Heterocyclic inhibitors of PTPN11

A method of treatment of a PTPN11-mediated disease comprising the administration of a therapeutically effective amount of a compound of Formula I:

• or a salt or tautomer thereof to a patient in need thereof,
• wherein:
• the patient has the PTPN11-mediated disease;
• the PTPN11-mediated disease is a Noonan Syndrome, LEOPARD Syndrome, or cancer selected from the group consisting of breast cancer, colon cancer, lung cancer, leukemia, and melanoma;
• a is 0 or 1;
• b is 0 or 1;
• R1 is halo, C6-10aryl, C3-8cycloalkyl, C3-8cycloalkenyl, or a 5-9 membered heteroaryl group containing 1 to 4 heteroatoms or groups independently selected from N, C(O), O, and S;
• said aryl or heteroaryl of R1 is optionally substituted with 1 to 5 R12 groups independently selected from the group consisting of halo, hydroxy, amino, C1-4alkylamino, C1-4dialkylamino, cyano, C1-4alkyl, C1-4alkoxy, C1-4hydroxyalkyl, C1-4haloalkyl, C1-4aminoalkyl, C3-8cycloalkyl, C3-8cycloalkenyl, NR15C(O)R13, NR15C(O)OR13, NR13C(O)NR15R16, NR15S(O)R13, NR15S(O)2R13, C(O)NR15R16, S(O)NR15R16, S(O)2NR15R16, C(O)R13, C(O)OR13, SR13, S(O)R13, and S(O)2R13;
• R2, R3, R10, and R11 are independently hydrogen, C1-4alkyl, or C3-8cycloalkyl;
• R4, R5, R8, and R9 are independently hydrogen, cyano, C1-4alkyl, C1-4alkoxy, amino, hydroxy, C3-8cycloalkyl, halo, or C1-4alkylamino;
• R6 is amino, C1-4aminoalkyl, or C1-4alkylamino;
• R7 is hydrogen, cyano, amido, halo, hydroxy, C1-4alkyl, C1-4hydroxyalkyl, C3-6cycloalkyl, phenyl, or 5- or 6-membered heteroaryl, each of which is optionally substituted with one or more R17 groups;
• or R6 and R7 together with the carbon atom to which they are both attached form a 3- to 7-membered saturated or unsaturated ring that can contain 1 to 3 heteroatoms or groups independently selected from N, C(O), O, and S(O)m, and that is optionally substituted with one R17 group, and that is optionally substituted with one or more R18 groups;
• m is 0, 1, or 2;
• any two groups selected from R2, R3, R4, R5, R7, R8, R9, R10 and R11 can form a 5- to 6-membered ring, optionally containing a N, O or S heteroatom;
• any two groups selected from R2, R4, R6, R8 and R10 can form a direct bond, or a 1 or 2 atom carbon bridge;
• R13, R15, and R16 are independently hydrogen, C1-4alkyl, or C3-8cycloakyl, wherein said alkyl or cycloalkyl is optionally substituted by one or more substituents selected from the group consisting of hydroxy, cyano and halo;
• R17 is amino, halo, hydroxy, cyano, trifluoromethyl, trifluoromethoxy, C1-4alkyl, or C1-4alkoxy;
• and
• each R18 is independently halo, hydroxy, or cyano.