Tyrosine kinase inhibitors

A compound of Formula I

• or a pharmaceutically acceptable salt or stereoisomer thereof, wherein
• A and B are independently N or N+—O−;
• Y is O, S or N—R4;
• R1 and R2 are independently:
• 1) H,
• 2) Or(C1–C6)perfluoroalkyl,
• 3) OH,
• 4) CN,
• 5) halogen,
• 6) (C═O)rOs(C1–C10)alkyl,
• 7) (C═O)rOs(C2–C10)alkenyl,
• 8) (C═O)rOs(C2–C10)alkynyl,
• 9) (C═O)rOsaryl,
• 10) (C═O)rOsheterocyclyl,
• 11) (C0–C6)alkyl-NRaRb, or
• 12) (C1–C6)heterocyclyl,
• wherein r and s are independently 0 or 1, and said alkyl, alkenyl, alkynyl, aryl, and heterocyclyl is optionally substituted with one or more substituents selected from R7;
• R4 is H, aryl or (C1–C6)alkyl;
• R5 is:
• 1) H,
• 2) SO2Rc,
• 3) (C═O)rRc, wherein r is 0 or 1, or
• 4) CO2Rc;
• R6 is:
• 1) phenyl,
• 2) CN,
• 3) halogen, or
• 4) heterocyclyl,
• wherein said phenyl and heterocyclyl are optionally substituted with one or more substituents selected from R7;
• R7 is:
• 1) Or(C═O)SNRaRb,
• 2) (C═O)rOsaryl,
• 3) (C═O)rOs-heterocyclyl,
• 4) halogen,
• 5) OH,
• 6) oxo,
• 7) O(C1–C3)perfluoroalkyl,
• 8) (C1–C3)perfluoroalkyl,
• 9) (C═O)rOs(C1–C6)alkyl,
• 10) CHO,
• 11) CO2H,
• 12) CN,
• 13) (C1–C6)alkyl-NRaRb, or
• 14) (C1–C6)alkyl-heterocyclyl,
• wherein r and s are independently 0 or 1, and said aryl, heterocyclyl and alkyl are optionally substituted with one to three substituents selected from Rd;
• Ra and Rb are 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 Rd;
• Rc is (C1–C6)alkyl, aryl, or heterocyclyl;
• and
• Rd is:
• 1) (C═O)rOs(C1–C10)alkyl, wherein r and s are independently 0 or 1, optionally substituted with up to three substituents selected from OH, (C1–C6)alkoxy, halogen, heterocyclyl, CN, oxo, N(Re)2 and S(O)2Rc,
• 2) Or(C1–C3)perfluoroalkyl,
• 3) (C0–C6)alkylene-S(O)mRc, wherein m is 0, 1, or 2,
• 4) oxo,
• 5) OH,
• 6) halo,
• 7) CN,
• 8) (C0–C6)alkylene-aryl, optionally substituted with up to three substituents selected from Re,
• 9) (C0–C6)alkylene-heterocyclyl, optionally substituted with up to three substituents selected from Re,
• 10) C(O)Rc,
• 11) CO2Rc,
• 12) C(O)H,
• 13) N(Re)2, or
• 14) CO2H;
• Re is:
• 1) H,
• 2) (C1–C6)alkyl, optionally substituted with one or more substituents selected from OH, heterocyclyl, (C1–C6)alkoxy, halogen, CN, oxo, N(Rf)2 and S(O)2Rc,
• 3) aryl, optionally substituted with one or more substituents selected from OH, heterocyclyl, (C1–C6)alkoxy, halogen, CN, N(Rf)2 and S(O)2Rc,
• 4) heterocyclyl, optionally substituted with one or more substituents selected from OH, heterocyclyl, (C1–C6)alkoxy, halogen, CN, oxo, N(Rf)2 and S(O)2Rc, or
• 6) S(O)2Rc, or
• if two Re's are on a nitrogen atom, they can be taken together with the nitrogen to form a heterocycle with 5–7 atoms, optionally containing, in addition to the nitrogen, one or two additional heteroatoms selected from N, O and S, said heterocycle optionally substituted with one or more substituents selected from OH, (C1–C6)alkoxy, halogen, CN, oxo, N(Rf)2 and S(O)2Rc;
• and
• Rf is H, aryl or (C1–C6)alkyl.