Fused bicyclic derivatives of 2,4-diaminopyrimidine as ALK and c-Met inhibitors

A compound of formula I or II

• or a pharmaceutically acceptable salt form thereof,
• wherein
• R1 is H, halogen, —NO2, —OR10, —C(═O)R10, —C(═O)OR10, —C(═O)NR12R13, —NR10R11, C1-6-alkyl, —C1-6-alkyl-OR10, —C1-6-alkyl-NR12R13, C1-6-haloalkyl, C2-6-alkenyl, C2-6-alkynyl, C6-15-aryl, 5-15 membered heteroaryl, C3-10 cycloalkyl, 3-15 membered heterocycloalkyl, pseudohalogen, —S(═O)nR10, —S(═O)2NR12R13, —OCH2F, —OCHF2, —OCF3, —NHOH, —OC(═O)R10, —OC(═O)NR12R13, —NR10C(═O)R11, —NR10C(═O)OR11, —NR10S(═O)2R11, —NR10C(═O)NR12R13, —NR10S(═O)2NR12R13, or —SCF3;
• R2 is a group chosen from C1-6-alkyl, C2-6-alkenyl, C2-6-alkynyl, C6-15-aryl, C3-10-cycloalkyl, 3-15 membered heterocycloalkyl, and 5-15 membered heteroaryl, wherein the R2 group is optionally substituted by one or more members independently chosen from halogen, —NO2, —OR20, ═O, —C(═O)R20, —C(═O)OR20, —C(═O)NR22R23, —NR20R21, C1-6-alkyl-(R25)x, C6-15-aryl-(R25)x, 5-15 membered heteroaryl-(R25)x, C3-10 cycloalkyl-(R25)x, 3-15 membered heterocycloalkyl-(R25)x, pseudohalogen, —S(═O)nR20, —S(═O)2NR22R23, —OCH2F, —OCHF2, —OCF3, —NHOH, —OC(═O)R20, —OC(═O)NR22R23, —NR20C(═O)R21, —NR20C(═O)OR21, —NR20S(═O)2R21, —NR20C(═O)NR22R23, —NR20S(═O)2NR22R23, and —SCF3;
• R3, R4, and R5 are independently chosen from H, halogen, —NO2, —OR30, —C(═O)R30, —C(═O)OR30, —C(═O)NR32R33, —NR30R31, C1-6-alkyl-(R35)x, C6-15-aryl-(R35)x, 5-15 membered heteroaryl-(R35)x, C3-10 cycloalkyl-(R35)x, 3-15 membered heterocycloalkyl-(R35)x, pseudohalogen, —S(═O)R30, —S(═O)2NR32R33, —OCH2F, —OCHF2, —OCF3, —NHOH, —OC(═O)R30, —OC(═O)NR32R33, —NR30C(═O)R31, —NR30C(═O)OR31, —NR30S(═O)2R31, —NR30C(═O)NR32R33, —NR30S(═O)2NR32R33, and —SCF3;
• A1, A2, A3, A4, and A5 are each independently —CZ1Z2—, wherein:
• (a) when any two of Z1 and Z2 are located on adjacent atoms, they may form a bond between the atoms,
• (b) any of Z1 and Z2 may be independently chosen from H, halogen, —NO2, —OR40, —C(═O)R40, —C(═O)OR40, —C(═O)NR42R43, —NR40R41, C1-6-alkyl-(R45)x, C6-15-aryl-(R45)x, 5-15 membered heteroaryl-(R45)x, C3-10 cycloalkyl-(R45)x, 3-15 membered heterocycloalkyl-(R45)x, C2-6-alkenyl-(R45)x, C2-6-alkynyl-(R45)x, pseudohalogen, —S(═O)nR40, —S(═O)2NR42R43, —OCH2F, —OCHF2, —OCF3, —NHOH, —OC(═O)R40, —OC(═O)NR42R43, —NR40C(═O)R41, —NR40C(═O)OR41, —NR40S(═O)2R41, —NR40C(═O)NR42R43, —NR40S(═O)2NR42R43, and —SCF3, and
• (c) any two of Z1 and Z2 may together form a group of formula -A6-A7-A8-A9-A10-,
• wherein A6, A7, A8, A9, and A10 are independently chosen from a bond, —CZ4Z5—, —C(═O)—, —NZ6—, —S—, —S(═O)—, —S(═O)2—, or —O—, wherein:
• (i) when any two of Z1, Z2, Z3, Z4, Z5, and Z6 are located on adjacent atoms, they may form a bond between the atoms, and
• (ii) any of Z4, Z5, and Z6 may be independently chosen from H, halogen, —NO2, —OR50, —C(═O)R50, —C(═O)OR50, —C(═O)NR52R53, —NR50R51, C1-6-alkyl-(R55)x, C6-15-aryl-(R55)x, 5-15 membered heteroaryl-(R55)x, C3-10 cycloalkyl-(R55)x, 3-15 membered heterocycloalkyl-(R55)x, pseudohalogen, —S(═O)nR50, —S(═O)2NR52R53, —OCH2F, —OCHF2, —OCF3, —NHOH, —OC(═O)R50, —OC(═O)NR52R53, —NR50C(═O)R51, —NR50C(═O)OR51, —NR50S(═O)2R51, —NR50C(═O)NR52R53, —NR50S(═O)2NR52R53, and —SCF3;
• R25, R35, R45, and R55 at each occurrence are independently chosen from halogen, —NO2, —OR60, ═O, —C(═O)R60, —C(═O)OR60, —C(═O)NR62R63, —NR60R61, C1-6-alkyl, C1-6-haloalkyl, C2-6-alkenyl, C2-6-alkynyl, C6-15-aryl, 5-15 membered heteroaryl, C3-10 cycloalkyl, 3-15 membered heterocycloalkyl, pseudohalogen, —S(═O)nR60, —S(═O)2NR62R63, —OCH2F, —OCHF2, —OCF3, —NHOH, —OC(═O)R60—OC(═O)NR62R63, —OP(═O)(OH)2, —NR60C(═O)R61, —NR60C(═O)OR61, —NR60S(═O)2R61, —NR60C(═O)NR62R63, —NR60S(═O)2NR62R63, and —SCF3, in which said C1-6-alkyl, C1-6-haloalkyl, C2-6-alkenyl, C2-6-alkynyl, C6-15-aryl, 5-15 membered heteroaryl, C3-10 cycloalkyl, and 3-15 membered heterocycloalkyl groups are optionally substituted by one or more substituents independently chosen from C1-6-alkyl, C2-6-alkenyl, C2-6-alkynyl, halogen, cyano, C3-10 cycloalkyl, phenyl, 5-10 membered heteroaryl-(R79)x, 3-10 membered heterocycloalkyl, —N(R76)2, —C(═O)OR76, —C(═O)N(R76)2, ═O, and —OR76;
• R10, R11, R20, R21, R30, R31, R40, R41, R50, R51, R60, R61 at each occurrence are independently chosen from H, C1-6-alkyl, C2-6-alkynyl, C1-6-haloalkyl, C6-15-aryl, 5-15 membered heteroaryl, C3-10 cycloalkyl, and 3-15 membered heterocycloalkyl, in which said C1-6-alkyl, C2-6-alkynyl, C1-6-haloalkyl, C6-15-aryl, 5-15 membered heteroaryl, C3-10 cycloalkyl, and 3-15 membered heterocycloalkyl groups are optionally substituted by one or more substituents independently chosen from C1-6-alkyl, C2-6-alkenyl, C2-6-alkynyl, halogen, cyano, phenyl, 5-10 membered heteroaryl-(R79)x, 3-10 membered heterocycloalkyl, —N(R76)2, —C(═O)OR76, —C(═O)N(R76)2, ═O, and —OR76;
• R12, R13, R22, R23, R32, R33, R42, R43, R52, R53, R62, and R63 at each occurrence are independently chosen from H, C1-6-alkyl, C2-6-alkynyl, C1-6-haloalkyl, C6-15-aryl, 5-15 membered heteroaryl, C3-10 cycloalkyl, and 3-15 membered heterocycloalkyl, in which said C1-6-alkyl, C2-6-alkynyl, C1-6-haloalkyl, C6-15-aryl, 5-15 membered heteroaryl, C3-10 cycloalkyl, and 3-15 membered heterocycloalkyl groups are optionally substituted by one or more substitutents independently chosen from C1-6-alkyl, halogen, C3-10 cycloalkyl, 3-10 membered heterocycloalkyl-(R87)x, —N(R86)2, cyano, C2-6-alkynyl, ═O, and —OR86;
• or R12 and R13, R22 and R23, R32 and R33, R42 and R43, R52 and R53, or R62 and R63 may form, together with the nitrogen atom to which they are attached, a 3-15 membered heterocycloalkyl group or a 5-15 membered heteroaryl group, in which said 3-15 membered heterocycloalkyl group or 5-15 membered heteroaryl group is optionally substituted by one or more substituents independently chosen from C1-6-alkyl, halogen, and —OH;
• R76 and R86 at each occurrence are independently chosen from H, C1-6-alkyl-(R78)x, and —C(═O)—C1-6-alkyl;
• R78 at each occurrence is independently chosen from ═O and phenyl;
• R79 at each occurrence is ═O;
• R87 at each occurrence is independently chosen from C1-6-alkyl;
• n at each occurrence is independently chosen from 0, 1, and 2;
• and
• x at each occurrence is independently chosen from 0, 1, 2, 3, 4, 5, and 6;
• with the proviso that the compound is not:
• (a)