Pyrimidine Inhibitors of Kinase Activity

A compound of formula (I)

• or a pharmaceutically acceptable salt, solvate, prodrug, or a combination thereof, wherein
• G1 is formula (i), (ii), (iii), or (iv)
• m is 0, 1, 2, 3, or 4;
• m′ is 0, 1, 2, or 3;
• m″ is 0, 1, or 2;
• n is 0, 1, or 2;
• p is 0, 1, 2, 3, or 4;
• R1, R2, and R3 are optional substituents, and if present, are each independently alkyl, halogen, —O(alkyl), —O(haloalkyl), or haloalkyl;
• a and b designate the points of attachment at which formula (i), (ii), (iii), (iv) are bound to formula (I);
• R4 and R5, at each occurrence, are each independently hydrogen, alkyl, halogen, or haloalkyl;
• q is 1, 2, 3, or 4;
• Ar1 is aryl or heteroaryl;
• each of which is independently unsubstituted or substituted with 1, 2, 3, 4, or 5 substituents as represented by T, wherein each T is selected from the group consisting of oxo, alkyl, alkenyl, alkynyl, halogen, haloalkyl, CN, NO2, G2, —OR6, —OC(O)R7, —SR6, —S(O)R7, —S(O)2R7, —S(O)2N(R8)(R9), —N(R8)(R9), —N(R8)C(O)R7, —N(R8)C(O)OR7, —N(R8)S(O)2R7, —N(R8)C(O)N(R8)(R9), —N(R8)C(O)—(C1-6 alkylenyl)-N(R8)(R9), —N(R8)S(O)2N(R8)(R9), —C(O)R6, —C(O)OR6, —C(O)N(R8)(R9), —(C1-6 alkylenyl)-G2, —(C1-6 alkylenyl)-OR6, —(C1-6 alkylenyl)-OC(O)R7, —(C1-6 alkylenyl)-SR6, —(C1-6 alkylenyl)-S(O)R7, —(C1-6 alkylenyl)-S(O)2R7, —(C1-6 alkylenyl)-S(O)2N(R8)(R9), —(C1-6 alkylenyl)-N(R8)(R9), —(C1-6 alkylenyl)-N(R8)C(O)R7, —(C1-6 alkylenyl)-N(R8)C(O)OR7, —(C1-6 alkylenyl)-N(R8)S(O)2R7, —(C1-6 alkylenyl)-N(R8)C(O)N(R8)(R9), —(C1-6 alkylenyl)-N(R8)S(O)2N(R8)(R9), —(C1-6 alkylenyl)-C(O)R6, —(C1-6 alkylenyl)-C(O)OR6, and —(C1-6 alkylenyl)-C(O)N(R8)(R9),
• two substituents on the vicinal carbon atoms of Ar1, together with the carbon atoms to which they are attached, optionally form a monocyclic 5- or 6-membered heterocycle containing one or two heteroatoms selected from N(H), O, S, S(O), or S(O)2, wherein each of the monocyclic ring is optionally substituted with 1, 2, 3, or 4 alkyl groups;
• each occurrence of R6 and R9 are each independently hydrogen, alkyl, haloalkyl, —(C1-6 alkylenyl)-CN, —(C1-6 alkylenyl)-OH, —(C1-6 alkylenyl)-C(O)OH, G3, or —(C1-6 alkylenyl)-G3;
• each occurrence of R7 is independently alkyl, haloalkyl, —(C1-6 alkylenyl)-CN, —(C1-6 alkylenyl)-OH, G3, or —(C1-6 alkylenyl)-G3;
• each occurrence of R8 is independently hydrogen, alkyl, or haloalkyl;
• each occurrence of G2 is independently aryl, heteroaryl, heterocycle, cycloalkyl, or cycloalkenyl, each of which is independently unsubstituted or substituted with 1, 2, 3, 4, or 5 substituents selected from the group consisting of G3, —(C1-6 alkylenyl)-G3, and R10,
• each occurrence of G3 is independently aryl, heteroaryl, heterocycle, cycloalkyl, or cycloalkenyl, each of which is independently unsubstituted or substituted with 1, 2, 3, 4, or 5 R10 groups;
• Ar2 is aryl or heteroaryl, each of which is independently unsubstituted or substituted with 1, 2, 3, 4, or 5 R10 groups;
• each occurrence of R10 is independently alkyl, alkenyl, alkynyl, halogen, haloalkyl, oxo, CN, NO2, —ORZ1, —OC(O)RZ2, —SRZ1, —S(O)RZ2, —S(O)2RZ2, —S(O)2N(RZ3)(RZ4), —N(RZ3)(RZ4), —N(RZ3)C(O)RZ2, —N(RZ3)C(O)ORZ2, —N(RZ3)S(O)2RZ2, —N(RZ3)C(O)N(RZ3)(RZ4), —N(RZ3)S(O)2N(RZ3)(RZ4), —C(O)RZ1, —C(O)ORZ1, —C(O)N(RZ3)(RZ4), —(C1-6 alkylenyl)-ORZ1, —(C1-6 alkylenyl)-OC(O)RZ2, —(C1-6 alkylenyl)-SRZ1, —(C1-6 alkylenyl)-S(O)RZ2, —(C1-6 alkylenyl)-S(O)2RZ2, —(C1-6 alkylenyl)-S(O)2N(RZ3)(RZ4), —(C1-6 alkylenyl)-N(RZ3)(RZ4), —(C1-6 alkylenyl)-N(RZ3)C(O)RZ2, —(C1-6 alkylenyl)-N(RZ3)C(O)ORZ2, —(C1-6 alkylenyl)-N(RZ3)S(O)2RZ2, —(C1-6 alkylenyl)-N(RZ3)C(O)N(RZ3)(RZ), —(C1-6 alkylenyl)-N(RZ3)S(O)2N(RZ3)(RZ4), —(C1-6 alkylenyl)-C(O)RZ1, —(C1-6 alkylenyl)-C(O)ORZ1, or —(C1-6 alkylenyl)-C(O)N(RZ3)(RZ4),
• each occurrence of RZ1, RZ3, and RZ4, are each independently hydrogen, alkyl, or haloalkyl;
• and
• each occurrence of RZ2 is independently alkyl or haloalkyl.