Inhibitors of the oncogenic shp2 phosphatase and uses thereof

A method of treating cancer comprising administering a therapeutically effective dose of an SHP2 inhibiting compound of Formula Ia:

• or a pharmaceutically acceptable salt thereof, wherein,
• R1 is:
• or hydrogen;
• R2 is selected from the group of:
• —H, halogen, —OH, —C═O—N(R13)2, —CN, —C═O—OH, —C═O—NR13—N(R13)2, —C═O—R12, —C(═O)O—R13, —R12, —O—R13, C1-C16 substituted or unsubstituted alkyl, C1-C16 substituted or unsubstituted alkenyl, substituted or unsubstituted C6 aryl, substituted or unsubstituted C3-C8 cycloalkyl, substituted or unsubstituted C3-C8 cycloalkenyl, substituted or unsubstituted C3-C8 cycloalkynyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted heterocycloalkenyl, substituted or unsubstituted heterocycloalkynyl, C1-C16 substituted or unsubstituted alkynyl,
• A is —CH2—, —S—, —O—, —CH2—CH2—, —C(R12)2—, or —C(R12)2—C(R12)2—;
• Y is —O—, —S—, —NH— or —CH═CH—;
• L is a bond, —CH═, or —C(═O)CH═CH—.
• R3 is selected from the group of hydrogen, halogens, —C═O—N(R13)2, —CN, —C═O—OH, —C═O—NR13—N(R13)2, —C═O—R12, —C(═O)O—R13, —R12, —O—R13, —OH, —F, —Cl, —CF3, —OCF3, C1-C16 substituted or unsubstituted alkyl, C1-C16 substituted or unsubstituted alkenyl, substituted or unsubstituted C6 aryl, substituted or unsubstituted C3-C8 cycloalkyl, substituted or unsubstituted C3-C8 cycloalkenyl, substituted or unsubstituted C3-C8 cycloalkynyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted heterocycloalkenyl, substituted or unsubstituted heterocycloalkynyl, or C1-C16 substituted or unsubstituted alkynyl;
• R4, R5, R6, R7, R8, and R9 are each independently hydrogen, halogen, —OR13, —SR13, —N(R13)2, —NO2, —C(O)OR13, —C(O)N(R13)2, —C(S)OR13, —C(S)SR13, —C(O)SR13, C1-C16 substituted or unsubstituted alkyl, C1-C16 substituted or unsubstituted alkenyl, substituted or unsubstituted C6 aryl, substituted or unsubstituted C3-C8 cycloalkyl, substituted or unsubstituted C3-C8 cycloalkenyl, substituted or unsubstituted C3-C8 cycloalkynyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted heterocycloalkenyl, substituted or unsubstituted heterocycloalkynyl, or C1-C16 substituted or unsubstituted alkynyl;
• R10 and R11 either together form a substituted or unsubstituted 6 membered aryl ring, or are each independently hydrogen, —OR13, —SR13, —N(R13)2, —NO2, —CN, —C(O)OR13, —C(O)N(R13)2, —C(S)OR13, —C(S)SR13, —C(O)SR13, C1-C16 substituted or unsubstituted alkyl, C1-C16 substituted or unsubstituted alkenyl, substituted or unsubstituted C6 aryl, substituted or unsubstituted C3-C8 cycloalkyl, substituted or unsubstituted C3-C8 cycloalkenyl, substituted or unsubstituted C3-C8 cycloalkynyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted heterocycloalkenyl, substituted or unsubstituted heterocycloalkynyl, or C1-C16 substituted or unsubstituted alkynyl;
• R12 are each independently hydrogen, halogens, —OH, —CN, —SH, —NO2,
• C1-C16 substituted or unsubstituted alkyl, C1-C16 substituted or unsubstituted alkyl, C1-C16 substituted or unsubstituted alkenyl, substituted or unsubstituted C6 aryl, substituted or unsubstituted C3-C8 cycloalkyl, substituted or unsubstituted C3-C8 cycloalkenyl, substituted or unsubstituted C3-C8 cycloalkynyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted heterocycloalkenyl, substituted or unsubstituted heterocycloalkynyl, or C1-C16 substituted or unsubstituted alkynyl;
• R13 are each independently C1-C16 substituted or unsubstituted alkyl, C1-C16 substituted or unsubstituted alkyl, C1-C16 substituted or unsubstituted alkenyl, substituted or unsubstituted C6 aryl, substituted or unsubstituted C3-C8 cycloalkyl, substituted or unsubstituted C3-C8 cycloalkenyl, substituted or unsubstituted C3-C8 cycloalkynyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted heterocycloalkenyl, substituted or unsubstituted heterocycloalkynyl, or C1-C16 substituted or unsubstituted alkynyl;
• with the proviso that the compound is not: