Bicyclic compounds as kinases inhibitors

1. A compound according to Formula I:

or a pharmaceutically acceptable salt, solvate, stereoisomer or a tautomer thereof, wherein

X is N;

Y is O, S, or NH;

W is CHR 3 , O, S, NH, C(O), S(O), or S(O) 2 ;

Ar is C 6 -C 12 aryl, 5-12 membered heteroaryl, C 3 -C 12 cycloalkyl, or 3-12 membered heteroalicyclic, and Ar is optionally substituted by one or more R 10 ) groups;

R 1 is hydrogen, —(CHR 3 ) m N(O)R 11 R 12 , —(CHR 3 ) m NR 11 R 12 , or —(CHR 3 ) m R 13 ;

R 2 is OCH 3 , or OCH 2 CH 3 ;

each R 3 is independently hydrogen or C 1 -C 6 alkyl;

R 4 , R 5 , R 6 , R 7 , R 8 and R 9 are independently hydrogen, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, F, Cl, CN, or CF 3 ;

each R 10 is independently halogen, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 6 cycloalkyl, C 6 -C 12 aryl, 3-12 membered heteroalicyclic, 5-12 membered heteroaryl, NO 2 , —NR 15 R 16 , —(CR 17 R 18 ) n OR 15 , CN, —C(O)R 15 , —O(CO)R 15 , —O(CR 17 R 18 ) n R 15 , —OCR 17 R 18 (CR 17 R 18 ) n NR 15 R 16 , —OCR 17 R 18 (CR 17 R 18 ) n OR 15 , —NR 15 C(O)R 16 , —(CR 17 R 18 ) n C(O)OR 15 , —(CR 17 R 18 ) n NR 15 R 16 , —NR 15 (CO)—NR 15 R 16 , —NR 15 S(O) p R 16 , —S(O) t R 15 , or —S(O) 2 NR 15 R 16 , wherein two R 10 groups on adjacent atoms of Ar may, together with the adjacent atoms to which two R 10 groups are bound, be combined to form a C 6 -C 12 aryl, 5-12 membered heteroaryl, C 3 -C 12 cycloalkyl or 3-12 membered heteroalicyclic;

R 11 and R 12 are independently hydrogen, C 1 -C 6 alkyl, or —CR 17 R 18 (CR 17 R 18 ) n OR 15 ;

R 13 is morpholine, piperidine, piperazine, piperazine-N(C 1 -C 6 alkyl), or pyrrolidine, and each hydrogen in R 13 is optionally substituted by one or more C 1 -C 6 alkyl, C 1 -C 6 alkoxy, halogen, OH, NH 2 , NH(C 1 -C 6 alkyl), or N(C 1 -C 6 alkyl) 2 ;

each R 15 , R 16 , R 17 , and R 18 is independently hydrogen, C 1 -C 6 alkyl; C 6 -C 12 aryl, 5-12 membered heteroaryl, C 3 -C 12 cycloalkyl or 3-12 membered heteroalicyclic; or any two of R 15 , R 16 , R 17 , and R 18 bound to the same nitrogen atom may, together with the nitrogen to which they are bound, be combined to form a 3 to 12 membered heteroalicyclic or 5-12 membered heteroaryl group optionally containing 1 to 3 additional heteroatoms selected from the group consisting of N, O, and S; or any two of R 15 , R 16 , R 17 , and R 18 bound to the same carbon atom may, together with the carbon to which they are bound, be combined to form a C 6 -C 12 aryl, 5-12 membered heteroaryl, C 3 -C 12 cycloalkyl, or 3-12 membered heteroalicyclic group;

each m is independently 1, 2, or 3;

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

each p is independently 1 or 2; and

each t is independently 0, 1, or 2.

2. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein Y is NH, and W is O.

3. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein R 1 is H, CH 2 NR 11 R 12 , or CH 2 —N-piperidine.

4. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein R 4 , R 5 , R 6 , R 7 , R 8 and R 9 are independently selected from the group consisting of hydrogen, CH 3 , OCH 3 , F, Cl, CN, and CF 3 .

5. A compound according to Formula II:

or a pharmaceutically acceptable salt, solvate, stereoisomer or tautomer thereof, wherein

R 1 is hydrogen, —(CHR 3 ) m N(O)R 11 R 12 , —(CHR 3 ) m NR 11 R 12 , or —(CHR 3 ) m R 13 ;

R 2 is F, Cl, CN, CF 3 , or OR 14 ;

each R 3 is independently hydrogen or C 1 -C 6 alkyl;

R 8 is hydrogen, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, F, Cl, CN, or CF 3 ;

R 11 and R 12 are independently hydrogen, C 1 -C 6 alkyl, or —CR 17 R 18 (CR 17 R 18 ) n OR 15 ;

R 13 is morpholine, piperidine, piperazine, piperazine-N(C 1 -C 6 alkyl), or pyrrolidine, and each hydrogen in R 13 is optionally substituted by one or more C 1 -C 6 alkyl, C 1 -C 6 alkoxy, halogen, OH, NH 2 , NH(C 1 -C 6 alkyl), or N(C 1 -C 6 alkyl) 2 ;

R 14 is C 1 -C 6 alkyl, —CR 17 R 18 (CR 17 R 18 ) n OR 15 , or tetrahydrofuran-3-yl;

each R 15 , R 16 , R 17 , and R 18 is independently hydrogen, C 1 -C 6 alkyl; C 6 -C 12 aryl, 5-12 membered heteroaryl, C 3 -C 12 cycloalkyl or 3-12 membered heteroalicyclic; or any two of R 15 , R 16 , R 17 , and R 18 bound to the same nitrogen atom may, together with the nitrogen to which they are bound, be combined to form a 3 to 12 membered heteroalicyclic or 5-12 membered heteroaryl group optionally containing 1 to 3 additional heteroatoms selected from the group consisting of N, O, and S; or any two of R 15 , R 16 , R 17 , and R 18 bound to the same carbon atom may, together with the carbon to which they are bound, be combined to form a C 6 -C 12 aryl, 5-12 membered heteroaryl, C 3 -C 12 cycloalkyl, or 3-12 membered heteroalicyclic group;

each R 19 , R 20 , R 22 and R 23 is independently hydrogen, halogen, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 6 cycloalkyl, C 6 -C 12 aryl, 3-12 membered heteroalicyclic, 5-12 membered heteroaryl, NO 2 , —NR 15 R 16 , —(CR 17 R 18 n OR 15 , CN, —C(O)R 15 , —O(CO)R 15 , —O(CR 17 R 18 ) n R 15 , —OCR 17 R 18 (CR 17 R 18 ) n NR 15 R 16 , —OCR 17 R 18 (CR 17 R 18 ) n OR 15 , —NR 15 C(O)R 16 , —(CR 17 R 18 ) n C(O)OR 15 , —(CR 17 R 18 ) n NR 15 R 16 , —NR 15 (CO)—NR 15 R 16 , —NR 15 S(O) p R 16 , —S(O) t R 15 , and —S(O) 2 NR 15 R 16 ;

R 21 is halogen, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 6 cycloalkyl, C 6 -C 12 aryl, 3-12 membered heteroalicyclic, 5-12 membered heteroaryl, NO 2 , —NR 15 R 16 , —(CR 17 R 18 ) n OR 15 , CN, —C(O)R 15 , —O(CO)R 15 , —O(CR 17 R 18 ) n R 15 , —OCR 17 R 18 (CR 17 R 18 ) n NR 15 R 16 , —OCR 17 R 18 (CR 17 R 18 ) n OR 15 , —NR 15 C(O)R 16 , —(CR 17 R 18 ) n C(O)OR 15 , —(CR 17 R 18 ) n NR 15 R 16 , —NR 15 (CO)—NR 15 R 16 , —NR 15 S(O) p R 16 , —S(O) t R 15 , and —S(O) 2 NR 15 R 16 ;

each m is independently 1, 2, or 3;

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

each p is independently 1 or 2; and

each t is independently 0, 1, or 2.

6. The compound of claim 5 or a pharmaceutically acceptable salt thereof, wherein R 1 is H or CH 2 N(C 1 -C 6 alkyl) 2 .

7. The compound of claim 5 or a pharmaceutically acceptable salt thereof, wherein R 2 is OCH 3 , OCH 2 CH 3 , or tetrahydrofuran-3-yloxy.

8. The compound of claim 5 or a pharmaceutically acceptable salt thereof, wherein R 8 is hydrogen, F, Cl, CN, or CF 3 .

9. A compound, or its pharmaceutically acceptable salt, solvate, stereoisomer or tautomer thereof, wherein the compound is selected from the group consisting of:

(E)-4-(dimethylamino)-N-(7-methoxy-4((4-phenoxypheny)amino)quinazolin-6-yl)but-2-enamide;

(E)-4-(dimethylamino)-N-(7-ethoxy-4((4-phenoxyphenyl)amino)quinazolin-6-yl)but-2-enamide;

(S,E)-4-(dimethylamino)-N-(4((4-phenoxyphenyl)amino)-7-((tetrahydrofuran-3-yl)oxy)quinazolin-6-yl)but-2-enamide;

(E)-4-(dimethylamino)-N-(4-((4-(4-fluorophenoxy)phenyl)amino)-7-methoxyquinazolin-6-yl)but-2-enamide;

(E)-N-(4-((4-(3-cyanophenoxy)phenyl)amino)-7-methoxyquinazolin-6-yl)-4-(dimethylamino)but-2-enamide;

(E)-4-(dimethylamino)-N-(7-methoxy-4-((4-(pyridin-2-yloxy)phenyl)amino)quinazolin-6-yl)but-2-enamide;

(E)-N-(4-((4-(3,4-dichlorophenoxy)phenyl)amino)-7-methoxyquinazolin-6-yl)-4-(dimethylamino)but-2-enamide;

(E)-4-(diethylamino)-N-(7-methoxy-4-((4-phenoxyphenyl)amino)quinazolin-6-yl)but-2-enamide;

(E)-4-(diethylamino)-N-(4-((4-phenoxyphenyl)amino)quinazolin-6-yl)but-2-enamide;

(E)-N-(4-((4-phenoxyphenyl)amino)quinazolin-6-yl)-4-(piperidin-1-yl)but-2-enamide;

(E)-N-(7-methoxy-4-((4-phenoxyphenyl)amino)quinazolin-6-yl)-4-(piperidin-1-yl)but-2-enamide;

N-(7-methoxy-4-((4-phenoxyphenyl)amino)quinazolin-6-yl)acrylamide;

N-(7-ethoxy-4-((4-phenoxyphenyl)amino)quinazolin-6-yl)acrylamide; and

(S)-N-(4-((4-phenoxyphenyl)amino)-7-((tetrahydrofuran-3-yl)oxy)quinazolin-6-yl)acrylamide.

10. A pharmaceutical composition comprising a compound of claim 1 or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier.