Bicyclic heterocyclyl derivatives as IRAK4 inhibitors
The present invention provides bicyclic heterocyclyl kinase enzyme inhibitor compounds of formula (I), which are therapeutically useful as kinase inhibitors, particularly IRAK4 inhibitors, wherein A, Y, Z, X 1 , X 2 , R 1 , R 3 , ‘m’, ‘n’ and ‘p’ have the meanings given in the specification and pharmaceutically acceptable salt or stereoisomer thereof that are useful in the treatment and prevention of diseases or disorder, in particular their use in diseases or disorder mediated by kinase enzyme, particularly IRAK4 enzyme. The present invention also provides pharmaceutical composition comprising at least one of the compounds of compound of formula (I) together with a pharmaceutically acceptable carrier, diluent or excipient therefor.
1. A compound of formula (I):
or a pharmaceutically acceptable salt or a stereoisomer thereof;
wherein
X 1 and X 3 independently are CH or N; X 2 is CR 2 or N; provided one and not more than one of X 1 , X 2 or X 3 is N;
A is O or S;
Y is —CH 2 — or O;
Z is aryl or heterocyclyl;
R 1 , at each occurrence, is independently halo or optionally substituted heterocyclyl; wherein the substituent is alkyl, alkoxy, aminoalkyl, halo, hydroxyl, hydroxyalkyl or —NR a R b ;
R 2 is hydrogen, optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted heterocyclyl or —NR a R b ; wherein the substituent is alkyl, amino, halo or hydroxyl;
R 3 , at each occurrence, is alkyl or hydroxyl;
R a and R b are independently hydrogen, alkyl, acyl or heterocyclyl;
‘m’ and ‘n’ are independently 0, 1 or 2;
‘p’ is 0 or 1.
2. The compound of claim 1 , wherein
A is O or S;
Y is —CH 2 — or O;
Z is aryl or heterocyclyl;
R 1 , at each occurrence, is independently halo or optionally substituted heterocyclyl, wherein the substituent is alkyl, aminoalkyl, halo, or NR a R b ; where R a and R b are independently hydrogen, alkyl, or heterocyclyl;
R 2 is hydrogen, cycloalkyl, heterocyclyl or NR a R b ;
m is 0; and
n is 1.
3. The compound of claim 1 , wherein
A is O or S;
Y is —CH 2 — or O;
Z is aryl or heterocyclyl;
R 1 , at each occurrence, is independently halo or optionally substituted heterocyclyl; wherein the substituent is alkyl, alkoxy, aminoalkyl, halo, hydroxyl or NR a R b ; where R a and R b are independently hydrogen, alkyl, or heterocyclyl;
R 2 is hydrogen, cycloalkyl, optionally substituted heterocyclyl or NR a R b , where the substituent is selected from amino, halo or hydroxyl;
‘m’ and ‘n’ are independently 0, 1 or 2; and
‘p’ is 0 or 1.
4. The compound of claim 1 , or a pharmaceutically acceptable salt or a stereoisomer thereof, wherein the group
wherein R 2 is as defined in claim 1 .
5. The compound of claim 1 , wherein Z is aryl or 5- or 6-membered heterocyclyl.
6. The compound of claim 1 , wherein Z is an optionally substituted heterocyclyl selected from phenyl, furanyl, thienyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, 1H-tetrazolyl, oxadiazolyl, triazolyl, pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl, azetidinyl, oxetanyl, imidazolidinyl, pyrrolidinyl, oxazolidinyl, thiazolidinyl, pyrazolidinyl, tetrahydrofuranyl, piperidinyl, piperazinyl, tetrahydropyranyl, morpholinyl, thiomorpholinyl, 1,4-dioxanyl, dioxidothiomorpholinyl, oxapiperazinyl, oxapiperidinyl, tetrahydrofuryl, tetrahydropyranyl, tetrahydrothiophenyl, dihydropyranyl or azabicyclo[3.2.1]octanyl; each of which is optionally substituted with alkyl, alkoxy, halo, hydroxyl, hydroxyalkyl or —NR a R b ; R a and R b are independently hydrogen, alkyl or acyl.
7. The compound of claim 1 represented by formula (IA):
or a pharmaceutically acceptable salt or a stereoisomer thereof;
wherein A, Y, R 1 , R 2 , R 3 , ‘m’, ‘p’ and ‘n’ are same as defined in claim 1 .
8. The compound of claim 7 , wherein
A is O or S;
Y is —CH 2 — or O;
R 1 , at each occurrence, is independently halo or optionally substituted heterocyclyl, wherein the substituent is alkyl, aminoalkyl, halo, or NR a R b ; where R a and R b are independently hydrogen, alkyl, or heterocyclyl;
R 2 is hydrogen, cycloalkyl, heterocyclyl or NR a R b ;
m is 0; and
n is 1.
9. The compound of claim 7 , wherein
A is O or S;
Y is —CH 2 — or O;
R 1 , at each occurrence, is independently halo or optionally substituted heterocyclyl; wherein the substituent is alkyl, alkoxy, aminoalkyl, halo, hydroxyl or NR a R b ; where R a and R b are independently hydrogen, alkyl, or heterocyclyl;
R 2 is hydrogen, cycloalkyl, optionally substituted heterocyclyl or NR a R b , where the substituent is selected from amino, halo or hydroxyl; and
‘m’ and ‘n’ are independently 0, 1 or 2.
10. The compound of claim 1 , represented by (TB):
or a pharmaceutically acceptable salt or a stereoisomer thereof;
wherein A, Y, R 1 , R 2 and ‘n’ are same as defined in claim 1 .
11. The compound of claim 10 , wherein
A is O or S;
Y is —CH 2 — or O;
R 1 , at each occurrence, is independently halo or optionally substituted heterocyclyl, wherein the substituent is alkyl, aminoalkyl, halo, or NR a R b ; where R a and R b are independently hydrogen, alkyl, or heterocyclyl;
R 2 is hydrogen, cycloalkyl, heterocyclyl or NR a R b ; and
n is 1.
12. The compound of claim 10 , wherein
A is O or S;
Y is —CH 2 — or O;
R 1 , at each occurrence, is independently halo or optionally substituted heterocyclyl; wherein the substituent is alkyl, alkoxy, aminoalkyl, halo, hydroxyl or NR a R b ; where R a and R b are independently hydrogen, alkyl, or heterocyclyl; and
R 2 is hydrogen, cycloalkyl, optionally substituted heterocyclyl or NR a R b , where the substituent is selected from amino, halo or hydroxyl.
13. The compound of formula (I) according to claim 1 , is a compound of formula (IC)
or a pharmaceutically acceptable salt or a stereoisomer thereof;
wherein A, Y, R 1 , R 2 and ‘n’ are same as defined in claim 1 .
14. The compound of claim 1 , wherein R 1 is optionally substituted heterocyclyl; wherein the substituent is alkyl, alkoxy, aminoalkyl, halo, hydroxyl, hydroxyalkyl or —NR a R b ; R a and R b are independently hydrogen or acyl.
15. The compound of claim 2 , wherein R 1 is optionally substituted heterocyclyl; wherein the substituent is alkyl, alkoxy, aminoalkyl, halo, hydroxyl, hydroxyalkyl or —NR a R b ; R a and R b are independently hydrogen or acyl.
16. The compound of claim 3 , wherein R 1 is optionally substituted heterocyclyl; wherein the substituent is alkyl, alkoxy, aminoalkyl, halo, hydroxyl, hydroxyalkyl or —NR a R b ; R a and R b are independently hydrogen or acyl.
17. The compound of claim 8 , wherein R 1 is optionally substituted heterocyclyl; wherein the substituent is alkyl, alkoxy, aminoalkyl, halo, hydroxyl, hydroxyalkyl or —NR a R b ; R a and R b are independently hydrogen or acyl.
18. The compound of claim 9 , wherein R 1 is optionally substituted heterocyclyl; wherein the substituent is alkyl, alkoxy, aminoalkyl, halo, hydroxyl, hydroxyalkyl or —NR a R b ; R a and R b are independently hydrogen or acyl.
19. The compound of claim 11 , wherein R 1 is optionally substituted heterocyclyl; wherein the substituent is alkyl, alkoxy, aminoalkyl, halo, hydroxyl, hydroxyalkyl or —NR a R b ; R a and R b are independently hydrogen or acyl.
20. The compound of claim 12 , wherein R 1 is optionally substituted heterocyclyl; wherein the substituent is alkyl, alkoxy, aminoalkyl, halo, hydroxyl, hydroxyalkyl or —NR a R b ; R a and R b are independently hydrogen or acyl.
21. The compound of claim 1 , wherein R 1 is optionally substituted heterocyclyl; and the substituent is alkyl, aminoalkyl, halo, or NR a R b ; where R a and R b are independently hydrogen, alkyl, or heterocyclyl.
22. The compound of claim 1 , wherein R 1 is optionally substituted heterocyclyl; and the substituent is alkyl, alkoxy, aminoalkyl, halo, hydroxyl or NR a R b ; where R a and R b are independently hydrogen, alkyl, or heterocyclyl.
23. The compound of claim 2 , wherein R 1 is optionally substituted heterocyclyl; and the substituent is alkyl, aminoalkyl, halo, or NR a R b ; where R a and R b are independently hydrogen, alkyl, or heterocyclyl.
24. The compound of claim 3 , wherein R 1 is optionally substituted heterocyclyl; and the substituent is alkyl, alkoxy, aminoalkyl, halo, hydroxyl or NR a R b ; where R a and R b are independently hydrogen, alkyl, or heterocyclyl.
25. The compound of claim 8 , wherein R 1 is optionally substituted heterocyclyl; and the substituent is alkyl, aminoalkyl, halo, or NR a R b ; where R a and R b are independently hydrogen, alkyl, or heterocyclyl.
26. The compound of claim 9 , wherein R 1 is optionally substituted heterocyclyl; and the substituent is alkyl, alkoxy, aminoalkyl, halo, hydroxyl or NR a R b ; where R a and R b are independently hydrogen, alkyl, or heterocyclyl.
27. The compound of claim 11 , wherein R 1 is optionally substituted heterocyclyl; and the substituent is alkyl, aminoalkyl, halo, or NR a R b ; where R a and R b are independently hydrogen, alkyl, or heterocyclyl.
28. The compound of claim 12 , wherein R 1 is optionally substituted heterocyclyl; and the substituent is alkyl, alkoxy, aminoalkyl, halo, hydroxyl or NR a R b ; where R a and R b are independently hydrogen, alkyl, or heterocyclyl.
29. The compound of claim 14 , wherein R 1 is pyridyl, pyrazolyl, pyrrolidinyl or piperidinyl.
30. The compound of claim 16 , wherein R 1 is optionally substituted pyrazolyl, wherein the substituent is alkyl, hydroxyl or —NR a R b .
31. The compound of claim 1 , wherein R 1 is halo.
32. The compound of claim 2 , wherein R 1 is halo.
33. The compound of claim 3 , wherein R 1 is halo.
34. The compound of claim 8 , wherein R 1 is halo.
35. The compound of claim 9 , wherein R 1 is halo.
36. The compound of claim 11 , wherein R 1 is halo.
37. The compound of claim 12 , wherein R 1 is halo.
38. The compound of claim 1 , wherein R 2 is hydrogen, cycloalkyl, heterocyclyl or NR a R b .
39. The compound of claim 1 , wherein R 2 is hydrogen, cycloalkyl, optionally substituted heterocyclyl or NR a R b , where the substituent is selected from amino, halo or hydroxyl.
40. The compound of claim 2 , wherein R 2 is hydrogen, cycloalkyl, heterocyclyl or NR a R b .
41. The compound of claim 3 , wherein R 2 is hydrogen, cycloalkyl, optionally substituted heterocyclyl or NR a R b , where the substituent is selected from amino, halo or hydroxyl.
42. The compound of claim 8 , wherein R 2 is hydrogen, cycloalkyl, heterocyclyl or NR a R b .
43. The compound of claim 9 , wherein R 2 is hydrogen, cycloalkyl, optionally substituted heterocyclyl or NR a R b , where the substituent is selected from amino, halo or hydroxyl.
44. The compound of claim 11 , wherein R 2 is hydrogen, cycloalkyl, heterocyclyl or NR a R b .
45. The compound of claim 12 , wherein R 2 is hydrogen, cycloalkyl, optionally substituted heterocyclyl or NR a R b , where the substituent is selected from amino, halo or hydroxyl.
46. The compound of claim 1 , wherein R 2 is optionally substituted heterocyclyl selected from piperidinyl, pyrrolidinyl, morpholinyl, piperazinyl, azetidinyl, pyrazolyl, furanyl or azabicyclo[3.2.1]octanyl; wherein the substituent is hydroxyl, halo, alkyl or amino.
47. The compound of claim 1 , wherein R 2 is piperidinyl, pyrrolidinyl, morpholinyl, or piperazinyl.
48. The compound of claim 3 , wherein R 2 is piperidinyl, pyrrolidinyl, morpholinyl, or piperazinyl.
49. The compound of claim 1 , wherein R 2 is hydrogen.
50. The compound of claim 2 , wherein R 2 is hydrogen.
51. The compound of claim 3 , wherein R 2 is hydrogen.
52. The compound of claim 42 , wherein R 2 is hydrogen.
53. The compound of claim 43 , wherein R 2 is hydrogen.
54. The compound of claim 44 , wherein R 2 is hydrogen.
55. The compound of claim 45 , wherein R 2 is hydrogen.
56. The compound of claim 1 , wherein R 2 is cycloalkyl.
57. The compound of claim 2 , wherein R 2 is cycloalkyl.
58. The compound of claim 3 , wherein R 2 is cycloalkyl.
59. The compound of claim 42 , wherein R 2 is cycloalkyl.
60. The compound of claim 43 , wherein R 2 is cycloalkyl.
61. The compound of claim 44 , wherein R 2 is cycloalkyl.
62. The compound of claim 45 , wherein R 2 is cycloalkyl.
63. The compound of claim 56 , wherein R 2 is cyclopropyl.
64. The compound of claim 1 , wherein R 3 is alkyl.
65. The compound of claim 3 , wherein R 3 is alkyl.
66. The compound of claim 9 , wherein R 3 is alkyl.
67. The compound of claim 12 , wherein R 3 is alkyl.
68. The compound of claim 1 , wherein m is O and p is 1.
69. The compound of claim 1 , wherein m is O or 2, and p is O or 1.
70. The compound of claim 2 , wherein m is O and p is 1.
71. The compound of claim 3 , wherein m is O or 2, and p is O or 1.
72. The compound of claim 8 , wherein m is O and p is 1.
73. The compound of claim 9 , wherein m is O or 2, and p is O or 1.
74. The compound of claim 11 , wherein m is O and p is 1.
75. The compound of claim 12 , wherein m is O or 2, and p is O or 1.
76. A compound is selected from:
Example No
IUPAC name
1.
6′-amino-N-(2-morpholinooxazolo[4,5-b]pyridin-6-yl)-[2,3′-bipyridine]-6-
carboxamide;
2.
6′-amino-N-(5-cyclopropyl-2-morpholinooxazolo[4,5-b]pyridin-6-yl)-[2,3′-
bipyridine]-6-carboxamide hydrochloride;
3.
N-(5-cyclopropyl-2-morpholinooxazolo[4,5-b]pyridin-6-yl)-2-(2-methylpyridin-4-
yl)oxazole-4-carboxamide hydrochloride;
4.
N-(2,5-di(piperidin-1-yl)oxazolo[4,5-b]pyridin-6-yl)-6-(1H-pyrazol-4-yl)picolinamide
hydrochloride;
5.
N-(2,5-di(piperidin-1-yl)oxazolo[4,5-b]pyridin-6-yl)-2-(2-methylpyridin-4-
yl)oxazole-4-carboxamide;
6.
N-(2-morpholino-5-(piperidin-1-yl)oxazolo[4,5-b]pyridin-6-yl)-6-(1H-pyrazol-4-
yl)picolinamide;
7.
2-(2-methylpyridin-4-yl)-N-(2-morpholino-5-(piperidin-1-yl)oxazolo[4,5-b]pyridin-6-
yl)oxazole-4-carboxamide;
8.
6-chloro-N-(2-morpholino-5-(piperidin-1-yl)oxazolo[4,5-b]pyridin-6-yl)picolinamide;
9.
N-(2,5-di(piperidin-1-yl)oxazolo[4,5-b]pyridin-6-yl)-6-(1-methyl-1H-pyrazol-4-
yl)picolinamide;
10.
2-(2-chloropyridin-4-yl)-N-(2,5-di(piperidin-1-yl)oxazolo[4,5-b]pyridin-6-yl)oxazole-
4-carboxamide;
11.
(S)-2-(2-methylpyridin-4-yl)-N-(2-morpholino-5-(pyrrolidin-3-ylamino)oxazolo[4,5-
b]pyridin-6-yl)oxazole-4-carboxamide;
12.
6′-amino-N-(2-morpholinooxazolo[5,4-b]pyridin-5-yl)-[2,3′-bipyridine]-6-
carboxamide;
13.
6′-amino-N-(2-morpholinothiazolo[4,5-c]pyridin-6-yl)-[2,3′-bipyridine]-6-
carboxamide;
14.
6′-amino-N-(2-morpholinothiazolo[5,4-b]pyridin-5-yl)-[2,3′-bipyridine]-6-
carboxamide;
15.
2-(2-methylpyridin-4-yl)-N-(2-morpholinothiazolo[4,5-b]pyridin-6-yl)oxazole-4-
carboxamide;
16.
6′-amino-N-(2-morpholinothiazolo[4,5-b]pyridin-6-yl)-[2,3′-bipyridine]-6-
carboxamide;
17.
N-(2-morpholinothiazolo[4,5-b]pyridin-6-yl)-6-(1H-pyrazol-4-yl)picolinamide;
18.
3-(4-(aminomethyl)piperidin-1-yl)-5-fluoro-N-(2-morpholinothiazolo[4,5-b]pyridin-
6-yl)benzamide;
19.
2-(4-(aminomethyl)piperidin-1-yl)-5-fluoro-N-(2-morpholinothiazolo[4,5-b]pyridin-
6-yl)benzamide;
20.
2-(2-methylpyridin-4-yl)-N-(2-morpholino-5-(piperidin-1-yl)thiazolo[4,5-b]pyridin-6-
yl)oxazole-4-carboxamide;
21.
N-(2-morpholino-5-(piperidin-1-yl)thiazolo[4,5-b]pyridin-6-yl)-6-(1H-pyrazol-4-
yl)picolinamide;
22.
N-(2,5-di(piperidin-1-yl)thiazolo[4,5-b]pyridin-6-yl)-6-(1H-pyrazol-4-
yl)picolinamide;
23.
N-(2,5-di(piperidin-1-yl)thiazolo[4,5-b]pyridin-6-yl)-2-(2-methylpyridin-4-
yl)oxazole-4-carboxamide;
24.
N-(2,5-dimorpholinooxazolo[4,5-b]pyridin-6-yl)-2-(2-methylpyridin-4-yl)oxazole-4-
carboxamide;
25.
N-(5-(4-methylpiperazin-1-yl)-2-morpholinooxazolo[4,5-b]pyridin-6-yl)-2-(2-
methylpyridin-4-yl)oxazole-4-carboxamide;
26.
N-(2,5-di(piperidin-1-yl)oxazolo[4,5-b]pyridin-6-yl)-2-(6-methoxypyridin-3-
yl)oxazole-4-carboxamide;
27.
N-(2,5-di(piperidin-1-yl)oxazolo[4,5-b]pyridin-6-yl)-2-(2-methylpyridin-3-
yl)oxazole-4-carboxamide;
28.
N-(2,5-di(piperidin-1-yl)oxazolo[4,5-b]pyridin-6-yl)-2-(2-hydroxypyridin-3-
yl)oxazole-4-carboxamide;
29.
2-(2-hydroxypyridin-3-yl)-N-(2-morpholino-5-(piperidin-1-yl)oxazolo[4,5-b]pyridin-
6-yl)oxazole-4-carboxamide;
30.
N-(2,5-di(piperidin-1-yl)oxazolo[4,5-b]pyridin-6-yl)-2-(6-hydroxypyridin-3-
yl)oxazole-4-carboxamide;
31.
2-(2-methoxypyridin-4-yl)-N-(2-morpholino-5-(piperidin-1-yl)oxazolo[4,5-b]pyridin-
6-yl)oxazole-4-carboxamide;
32.
2-(2-methylpyridin-3-yl)-N-(2-morpholino-5-(piperidin-1-yl)oxazolo[4,5-b]pyridin-6-
yl)oxazole-4-carboxamide;
33.
2-(3-methylpyridin-4-yl)-N-(2-morpholino-5-(piperidin-1-yl)oxazolo[4,5-b]pyridin-6-
yl)oxazole-4-carboxamide;
34.
N-(2,5-di(piperidin-1-yl)oxazolo[4,5-b]pyridin-6-yl)-2-(3-methylpyridin-4-
yl)oxazole-4-carboxamide;
35.
2-(6-methylpyridin-3-yl)-N-(2-morpholino-5-(piperidin-1-yl)oxazolo[4,5-b]pyridin-6-
yl)oxazole-4-carboxamide;
36.
6-(1-methyl-1H-pyrazol-4-yl)-N-(2-morpholino-5-(piperidin-1-yl)oxazolo[4,5-
b]pyridin-6-yl)picolinamide;
37.
N-(2,5-di(piperidin-1-yl)oxazolo[4,5-b]pyridin-6-yl)-2-(6-methylpyridin-3-
yl)oxazole-4-carboxamide;
38.
(S)-N-(5-(3-aminopyrrolidin-1-yl)-2-morpholinooxazolo[4,5-b]pyridin-6-yl)-2-(2-
methylpyridin-4-yl)oxazole-4-carboxamide;
39.
(S)-N-(5-(3-hydroxypyrrolidin-1-yl)-2-morpholinooxazolo[4,5-b]pyridin-6-yl)-2-(2-
methylpyridin-4-yl)oxazole-4-carboxamide;
40.
(R)-N-(5-(3-aminopyrrolidin-1-yl)-2-morpholinooxazolo[4,5-b]pyridin-6-yl)-2-(2-
methylpyridin-4-yl)oxazole-4-carboxamide;
41.
(R)-N-(5-(3-hydroxypyrrolidin-1-yl)-2-morpholinooxazolo[4,5-b]pyridin-6-yl)-2-(2-
methylpyridin-4-yl)oxazole-4-carboxamide;
42.
(S)-2-(3-aminopyrrolidin-1-yl)-N-(2-morpholino-5-(piperidin-1-yl)oxazolo[4,5-
b]pyridin-6-yl)oxazole-4-carboxamide;
43.
(S)-6-(3-hydroxypyrrolidin-1-yl)-N-(2-morpholino-5-(piperidin-1-yl)oxazolo[4,5-
b]pyridin-6-yl)picolinamide;
44.
(S)-6-(3-aminopyrrolidin-1-yl)-N-(2-morpholino-5-(piperidin-1-yl)oxazolo[4,5-
b]pyridin-6-yl)picolinamide;
45.
(S)-2-(3-hydroxypyrrolidin-1-yl)-N-(2-morpholino-5-(piperidin-1-yl)oxazolo[4,5-
b]pyridin-6-yl)oxazole-4-carboxamide;
46.
(S)-N-(5-cyclopropyl-2-morpholinooxazolo[4,5-b]pyridin-6-yl)-2-(3-
hydroxypyrrolidin-1-yl)oxazole-4-carboxamide;
47.
(S)-2-(3-aminopyrrolidin-1-yl)-N-(5-cyclopropyl-2-morpholinooxazolo[4,5-b]pyridin-
6-yl)oxazole-4-carboxamide;
48.
2-(2-methylpyridin-4-yl)-N-(5-(piperidin-1-yl)-2-(pyrrolidin-1-yl)oxazolo[4,5-
b]pyridin-6-yl)oxazole-4-carboxamide hydrochloride;
49.
N-(2-(2,6-dimethylmorpholino)-5-(piperidin-1-yl)oxazolo[4,5-b]pyridin-6-yl)-2-(2-
methylpyridin-4-yl)oxazole-4-carboxamide hydrochloride;
50.
N-(2,5-di(piperidin-1-yl)thiazolo[4,5-b]pyridin-6-yl)-6-(1-methyl-1H-pyrazol-4-
yl)picolinamide hydrochloride;
51.
6-(1-methyl-1H-pyrazol-4-yl)-N-(2-morpholino-5-(piperidin-1-yl)thiazolo[4,5-
b]pyridin-6-yl)picolinamide;
52.
N-(2,5-di(piperidin-1-yl)thiazolo[4,5-b]pyridin-6-yl)-2-(2-methylpyridin-3-
yl)oxazole-4-carboxamide hydrochloride;
53.
N-(2-((2S,6R)-2,6-dimethylmorpholino)-5-(piperidin-1-yl)thiazolo[4,5-b]pyridin-6-
yl)-2-(2-methylpyridin-4-yl)oxazole-4-carboxamide;
54.
2-(2-methylpyridin-3-yl)-N-(2-morpholino-5-(piperidin-1-yl)thiazolo[4,5-b]pyridin-6-
yl)oxazole-4-carboxamide;
55.
2-(2-hydroxypyridin-3-yl)-N-(2-morpholino-5-(piperidin-1-yl)thiazolo[4,5-b]pyridin-
6-yl)oxazole-4-carboxamide;
56.
N-(2,5-di(piperidin-1-yl)thiazolo[4,5-b]pyridin-6-yl)-2-(2-methoxypyridin-4-
yl)oxazole-4-carboxamide;
57.
2-(6-methoxypyridin-3-yl)-N-(2-morpholino-5-(piperidin-1-yl)thiazolo[4,5-b]pyridin-
6-yl)oxazole-4-carboxamide;
58.
2-(2-methoxypyridin-4-yl)-N-(2-morpholino-5-(piperidin-1-yl)thiazolo[4,5-b]pyridin-
6-yl)oxazole-4-carboxamide;
59.
(S)-N-(5-(3-fluoropiperidin-1-yl)-2-morpholinothiazolo[4,5-b]pyridin-6-yl)-2-(2-
methylpyridin-4-yl)oxazole-4-carboxamide;
60.
2-(6-methylpyridin-3-yl)-N-(2-morpholino-5-(piperidin-1-yl)thiazolo[4,5-b]pyridin-6-
yl)oxazole-4-carboxamide;
61.
2-(3-methylpyridin-4-yl)-N-(2-morpholino-5-(piperidin-1-yl)thiazolo[4,5-b]pyridin-6-
yl)oxazole-4-carboxamide;
62.
(S)-6-(3-aminopyrrolidin-1-yl)-N-(2-morpholino-5-(piperidin-1-yl)thiazolo[4,5-
b]pyridin-6-yl)picolinamide;
63.
(S)-6-(3-hydroxypyrrolidin-1-yl)-N-(2-morpholino-5-(piperidin-1-yl)thiazolo[4,5-
b]pyridin-6-yl)picolinamide;
64.
(S)-6-(3-aminopyrrolidin-1-yl)-N-(2,5-di(piperidin-1-yl)thiazolo[4,5-b]pyridin-6-
yl)picolinamide;
65.
(S)-N-(2,5-di(piperidin-1-yl)thiazolo[4,5-b]pyridin-6-yl)-6-(3-hydroxypyrrolidin-1-
yl)picolinamide;
66.
(S)-2-(3-aminopyrrolidin-1-yl)-N-(2-morpholino-5-(piperidin-1-yl)thiazolo[4,5-
b]pyridin-6-yl)oxazole-4-carboxamide;
67.
(S)-N-(5-(3-aminopyrrolidin-1-yl)-2-morpholinothiazolo[4,5-b]pyridin-6-yl)-2-(2-
methylpyridin-4-yl)oxazole-4-carboxamide;
68.
(S)-2-(3-aminopyrrolidin-1-yl)-N-(5-cyclopropyl-2-morpholinothiazolo[4,5-
b]pyridin-6-yl)oxazole-4-carboxamide;
69.
N-(5-cyclopropyl-2-morpholinothiazolo[4,5-b]pyridin-6-yl)-2-(2-methylpyridin-4-
yl)oxazole-4-carboxamide;
70.
(S)-2-(3-hydroxypyrrolidin-1-yl)-N-(2-morpholino-5-(piperidin-1-yl)thiazolo[4,5-
b]pyridin-6-yl)oxazole-4-carboxamide;
71.
(S)-N-(5-(3-hydroxypyrrolidin-1-yl)-2-morpholinothiazolo[4,5-b]pyridin-6-yl)-2-(2-
methylpyridin-4-yl)oxazole-4-carboxamide;
72.
(S)-N-(5-cyclopropyl-2-morpholinothiazolo[4,5-b]pyridin-6-yl)-6-(3-
hydroxypyrrolidin-1-yl)picolinamide;
73.
(S)-N-(5-cyclopropyl-2-morpholinothiazolo[4,5-b]pyridin-6-yl)-2-(3-
hydroxypyrrolidin-1-yl)oxazole-4-carboxamide;
74.
(S)-N-(5-cyclopropyl-2-morpholinothiazolo[4,5-b]pyridin-6-yl)-6-(1-(2-
hydroxypropyl)-1H-pyrazol-4-yl)picolinamide;
75.
(S)-N-(5-cyclopropyl-2-morpholinothiazolo[4,5-b]pyridin-6-yl)-2-(1-(2-
hydroxypropyl)-1H-pyrazol-4-yl)oxazole-4-carboxamide;
76.
N-(5-(3-hydroxypyrrolidin-1-yl)-2-morpholinothiazolo[4,5-b]pyridin-6-yl)-2-(6-
methoxypyridin-3-yl)oxazole-4-carboxamide;
77.
(S)-N-(5-(3-hydroxypyrrolidin-1-yl)-2-morpholinothiazolo[4,5-b]pyridin-6-yl)-2-(6-
methoxypyridin-3-yl)oxazole-4-carboxamide;
78.
(R)-N-(5-(3-hydroxypyrrolidin-1-yl)-2-morpholinothiazolo[4,5-b]pyridin-6-yl)-2-(6-
methoxypyridin-3-yl)oxazole-4-carboxamide;
79.
(S)-N-(5-(azetidin-1-yl)-2-morpholinothiazolo[4,5-b]pyridin-6-yl)-6-(3-
hydroxypyrrolidin-1-yl)picolinamide;
80.
N-(5-(3-hydroxyazetidin-1-yl)-2-morpholinothiazolo[4,5-b]pyridin-6-yl)-2-(2-
methylpyridin-4-yl)oxazole-4-carboxamide;
81.
(S)-N-(5-(3-hydroxypyrrolidin-1-yl)-2-morpholinothiazolo[4,5-b]pyridin-6-yl)-5-(2-
methylpyridin-4-yl)thiophene-2-carboxamide;
82.
(S)-N-(5-(3-hydroxypyrrolidin-1-yl)-2-morpholinothiazolo[4,5-b]pyridin-6-yl)-5-(2-
methylpyridin-4-yl)furan-2-carboxamide;
83.
(S)-N-(5-(3-hydroxypiperidin-1-yl)-2-morpholinothiazolo[4,5-b]pyridin-6-yl)-2-(2-
methylpyridin-4-yl)oxazole-4-carboxamide;
84.
N-(5-(4-hydroxypiperidin-1-yl)-2-morpholinothiazolo[4,5-b]pyridin-6-yl)-2-(2-
methylpyridin-4-yl)oxazole-4-carboxamide
85.
(R)-N-(5-(3-hydroxypyrrolidin-1-yl)-2-morpholinothiazolo[4,5-b]pyridin-6-yl)-2-(2-
methylpyridin-4-yl)oxazole-4-carboxamide;
86.
N-(5-(4-hydroxypiperidin-1-yl)-2-morpholinothiazolo[4,5-b]pyridin-6-yl)-5-(2-
methylpyridin-4-yl)furan-2-carboxamide;
87.
N-(5-(azetidin-1-yl)-2-(piperidin-1-yl)thiazolo[4,5-b]pyridin-6-yl)-2-(2-
methylpyridin-4-yl)oxazole-4-carboxamide;
88.
2-(2-methylpyridin-4-yl)-N-(2-(piperidin-1-yl)-5-(pyrrolidin-1-yl)thiazolo[4,5-
b]pyridin-6-yl)oxazole-4-carboxamide;
89.
2-(2-methylpyridin-4-yl)-N-(2-morpholino-5-(pyrrolidin-1-yl)thiazolo[4,5-b]pyridin-
6-yl)oxazole-4-carboxamide;
90.
5-(2-methylpyridin-4-yl)-N-(2-morpholino-5-(piperidin-1-yl)thiazolo[4,5-b]pyridin-6-
yl)furan-2-carboxamide;
91.
N-(5-(azepan-1-yl)-2-morpholinothiazolo[4,5-b]pyridin-6-yl)-2-(2-methylpyridin-4-
yl)oxazole-4-carboxamide;
92.
2-(2-aminopyridin-4-yl)-N-(2-morpholino-5-(piperidin-1-yl)thiazolo[4,5-b]pyridin-6-
yl)oxazole-4-carboxamide hydrochloride;
93.
N-(5-(azetidin-1-yl)-2-morpholinothiazolo[4,5-b]pyridin-6-yl)-2-(2-methylpyridin-4-
yl)oxazole-4-carboxamide;
94.
(R)-N-(5-(3-hydroxypiperidin-1-yl)-2-morpholinothiazolo[4,5-b]pyridin-6-yl)-2-(2-
methylpyridin-4-yl)oxazole-4-carboxamide;
95.
(R)-N-(5-(3-hydroxypiperidin-1-yl)-2-morpholinothiazolo[4,5-b]pyridin-6-yl)-5-(2-
methylpyridin-4-yl)furan-2-carboxamide;
96.
(S)-6-(1-(2-hydroxypropyl)-1H-pyrazol-4-yl)-N-(2-morpholino-5-(piperidin-1-
yl)thiazolo[4,5-b]pyridin-6-yl)picolinamide
97.
N-(5-(4-fluoropiperidin-1-yl)-2-morpholinothiazolo[4,5-b]pyridin-6-yl)-5-(2-
methylpyridin-4-yl)furan-2-carboxamide
98.
N-(5-(4-fluoropiperidin-1-yl)-2-morpholinothiazolo[4,5-b]pyridin-6-yl)-2-(2-
methylpyridin-4-yl)oxazole-4-carboxamide hydrochloride
99.
N-(5-(1-methyl-1H-pyrazol-4-yl)-2-morpholinothiazolo[4,5-b]pyridin-6-yl)-2-(2-
methylpyridin-4-yl)oxazole-4-carboxamide;
100.
N-(5-(3-fluorophenyl)-2-morpholinothiazolo[4,5-b]pyridin-6-yl)-2-(2-methylpyridin-
4-yl)oxazole-4-carboxamide;
101.
N-(5-(4-hydroxypiperidin-1-yl)-2-morpholinothiazolo[4,5-b]pyridin-6-yl)-5-(2-
methylpyridin-4-yl)furan-2-carboxamide;
102.
N-(5-(3-fluoropiperidin-1-yl)-2-morpholinothiazolo[4,5-b]pyridin-6-yl)-5-(2-
methylpyridin-4-yl)furan-2-carboxamide;
103.
(S)-N-(5-(3-hydroxypyrrolidin-1-yl)-2-morpholinooxazolo[4,5-b]pyridin-6-yl)-2-(6-
methoxypyridin-3-yl)oxazole-4-carboxamide;
104.
N-(5-(3-hydroxypyrrolidin-1-yl)-2-morpholinooxazolo[4,5-b]pyridin-6-yl)-2-(2-
methylpyridin-4-yl)oxazole-4-carboxamide;
105.
(R)-N-(5-(3-hydroxypyrrolidin-1-yl)-2-morpholinooxazolo[4,5-b]pyridin-6-yl)-2-(6-
methoxypyridin-3-yl)oxazole-4-carboxamide;
106.
N-(5-(3-hydroxypyrrolidin-1-yl)-2-morpholinooxazolo[4,5-b]pyridin-6-yl)-2-(6-
methoxypyridin-3-yl)oxazole-4-carboxamide;
107.
(S)-N-(5-(3-hydroxypyrrolidin-1-yl)-2-morpholinooxazolo[4,5-b]pyridin-6-yl)-5-(2-
methylpyridin-4-yl)furan-2-carboxamide;
108.
(S)-N-(5-(3-hydroxypyrrolidin-1-yl)-2-morpholinooxazolo[4,5-b]pyridin-6-yl)-5-(2-
methylpyridin-4-yl)thiophene-2-carboxamide;
109.
N-(5-(azetidin-1-yl)-2-(piperidin-1-yl)oxazolo[4,5-b]pyridin-6-yl)-2-(2-
methylpyridin-4-yl)oxazole-4-carboxamide;
110.
2-(2-methylpyridin-4-yl)-N-(2-(piperidin-1-yl)-5-(pyrrolidin-1-yl)oxazolo[4,5-
b]pyridin-6-yl)oxazole-4-carboxamide;
111.
5-(2-methylpyridin-4-yl)-N-(2-morpholino-5-(piperidin-1-yl)oxazolo[4,5-b]pyridin-6-
yl)furan-2-carboxamide;
112.
N-(5-(azetidin-1-yl)-2-morpholinooxazolo[4,5-b]pyridin-6-yl)-2-(2-methylpyridin-4-
yl)oxazole-4-carboxamide;
113.
2-(2-methylpyridin-4-yl)-N-(2-morpholino-5-(pyrrolidin-1-yl)oxazolo[4,5-b]pyridin-
6-yl)oxazole-4-carboxamide;
114.
N-(5-(4-hydroxypiperidin-1-yl)-2-morpholinooxazolo[4,5-b]pyridin-6-yl)-5-(2-
methylpyridin-4-yl)furan-2-carboxamide;
115.
(R)-N-(5-(3-hydroxypiperidin-1-yl)-2-morpholinooxazolo[4,5-b]pyridin-6-yl)-5-(2-
methylpyridin-4-yl)furan-2-carboxamide;
116.
N-(5-(furan-3-yl)-2-morpholinooxazolo[4,5-b]pyridin-6-yl)-2-(2-methylpyridin-4-
yl)oxazole-4-carboxamide;
117.
N-(5-(3-fluoropiperidin-1-yl)-2-morpholinooxazolo[4,5-b]pyridin-6-yl)-2-(2-
methylpyridin-4-yl)oxazole-4-carboxamide;
118.
N-(5-(4-hydroxypiperidin-1-yl)-2-morpholinooxazolo[4,5-b]pyridin-6-yl)-2-(2-
methylpyridin-4-yl)oxazole-4-carboxamide;
119.
N-(5-(4-fluoropiperidin-1-yl)-2-morpholinooxazolo[4,5-b]pyridin-6-yl)-2-(2-
methylpyridin-4-yl)oxazole-4-carboxamide;
120.
(S)-N-(5-(3-aminopiperidin-1-yl)-2-morpholinothiazolo[4,5-b]pyridin-6-yl)-2-(2-
methylpyridin-4-yl)oxazole-4-carboxamide;
121.
2-(2-methylpyridin-4-yl)-N-(2-morpholino-5-(1H-pyrazol-4-yl)thiazolo[4,5-
b]pyridin-6-yl)oxazole-4-carboxamide;
122.
N-(5-(6-fluoropyridin-3-yl)-2-morpholinothiazolo[4,5-b]pyridin-6-yl)-2-(2-
methylpyridin-4-yl)oxazole-4-carboxamide;
123.
N-(5-(3-hydroxy-8-azabicyclo[3.2.1]octan-8-yl)-2-morpholinothiazolo[4,5-b]pyridin-
6-yl)-2-(2-methylpyridin-4-yl)oxazole-4-carboxamide;
124.
N-(2-(3-hydroxypiperidin-1-yl)-5-(piperidin-1-yl)thiazolo[4,5-b]pyridin-6-yl)-2-(2-
methylpyridin-4-yl)oxazole-4-carboxamide;
125.
2-(2-acetamidopyridin-4-yl)-N-(5-(4-hydroxypiperidin-1-yl)-2-
morpholinothiazolo[4,5-b]pyridin-6-yl)oxazole-4-carboxamide;
126.
N-(2-(3-hydroxypiperidin-1-yl)-5-(4-hydroxypiperidin-1-yl)thiazolo[4,5-b]pyridin-6-
yl)-2-(2-methylpyridin-4-yl)oxazole-4-carboxamide;
127.
2-(2-acetamidopyridin-4-yl)-N-(5-(3-hydroxypiperidin-1-yl)-2-
morpholinothiazolo[4,5-b]pyridin-6-yl)oxazole-4-carboxamide;
128.
2-(2-aminopyridin-4-yl)-N-(5-(3-hydroxypiperidin-1-yl)-2-morpholinothiazolo[4,5-
b]pyridin-6-yl)oxazole-4-carboxamide hydrochloride;
129.
5-(2-aminopyridin-4-yl)-N-(5-(4-hydroxypiperidin-1-yl)-2-morpholinothiazolo[4,5-
b]pyridin-6-yl)furan-3-carboxamide hydrochloride;
130.
2-(2-aminopyridin-4-yl)-N-(5-(4-hydroxypiperidin-1-yl)-2-morpholinothiazolo[4,5-
b]pyridin-6-yl)oxazole-4-carboxamide hydrochloride;
131.
2-(2-aminopyridin-4-yl)-N-(5-(4-fluoropiperidin-1-yl)-2-morpholinothiazolo[4,5-
b]pyridin-6-yl)oxazole-4-carboxamide hydrochloride;
132.
N-(5-(2-fluoropyridin-4-yl)-2-morpholinothiazolo[4,5-b]pyridin-6-yl)-2-(2-
methylpyridin-4-yl)oxazole-4-carboxamide;
133.
N-(5-(4-fluoropiperidin-1-yl)-2-(3-hydroxypiperidin-1-yl)thiazolo[4,5-b]pyridin-6-
yl)-2-(2-methylpyridin-4-yl)oxazole-4-carboxamide;
134.
N-(5-(4-aminopiperidin-1-yl)-2-(3-hydroxypiperidin-1-yl)thiazolo[4,5-b]pyridin-6-
yl)-2-(2-methylpyridin-4-yl)oxazole-4-carboxamide hydrochloride; and
135.
N-(5-(2-hydroxypyridin-4-yl)-2-morpholinothiazolo[4,5-b]pyridin-6-yl)-2-(2-
methylpyridin-4-yl)oxazole-4-carboxamide hydrochloride;
or a pharmaceutically acceptable salt or a stereoisomer thereof.
77. A pharmaceutical composition comprising at least one compound according to claim 1 , or a pharmaceutically acceptable salt or a stereoisomer thereof, and a pharmaceutically acceptable carrier or excipient.