Tyrosine kinase inhibitors

A compound of Formula I

• or a pharmaceutically acceptable salt or stereoisomer thereof, wherein
• a is 0 or 1;
• b is 0 or 1;
• m is 0, 1, or 2;
• s is 1 or 2;
• t is 1, 2, or3;
• X═Y is C═N, N═C, or C═C;
• R is H or C1-C6 alkyl;
• R1 and R5 are independently selected from:
• 1) H,
• 2) (C═O)aObC1-C10 alkyl,
• 3) (C═O)aObaryl,
• 4) (C═O)aObC2-C10 alkenyl,
• 5) (C═O)aObC2-C10 alkynyl,
• 6) CO2H,
• 7) halo,
• 8) OH,
• 9) ObH-Cl6 perfluoroalkyl,
• 10) (C═O)aNR7R8,
• 11) CN,
• 12) (C═O)aObC3-C8 cycloalkyl, and
• 13) (C═O)aObheterocyclyl,
• said alkyl, aryl, alkenyl, alkynyl, cycloalkyl, and heterocyclyl is optionally substituted with one or more substituents selected from R6;
• R2 and R3 are independently selected from:
• 1) H,
• 2) (C═O)OaC1-C6 alkyl,
• 3) (C═O)Oaaryl,
• 4) C1-C6 alkyl,
• 5) SO2Ra, and
• 6) aryl;
• R4 is selected from:
• 1) (C═O)aObC1-C10 alkyl,
• 2) (C═O)aObaryl,
• 3) (C═O)aObC2-C10 alkenyl,
• 4) (C═O)aObC2-C10 alkynyl,
• 5) CO2H,
• 6) halo,
• 7) OH,
• 8) ObC1-C6 perfluoroalkyl,
• 9) (C═O)aNR7R8,
• 10) CN,
• 11) (C═O)aObC3-C8 cycloalkyl, and
• 12) (C═O)aObheterocyclyl,
• said alkyl, aryl, alkenyl, alkynyl, cycloalkyl, and heterocyclyl is optionally substituted with one or more substituents selected from R6;
• R6 is:
• 1) (C═O)aObC1-C10 alkyl,
• 2) (C═O)aObaryl,
• 3) C2-C10 alkenyl,
• 4) C2-C10 alkynyl,
• 5) (C═O)aObheterocyclyl,
• 6) CO2H,
• 7) halo,
• 8) CN,
• 9) OH,
• 10) ObC1-C6 perfluoroalkyl,
• 11) Oa(C═O)NR7R8,
• 12) oxo,
• 13) CHO,
• 14) NR7R8 or the N-oxide, or
• 15) (C═O)aObC3-C8 cycloalkyl,
• said alkyl, aryl, alkenyl, alkynyl, heterocyclyl, and cycloalkyl optionally substituted with one or more substituents selected from R6a;
• R6a is selected from:
• 1) (C═O)rOs(C1-C10)alkyl, wherein r and s are independently 0 or 1,
• 2) Or(C1-C3)perfluoroalkyl, wherein r is 0 or 1,
• 3) (C0-C6)alkylene-S(O)mRa, wherein m is 0, 1, or 2,
• 4) oxo,
• 5) OH,
• 6) halo,
• 7) CN,
• 8) (C2-C10)alkenyl,
• 9) (C2-C10)alkynyl,
• 10) (C3-C6)cycloalkyl,
• 11) (C0-C6)alkylene-aryl,
• 12) (C0-C6)alkylene-heterocyclyl,
• 13) (C0-C6)alkylene-N(Rb)2,
• 14) C(O)Ra,
• 15) (C1-C6)alkylene-CO2Ra,
• 16) C(O)H, and
• 17) (C0-C6)alkylene-CO2H,
• said alkyl, alkenyl, alkynyl, cycloalkyl, aryl, and heterocyclyl is optionally substituted with up to three substituents selected from Rb, OH, (C1-C6)alkoxy, halogen, CO2H, CN, O(C═O)C1-C6 alkyl, oxo, and N(Rb)2;
• R7 and R8 are independently selected from:
• 1) H,
• 2) (C═O)ObC1-C10 alkyl,
• 3) (C═O)ObC3-C8 cycloalkyl,
• 4) (C═O)Obaryl,
• 5) (C═O)Obheterocyclyl,
• 6) C1-C10 alkyl,
• 7) aryl,
• 8) C2-C10 alkenyl,
• 9) C2-C10 alkynyl,
• 10) heterocyclyl,
• 11) C3-C8 cycloalkyl,
• 12) SO2Ra, and
• 13) (C═O)NRb2,
• said alkyl, cycloalkyl, aryl, heterocyclyl, alkenyl, and alkynyl is optionally substituted with one or more substituents selected from R6a, or
• R7 and R8 can be taken together with the nitrogen to which they are attached to form a monocyclic or bicyclic heterocycle with 5-7 members in each ring and optionally containing, in addition to the nitrogen, one or two additional heteroatoms selected from N, O and S, said monocyclic or bicyclic heterocycle optionally substituted with one or more substituents selected from R6a;
• Ra is:
• (1) (C1-C6)alkyl,
• (2) (C3-C6)cycloalkyl,
• (3) aryl, or
• (4) heterocyclyl;
• and
• (5)
• Rb is:
• (1) H,
• (2) (C1-C6)alkyl,
• (3) aryl,
• (4) heterocyclyl,
• (5) (C3-C6)cycloalkyl,
• (6) (C═O)OC1-C6 alkyl,
• (7) (C═O)C1-C6 alkyl, or
• (8) S(O)2Ra.