High activity hpk1 kinase inhibitor

A compound having the structure represented by formula I or a pharmaceutically acceptable salt, an isotopic derivative, a stereoisomer thereof:

• wherein R1 represents hydrogen, halogen, (C1-C6) alkyl, (C2-C6) alkenyl, (C1-C6) alkoxy;
• wherein R2 represents hydrogen, halogen, hydroxyl, (C1-C6) alkyl, (C2-C6) alkenyl, —(C0-C6 alkylene) (C1-C6) alkoxy, —(C0-C6 alkylene) (C6-C10) aryl, —(C0-C6 alkylene) (5-10) membered heteroaryl, —(C0-C6 alkylene) (4-10 membered) heterocycloalkyl, —(C0-C6 alkylene) (C3-C8) cycloalkyl, —NRLRL′, —ORL′, —SRL;
• wherein R3 represents hydrogen, halogen, hydroxyl, (C1-C6) alkyl, (C2-C6) alkenyl, —(C0-C6 alkylene) (C3-C8) cycloalkyl, —(C0-C6 alkylene) (4-8 membered) heterocycloalkyl, (C1-C6) alkoxy, —(C0-C6 alkylene) (4-8 membered) heterocycloalkyloxy;
• wherein R4 and R4′ independently represent hydrogen, C1-C6 alkyl, (C2-C6) alkenyl, halogen;
• alternatively, R4 and R4′ form a 3-6 membered ring together with the carbon atom connected to it, and the ring can also optionally contain 0, 1, 2 heteroatoms selected from N, O, and S;
• wherein R5 represents hydrogen, C1-C6 alkyl, (C3-C6) alkenyl, (C3-C8) cycloalkyl, (4-8 membered) heterocycloalkyl;
• wherein R6 and R6′ independently represent hydrogen, C1-C6 alkyl, (C2-C6) alkenyl, halogen;
• alternatively, R6 and R6′ form a 3-6 membered ring together with the carbon atom connected to it, and the ring can also optionally contain 0, 1, 2 heteroatoms selected from N, O, and S;
• wherein X1 represents N or CH;
• wherein X2 represents N or CR7;
• wherein X3 represents N or CR8;
• wherein R7 represents hydrogen, halogen, (C1-C6) alkyl, (C2-C6) alkenyl, (C3-C8) cycloalkyl;
• wherein R represents hydrogen, halogen, (C1-C6) alkyl, (C2-C6) alkenyl, —(C0-C6 alkylene) (C3-C8) cycloalkyl, —(C0-C6 alkylene)(4-10 membered) heterocycloalkyl, —(C0-C6 alkylene) (C6-C10) aryl, —(C0-C6 alkylene) (5-10 membered) heteroaryl,
• alternatively, R8 can form (5-10 membered) cycloalkyl or (5-10 membered) heterocycloalkyl together with adjacent R3;
• wherein RL and RL′ each independently represent hydrogen, (C1-C6) alkyl, (C3-C6) alkenyl, (C3-C6) cycloalkyl, (4-8 membered) heterocycloalkyl, (C0-C6 alkylene) (C6-C10) aryl, —(C0-C6 alkylene) (5-10) membered heteroaryl, —(C0-C6) alkylene-(CRMRM′)—(C0-C6)alkyl, —(C0-C6)alkylene-(CRMRM′)-halogen;
• alternatively, RL and RL′ form a 4-8 membered ring together with the nitrogen atom connected to it, which can additionally contain 0, 1, or 2 heteroatoms selected from nitrogen, oxygen, and sulfur;
• wherein the ring can also be optionally fused to another 5-6 membered carbocycle, 5-6 cycloheteroalkane, 3-4 membered carbocycle, 3-4 cycloheteroalkane, 5-6 membered aromatic heterocycle or benzene ring to form a fused ring bicyclic system;
• or the ring can also be connected to another (4-6 membered) ring carbocycle or (4-6 membered) heterocycle through a spiro carbon atom to form a spirobicyclic ring system;
• wherein the fused ring bicyclic system or spirocyclic bicyclic system can be optionally substituted by 0, 1, 2, 3 members selected from halogen, cyano, (C1-C6) alkyl, (C2-C6) alkenyl, —NRaRa′, —ORa, —SRa, —(C1-C6)alkylene-ORa, —(C1-C6)alkylene-SRa, —(C1-C6 alkylene)hydroxyl, —C(O)Ra, —N(Ra)C(O)Ra, —N(Ra)C(O)ORa, —N(Ra)SO2Ra, —C(O)ORa, —C(O)NRaRa′, —S(O)2NRaRa′, —S(O)Ra, —S(O)2Ra;
• wherein RM and RM′ independently represent hydrogen, C1-C6 alkyl;
• alternatively, RM and RM′ form a 3-8 membered ring together with the carbon atom connected to it, and the ring can also optionally contain 0, 1, or 2 heteroatoms selected from N, O, and S;
• For the above defined alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, it can be optionally substituted by 0, 1, 2, 3 substituents selected from the following:
• (C1-C6) alkyl, (C2-C6) alkenyl, halo (C1-C6) alkyl, halo (C1-C6) alkoxy, —(C1-C6 alkylene)-O—(C1-C6) alkyl, (C3-C8) cycloalkyl, halogenated (C3-C8) cycloalkyl, halogen, —CN, oxo, —NRaRa′, —ORa, —SRa, —(C1-C6 alkylene) hydroxyl, —C(O)Ra, —N(Ra)C(O)Ra, —NRaC(O)ORa, —NRaSO2Ra, —C(O)ORa, —C(O)NRaRa′, —S(O)2NRaRa′, —S(O)Ra, —S(O)2Ra, —P(O)RaRa′;
• wherein Ra and Ra′ each independently represent hydrogen, (C1-C6) alkyl, (C2-C6) alkenyl, (C3-C8) cycloalkyl;
• or when Ra and Ra′ are connected together on the N atom, they can form a 4-7 membered cycloheteroalkane together with the N atom connected to it;
• wherein m and n represent 0, 1, 2, 3.