Carboxamide-pyrimidine derivatives as SHP2 antagonists

A method of treating cancer in a subject in need thereof, comprising administering an effective amount of a compound according to formula (I):

• or a pharmaceutically acceptable salt thereof, wherein
• X is —N— or —N(Me)- when R1 is cyclohexyl, cyclopentyl, or piperidinyl, each optionally substituted with 1 or two groups selected from —F, —NH2, and —CH2NH2;
• or
• X is a bond when R1 is
• R2 is an aryl or heteroaryl which is substituted with 1-3 groups selected from —F, —Cl, —CF3, C1-C3 alkoxy and C1-C3 alkyl;
• R3 is —H, —NH2, —OH, —Cl, —F, —Br, or —CH3;
• Y is —N—;
• R4 and R5 are independently —H, —NH2, —OH, C1-C3 alkyl, or C1-C3 hydroxyalkyl;
• n is 0, 1, 2, or 3;
• and
• each of R9, R10, R11, R12, R13, R14, R15, and R16, when present, are independently selected from —H, C1-C3 alkyl, —NH2, —OH, —Cl, —F, —Br, C1-C3 aminoalkyl, C1-C3 hydroxyalkyl, C1-C3 alkoxy, and phenyl;
• or
• two of R9, R11, R13 and R16 are taken together to form a bridged bicyclic heterocyclic system which is optionally substituted with 1-3 substituents selected from C1-C3 alkyl, —NH2, —OH, —Cl, —F, —Br, C1-C3 aminoalkyl, C1-C3 hydroxyalkyl, C1-C3 alkoxy, and phenyl;
• or
• two of R9, R10, R11, R12, R13, R14, R15 and R16, which are attached to the same carbon atom, are taken together to form a monocyclic or bicyclic spirocyclyl, which is optionally substituted with 1-3 substituents selected from C1-C3 alkyl, —NH2, —OH, —Cl, —F, —Br, C1-C3 aminoalkyl, C1-C3 hydroxyalkyl, C1-C3 alkoxy, and phenyl;
• or
• two of R9, R10, R11, R12, R13, R14, R15, and R16, which are attached to adjacent carbon atoms, are taken together to form a fused carbocyclyl or heterocyclyl, which is optionally substituted with 1-3 substituents selected from C1-C3 alkyl, —NH2, —OH, —Cl, —F, —Br, C1-C3 aminoalkyl, C1-C3 hydroxyalkyl, C1-C3 alkoxy, and phenyl, to said subject.