Substituted heteroaryl compounds and methods of use

1. A compound having Formula (I):

or a stereoisomer, a tautomer, an N-oxide, a solvate, or a pharmaceutically acceptable salt thereof,

wherein:

W is a 4-7 membered saturated monocyclic heterocyclylene or saturated monocyclic C 5 -C 7 carbocyclylene, wherein W is optionally substituted by 1, 2, 3, 4 or 5 R 2 groups;

T is C 6 -C 12 aryl or 5-12 membered heteroaryl, wherein T is optionally substituted by 1, 2, 3, 4 or 5 R 3 groups;

A is an optionally substituted 9-membered heteroaryl group, having Formula (A-1), (A-2), (A-3), (A-4), (A-5) or (A-6):

wherein each V 1 and V 2 is independently CR 4 or N;

each U 1 , U 2 and U 3 is independently CR 4 or N;

each of U 4 and U 6 is independently CR 4 , N, NR 5 , O or S;

U 5 is independently CR 4 , O or S;

wherein at least one of V 1 , V 2 , U 3 , U 4 , U 5 and U 6 is not CR 4 ;

Z is H, C 1 -C 12 alkyl, C 3 -C 12 cycloalkyl or 3-12 membered heterocyclyl, wherein each of the C 1 -C 12 , alkyl, C 3 -C 12 cycloalkyl and 3-12 membered heterocyclyl is optionally substituted by 1, 2, 3, 4 or 5 R 9 groups;

R 1 is H, F, Cl, Br, I, NO 2 , N 3 , CN, C 1 -C 12 alkyl, C 1 -C 12 heteroalkyl, C 3 -C 12 cycloalkyl or 3-12 membered heterocyclyl, wherein each of the C 1 -C 12 alkyl, C 1 -C 12 heteroalkyl, C 3 -C 12 cycloalkyl and 3-12 membered heterocyclyl is optionally substituted by 1, 2 or 3 R 9 groups;

each R 2 and R 3 is independently F, Cl, Br, I, NO 2 , N 3 , CN, OH, C 1 -C 12 alkyl, C 1 -C 12 heteroalkyl, C 1 -C 12 hydroxyalkyl, C 2 -C 12 alkenyl, C 2 -C 12 alkynyl, C 3 -C 12 cycloalkyl, C 6 -C 12 aryl, 3-12 membered heterocyclyl, 5-12 membered heteroaryl, —(C 1 -C 4 alkylene)-(C 3 -C 12 cycloalkyl), —(C 1 -C 4 alkylene)-(3-12 membered heterocyclyl), —(C 1 -C 4 alkylene)-(C 6 -C 12 aryl), —(C 1 -C 4 alkylene)-(5-12 membered heteroaryl), —(CR 6 R 7 ) n —OR c , —(CR 6 R 7 ) n —NR a R b , —(CR 6 R 7 ) n C(═O)R 8 , —(CR 6 R 7 ) n OC(═O)R 8 , —O(CR 6 R 7 ) n —R c , —(CR 6 R 7 ) n —N(R c )C(═O)R 8 , —(CR 6 R 7 ) n C(═O)OR c , —(CR 6 R 7 ) n C(═O)NR a R b , —N(R c )C(═O)NR a R b , —N(R c )S(═O) m NR a R b , —C(═O)N(R c )C(═O)R 8 , —(CR 6 R 7 ) n S(═O) m R 8 , —N(R c )S(═O) m R 8 or —(CR 6 R 7 ) n S(═O) m NR a R b , wherein each of the C 1 -C 12 alkyl, C 1 -C 12 heteroalkyl, C 1 -C 12 hydroxyalkyl, C 2 -C 12 alkenyl, C 2 -C 12 alkynyl, C 3 -C 12 cycloalkyl, C 6 -C 12 aryl, 3-12 membered heterocyclyl, 5-12 membered heteroaryl, —(C 1 -C 4 alkylene)-(C 3 -C 12 cycloalkyl), —(C 1 -C 4 alkylene)-(3-12 membered heterocyclyl), —(C 1 -C 4 alkylene)-(C 6 -C 12 aryl) and —(C 1 -C 4 alkylene)-(5-12 membered heteroaryl) is optionally independently substituted by 1, 2, 3, 4 or 5 R 9 groups;

each R 4 is independently H, F, Cl, Br, I, NO 2 , N 3 , CN, C 1 -C 12 alkyl, C 1 -C 12 heteroalkyl, C 1 -C 12 hydroxyalkyl, C 2 -C 12 alkenyl, C 2 -C 12 alkynyl, C 3 -C 12 cycloalkyl, C 6 -C 12 aryl, 3-12 membered heterocyclyl, 5-12 membered heteroaryl, —(CR 6 R 7 ) n —OR c , —(CR 6 R 7 ) n —NR a R b , —(CR 6 R 7 ) n C(═O)R 8 , —(CR 6 R 7 ) n OC(═O)R 8 , —O(CR 6 R 7 ) n —R c , —(CR 6 R 7 ) n —N(R c )C(═O)R 8 , —(CR 6 R 7 ) n C(═O)OR c , —(CR 6 R 7 ) n C(═O)NR a R b , —N(R c )C(═O)NR a R b , —N(R c )S(═O) m NR a R b , —(CR 6 R 7 ) n S(═O) m R 8 , —N(R c )S(═O) m R 8 or —(CR 6 R 7 ) n S(═O) m NR a R b , or two adjacent R 4 taken together with the carbon atoms to which they are attached form a C 3 -C 12 carbocycle or 3-12 membered heterocycle, wherein each of the C 1 -C 12 alkyl, C 1 -C 12 heteroalkyl, C 1 -C 12 hydroxyalkyl, C 2 -C 12 alkenyl, C 2 -C 12 alkynyl, C 3 -C 12 cycloalkyl, C 6 -C 12 aryl, 3-12 membered heterocyclyl, 5-12 membered heteroaryl, C 3 -C 12 carbocycle and 3-12 membered heterocycle is optionally independently substituted by 1, 2, 3, 4 or 5 R 9 groups;

each R 5 is independently absent, or H, C 1 -C 12 alkyl, C 1 -C 12 heteroalkyl, C 1 -C 12 hydroxyalkyl, C 2 -C 12 alkenyl, C 2 -C 12 alkynyl, C 3 -C 12 cycloalkyl, C 6 -C 12 aryl, 3-12 membered heterocyclyl, 5-12 membered heteroaryl, —(CR 6 R 7 ) n —OR c , —(CR 6 R 7 ) n —NR a R b , —(CR 6 R 7 ) n C(═O)R 8 , —(CR 6 R 7 ) n OC(═O)R 8 , —(CR 6 R 7 ) n C(═O)OR c , —(CR 6 R 7 ) n C(═O)NR a R b , —(CR 6 R 7 ) n S(═O) m R 8 or —(CR 6 R 7 ) n S(═O) m NR a R b , wherein each of the C 1 -C 12 alkyl, C 1 -C 12 heteroalkyl, C 1 -C 12 hydroxyalkyl, C 2 -C 12 alkenyl, C 2 -C 12 alkynyl, C 3 -C 12 cycloalkyl, C 6 -C 12 aryl, 3-12 membered heterocyclyl and 5-12 membered heteroaryl is optionally independently substituted by 1, 2 or 3 R 9 groups;

each R 6 and R 7 is independently H, F, Cl, Br, I, NO 2 , N 3 , CN, C 1 -C 12 alkyl, C 1 -C 12 heteroalkyl, C 2 -C 12 alkenyl, C 2 -C 12 alkynyl, C 3 -C 12 cycloalkyl, C 6 -C 12 aryl, 3-12 membered heterocyclyl or 5-12 membered heteroaryl, or R 6 and R 7 taken together with the carbon atom to which they are attached form a C 3 -C 12 carbocycle or 3-12 membered heterocycle, wherein each of the C 1 -C 12 alkyl, C 1 -C 12 heteroalkyl, C 2 -C 12 alkenyl, C 2 -C 12 alkynyl, C 3 -C 12 cycloalkyl, C 6 -C 12 aryl, 3-12 membered heterocyclyl, 5-12 membered heteroaryl, C 3 -C 12 carbocycle and 3-12 membered heterocycle is optionally independently substituted by 1, 2 or 3 R 9 groups;

each R 8 is independently C 1 -C 12 alkyl, C 1 -C 12 heteroalkyl, C 2 -C 12 alkenyl, C 2 -C 12 alkynyl, C 3 -C 12 cycloalkyl, C 6 -C 12 aryl, 3-12 membered heterocyclyl, 5-12 membered heteroaryl, —(C 1 -C 4 alkylene)-(C 3 -C 12 cycloalkyl), —(C 1 -C 4 alkylene)-(3-12 membered heterocyclyl), —(C 1 -C 4 alkylene)-(C 6 -C 12 aryl) or —(C 1 -C 4 alkylene)-(5-12 membered heteroaryl), wherein each R 8 is optionally substituted by 1, 2 or 3 R 9 groups;

each R 9 is independently F, Cl, Br, I, CN, NO 2 , N 3 , —OH, —NH 2 , C 1 -C 12 , alkyl, C 1 -C 12 heteroalkyl, C 2 -C 12 alkenyl, C 2 -C 12 alkynyl, C 3 -C 12 cycloalkyl, C 6 -C 12 aryl, 3-12 membered heterocyclyl, 5-12 membered heteroaryl, —NH(C 1 -C 12 alkyl), —NH(CH 2 ) n —(C 3 -C 12 cycloalkyl), —NH(CH 2 ) n —(C 6 -C 12 aryl), —NH(CH 2 ) n -(3-12 membered heterocyclyl), —NH(CH 2 ) n -(5-12 membered heteroaryl), —N(C 1 -C 12 alkyl) 2 , —N[(CH 2 ) n —(C 3 -C 12 cycloalkyl)] 2 , —N[(CH 2 ) n —(C 6 -C 12 aryl)] 2 , —N[(CH 2 ) n -(3-12 membered heterocyclyl)] 2 , —N[(CH 2 ) n -(5-12 membered heteroaryl)] 2 , —O(C 1 -C 12 alkyl), —O(CH 2 ) n —(C 3 -C 12 cycloalkyl), —O(CH 2 ) n —(C 6 -C 12 aryl), —O(CH 2 ) n -(3-12 membered heterocyclyl) or —O(CH 2 ) n -(5-12 membered heteroaryl);

each R a , R b and R c is independently H, C 1 -C 6 alkyl, C 1 -C 6 heteroalkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 6 cycloalkyl, —(C 1 -C 4 alkylene)-(C 3 -C 6 cycloalkyl), 4-7 membered heterocyclyl, —(C 1 -C 4 alkylene)-(4-7 membered heterocyclyl), C 6 -C 12 aryl, —(C 1 -C 4 alkylene)-(C 6 -C 12 aryl), 5-12 membered heteroaryl or —(C 1 -C 4 alkylene)-(5-12 membered heteroaryl), or R a and R b taken together with the nitrogen atom to which they are attached form a 4-7 membered heterocycle, wherein each of the C 1 -C 6 alkyl, C 1 -C 6 heteroalkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 6 cycloalkyl, —(C 1 -C 4 alkylene)-(C 3 -C 6 cycloalkyl), 4-7 membered heterocyclyl, —(C 1 -C 4 alkylene)-(4-7 membered heterocyclyl), C 6 -C 12 aryl, —(C 1 -C 4 alkylene)-(C 6 -C 12 aryl), 5-12 membered heteroaryl, —(C 1 -C 4 alkylene)-(5-12 membered heteroaryl) and 4-7 membered heterocycle is optionally independently substituted by 1, 2, 3 or 4 substitutents independently selected from F, Cl, Br, CN, N 3 , —OH, —NH 2 , C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxy and C 1 -C 6 alkylamino;

each n is independently 0, 1, 2, 3 or 4; and

each m is independently 1 or 2.

2. The compound according to claim 1 , wherein W is a saturated monocyclic heterocyclylene derived from one of the following heterocyclic compounds:

and wherein W is optionally substituted by 1, 2 or 3 R 2 groups.

3. The compound according to claim 1 , wherein W is:

and wherein W is optionally substituted by 1, 2 or 3 R 2 groups.

4. The compound according to claim 1 , wherein T is phenyl or 5-6 membered heteroaryl, wherein T is optionally substituted by 1, 2, 3 or 4 R 3 groups.

5. The compound according to claim 1 , wherein T is phenyl, pyridyl, pyridonyl, pyrimidinyl, pyrimidonyl, pyridazinyl, pyrazinyl, 1,2,4-triazinyl, 1,3,5-triazinyl, furanyl, imidazolyl, isoxazolyl, oxazolyl, pyrrolyl, thiazolyl, isothiazolyl, tetrazolyl, triazolyl, thienyl, pyrazolyl, oxadiazolyl, thiadiazolyl or triazinyl, wherein T is optionally substituted by 1, 2 or 3 R 3 groups.

6. The compound according to claim 1 , wherein A is:

wherein each CH in A is optionally independently substituted by a R 4 group; each NH in A is optionally independently substituted by a R 5 group.

7. The compound according to claim 1 , wherein Z is H, C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl or 4-7 membered heterocyclyl, wherein each of the C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl and 4-7 membered heterocyclyl is optionally substituted by 1, 2 or 3 R 9 groups.

8. The compound according claim 1 , wherein Z is H, methyl, ethyl, n-propyl, i-propyl, cyclopropyl or cyclobutyl.

9. The compound according to claim 1 , wherein R 1 is H, F, Cl, Br, NO 2 , N 3 , CN, C 1 -C 4 alkyl, C 1 -C 4 heteroalkyl, C 3 -C 6 cycloalkyl or 4-7 membered heterocyclyl, wherein each of the C 1 -C 4 alkyl, C 1 -C 4 heteroalkyl, C 3 -C 6 cycloalkyl and 4-7 membered heterocyclyl is optionally substituted by 1, 2 or 3 R 9 groups.

10. The compound according to claim 1 , wherein R 2 and/or R 3 is independently F, Cl, Br, NO 2 , N 3 , CN, OH, C 1 -C 4 alkyl, C 1 -C 6 heteroalkyl, C 1 -C 6 hydroxyalkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 6 cycloalkyl, phenyl, 4-7 membered heterocyclyl, 5-6 membered heteroaryl, —(CR 6 R 7 ) n —OR c , —(CR 6 R 7 ) n —NR a R b , —(CR 6 R 7 ) n OC(═O)R 8 , —(CR 6 R 7 ) n —N(R c )C(═O)R 8 , —(CR 6 R 7 ) n C(═O)OR c , —(CR 6 R 7 ) n C(═O)NR a R b , —(CR 6 R 7 ) n S(═O) m R 8 , —N(R c )S(═O) m R 8 or —(CR 6 R 7 ) n S(═O) m NR a R b , wherein each of the C 1 -C 6 alkyl, C 1 -C 6 heteroalkyl, C 1 -C 6 hydroxyalkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 6 cycloalkyl, phenyl, 4-7 membered heterocyclyl and 5-6 membered heteroaryl is optionally independently substituted by 1, 2 or 3 R 9 groups.

11. The compound according to claim 1 , wherein each R 4 is independently H, F, Cl, Br, NO 2 , N 3 , CN, C 1 -C 6 alkyl, C 1 -C 6 heteroalkyl, C 1 -C 6 hydroxyalkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 6 cycloalkyl, phenyl, 4-7 membered heterocyclyl, 5-6 membered heteroaryl, —(CR 6 R 7 ) n —OR c , —(CR 6 R 7 ) n —NR a R b , —(CR 6 R 7 ) n OC(═O)R 8 , —(CR 6 R 7 ) n —N(R c )C(═O)R 8 , —(CR 6 R 7 ) n C(═O)OR c , —(CR 6 R 7 ) n C(═O)NR a R b , —(CR 6 R 7 ) n S(═O) m R 8 , —N(R c )S(═O) m R 8 or —(CR 6 R 7 ) n S(═O) m NR a R b , or two adjacent R 4 taken together with the carbon atoms to which they are attached form a C 3 -C 6 carbocycle or 4-7 membered heterocycle, wherein each of the C 1 -C 6 alkyl, C 1 -C 6 heteroalkyl, C 1 -C 6 hydroxyalkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 6 cycloalkyl, phenyl, 4-7 membered heterocyclyl, 5-6 membered heteroaryl, C 3 -C 6 carbocycle and 4-7 membered heterocycle is optionally independently substituted by 1, 2 or 3 R 9 groups.

12. The compound according to claim 1 , wherein each R 4 is independently H, F, Cl, Br, N 3 , CN, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, —CH 2 OH, —CH 2 CH 2 OH, —CH(OH)CH 3 , —C(CH 3 ) 2 OH, —CH 2 CH(OH)CH 3 , —CH 2 C(CH 3 ) 2 OH, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, piperidinyl, pyrrolidinyl, morpholinyl, piperazinyl, —(CR 6 R 7 ) n —C(═O)OR c or —(CR 6 R 7 ) n —C(═O)NR a R b , or two adjacent R 4 taken together with the carbon atoms to which they are attached form a C 4 -C 6 carbocycle or 4-7 membered heterocycle, wherein each of the methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, —CH 2 OH, —CH 2 CH 2 OH, —CH(OH)CH 3 , —C(CH 3 ) 2 OH, —CH 2 CH(OH)CH 3 , —CH 2 C(CH 3 ) 2 OH, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, piperidinyl, pyrrolidinyl, morpholinyl, piperazinyl, C 4 -C 6 carbocycle and 4-7 membered heterocycle is optionally independently substituted by 1, 2 or 3 R 9 groups.

13. The compound according to claim 1 , wherein each R 5 is independently absent, or H, C 1 -C 6 alkyl, C 1 -C 6 heteroalkyl, C 1 -C 6 hydroxyalkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 6 cycloalkyl, phenyl, 4-7 membered heterocyclyl, 5-6 membered heteroaryl, —(CR 6 R 7 ) n —OR c , —(CR 6 R 7 ) n —NR a R b , —(CR 6 R 7 ) n OC(═O)R 8 , —(CR 6 R 7 ) n C(═O)OR c , —(CR 6 R 7 ) n C(═O)NR a R b , —(CR 6 R 7 ) n S(═O) m R 8 or —(CR 6 R 7 ) n S(═O) m NR a R b , wherein each of the C 1 -C 6 alkyl, C 1 -C 6 heteroalkyl, C 1 -C 6 hydroxyalkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 6 cycloalkyl, phenyl, 4-7 membered heterocyclyl and 5-6 membered heteroaryl is optionally independently substituted by 1, 2 or 3 R 9 groups.

14. The compound according to claim 1 , wherein each R 5 is independently absent, or H, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, —CH 2 OH, —CH 2 CH 2 OH, —CH(OH)CH 3 , —C(CH 3 ) 2 OH, —CH 2 CH(OH)CH 3 , —CH 2 C(CH 3 ) 2 OH, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, piperidinyl, pyrrolidinyl, morpholinyl, piperazinyl, —(CR 6 R 7 ) n C(═O)OR c or —(CR 6 R 7 )—C(═O)NR a R b , wherein each of the methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, —CH 2 OH, —CH 2 CH 2 OH, —CH(OH)CH 3 , —C(CH 3 ) 2 OH, —CH 2 CH(OH)CH 3 , —CH 2 C(CH 3 ) 2 OH, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, piperidinyl, pyrrolidinyl, morpholinyl and piperazinyl is optionally independently substituted by 1, 2 or 3 R 9 groups.

15. The compound according to claim 1 , wherein each R 6 and R 7 is independently H, F, Cl, Br, CN, C 1 -C 4 alkyl, C 1 -C 4 heteroalkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 3 -C 6 cycloalkyl, phenyl, 4-7 membered heterocyclyl or 5-6 membered heteroaryl, or R 6 and R 7 taken together with the carbon atom to which they are attached form a C 3 -C 6 carbocycle or 4-7 membered heterocycle, wherein each of the C 1 -C 4 alkyl, C 1 -C 4 heteroalkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 3 -C 6 cycloalkyl, phenyl, 4-7 membered heterocyclyl, 5-6 membered heteroaryl, C 3 -C 6 carbocycle and 4-7 membered heterocycle is optionally independently substituted by 1, 2 or 3 R 9 groups.

16. The compound according to claim 1 , each R 8 is independently C 1 -C 6 alkyl, C 1 -C 6 heteroalkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 6 cycloalkyl, phenyl, 4-7 membered heterocyclyl, 5-6 membered heteroaryl, —(C 1 -C 3 alkylene)-(C 3 -C 6 cycloalkyl), —(C 1 -C 3 alkylene)-(4-7 membered heterocyclyl), —(C 1 -C 3 alkylene)-phenyl or —(C 1 -C 3 alkylene)-(5-6 membered heteroaryl), wherein each R 8 is optionally substituted by 1, 2 or 3 R 9 groups.

17. The compound according to claim 1 , wherein each R 9 is independently F, Cl, Br, CN, N 3 , —NH 2 , —OH, C 1 -C 6 alkyl, C 1 -C 6 heteroalkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 6 cycloalkyl, phenyl, 4-7 membered heterocyclyl, 5-6 membered heteroaryl, —NH(C 1 -C 6 alkyl), —NH(CH 2 ) n —(C 3 -C 6 cycloalkyl), —NH(CH 2 ) n -phenyl, —NH(CH 2 ) n -(4-7 membered heterocyclyl), —NH(CH 2 ) n -(5-6 membered heteroaryl), —N(C 1 -C 6 alkyl) 2 , —N[(CH 2 ) n —(C 3 -C 6 cycloalkyl)] 2 , —N[(CH 2 ) n -phenyl] 2 , —N[(CH 2 ) n -(4-7 membered heterocyclyl)] 2 , —N[(CH 2 ) n -(5-6 membered heteroaryl)] 2 , —O(CH 2 ) n —(C 3 -C 6 alkyl), —O(CH 2 ) n —(C 3 -C 6 cycloalkyl), —O(CH 2 ) n -phenyl, —O(CH 2 ) n —(4-7 membered heterocyclyl) or —O(CH 2 ) n -(5-6 membered heteroaryl).

18. The compound according to claim 1 , wherein each R a , R b and R c is independently H, methyl, ethyl, n-propyl, isopropyl, n-butyl, C 1 -C 4 heteroalkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, 4-6 membered heterocyclyl, phenyl, 5-6 membered heteroaryl, —(C 1 -C 2 alkylene)-(C 3 -C 6 cycloalkyl), alkylene)-(4-7 membered heterocyclyl), —(C 1 -C 2 alkylene)-phenyl or —(C 1 -C 2 alkylene)-(5-6 membered heteroaryl), or R a and R b taken together with the nitrogen atom to which they are attached form azetidinyl, pyrrolidinyl, piperidinyl or morpholinyl, wherein each of the methyl, ethyl, n-propyl, isopropyl, n-butyl, C 1 -C 4 heteroalkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, —(C 1 -C 2 alkylene)-(C 3 -C 6 cycloalkyl), 4-6 membered heterocyclyl, alkylene)-(4-7 membered heterocyclyl), phenyl, —(C 1 -C 2 alkylene)-phenyl, 5-6 membered heteroaryl, alkylene)-(5-6 membered heteroaryl), azetidinyl, pyrrolidinyl, piperidinyl and morpholinyl is optionally independently substituted by 1, 2 or 3 substitutents independently selected from F, C 1 , CN, N 3 , —OH, —NH 2 , C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy and C 1 -C 4 alkylamino.

19. The compound according to claim 1 having one of the following structures:

or a stereoisomer, a tautomer, an N-oxide, a solvate, or a pharmaceutically acceptable salt thereof.

20. A pharmaceutical composition comprising the compound of claim 1 , and a pharmaceutically acceptable excipient, carrier, adjuvant, vehicle or a combination thereof.

21. The pharmaceutical composition of claim 20 further comprising a therapeutic agent selected from the group consisting of chemotherapeutic agents, anti-proliferative agents, phosphodiesterase 4 (PDE4) inhibitors, β 2 -adrenoreceptor agonists, corticosteroids, non-steroidal GR agonists, anticholinergic agents, antihistamines, anti-inflammatory agents, immunosuppressants, immunomodulators, agents for treating atherosclerosis, agents for treating pulmonary fibrosis and combinations thereof.

22. A method of treating or lessening the severity of a protein kinase-mediated disease in a patient by administering to the patient with the compound of claim 1 , wherein the protein kinase-mediated disease is a JAK-mediated disease, a FLT3-mediated disease, an Aurora-mediated disease, dermatitis, lung cancer, polycythemia vera, essential thrombocytosis, myelofibrosis, chronic myelogenous leukemia (CML), acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), psoriasis or rheumatoid arthritis.

23. A method of treating or lessening the severity of a protein kinase-mediated disease in a patient by administering to the patient with the pharmaceutical composition of claim 20 , wherein the protein kinase-mediated disease is a JAK-mediated disease, a FLT3-mediated disease, an Aurora-mediated disease, dermatitis, lung cancer, polycythemia vera, essential thrombocytosis, myelofibrosis, chronic myelogenous leukemia (CML), acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), psoriasis or rheumatoid arthritis.

24. A method of inhibiting the activity of a protein kinase with the compound of claim 1 , wherein the protein kinase is JAK kinase, FLT3 kinase, Aurora kinase or a combination thereof.

25. A method of inhibiting the activity of a protein kinase with the pharmaceutical composition of claim 20 , wherein the protein kinase is JAK kinase, FLT3 kinase, Aurora kinase or a combination thereof.