Benzoxazole kinase inhibitors and methods of use

An isolated compound of Formula II-A-1:

• or a pharmaceutically acceptable salt thereof, wherein:
• X1 is N and X2 is N;
• R1 is hydrogen, -L-C1-10alkyl, -L-C3-8cycloalkyl, -L-C1-10alkylheterocyclyl,
• -L-heteroalkyl, or -L-heterocyclyl, each of which is unsubstituted or substituted by one or more independent R3 substituents;
• L is a bond, C═O, —C(═O)O—, —C(═O)N(R31)—, —S—, —S(O)—, —S(O)2—, —S(O)2N(R31)—, or —N(R31)—;
• k is 1;
• E2 is H;
• W2 is —O—, —NR7—, —S(O)0-2—, —C(O)—, —C(O)N(R7)—, —N(R7)C(O)—, —N(R7)C(O)N(R8)—, —N(R7)S(O)—, —N(R7)S(O)2—, —C(O)O—, —CH(R7)N(C(O)OR8)—, —CH(R7)N(C(O)R8)—, —CH(R7)N(SO2R8)—, —CH(R7)N(R8)—, —CH(R7)C(O)N(R8)—, —CH(R7)N(R8)C(O)—, —CH(R7)N(R8)S(O)—, or —CH(R7)N(R8)S(O)2—;
• R3 is hydrogen, halogen, —OH, —R31, —CF3, —OCF3, —OR31, —NR31R32, —NR34R35, —C(O)R31, or —CO2R31;
• R2 is hydrogen, halogen, —OH, —R31, —CF3, —OCF3, —OR31, —NR31R32, —NR34R35, —C(O)R31, —CO2R31, —C(═O)NR31R32, —C(═O)NR34R35, —NO2, —CN, —S(O)0-2R31, —SO2NR31R32, —SO2NR34R35, —NR31C(═O)R32, —NR31C(═O)OR32, —NR31C(═O)NR32R33, —NR31S(O)0-2R32, —C(═S)OR31, —C(═O)SR31, —NR31C(═NR32)NR33R32, —NR31C(═NR32)OR33, —NR31C(═NR32)SR33, —OC(═O)OR33, —OC(═O)NR31R32, —OC(═O)SR31, —SC(═O)OR31, —P(O)OR31OR32, —SC(═O)NR31R32, bicyclic aryl, substituted monocyclic aryl, hetaryl, C1-10alkyl, C3-8cycloalkyl, C1-10alkyl-C3-8cycloalkyl, C3-8cycloalkyl- C1-10alkyl, C3-8cycloalkyl- C2-10alkenyl, C3-8cycloalkyl- C2-10alkynyl, C2-10alkyl-monocyclic aryl, monocyclic aryl-C2-10alkyl, C1-10alkylbicycloaryl, bicycloaryl —C1-10alkyl, substituted C1-10alkylaryl, substituted aryl-C1-10alkyl, C1-10alkylhetaryl, C1-10alkylheterocyclyl, C2-10alkenyl, C2-10alkynyl, C2-10alkenylaryl, C2-10alkenylhetaryl, C2-10alkenylheteroalkyl, C2-10alkenylheterocyclyl, C2-10alkynylaryl, C2-10alkynylhetaryl, C2-10 alkynylheteroalkyl, C2-10alkynylheterocylyl, C2-10alkenyl-C3-8cycloalkyl, C2-10alkynyl-C3-8cycloalkenyl, C1-10alkoxy C1-10alkyl, C1-10alkoxyC2-10alkenyl, C1-10alkoxyC2-10alkynyl, heterocyclyl, heterocyclyl C1-10alkyl, heterocyclylC2-10alkenyl, heterocyclyl-C2-10alkynyl, aryl-C2-10alkenyl, aryl-C2-10alkynyl, aryl-heterocyclyl, hetaryl- C1-10alkyl, hetaryl-C2-10alkenyl, hetaryl-C2-10alkynyl, hetaryl-C3-8cycloalkyl, hetaryl-heteroalkyl, or hetaryl-heterocyclyl, wherein each of said bicyclic aryl, monocyclic aryl, or heteroaryl moiety is unsubstituted or is substituted with one or more independent halo, —OH, —R31, —CF3, —OCF3, —OR31, —NR31R32, —NR34R35, —C(O)R31, —CO2R31, —C(═O)NR31R32, —C(═O)NR34R35, —NO2, —CN, —S(O)0-2R31, —SO2NR31R32, —SO2NR34R35, —NR31C(═O)R32, —NR31C(═O)OR32, —NR31C(═O)NR32R33, —NR31S(O)0-2R32, —C(═S)OR31, —C(═O)SR31, —NR31C(═NR32)NR33R32, —NR31C(═NR32)OR33, —NR31C(═NR32)SR33, —OC(═O)OR33, —OC(═O)NR31R32, —OC(═O)SR31, —SC(═O)OR31, —P(O)OR31OR32, or —SC(═O)NR31R32, and wherein each of said alkyl, cycloalkyl, heterocyclyl, or heteroalkyl moiety is unsubstituted or is substituted with one or more halo, —OH, —R31, —CF3, —OCF3, —OR31, —O-aryl, —NR31R32, —NR34R35, —C(O)R31, —CO2R31, —C(═O)NR34R35, or —C(═O)NR31R32;
• each of R31, R32, and R33 is independently H or unsubstituted C1-10alkyl;
• R34 and R35 in —NR34R35, —C(═O)NR34R35, or —SO2NR34R35, are taken together with the nitrogen atom to which they are attached to form a 3-10 membered saturated or unsaturated ring;
• wherein said ring is independently unsubstituted or is substituted by one or more —NR31R32 hydroxyl, halogen, oxo, aryl, hetaryl, C1-6alkyl, or O-aryl, and wherein said 3-10 membered saturated or unsaturated ring independently contains 0, 1, or 2 more heteroatoms in addition to the nitrogen atom;
• and
• each of R7 and R8 is independently hydrogen or C1-10alkyl.