Shp2 inhibitor and use thereof

A compound of Formula 1A-1, or a stereoisomer, solvate or pharmaceutically acceptable salt thereof:

• wherein,
• R1 is H, halogen, hydroxy, cyano or C1-C6 haloalkyl;
• R2 is selected from a group consisting of H, halogen, hydroxy, oxo, C1-C20 alkyl, C1-C20 alkoxy, C1-C20 haloalkyl, hydroxy-(C1-C20 alkyl)-, (C1-C10 alkoxy)-(C1-C10 alkyl)-, H2N—(C1-C20 alkyl)-, —NH2, —NH(C1-C20 alkyl), —N(C1-C20 alkyl)2, ═NH, nitro, cyano, amidino, —C(O)NH2, —C(O)(C1-C20 alkyl), —C(O)O(C1-C20 alkyl), and carboxy or a salt thereof;
• R3 and R4 are each independently H, C1-C6 alkyl, —NH2, —NH(C1-C6 alkyl), —N(C1-C6 alkyl)2, or H2N—(C1-C6 alkyl)-, or R3 and R4 are connected to each other to form Ring B,
• Ring B is a 3- to 8-membered cyclic ring group optionally containing one oxygen atom and optionally substituted, wherein Ring B can be optionally fused with a cycloalkyl, aryl or heteroaryl ring, and the cycloalkyl, aryl and heteroaryl rings fused with Ring B can be optionally substituted;
• R5 is each independently selected from:
• (i) H, halogen, hydroxy, —NH2, ═NH, —C(O)NH2, nitro, cyano, amidino, or carboxy or a salt thereof,
• (ii) C1-C20 alkyl or C1-C20 alkoxy, which is optionally substituted with at least one substituent selected from a group consisting of halogen, hydroxy, C1-C20 alkyl, C1-C20 haloalkyl, C1-C20 alkoxy, C1-C20 haloalkoxy, —NR′R″, R′C(O)—, R′S(O)2—, R′S(O)2NR″—, R″R′NC(O)—, and R′C(O)NR″—;
• (iii) C6-C20 aryl, (C6-C12 aryl)-(C1-C8 alkyl)-, C6-C20 aryloxy, (C6-C12 aryloxy)-(C1-C8 alkyl)-, C6-C20 arylcarbonyl, (C6-C12 arylcarbonyl)-(C1-C8 alkyl)-, —CONH—(C6-C12 aryl), —CONH—(C1-C8 alkyl)-(C6-C12 aryl), —NHCO—(C6-C12 aryl), or —NHCO—(C1-C8 alkyl)-(C6-C12 aryl);
• (iv) heteroaryl, heteroaryl-(C1-C8 alkyl)-, heteroaryloxy, heteroaryloxy-(C1-C8 alkyl)-, heteroarylcarbonyl, heteroarylcarbonyl-(C1-C8 alkyl)-, —CONH-heteroaryl, —CONH—(C1-C8 alkyl)-heteroaryl, —NHCO-heteroaryl, or —NHCO—(C1-C8 alkyl)-heteroaryl, wherein the heteroaryl ring is 4- to 10-membered heteroaryl containing at least one heteroatom selected from N, O and S;
• (v) heterocycloalkyl, heterocycloalkyl-(C1-C8 alkyl)-, heterocycloalkyloxy, heterocycloalkyloxy-(C1-C8 alkyl)-, heterocycloalkylcarbonyl, heterocycloalkylcarbonyl-(C1-C8 alkyl)-, —CONH-heterocycloalkyl, —CONH—(C1-C8 alkyl)-heterocycloalkyl, —NHCO— heterocycloalkyl, or —NHCO—(C1-C8 alkyl)-heterocycloalkyl, wherein the heterocycloalkyl ring is 3- to 10-membered fully saturated or partially unsaturated heterocycloalkyl containing at least one heteroatom selected from N, O and S;
• or
• (vi) C3-C10 cycloalkyl, (C3-C10 cycloalkyl)-(C1-C8 alkyl)-, C3-C10 cycloalkyloxy, (C3-C10 cycloalkyloxy)-(C1-C8 alkyl)-, C3-C10 cycloalkylcarbonyl, (C3-C10 cycloalkylcarbonyl)-(C1-C8 alkyl)-, —CONH—(C3-C10 cycloalkyl), —CONH—(C1-C8 alkyl)-(C3-C10 cycloalkyl), —NHCO—(C3-C10 cycloalkyl), or —NHCO—(C1-C8 alkyl)-(C3-C10 cycloalkyl);
• wherein the aryl ring, heteroaryl ring, heterocycloalkyl ring and cycloalkyl ring as described in (iii) to (vi) can be each optionally substituted;
• R′ and R″ are each independently H or C1-C10 alkyl;
• R6 is H or C1-C6 alkyl;
• and
• p is an integer from 0 to 2.