SHP2 phosphatase inhibitors and methods of use thereof

A compound of formula (I), or a pharmaceutically acceptable salt thereof,

• wherein:
• X is N—R66, O, S, S(O), SO2, CR13R14, —O—C(R13R14)—, —C(R13R14)O—, C(O), or —C(═C(R15R16))—;
• R1 is selected from the group consisting of a 5-10 membered monocyclic or bicyclic aryl or heteroaryl, and a 4-7 membered heterocycle, wherein R1 is optionally substituted with one or more substituents each independently selected from the group consisting of —R10, —OR10, —S(O)wR10 wherein w is 0, 1 or 2, —N(R10)2, —OS(O)w—R10 wherein w is 0, 1, or 2, —S(O)w—N(R10)2 wherein w is 0, 1 or 2, —S(O)(NH)R10, —P(O)(R10)2, —C(O)R10, —C(O)N(R10)2, oxo, halogen and nitrile;
• wherein each R10 is independently selected from the group consisting of H, —(C1-C6)alkyl, —(C1-C6)haloalkyl, (C3-C6)cycloalkyl, heterocycloalkyl, aryl, and heteroaryl, wherein R10 in turn may be substituted with one or more substituents each selected from the group consisting of halo, —C(O)R20, —(C1-C6)alkyl, and —(C1-C6)haloalkyl;
• wherein R20 is —OH, halo, or —(C1-C6)alkyl;
• R4 and R5 are each independently selected from the group consisting of H, —OH, —(C1-C6)alkyl, —O(C1-C6)alkyl, —(C1-C6)alkyl-O—R6, —C(O)N(R6)2, —N(R6)2, halogen, —(C1-C6)alkyl-N(R6)2, and nitrile, wherein said —(C1-C6)alkyl, —O(C1-C6)alkyl, —(C1-C6)alkyl-O—R6, or —(C1-C6)alkyl-N(R6)2 is optionally substituted with one or more substituents selected from the group consisting of —OH, —NH2, oxo, and halogen,
• or R4 and R5, taken together with the atoms to which they are attached, form a 3-7 membered carbocyclic or heterocyclic saturated or partially unsaturated ring, which ring is optionally substituted with —OH, —(C1-C6)alkyl, —O(C1-C6)alkyl, —N(R6)2, halogen, oxo, or nitrile;
• or R4 and R8, taken together with the atoms to which they are attached, form a 4-7 membered carbocyclic or heterocyclic ring, which ring is optionally substituted with —OH, —(C1-C6)alkyl, —O(C1-C6)alkyl, —N(R6)2, halogen, oxo, or nitrile;
• or R4 and R8, taken together with the atoms to which they are attached, form a 3-membered carbocyclic or heterocyclic ring, which ring is optionally substituted with —OH, —(C1-C6)alkyl, —O(C1-C6)alkyl, —N(R6)2, halogen, oxo, or nitrile;
• R6 is independently for each occurrence selected from the group consisting of H, —(C1-C6)alkyl, and phenyl;
• R66 is selected from the group consisting of H, —(C1-C6)alkyl, and phenyl;
• R11 and R12 are each independently selected from the group consisting of H, —OH, —(C1-C6)alkyl, —O(C1-C6)alkyl, —(C1-C6)alkyl-O—R6, aryl, arylalkylene, heteroaryl, heteroarylalkylene, —C(O)N(R6)2, —N(R6)2, halogen, —(C1-C6)alkyl-N(R6)2, —CO2H, and nitrile, wherein said —(C1-C6)alkyl, —O(C1-C6)alkyl, —(C1-C6)alkyl-O—R6, aryl, arylalkylene, heteroaryl, heteroarylalkylene, or —(C1-C6)alkyl-N(R6)2 is optionally substituted with one or more substituents selected from the group consisting of —OH, —N(H)2, and halogen;
• or R11 and R12, taken together with the atoms to which they are attached, form a 5-7 membered heterocyclic ring;
• or R4 and R12, taken together with the atoms to which they are attached, form a 5-7 membered carbocyclic or heterocyclic ring;
• or R4 and R11, taken together with the atoms to which they are attached, form a 5-7 membered carbocyclic or heterocyclic ring;
• R8 and R9 are each independently selected from the group consisting of H, —(C1-C6)alkyl, —(C1-C6)alkyl-N(R6)2, —OR6, —(C1-C6)alkyl-O—R6, —C(O)NH2, —N(R6)2, halogen, and nitrile;
• R13 and R14 for each occurrence, are independently selected from the group consisting of H, —OH, —(C1-C6)alkyl, —O(C1-C6)alkyl, —C(O)N(R6)2, —N(R6)2, halogen, and —(C1-C6)alkyl-N(R6);
• R15 and R16 for each occurrence, are independently selected from the group consisting of H, —OH, —(C1-C6)alkyl, —O(C1-C6)alkyl, —C(O)N(R6)2, —N(R6)2, halogen, and —(C1-C6)alkyl-N(R6)2, or R15 and R16 taken together with the carbon to which they are attached may form a (C3-C4)cycloalkyl;
• and each of m and n is, independently, 0, 1, 2, or 3, with m+n being at least 2 and no more than 4.