Compounds and compositions as c-Kit kinase inhibitors
View Patent ↗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.
1. A compound of Formula (I) or Formula (II), or pharmaceutically acceptable salt thereof:
wherein:
m is 1 and R 20 is selected from H, halo, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 haloalkoxy, deuterium, deuterated C 1 -C 6 alkyl, —CN, —(CR 9 2 ) n OR 4 , —C(O)R 4 , —(CR 9 2 ) n C(═O)OR 4 , R 10 , —(CR 9 2 ) n R 10 , —((CR 9 2 ) n O) t R 4 , —(CR 9 2 ) n O(CR 9 2 ) n R 7 , —(CR 9 2 ) n C(═O)R 4 , —C(═O)N(R 4 ) 2 , —OR 4 , and —(CR 9 2 ) n CN;
or m is 4 and R 20 is deuterium;
R 1 is selected from C 1 -C 6 alkyl and halo;
each R 11 is independently selected from H, halo and C 1 -C 6 alkyl;
L 1 is a bond, —NH— or —C(O)NH—;
L 2 is —(CR 9 2 ) n —, —CHR 6 —, —(CR 9 2 ) n O—, —NH—, —(CR 9 2 ) n C(═O)—, —C(═O)O(CR 9 2 ) n —, —(CR 9 2 ) n OC(═O)NR 4 —, —(CR 9 2 ) n NR 4 C(═O)(CR 9 2 ) n —, —(CR 9 2 ) n NR 4 C(═O)—, or —(CR 9 2 ) n NR 4 C(═O)O—;
R 2 is R 3 or L 2 R 3 ;
R 3 is selected from an unsubstituted 4-6 membered heterocycloalkyl with 1-2 heteroatoms independently selected from N, O and S, a piperidinone, a oxazolidin-2-one, pyrrolidinone, a pyrrolidin-2-one and a substituted 4-6 membered heterocycloalkyl with 1-2 heteroatoms independently selected from N, O and S, wherein the substituted 4-6 membered heterocycloalkyl of R 3 is substituted with 1-4 substituents independently selected from C 1 -C 6 alkyl halo, —CN, C 1 -C 6 haloalkyl, —OR 4 , —C(═O)OR 4 , —C(═O)R 4 , —C(═O)R 7 , —C(═O)OR 5 , —(CR 9 2 ) n OR 4 , —C(CR 9 2 ) n OR 4 , —C(═O)O(CR 9 2 ) n OR 4 , —N(R 4 ) 2 , —C(═O)NR 4 2 , —NR 4 C(═O)OR 4 , —NR 4 C(═O)(CR 9 2 ) n OR 4 , —NR 4 (CR 9 2 ) n OR 4 , —NR 4 S(═O) 2 R 4 , —N(C(═O)OR 4 ) 2 , R 8 , —(CR 9 2 ) n R 8 , deuterated C 1 -C 6 alkoxy, —S(═O) 2 R 4 , —S(═O) 2 R 7 , —S(═O) 2 R 8 , —S(═O) 2 N(R 4 ) 2 , —S(═O) 2 NHC(═O)OR 4 , —S(═O) 2 (CR 9 2 ) n C(═O)OR 4 , S(═O) 2 (CR 9 2 ) n OR 4 , a spiro attached dioxolane, a spiro attached dioxolane which is substituted with C 1 -C 6 alkyl, a spiro attached dioxane, a spiro attached tetrahydrofuranly, a spiro attached oxetane, a spiro attached cyclobutanone, a spiro attached cyclobutanol, a C 1 alkyl bridge, an unsubstituted 5-6 membered heterocycloalkyl with 1-2 heteroatoms independently selected from N, O and S and a 5-6 membered heterocycloalkyl with 1-2 heteroatoms independently selected from N, O and S substituted with 1-3 substituents independently selected from C 1 -C 6 alkyl, halo, C 1 -C 6 haloalkyl, C 1 -C 6 haloalkoxy, —OR 4 and R 8 ;
each R 4 is independently selected from H and C 1 -C 6 alkyl;
R 5 is an unsubstituted C 3 -C 8 cycloalkyl, an unsubstituted 5-6 membered heterocycloalkyl with 1-2 heteroatoms independently selected from N or O or a C 3 -C 8 cycloalkyl substituted with 1-3 substituents independently selected from C 1 -C 6 alkyl;
each R 6 is independently selected from —NR 4 C(O)OR 4 , —OR 4 and —(CR 9 2 ) n OR 4 ;
each R 7 is independently selected from C 1 -C 6 haloalkyl;
R 8 is selected from an unsubstituted phenyl, unsubstituted 5-6 membered heteroaryl with 1-3 heteroatoms independently selected from N, O and S, an unsubstituted 5 membered heteroaryl with 1-4 heteroatoms selected from N, an unsubstituted 4-6 membered heterocycloalkyl with 1-2 heteroatoms independently selected from N, O and S, an unsubstituted C 3 -C 8 cycloalkyl, a substituted 5-6 membered heteroaryl with 1-3 heteroatoms independently selected from N, O and S, a substituted phenyl, a substituted 5 membered heteroaryl with 1-4 heteroatoms selected from N, a substituted 4-6 membered heterocycloalkyl with 1-2 heteroatoms independently selected from N, O and S, a substituted C 3 -C 8 cycloalkyl, a tetrahydro-1H-oxazolo[3,4-a]pyrazin-3(5H)-one, a oxazolidin-2-one, pyrrolidinone and a pyrrolidin-2-one,
wherein the substituted phenyl, the substituted 5-6 membered heteroaryl with 1-2 heteroatoms independently selected from N, O and S, the substituted 5 membered heteroaryl with 1-4 heteroatoms selected from N, substituted C 3 -C 8 cycloalkyl and substituted 4-6 membered heterocycloalkyl of R 8 are substituted with 1-3 substituents independently selected from C 1 -C 6 alkyl, —(C(R 9 ) 2 ) n OR 4 , —C(R 9 ) 2 ) n R 5 , —(C(R 9 ) 2 ) n C(O)OR 4 , —C(O)OR 4 and —S(O) 2 R 4 ;
each R 9 is independently selected from H and C 1 -C 6 alkyl;
R 10 is selected from an unsubstituted phenyl, unsubstituted 5-6 membered heteroaryl with 1-2 heteroatoms independently selected from N, O and S, an unsubstituted 5 membered heteroaryl with 1-4 heteroatoms selected from N, an unsubstituted 4-6 membered heterocycloalkyl with 1-2 heteroatoms independently selected from N, O and S, an unsubstituted C 3 -C 8 cycloalkyl, a substituted 5-6 membered heteroaryl with 1-2 heteroatoms independently selected from N, O and S, a substituted phenyl, a substituted 5 membered heteroaryl with 1-4 heteroatoms selected from N, a substituted 4-6 membered heterocycloalkyl with 1-2 heteroatoms independently selected from N, O and S, a substituted C 3 -C 8 cycloalkyl, a oxazolidin-2-one, pyrrolidinone and a pyrrolidin-2-one,
wherein the substituted phenyl, the substituted 5-6 membered heteroaryl with 1-2 heteroatoms independently selected from N, O and S, the substituted 5 membered heteroaryl with 1-4 heteroatoms selected from N, substituted C 3 -C 8 cycloalkyl and substituted 4-6 membered heterocycloalkyl of R 8 are substituted with 1-3 substituents independently selected from C 1 -C 6 alkyl [Me], —(C(R 9 ) 2 ) n OR 4 , —(C(R 9 ) 2 ) n R 5 , —(C(R 9 ) 2 ) n C(O)OR 4 and —S(O) 2 R 4 ;
t is 1, 2 or 3, and
each n is independently selected from 1, 2, 3 and 4.
2. The compound of claim 1 , wherein the compound is a compound of Formula (Ia), Formula (IIa), Formula (Ib) or Formula (IIb):
wherein:
m is 1 and R 20 is selected from H, halo, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 haloalkoxy, deuterium, deuterated C 1 -C 6 alkyl, —CN, —(CR 9 2 ) n OR 4 , —C(O)R 4 , —(CR 9 2 ) n C(═O)OR 4 , R 10 , —(CR 9 2 ) n R 10 , —((CR 9 2 ) n O) t R 4 , —(CR 9 2 ) n O(CR 9 2 ) n R 7 , —(CR 9 2 ) n C(═O)R 4 , —C(═O)N(R 4 ) 2 , —OR 4 , and —(CR 9 2 ) n CN;
or m is 4 and R 20 is deuterium;
R 1 is selected from C 1 -C 6 alkyl and halo;
each R 11 is independently selected from H, halo and C 1 -C 6 alkyl;
L 2 is —(CR 9 2 ) n —, —CHR 6 —, —(CR 9 2 ) n O—, —NH—, —(CR 9 2 ) n C(═O)—, —C(═O)O(CR 9 2 ) n —, —(CR 9 2 ) n OC(═O)NR 4 —, —(CR 9 2 ) n NR 4 C(═O)(CR 9 2 ) n —, —(CR 9 2 ) n NR 4 C(═O)—, or —(CR 9 2 ) n NR 4 C(═O)O—;
R 2 is R 3 or L 2 R 3 ;
R 3 is selected from an unsubstituted 4-6 membered heterocycloalkyl with 1-2 heteroatoms independently selected from N, O and S, a piperidinone, a oxazolidin-2-one, pyrrolidinone, a pyrrolidin-2-one and a substituted 4-6 membered heterocycloalkyl with 1-2 heteroatoms independently selected from N, O and S, wherein the substituted 4-6 membered heterocycloalkyl of R 3 is substituted with 1-4 substituents independently selected from C 1 -C 6 alkyl halo, —CN, C 1 -C 6 haloalkyl, —OR 4 , —C(═O)OR 4 , —C(═O)R 4 , —C(═O)R 7 , —C(═O)OR 5 , —(CR 9 2 ) n OR 4 , —O(CR 9 2 ) n OR 4 , —C(═O)O(CR 9 2 ) n OR 4 , —N(R 4 ) 2 , —C(═O)NR 4 2 , —NR 4 C(═O)OR 4 , —NR 4 C(═O)(CR 9 2 ) n OR 4 , —NR 4 (CR 9 2 ) n OR 4 , —NR 4 S(═O) 2 R 4 , —N(C(═O)OR 4 ) 2 , R 8 , —(CR 9 2 ) n R 8 , deuterated C 1 -C 6 alkoxy, —S(═O) 2 R 4 , —S(═O) 2 R 7 , —S(═O) 2 R 8 , —S(═O) 2 N(R 4 ) 2 , —S(═O) 2 NHC(═O)OR 4 , —S(═O) 2 (CR 9 2 ) n C(═O)OR 4 , S(═O) 2 (CR 9 2 ) n OR 4 , a Spiro attached dioxolane, a Spiro attached dioxolane which is substituted with C 1 -C 6 alkyl, a spiro attached dioxane, a spiro attached tetrahydrofuranly, a spiro attached oxetane, a spiro attached cyclobutanone, a spiro attached cyclobutanol, a C 1 alkyl bridge, an unsubstituted 5-6 membered heterocycloalkyl with 1-2 heteroatoms independently selected from N, O and S and a 5-6 membered heterocycloalkyl with 1-2 heteroatoms independently selected from N, O and S substituted with 1-3 substituents independently selected from C 1 -C 6 alkyl, halo, C 1 -C 6 haloalkyl, C 1 -C 6 haloalkoxy, —OR 4 and R 8 ;
each R 4 is independently selected from H and C 1 -C 6 alkyl;
R 5 is an unsubstituted C 3 -C 8 cycloalkyl, an unsubstituted 5-6 membered heterocycloalkyl with 1-2 heteroatoms independently selected from N or O or a C 3 -C 8 cycloalkyl substituted with 1-3 substituents independently selected from C 1 -C 6 alkyl;
each R 6 is independently selected from —NR 4 C(O)OR 4 , —OR 4 and —(CR 9 2 ) n OR 4 ;
each R 7 is independently selected from C 1 -C 6 haloalkyl;
R 8 is selected from an unsubstituted phenyl, unsubstituted 5-6 membered heteroaryl with 1-3 heteroatoms independently selected from N, O and S, an unsubstituted 5 membered heteroaryl with 1-4 heteroatoms selected from N, an unsubstituted 4-6 membered heterocycloalkyl with 1-2 heteroatoms independently selected from N, O and S, an unsubstituted C 3 -C 8 cycloalkyl, a substituted 5-6 membered heteroaryl with 1-3 heteroatoms independently selected from N, O and S, a substituted phenyl, a substituted 5 membered heteroaryl with 1-4 heteroatoms selected from N, a substituted 4-6 membered heterocycloalkyl with 1-2 heteroatoms independently selected from N, O and S, a substituted C 3 -C 8 cycloalkyl, a tetrahydro-1H-oxazolo[3,4-a]pyrazin-3(5H)-one, a oxazolidin-2-one, pyrrolidinone and a pyrrolidin-2-one, wherein the substituted phenyl, the substituted 5-6 membered heteroaryl with 1-2 heteroatoms independently selected from N, O and S, the substituted 5 membered heteroaryl with 1-4 heteroatoms selected from N, substituted C 3 -C 8 cycloalkyl and substituted 4-6 membered heterocycloalkyl of R 8 are substituted with 1-3 substituents independently selected from C 1 -C 6 alkyl, —(C(R 9 ) 2 ) n OR 4 , —(C(R 9 ) 2 ) n R 5 , —(C(R 9 ) 2 ) n C(O)OR 4 , —C(O)OR 4 and —S(O) 2 R 4 ;
each R 9 is independently selected from H and C 1 -C 6 alkyl;
R 10 is selected from an unsubstituted phenyl, unsubstituted 5-6 membered heteroaryl with 1-2 heteroatoms independently selected from N, O and S, an unsubstituted 5 membered heteroaryl with 1-4 heteroatoms selected from N, an unsubstituted 4-6 membered heterocycloalkyl with 1-2 heteroatoms independently selected from N, O and S, an unsubstituted C 3 -C 8 cycloalkyl, a substituted 5-6 membered heteroaryl with 1-2 heteroatoms independently selected from N, O and S, a substituted phenyl, a substituted 5 membered heteroaryl with 1-4 heteroatoms selected from N, a substituted 4-6 membered heterocycloalkyl with 1-2 heteroatoms independently selected from N, O and S, a substituted C 3 -C 8 cycloalkyl, a oxazolidin-2-one, pyrrolidinone and a pyrrolidin-2-one,
wherein the substituted phenyl, the substituted 5-6 membered heteroaryl with 1-2 heteroatoms independently selected from N, O and S, the substituted 5 membered heteroaryl with 1-4 heteroatoms selected from N, substituted C 3 -C 8 cycloalkyl and substituted 4-6 membered heterocycloalkyl of R 8 are substituted with 1-3 substituents independently selected from C 1 -C 6 alkyl [Me], —(C(R 9 ) 2 ) n OR 4 , —(C(R 9 ) 2 ) n R 5 , —(C(R 9 ) 2 ) n C(O)OR 4 and —S(O) 2 R 4 ;
t is 1, 2 or 3, and
each n is independently selected from 1, 2, 3 and 4.
3. The compound of claim 1 , wherein R 1 is selected from —CH 3 and F.
4. The compound of claim 3 , wherein R 1 is —CH 3 .
5. The compound of claim 1 , wherein each R 11 is independently selected from H, F and —CH 3 .
6. The compound of claim 5 , wherein each R 11 is H.
7. The compound of claim 1 , wherein R 3 is selected from an unsubstituted 4-6 membered heterocycloalkyl with 1-2 heteroatoms independently selected from N and O, a piperidinone, a oxazolidin-2-one, pyrrolidinone, a pyrrolidin-2-one and a substituted 4-6 membered heterocycloalkyl with 1-2 heteroatoms independently selected from N and O,
wherein the substituted 4-6 membered heterocycloalkyl of R 3 is substituted with 1-4 substituents independently selected from C 1 -C 6 alkyl, halo, —CN, C 1 -C 6 haloalkyl, —OR 4 , —C(═O)OR 4 , —C(═O)R 4 , —C(═O)R 7 , —C(═O)OR 5 , —(CR 9 2 ) n OR 4 , —C(═O)O(CR 9 2 ) n OR 4 , —C(═O)NR 4 2 , —NR 4 C(═O)OR 4 , —NR 4 C(═O)(CR 9 2 ) n OR 4 , —R 8 , —(CR 9 2 ) n R 8 , —S(═O) 2 R 4 , —S(═O) 2 R 7 , —S(═O) 2 R 8 , —S(═O) 2 N(R 4 ) 2 , —S(═O) 2 NHC(═O)OR 4 , —S(═O) 2 (CR 9 2 ) n OR 4 , —S(═O) 2 (CR 9 2 ) n C(═O)OR 4 and a C 1 alkyl bridge.
8. The compound of claim 7 , wherein each R 4 is independently selected from H, methyl, ethyl, propyl, butyl, i-propyl and t-butyl.
9. The compound of claim 7 , wherein each R 5 is cyclopropyl, cyclopropyl substituted with a methyl or morpholinyl.
10. The compound of claim 7 , wherein each R 7 is independently selected from CH 2 F, —CHF 2 , —CH 2 CHF 2 , —CH 2 CF 3 and —CF 3 .
11. The compound of claim 7 , wherein each R 9 is independently selected from H, methyl and ethyl.
12. The compound of claim 7 , wherein R 8 is selected from an unsubstituted phenyl, unsubstituted 5-6 membered heteroaryl with 1-3 heteroatoms independently selected from N and O, an unsubstituted 5 membered heteroaryl with 1-4 heteroatoms selected from N, an unsubstituted 4-6 membered heterocycloalkyl with 1-2 heteroatoms independently selected from N and O, a substituted 5-6 membered heteroaryl with 1-3 heteroatoms independently selected from N and O, a substituted 5 membered heteroaryl with 1-4 heteroatoms selected from N, a substituted 4-6 membered heterocycloalkyl with 1-2 heteroatoms independently selected from N and O, and a tetrahydro-1H-oxazolo[3,4-a]pyrazin-3(5H)-one, wherein the substituted 5-6 membered heteroaryl with 1-3 heteroatoms independently selected from N and O, the substituted 5 membered heteroaryl with 1-4 heteroatoms selected from N and substituted 4-6 membered heterocycloalkyl of R 8 are substituted with 1-3 substituents independently selected from C 1 -C 6 alkyl and —C(═O)OR 4 .
13. The compound of claim 12 , wherein R 8 is selected from pyridinyl, pyrazolyl tetrahydrofuranyl, tetrahydropyranyl, pyrrolidinyl, piperidinyl, pyrimidinyl and oxadiazolyl, each of which is unsubstituted or substituted with 1-2 substituents independently selected from —CH 3 and —C(═O)OC(CH 3 ) 3 .
14. The compound of claim 7 , wherein R 3 is selected from azetidinyl, azetidin-1-yl, azetidin-2-yl, azetidin-3-yl, pyrrolidinyl, pyrrolidin-1-yl, pyrrolidin-2-yl, pyrrolidin-3-yl, piperidinyl, piperidin-1-yl, piperidin-2-yl, piperidin-3-yl, piperidin-4-yl, tetrahydropyranyl, tetrahydropyran-2-yl, tetrahydropyran-3-yl, tetrahydropyran-4-yl, tetrahydrofuranyl, tetrahydrofuran-2-yl, tetrahydrofuran-3-yl, oxetanyl, oxetan-2-yl, oxetan-3-yl, morpholinyl, morpholin-2-yl, morpholin-3-yl and morpholin-4-yl, each of which is unsubstituted or each of which is substituted with 1-4 substituents independently selected from —CH 3 , —CH 2 CH 3 , F, —CF 3 , —CN, —OH, —C(═O)CF 3 , —OCH 3 , —C(═O)OCH 3 , —C(═O)CH 3 , —C(═O)OCH 2 CH 2 OCH 3 , —C═(O)OCH 2 CH 3 , —C(═O)OC(CH 3 ) 3 , —CH 2 OH, —CH 2 OCH 3 , —CH 2 CH 2 CH 2 OCH 3 , —NHC(═O)OC(CH 3 ) 3 , —NHC(═O)OCH 3 , —C(═O)N(CH 3 ) 2 , —S(═O) 2 CH 3 , —S(═O) 2 CH 2 CH 3 , —S(═O) 2 CH 2 CH 2 CH 3 , —S(═O) 2 CH 2 CH 2 CH 2 CH 3 , —S(═O) 2 CH(CH 3 ) 2 , —S(═O) 2 CH 2 CH 2 C(═O)OCH 3 , —S(═O) 2 CH 2 CH 2 OCH 3 , —S(═O) 2 CHF 2 , —S(═O) 2 NH 2 , —S(═O) 2 NHC(═O)OC(CH 3 ) 3 , a C 1 alkyl bridge, —C(═O)OR 5 , —S(═O) 2 R 8 , —(CR 9 2 ) n R 8 and R 8 .
15. The compound of claim 14 , wherein:
R 3 is azetidinyl substituted with —C(═O)OCH 3 .
16. The compound of claim 14 , wherein m is 1 and R 20 is selected from H, halo, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, deuterium, deuterated C 1 -C 6 alkyl, —CN, —(CR 9 2 ) n OR 4 , —C(O) R 4 , —(CR 9 2 ) n C(═O)OR 4 , R 10 , —(CR 9 2 ) n R 10 , —(CR 9 2 ) n O(CR 9 2 ) n R 7 , —(CR 9 2 ) n C(═O)R 4 , —OR 4 , and —(CR 9 2 ) n CN.
17. The compound of claim 16 , wherein m is 1 R 20 is selected from H, -D, —F, —CH 3 , —CF 3 , —CN, —CH 2 CH 2 CH 2 CN, —CH 2 CH 2 CN, —OCH3, —CH 2 CH 2 C(═O)OC(CH 3 ) 3 , —C(═O)CH 3 , —CH 2 CH 2 C(═O)CH 3 , —CD 3 , —CH 2 OH, —CH 2 CH 2 C(CH 3 ) 2 OH, —CH 2 C(CH 3 ) 2 OH, —C(CH 3 ) 2 OH, —CH 2 OCH 3 , —CH 2 OCH 2 CF 3 , —CH 2 OCH 2 CHF 2 , and —CH 2 OCH 2 CH 2 F.
18. The compound of claim 17 , wherein m is 1 and R 20 is —CH 3 .
19. The compound of claim 17 , wherein m is 1 and R 20 is H.
20. The compound of claim 16 , wherein:
R 10 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 C 1 -C 6 alkyl, —(CR 9 2 ) n OR 4 , —(C(R 9 ) 2 ) n C(O)OR 4 , —(C(R 9 ) 2 ) n R 5 and —S(═O) 2 R 4 ,
or R 10 is selected from a oxazolidin-2-one and a pyrrolidin-2-one.
21. The compound of claim 20 , wherein:
R 10 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 —CH 3 , —CH 2 CH 2 OH, —CH 2 C(O)OH, —CH 2 CH 2 OH, —CH 2 C(CH 3 ) 2 OH, —S(O) 2 CH 3 and —CH 2 CH 2 —R 5 .
22. The compound of claim 15 , wherein m is 4 and R 20 is deuterium.
23. The compound of claim 1 selected from:
N-{5-[3-(azetidin-1-yl)-1,2,4-oxadiazol-5-yl]-2-methylphenyl}imidazo[1,2-a]pyridine-3-carboxamide;
N-{5-[3-(3,3-difluoroazetidin-1-yl)-1,2,4-oxadiazol-5-yl]-2-methylphenyl}imidazo[1,2-a]pyridine-3-carboxamide;
N-(2-methyl-5-{3-[(1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl]-1,2,4-oxadiazol-5-yl}phenyl)imidazo[1,2-a]pyridine-3-carboxamide;
N-{5-[3-(4,4-difluoropiperidin-1-yl)-1,2,4-oxadiazol-5-yl]-2-methylphenyl}imidazo[1,2-a]pyridine-3-carboxamide;
N-{5-[3-(4-fluoropiperidin-1-yl)-1,2,4-oxadiazol-5-yl]-2-methylphenyl}imidazo[1,2-a]pyridine-3-carboxamide;
N-(5-{5-[3-hydroxy-3-(trifluoromethyl)azetidin-1-yl]-1,2,4-oxadiazol-3-yl}-2-methylphenyl)-6-methylimidazo[1,2-a]pyridine-3-carboxamide;
N-{2-methyl-5-[5-(oxolan-3-yl)-1,2,4-oxadiazol-3-yl]phenyl}imidazo[1,2-a]pyridine-3-carboxamide;
N-{2-methyl-5-[5-(oxan-2-yl)-1,2,4-oxadiazol-3-yl]phenyl}imidazo[1,2-a]pyridine-3-carboxamide;
methyl 2-[3-(3-{imidazo[1,2-a]pyridine-3-amido}-4-methylphenyl)-1,2,4-oxadiazol-5-yl]piperidine-1-carboxylate;
N-{5-[5-(5,5-difluorooxan-2-yl)-1,2,4-oxadiazol-3-yl]-2-methylphenyl}imidazo[1,2-a]pyridine-3-carboxamide;
N-(5-{5-[(2S)-5,5-difluorooxan-2-yl]-1,2,4-oxadiazol-3-yl}-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide;
N-(5-{5-[(2R)-5,5-difluorooxan-2-yl]-1,2,4-oxadiazol-3-yl}-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide;
tert-butyl 3-[3-(3-{imidazo[1,2-a]pyridine-3-amido}-4-methylphenyl)-1,2,4-oxadiazol-5-yl]azetidine-1-carboxylate;
N-{5-[5-(1-methanesulfonylazetidin-3-yl)-1,2,4-oxadiazol-3-yl]-2-methylphenyl}imidazo[1,2-a]pyridine-3-carboxamide;
methyl 3-[3-(3-{imidazo[1,2-a]pyridine-3-amido}-4-methylphenyl)-1,2,4-oxadiazol-5-yl]azetidine-1-carboxylate;
N-(2-methyl-5-{5-[1-(propane-1-sulfonyl)azetidin-3-yl]-1,2,4-oxadiazol-3-yl}phenyl)imidazo[1,2-a]pyridine-3-carboxamide;
N-{2-methyl-5-[5-(oxan-4-ylmethyl)-1,2,4-oxadiazol-3-yl]phenyl}imidazo[1,2-a]pyridine-3-carboxamide;
N-{2-methyl-5-[5-(oxolan-2-ylmethyl)-1,2,4-oxadiazol-3-yl]phenyl}imidazo[1,2-a]pyridine-3-carboxamide;
N-(5-{5-[1-(ethanesulfonyl)azetidin-3-yl]-1,2,4-oxadiazol-3-yl}-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide;
N-(2-methyl-5-{5-[3-(morpholin-4-yl)propyl]-1,2,4-oxadiazol-3-yl}phenyl)imidazo[1,2-a]pyridine-3-carboxamide;
N-(5-{5-[(3,3-difluoroazetidin-1-yl)methyl]-1,2,4-oxadiazol-3-yl}-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide;
N-{2-methyl-5-[5-(morpholin-4-ylmethyl)-1,2,4-oxadiazol-3-yl]phenyl}imidazo[1,2-a]pyridine-3-carboxamide;
N-{2-methyl-5-[5-(1-sulfamoylazetidin-3-yl)-1,2,4-oxadiazol-3-yl]phenyl}imidazo[1,2-a]pyridine-3-carboxamide;
tert-butyl (2S)-2-[3-(3-{imidazo[1,2-a]pyridine-3-amido}-4-methylphenyl)-1,2,4-oxadiazol-5-yl]azetidine-1-carboxylate;
N-(5-{5-[(2S)-1-methanesulfonylazetidin-2-yl]-1,2,4-oxadiazol-3-yl}-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide;
methyl N-{3-[3-(3-{imidazo[1,2-a]pyridine-3-amido}-4-methylphenyl)-1,2,4-oxadiazol-5-yl}oxetan-3-yl]carbamate;
tert-butyl 3-[3-(4-fluoro-3-{imidazo[1,2-a]pyridine-3-amido}phenyl)-1,2,4-oxadiazol-5-yl]azetidine-1-carboxylate;
N-(5-{5-[1-(ethanesulfonyl)azetidin-3-yl]-1,2,4-oxadiazol-3-yl}-2-fluorophenyl)imidazo[1,2-a]pyridine-3-carboxamide;
N-(5-{5-[(3,3-difluoropyrrolidin-1-yl)methyl]-1,2,4-oxadiazol-3-yl}-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide;
N-(5-{5-[(4,4-difluoropiperidin-1-yl)methyl]-1,2,4-oxadiazol-3-yl}-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide;
N-(5-{5-[1-(butane-1-sulfonyl)azetidin-3-yl]-1,2,4-oxadiazol-3-yl}-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide;
N-(5-{5-[(2S)-4,4-difluoro-1-methanesulfonylpyrrolidin-2-yl]-1,2,4-oxadiazol-3-yl}-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide;
methyl 4-[3-(3-{imidazo[1,2-a]pyridine-3-amido}-4-methylphenyl)-1,2,4-oxadiazol-5-yl]piperidine-1-carboxylate;
N-{5-[5-(1-methanesulfonylpiperidin-4-yl)-1,2,4-oxadiazol-3-yl]-2-methylphenyl}imidazo[1,2-a]pyridine-3-carboxamide;
N-{5-[5-(4-methanesulfonylmorpholin-2-yl)-1,2,4-oxadiazol-3-yl]-2-methylphenyl}imidazo[1,2-a]pyridine-3-carboxamide;
N-(5-{5-[(2S)-1-methanesulfonylpyrrolidin-2-yl]-1,2,4-oxadiazol-3-yl}-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide;
N-(5-{5-[(2R)-4-methanesulfonylmorpholin-2-yl]-1,2,4-oxadiazol-3-yl}-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide;
N-[5-(5-{[(3S)-1-methanesulfonylpyrrolidin-3-yl]methyl}-1,2,4-oxadiazol-3-yl)-2-methylphenyl]imidazo[1,2-a]pyridine-3-carboxamide;
N-(5-{5-[(3R)-1-methanesulfonylpiperidin-3-yl]-1,2,4-oxadiazol-3-yl}-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide;
methyl (2S)-2-{[3-(3-{imidazo[1,2-a]pyridine-3-amido}-4-methylphenyl)-1,2,4-oxadiazol-5-yl]methyl}pyrrolidine-1-carboxylate;
N-[5-(5-{[(2S)-1-methanesulfonylpyrrolidin-2-yl]methyl]-1,2,4-oxadiazol-3-yl)-2-methylphenyl}imidazo[1,2-a]pyridine-3-carboxamide;
N-(2-methyl-5-{5-[(3,3,4,4-tetrafluoropyrrolidin-1-yl)methyl]-1,2,4-oxadiazol-3-yl}phenyl)imidazo[1,2-a]pyridine-3-carboxamide;
N-(5-{5-[1-(difluoromethane)sulfonylazetidin-3-yl]-1,2,4-oxadiazol-3-yl}-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide;
N-{2-methyl-5-[5-(oxan-2-ylmethyl)-1,2,4-oxadiazol-3-yl]phenyl}imidazo[1,2-a]pyridine-3-carboxamide;
N-(5-[5-[(3,3-difluoropyrrolidin-1-yl)methyl]-1,2,4-oxadiazol-3-yl]-2-fluorophenyl)imidazo[1,2-a]pyridine-3-carboxamide;
N-(5-[5-[(4,4-difluoropiperidin-1-yl)methyl]-1,2,4-oxadiazol-3-yl]-2-fluorophenyl)imidazo[1,2-a]pyridine-3-carboxamide;
N-(2-methyl-5-{5-[(2S)-1-(propane-2-sulfonyl)azetidin-2-yl]-1,2,4-oxadiazol-3-yl}phenyl)imidazo[1,2-a]pyridine-3-carboxamide;
methyl 3-[3-(4-methyl-3-{pyrazolo[1,5-a]pyridine-3-amido}phenyl)-1,2,4-oxadiazol-5-yl]azetidine-1-carboxylate;
N-{2-methyl-5-[5-(oxan-3-ylmethyl)-1,2,4-oxadiazol-3-yl]phenyl}imidazo[1,2-a]pyridine-3-carboxamide;
N-(5-{5-[(1S)-1-(3,3-difluoroazetidin-1-yl)ethyl]-1,2,4-oxadiazol-3-yl}-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide;
N-(5-{5-[(1S)-1-(3,3-difluoropyrrolidin-1-yl)ethyl]-1,2,4-oxadiazol-3-yl}-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide;
methyl 3-(3-{4-methyl-3-[6-(trifluoromethyl)imidazo[1,2-a]pyridine-3-amido]phenyl}-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate;
ethyl 3-[3-(3-{imidazo[1,2-a]pyridine-3-amido}-4-methylphenyl)-1,2,4-oxadiazol-5-yl]azetidine-1-carboxylate;
methyl 3-[3-(3-{7-fluoroimidazo[1,2-a]pyridine-3-amido}-4-methylphenyl)-1,2,4-oxadiazol-5-yl]azetidine-1-carboxylate;
methyl 3-[3-(3-{6-fluoroimidazo[1,2-a]pyridine-3-amido}-4-methylphenyl)-1,2,4-oxadiazol-5-yl]azetidine-1-carboxylate;
methyl 3-(3-{4-methyl-3-[7-(1-methyl-1H-pyrazol-3-yl)imidazo[1,2-a]pyridine-3-amido]phenyl}-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate;
methyl 3-(3-{4-methyl-3-[7-(trifluoromethyl)imidazo[1,2-a]pyridine-3-amido]phenyl}-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate;
N-{5-[5-(1-methanesulfonyl-3-methylazetidin-3-yl)-1,2,4-oxadiazol-3-yl]-2-methylphenyl}imidazo[1,2-a]pyridine-3-carboxamide;
methyl 3-(3-{3-[6-(3-cyanopropyl)imidazo[1,2-a]pyridine-3-amido]-4-methylphenyl}-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate;
methyl 3-[3-(3-{6-methoxyimidazo[1,2-a]pyridine-3-amido}-4-methylphenyl)-1,2,4-oxadiazol-5-yl]azetidine-1-carboxylate;
methyl 3-[3-(4-methyl-3-{7-methylimidazo[1,2-a]pyridine-3-amido}phenyl)-1,2,4-oxadiazol-5-yl]azetidine-1-carboxylate;
methyl 3-[3-(4-methyl-3-{6-methylimidazo[1,2-a]pyridine-3-amido}phenyl)-1,2,4-oxadiazol-5-yl]azetidine-1-carboxylate;
methyl 3-{3-[4-methyl-3-(7-{1-[2-(morpholin-4-yl)ethyl]-1H-pyrazol-4-yl}imidazo[1,2-a]pyridine-3-amido)phenyl]-1,2,4-oxadiazol-5-yl}azetidine-1-carboxylate;
methyl 3-(3-{3-[6-(2-cyanoethyl)imidazo[1,2-a]pyridine-3-amido]-4-methylphenyl}-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate;
methyl 3-(3-{4-methyl-3-[6-(3-oxobutyl)imidazo[1,2-a]pyridine-3-amido]phenyl}-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate;
methyl 3-[3-(4-methyl-3-{6-[2-(morpholin-4-yl)ethyl]imidazo[1,2-a]pyridine-3-amido}phenyl)-1,2,4-oxadiazol-5-yl]azetidine-1-carboxylate;
methyl 3-(3-{3-[6-(3-hydroxy-3-methylbutyl)imidazo[1,2-a]pyridine-3-amido]-4-methylphenyl}-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate;
methyl 3-(3-{4-methyl-3-[7-(1H-pyrazol-3-yl)imidazo[1,2-a]pyridine-3-amido]phenyl}-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate;
N-(2-methyl-5-{[5-(oxan-4-yl)-1,2,4-oxadiazol-3-yl]amino}-phenyl)imidazo[1,2-a]pyridine-3-carboxamide;
N-(2-methyl-5-{[5-(oxan-2-yl)-1,2,4-oxadiazol-3-yl]amino}-phenyl)imidazo[1,2-a]pyridine-3-carboxamide;
N-[2-methyl-5-({5-[(2R)-oxolan-2-yl]-1,2,4-oxadiazol-3-yl}amino)phenyl]imidazo[1,2-a]pyridine-3-carboxamide;
N-[2-methyl-5-({5-[(2S)-oxolan-2-yl]-1,2,4-oxadiazol-3-yl}amino)phenyl]imidazo[1,2-a]pyridine-3-carboxamide;
methyl 3-(3-{4-methyl-3-[7-(3-oxobutyl)imidazo[1,2-a]pyridine-3-amido]phenyl}-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate;
methyl 3-(3-{3-[7-(3-hydroxy-3-methylbutyl)imidazo[1,2-a]pyridine-3-amido]-4-methylphenyl}-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate;
N-{2-methyl-5-[3-(morpholin-4-yl)-1,2,4-oxadiazol-5-yl]phenyl}imidazo[1,2-a]pyridine-3-carboxamide;
methyl 3-[3-(4-methyl-3-{5,6,7,8-tetradeuteroimidazo[1,2-a]pyridine-3-amido}phenyl)-1,2,4-oxadiazol-5-yl]azetidine-1-carboxylate;
N-{5-[5-(azetidin-1-yl)-1,2,4-oxadiazol-3-yl]-2-methylphenyl}imidazo[1,2-a]pyridine-3-carboxamide;
N-{5-[5-(3,3-difluoroazetidin-1-yl)-1,2,4-oxadiazol-3-yl]-2-methylphenyl}imidazo[1,2-a]pyridine-3-carboxamide;
methyl 3-[3-(5-{imidazo[1,2-a]pyridine-3-amido}-2,4-dimethylphenyl)-1,2,4-oxadiazol-5-yl]azetidine-1-carboxylate;
methyl 3-[3-(4-methyl-3-{7-methylimidazo[1,2-a]pyridine-3-amido}-phenyl)-1,2,4-oxadiazol-5-yl]azetidine-1-carboxylate;
7-fluoro-N-{2-methyl-5-[5-(oxan-4-ylamino)-1,2,4-oxadiazol-3-yl]phenyl}imidazo[1,2-a]pyridine-3-carboxamide;
6-methyl-N-{2-methyl-5-[5-(oxan-4-ylamino)-1,2,4-oxadiazol-3-yl]phenyl}imidazo[1,2-a]pyridine-3-carboxamide;
methyl 3-(3-[4-methyl-3-[6-(morpholin-4-yl)imidazo[1,2-a]pyridine-3-amido]phenyl]-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate;
methyl 3-[3-(4-methyl-3-{6-[(2,2,2-trifluoroethoxy)methyl]imidazo[1,2-a]pyridine-3-amido}phenyl)-1,2,4-oxadiazol-5-yl]azetidine-1-carboxylate;
N-(5-{5-[3-hydroxy-3-(trifluoromethyl)azetidin-1-yl]-1,2,4-oxadiazol-3-yl}-2-methylphenyl)-6-methylimidazo[1,2-a]pyridine-3-carboxamide;
N-{5-[5-(3,3-difluoroazetidin-1-yl)-1,2,4-oxadiazol-3-yl]-2-methylphenyl}-7-methylimidazo[1,2-a]pyridine-3-carboxamide;
N-{5-[5-(3,3-difluoroazetidin-1-yl)-1,2,4-oxadiazol-3-yl]-2-methylphenyl}-7-fluoroimidazo[1,2-a]pyridine-3-carboxamide;
N-{5-[5-[3-hydroxy-3-methylazetidin-1-yl)-1,2,4-oxadiazol-3-yl]-2-methylphenyl}-7-methylimidazo[1,2-a]pyridine-3-carboxamide;
N-{5-[5-(4,4-difluoropiperidin-1-yl)-1,2,4-oxadiazol-3-yl]-2-methylphenyl}-7-methylimidazo[1,2-a]pyridine-3-carboxamide;
N-{5-[5-(4-fluoropiperidin-1-yl)-1,2,4-oxadiazol-3-yl]-2-methylphenyl}-7-methylimidazo[1,2-a]pyridine-3-carboxamide;
7-methyl-N-{2-methyl-5-[5-(morpholin-4-yl)-1,2,4-oxadiazol-3-yl]phenyl}imidazo[1,2-a]pyridine-3-carboxamide;
N-{5-[5-(3,3-difluoropyrrolidin-1-yl)-1,2,4-oxadiazol-3-yl]-2-methylphenyl}-7-methylimidazo[1,2-a]pyridine-3-carboxamide;
7-methyl-N-(2-methyl-5-{5-[3-(trifluoromethyl)piperidin-1-yl]-1,2,4-oxadiazol-3-yl}phenyl)imidazo[1,2-a]pyridine-3-carboxamide;
N-(2-methyl-5-{3-[(1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl]-1,2,4-oxadiazol-5-yl}phenyl)imidazo[1,2-a]pyridine-3-carboxamide;
methyl 3-[3-(3-{6-[(2,2-difluoroethoxy)methyl]imidazo[1,2-a]pyridine-3-amido}-4-methylphenyl)-1,2,4-oxadiazol-5-yl]azetidine-1-carboxylate;
methyl 3-[3-(3-{6-[(2-fluoroethoxy)methyl]imidazo[1,2-a]pyridine-3-amido}-4-methylphenyl)-1,2,4-oxadiazol-5-yl]azetidine-1-carboxylate;
methyl 3-[3-(3-{7-hydrogenioimidazo[1,2-a]pyridine-3-amido}-4-methylphenyl)-1,2,4-oxadiazol-5-yl]azetidine-1-carboxylate;
methyl 3-[3-(3-{6-hydrogenioimidazo[1,2-a]pyridine-3-amido}-4-methylphenyl)-1,2,4-oxadiazol-5-yl]azetidine-1-carboxylate, and
N-(5-{5-[(3-cyanoazetidin-1-yl)methyl]-1,2,4-oxadiazol-3-yl}-2-methylphenyl)-6-(2,4-dimethyl-1,3-thiazol-5-yl)imidazo[1,2-a]pyridine-3-c arboxamide.
24. The compound of claim 1 selected from methyl 3-[3-(4-methyl-3-{5,6,7,8-tetradeuteroimidazo[1,2-a]pyridine-3-amido}phenyl)-1,2,4-oxadiazol-5-yl]azetidine-1-carboxylate.
25. A pharmaceutical composition comprising a therapeutically effective amount a compound of claim 1 and a pharmaceutically acceptable carrier.
26. 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 PDGFFRβ and wherein the disease is selected from irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), pulmonary arterial hypertension (PAH), primary pulmonary hypertension (PPH), pulmonary fibrosis, hepatic fibrosis, cardiac fibrosis, scleroderma, uticaria, dermatosis, type I diabetes or type II diabetes.