Compounds and compositions for inhibiting the activity of shp2

A method of treating or preventing a disease or disorder that is mediated by the activity of SHP2 in a subject in need thereof, said method comprising administering to the subject an effective amount of a compound of Formula I:

• or a pharmaceutically acceptable salt thereof, wherein:
• R1 is selected from:
• R2 and R3 together with the nitrogen to which both R2 and R3 are attached form a ring selected from piperidinyl, piperazinyl, 2-oxa-8-azaspiro[4.5]decan-8-yl, 8-azaspiro[4.5]decan-8-yl and pyrrolidinyl;
• wherein said pyrrolidinyl, piperazinyl, 2-oxa-8-azaspiro[4.5]decan-8-yl, 8-azaspiro[4.5]decan-8-yl or piperidinyl is unsubstituted or substituted with 1 to 3 groups independently selected from amino, methyl, ethyl, amino-methyl, methyl-amino, hydroxyl, cyano, fluoro-methyl, fluoro and ((((5-methyl-2-oxo-1,3-dioxol-4-yl)methoxy)carbonyl)amino)methyl;
• R4 is selected from hydroxyl, C1-3alkoxy and OC(O)C1-3alkyl;
• R5 is selected from H and methyl;
• R6 is selected from hydrogen, methyl and phenyl;
• R, is selected from hydrogen, methyl, ethyl, phenyl and benzyl;
• R3 is selected from hydrogen and methyl;
• Y1 is selected from N and CH;
• Y2 is selected from N and CH;
• Y3 is selected from NH and CH2;
• Y4 is selected from N and CH;
• and
• Y5 is selected from N and CH;
• or a pharmaceutically acceptable salt thereof.

A method of treating or preventing a disease or disorder that is mediated by the activity of SHP2 in a subject in need thereof, said method comprising administering to the subject an effective amount of a compound of Formula II:

• or a pharmaceutically acceptable salt thereof, wherein:
• R1 is selected from:
• R2 and R3 together with the nitrogen to which both R2 and R3 are attached form a ring selected from piperidinyl, piperazinyl, 2-oxa-8-azaspiro[4.5]decan-8-yl, 8-azaspiro[4.5]decan-8-yl and pyrrolidinyl;
• wherein said pyrrolidinyl, piperazinyl, 2-oxa-8-azaspiro[4.5]decan-8-yl, 8-azaspiro[4.5]decan-8-yl or piperidinyl is unsubstituted or substituted with 1 to 3 groups independently selected from amino, methyl, ethyl, amino-methyl, methyl-amino, hydroxyl, cyano, fluoro-methyl, fluoro and ((((5-methyl-2-oxo-1,3-dioxol-4-yl)methoxy)carbonyl)amino)methyl;
• R4 is selected from hydroxyl, C1-3alkoxy and OC(O)C1-3alkyl;
• R5 is selected from H and methyl;
• R6 is selected from hydrogen, methyl and phenyl;
• R7 is selected from hydrogen, methyl, ethyl, phenyl and benzyl;
• R8 is selected from hydrogen and methyl;
• Y1 is selected from N and CH;
• Y2 is selected from N and CH;
• Y3 is selected from NH and CH2;
• Y4 is selected from N and CH;
• and
• Y5 is selected from N and CH.