Novel heterocyclic derivatives useful as shp2 inhibitors

A compound of Formula I or a pharmaceutically acceptable salt thereof:

• wherein:
• Each R1 is independently —H;
• halogen;
• —NH2;
• —CN;
• —OH;
• —NO2;
• carboxyl;
• —C1-6alkoxy;
• —C1-6alkyl;
• —C1-6alkyl substituted with halogen, —NH2, —CN, —OH, —NO2, carboxyl, —C1-3alkyl or —C1-3alkoxy;
• or —C1-6alkoxy substituted with halogen, —NH2, —CN, —OH, —NO2, carboxyl, —C1-3alkyl or —C1-3alkoxy;
• R2 is —H;
• halogen;
• —NH2;
• —CN;
• —OH;
• —NO2;
• —N3;
• carboxyl;
• —NHC1-6alkyl;
• —N(C1-6alkyl)2;
• —CONH2;
• —CONHC1-6alkyl;
• —CON(C1-6alkyl)2;
• —COC1-6alkyl;
• —NHCOC1-6alkyl;
• —NC1-6alkyl-CO—C1-6alkyl;
• —C1-6alkoxy;
• —C1-6alkyl;
• —C1-6alkyl substituted with halogen, —NH2, —CN, —OH, —NO2, carboxyl, —C1-3alkyl or —C1-3alkoxy;
• or —C1-6alkoxy substituted with halogen, —NH2, —CN, —OH, —NO2, carboxyl, —C1-3alkyl or —C1-3alkoxy;
• or —C5-10heterocyclic;
• or
• R2 combines with R1 to which it is adjacent to form a 6-10 membered aryl, 5-10 membered heteroaryl or 5-10 membered heterocyclic ring, and each of the ring systems is independently optionally substituted with halogen, —NH2, —CN, —OH, —NO2, carboxyl, oxo, ═O, —CONH2, substituted or unsubstituted —C1-6alkoxy, substituted or unsubstituted —C1-6alkyl, —C1-6alkylene-O—C1-6alkyl, —C1-6alkylene-COOH, —C1-6alkylene-NHCONH2, —CO—N(C1-6alky)2, —C1-6alkylene-NHCO—C1-6alkyl, —CO—CO—N(C1-6alkyl)2, —CO—C1-6alkyl, —SONH2, —SO2NH2, —SOCH3, —SO2CH3, —C5-10heterocyclic or —C5-10heteroaryl;
• Each Y1 is independently N or CR1a;
• Each R1a is independently —H, halogen, —NH2, —CN, —OH, —NO2, carboxyl, —C1-6alkoxy, or —C1-6alkyl;
• R3 is —H or —NH2;
• Each of R4a and R4b is independently —H;
• halogen;
• —NH2;
• —CN;
• —OH;
• —NO2;
• carboxyl;
• —C1-6alkoxy;
• —C1-6alkyl;
• —C1-6alkyl substituted with —F, —Cl, —Br, —I, —NH2, —CN, —OH, —NO2, carboxyl, —C1-3alkyl or —C1-3alkoxy;
• or C1-6alkoxy substituted with —F, —Cl, —Br, —I, —NH2, —CN, —OH, —NO2, carboxyl, —C1-3alkyl or —C1-3alkoxy;
• or
• R4a and R4b together with the carbon atom to which they are both attached form C═O, C═NH, or C═N—OH;
• p is 0, 1, 2 or 3;
• Each of R5a and R5b is independently —H;
• halogen;
• —NH2;
• —CN;
• —OH;
• —NO2;
• carboxyl;
• —C1-6alkoxy;
• —C1-6alkyl;
• —C1-6alkyl substituted with —F, —Cl, —Br, —I, —NH2, —CN, —OH, —NO2, carboxyl, —C1-3alkyl or —C1-3alkoxy;
• or —C1-6alkoxy substituted with —F, —Cl, —Br, —I, —NH2, —CN, —OH, —NO2, carboxyl, —C1-3alkyl or —C1-3alkoxy;
• or
• R5a and R5b together with the carbon atom to which they are both attached form a 3-10 membered heterocyclic or 5-10 membered heteroaryl or C═NR5c, and R5c is —H, or —C1-6alkyl;
• and each of the ring systems is independently optionally substituted with —H, —F, —Cl, —Br, —I, —NH2, —CN, —OH, —NO2, carboxyl, —C1-3alkoxy, or —C1-3alkyl;
• q is 0, 1, 2, 3 or 4;
• W is absent, —O, —S or —NRw;
• and Rw is —H;
• halogen;
• —NH2;
• —CN;
• —OH;
• —NO2;
• carboxyl;
• —CO—C1-6alkyl;
• —CO—OC1-6alkyl;
• —C1-6alkyl-O— C1-6alkoxy;
• —C1-6alkoxy;
• —C1-6alkyl;
• —C1-3alkyl substituted with —F, —Cl, —Br, —NH2, —CN, —OH, —NO2, carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy;
• or C1-3alkoxy substituted with —F, —Cl, —Br, —NH2, —CN, —OH, —NO2, carboxyl, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, propoxy or isopropoxy;
• Ring A is absent or a 3-10 membered ring;
• represents a single bond or a double bond;
• When ring A is absent, Y2 is CR2aR2b, NR2a or O, and Y3 is CR3aR3b, NR3a or O;
• When ring A is a 3-10 membered ring,
• i) Y2 is CR2a or N, and Y3 is CR3a or N, when represents a single bond;
• or
• ii) Y2 is C, and Y3 is C, when represents a double bond;
• Each of R2a and R2b is independently —H;
• halogen;
• —NH2;
• —CN;
• —OH;
• —NO2;
• carboxyl;
• —C1-6alkoxy;
• —C1-6alkyl;
• —C1-6alkyl substituted with —F, —Cl, —Br, —I, —NH2, —CN, —OH, —NO2, carboxyl, —C1-3alkyl or —C1-3alkoxy;
• or —C1-6alkoxy substituted with —F, —Cl, —Br, —I, —NH2, —CN, —OH, —NO2, carboxyl, —C1-3alkyl or —C1-3alkoxy;
• Each of R3a and R3b is independently —H;
• halogen;
• —NH2;
• —CN;
• —OH;
• —NO2;
• carboxyl;
• —C1-6alkoxy;
• —C1-6alkyl;
• —C1-6alkyl or —C1-6alkoxy substituted with —F, —Cl, —Br, —I, —NH2, —CN, —OH, —NO2, carboxyl, —C1-3alkyl or —C1-3alkoxy;
• Each R6 is independently —H, halogen, —NR6aR6b, —CN, —OH, —NO2, oxo, ═O, carboxyl, —C1-6alkoxy, —C1-6alkyl, —C1-6alkylene-NR6aR6b, —C1-6alkylene-O—C1-6alkyl, —C1-6alkylene-CO—OR6a, —C1-6alkylene-C3-10heterocyclic, —C1-6alkylene-C5-10heteoaryl, —C1-6alkylene-CO—NR6aR6b, —C1-6alkylene-NR6a—CO—NR6aR6b, —C1-6alkylene-NR6a—CO—C1-6alkyl, —CO—NR6aR6b, —CO—CO—NR6aR6b, —C3-10carbocyclic, —C3-10heterocyclic, —CO—C1-6alkyl, —CO—C1-6alkylene-NR6aR6b, —CO—NR6a—C3-10heterocyclic, —CO—C3-10heteocyclic, —O—C1-6alkylene-CO—OR6a, —O—C1-6alkylene-CO—NR6aR6b, —O—C1-6alkylene-NR6aR6b, —O—C3-10carbocyclic, —O—C3-10heterocyclic, —NR6a—CO—C1-6alkyl, —NR6a—CO—NR6aR6b, —NR6a—CO—C5-10heteoaryl, —NR6a—C1-6alkylene-NR6aR6b, —NR6a—C1-6alkylene-C3-10heterocyclic, —NR6a—C1-6alkylene-C5-10heteroaryl, —NR6a—SO2C1-6alkyl, —S—C1-6alkyl, —SONR6aR6b, —SO2NR6aR6b, —SO—C1-6alkyl, —SO2C1-6alkyl, —PO(C1-6alkyl)2, —PO(C1-6alkoxy)2, —C3-10heterocyclic or —C5-10heteroaryl;
• each of which is independently optionally substituted with —F, —Cl, —Br, —I, —NH2, —CN, —OH, —NO2, carboxyl, oxo, ═O, —C1-3alkoxy, or —C1-3alkyl;
• and n is 0, 1, 2, 3, 4, 5 or 6;
• or
• Two adjacent R6 can be joined together to form a 6-membered aryl, 5-membered heteroaryl, 6-membered heteroaryl, —C3-6heterocyclic or —C3-6carbocyclic, wherein each of the ring systems is independently optionally substituted with halogen, —NH2, —CN, —OH, —NO2, ═O, oxo, carboxyl, —CONH2, —PO(C1-6alkyl)2, —C1-6alkoxy or —C1-6alkyl;
• Each of R6a and R6b is independently —H;
• halogen;
• —NH2;
• —CN;
• —OH;
• —NO2;
• carboxyl;
• —C1-6alkoxy;
• —C1-6alkyl;
• —C1-3alkyl substituted with halogen, —NH2, —CN, —OH, —NO2, -carboxyl, —C1-3alkyl or —C1-3alkoxy;
• or —C1-3alkoxy substituted with halogen, —NH2, —CN, —OH, —NO2, carboxyl, —C1-3alkyl or —C1-3alkoxy.