Compounds and compositions for inhibiting the activity of SHP2

A compound of formula I:

• in which:
• X1 is selected from N and CH;
• X2 is CR3b;
• X3 is selected from S and a bond;
• Y1 is selected from N and CR7;
• wherein R7 is selected from hydrogen, amino, halo, C1-3alkyl, C1-3alkoxy and hydroxy;
• Y2 is selected from N and CR8;
• wherein R8 is selected from hydrogen, halo, amino, dimethyl-amino, cyano, C3-6cycloalkyl, C1-4alkyl, halo-substituted-C1-3alkyl, halo-substituted-C1-3alkyl-sulfanyl, C1-3alkoxy, halo-substituted-C1-3alkoxy, C1-3alkoxy-C1-3alkoxy, C6-10aryl and C6-10aryl-C0-1alkoxy;
• Y3 is selected from N and CR9;
• wherein R9 is selected from hydrogen, amino, halo, C1-3alkyl, —NH(C3-5cycloalkyl), C1-3alkoxy and hydroxy;
• R1 is selected from hydrogen, halo, halo-substituted-C1-2alkyl, halo-substituted-C1-2alkoxy, C1-2alkyl-hydroxy and cyano;
• or R1 and R8 together with the carbon atoms to which R1 and R8 are attached form a ring selected from 1,3-dioxole, phenyl, pyridine, cyclopentene, dihydrofuran, dihydropyrane;
• wherein said 1,3-dioxole, phenyl, pyridine, cyclopentene, 2,3-dihydrofuran, 2,3-dihydropyrrole, or dihydropyrane can be unsubstituted or substituted 1 to 2 halo groups;
• R2 is selected from hydrogen and halo;
• R3a is selected from hydrogen, methyl and halo-substituted-C1-2alkyl;
• R3b is selected from hydrogen, methyl and amino;
• R4a and R4b are each independently selected from hydrogen, hydroxy and fluoro;
• with proviso that R4a and R4b cannot both be OH;
• with the proviso that R4a and R4b cannot be OH and F simultaneously;
• R5a is selected from amino and amino-methyl;
• R5b is selected from OH, amino, fluoro, C1-6alkyl, methoxy-carbonyl, C3-6cycloalkyl-C1-3alkyl, hydroxy-substituted C1-3alkyl, C1-2alkoxy-substituted C1-3alkyl and a 5 to 6 member heteroaryl ring containing 1 to 4 heteroatoms selected from O, S and N;
• wherein said C1-6alkyl or C1-2alkoxy-substituted C1-3alkyl of R5b is unsubstituted or substituted with 1-3 fluorines;
• with the proviso that if R5a is amino, R5b cannot be OH, amino or fluoro;
• or R5a and R5b, together with the carbon atom to which R5a and R5b are attached, form a group selected from:
• wherein *C represents the carbon atom to which R5a and R5b are attached;
• R10 is amino;
• R11a is selected from hydrogen, hydroxy, fluoro, C1-3alkyl and hydroxy-methyl;
• R11b is selected from fluoro, methyl and hydrogen;
• with proviso that R11a and R11b cannot both be OH and fluoro simultaneously;
• R11c is selected from hydrogen, C1-3alkyl and hydroxy-methyl;
• R12 is selected from hydrogen, halo, hydroxy, C1-3alkyl, halo-substituted-C1-3alkyl, halo-substituted-C1-3alkoxy and C1-3alkoxy;
• R13 is selected from hydrogen, halo and C1-3alkyl;
• R14 is selected from hydrogen and fluoro;
• with proviso that R12 and R13 cannot both be OH and fluoro simultaneously;
• R15 is selected from hydrogen and fluoro;
• and
• R6a and R6b are each independently selected from hydrogen, hydroxy and fluoro;
• with proviso that R6a and R6b cannot both be OH;
• with proviso that R6a and R6b cannot both be OH and fluoro simultaneously;
• or the pharmaceutically acceptable salts thereof;
• with the proviso that a compound of formula I does not include a compound selected from: