Fgfr inhibitor, preparation method therefor and application thereof

A compound of formula (I), a stereoisomer, prodrug or pharmaceutically acceptable salt thereof:

• wherein, X is CH or N;
• R1 is selected from the group consisting of H, deuterium, hydroxy, C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, C3-10 cycloalkyl, 3-10 membered heterocyclyl, C5-10 aryl, 5-10 membered heteroaryl, —S(O)R5, —S(O)2R6 and —C(O)R7, above groups are optionally further substituted by one or more substituents selected from the group consisting of deuterium, halogen, cyano, nitro, azido, C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, C3-10 cycloalkyl, 3-10 membered heterocyclyl, C5-10 aryl, 5-10 membered heteroaryl, ═O, —C0-8—S(O)rR10, —C0-8—O—R11, —C0-8—C(O)OR11, —C0-8—C(O)R12, —C0-8—O—C(O)R12, —C0-8—NR13R14, —C0-8—C(═NR13)R12, —C0-8—N(R13)—C(═NR14)R12, —C0-8—C(O)NR13R14 and —C0-8—N(R13)—C(O)R12;
• R2 is selected from the group consisting of C3-10 cycloalkyl, 3-10 membered heterocyclyl, C5-10 aryl, 5-10 membered heteroaryl and —NR8R9, above groups are optionally further substituted by one or more substituents selected from the group consisting of deuterium, halogen, cyano, nitro, azido, C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, C3-10 cycloalkyl, 3-10 membered heterocyclyl, C5-10 aryl, 5-10 membered heteroaryl, ═O, —C0-8—S(O)rR10, —C0-8—O—R11, —C0-8—C(O)OR11, —C0-8—C(O)R12, —C0-8—O—C(O)R12, —C0-8—NR13R14, —C0-8—C(═NR13)R12, —C0-8—N(R13)—C(═NR14)R12, —C0-8—C(O)NR13R14 and —C0-8—N(R13)—C(O)R12, above groups are optionally more further substituted by one or more substituents selected from the group consisting of deuterium, halogen, cyano, nitro, azido, C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, C1-10 haloalkyl, C1-10 deuterioalkyl, C3-10 cycloalkyl, 3-10 membered heterocyclyl, C5-10 aryl, 5-10 membered heteroaryl, ═O, —C0-8—S(O)rR10, —C0-8—O—R11, —C0-8—C(O)OR11, —C0-8—C(O)R12, —C0-8—O—C(O)R12, —C0-8—NR13R14, —C0-8—C(═NR13)R12, —C0-8—N(R13)—C(═NR14)R12, —C0-8—C(O)NR13R14 and —C0-8—N(R13)—C(O)R12;
• each R3 is independently selected from the group consisting of H, deuterium, halogen, cyano, C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, C3-10 cycloalkyl, 3-10 membered heterocyclyl, C5-10 aryl, 5-10 membered heteroaryl, —C0-8—S(O)rR10, —C0-8—O—R11, —C0-8—C(O)OR11, —C0-8—C(O)R12, —C0-8—O—C(O)R12, —C0-8—NR13R14, —C0-8—C(═NR13)R12, —C0-8—N(R13)—C(═NR14)R12, —C0-8—C(O)NR13R14 and —C0-8—N(R13)—C(O)R12, above groups are optionally further substituted by one or more substituents selected from the group consisting of deuterium, halogen, cyano, nitro, azido, C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, C3-10 cycloalkyl, 3-10 membered heterocyclyl, C5-10 aryl, 5-10 membered heteroaryl, ═O, —C0-8—S(O)rR10, —C0-8—O—R11, —C0-8—C(O)OR11, —C0-8—C(O)R12, —C0-8—O—C(O)R12, —C0-8—NR13R14, —C0-8—C(═NR13)R12, —C0-8—N(R13)—C(═NR14)R12, —C0-8—C(O)NR13R14 and —C0-8—N(R13)—C(O)R12, above groups are optionally more further substituted by one or more substituents selected from the group consisting of deuterium, halogen, cyano, nitro, azido, C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, C1-10 haloalkyl, C1-10 deuterioalkyl, C3-10 cycloalkyl, 3-10 membered heterocyclyl, C5-10 aryl, 5-10 membered heteroaryl, ═O, —C0-8—S(O)rR10, —C0-8—O—R11, —C0-8—C(O)OR11, —C0-8—C(O)R12, —C0-8—O—C(O)R12, —C0-8—NR13R14, —C0-8—C(═NR13)R12, —C0-8—N(R13)—C(═NR14)R12, —C0-8—C(O)NR13R14 and —C0-8—N(R13)—C(O)R12;
• each R4 is independently selected from the group consisting of H, deuterium, halogen, cyano, nitro, azido, C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, C3-10 cycloalkyl, 3-10 membered heterocyclyl, C5-10 aryl, 5-10 membered heteroaryl, —C0-8—S(O)rR10, —C0-8—O—R11, —C0-8—C(O)OR11, —C0-8—C(O)R12, —C0-8—O—C(O)R12, —C0-8—NR13R14, —C0-8—C(═NR13)R12, —C0-8—N(R13)—C(═NR14)R12, —C0-8—C(O)NR13R14 and —C0-8—N(R13)—C(O)R12, above groups are optionally further substituted by one or more substituents selected from the group consisting of deuterium, halogen, cyano, nitro, azido, C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, C1-10 haloalkyl, C1-10 deuterioalkyl, C3-10 cycloalkyl, 3-10 membered heterocyclyl, C5-10 aryl, 5-10 membered heteroaryl, ═O, —C0-8—S(O)rR10, —C0-8—O—R11, —C0-8—C(O)OR11, —C0-8—C(O)R12, —C0-8—O—C(O)R12, —C0-8—NR13R14, —C0-8—C(═NR13)R12, —C0-8—N(R13)—C(═NR14)R12, —C0-8—C(O)NR13R14 and —C0-8—N(R13)—C(O)R12;
• R5 and R6 are each independently selected from the group consisting of H, deuterium, hydroxy, C1-10 alkyl, C1-10 alkoxy, C2-10 alkenyl, C3-10 cycloalkyl, C3-10 cycloalkoxy, 3-10 membered heterocyclyl, 3-10 membered heterocyclyloxy, C5-10 aryl, C5-10 aryloxy, 5-10 heteroaryl, 5-10 membered heteroaryloxy and —NR13R14, above groups are optionally further substituted by one or more substituents selected from the group consisting of deuterium, halogen, hydroxy, oxo, C1-10 alkyl, C1-10 alkoxy, C3-10 cycloalkyl, C3-10 cycloalkoxy, 3-10 membered heterocyclyl, 3-10 membered heterocyclyloxy, C5-10 aryl, C5-10 aryloxy, 5-10 heteroaryl, 5-10 membered heteroaryloxy and —NR13R14;
• R7 is selected from the group consisting of C1-10 alkyl, C1-10 alkoxy, C2-10 alkenyl, C2-10 alkynyl, C3-10 cycloalkyl, C3-10 cycloalkoxy, 3-10 membered heterocyclyl, 3-10 membered heterocyclyloxy, C5-10 aryl, C5-10 aryloxy, 5-10 heteroaryl, 5-10 membered heteroaryloxy and —NR13R14, above groups are optionally further substituted by one or more substituents selected from the group consisting of deuterium, halogen, hydroxy, cyano, C1-10 alkyl, C1-10 alkoxy, C3-10 cycloalkyl, C3-10 cycloalkoxy, 3-10 membered heterocyclyl, 3-10 membered heterocyclyloxy, C5-10 aryl, C5-10 aryloxy, 5-10 heteroaryl, 5-10 membered heteroaryloxy and —NR13R14;
• R8 and R9 are each independently selected from the group consisting of deuterium, hydroxy, C1-10 alkyl, C3-10 cycloalkyl, 3-10 membered heterocyclyl, C5-10 aryl, 5-10 membered heteroaryl, —S(O)rR10, —C(O)R12 and —C(O)NR13R14, above groups are optionally further substituted by one or more substituents selected from the group consisting of deuterium, halogen, cyano, nitro, azido, C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, C1-10 haloalkyl, C1-10 deuterioalkyl, C3-10 cycloalkyl, 3-10 membered heterocyclyl, C5-10 aryl, 5-10 membered heteroaryl, ═O, —C0-8—S(O)rR10, —C0-8—O—R11, —C0-8—C(O)OR11, —C0-8—C(O)R12, —C0-8—O—C(O)R12, —C0-8—NR13R14, —C0-8—C(═NR13)R12, —C0-8—N(R13)—C(═NR14)R12, —C0-8—C(O)NR13R14 and —C0-8—N(R13)—C(O)R12, or, R8 and R9, together with the nitrogen atom directly attached thereto, form a 4-10 membered heterocyclyl, above groups are optionally further substituted by one or more substituents selected from the group consisting of deuterium, halogen, cyano, nitro, azido, C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, C1-10 haloalkyl, C1-10 deuterioalkyl, C3-10 cycloalkyl, 3-10 membered heterocyclyl, C5-10 aryl, 5-10 membered heteroaryl, ═O, —C0-8—S(O)rR10, —C0-8—O—R11, —C0-8—C(O)OR11, —C0-8—C(O)R12, —C0-8—O—C(O)R12, —C0-8—NR13R14, —C0-8—C(═NR13)R12, —C0-8—N(R13)—C(═NR14)R12, —C0-8—C(O)NR13R14 and —C0-8—N(R13)—C(O)R12;
• each R10 is selected from the group consisting of H, deuterium, hydroxy, C1-10 alkyl, C1-10 alkoxy, C2-10 alkenyl, C3-10 cycloalkyl, C3-10 cycloalkoxy, 3-10 membered heterocyclyl, 3-10 membered heterocyclyloxy, C5-10 aryl, C5-10 aryloxy, 5-10 membered heteroaryl, 5-10 membered heteroaryloxy and —NR13R14, above groups are optionally further substituted by one or more substituents selected from the group consisting of deuterium, halogen, hydroxy, oxo, C1-10 alkyl, C1-10 alkoxy, C3-10 cycloalkyl, C3-10 cycloalkoxy, 3-10 membered heterocyclyl, 3-10 membered heterocyclyloxy, C5-10 aryl, C5-10 aryloxy, 5-10 heteroaryl, 5-10 membered heteroaryloxy and —NR13R14;
• each R11 is selected from the group consisting of H, deuterium, C1-10 alkyl, C2-10 alkenyl, C3-10 cycloalkyl, 3-10 membered heterocyclyl, C5-10 aryl and 5-10 membered heteroaryl, above groups are optionally further substituted by one or more substituents selected from the group consisting of deuterium, halogen, hydroxy, oxo, cyano, C1-10 alkyl, C1-10 alkoxy, C3-10 cycloalkyl, C3-10 cycloalkoxy, 3-10 membered heterocyclyl, 3-10 membered heterocyclyloxy, C5-10 aryl, C5-10 aryloxy, 5-10 heteroaryl, 5-10 membered heteroaryloxy and —NR13R14;
• each R12 is selected from the group consisting of H, deuterium, hydroxy, C1-10 alkyl, C1-10 alkoxy, C2-10 alkenyl, C2-10 alkynyl, C3-10 cycloalkyl, C3-10 cycloalkoxy, 3-10 membered heterocyclyl, 3-10 membered heterocyclyloxy, C5-10 aryl, C5-10 aryloxy, 5-10 heteroaryl, 5-10 membered heteroaryloxy and —NR13R14, above groups are optionally further substituted by one or more substituents selected from the group consisting of deuterium, halogen, hydroxy, cyano, C1-10 alkyl, C1-10 alkoxy, C3-10 cycloalkyl, C3-10 cycloalkoxy, 3-10 membered heterocyclyl, 3-10 membered heterocyclyloxy, C5-10 aryl, C5-10 aryloxy, 5-10 heteroaryl, 5-10 membered heteroaryloxy and —NR13R14;
• R13 and R14 are each independently selected from the group consisting of H, deuterium, hydroxy, C1-10 alkoxy, C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, C3-10 cycloalkyl, 3-10 membered heterocyclyl, C5-10 aryl, 5-10 membered heteroaryl, sulfinyl, sulfonyl, methylsulfonyl, isopropylsulfonyl, cyclopropylsulfonyl, p-toluenesulfonyl, aminosulfonyl, dimethylaminosulfonyl, amino, monoalkylamino, dialkylamino and C1-10 alkanoyl, above groups are optionally further substituted by one or more substituents selected from the group consisting of deuterium, halogen, hydroxy, C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, C1-10 haloalkyl, C1-10 deuterioalkyl, C1-10 alkoxy, C3-10 cycloalkyl, C3-10 cycloalkoxy, 3-10 membered heterocyclyl, 3-10 membered heterocyclyloxy, C5-10 aryl, C5-10 aryloxy, 5-10 heteroaryl, 5-10 membered heteroaryloxy, amino, monoalkylamino, dialkylamino and C1-10 alkanoyl,
• or, R13 and R14, together with the nitrogen atom directly attached thereto, form a 4-10 membered heterocyclyl or 4-10 membered heteroaryl, above groups are optionally further substituted by one or more substituents selected from the group consisting of deuterium, halogen, hydroxy, C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, C1-10 haloalkyl, C1-10 deuterioalkyl, C1-10 alkoxy, C3-10 cycloalkyl, C3-10 cycloalkoxy, 3-10 membered heterocyclyl, 3-10 membered heterocyclyloxy, C5-10 aryl, C5-10 aryloxy, 5-10 heteroaryl, 5-10 membered heteroaryloxy, amino, monoalkylamino, dialkylamino and C1-10 alkanoyl;
• each r is independently 0, 1 or 2.