidazo[1,2-a]pyridine-3-carboxamide;

N-{5-[5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-3-yl]-2-methylphenyl}-7-(morpholin-4-yl) imidazo[1,2-a]pyridine-3-carboxamide;

6-cyano-N-{5-[5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-3-yl]-2-methylphenyl}imidazo[1,2-a]pyridine-3-carboxamide;

N-{5-[5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-3-yl]-2-fluorophenyl}-6-(5-methyl-4H-1,2,4-triazol-3-yl) imidazo[1,2-a]pyridine-3-carboxamide;

3-N-{5-[5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-3-yl]-2-methylphenyl}imidazo[1,2-a]pyridine-3,6-dicarboxamide;

N-{5-[5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-3-yl]-2-methylphenyl}-6-[2-(4-methylpiperazin-1-yl)ethyl]imidazo[1,2-a]pyridine-3-carboxamide;

N-{5-[5-(2,2-difluorocyclopropyl)-1,2,4-oxadiazol-3-yl]-2-methylphenyl}imidazo[1,2-a]pyridine-3-carboxamide;

N-{5-[5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-3-yl]-2-methylphenyl}-7-(1H-1,2,3-triazol-4-yl)imidazo[1,2-a]pyridine-3-carboxamide;

N-{5-[5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-3-yl]-2-methylphenyl}-7-[1-(2-hydroxyethyl)-1H-1,2,3-triazol-4-yl]imidazo[1,2-a]pyridine-3-carboxamide;

N-{5-[5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-3-yl]-2,4-dimethylphenyl}imidazo[1,2-a]pyridine-3-carboxamide;

N-{5-[5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-3-yl]-2-methylphenyl}-7-(2-oxo-1,3-oxazolidin-3-yl)imidazo[1,2-a]pyridine-3-carboxamide;

N-{5-[5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-3-yl]-2-methylphenyl}-7-methylimidazo[1,2-a]pyridine-3-carboxamide;

N-{5-[5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-3-yl]-2-methylphenyl}-6-methylimidazo[1,2-a]pyridine-3-carboxamide;

N-{5-[5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-3-yl]-2-methylphenyl}-6-fluoroimidazo[1,2-a]pyridine-3-carboxamide;

N-{5-[5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-3-yl]-2-methylphenyl}-7-fluoroimidazo[1,2-a]pyridine-3-carboxamide;

7-cyano-N-{5-[5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-3-yl]-2-methylphenyl}imidazo[1,2-a]pyridine-3-carboxamide;

N-[5-(5-cyclopentyl-1,2,4-oxadiazol-3-yl)-2-methylphenyl]imidazo[1,2-a]pyridine-3-carboxamide;

N-[2-methyl-5-(5-{6-oxospiro[3.3]heptan-2-yl}-1,2,4-oxadiazol-3-yl)phenyl]imidazo[1,2-a]pyridine-3-carboxamide;

N-{5-[5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-3-yl]-2-methylphenyl}-7-(2-oxopyrrolidin-1-yl)imidazo[1,2-a]pyridine-3-carboxamide;

N-{5-[5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-3-yl]-2-methylphenyl}-6-[(2,2-difluoroethoxy)methyl]imidazo[1,2-a]pyridine-3-carboxamide;

N-{5-[5-(3-ethylcyclobutyl)-1,2,4-oxadiazol-3-yl]-2-methylphenyl}imidazo[1,2-a]pyridine-3-carboxamide;

N-{5-[5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-3-yl]-2-methylphenyl}-6-(5-methyl-4H-1,2,4-triazol-3-yl)imidazo[1,2-a]pyridine-3-carboxamide;

N-{5-[5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-3-yl]-2-methylphenyl}-7-methylimidazo[1,2-a]pyridine-3-carboxamide;

N-{5-[5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-3-yl]-2-methylphenyl}-6-(morpholin-4-yl)imidazo[1,2-a]pyridine-3-carboxamide;

N-{5-[5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-3-yl]-2-methylphenyl}-6-(1H-imidazol-1-yl)imidazo[1,2-a]pyridine-3-carboxamide;

N-{5-[5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-3-yl]-2-methylphenyl}-6-[(2-fluoroethoxy)methyl]imidazo[1,2-a]pyridine-3-carboxamide;

N-{5-[5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-3-yl]-2-methylphenyl}-6-[3-(methoxymethyl)-1H-1,2,4-triazol-5-yl]imidazo[1,2-a]pyridine-3-carboxamide;

N-{5-[5-(2,2-difluorocyclopropyl)-1,2,4-oxadiazol-3-yl]-2-methylphenyl}-6-[(2,2,2-trifluoroethoxy)methyl]imidazo[1,2-a]pyridine-3-carboxamide;

N-[5-(5-cyclobutyl-1,2,4-oxadiazol-3-yl)-2-methylphenyl]-6-[(2,2,2-trifluoroethoxy)methyl]imidazo[1,2-a]pyridine-3-carboxamide;

N-(5-{5-[(1R)-2,2-difluorocyclopropyl]-1,2,4-oxadiazol-3-yl}-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide;

N-(5-{5-[(1S)-2,2-difluorocyclopropyl]-1,2,4-oxadiazol-3-yl}-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide;

N-(5-{5-[3-hydroxy-3-(trifluoromethyl)cyclobutyl]-1,2,4-oxadiazol-3-yl}-2-methylphenyl)-7-methylimidazo[1,2-a]pyridine-3-carboxamide;

6-fluoro-N-(5-{5-[3-hydroxy-3-(trifluoromethyl)cyclobutyl]-1,2,4-oxadiazol-3-yl}-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide;

N-(5-{5-[(1R,2S)-2-fluorocyclopropyl]-1,2,4-oxadiazol-3-yl}-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide;

N-{5-[5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-3-yl]-2-methylphenyl}-5,6,7,8-tetradeuteroimidazo[1,2-a]pyridine-3-carboxamide;

N-{5-[(3,3-difluorocyclobutyl)carbamoyl]-2-methylphenyl}imidazo[1,2-a]pyridine-3-carboxamide;

7-fluoro-N-(5-{5-[3-hydroxy-3-(trifluoromethyl)cyclobutyl]-1,2,4-oxadiazol-3-yl}-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide;

N-{5-[5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-3-yl]-2-methylphenyl}-6-(4-methyl-1H-imidazol-1-yl)imidazo[1,2-a]pyridine-3-carboxamide;

N-{5-[5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-3-yl]-2-methylphenyl}-6-[(2R,6S)-2,6-dimethylmorpholin-4-yl]imidazo[1,2-a]pyridine-3-carboxamide;

N-(5-{5-[3-methoxy-3-(trifluoromethyl)cyclobutyl]-1,2,4-oxadiazol-3-yl}-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide;

6-fluoro-N-(5-{5-[1-(methoxymethyl)cyclobutyl]-1,2,4-oxadiazol-3-yl}-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide;

N-{5-[5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-3-yl]-2-methylphenyl}-6-[1-(2-methoxyethyl)-5-methyl-1H-1,2,4-triazol-3-yl]imidazo[1,2-a]pyridine-3-carboxamide;

N-[5-(5-{6-hydroxyspiro[3.3]heptan-2-yl}-1,2,4-oxadiazol-3-yl)-2-methylphenyl]imidazo[1,2-a]pyridine-3-carboxamide;

N-(5-{5-[(1S,2S)-2-fluorocyclopropyl]-1,2,4-oxadiazol-3-yl}-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide;

7-methyl-N-(2-methyl-5-{5-[(2,2,3,3-tetrafluorocyclobutoxy)methyl]-1,2,4-oxadiazol-3-yl}phenyl)imidazo[1,2-a]pyridine-3-carboxamide;

6-methyl-N-(2-methyl-5-{5-[(2,2,3,3-tetrafluorocyclobutoxy)methyl]-1,2,4-oxadiazol-3-yl}phenyl)imidazo[1,2-a]pyridine-3-carboxamide;

N-[5-(5-cyclopropyl-1,2,4-oxadiazol-3-yl)-2-methylphenyl]imidazo[1,2-a]pyridine-3-carboxamide;

N-{5-[5-(cyclopropylmethyl)-1,2,4-oxadiazol-3-yl]-2-methylphenyl}imidazo[1,2-a]pyridine-3-carboxamide;

N-(5-{5-[(1R,2S)-2-fluorocyclopropyl]-1,2,4-oxadiazol-3-yl}-2-methylphenyl)-7-methylimidazo[1,2-a]pyridine-3-carboxamide;

N-(5-{5-[(1S,2R)-2-fluorocyclopropyl]-1,2,4-oxadiazol-3-yl}-2-methylphenyl)-7-methylimidazo[1,2-a]pyridine-3-carboxamide;

N-(5-{5-[(1R)-2,2-difluorocyclopropyl]-1,2,4-oxadiazol-3-yl}-2,4-dimethylphenyl)imidazo[1,2-a]pyridine-3-carboxamide;

N-(5-{5-[(1S)-2,2-difluorocyclopropyl]-1,2,4-oxadiazol-3-yl}-2,4-dimethylphenyl)imidazo[1,2-a]pyridine-3-carboxamide;

N-(5-{5-[(1R,2S)-2-fluorocyclopropyl]-1,2,4-oxadiazol-3-yl}-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide;

N-{5-[5-(3-fluorocyclobutyl)-1,2,4-oxadiazol-3-yl]-2-methylphenyl}-7-methylimidazo[1,2-a]pyridine-3-carboxamide;

N-{5-[5-(3-fluorocyclobutyl)-1,2,4-oxadiazol-3-yl]-2-methylphenyl}-6-methylimidazo[1,2-a]pyridine-3-carboxamide;

N-(5-{5-[(1S,2R)-2-fluorocyclopropyl]-1,2,4-oxadiazol-3-yl}-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide;

methyl N-{3,3-difluoro-1-[3-(3-{imidazo[1,2-a]pyridine-3-amido}-4-methylphenyl)-1,2,4-oxadiazol-5-yl]cyclobutyl}carbamate;

methyl N-{3,3-difluoro-1-[3-(4-methyl-3-{7-methylimidazo[1,2-a]pyridine-3-amido}phenyl)-1,2,4-oxadiazol-5-yl]cyclobutyl}carbamate, and

N-{5-[5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-3-yl]-2-methylphenyl}-6-[(2-fluoroethoxy)methyl]imidazo[1,2-a]pyridine-3-carboxamide.

23. The compound of claim 1 selected from:

N-{5-[5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-3-yl]-2-methylphenyl}imidazo[1,2-a]pyridine-3-carboxamide;

N-(5-{5-[(1R)-2,2-difluorocyclopropyl]-1,2,4-oxadiazol-3-yl}-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide;

N-(5-{5-[(1S)-2,2-difluorocyclopropyl]-1,2,4-oxadiazol-3-yl}-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide;

N-(5-{5-[(1S,2R)-2-fluorocyclopropyl]-1,2,4-oxadiazol-3-yl}-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide, and

N-(5-{5-[(1R,2S)-2-fluorocyclopropyl]-1,2,4-oxadiazol-3-yl}-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide.

24. A pharmaceutical composition comprising a therapeutically effective amount a compound of claim 1 and a pharmaceutically acceptable carrier.

25. A method for treating a disease or disorder where modulation of a kinase is implicated, wherein the method comprises administering to a system or subject in need of such treatment an effective amount of a compound of claim 1, wherein the kinase is selected from c-kit, PDGFRα

and PDGFRβ and

wherein the disease is selected from a mast-cell associated disease, a respiratory disease, an inflammatory disorder, irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), an autoimmune disorder, a metabolic disease, a fibrosis disease, a dermatological disease, pulmonary arterial hypertension (PAH) and primary pulmonary hypertension (PPH).

26. The method of claim 25, wherein the disease is asthma, allergic rhinitis, pulmonary arterial hypertension (PAH), pulmonary fibrosis, hepatic fibrosis, cardiac fibrosis, scleroderma, irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), uticaria, dermatosis, type I diabetes or type II diabetes.