Ring-fused compound as well as preparation method and application thereof

Abstract

The invention discloses a ring-fused compound and a preparation method and application thereof, and the ring-fused compound (V) is a Myt1 kinase inhibitor, can be used for treating tumors and has good selectivity.

Description

Cyclic compound and its preparation method and use

[0001] This application claims priority to the following prior application: Patent application number 202311047143.3, filed with the State Intellectual Property Office of China on August 18, 2023, entitled “Annular compounds, preparation methods and uses thereof.” The entire text of that prior application is incorporated herein by reference. Technical Field

[0002] The present invention belongs to the field of medical technology, and in particular relates to a cyclic compound and a preparation method and use thereof. Background Art

[0003] PKMYT1 (also known as Myt1), a member of the Wee family, is a kinase that efficiently phosphorylates Cdc2 at threonine 14 and tyrosine 15. PKMYT1 arrests cell cycle progression by inhibiting the activity of cell cycle-related proteins, such as Cyclin A, CDK1, and CDK2. PKMYT1 also promotes the development of various tumors.

[0004] Inhibitory phosphorylation of cdc2 is crucial for accurate entry into mitosis. Mitosis is initiated by the M-phase promoting factor (MPF), a complex comprising the cdc2 protein kinase and Cyclin B. Proper regulation of MPF ensures that mitosis occurs only after the early stages of the cell cycle are completed. During interphases G1, S, and G2, phosphorylation of cdc2 at tyrosine 15 and threonine 14 inhibits its activity. During the G2-M transition, phosphorylation of cdc2 at tyrosine 15 and threonine 14 is removed, allowing MPF to phosphorylate its mitotic substrates.

[0005] Studies have shown that premature activation of CDC2 can lead to mitotic catastrophe and cell death. Inhibiting Myt1 can lead to premature activation of CDC2, thereby killing rapidly proliferating cells. Furthermore, Myt1 inhibition may reduce resistance to traditional DNA-damaging chemotherapies, as cell death avoidance involves arrest in the G2 phase of the cell cycle and repair or pre-mitotic DNA damage. Blocking Myt1's inhibitory phosphorylation of CDC2 prevents this arrest, forcing cells into mitosis prematurely. Therefore, Myt1 kinase plays a crucial regulatory role during the G2 / M phase of the cell cycle. This phase is a key point in cell cycle regulation and DNA damage repair during mitosis, and is the target of the most effective chemotherapeutic agents. Inhibiting Myt1 may have therapeutic benefits in itself by reducing tumor proliferation, and it could also be used in combination with traditional chemotherapeutic agents to overcome drug resistance.

[0006] Summary of the Invention

[0007] To solve the above technical problems, the present invention provides a compound represented by the following formula V, and a pharmaceutically acceptable salt or stereoisomer thereof:

[0008] in, is a heterocyclic group or heteroaryl group composed of M, E, J, L, and Q;

[0009] M is selected from N or CA; A is selected from H, halogen, CN, OH, NH2, SO2NH2, CONH2, =O, C 1-12 Alkyl, C 1-12 Alkoxy, C 1-12 Amine alkyl, C 1-12 Alkylthio, C 2-12 Alkenyl, C 2-12 Alkynyl, cycloalkyl, heterocyclyl, aryl or heteroaryl, the C 1-12 Alkyl, C 1-12 Alkoxy, C 1-12 Amine alkyl, C 1-12 Alkylthio, C 2-12 Alkenyl, C 2-12 Alkynyl, cycloalkyl, heterocyclyl, aryl or heteroaryl is optionally substituted by 1, 2 or more R AA replace;

[0010] R AA are independently selected from halogen, -CN, -NH2, -OH, -OR a 、-OC(=O)R a 、-OC(=O)OR b 、-OC(=O)NR c R d 、-SH、-SR a 、-S(=O)R a 、-S(=O)2R a 、-S(=O)2NR c R d 、-NR c R d 、-NR b C(=O)NR c R d 、-NR b C(=O)R a 、-NR b C(=O)OR b 、-NR b S(=O)2R a 、-C(=O)R a 、-C(=O)OR b 、-C(=O)NR c R d、C 1-12 Alkyl, C 1-12 Alkoxy, C 1-12 Alkylthio, halo C 1-12 Alkyl, C 1-12 Hydroxyalkyl, C 1-12 Amine alkyl, C 2-12 Alkenyl, C 2-12 Alkynyl, cycloalkyl, heterocyclyl, aryl or heteroaryl, the C 1-12 Alkyl, C 1-12 Alkoxy, C 1-12 Alkylthio, halo C 1-12 Alkyl, C 1-12 Hydroxyalkyl, C 1-12 Amine alkyl, C 2-12 Alkenyl, C 2-12 Alkynyl, cycloalkyl, heterocyclyl, aryl or heteroaryl is optionally substituted by 1, 2 or more R 1a replace;

[0011] or two R AA Substituted on the same atom, and linked together to form =O, =C(R 1a )2, =CHR 1a , cycloalkyl or heterocyclic group; the cycloalkyl or heterocyclic group is optionally substituted by 1, 2 or more R 1a Substitution; the number of said =O is 1, 2 or 3;

[0012] R 1a are independently selected from halogen, -CN, -OH, -OR a 、-OC(=O)R a 、-OC(=O)OR b 、-OC(=O)NR c R d 、-SH、-SR a 、-S(=O)R a 、-S(=O)2R a 、-S(=O)2NR c R d 、-NR c R d 、-NR b C(=O)NR c R d 、-NR b C(=O)R a 、-NR b C(=O)OR b 、-NR b S(=O)2R a 、-C(=O)R a 、-C(=O)OR b、-C(=O)NR c R d 、C 1-12 Alkyl, C 1-12 Alkoxy, C 1-12 Alkylthio, halo C 1-12 Alkyl, C 1-12 Hydroxyalkyl, C 1-12 Amine alkyl, C2- 12 Alkenyl, C 2-12 Alkynyl, cycloalkyl, heterocyclyl, aryl or heteroaryl, the C 1-12 Alkyl, C 1-12 Alkoxy, C 1-12 Alkylthio, halo C 1-12 Alkyl, C 1-12 Hydroxyalkyl, C 1-12 Amine alkyl, C 2-12 Alkenyl, C 2-12 Alkynyl, cycloalkyl, heterocyclyl, aryl or heteroaryl is optionally substituted with 1, 2 or more R;

[0013] Q is selected from N, NR 1 or CR 1 ;

[0014] R 1 Selected from H, halogen, -CN, -OH, -OR a 、-SH、-SR a 、-NR c R d 、-C(=O)R a 、-C(=O)OR b 、-C(=O)NR c R d 、-NHCOR a 、-NH-C 1-12 Alkyl-R a 、-C 1-12 Alkyl-OR a 、C 1-12 Alkyl, C 1-12 Alkoxy, C 1-12 Amine alkyl, C 1-12 Alkylthio, C 2-12 Alkenyl, -cycloalkylC 2-12 Alkenyl, C 2-12 Alkynyl, cycloalkyl, heterocyclyl, aryl or heteroaryl, the C 1-12 Alkyl, C 1-12 Alkoxy, C 1-12 Amine alkyl, C 1-12 Alkylthio, C 2- 12 Alkenyl, -cycloalkylC 2-12 Alkenyl, C2-12 Alkynyl, cycloalkyl, heterocyclyl, aryl or heteroaryl is optionally substituted by one or more R Qa Substituted; said -cycloalkylC 2- 12 C in alkenyl 2-12 The C at one end of the alkenyl group is the same carbon atom as the carbon to which the cycloalkyl group is connected;

[0015] R Qa are independently selected from halogen, =O, -CN, -OH, -OR a 、-OC(=O)R a 、-OC(=O)OR b 、-OC(=O)NR c R d 、-SH、-SR a 、-S(=O)R a 、-S(=O)2R a 、-S(=O)2NR c R d 、-NR c R d 、-NR b C(=O)NR c R d 、-NR b C(=O)R a 、-NR b C(=O)OR b 、-NR b S(=O)2R a 、-C(=O)R a 、-C(=O)OR b 、-C(=O)NR c R d , =C(R 1a )2、C 1-12 Alkyl, C 1-12 Alkoxy, C 1-12 Alkylthio, halo C 1-12 Alkyl, C 1-12 Hydroxyalkyl, C 1-12 Amine alkyl, C 2-12 Alkenyl, C 2-12 Alkynyl, cycloalkyl, heterocyclyl, aryl or heteroaryl, the C 1-12 Alkyl, C 1-12 Alkoxy, C 1-12 Alkylthio, halo C 1-12 Alkyl, C 1-12 Hydroxyalkyl, C 1-12 Amine alkyl, C 2-12 Alkenyl, C 2-12Alkynyl, cycloalkyl, heterocyclyl, aryl or heteroaryl is optionally substituted with 1, 2 or more R;

[0016] E is selected from N or C;

[0017] J is selected from N or C;

[0018] L is selected from N, NR 2 or CR 2 ;

[0019] R 2 Selected from H, C 1-12 Alkyl, C 1-12 Alkoxy, C 1-12 Alkylthio, halo C 1-12 Alkyl, C 1-12 Hydroxyalkyl, C 1-12 Amine alkyl, C 2-12 Alkenyl, C2- 12 alkynyl, cycloalkyl or heterocyclyl;

[0020] X is C(Rx) or N;

[0021] Y is C(Ry) or N;

[0022] Z is N or C (Rz);

[0023] Rx, Ry, Rz, R 3 、R 4 、R 5 、R 6 The same or different, independently selected from H, halogen, -CN, -OH, -OR a 、-OC(=O)R a 、-OC(=O)OR b 、-OC(=O)NR c R d 、-SH、-SR a 、-S(=O)R a 、-S(=O)2R a 、-S(=O)2NR c R d 、-NR c R d 、-NR b C(=O)NR c R d 、-NR b C(=O)R a 、-NR b C(=O)OR b 、-NR b S(=O)2R a 、-C(=O)R a、-C(=O)OR b 、-C(=O)NR c R d 、C 1-12 Alkyl, C 1-12 Alkoxy, C 1-12 Alkylthio, halo C 1-12 Alkyl, halogenated C 1-12 Alkoxy, C 1-12 Hydroxyalkyl, C 1-12 Amine alkyl, C 2-12 Alkenyl, C 2-12 Alkynyl, cycloalkyl, heterocyclyl, aryl or heteroaryl, the C 1-12 Alkyl, C 1-12 Alkoxy, C 1-12 Alkylthio, halo C 1-12 Alkyl, halogenated C 1-12 Alkoxy, C 1-12 Hydroxyalkyl, C 1-12 Amine alkyl, C 2-12 Alkenyl, C 2-12 Alkynyl, cycloalkyl, heterocyclyl, aryl or heteroaryl is optionally substituted with 1, 2 or more R;

[0024] R a 、R b 、R c 、R d The same or different, independently selected from H, C 1-12 Alkyl, C 1-12 Alkoxy, C 1-12 Alkylthio, halo C 1-12 Alkyl, C 1-12 Hydroxyalkyl, C 1-12 Amine alkyl, C 2-12 Alkenyl, C 2-12 Alkynyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, C 1-12 Alkyl-cycloalkyl, C 1-12 Alkyl-heterocyclyl, C 1-12 Alkyl-aryl or C 1-12 Alkyl-heteroaryl; said C 1-12 Alkyl, C 1-12 Alkoxy, C 1-12 Alkylthio, halo C 1-12 Alkyl, C 1-12 Hydroxyalkyl, C 1-12 Amine alkyl, C 2-12 Alkenyl, C 2-12 Alkynyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, C 1-12 Alkyl-cycloalkyl, C 1-12 Alkyl-heterocyclyl, C 1-12 Alkyl-aryl or C1-12 Alkyl-heteroaryl is optionally substituted with 1, 2 or more R;

[0025] or R c and R d are linked together to form a heterocyclic group, which is optionally substituted with 1, 2 or more R;

[0026] G is N or CR G ;

[0027] R G is H, OH or NH2;

[0028] or R G With R 3 are linked together to form a cycloalkyl, heterocyclyl, aryl or heteroaryl group; the cycloalkyl, heterocyclyl, aryl or heteroaryl group is optionally substituted by 1, 2 or more R;

[0029] or R G With R 6 are linked together to form a cycloalkyl, heterocyclyl, aryl or heteroaryl group; the cycloalkyl, heterocyclyl, aryl or heteroaryl group is optionally substituted by 1, 2 or more R;

[0030] R is independently selected from halogen, -SH, -CN, -OH, -S(=O)CH3, -S(=O)2CH3, -S(=O)2NH2, -S(=O)2NHCH3, -S(=O)2N(CH3)2, -NH2, -NHCH3, -N(CH3)2, -C(=O)CH3, -C(=O)OH, -C(=O)OCH3, =C(R 1a )2、C 1-12 Alkyl, C 2-12 Alkenyl, C 2-12 Alkynyl, C 1-12 Alkoxy, C 1-12 Alkylthio, halo C 1-12 Alkyl, halogenated C 1-12 Alkoxy, C 1-12 Hydroxyalkyl, C 1-12 Amine alkyl or C 3-12 Cycloalkyl;

[0031] Or two Rs are substituted on the same atom and are linked together to form =O, a cycloalkyl group or a heterocyclyl group.

[0032] According to an embodiment of the present invention, the compound shown in Formula V has a structure as shown in Formula V-1:

[0033] Here, each group has the same definition as above.

[0034] According to an embodiment of the present invention, G in formula V-1 is N or CR G ; R G Selected from H, OH, NH2; or, G and R 3 or R 6 are connected together to form a 3-12 membered heterocyclic group or a 5-12 membered heteroaryl group; the 3-12 membered heterocyclic group or the 5-12 membered heteroaryl group is optionally substituted by 1, 2 or more of the following groups: C 1-12 Alkyl, C 1-12 Alkoxy.

[0035] The present invention also provides compounds represented by the following formulas I to XI, and pharmaceutically acceptable salts or stereoisomers thereof:

[0036] wherein A is selected from H, halogen, CN, OH, NH2, SO2NH2, CONH2, (=O), C 1-12 Alkyl, C 1-12 Alkoxy, C 1-12 Amine alkyl, C 1- 12 Alkylthio, C 2-12 Alkenyl, C 2-12 Alkynyl, cycloalkyl, heterocyclyl, aryl or heteroaryl, the C 1-12 Alkyl, C 1-12 Alkoxy, C 1-12 Amine alkyl, C 1- 12 Alkylthio, C 2-12 Alkenyl, C 2-12 Alkynyl, cycloalkyl, heterocyclyl, aryl or heteroaryl is optionally substituted by 1, 2 or more R AA replace;

[0037] R AA are independently selected from halogen, -CN, -NH2, -OH, -OR a 、-OC(=O)R a 、-OC(=O)OR b 、-OC(=O)NR c R d 、-SH、-SR a 、-S(=O)R a 、-S(=O)2R a 、-S(=O)2NR c R d 、-NR c R d 、-NR b C(=O)NR c R d 、-NRb C(=O)R a 、-NR b C(=O)OR b 、-NR b S(=O)2R a 、-C(=O)R a 、-C(=O)OR b 、-C(=O)NR c R d 、C 1-12 Alkyl, C 1-12 Alkoxy, C 1-12 Alkylthio, halo C 1-12 Alkyl, C 1-12 Hydroxyalkyl, C 1-12 Amine alkyl, C 2-12 Alkenyl, C 2-12 Alkynyl, cycloalkyl, heterocyclyl, aryl or heteroaryl, the C 1-12 Alkyl, C 1-12 Alkoxy, C 1-12 Alkylthio, halo C 1-12 Alkyl, C 1-12 Hydroxyalkyl, C 1-12 Amine alkyl, C 2-12 Alkenyl, C 2-12 Alkynyl, cycloalkyl, heterocyclyl, aryl or heteroaryl is optionally substituted by 1, 2 or more R 1a replace;

[0038] or two R AA Substituted on the same carbon atom and connected together to form =O, =C(R 1a )2, =CHR 1a , cycloalkyl or heterocyclic group; the cycloalkyl or heterocyclic group is optionally substituted by 1, 2 or more R 1a Substitution; the number of said =O is 1, 2 or 3;

[0039] R 1a are independently selected from halogen, -CN, -OH, -OR a 、-OC(=O)R a 、-OC(=O)OR b 、-OC(=O)NR c R d 、-SH、-SR a 、-S(=O)R a 、-S(=O)2R a 、-S(=O)2NR c R d 、-NR c R d 、-NR bC(=O)NR c R d 、-NR b C(=O)R a 、-NR b C(=O)OR b 、-NR b S(=O)2R a 、-C(=O)R a 、-C(=O)OR b 、-C(=O)NR c R d 、C 1-12 Alkyl, C 1-12 Alkoxy, C 1-12 Alkylthio, halo C 1-12 Alkyl, C 1-12 Hydroxyalkyl, C 1-12 Amine alkyl, C2- 12 Alkenyl, C 2-12 Alkynyl, cycloalkyl, heterocyclyl, aryl or heteroaryl, the C 1-12 Alkyl, C 1-12 Alkoxy, C 1-12 Alkylthio, halo C 1-12 Alkyl, C 1-12 Hydroxyalkyl, C 1-12 Amine alkyl, C 2-12 Alkenyl, C 2-12 Alkynyl, cycloalkyl, heterocyclyl, aryl or heteroaryl is optionally substituted with 1, 2 or more R;

[0040] Q is selected from N or CR 1 ;

[0041] R 1 Selected from H, halogen, -CN, -OH, -OR a 、-SH、-SR a 、-NR c R d 、-C(=O)R a 、-C(=O)OR b 、-C(=O)NR c R d 、-NHCOR a 、-NH-C 1-12 Alkyl-R a 、-C 1-12 Alkyl-OR a 、C 1-12 Alkyl, C 1-12 Alkoxy, C 1-12 Amine alkyl, C 1-12 Alkylthio, C 2-12 Alkenyl, C 2-12Alkynyl, cycloalkyl, heterocyclyl, aryl or heteroaryl, the C 1-12 Alkyl, C 1-12 Alkoxy, C 1-12 Amine alkyl, C 1-12 Alkylthio, C 2-12 Alkenyl, C 2-12 Alkynyl, cycloalkyl, heterocyclyl, aryl or heteroaryl is optionally substituted by one or more R Qa replace;

[0042] R Qa are independently selected from halogen, =O, -CN, -OH, -OR a 、-OC(=O)R a 、-OC(=O)OR b 、-OC(=O)NR c R d 、-SH、-SR a 、-S(=O)R a 、-S(=O)2R a 、-S(=O)2NR c R d 、-NR c R d 、-NR b C(=O)NR c R d 、-NR b C(=O)R a 、-NR b C(=O)OR b 、-NR b S(=O)2R a 、-C(=O)R a 、-C(=O)OR b 、-C(=O)NR c R d 、C 1-12 Alkyl, C 1-12 Alkoxy, C 1-12 Alkylthio, halo C 1-12 Alkyl, C 1-12 Hydroxyalkyl, C 1-12 Amine alkyl, C 2-12 Alkenyl, C 2-12 Alkynyl, cycloalkyl, heterocyclyl, aryl or heteroaryl, the C 1-12 Alkyl, C 1-12 Alkoxy, C 1-12 Alkylthio, halo C 1-12 Alkyl, C 1-12 Hydroxyalkyl, C 1-12 Amine alkyl, C 2-12 Alkenyl, C 2-12Alkynyl, cycloalkyl, heterocyclyl, aryl or heteroaryl is optionally substituted with 1, 2 or more R;

[0043] R 2 Selected from H, C 1-12 Alkyl, C 1-12 Alkoxy, C 1-12 Alkylthio, halo C 1-12 Alkyl, C 1-12 Hydroxyalkyl, C 1-12 Amine alkyl, C 2-12 Alkenyl, C 2-12 alkynyl, cycloalkyl or heterocyclyl;

[0044] X is C(Rx) or N;

[0045] Y is C(Ry) or N;

[0046] Z is N or C (Rz);

[0047] Rx, Ry, Rz, R 3 、R 4 、R 5 、R 6 The same or different, independently selected from halogen, -CN, -OH, -OR a 、-OC(=O)R a 、-OC(=O)OR b 、-OC(=O)NR c R d 、-SH、-SR a 、-S(=O)R a 、-S(=O)2R a 、-S(=O)2NR c R d 、-NR c R d 、-NR b C(=O)NR c R d 、-NR b C(=O)R a 、-NR b C(=O)OR b 、-NR b S(=O)2R a 、-C(=O)R a 、-C(=O)OR b 、-C(=O)NR c R d 、C 1-12 Alkyl, C 1-12 Alkoxy, C 1-12 Alkylthio, halo C 1-12 Alkyl, C1-12 Hydroxyalkyl, C 1-12 Amine alkyl, C 2-12 Alkenyl, C 2-12 Alkynyl, cycloalkyl, heterocyclyl, aryl or heteroaryl, the C 1-12 Alkyl, C 1-12 Alkoxy, C 1-12 Alkylthio, halo C 1-12 Alkyl, C 1-12 Hydroxyalkyl, C 1-12 Amine alkyl, C 2-12 Alkenyl, C 2-12 Alkynyl, cycloalkyl, heterocyclyl, aryl or heteroaryl is optionally substituted with 1, 2 or more R;

[0048] R a 、R b 、R c 、R d The same or different, independently selected from H, C 1-12 Alkyl, C 1-12 Alkoxy, C 1-12 Alkylthio, halo C 1-12 Alkyl, C 1-12 Hydroxyalkyl, C 1-12 Amine alkyl, C 2-12 Alkenyl, C 2-12 Alkynyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, C 1-12 Alkyl-cycloalkyl, C 1-12 Alkyl-heterocyclyl, C 1-12 Alkyl-aryl or C 1-12 Alkyl-heteroaryl; said C 1-12 Alkyl, C 1-12 Alkoxy, C 1-12 Alkylthio, halo C 1-12 Alkyl, C 1-12 Hydroxyalkyl, C 1-12 Amine alkyl, C 2-12 Alkenyl, C 2-12 Alkynyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, C 1-12 Alkyl-cycloalkyl, C 1-12 Alkyl-heterocyclyl, C 1-12 Alkyl-aryl or C 1-12 Alkyl-heteroaryl is optionally substituted with 1, 2 or more R;

[0049] or R c and R d are linked together to form a heterocyclic group, which is optionally substituted with 1, 2 or more R;

[0050] R is independently selected from halogen, -CN, -OH, -S(=O)CH3, -S(=O)2CH3, -S(=O)2NH2, -S(=O)2NHCH3, -S(=O)2N(CH3)2, -NH2, -NHCH3, -N(CH3)2, -C(=O)CH3, -C(=O)OH, -C(=O)OCH3, =C(R 1a )2、C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, halo C 1-6 Alkyl, C 1-6 Hydroxyalkyl, C 1-6 Amine alkyl or C 3-6 Cycloalkyl;

[0051] Or two Rs are substituted on the same carbon atom and are linked together to form =0, a cycloalkyl group or a heterocyclic group.

[0052] According to an embodiment of the present invention, in Formula V, Formula V-1 or Formula I, A is selected from H, =O, halogen, CN, OH, NH2, SO2NH2, CONH2, C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 Aryl or 5-12 membered heteroaryl, the C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 Aryl or 5-12 membered heteroaryl is optionally substituted by 1, 2 or more R AA replace;

[0053] R AA are independently selected from halogen, -CN, -NH2, -OH, -OR a 、-OC(=O)R a 、-OC(=O)OR b 、-OC(=O)NR c R d 、-SH、-SR a 、-S(=O)R a 、-S(=O)2R a 、-S(=O)2NR c R d 、-NRc R d 、-NR b C(=O)NR c R d 、-NR b C(=O)R a 、-NR b C(=O)OR b 、-NR b S(=O)2R a 、-C(=O)R a 、-C(=O)OR b 、-C(=O)NR c R d 、C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, halo C 1-6 Alkyl, C 1-6 Hydroxyalkyl, C 1-6 Amine alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 Aryl or 5-12 membered heteroaryl, the C 1-6 Alkyl, C 1-6 Alkoxy, C 1- 6-alkylthio, halo C 1-6 Alkyl, C 1-6 Hydroxyalkyl, C 1-6 Amine alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 Aryl or 5-12 membered heteroaryl is optionally substituted by 1, 2 or more R 1a replace;

[0054] or two R AA Substituted on the same atom, and linked together to form =O, =C(R 1a )2, =CHR 1a 、C 3-12 Cycloalkyl or 3-12 membered heterocyclic group; said C 3-12 Cycloalkyl or 3-12 membered heterocyclic group is optionally substituted by 1, 2 or more R 1a Substitution; the number of said =O is 1, 2 or 3;

[0055] R 1a are independently selected from halogen, -CN, -OH, -OR a 、-OC(=O)R a 、-OC(=O)ORb 、-OC(=O)NR c R d 、-SH、-SR a 、-S(=O)R a 、-S(=O)2R a 、-S(=O)2NR c R d 、-NR c R d 、-NR b C(=O)NR c R d 、-NR b C(=O)R a 、-NR b C(=O)OR b 、-NR b S(=O)2R a 、-C(=O)R a 、-C(=O)OR b 、-C(=O)NR c R d 、C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, halo C 1-6 Alkyl, C 1-6 Hydroxyalkyl, C 1-6 Amine alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 Aryl or 5-12 membered heteroaryl, the C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, halo C 1-6 Alkyl, C 1-6 Hydroxyalkyl, C 1-6 Amine alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 Aryl or 5-12 membered heteroaryl is optionally substituted with 1, 2 or more R;

[0056] Q is selected from N, NR 1 or CR 1 ;

[0057] R 1 Selected from H, halogen, -CN, -OH, -OR a 、-SH、-SR a 、-NR cR d 、-C(=O)R a 、-C(=O)OR b 、-C(=O)NR c R d 、-NHCOR a 、-NH-C 1-6 Alkyl-R a 、-C 1-6 Alkyl-OR a 、C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 Aryl or 5-12 membered heteroaryl, the C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 Aryl or 5-12 membered heteroaryl is optionally substituted by 1, 2 or more R Qa replace;

[0058] R Qa are independently selected from halogen, =O, -CN, -OH, -OR a 、-OC(=O)R a 、-OC(=O)OR b 、-OC(=O)NR c R d 、-SH、-SR a 、-S(=O)R a 、-S(=O)2R a 、-S(=O)2NR c R d 、-NR c R d 、-NR b C(=O)NR c R d 、-NR b C(=O)R a 、-NR b C(=O)OR b 、-NR b S(=O)2R a 、-C(=O)R a 、-C(=O)OR b 、-C(=O)NRc R d , =C(R 1a )2、C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, halo C 1-6 Alkyl, C 1-6 Hydroxyalkyl, C 1-6 Amine alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 Aryl or 5-12 membered heteroaryl, the C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, halo C 1-6 Alkyl, C 1-6 Hydroxyalkyl, C 1-6 Amine alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 Aryl or 5-12 membered heteroaryl is optionally substituted by 1, 2 or more R;

[0059] R 2 Selected from H, C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, halo C 1-6 Alkyl, C 1-6 Hydroxyalkyl, C 1-6 Amine alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-12 Cycloalkyl or 3-12 membered heterocyclic group;

[0060] X is C(Rx) or N;

[0061] Y is C(Ry) or N;

[0062] Z is N or C (Rz);

[0063] Rx, Ry, Rz, R 3 、R 4 、R 5 、R 6 The same or different, independently selected from H, halogen, -CN, -OH, -OR a 、-OC(=O)R a 、-OC(=O)OR b 、-OC(=O)NR c R d 、-SH、-SRa 、-S(=O)R a 、-S(=O)2R a 、-S(=O)2NR c R d 、-NR c R d 、-NR b C(=O)NR c R d 、-NR b C(=O)R a 、-NR b C(=O)OR b 、-NR b S(=O)2R a 、-C(=O)R a 、-C(=O)OR b 、-C(=O)NR c R d 、C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, halo C 1-6 Alkyl, C 1-6 Hydroxyalkyl, C 1-6 Amine alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 Aryl or 5-12 membered heteroaryl, the C 1-6 Alkyl, halogenated C 1-6 Alkyl, C 1-6 Hydroxyalkyl, C 1-6 Amine alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 Aryl or 5-12 membered heteroaryl is optionally substituted with 1, 2 or more R;

[0064] R a 、R b 、R c 、R d The same or different, independently selected from H, C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, halo C 1-6 Alkyl, C 1-6 Hydroxyalkyl, C 1-6 Amine alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-12Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 Aryl, 5-12 membered heteroaryl, C 1-6 Alkyl-C 3-12 Cycloalkyl, C 1-6 Alkyl-3-12 membered heterocyclic group, C 1-6 Alkyl-C 6-14 Aryl or C 1-6 Alkyl-5-12 membered heteroaryl; said C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, halo C 1-6 Alkyl, C 1-6 Hydroxyalkyl, C 1-6 Amine alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 Aryl, 5-12 membered heteroaryl, C 1-6 Alkyl-C 3-12 Cycloalkyl, C 1-6 Alkyl-3-12 membered heterocyclic group, C 1-6 Alkyl-C 6-14 Aryl or C 1-6 Alkyl-5-12 membered heteroaryl is optionally substituted with 1, 2 or more R;

[0065] or R c and R d are linked together to form a 3-12 membered heterocyclic group, wherein the 3-12 membered heterocyclic group is optionally substituted by 1, 2 or more R;

[0066] R is independently selected from halogen, -CN, -OH, -S(=O)CH3, -S(=O)2CH3, -S(=O)2NH2, -S(=O)2NHCH3, -S(=O)2N(CH3)2, -NH2, -NHCH3, -N(CH3)2, -C(=O)CH3, -C(=O)OH, -C(=O)OCH3, =C(R 1a )2、C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, halo C 1-6 Alkyl, C 1-6 Hydroxyalkyl, C 1-6 Amine alkyl or C 3-12 Cycloalkyl;

[0067] Or two Rs are substituted on the same carbon atom and are linked together to form =0, a cycloalkyl group or a heterocyclic group.

[0068] According to an embodiment of the present invention, A is H, halogen, CN, OH, NH2, -SO2NH2, -Ra1-Rb1, -C≡C-Rc1 or -CH=CH-Rc 2；

[0069] Ra1 is selected from 5-12 membered heteroaryl, C 6-14 Aryl, C 3-12 Cycloalkyl or 3-12 membered heterocyclic group;

[0070] Rb1 is selected from H, NH2, OH, C 1-12 Alkyl, C 2-12 Alkenyl, C 2-12 Alkynyl, =O, unsubstituted or optionally substituted by one, two or more Rb': C 3-12 Cycloalkyl or 3-12 membered heterocyclic group; Rb' is selected from CN, OH, NH2, halogen, mercapto or -SO2NH2; the number of substituents Rb1 is 1, 2 or 3; when Rb1 is 2 or 3, the Rb1 is substituted on the same atom or different atoms of the group represented by Ra1;

[0071] Rc1 and Rc2 are the same or different and are independently selected from the following groups which are unsubstituted or optionally substituted by one, two or more Rc': 1-12 Alkyl, C 2-12 Alkenyl, C 2-12 Alkynyl, 3-12 membered heterocyclic group, C 3-12 Cycloalkyl, 5-12 membered heteroaryl or C 6-14 Aryl; Rc' is selected from NH2, OH, CN, halogen, mercapto, -SO2NH2, C 1-12 Alkyl, C 1-12 Alkoxy, halogenated C 1-12 Alkyl or halogenated C 1-12 alkoxy;

[0072] Q is N or CR 1 , R 1 Selected from H, -LR 7 、C 1-12 Alkyl, C 2-12 Alkenyl, C 2-12 Alkynyl; wherein L is selected from -NHCO-, -NH-C 1-12 Alkyl-, -C≡C-, -CO-, -C 1-12 Alkyl-O-, -CONH-, -C 1-12 Alkyl- or -CH=CH-; R 7 The same or different, independently selected from H, unsubstituted or optionally substituted by one, two or more Rd1: 5-12 membered heteroaryl, C 6-14 Aryl, C3-12 Cycloalkyl, 3-12 membered heterocyclic group or C 1-12 Alkyl; Rd1 is selected from OH, NH2, CN, halogen, mercapto, -SO2NH2, C 1-12 Alkyl, C 1-12 Alkoxy, halogenated C 1-12 Alkyl or halogenated C 1-12 alkoxy;

[0073] R 2 H, C 1-12 Alkyl or halogenated C 1-12 alkyl;

[0074] X is C(Rx) or N;

[0075] Y is C(Ry) or N;

[0076] Z is N or C (Rz);

[0077] Rx, Ry, Rz, R 3 、R 4 、R 5 、R 6 The same or different, independently selected from H, OH, NH2, CN, halogen, mercapto, -SO2NH2; unsubstituted or optionally substituted by one, two or more Rs: C 1-12 Alkyl, C 2-12 Alkenyl, C 2-12 Alkynyl, C 1-12 Alkoxy, halogenated C 1-12 Alkyl, halogenated C 1-12 Alkoxy, 3-12 membered heterocyclic group, C 3-12 Cycloalkyl, -COC 1-12 Alkyl, -COC 6-14 Aryl, -CO-5-12 membered heteroaryl, C 1-12 Alkylthio, -SO2C 1-12 Alkyl, C 6-14 Aryl, -OC 6-14 Aryl, -O-5-12 membered heteroaryl or 5-12 membered heteroaryl; wherein Rs is selected from halogen, CN, OH, NH2, mercapto, -SO2NH2, C 1-12 Alkyl, C 2-12 Alkenyl, C 2-12 Alkynyl, C 1-12 Alkoxy, halogenated C 1-12 Alkyl or halogenated C 1-12 Alkoxy.

[0078] According to an embodiment of the present invention, E is selected from N or C;

[0079] According to an embodiment of the present invention, X is selected from C(Rx) or N; Rx is selected from H, OH, NH2, CN, halogen, unsubstituted or optionally substituted by one, two or more Rs: C 1-6 Alkyl or halogenated C 1-6 Alkyl; said Rs is selected from halogen, CN, OH, NH2 or C 1-6 alkyl.

[0080] According to an embodiment of the present invention, X is selected from N, CH or C-CN;

[0081] According to an embodiment of the present invention, J is selected from N or C;

[0082] According to an embodiment of the present invention, L is selected from NH or CH;

[0083] According to an embodiment of the present invention, Z is N.

[0084] According to an embodiment of the present invention, Z is CH.

[0085] According to an embodiment of the present invention, Y is N.

[0086] According to an embodiment of the present invention, Y is C(Ry), Ry is H, OH, NH2, CN, halogen, unsubstituted or optionally substituted by one, two or more Rs: 1-6 Alkyl or halogenated C 1-6 Alkyl, wherein Rs is selected from halogen, CN, OH, NH2 or C 1-6 alkyl.

[0087] According to an embodiment of the present invention, Y is CH, C—Cl, C—CH 3 or C—CF 3 .

[0088] According to an embodiment of the present invention, the compound represented by Formula I has a structure represented by Formula Ia or Ic:

[0089] Among them, A, Q, X, R 3 、R 4 、R 5 、R 6 Having the above definition;

[0090] Optionally, X is CH, C-CH3, C-Cl or C-CN.

[0091] In some specific embodiments of the present invention, the compound represented by Formula I has a structure represented by Formula Ia', Ib' or Ic':

[0092] Wherein, A and Q have the same definitions as above.

[0093] In some more specific embodiments of the present invention, the compound represented by Formula I has a structure represented by Formula Ia", Ib" or Ic":

[0094] Wherein, A and Q have the same definitions as above.

[0095] According to an embodiment of the present invention, the compound represented by Formula V has a structure represented by Formula Id, Ie, If, Ig, Ih, Ii, Ij, Ik, Il or Im:

[0096] Wherein, Q has the above definition.

[0097] According to an embodiment of the present invention, A is selected from H, halogen, -5-12 membered heteroaryl-C 3-12 Cycloalkyl-CN, -C 6-14 Aryl-C 3-12 Cycloalkyl-CN, 5-12 membered heteroaryl, C 6-14 Aryl, -5-12 membered heteroaryl-NH2, -C 6-14 Aryl-NH2, -C 1-12 Alkyl -NH2, -C≡CC 1-12 Alkyl-NH2, -CH=CH-C 1- 12 Alkyl-NH2, -C≡C-3-12 membered heterocyclyl-OH, -CH=CH-3-12 membered heterocyclyl-OH, -C≡CC 3-12 Cycloalkyl-OH, -CH=CH-C 3-12 Cycloalkyl-OH, 3-12 membered heterocyclyl, -5-12 membered heteroaryl-C 1-12 Alkyl, -C 6-14 Aryl-C 1-12 Alkyl, -C≡CC 3-12 Cycloalkyl, -CH=CH-C 3-12 Cycloalkyl, -C≡C-3-12 membered heterocyclic group, -CH=CH-3-12 membered heterocyclic group, -C≡CC 1-12 Alkyl-OH, -CH=CH-C 1-12 Alkyl-OH, C 3-12 Cycloalkyl, -C 3-12 Cycloalkyl (C 1-12 alkyl)-NH2, 3-12 membered heterocyclic group substituted by 1 or 2 =O, -C 3-12 Cycloalkyl (C 1-12 alkyl)-OH, -3-12 membered heterocyclic group (C 1-12 alkyl)-OH, -3-12 membered heterocyclic group (C 1-12 Alkyl)-NH2, CN, =O, -C3-12 Cycloalkyl = C (halogen) 2, -3-12 membered heterocyclic group = CH-halogen, -3-12 membered heterocyclic group = C (halogen) 2, -C 3-12 Cycloalkyl=CH-halogen, -CH=CH-3-12 membered heterocyclyl-C 1-12 Alkyl, -3-12 membered heterocyclic group -COC 1-12 Alkyl, -3-12 membered heterocyclic group-C 1-12 Alkyl, -C≡C-5-12 membered heteroaryl-C 1-12 Alkyl or -CH=CH-3-12 membered heterocyclic group C 1-12 alkyl.

[0098] According to an embodiment of the present invention, when A is selected from -5-12 membered heteroaryl-C 3-12 When cycloalkyl-CN, CN is substituted at C 3-12 cycloalkyl, and is on the carbon atom to which the 5-12 membered heteroaryl is attached.

[0099] According to an embodiment of the present invention, when A is selected from -C 6-14 Aryl-C 3-12 When cycloalkyl-CN, CN is substituted at C 3-12 Cycloalkyl, and C 6-14 The carbon to which the aryl group is attached.

[0100] According to an embodiment of the present invention, when A is selected from -C≡C-3-12 membered heterocyclyl-OH, OH is substituted on the carbon of the 3-12 membered heterocyclyl and to which the -C≡C- group is attached.

[0101] According to an embodiment of the present invention, when A is selected from -C≡CC 3-12 In the case of cycloalkyl-OH, OH is substituted at C 3-12 Cycloalkyl, and on the carbon to which the -C≡C- group is attached.

[0102] According to an embodiment of the present invention, when A is selected from -CH=CH-3-12 membered heterocyclyl-OH, OH is substituted on the carbon of the 3-12 membered heterocyclyl to which the -CH=CH- group is attached.

[0103] According to an embodiment of the present invention, when A is selected from -CH=CH-C 3-12 In the case of cycloalkyl-OH, OH is substituted at C 3-12 Cycloalkyl, and on the carbon to which the -C≡C- group is attached.

[0104] According to an embodiment of the present invention, when A is selected from -5-12 membered heteroaryl-C 1-12 When alkyl, C 1-12 The alkyl group is substituted on a heteroatom or on C in a 5-12 membered heteroaryl group.

[0105] According to an embodiment of the present invention, when A is selected from a 3-12 membered heterocyclic group substituted by two =O, the =O are all substituted on a heteroatom (such as S) of the 3-12 membered heterocyclic group.

[0106] According to an embodiment of the present invention, when A is selected from -C 3-12 Cycloalkyl = C (halogen) 2, -3-12 membered heterocyclyl = CH-halogen, -3-12 membered heterocyclyl = C (halogen) 2 or -C 3-12 When cycloalkyl = CH-halogen, the double bond is directly connected to C 3-12 The C groups on the cycloalkyl or 3-12 membered heterocyclic group are connected.

[0107] According to an embodiment of the present invention, when A is selected from -3-12 membered heterocyclyl-COC 1-12 When alkyl, the -COC 1-12 The alkyl group is substituted on a heteroatom (such as N) or on C of a 3-12 membered heterocyclic group.

[0108] According to an embodiment of the present invention, Q is selected from N or CR 1 , R 1 Selected from H, -NHCO-5-12 membered heteroaryl, -NHCO-C 6-14 Aryl, -NH-C 1-12 Alkyl-5-12 membered heteroaryl-C 1-12 Alkyl, -NH-C 1-12 Alkyl-C 6-14 Aryl-C 1-12 Alkyl, -C≡C-5-12 membered heteroaryl-C 1-12 Alkyl, -CH=CH-5-12 membered heteroaryl-C 1-12 Alkyl, -C≡CC 6-14 Aryl-C 1-12 Alkyl, -CH=CH-C 6-14 Aryl-C 1-12 Alkyl, -CONH-5-12 membered heteroaryl, -CONH-C 6-14 Aryl, -CONH2, -C 1-12 Alkyl-OC 3-12 Cycloalkyl, -C 1-12 Alkyl-O-3-12 membered heterocyclic group, -CONH-C 3-12 Cycloalkyl, -CONH-3-12 membered heterocyclic group, -C 1-12 Alkyl-C 3-12 Cycloalkyl, -C 1-12 Alkyl-3-12 membered heterocyclic group, C 1-12 Alkyl, C 1-12 Alkoxy, -C≡CC 1-12 Alkyl-OH, -CH=CH-C 1-12Alkyl-OH, -C≡CC 1-12 Alkyl-NH2, -CH=CH-C 1-12 Alkyl-NH2, -CH=CH-C 3-12 Cycloalkyl, -CH=CH-OC 3-12 Cycloalkyl, -CH=CH-3-12 membered heterocyclic group, -C≡CC 3-12 Cycloalkyl, -C≡C-3-12 membered heterocyclic group, -C 1-12 Alkyl-O-5-12 membered heteroaryl, -C 1-12 Alkyl-OC 6-14 Aryl, -5-12 membered heteroaryl-NH2, -5-12 membered heteroaryl [C 3-12 Cycloalkyl=C(halogen)2]-NH2, -5-12 membered heteroaryl-3-12 membered heterocyclic group, -5-12 membered heteroaryl-3-12 membered heterocyclic group (C 1-12 alkyl)-NH2, -5-12 membered heteroaryl-C 1-12 Alkyl, 3-12 membered heterocyclic group substituted by =O, -C 3-12 Cycloalkyl=C(halogen)2, -C=C-3-12 membered heterocyclic group-C 1-12 Alkyl, -C=CC 3-12 Cycloalkyl-OH, -3-12 membered heterocyclyl-C 1-12 Alkyl, C substituted by =O 3-12 Cycloalkyl, -C 3-12 Cycloalkyl=C(halogen)2 or -C 3-12 Cycloalkyl=CC 1-12 Alkyl-OC 1-12 alkyl.

[0109] According to an embodiment of the present invention, A is selected from H, halogen, -5-6 membered heteroaryl-C 3-6 Cycloalkyl-CN, -phenyl-C 3-6 Cycloalkyl-CN, 5-6 membered heteroaryl, phenyl, -5-6 membered heteroaryl-NH2, -phenyl-NH2, -C 1-6 Alkyl -NH2, -C≡CC 1-6 Alkyl-NH2, -C≡C-3-6 membered heterocyclic group-OH, -C≡CC 3-6 Cycloalkyl-OH, -CH=CH-3-6 membered heterocyclic-OH, -CH=CH-C 3-6 Cycloalkyl-OH, 3-6 membered heterocyclyl, -5-6 membered heteroaryl-C 1-6 Alkyl, -phenyl-C 1- 6-alkyl, -C≡CC 3-6 Cycloalkyl, -C≡C-3-6 membered heterocyclic group, -CH=CH-C 3-6Cycloalkyl, -CH=CH-3-6 membered heterocyclic group, -C≡CC 1-6 Alkyl-OH, -CH=CH-C 1-6 Alkyl-OH, C 3-6 Cycloalkyl, -C 3-6 Cycloalkyl (C 1-6 Alkyl)-NH2, -3-6 membered heterocyclic group (C 1-6 alkyl)-NH2, 3-6 membered heterocyclic group substituted by 1 or 2 =O, -5-6 membered heteroaryl-C 1-6 Alkyl, -C 3-6 Cycloalkyl (C 1-6 Alkyl)-OH, -3-6 membered heterocyclic group (C 1-6 Alkyl)-OH or -3-6 membered heterocyclic group (C 1- 6 alkyl)-NH2, CN, =O, -C 3-6 Cycloalkyl = C (halogen) 2, -3-6 membered heterocyclic group = CH-halogen, -3-6 membered heterocyclic group = C (halogen) 2, -C 3-6 Cycloalkyl=CH-halogen, -CH=CH-3-6 membered heterocyclic group-C 1-6 Alkyl, -3-6 membered heterocyclic group -COC 1-6 Alkyl, -3-6 membered heterocyclic group-C 1-6 Alkyl, -C≡C-5-6 membered heteroaryl-C 1- 6-alkyl or -CH=CH-3-6-membered heterocyclic group-C 1-6 alkyl.

[0110] According to an embodiment of the present invention, when A is selected from a 5-6 membered heteroaryl group, it is selected from thienyl, furyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyrazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, triazolyl, thiadiazolyl, thia-4H-pyrazolyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl or triazinyl.

[0111] According to an embodiment of the present invention, A is selected from C 3-6 When it is a cycloalkyl group, it is selected from cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl.

[0112] According to an embodiment of the present invention, A is selected from -5-6 membered heteroaryl-C 3-6 When cycloalkyl-CN, it can be a 5-6 membered heteroaryl group and C 3-6 The group formed by connecting cycloalkyl groups, where CN replaces C 3-6On the cycloalkyl group, and on the carbon to which the 5-6 membered heteroaryl group is attached. For example, A is selected from -pyridine-cyclopropyl-CN, -pyridine-cyclobutyl-CN, -pyridine-cyclopentyl-CN, -pyridine-cyclohexyl-CN, -pyrrole-cyclopropyl-CN, -pyrrole-cyclobutyl-CN, -pyrrole-cyclopentyl-CN or -pyrrole-cyclohexyl-CN; the CN substituted on C 3-6 On the cycloalkyl group, if A is selected from

[0113] According to an embodiment of the present invention, A is selected from -phenyl-C 3-6 In the case of cycloalkyl-CN, it may be -phenyl-cyclopropyl-CN, -phenyl-cyclobutyl-CN, -phenyl-cyclopentyl-CN or -phenyl-cyclohexyl-CN.

[0114] According to an embodiment of the present invention, when A is selected from 5-6 membered heteroaryl -NH2, it can be thienyl, furyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyrazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, triazolyl, thiadiazolyl, thia-4H-pyrazolyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl or triazinyl as described above, and 1, 2 or 3 H on any one ring is substituted by NH2. For example, A is

[0115] According to an embodiment of the present invention, A is selected from -C≡CC 1-6 Alkyl-NH2, -CH=CH-C 1-6 Alkyl -NH2, -C≡CC 1-6 Alkyl-OH or -CH=CH-C 1-6 When alkyl-OH, the C 1-6 The alkyl group is methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, isobutyl, sec-butyl, tert-butyl, isopentyl, 2-methylbutyl, 1-methylbutyl, 1-ethylpropyl, 1,2-dimethylpropyl, neopentyl, 1,1-dimethylpropyl, 4-methylpentyl, 3-methylpentyl, 2-methylpentyl, 1-methylpentyl, 2-ethylbutyl, 1-ethylbutyl, 3,3-dimethylbutyl, 2,2-dimethylbutyl, 1,1-dimethylbutyl, 2,3-dimethylbutyl, 1,3-dimethylbutyl or 1,2-dimethylbutyl, and the number of OH or NH2 is independently 1, 2 or 3, for example, A is selected from

[0116] According to an embodiment of the present invention, when A is selected from a 3-6 membered heterocyclic group, it is selected from azetidinyl, azetidinyl, oxetanyl, oxetanyl, tetrahydrofuranyl, dihydrofuranyl, dioxolyl, pyrrolidinyl, dihydroimidazolyl, imidazolidinyl, dihydropyrazolyl, pyrazolidinyl, pyrrolinyl, oxazolinyl, oxazolidinyl, thiazolinyl, thiazolidinyl, pyranyl, tetrahydropyranyl, tetrahydropyridinyl, thiopyranyl , dihydropyrimidinyl, piperidinyl, morpholinyl, dithianyl, thiomorpholinyl, piperazinyl, trithianyl, 2,5-dihydro-1H-pyrrolyl, 3,6-dihydro-2H-pyranyl, 1,2,3,6-tetrahydropyridinyl, 4H-[1,3,4]thiadiazinyl, 4,5-dihydrooxazolyl, 4H-[1,4]thiazinyl, 5H,6H,8H-[1,2,4]triazolo[4,3-a]pyrazinyl or

[0117] According to an embodiment of the present invention, A is selected from -3-6 membered heterocyclyl-C 1-6 When alkyl, the -3-6 membered heterocyclic group, C 1-6 Alkyl groups have the above definitions, for example, A is

[0118] According to an embodiment of the present invention, when A is selected from -C≡C-3-6 membered heterocyclyl-OH or -CH=CH-3-6 membered heterocyclyl-OH, the 3-6 membered heterocyclyl has the above-mentioned definition, and the OH is substituted on the carbon of the 3-6 membered heterocyclyl and connected to the -CH=CH- or -C≡C- group; the number of the OH substituents is 1, 2 or 3, for example, A is

[0119] According to an embodiment of the present invention, A is selected from -C≡CC 3-6 Cycloalkyl-OH or -CH=CH-C 3-6 When cycloalkyl-OH, the C 3-6 Cycloalkyl has the above definition, the OH substituted at C 3-6 Cycloalkyl, and on the carbon to which the -CH=CH- or -C≡C- group is attached; the number of the OH substituents is 1, 2 or 3.

[0120] According to an embodiment of the present invention, A is selected from -5-6 membered heteroaryl-C 1-6 Alkyl or -phenyl-C 1-6 When alkyl, the 5-6 membered heteroaryl group has the above definition, the C 1-6The alkyl group is methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, isobutyl, sec-butyl, tert-butyl, isopentyl, 2-methylbutyl, 1-methylbutyl, 1-ethylpropyl, 1,2-dimethylpropyl, neopentyl, 1,1-dimethylpropyl, 4-methylpentyl, 3-methylpentyl, 2-methylpentyl, 1-methylpentyl, 2-ethylbutyl, 1-ethylbutyl, 3,3-dimethylbutyl, 2,2-dimethylbutyl, 1,1-dimethylbutyl, 2,3-dimethylbutyl, 1,3-dimethylbutyl or 1,2-dimethylbutyl, and the C 1-6 The number of alkyl groups is 1, 2 or 3. For example, A is

[0121] According to an embodiment of the present invention, A is selected from -C≡CC 3-6 Cycloalkyl or -CH=CH-C 3-6 When A is cycloalkyl, A is selected from -CH=CH-cyclopropyl, -CH=CH-cyclobutyl, -CH=CH-cyclopentyl, -CH=CH-cyclohexyl, -C≡C-cyclopropyl, -C≡C-cyclobutyl, -C≡C-cyclopentyl or -C≡C-cyclohexyl.

[0122] According to an embodiment of the present invention, when A is selected from -C≡C-3-6 membered heterocyclyl or -CH=CH-3-6 membered heterocyclyl, A is selected from -CH=CH-azetidine or -C≡C-azetidine.

[0123] According to an embodiment of the present invention, A is selected from -C 3-6 Cycloalkyl (C 1-6 Alkyl)-NH2 or -C 3-6 Cycloalkyl (C 1-6 alkyl)-OH, the C 3-6 Cycloalkyl and C 1-6 The alkyl group has the above definition, and the number of OH or NH2 is independently 1, 2 or 3, for example, A is selected from

[0124] According to an embodiment of the present invention, A is selected from -3-6 membered heterocyclic group (C 1-6 Alkyl)-OH or -3-6 membered heterocyclic group (C 1-6 alkyl)-NH2, the 3-6 membered heterocyclic group and C 1-6 The alkyl group has the above definition, and the number of OH or NH2 is independently 1, 2 or 3, for example, A is selected from

[0125] According to an embodiment of the present invention, when A is selected from a 3-6 membered heterocyclic group substituted by =O, the 3-6 membered heterocyclic group has the above definition, for example, A is

[0126] According to an embodiment of the present invention, A is selected from -C 3-6 When cycloalkyl=C(halogen)2, it is selected from -cyclopropyl=C(halogen)2, -cyclobutyl=C(halogen)2, -cyclopentyl=C(halogen)2 or -cyclohexyl=C(halogen)2. For example,

[0127] According to an embodiment of the present invention, when A is selected from -3-6 membered heterocyclyl=CH-halogen, -3-6 membered heterocyclyl=C(halogen)2, the 3-6 membered heterocyclyl has the above-mentioned definition. For example, A is

[0128] According to an embodiment of the present invention, A is selected from -CH=CH-3-6 membered heterocyclyl-C 1-6 When alkyl, the 3-6 membered heterocyclic group and C 1-6 Alkyl has the definition as described above. For example, A is

[0129] According to an embodiment of the present invention, A is selected from -3-6 membered heterocyclyl-COC 1-6 When alkyl, the 3-6 membered heterocyclic group and C 1-6 Alkyl has the definition as described above. For example, A is

[0130] According to an embodiment of the present invention, A is selected from -C≡C-5-6 membered heteroaryl-C 1-6 When alkyl, 5-6 membered heteroaryl and C 1-6 Alkyl has the definition as described above. For example, A is

[0131] According to an embodiment of the present invention, Q is selected from N or CR 1 , R 1 Selected from H, -NHCO-5-6 membered heteroaryl, -NHCO-phenyl, -NH-C 1-6 Alkyl-5-6 membered heteroaryl-C 1-6 Alkyl, -NH-C 1-6 Alkyl-phenyl-C 1-6 Alkyl, -C≡C-5-6 membered heteroaryl-C 1-6 Alkyl, -C≡C-phenyl-C 1-6 Alkyl, -CH=CH-5-6 membered heteroaryl-C 1-6 Alkyl, -CH=CH-phenyl-C 1-6 Alkyl, -CONH-5-6 membered heteroaryl, -CONH-phenyl, -CONH2, -C 1-6 Alkyl-OC 3-6 Cycloalkyl, -CONH-C 3-6Cycloalkyl, -CONH-3-6 membered heterocyclic group, -C 1-6 Alkyl-C 3-6 Cycloalkyl, -C 1-6 Alkyl-3-6 membered heterocyclic group, C 1-6 Alkyl, C 1-6 Alkoxy, -C≡CC 1-6 Alkyl-OH, -CH=CH-C 1-6 Alkyl-OH, -C≡CC 1-6 Alkyl-NH2, -CH=CH-C 1-6 Alkyl-NH2, -CH=CH-C 3-6 Cycloalkyl, -CH=CH-OC 3-6 Cycloalkyl, -CH=CH-3-6 membered heterocyclic group, -C≡CC 3-6 Cycloalkyl, -C≡C-3-6 membered heterocyclic group, -C 1-6 Alkyl-O-5-6 membered heteroaryl, -C 1-6 Alkyl-O-3-6 membered heterocyclic group, -5-6 membered heteroaryl-NH2, -5-6 membered heteroaryl [C 3-6 Cycloalkyl = C (halogen) 2] -NH 2, -5-6 membered heteroaryl-3-6 membered heterocyclic group, -5-6 membered heteroaryl-3-6 membered heterocyclic group (C 1-6 Alkyl)-NH2, -5-6 membered heteroaryl-C 1-6 Alkyl, 3-6 membered heterocyclic group substituted by =O, -C 3-6 Cycloalkyl=C(halogen)2, -C=C-3-6 membered heterocyclic group-C 1-6 Alkyl, -C=CC 3-6 Cycloalkyl-OH, -3-6 membered heterocyclic-C 1-6 Alkyl, C substituted by =O 3- 6-cycloalkyl, -C 3-6 Cycloalkyl=C(halogen)2 or -C 3-6 Cycloalkyl=CC 1-6 Alkyl-OC 1-6 alkyl.

[0132] According to an embodiment of the present invention, Q is selected from N or CR 1 , R 1 When selected from H, -NHCO-5-6 membered heteroaryl or -CONH-5-6 membered heteroaryl, the 5-6 membered heteroaryl is selected from thienyl, furyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyrazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, triazolyl, thiadiazolyl, thia-4H-pyrazolyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl or triazinyl; for example, R 1 for

[0133] According to an embodiment of the present invention, Q is selected from N or CR 1 , R 1 Selected from C 1-6 When the alkyl group is a methyl group, an ethyl group, a propyl group, a butyl group, a pentyl group, a hexyl group, an isopropyl group, an isobutyl group, a sec-butyl group, a tert-butyl group, an isopentyl group, a 2-methylbutyl group, a 1-methylbutyl group, a 1-ethylpropyl group, a 1,2-dimethylpropyl group, a neopentyl group, a 1,1-dimethylpropyl group, a 4-methylpentyl group, a 3-methylpentyl group, a 2-methylpentyl group, a 1-methylpentyl group, a 2-ethylbutyl group, a 1-ethylbutyl group, a 3,3-dimethylbutyl group, a 2,2-dimethylbutyl group, a 1,1-dimethylbutyl group, a 2,3-dimethylbutyl group, a 1,3-dimethylbutyl group or a 1,2-dimethylbutyl group.

[0134] According to an embodiment of the present invention, Q is selected from N or CR 1 , R 1 Selected from H, -NH-C 1-6 Alkyl-5-6 membered heteroaryl-C 1-6 Alkyl, -C≡C-5-6 membered heteroaryl-C 1-6 Alkyl, -CH=CH-5-6 membered heteroaryl-C 1-6 Alkyl or -C 1-6 When alkyl-O-5-6 membered heteroaryl, the 5-6 membered heteroaryl and C 1-6 Alkyl has the above definition, the C 1-6 The number of alkyl groups is 1, 2 or 3, for example, R 1 for

[0135] According to an embodiment of the present invention, Q is selected from N or CR 1 , R 1 Selected from H, -C 1-6 Alkyl-OC 3-6 Cycloalkyl, -C 1-6 Alkyl-C 3-6 Cycloalkyl, -CONH- C 3-6 Cycloalkyl, -CH=CH-C 3-6 Cycloalkyl or -C≡CC 3-6 When cycloalkyl, the C 1-6 Alkyl has the above definition, the C 3-6 Cycloalkyl is selected from cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl, for example R 1is -CH2-O-cyclopropyl, -CH2-cyclopropyl, -CH2-cyclobutyl, -CH2-cyclopentyl, -CH2-cyclohexyl, -C2H4-cyclopropyl, -C2H4-cyclobutyl, -C2H4-cyclopentyl, -C2H4-cyclohexyl, -CH=CH-cyclopropyl, -CH=CH-cyclobutyl, -CH=CH-cyclopentyl, -CH=CH-cyclohexyl, -CH2-O-cyclobutyl, -CH2-O-cyclopentyl, -CH2-O-cyclohexyl, -C2H4-O-cyclopropyl, -C2H4-O-cyclobutyl, -C2H4-O-cyclopentyl, -C2H4-O-cyclohexyl or

[0136] According to an embodiment of the present invention, Q is selected from N or CR 1 , R 1 Selected from H, -CONH-3-6 membered heterocyclic group, -C 1-6 Alkyl-3-6 membered heterocyclic group, -CH=CH-3-6 membered heterocyclic group, -C≡C-3-6 membered heterocyclic group or -C 1-6 When alkyl-O-3-6 membered heterocyclic group, the C 1-6 Alkyl is as defined above; the 3-6 membered heterocyclic group is selected from azetidinyl, azetidinyl, oxetanyl, oxetanyl, tetrahydrofuranyl, dihydrofuranyl, dioxolyl, pyrrolidinyl, dihydroimidazolyl, imidazolidinyl, dihydropyrazolyl, pyrazolidinyl, pyrrolinyl, oxazolinyl, oxazolidinyl, thiazolinyl, thiazolidinyl, pyranyl, tetrahydropyranyl, tetrahydropyridinyl, thiopyranyl, For example, R 1 Selected from

[0137] According to an embodiment of the present invention, Q is selected from N or CR 1 , R 1 is selected from 5-6 membered heteroaryl-NH2, wherein the 5-6 membered heteroaryl is selected from thienyl, furyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyrazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, triazolyl, thiadiazolyl, thia-4H-pyrazolyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl or triazinyl; for example, R 1 for

[0138] According to an embodiment of the present invention, Q is selected from N or CR 1, R 1 Selected from -5-12 membered heteroaryl[C 3-12 Cycloalkyl = C (halogen) 2] -NH 2, the 5-6 membered heteroaryl is selected from thienyl, furyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyrazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, triazolyl, thiadiazolyl, thia-4H-pyrazolyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl or triazinyl; for example, R 1 for

[0139] According to an embodiment of the present invention, Q is selected from N or CR 1 , R 1 -5-6 membered heteroaryl-3-6 membered heterocyclic group; the 5-6 membered heteroaryl and 3-6 membered heterocyclic group have the above-mentioned definitions; for example, R 1 for

[0140] According to an embodiment of the present invention, Q is selected from N or CR 1 , R 1 -5-6 membered heteroaryl-3-6 membered heterocyclic group (C 1-6 Alkyl)-NH2; the 5-6 membered heteroaryl, 3-6 membered heterocyclic group and C 1-6 Alkyl groups have the same meaning as above; for example, R 1 for

[0141] According to an embodiment of the present invention, Q is selected from N or CR 1 , R 1 -5-6 membered heteroaryl-C 1-6 Alkyl, the 5-6 membered heteroaryl and C 1-6 Alkyl groups have the same meaning as above; for example, R 1 for

[0142] According to an embodiment of the present invention, Q is selected from N or CR 1 , R 1 Selected from C substituted by =O 3-6 Cycloalkyl, the C 3-6 Cycloalkyl has the same meaning as above; for example, R 1 for

[0143] According to an embodiment of the present invention, Q is selected from N or CR 1 , R 1 Selected from -C 3-6 Cycloalkyl=C(halogen)2, the C 3-6 Cycloalkyl has the above definition, and the halogen is selected from F or Cl, for example R 1for

[0144] According to an embodiment of the present invention, Q is selected from N or CR 1 , R 1 Selected from -CH=CH-3-6 membered heterocyclyl-C 1-6 When alkyl, the 3-6 membered heterocyclic group and C 1-6 Alkyl has the same meaning as above. 1 for

[0145] According to an embodiment of the present invention, Q is selected from N or CR 1 , R 1 Selected from -C=CC 3-6 Cycloalkyl-OH, where C 3-6 Cycloalkyl has the same meaning as above, for example R 1 Selected from

[0146] According to an embodiment of the present invention, Q is selected from N or CR 1 , R 1 -3-6 membered heterocyclyl-C 1-6 When alkyl, the -3-6 membered heterocyclic group and C 1-6 Alkyl groups have the same meaning as above, for example R 1 for

[0147] According to an embodiment of the present invention, Q is selected from N or CR 1 , R 1 Selected from -C 3-6 Cycloalkyl=CC 1-6 Alkyl-OC 1-6 Alkyl, wherein the C 3-6 Cycloalkyl and C 1-6 Alkyl groups have the same meaning as above, for example R 1 Selected from

[0148] According to an embodiment of the present invention, G and R in formula V-1 3 or R 6 are connected together to form a 3-6 membered heterocyclic group or a 5-6 membered heteroaryl group; the 3-6 membered heterocyclic group or the 5-6 membered heteroaryl group is optionally substituted by 1, 2 or more of the following groups: C 1-6 alkyl.

[0149] In some specific embodiments of the present invention, A is selected from H, =O, CN, F, Cl, Br, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl,

[0150] In some specific embodiments of the present invention, Q is selected from N or CR 1 , R 1 is selected from H, -CH2-O-cyclopropyl, -CH2-cyclopropyl, -CH2-cyclobutyl, -CH2-cyclopentyl, -CH2-cyclohexyl, -C2H4-cyclopropyl, -C2H4-cyclobutyl, -C2H4-cyclopentyl, -C2H4-cyclohexyl, methyl, ethyl, propyl, -CH2-O-cyclobutyl, -CH2-O-cyclopentyl, -CH2-O-cyclohexyl, -C2H4-O-cyclopropyl, -C2H4-O-cyclobutyl, -C2H4-O-cyclopentyl, -C2H4-O-cyclohexyl, methoxy, ethoxy, propyloxy, -CH=CH-cyclopropyl, -CH=CH-cyclobutyl, -CH=CH-cyclopentyl, -CH=CH-cyclohexyl,

[0151] As an example, the compound is selected from the following compounds 1 to 62:

[0152] The present invention also provides a pharmaceutical composition comprising the compound as described above, a pharmaceutically acceptable salt or stereoisomer thereof, and a pharmaceutically acceptable excipient.

[0153] The present invention also provides use of the above compound, its pharmaceutically acceptable salt or stereoisomer in the preparation of Myt1 kinase inhibitors.

[0154] According to an embodiment of the present invention, the Myt1 kinase inhibitor is used for treating tumors.

[0155] In some embodiments of the invention, the tumor overexpresses CCNE1.

[0156] In some embodiments of the invention, the tumor has an inactivating mutation in the FBXW7 gene.

[0157] In some embodiments of the invention, the tumor is a solid tumor.

[0158] In some embodiments of the invention, the tumor is breast cancer, colorectal cancer, endometrial cancer, esophageal cancer, glioblastoma, hepatocellular carcinoma, lung cancer, neuroblastoma, ovarian cancer, prostate cancer, gastric cancer, or uterine cancer.

[0159] The present invention also provides a method for treating a disease, comprising: administering at least one of the above compounds, pharmaceutically acceptable salts or stereoisomers thereof to an individual in need thereof.

[0160] In some embodiments of the present invention, the disease is a disease mediated by a Myt1 kinase inhibitor; further, the disease is a tumor.

[0161] In some embodiments of the invention, the tumor is a solid tumor.

[0162] In some embodiments of the invention, the tumor is breast cancer, colorectal cancer, endometrial cancer, esophageal cancer, glioblastoma, hepatocellular carcinoma, lung cancer, neuroblastoma, ovarian cancer, prostate cancer, gastric cancer, or uterine cancer. Beneficial effects

[0163] The present invention provides a novel cyclopentadiene compound, which is a Myt1 kinase inhibitor and can be used for treating tumors with good selectivity.

[0164] Definitions and Explanations of Terms

[0165] The term "halogen" means fluorine, chlorine, bromine and / or iodine. Correspondingly, the term "halo" refers to fluoro, chloro, bromo and / or iodo. Within the scope of this document, when an atom, residue, group or moiety is halogenated, the atom at the halogenated position may be monosubstituted, disubstituted or polysubstituted up to full substitution by halogen atoms, for example, "haloC 1-12 Alkyl" and "halogenated C 1-12 Alkoxy" etc.

[0166] In this application, some substituents marked with "*" represent the connection site.

[0167] The term "C 1-12 "Alkyl" should be understood to mean a straight or branched saturated monovalent hydrocarbon group having 1 to 12 carbon atoms, which can be C 1-6 Alkyl. "C 1-6 The term "alkyl" is understood to mean a linear or branched saturated monovalent hydrocarbon radical having 1, 2, 3, 4, 5 or 6 carbon atoms. The alkyl radical is, for example, methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, isobutyl, sec-butyl, tert-butyl, isopentyl, 2-methylbutyl, 1-methylbutyl, 1-ethylpropyl, 1,2-dimethylpropyl, neopentyl, 1,1-dimethylpropyl, 4-methylpentyl, 3-methylpentyl, 2-methylpentyl, 1-methylpentyl, 2-ethylbutyl, 1-ethylbutyl, 3,3-dimethylbutyl, 2,2-dimethylbutyl, 1,1-dimethylbutyl, 2,3-dimethylbutyl, 1,3-dimethylbutyl or 1,2-dimethylbutyl, or the like or isomers thereof. In particular, the radical has 1, 2 or 3 carbon atoms ("C 1-3 "alkyl"), for example methyl, ethyl, n-propyl or isopropyl.

[0168] The term "C 2-12"Alkenyl" is understood to mean a linear or branched monovalent hydrocarbon radical containing one or more double bonds and having 2 to 12 carbon atoms, optionally "C 2-6 Alkenyl". "C 2-6 "Alkenyl" is understood to mean optionally a linear or branched monovalent hydrocarbon radical containing one or more double bonds and having 2, 3, 4, 5, 6 carbon atoms, in particular 2 or 3 carbon atoms ("C 2-3 "alkenyl"), it being understood that where the alkenyl contains more than one double bond, the double bonds may be separated from one another or conjugated. The alkenyl is, for example, vinyl, allyl, (E)-2-methylvinyl, (Z)-2-methylvinyl, (E)-but-2-enyl, (Z)-but-2-enyl, (E)-but-1-enyl, (Z)-but-1-enyl, pent-4-enyl, (E)-pent-3-enyl, (Z)-pent-3-enyl. -enyl, (E)-pent-2-enyl, (Z)-pent-2-enyl, (E)-pent-1-enyl, (Z)-pent-1-enyl, hex-5-enyl, (E)-hex-4-enyl, (Z)-hex-4-enyl, (E)-hex-3-enyl, (Z)-hex-3-enyl, (E)-hex-2-enyl, (Z)-hex-2-enyl, (E)-hex-1-enyl, (Z)-hex-1-enyl, isopropenyl, 2-enyl -methylprop-2-enyl, 1-methylprop-2-enyl, 2-methylprop-1-enyl, (E)-1-methylprop-1-enyl, (Z)-1-methylprop-1-enyl, 3-methylbut-3-enyl, 2-methylbut-3-enyl, 1-methylbut-3-enyl, 3-methylbut-2-enyl, (E)-2-methylbut-2-enyl, (Z)-2-methylbut-2-enyl, (E)-1-methylbut-2-enyl 1-ethylprop-1-enyl, 1-propylvinyl or 1-isopropylvinyl.

[0169] The term "C 2-12The term "alkynyl" is understood as meaning a linear or branched monovalent hydrocarbon radical containing one or more triple bonds and having 2 to 12 carbon atoms, optionally a "C2-C6-alkynyl" radical. The term "C2-C6-alkynyl" is understood as optionally meaning a linear or branched monovalent hydrocarbon radical containing one or more triple bonds and having 2, 3, 4, 5, 6 carbon atoms, in particular 2 or 3 carbon atoms ("C2-C3-alkynyl"). Such alkynyl radicals are, for example, ethynyl, prop-1-ynyl, prop-2-ynyl, but-1-ynyl, but-2-ynyl, but-3-ynyl, pent-1-ynyl, pent-2-ynyl, pent-3-ynyl, pent-4-ynyl, hex-1-ynyl, hex-2-ynyl, hex-3-ynyl, hex-4-ynyl, hex-5-ynyl, 1-methylprop-2-ynyl, 2-methylbut-3-ynyl, 1-methylbut-3-ynyl, -ynyl, 1-methylbut-2-ynyl, 3-methylbut-1-ynyl, 1-ethylprop-2-ynyl, 3-methylpent-4-ynyl, 2-methylpent-4-ynyl, 1-methylpent-4-ynyl, 2-methylpent-3-ynyl, 1-methylpent-3-ynyl, 4-methylpent-2-ynyl, 1-methylpent-2-ynyl, 4-methylpent-1-ynyl, 3-methylpent-1 ...2-ynyl, 4-methylpent-1-ynyl, 3-methylpent-1-ynyl, 2-methylpent-4-ynyl, 1-methylpent-4-ynyl, 2-methylpent-3-ynyl, 1-methylpent-3-ynyl, 4-methylpent-2-ynyl, In some embodiments, the alkynyl group is ethynyl, prop-1-ynyl or prop-2-ynyl.

[0170] The term "aryl" means a cyclic aromatic hydrocarbon group having from one to three aromatic rings (including monocyclic, bicyclic or tricyclic groups), such as phenyl, biphenyl or naphthyl. When containing two aromatic rings (bicyclic, etc.), the aromatic rings of the aryl group are optionally connected at a single point (e.g., biphenyl) or fused (e.g., naphthyl). The term "C 6-14 "Aryl" is understood to mean a monovalent aromatic monocyclic, bicyclic or tricyclic hydrocarbon ring ("C 6-14 aryl"), optionally "C 6-12 Aryl", especially a ring having 6 carbon atoms ("C6 aryl"), such as phenyl; or biphenyl, or a bicyclic ring having 10 carbon atoms ("C 10 aryl) such as naphthyl, or a tricyclic ring ("C 13 aryl), such as fluorenyl, or a tricyclic ring ("C 14 "aryl"), for example anthracenyl.

[0171] The term "heteroaryl" is understood to include monovalent monocyclic, bicyclic (e.g. fused, bridged, spiro) or tricyclic aromatic ring systems: The term "5-12 membered heteroaryl" has 5, 6, 7, 8, 9, 10, 11, 12 ring atoms, in particular 5 or 6 or 9 or 10 carbon atoms, and which contains 1 to 5, optionally 1 to 3 heteroatoms independently selected from N, O and S, and, in addition, in each case may be benzo-fused. In particular, the heteroaryl group is selected from thienyl, furyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyrazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, triazolyl, thiadiazolyl, thia-4H-pyrazolyl and the like and benzo derivatives thereof, such as benzofuranyl, benzothienyl, benzoxazolyl, benzisoxazolyl, benzimidazolyl, benzotriazolyl, indazolyl, indolyl, isoindolyl and the like; or pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl and the like and benzo derivatives thereof, such as quinolyl, quinazolinyl, isoquinolyl and the like; or acininyl, indolizinyl, purinyl and the like and benzo derivatives thereof; or cinnolinyl, phthalazinyl, quinazolinyl, quinoxalinyl, naphthyridinyl, pteridinyl, carbazolyl, acridinyl, phenazinyl, phenothiazinyl, phenoxazinyl and the like.

[0172] The term "cycloalkyl" is understood to mean a saturated or partially unsaturated monovalent monocyclic, bicyclic or polycyclic hydrocarbon ring. 3-12 "Cycloalkyl" should be understood to mean a saturated or partially unsaturated monovalent monocyclic, bicyclic or polycyclic hydrocarbon ring having 3-12 carbon atoms. Bicyclic or polycyclic cycloalkyl groups include paracyclic cycloalkyl, bridged cycloalkyl and spirocyclic cycloalkyl groups; the paracyclic group refers to a condensed ring structure formed by two or more cyclic structures sharing two adjacent ring atoms (i.e., sharing a bond). The bridged ring refers to a condensed ring structure formed by two or more cyclic structures sharing two non-adjacent ring atoms. The spirocyclic group refers to a condensed ring structure formed by two or more cyclic structures sharing one ring atom. For example, the C 3- 12 The cycloalkyl group may be a fully saturated C 3-8 or C 3-6 Monocyclic cycloalkyl, such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, or C 7-12 Cycloalkyl, such as decahydronaphthalene ring; can also be C 7-12 Bridged ring cycloalkyl, such as norbornane, adamantane, bicyclo [2,2,2] octane; it can also be a partially unsaturated ring structure, such as C with 1-3 double bonds 3-8 Monocyclic cycloalkenyl or C 3-6 Monocyclic cycloalkenyl, such as cyclopropenyl, cyclobutenyl, cyclopentenyl, cyclohexenyl, cyclobutadienyl, cyclopentadienyl or cyclohexadienyl, etc. Two hydrogen atoms on the carbon atoms of the cycloalkyl group may be replaced by an exocyclic double bond.

[0173] The term "heterocyclyl" means a saturated or partially unsaturated monovalent monocyclic, bicyclic or polycyclic non-aromatic hydrocarbon ring containing carbon atoms and 1-5 heteroatoms independently selected from N, O and S, and wherein there are no shared delocalized n electrons (aromaticity) between the ring carbons or heteroatoms. The term "3-12 membered heterocyclyl" means a saturated or partially unsaturated monovalent monocyclic or bicyclic non-aromatic hydrocarbon ring containing 1-5 heteroatoms independently selected from N, O and S and having a total of 3-12 ring atoms; the term "3-10 membered heterocyclyl" means a saturated or partially unsaturated monovalent monocyclic or bicyclic hydrocarbon ring containing 1-5, optionally 1-3 heteroatoms selected from N, O and S, and is also exemplified by "3-6 membered heterocyclyl", "4-6 membered heterocyclyl" and "5-6 membered heterocyclyl". When all the ring atoms in the heterocyclic group are linked by saturated bonds, it is called a saturated heterocyclic group. When there are 1, 2, 3 or more olefinic or acetylenic bonds, but they do not form an aromatic ring, it is called a heterocycloalkenyl or heterocycloalkynyl. The heterocyclic group can be linked to the rest of the molecule through any carbon atom or nitrogen atom (if present) among the carbon atoms that do not form an acetylenic bond. For example, "3-6 membered heterocyclic group" is further divided into "3-6 membered saturated heterocyclic group", "3-6 membered heterocycloalkenyl" and "3-6 membered heterocycloalkynyl". In particular, the heterocyclic group may include, but is not limited to, a 4-membered ring such as azetidinyl, azetidinyl, oxetanyl or oxetanyl; a 5-membered ring such as tetrahydrofuranyl, dihydrofuranyl, dioxolyl, pyrrolidinyl, dihydroimidazolyl, imidazolidinyl, dihydropyrazolyl, pyrazolidinyl, pyrrolinyl, oxazolinyl, oxazolidinyl, thiazolinyl or thiazolidinyl; or a 6-membered ring such as pyranyl, tetrahydropyranyl, thiopyranyl, dihydropyrimidinyl, piperidinyl, morpholinyl, dithianyl, thiomorpholinyl, piperazinyl or trithianyl; or a 7-membered ring such as diazepanyl or diazepanyl. Optionally, the heterocyclic group may be a fused ring, a bridged ring or a spirocyclic ring. The heterocyclic group may be bicyclic, such as, but not limited to, hexahydropyrrolo[1,2-a]pyrazine-2(1H)-yl. The heterocyclic group may be partially unsaturated, i.e., it may contain one, two, or more double bonds, such as, but not limited to, 2,5-dihydro-1H-pyrrolyl, 3,6-dihydro-2H-pyranyl, 1,2,3,6-tetrahydropyridinyl, 4H-[1,3,4]thiadiazinyl, 4,5-dihydrooxazolyl, or 4H-[1,4]thiazinyl, 5H,6H,8H-[1,2,4]triazolo[4,3-a]pyrazinyl. Two hydrogen atoms on the carbon atoms of the heterocyclic group may be replaced by an exocyclic double bond. The heterocyclic group may be fused to a 4-membered, 5-membered, 6-membered, or 7-membered ring, such as 2,3-dihydrobenzofuran, benzopyran, 1,2-dihydroquinazoline, 3,4-dihydroquinazoline, and the like. The heterocyclic group can also be a spirocyclic group formed by two or more 3-6 membered heterocyclic groups containing 1-3 heteroatoms (N, O and S) sharing one carbon atom. The heterocyclic group can also be a bridged ring group formed by two or more 3-6 membered heterocyclic groups containing 1-3 heteroatoms (N, O and S) sharing two carbon atoms.

[0174] Unless otherwise indicated, a heterocyclyl, heteroaryl, or heteroarylene group includes all possible isomeric forms thereof, such as positional isomers thereof. Thus, for some illustrative, non-limiting examples, pyridyl or pyridylene includes pyridin-2-yl, pyridin-2-ylene, pyridin-3-yl, pyridin-3-ylene, pyridin-4-ylene, and pyridin-4-ylene; thienyl or thienylene includes thien-2-yl, thien-2-ylene, thien-3-ylene, and thien-3-ylene.

[0175] The term "halogenated C 1-12 "Alkyl" means C 1-12 In the case where the H on the alkyl group is optionally substituted by 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 halogens, the “halogen” and “C 1-12 "Alkyl" has the above definition. The substitution is substituted on the same carbon atom or on different carbon atoms. Optionally "halogenated C 1-6 Alkyl". The "halogenated C 1-12 "Alkyl" is, for example, trifluoromethyl.

[0176] The term "C 1-12 "Alkoxy" means C 1-12 In the case where 1, 2 or 3 carbon atoms in the alkyl group are replaced by O, the above and "C 1-12 Alkyl" has the above definition. Optionally "C 1-6 Alkoxy". The "C 1-12 "Alkoxy" is, for example, methoxy, ethoxy or propoxy.

[0177] The term "halogenated C 1-12 "Alkoxy" means a halogenated C 1-12 In the case where 1, 2 or 3 carbon atoms in the alkyl group are replaced by O, the "halogenated C 1-12 Alkyl" has the above definition. Optionally "halogenated C 1-6 Alkoxy".

[0178] The term "C 1-12 "Alkylthio" means C 1-12 In the case where 1, 2 or 3 carbons in the alkyl group are replaced by S, the above and "C 1-12 "Alkyl" has the above definition. Optionally "C 1-6 "Alkylthio".

[0179] The term "C 1-12 "Hydroxyalkyl" means C 1-12In the case where the H on the alkyl group is optionally substituted by 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 OH groups, the “C 1-12 "Alkyl" has the above definition. The substitution is substituted on the same carbon atom or on different carbon atoms. 1-6 Hydroxyalkyl". The "C 1-12 "Hydroxyalkyl" is, for example, hydroxymethyl, hydroxyethyl or

[0180] The term "C 1-12 "Aminoalkyl" means C 1-12 In the case where the H on the alkyl group is optionally substituted by 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 NH2, the "C 1-12 The "alkyl" has the above definition. The substitution is substituted on the same carbon atom or on different carbon atoms. 1-12 "Aminoalkyl" is, for example,

[0181] The term "-5-12 membered heteroaryl-C 3-12 Cycloalkyl-CN, 5-12 membered heteroaryl, -5-12 membered heteroaryl-NH2, -C≡CC 1-12 Alkyl-NH2, -CH=CH-C 1-12 Alkyl-NH2, -C≡C-3-12 membered heterocyclyl-OH, -CH=CH-3-12 membered heterocyclyl-OH, 3-12 membered heterocyclyl, -5-12 membered heteroaryl-C 1-12 Alkyl, -C≡CC 3-12 Cycloalkyl, -CH=CH-C 3-12 Cycloalkyl, -C≡CC 1-12 Alkyl-OH, -CH=CH-C 1-12 Alkyl-OH, C 3-12 Cycloalkyl, -C 3-12 Cycloalkyl (C 1-12 alkyl)-NH2, 3-12 membered heterocyclyl substituted by =O, -5-12 membered heteroaryl-C 1-12 Alkyl, -C 3-12 Cycloalkyl (C 1-12 alkyl)-OH, -3-12 membered heterocyclic group (C 1-12 Alkyl)-OH or -3-12 membered heterocyclic group (C 1-12 alkyl)-NH2" in 5-12 membered heteroaryl, 3-12 membered heterocyclic group, C 1-12 Alkyl, C 3-12 The cycloalkyl group and the like have the same meaning as described above.

[0182] The term "more" substituted refers to more than three substituents, for example, 3, 4, 5, 6, 7, 8, 9 or 10 substituents.

[0183] The compounds of the present invention may contain unnatural proportions of atomic isotopes at one or more of the atoms that constitute the compound. For example, the compounds may be labeled with radioactive isotopes, such as deuterium ( 2 H), tritium ( 3 H), iodine-125( 125 I) or C-14( 14 C) All isotopic variations of the compounds of the present invention, whether radioactive or not, are encompassed within the scope of the present invention. In some embodiments of the present invention, H is deuterium or tritium.

[0184] As used herein, "pharmaceutically acceptable salts" refer to salts of the compounds of the present invention, which are safe and effective when used in mammals and have the desired biological activity.

[0185] Pharmaceutically acceptable salts include acid addition salts of compounds of the present invention having nitrogen atoms in the chain or ring and having sufficient basicity. In addition, basic nitrogen-containing groups can be quaternized using reagents such as lower alkyl halides, such as methyl, ethyl, propyl, and butyl chlorides, bromides, and iodides; dialkyl sulfates, such as dimethyl sulfate, diethyl sulfate, dibutyl sulfate, and diamyl sulfate; long-chain halides, such as decyl, lauryl, myristyl, and stearyl chlorides, bromides, and iodides; aralkyl halides such as benzyl and phenethyl bromides, and the like. Physiologically / pharmaceutically acceptable salts include, but are not limited to, hydrochlorides, sulfates, nitrates, bisulfates, hydrobromides, acetates, oxalates, citrates, methanesulfonates, formates, or meglumine salts, among others.

[0186] Depending on their molecular structure, the compounds of the present invention may be chiral and therefore may exist in various enantiomeric forms. These compounds may thus exist in racemic or optically active forms. The compounds of the present invention or their intermediates can be separated into enantiomeric compounds by chemical or physical methods known to those skilled in the art, or used in this form for synthesis. In the case of racemic amines, diastereomers are prepared from the mixture by reaction with an optically active resolving agent. Examples of suitable resolving agents are optically active acids, such as the R and S forms of tartaric acid, diacetyltartaric acid, dibenzoyltartaric acid, mandelic acid, malic acid, lactic acid, suitable N-protected amino acids (e.g., N-benzoylproline or N-phenylsulfonylproline), or various optically active camphorsulfonic acids. Chromatographic enantiomeric resolution can also be advantageously performed with the aid of optically active resolving agents (e.g., dinitrobenzoylphenylglycine immobilized on silica gel, cellulose triacetate or other carbohydrate derivatives, or chirally derivatized methacrylate polymers). Suitable eluents for this purpose are aqueous or alcoholic solvent mixtures, for example hexane / isopropanol / acetonitrile. DETAILED DESCRIPTION

[0187] The technical solutions of the present invention will be described in further detail below in conjunction with specific embodiments. It should be understood that the following embodiments are intended only to illustrate and explain the present invention by way of example and should not be construed as limiting the scope of protection of the present invention. All technologies implemented based on the above content of the present invention are encompassed within the scope of protection intended by the present invention.

[0188] Unless otherwise stated, the raw materials and reagents used in the following examples are commercially available or can be prepared by known methods.

[0189] Example 1: Preparation of 1-(6-(5-(3-hydroxy-2,6-dimethylphenyl)-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)cyclopropane-1-carbonitrile

[0190] Step 1: Preparation of compound 1-2

[0191] To a solution of compound 1-1 (700 mg, 3.553 mmol) in tetrahydrofuran (10 mL) at 0°C were added 1,2-dibromoethane (0.400 mL, 4.619 mmol) and NaH (185 mg, 4.619 mmol, 60% dispersion in mineral oil). The mixture was stirred at room temperature for 3 hours under nitrogen. The reaction system was quenched with water (30 mL) and extracted with ethyl acetate (50 mL × 3). The combined organic phases were washed with saturated brine (50 mL × 2), dried over anhydrous sodium sulfate, filtered, and concentrated. The crude product was purified by silica gel column chromatography to obtain compound 1-2 (580 mg, 65.9%). LCMS: 224.9 [M+H] + .

[0192] Step 2: Preparation of compound 1-3

[0193] To a solution of compound 1-2 (500 mg, 0.224 mmol) in dioxane (5 mL) were added (n-Bu)6Sn2 (1.56 g, 2.69 mmol), LiCl (570.1 mg, 13.45 mmol), PCy (62.9 mg, 0.22 mmol), and Pd3(dba)2 (102.6 mg, 0.11 mmol) at room temperature. The mixture was stirred at 110°C for 16 hours, quenched with water (15 mL), and extracted with ethyl acetate (20 mL × 2). The combined organic phases were washed with saturated brine (20 mL × 2), dried over anhydrous sodium sulfate, filtered, and concentrated. The crude product was purified by silica gel column chromatography to give compound 1-3 (300 mg, 30.9%). LCMS: 435.2 [M+H] + .

[0194] Step 3: Preparation of compound 1-5

[0195] Compound 1-4 (375.92 mg, 0.829 mmol) and Pd(PPh3)4 (798.79 mg, 0.691 mmol) were added to a solution of compound 1-3 (300 mg, 0.691 mmol) in dioxane (2 mL) at room temperature, and the mixture was heated to 120°C and stirred for 3 hours. The mixture was quenched with water (20 mL) and extracted with ethyl acetate (15 mL × 2). The combined organic phases were washed with saturated brine (40 mL × 2), dried over anhydrous sodium sulfate, filtered, and concentrated. The crude product was purified by silica gel column chromatography to obtain compound 1-5. LCMS: 469.2 [M+H] + .

[0196] Step 4: Preparation of Compound 1-7

[0197] Pd(dtbpf)Cl2 (2.80 mg, 0.011 mmol), compound 1-6 (36.47 mg, 0.139 mmol), K2CO3 (44.36 mg, 0.321 mmol), and H2O (0.3 mL) were added to a solution of compound 1-5 (50 mg, 0.107 mmol) in dioxane (1.5 mL) at room temperature. The mixture was heated to 100°C under nitrogen for 2 hours. The mixture was quenched with water (15 mL) and extracted with ethyl acetate (20 mL × 3). The combined organic phases were washed with saturated brine (20 mL × 3), dried over anhydrous sodium sulfate, filtered, and concentrated. The crude product was purified by silica gel column chromatography to obtain compound 1-7. LCMS: 525.6 [M+H] + .

[0198] Step 5: Preparation of Compound 1

[0199] To a solution of compound 1-7 (40 mg, 0.076 mmol) in dichloromethane (1 mL) was added BBr3 (19.10 mg, 0.076 mmol) at 0°C and stirred at room temperature for 3 hours. Methanol (2 mL) was added to quench the mixture, and the mixture was concentrated. The crude product was purified by preparative HPLC to obtain compound 1. LCMS: 381.1 [M+H] + ; 1 H NMR (400MHz, DMSO-d6) δ12.15(s,1H),9.16(s,1H),8.55(s,1H),8.51(s,1H),8.33(s,1H),8.01(s,1H),7.92(d,J=8.4Hz,1 H),7.71(d,J=8.0Hz,1H),6.95(d,J=8.0Hz,1H),6.77(d,J=8.0Hz,1H),1.87(s,3H),1.80(s,3H),1.76(s,2H),1.57(s,2H).

[0200] Example 2: Preparation of 5-(3-hydroxy-2,6-dimethylphenyl)-3-(1H-pyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridine-4-carbonitrile

[0201] Step 1: Preparation of compound 2-2

[0202] To a solution of compound 2-1 (23.5 g, 49.255 mmol) in DMF (235 mL) were added Zn(CN)2 (2.891 g, 24.627 mmol) and Pd(PPh3)4 (5.692 g, 4.925 mmol). The mixture was heated to 110°C and stirred for 16 h. The mixture was quenched with water (100 mL) and extracted with ethyl acetate (500 mL x 3). The combined organic phases were washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated. The crude product was purified by silica gel column chromatography to obtain compound 2-2 (25 g, 73.1%). LCMS: 378.1 [M+H] + .

[0203] Step 2: Preparation of compound 2-3

[0204] To a mixed solution of compound 2-2 (10 g, 26.582 mmol) and compound 1-6 (10.5 g, 39.872 mmol) in dioxane (100 mL) and water (20 mL) were added Pd(dtbpf)Cl2 (1.7 g, 2.658 mmol) and K2CO3 (11.0 g, 79.745 mmol). The mixture was heated to 90°C under nitrogen for 16 hours. The reaction solution was concentrated, and the crude product was purified by silica gel column chromatography to obtain compound 2-3 (8.32 g, 72.6%). LCMS: 432.3 [M+H] + .

[0205] Step 3: Preparation of compound 2-4

[0206] Under nitrogen, a solution of compound 2-3 (2 g, 4.635 mmol) and NaOH (1.9 g, 46.350 mmol) in EtOH (50 mL) was heated to 60°C for 2 h. Hydrochloric acid (1 M aqueous solution) was added at 0°C to adjust the pH to 7. The reaction solution was extracted with ethyl acetate (50 mL x 3). The combined organic phases were washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated. The crude product was purified by silica gel column chromatography to yield compound 2-4 (1.29 g, 100.0%). LCMS: 278.1 [M+H] + .

[0207] Step 4: Preparation of compound 2-5

[0208] To a solution of compound 2-4 (500.0 mg, 1.803 mmol) in ACN (20.0 mL) at 0°C was added NIS (405.7 mg, 1.803 mmol). The mixture was stirred at room temperature overnight under nitrogen. The mixture was diluted with water (10 mL) and extracted with ethyl acetate (30 mL x 3). The combined organic phases were washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated. The crude product was purified by silica gel column chromatography to obtain compound 2-5. LCMS: 404.0 [M+H] + .

[0209] Step 5: Preparation of compound 2-7

[0210] Under nitrogen protection, a mixed solution of compound 2-5 (100.0 mg, 0.248 mmol), compound 2-6 (41.6 mg, 0.372 mmol), Na2CO3 (78.9 mg, 0.744 mmol), and Pd(dtbpf)Cl2 (16.2 mg, 0.025 mmol) in dioxane and water (5:1, 3.6 mL) was heated to 90°C for 3 hours. The mixture was diluted with water (20 mL) and extracted with ethyl acetate (20 mL × 3). The combined organic phases were washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated. The crude product was purified by preparative thin-layer chromatography to obtain compound 2-7. LCMS: 344.1 [M+H] + .

[0211] Step 6: Preparation of Compound 2

[0212] Similar to the synthesis of compound 1, compound 2-7 was subjected to BBr3-mediated demethylation and subsequent purification to obtain compound 2. LCMS: 330.2 [M+H] + ; 1 H NMR (400MHz, CD3OD) δ8.13(s,1H),7.86(s,2H),7.74(s,1H),6.99(d,J=8.2Hz,1H),6.80(d,J=8.2Hz,1H),1.91(s,3H),1.86(s,3H).

[0213] Example 3: Preparation of 3-(2-aminopyrimidin-5-yl)-5-(3-hydroxy-2,6-dimethylphenyl)-1H-pyrrolo[2,3-b]pyridine-4-carbonitrile

[0214] Step 1: Preparation of compound 3-2

[0215] Under nitrogen, a mixture of compound 2-5 (70.0 mg, 0.174 mmol), compound 3-1 (57.6 mg, 0.260 mmol), Na2CO3 (55.2 mg, 0.521 mmol), and Pd(dtbpf)Cl2 (11.3 mg, 0.017 mmol) in dioxane and water (5:1, 2.4 mL) was heated to 90°C for 3 hours. The mixture was diluted with water (20 mL) and extracted with ethyl acetate (20 mL x 3). The combined organic phases were washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated. The crude product was purified by preparative thin-layer chromatography to yield compound 3-2 (43 mg, 66.9%). LCMS: 371.1 [M+H] + .

[0216] Step 2: Preparation of compound 3

[0217] Referring to the synthesis method of compound 1, compound 3-2 was subjected to BBr3-mediated demethylation reaction and subsequent purification to obtain compound 3. LCMS: 357.2 [M+H] + ; 1 H NMR (400MHz, CD3OD) δ8.46 (s, 2H), 8.18 (s, 1H), 7.78 (s, 1H), 6.99 (d, J = 8.4Hz, 1H), 6.80 (d, J = 8.4Hz, 1H), 1.91 (s, 3H), 1.86 (s, 3H).

[0218] Example 4: Preparation of (S)-3-(3-amino-3-methyl-1-yn-1-yl)-5-(3-hydroxy-2,6-dimethylphenyl)-1H-pyrrolyl[2,3-b]pyridine-4-carbonitrile

[0219] Step 1: Preparation of compound 4-2

[0220] Compound 4-1 (27.2 mg, 0.327 mmol), CuI (11.3 mg, 0.060 mmol), and Pd(PPh3)2Cl2 (23.2 mg, 0.030 mmol) were added to a mixed solution of compound 2-5 (120.0 mg, 0.298 mmol) in TEA (3.0 mL) and THF (3.0 mL). The reaction was allowed to proceed at room temperature for 1 hour under nitrogen protection. The mixture was diluted with water (10 mL) and extracted with ethyl acetate (20 mL x 3). The combined organic phases were washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated. The crude product was purified by preparative thin-layer chromatography to yield compound 4-2 (52 mg, 48.7%). LCMS: 357.0 [MH] + .

[0221] Step 2: Preparation of compound 4

[0222] Referring to the synthesis method of compound 1, compound 4-2 was subjected to BBr3-mediated demethylation reaction and subsequent purification to obtain compound 4. LCMS: 343.0 [MH] + ; 1 H NMR (400MHz, DMSO-d6) δ9.38(s,1H),8.21(s,1H),8.08(s,1H),7.01(d,J=8.4Hz,1H),6.84(d,J=8.4Hz,1H),1.84(s,3H),1.76(s,3H),1.43(s,6H).

[0223] Example 5: Preparation of (R)-5-(3-hydroxy-2,6-dimethylphenyl)-3-((R)-3-hydroxytetrahydrofuran-3-yl)ethyl)-1H-pyrrolo[2,3-b]pyridine-4-carbonitrile

[0224] Step 1: Preparation of compound 5-1

[0225] To a solution of compound 2-3 (27 g, 62.571 mmol) in THF (500 mL) was added dropwise LDA (62.6 mL, 125.142 mmol) at -78°C. The reaction was allowed to proceed for 30 minutes at -78°C. Subsequently, a solution of 1,2-dibromo-1,1,2,2-tetrachloroethane (40.7 g, 125.142 mmol) in THF (5 mL) was added. The reaction was continued at 78°C for 1 hour and then at room temperature for 16 hours. The reaction system was quenched by the addition of saturated aqueous NH4Cl (100 mL) and extracted with ethyl acetate (50 mL x 3). The combined organic phases were washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated. The crude product was purified by silica gel column chromatography to obtain compound 5-1 (18 g, 56.4%). LCMS: 511.8 [M+H] + .

[0226] Step 2: Preparation of compound 5-2

[0227] A mixed solution of compound 5-1 (7 g, 13.715 mmol) and NaOH (1 M, 137.15 mL, 137.147 mmol) in EtOH (150 mL) and MeOH (150 mL) was heated to 60°C and reacted for 2 hours. The reaction solution was cooled to 0°C, 1N HCl was added to adjust the pH to 6, and extracted with ethyl acetate (200 mL × 3). The combined organic phase was washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated. The crude product was purified by silica gel column chromatography and then separated by chiral supercritical fluid chromatography to obtain a single isomer 5-2. LCMS: 357.9 [M+H]+ . 1 H NMR (400MHz, DMSO-d6) δ13.32 (s, 1H), 8.30-8.02 (m, 1H), 7.18 (d, J = 7.6Hz, 1H),7.06-6.92(m,1H),6.85(s,1H),3.83(s,3H),1.88(s,3H),1.80(s,3H).

[0228] Step 3: Preparation of compound 5-3

[0229] To a solution of compound 5-2 (300 mg, 0.842 mmol) in MeOH (6 mL) was added 10% Pd / C (60 mg), and the mixture was stirred at room temperature for 16 hours under a hydrogen atmosphere. After filtration and concentration, the crude product was purified by silica gel column chromatography to obtain compound 5-3 (212 mg, 30.3%). LCMS: 278.2 [M+H] + ; 1 H NMR (400MHz, DMSO-d6) δ12.46(s,1H),8.17(s,1H),7.88(t,J=2.8Hz,1H),7.19(d,J=8.4Hz ,1H),7.00(d,J=8.4Hz,1H),6.67(d,J=1.6Hz,1H),3.83(s,3H),1.89(s,3H),1.80(s,3H).

[0230] Step 4: Preparation of compound 5-4

[0231] To a solution of compound 5-3 (320 mg, 1.154 mmol) in ACN (15 mL) was added NIS (259.6 mg, 1.154 mmol) at 0°C. Stir at room temperature under nitrogen for 2 hours. Dilute with water (10 mL) and extract with ethyl acetate (30 mL x 3). The combined organic phases were washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated. The crude product was purified by silica gel column chromatography to obtain compound 5-4 (644 mg, 69.2%). LCMS: 404.0 [M+H] + ; 1 HNMR(400MHz,DMSO-d6)δ12.89(s,1H),8.18(s,1H),8.10(s,1H),7.19(d,J =8.4Hz,1H),7.01(d,J=8.4Hz,1H),3.83(s,3H),1.88(s,3H),1.80(s,3H).

[0232] Step 5: Preparation of compound 5-5

[0233] A solution of compound 5-4 (200 mg, 0.496 mmol) and BBr3 (0.25 mL, 2.595 mmol) in DCM (5 mL) was reacted at 0°C for 1 hour. NH3 / MeOH (2.5 mL, 7 M) was added at 0°C to quench the reaction. After concentration, the mixture was diluted with water (20 mL) and extracted with ethyl acetate (20 mL x 3). The combined organic phases were washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated to yield compound 5-5. LCMS: 389.7 [M+H] + ; 1 H NMR (400MHz, CD3OD) δ8.14(s,1H),7.84(s,1H),7.01(d,J=8.4Hz,1H),6.81(d,J=8.4Hz,1H),1.90(s,3H),1.86(s,3H).

[0234] Step 6: Preparation of compound 5

[0235] Under nitrogen, a mixture of compound 5-5 (80 mg, 0.206 mmol), compound 5-6 (34.6 mg, 0.308 mmol), Pd(PPh3)2Cl2 (16.0 mg, 0.021 mmol), and CuI (7.8 mg, 0.041 mmol) in THF (2.5 mL) and TEA (2.5 mL) was stirred at room temperature for 1 hour. The mixture was filtered and concentrated. The crude product was purified by preparative thin-layer chromatography to yield compound 5. LCMS: 372.2 [MH] + ; 1 H NMR (400MHz, DMSO-d6) δ12.80(s,1H),9.35(s,1H),8.22(s,1H),8.17(s,1H),7.01(d,J=8.2Hz,1H),6.84(d,J=8.2Hz,1H ),5.77(s,1H),3.87-3.83(m,3H),3.76(d,J=8.8Hz,1H),2.30-2.25(m,1H),2.19-2.10(m,1H),1.84(s,3H),1.76(s,3H).

[0236] Example 6: Preparation of (R)-3-(5,6-dihydro-2H-pyran-3-yl)-5-(3-hydroxy-2,6-dimethylphenyl)-1H-pyrrolo[2,3-b]pyridine-4-carbonitrile

[0237] Step 1: Preparation of compound 6

[0238] Under nitrogen protection, a mixed solution of compound 5-5 (50 mg, 0.128 mmol), compound 6-1 (32.4 mg, 0.154 mmol), Pd(dppf)Cl2 (9.4 mg, 0.013 mmol) and CsF (58.5 mg, 0.385 mmol) in dioxane (2.5 mL) and water (0.5 mL) was heated to 100°C for 2 hours. Diluted with water (20 mL) and extracted with ethyl acetate (20 mL × 3). The combined organic phases were washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated. The crude product was purified by preparative thin-layer chromatography to obtain compound 6. LCMS: 346.2 [M+H] + ; 1 H NMR (400MHz, CD3OD) δ12.49(s,1H),9.31(s,1H),8.14(s,1H),7.87(s,1H),6.99(d,J=8.2Hz,1H),6.83(d,J=8 .2Hz,1H),6.04-6.02(m,1H),4.34(s,2H),3.76(t,J=5.6Hz,2H),2.25-2.23(m,2H),1.84(s,3H),1.76(s,3H).

[0239] Example 7: Preparation of (R)-5-(3-hydroxy-2,6-dimethylphenyl)-3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridine-4-carbonitrile

[0240] Step 1: Preparation of compound 7-2

[0241] Under nitrogen, a mixture of compound 5-4 (70 mg, 0.174 mmol), compound 7-1 (43.8 mg, 0.348 mmol), Pd(dppf)Cl2 (12.7 mg, 0.0174 mmol), and CsF (79.3 mg, 0.522 mmol) in dioxane (3 mL) and water (0.6 mL) was heated to 100°C for 2 hours. The mixture was filtered and concentrated, and the crude product was purified by silica gel column chromatography to yield compound 7-2 (25 mg, 40.3%). LCMS: 358.3 [M+H] + ; 1H NMR (400MHz, DMSO-d6) δ12.53(s,1H),8.16(s,1H),7.91(s,1H),7.86(d,J=2.6Hz,1H),7.65(s,1H) ,7.17(d,J=8.4Hz,1H),6.99(d,J=8.4Hz,1H),3.86(s,3H),3.82(s,3H),1.89(s,3H),1.80(s,3H).

[0242] Step 2: Preparation of compound 7

[0243] Referring to the synthesis method of compound 1, compound 7-2 was subjected to BBr3-mediated demethylation reaction and subsequent purification to obtain compound 7. LCMS: 344.2 [M+H] + ; 1 H NMR (400MHz, DMSO-d6) δ12.51(d,J=2.2Hz,1H),9.30(s,1H),8.16(s,1H),7.91(s,1H),7.85(d,J=2.6Hz ,1H),7.65(s,1H),6.99(d,J=8.2Hz,1H),6.82(d,J=8.2Hz,1H),3.87(s,3H),1.84(s,3H),1.76(s,3H).

[0244] Example 8: Preparation of (R)-3-(cyclopropylethyl)-5-(3-hydroxy-2,6-dimethylphenyl)-1H-pyrrolo[2,3-b]pyridine-4-carbonitrile

[0245] Step 1: Preparation of compound 8-2

[0246] Under nitrogen, a mixture of compound 5-4 (60 mg, 0.149 mmol), compound 8-1 (14.8 mg, 0.223 mmol), Pd(PPh3)2Cl2 (11.6 mg, 0.015 mmol), and CuI (5.7 mg, 0.030 mmol) in THF (1 mL) and TEA (1 mL) was stirred at room temperature for 1 hour. The mixture was diluted with water (10 mL) and extracted with ethyl acetate (10 mL x 3). The combined organic phases were washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated. The crude product was purified by silica gel column chromatography to yield compound 8-2 (25 mg, 36.9%). LCMS: 342.2 [M+H] + .

[0247] Step 2: Preparation of compound 8

[0248] Referring to the synthesis method of compound 1, compound 8-2 was subjected to BBr3-mediated demethylation reaction and subsequent purification to obtain compound 8. LCMS: 328.0 [M+H] + ; 1 H NMR (400MHz, DMSO-d6) δ9.35(s,1H),8.14(s,1H),8.02(s,1H),7.00(d,J=8.2Hz,1H),6.83(d,J =8.2Hz,1H),1.83(s,3H),1.76(s,3H),1.52-1.50(m,1H),0.87-0.80(m,2H),0.79-0.70(m,2H).

[0249] Example 9: Preparation of (R)-N-(4-cyano-5-(3-hydroxy-2,6-dimethylphenyl)-1H-pyrrolo[2,3-b]pyridin-2-yl)-1H-pyrazole-3-carboxamide

[0250] Step 1: Preparation of compound 9-3

[0251] A solution of compound 5-2 (500 mg, 1.404 mmol) and BBr3 (0.7 mL, 7.019 mmol) in DCM (5 mL) was reacted at room temperature for 2 hours. Methanol (5 mL) was added to quench the reaction, and the mixture was concentrated. The crude product was purified by silica gel column chromatography to obtain compound 9-3 (480 mg, 99.9%). LCMS: 344.1 [M+H+CN] + ; 1 H NMR (400MHz, DMSO-d6) δ13.31(s,1H),8.16(d,J=4.0Hz,1H),7.00(d,J=8.2Hz,1H),6.85–6.83(m,2H),1.84(s,3H),1.76(s,3H).

[0252] Step 2: Preparation of compound 9-2

[0253] To a solution of compound 9-1 (2.0 g, 18.002 mmol) and 3,4-dihydro-2H-pyran (1.67 g, 19.802 mmol) in THF (40 mL) was added p-toluenesulfonic acid (31.0 mg, 0.180 mmol). The mixture was heated to 70°C and reacted for 16 hours. The reaction solution was concentrated, and the crude product was purified by silica gel column chromatography to obtain compound 9-2 (1.1 g, 31.3%). LCMS: 196.2 [M+H] + .

[0254] Step 3: Preparation of compound 9-5

[0255] Under nitrogen, a solution of compound 9-2 (80 mg, 0.234 mmol), compound 9-3 (68.5 mg, 0.351 mmol), compound 9-4 (6.6 mg, 0.047 mmol), t-BuONa (67.4 mg, 0.701 mmol), and CuI (8.9 mg, 0.047 mmol) in DMF (0.5 mL) was heated to 110°C for 16 hours. The mixture was diluted with water (10 mL), filtered, and the filter cake was washed with ethyl acetate and water, and dried to obtain compound 9-5. LCMS: 457.4 [M+H] + .

[0256] Step 4: Preparation of compound 9

[0257] A mixture of compound 9-5 (40 mg, 0.088 mmol) in methanol (1 mL) and hydrochloric acid / dioxane (4 M) (0.5 mL) was stirred at room temperature for 1 hour. The reaction solution was concentrated, and the crude product was purified by preparative HPLC to obtain compound 9. LCMS: 373.1 [M+H] + ; 1 H NMR (400MHz, DMSO-d6) δ13.67(s,1H),11.64(s,1H),11.00(s,1H),9.31(s,1H),8.00(d,J=4.0Hz,1H),7.95(s,1H), 6.99(d,J=8.0Hz,1H), 6.89(t,J=2.0Hz,1H), 6.83(d,J=8.0Hz,1H), 6.75(d,J=4.0Hz,1H), 1.86(s,3H), 1.78(s,3H).

[0258] Example 10: Preparation of (R)-5-(3-hydroxy-2,6-dimethylphenyl)-2-((1-methyl-1H-pyrazol-3-yl)methyl)amino)-1H-pyrrolo[2,3-b]pyridine-4-carbonitrile

[0259] Step 1: Preparation of compound 10-2

[0260] Compound 10-1 (62.5 mg, 0.562 mmol), BrettphosPdG3 (25.5 mg, 0.0281 mmol), and t-BuONa (81 mg, 0.843 mmol) were added to a solution of compound 5-2 (100 mg, 0.281 mmol) in DMF (5 mL). The mixture was heated to 100°C under nitrogen and reacted for 16 hours. The mixture was diluted with water (30 mL) and extracted with ethyl acetate (30 mL x 3). The combined organic phases were washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated. The crude product was purified by silica gel column chromatography to yield compound 10-2 (100 mg, 92.2%). LCMS: 387.3 [M+H] + .

[0261] Step 2: Preparation of compound 10

[0262] Similar to the synthesis of compound 1, compound 10-2 was subjected to BBr3-mediated demethylation and subsequent purification to obtain compound 10. LCMS: 373.1 [M+H] + ; 1 H NMR (400MHz, DMSO-d6) δ11.42(s,1H),9.21(s,1H),7.61(d,J=2.0Hz,1H),7.46(s,1H),7.07(t,J=6.0Hz,1H),6.94(d,J=8.2Hz ,1H),6.77(d,J=8.2Hz,1H),6.20(d,J=2.2Hz,1H),5.42(s,1H),4.36(d,J=6.0Hz,2H),3.81(s,3H),1.84(s,3H),1.77(s,3H).

[0263] Example 11: Preparation of (R)-5-(3-hydroxy-2,6-dimethylphenyl)-2-((1-methyl-1H-pyrazol-3-yl)ethyl)-1H-pyrrolo[2,3-b]pyridine-4-carbonitrile

[0264] Step 1: Preparation of compound 11-2

[0265] Under nitrogen, a mixed solution of compound 5-2 (135 mg, 0.379 mmol), compound 11-1 (60 mg, 0.569 mmol), Pd(PPh3)2Cl2 (27 mg, 0.038 mmol), and CuI (29 mg, 0.152 mmol) in tetrahydrofuran (1 mL) and triethylamine (1 mL) was heated to 80°C and stirred for 16 hours. The mixture was diluted with water (10 mL) and extracted with ethyl acetate (20 mL x 3). The combined organic phases were washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated. The crude product was purified by silica gel column chromatography to yield compound 11-2 (80 mg, 55.3%). LCMS: 382.2 [M+H] + .

[0266] Step 2: Preparation of compound 11

[0267] Similar to the synthesis method of compound 1, compound 11-2 was subjected to BBr3-mediated demethylation reaction and subsequent purification to obtain compound 11. LCMS: 368.0 [M+H] + ; 1 HNMR(400MHz,DMSO-d6)δ13.05(s,1H),9.36(s,1H),8.23(s,1H),7.86(d,J=4.0Hz,1H),7.01(d,J =5.2Hz,2H),6.84(d,J=8.0Hz,1H),6.64(d,J=4.0Hz,1H),3.91(s,3H),1.85(s,3H),1.77(s,3H).

[0268] Example 12: Preparation of (R)-4-cyano-5-(3-hydroxy-2,6-dimethylphenyl)-N-(1H-pyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridine-2-carboxamide

[0269] Step 1: Preparation of compound 12-1

[0270] To a solution of compound 2-3 (2.0 g, 4.635 mmol) in tetrahydrofuran (50 mL) at 78°C was added LDA (4.63 mL, 9.270 mmol). After stirring for 0.5 hour, a solution of methyl chloroformate (876.0 mg, 9.270 mmol) in tetrahydrofuran (15 mL) was added. The mixture was allowed to react at -78°C for 2 hours. The reaction was quenched by the addition of saturated aqueous NH4Cl (50 mL), diluted with water (200 mL), and extracted with ethyl acetate (100 mL x 3). The combined organic phases were washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated. The crude product was purified by silica gel column chromatography to yield compound 12-1 (1 g, 44.1%). LCMS: 489.8 [M+H]+ .

[0271] Step 2: Preparation of compound 12-3

[0272] To a solution of compound 12-2 (70 mg, 0.841 mmol) and compound 12-1 (200 mg, 0.421 mmol) in dioxane (5 mL) was added AlMe3-toluene solution (2.1 mL) at 0°C. The mixture was heated to 90°C and reacted for 10 hours. Methanol (10 mL) was added to quench the reaction and the mixture was concentrated. The crude product was diluted with methanol / dichloromethane (1:10) (30 mL) and stirred at room temperature for 1 hour. After filtration and concentration, the crude product was purified by preparative thin-layer chromatography to obtain compound 12-3. LCMS: 541.3 [M+H] + .

[0273] Step 3: Preparation of compound 12-4

[0274] A solution of compound 12-3 (70 mg, 0.129 mmol) and saturated NaOH (1.3 mL, 1.295 mmol) in ethanol (5 mL) was heated to 60°C for 1 hour. After cooling, the reaction solution was diluted with water (10 mL), 1N hydrochloric acid was added to adjust the pH to 7, and extraction was performed with ethyl acetate (10 mL x 3). The combined organic phases were washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated. The crude product was purified by preparative thin-layer chromatography to obtain compound 12-4. LCMS: 387.3 [M+H] + .

[0275] Step 4: Preparation of compound 12

[0276] Referring to the synthesis method of compound 1, compound 12-4 was subjected to BBr3-mediated demethylation reaction and subsequent chiral supercritical fluid chromatography purification to obtain compound 12. LCMS: 373.0 [M+H] + ; 1 H NMR(400MHz,DMSO-d6)δ13.06(s,1H),12.73(s,1H),10.75(s,1H),9.37(s,1H),8.32(s,1H),8.06(s, 1H),7.72(s,1H),7.53(s,1H),7.02(d,J=8.2Hz,1H),6.85(d,J=8.2Hz,1H),1.86(s,3H),1.79(s,3H).

[0277] Example 42: 2-(2-aminopyrimidin-5-yl)-5-(5-methyl-1H-indazol-4-yl)-1H-pyrrolo[2,3-b]pyridine-4-carbonitrile

[0278] Step 1: Preparation of compound 42-1

[0279] Compound 2-2 (1 g, 2.658 mmol) was dissolved in tetrahydrofuran (20 mL). LDA (2.66 mL, 5.316 mmol) was added at -78°C and stirred for 30 minutes. A solution of iodine (1.35 g, 5.316 mmol) in tetrahydrofuran (20 mL) was then added and the mixture was allowed to react at -78°C for 1 hour. The reaction was quenched by adding saturated ammonium chloride solution under ice-water bath and extracted with ethyl acetate (30 mL x 3). The combined organic phases were washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated. The crude product was purified by silica gel column chromatography to yield compound 42-1 (500 mg, 37.5%). LCMS: 503.8 [M+H] + .

[0280] Step 2: Preparation of compound 42-2

[0281] Referring to the synthesis method of compound 3-2, compound 42-1 (500 mg, 0.996 mmol) and compound 3-1 (264 mg, 1.195 mmol) were coupled to obtain compound 42-2. LCMS: 470.9 [M+H] + .

[0282] Step 3: Preparation of compound 42-4

[0283] Referring to the synthesis method of compound 1-7, compound 42-2 (170 mg, 0.362 mmol) and compound 42-3 (96 mg, 0.543 mmol) were coupled to obtain compound 42-4. LCMS: 521.1 [M+H] + .

[0284] Step 4: Preparation of compound 42

[0285] Referring to the synthesis method of compound 2-4, compound 42-4 (60 mg, 0.115 mmol) was deprotected with NaOH (1 mL, 1.000 mmol) to obtain compound 42. LCMS: 367.2 [M+H] + ; 1 H NMR(400MHz,DMSO-d6)δ13.21(s,1H),12.81(s,1H),8.98(s,2H),8.27(s,1H ),7.66–7.48(m,2H),7.41(d,J=7.7Hz,1H),7.16–7.14(m,3H),2.24(s,3H).

[0286] Example 43: 3-(2-(2-aminopyrimidin-5-yl)pyrazolo[1,5-a]pyrimidin-6-yl)-2,4-dimethylphenol

[0287] Step 1: Preparation of compound 43-2

[0288] Referring to the synthesis method of compound 3-2, compound 43-1 (1 g, 4.30 mmol) and compound 3-1 (1.236 g, 5.59 mmol) were coupled to obtain compound 43-2. ​​LCMS: 247.1 [M+H] + .

[0289] Step 2: Preparation of compound 43-3

[0290] Referring to the synthesis method of compound 1-7, compound 43-2 (230 mg, 0.932 mmol) and compound 1-6 (293 mg, 1.119 mmol) were coupled to obtain compound 43-3. LCMS: 347.1 [M+H] + .

[0291] Step 3: Preparation of compound 43

[0292] Referring to the synthesis method of compound 1, compound 43-3 (100 mg, 0.289 mmol) was deprotected by phenol methylation using BBr3 (0.15 mL, 1.587 mmol) to obtain compound 43. LCMS: 333.2 [M+H] + ; 1 H NMR(400MHz,DMSO-d6)δ9.35(s,1H),9.03(s,1H),8.88(s,2H),8.33(s,1H),7. 23(s,1H),7.01–6.86(m,3H),6.83(d,J=8.2Hz,1H),2.00(s,3H),1.92(s,3H).

[0293] Example 44: Preparation of (R)-2-(2-aminopyrimidin-5-yl)-5-(3-fluoro-5-hydroxy-2,6-dimethylphenyl)-1H-pyrrolo[2,3-b]pyridine-4-carbonitrile

[0294] Step 1: Preparation of compound 44-3

[0295] Referring to the preparation method of 1-7, compound 44-1 (150 mg, 0.320 mmol) and compound 44-2 (89.5 mg, 0.320 mmol) were reacted to give compound 44-3. LCMS: 584.0 [M+ACN+H]+ .

[0296] Step 2: Preparation of compound 44

[0297] Referring to the preparation method of compound 12, compound 44 was obtained from compound 44-3 (70 mg, 0.129 mmol) by deprotection, preparative thin layer chromatography purification and chiral supercritical fluid chromatography. LCMS: 375.1 [M+H] + ; 1 H NMR (400MHz, DMSO-d6) δ8.92(s,2H),8.00(s,1H),7.02(s,2H),6.73(d,J=11.4Hz,1H),1.77(s,3H),1.76(d,J=5.9Hz,3H).

[0298] Example 45: Preparation of (R)-5-(3-hydroxy-2,6-dimethylphenyl)-2-(2-(piperazin-1-yl)pyrimidin-5-yl)-1H-pyrrolo[2,3-b]pyridine-4-carbonitrile

[0299] Step 1: Preparation of compound 45-2

[0300] Under nitrogen, a mixture of compound 9-3 (50 mg, 0.146 mmol), compound 45-1 (90 mg, 0.292 mmol), Pd(dtbpf)Cl2 (9.4 mg, 0.015 mmol), and K2CO3 (61 mg, 0.438 mmol) in dioxane (2.5 mL) and water (0.5 mL) was heated to 90°C and stirred for 2 hours. The reaction system was filtered, and the filtrate was concentrated. The crude product was purified by preparative thin-layer chromatography to obtain compound 45-2. LCMS: 567.2 [M+H+ACN] + .

[0301] Step 2: Preparation of compound 45

[0302] To a solution of compound 45-2 (50 mg, 0.095 mmol) in dichloromethane (4 mL) and methanol (1 mL) was added a 4 M hydrochloric acid / dioxane solution (2 mL) and stirred at room temperature for 2 hours. The reaction system was concentrated and quenched with NH3 / MeOH. The filtrate was filtered and concentrated, and the crude product was purified by preparative HPLC to yield compound 45. LCMS: 426.2 [M+H] + ; 1H NMR(400MHz,DMSO-d6)δ9.06(s,2H),8.24(s,1H),8.07(s,1H),7.13(s,1H),6.99(d,J= 8.2Hz,1H),6.83(d,J=8.2Hz,1H),3.89(s,4H),2.96(s,4H),1.85(s,3H),1.78(s,3H).

[0303] Examples 46-48: Synthesis of Compounds 46-48 Refer to the synthesis method of Compound 45.

[0304] Example 49: Preparation of 6-(2-aminopyrimidin-5-yl)-2-(3-hydroxy-2,6-dimethylphenyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbonitrile

[0305] Step 1: Preparation of compound 49-2

[0306] Compound 49-1 was prepared from the corresponding starting materials according to the synthetic method. A solution of compound 49-1 (120 mg, 0.361 mmol) and NIS (81.2 mg, 0.361 mmol) in acetonitrile (20 mL) was stirred at room temperature for 1 hour. The reaction solution was concentrated and the crude product was purified by silica gel column chromatography to obtain compound 49-2. LCMS: 459.1 [M+H] + .

[0307] Step 2: Preparation of compound 49

[0308] Under nitrogen, a solution of compound 49-2 (15 mg, 0.033 mmol), Zn(CN)2 (3.8 mg, 0.033 mmol), Zn (12.8 mg, 0.196 mmol), Pd2(dba)3 (5.3 mg, 0.007 mmol), and Pd(dppf)Cl2 (5.3 mg, 0.007 mmol) in DMA (1 mL) was stirred at 100°C for 10 hours. The reaction mixture was concentrated and the crude product was purified by preparative HPLC to yield compound 49. LCMS: 357.8 [M+H] + ; 1 H NMR (400MHz, CD3OD) δ8.96(s,2H),8.25(s,1H),6.98(d,J=8.0Hz,1H),6.80(d,J=8.0Hz,1H),1.94(s,3H),1.89(s,3H).

[0309] Test Example A: PKMYT1 HTRF Assay

[0310] Compounds were serially diluted using Echo, with final concentrations ranging from 10 μM to 0.5 nM. 5 μL / well of PKMYT enzyme solution was added to the assay plate containing the compound for filling. Centrifuge at 1000 rpm for 1 minute and incubate at 25°C for 15 minutes. 5 μL / well of tracer solution (tracer 178) was then added to initiate the reaction and incubated at 25°C for 60 minutes. 5 μL of GST-Tb was then added to the assay plate, centrifuged at 1000 rpm for 1 minute, and incubated at 25°C for 15 minutes. The fluorescence values ​​of the assay plate at 615 nm and 665 nm were read on Envision. GraphPad 6.0 was used to fit the % inhibition value and the logarithm of the compound concentration to a nonlinear regression to calculate the IC 50 . Y=Bottom+(Top-Bottom) / (1+10^((LogIC 50 -X)*HillSlope)), X: logarithmic value of concentration; Y: % inhibition value.

[0311] Test Example B: WEE1 ADP-Glo ​​Assay

[0312] Compounds were serially diluted using Echo with final concentrations ranging from 10 μM to 0.5 nM. 5 μL / well of WEE1 enzyme solution was added to the assay plate containing the compound for filling. Centrifuge at 1000 rpm for 1 minute and incubate at 25°C for 15 minutes. 5 μL / well of substrate solution was then added to initiate the reaction and incubated at 25°C for 60 minutes. 10 μL of kinase assay reagent was then added to the assay plate, centrifuged at 1000 rpm for 1 minute, and incubated at 25°C for 60 minutes. The assay plate was read in RLU on Envision for US LUM. % inhibition values ​​and the logarithm of compound concentration were fitted to a nonlinear regression using GraphPad 6.0 to calculate IC 50 . Y=Bottom+(Top-Bottom) / (1+10^((LogIC 50 -X)*HillSlope)), X: logarithmic value of concentration; Y: % inhibition value.

[0313] The data of test cases A and B are shown in Table 1.

[0314] Table 1

[0315] MYT1 HTRF IC 50 (nM):0 <A≤10;10<B≤50;50<C≤500;500<D≤5000;5000<E。

[0316] WEE1 ADP-Glo ​​IC 50(nM):0 <A≤10;10<B≤50;50<C≤500;500<D≤5000;5000<E。

[0317] NT: Not tested.

[0318] The above describes the embodiments of the present invention. However, the present invention is not limited to the above embodiments. Any modifications, equivalent replacements, improvements, etc. made within the spirit and principles of the present invention shall be included in the scope of protection of the present invention.

Claims

1. A compound represented by formula V, or a pharmaceutically acceptable salt or stereoisomer thereof: in, is a heterocyclic group or heteroaryl group consisting of M, E, J, L, and Q; M is selected from N or CA; A is selected from H, halogen, CN, OH, NH2, SO2NH2, CONH2, =O, C 1-12 Alkyl, C 1-12 Alkoxy, C 1-12 Amine alkyl, C 1-12 Alkylthio, C 2-12 Alkenyl, C 2-12 Alkynyl, cycloalkyl, heterocyclyl, aryl or heteroaryl, the C 1-12 Alkyl, C 1-12 Alkoxy, C 1-12 Amine alkyl, C 1-12 Alkylthio, C 2-12 Alkenyl, C 2-12 The alkynyl, cycloalkyl, heterocyclyl, aryl or heteroaryl group is optionally substituted with 1, 2 or more R AA replace; R AA are independently selected from halogen, -CN, -NH2, -OH, -OR a 、-OC(=O)R a 、-OC(=O)OR b 、-OC(=O)NR c R d , -SH, -SR a 、-S(=O)R a 、-S(=O)2R a 、-S(=O)2NR c R d 、-NR c R d 、-NR b C(=O)NR c R d 、-NR b C(=O)R a 、-NR b C(=O)OR b 、-NR b S(=O)2R a 、-C(=O)R a 、-C(=O)OR b 、-C(=O)NR c R d , C 1-12 Alkyl, C 1-12 Alkoxy, C 1-12 Alkylthio, halo 1-12 Alkyl, C 1-12 Hydroxyalkyl, C 1-12 Amine alkyl, C 2-12 Alkenyl, C 2-12 Alkynyl, cycloalkyl, heterocyclyl, aryl or heteroaryl, the C 1-12 Alkyl, C 1-12 Alkoxy, C 1-12 Alkylthio, halo 1-12 Alkyl, C 1-12 Hydroxyalkyl, C 1-12 Amine alkyl, C 2-12 Alkenyl, C 2-12 The alkynyl, cycloalkyl, heterocyclyl, aryl or heteroaryl group is optionally substituted with 1, 2 or more R 1a replace; or two R AA Substituted on the same atom and connected together to form =O, =C(R 1a )2, =CHR 1a , cycloalkyl or heterocyclic group; the cycloalkyl or heterocyclic group is optionally substituted by 1, 2 or more R 1a Substitution; the number of =O is 1, 2 or 3; R 1a are independently selected from halogen, -CN, -OH, -OR a 、-OC(=O)R a 、-OC(=O)OR b 、-OC(=O)NR c R d , -SH, -SR a 、-S(=O)R a 、-S(=O)2R a 、-S(=O)2NR c R d 、-NR c R d 、-NR b C(=O)NR c R d 、-NR b C(=O)R a 、-NR b C(=O)OR b 、-NR b S(=O)2R a 、-C(=O)R a 、-C(=O)OR b 、-C(=O)NR c R d , C 1-12 Alkyl, C 1-12 Alkoxy, C 1-12 Alkylthio, halo 1-12 Alkyl, C 1-12 Hydroxyalkyl, C 1-12 Amine alkyl, C 2- 12 Alkenyl, C 2-12 Alkynyl, cycloalkyl, heterocyclyl, aryl or heteroaryl, the C 1-12 Alkyl, C 1-12 Alkoxy, C 1-12 Alkylthio, halo 1-12 Alkyl, C 1-12 Hydroxyalkyl, C 1-12 Amine alkyl, C 2-12 Alkenyl, C 2-12 The alkynyl, cycloalkyl, heterocyclyl, aryl or heteroaryl group is optionally substituted with 1, 2 or more R; Q is selected from N, NR 1 or CR 1 , R 1 Selected from H, halogen, -CN, -OH, -OR a , -SH, -SR a 、-NR c R d 、-C(=O)R a 、-C(=O)OR b 、-C(=O)NR c R d 、-NHCOR a 、-NH-C 1-12 Alkyl-R a , -C 1-12 Alkyl-OR a , C 1-12 Alkyl, C 1-12 Alkoxy, C 1-12 Amine alkyl, C 1-12 Alkylthio, C 2-12 Alkenyl, -cycloalkylC 2-12 Alkenyl, C 2-12 Alkynyl, cycloalkyl, heterocyclyl, aryl or heteroaryl, the C 1-12 Alkyl, C 1-12 Alkoxy, C 1-12 Amine alkyl, C 1-12 Alkylthio, C 2-12 Alkenyl, -cycloalkylC 2-12 Alkenyl, C 2-12 The alkynyl, cycloalkyl, heterocyclyl, aryl or heteroaryl group is optionally substituted with 1, 2 or more R Qa Substituted; said -cycloalkylC 2-12 C in alkenyl 2-12 The C at one end of the alkenyl group is the same carbon atom as the carbon to which the cycloalkyl group is attached; R Qa are independently selected from halogen, =O, -CN, -OH, -OR a 、-OC(=O)R a 、-OC(=O)OR b 、-OC(=O)NR c R d , -SH, -SR a 、-S(=O)R a 、-S(=O)2R a 、-S(=O)2NR c R d 、-NR c R d 、-NR b C(=O)NR c R d 、-NR b C(=O)R a 、-NR b C(=O)OR b 、-NR b S(=O)2R a 、-C(=O)R a 、-C(=O)OR b 、-C(=O)NR c R d , =C(R 1a 2. C 1-12 Alkyl, C 1-12 Alkoxy, C 1-12 Alkylthio, halo 1-12 Alkyl, C 1-12 Hydroxyalkyl, C 1-12 Amine alkyl, C 2-12 Alkenyl, C 2-12 Alkynyl, cycloalkyl, heterocyclyl, aryl or heteroaryl, the C 1-12 Alkyl, C 1-12 Alkoxy, C 1-12 Alkylthio, halo 1-12 Alkyl, C 1-12 Hydroxyalkyl, C 1-12 Amine alkyl, C 2-12 Alkenyl, C 2-12 The alkynyl, cycloalkyl, heterocyclyl, aryl or heteroaryl group is optionally substituted with 1, 2 or more R; E is selected from N or C; J is selected from N or C; L is selected from N, NR 2 or CR 2 ; R 2 Selected from H, C 1-12 Alkyl, C 1-12 Alkoxy, C 1-12 Alkylthio, halo 1-12 Alkyl, C 1-12 Hydroxyalkyl, C 1-12 Amine alkyl, C 2-12 Alkenyl, C 2- 12 Alkynyl, cycloalkyl or heterocyclyl; X is C (Rx) or N; Y is C (Ry) or N; Z is N or C (Rz); Rx, Ry, Rz, R 3 , R 4 , R 5 , R 6 are the same or different and are independently selected from H, halogen, -CN, -OH, -OR a 、-OC(=O)R a 、-OC(=O)OR b 、-OC(=O)NR c R d , -SH, -SR a 、-S(=O)R a 、-S(=O)2R a 、-S(=O)2NR c R d 、-NR c R d 、-NR b C(=O)NR c R d 、-NR b C(=O)R a 、-NR b C(=O)OR b 、-NR b S(=O)2R a 、-C(=O)R a 、-C(=O)OR b 、-C(=O)NR c R d , C 1-12 Alkyl, C 1-12 Alkoxy, C 1-12 Alkylthio, halo 1-12 Alkyl, halogenated C 1-12 Alkoxy, C 1-12 Hydroxyalkyl, C 1-12 Amine alkyl, C 2-12 Alkenyl, C 2-12 Alkynyl, cycloalkyl, heterocyclyl, aryl or heteroaryl, the C 1-12 Alkyl, C 1-12 Alkoxy, C 1-12 Alkylthio, halo 1-12 Alkyl, halogenated C 1-12 Alkoxy, C 1-12 Hydroxyalkyl, C 1-12 Amine alkyl, C 2-12 Alkenyl, C 2-12 The alkynyl, cycloalkyl, heterocyclyl, aryl or heteroaryl group is optionally substituted with 1, 2 or more R; R a , R b , R c , R d are the same or different, independently selected from H, C 1-12 Alkyl, C 1-12 Alkoxy, C 1-12 Alkylthio, halo 1-12 Alkyl, C 1-12 Hydroxyalkyl, C 1-12 Amine alkyl, C 2-12 Alkenyl, C 2-12 Alkynyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, C 1-12 Alkyl-cycloalkyl, C 1-12 Alkyl-heterocyclyl, C 1-12 Alkyl-aryl or C 1-12 Alkyl-heteroaryl; said C 1-12 Alkyl, C 1-12 Alkoxy, C 1-12 Alkylthio, halo 1-12 Alkyl, C 1-12 Hydroxyalkyl, C 1-12 Amine alkyl, C 2-12 Alkenyl, C 2-12 Alkynyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, C 1-12 Alkyl-cycloalkyl, C 1-12 Alkyl-heterocyclyl, C 1-12 Alkyl-aryl or C 1-12 Alkyl-heteroaryl is optionally substituted with 1, 2 or more R; or R c and R d are linked together to form a heterocyclic group, which is optionally substituted by 1, 2 or more R; G is N or CR G ; R G H, OH or NH2; or R G With R 3 are connected together to form a cycloalkyl, heterocyclic, aryl or heteroaryl group; the cycloalkyl, heterocyclic, aryl or heteroaryl group is optionally substituted by 1, 2 or more R; or R G With R 6 are connected together to form a cycloalkyl, heterocyclic, aryl or heteroaryl group; the cycloalkyl, heterocyclic, aryl or heteroaryl group is optionally substituted by 1, 2 or more R; R is independently selected from halogen, -SH, -CN, -OH, -S(=O)CH3, -S(=O)2CH3, -S(=O)2NH2, -S(=O)2NHCH3, -S(=O)2N(CH3)2, -NH2, -NHCH3, -N(CH3)2, -C(=O)CH3, -C(=O)OH, -C(=O)OCH3, =C(R 1a 2. C 1-12 Alkyl, C 2-12 Alkenyl, C 2-12 Alkynyl, C 1-12 Alkoxy, halogenated C 1-12 Alkoxy, C 1-12 Alkylthio, halo 1-12 Alkyl, C 1-12 Hydroxyalkyl, C 1-12 Amine alkyl or C 3-12 Cycloalkyl; Or two R are substituted on the same atom and are linked together to form =O, a cycloalkyl group or a heterocyclyl group.

2. Compounds represented by Formula I to Formula XI, and pharmaceutically acceptable salts or stereoisomers thereof: in, A is selected from H, halogen, CN, OH, NH2, mercapto, SO2NH2, CONH2, C 1-12 Alkyl, C 1-12 Alkoxy, C 1-12 Amine alkyl, C 1-12 Alkylthio, C 2-12 Alkenyl, C 2-12 Alkynyl, cycloalkyl, heterocyclyl, aryl or heteroaryl, the C 1-12 Alkyl, C 1-12 Alkoxy, C 1-12 Amine alkyl, C 1-12 Alkylthio, C 2-12 Alkenyl, C 2-12 The alkynyl, cycloalkyl, heterocyclyl, aryl or heteroaryl group is optionally substituted with 1, 2 or more R AA replace; R AA are independently selected from halogen, -CN, -NH2, -OH, -OR a 、-OC(=O)R a 、-OC(=O)OR b 、-OC(=O)NR c R d , -SH, -SR a 、-S(=O)R a 、-S(=O)2R a 、-S(=O)2NR c R d 、-NR c R d 、-NR b C(=O)NR c R d 、-NR b C(=O)R a 、-NR b C(=O)OR b 、-NR b S(=O)2R a 、-C(=O)R a 、-C(=O)OR b 、-C(=O)NR c R d , C 1-12 Alkyl, C 1-12 Alkoxy, C 1-12 Alkylthio, halo 1-12 Alkyl, C 1-12 Hydroxyalkyl, C 1-12 Amine alkyl, C 2-12 Alkenyl, C 2-12 Alkynyl, cycloalkyl, heterocyclyl, aryl or heteroaryl, the C 1-12 Alkyl, C 1-12 Alkoxy, C 1-12 Alkylthio, halo 1-12 Alkyl, C 1-12 Hydroxyalkyl, C 1-12 Amine alkyl, C 2-12 Alkenyl, C 2-12 The alkynyl, cycloalkyl, heterocyclyl, aryl or heteroaryl group is optionally substituted with 1, 2 or more R 1a replace; or two R AA Substituted on the same carbon atom and connected together to form =O, =C(R 1a )2, =CHR 1a , cycloalkyl or heterocyclic group; the cycloalkyl or heterocyclic group is optionally substituted by 1, 2 or more R 1a replace; The number of the =O is 1, 2 or 3; R 1a are independently selected from halogen, -CN, -OH, -OR a 、-OC(=O)R a 、-OC(=O)OR b 、-OC(=O)NR c R d , -SH, -SR a 、-S(=O)R a 、-S(=O)2R a 、-S(=O)2NR c R d 、-NR c R d 、-NR b C(=O)NR c R d 、-NR b C(=O)R a 、-NR b C(=O)OR b 、-NR b S(=O)2R a 、-C(=O)R a 、-C(=O)OR b 、-C(=O)NR c R d , C 1-12 Alkyl, C 1-12 Alkoxy, C 1-12 Alkylthio, halo 1-12 Alkyl, C 1-12 Hydroxyalkyl, C 1-12 Amine alkyl, C 2- 12 Alkenyl, C 2-12 Alkynyl, cycloalkyl, heterocyclyl, aryl or heteroaryl, the C 1-12 Alkyl, C 1-12 Alkoxy, C 1-12 Alkylthio, halo 1-12 Alkyl, C 1-12 Hydroxyalkyl, C 1-12 Amine alkyl, C 2-12 Alkenyl, C 2-12 The alkynyl, cycloalkyl, heterocyclyl, aryl or heteroaryl group is optionally substituted with 1, 2 or more R; Q is selected from N or CR 1 , R 1 Selected from H, halogen, -CN, -OH, -OR a , -SH, -SR a 、-NR c R d 、-C(=O)R a 、-C(=O)OR b 、-C(=O)NR c R d 、-NHCOR a 、-NH-C 1-12 Alkyl-R a , -C 1-12 Alkyl-OR a , C 1-12 Alkyl, C 1-12 Alkoxy, C 1-12 Amine alkyl, C 1-12 Alkylthio, C 2-12 Alkenyl, C 2-12 Alkynyl, cycloalkyl, heterocyclyl, aryl or heteroaryl, the C 1-12 Alkyl, C 1-12 Alkoxy, C 1-12 Amine alkyl, C 1-12 Alkylthio, C 2-12 Alkenyl, C 2-12 The alkynyl, cycloalkyl, heterocyclyl, aryl or heteroaryl group is optionally substituted with 1, 2 or more R Qa replace; R Qa are independently selected from halogen, =O, -CN, -OH, -OR a 、-OC(=O)R a 、-OC(=O)OR b 、-OC(=O)NR c R d , -SH, -SR a 、-S(=O)R a 、-S(=O)2R a 、-S(=O)2NR c R d 、-NR c R d 、-NR b C(=O)NR c R d 、-NR b C(=O)R a 、-NR b C(=O)OR b 、-NR b S(=O)2R a 、-C(=O)R a 、-C(=O)OR b 、-C(=O)NR c R d , C 1-12 Alkyl, C 1-12 Alkoxy, C 1-12 Alkylthio, halo 1-12 Alkyl, C 1-12 Hydroxyalkyl, C 1-12 Amine alkyl, C 2-12 Alkenyl, C 2-12 Alkynyl, cycloalkyl, heterocyclyl, aryl or heteroaryl, the C 1-12 Alkyl, C 1-12 Alkoxy, C 1-12 Alkylthio, halo 1-12 Alkyl, C 1-12 Hydroxyalkyl, C 1-12 Amine alkyl, C 2-12 Alkenyl, C 2-12 The alkynyl, cycloalkyl, heterocyclyl, aryl or heteroaryl group is optionally substituted with 1, 2 or more R; R 2 Selected from H, C 1-12 Alkyl, C 1-12 Alkoxy, C 1-12 Alkylthio, halo 1-12 Alkyl, C 1-12 Hydroxyalkyl, C 1-12 Amine alkyl, C 2-12 Alkenyl, C 2-12 Alkynyl, cycloalkyl or heterocyclyl; X is C (Rx) or N; Y is C (Ry) or N; Z is N or C (Rz); Rx, Ry, Rz, R 3 , R 4 , R 5 , R 6 are the same or different and are independently selected from H, halogen, -CN, -OH, -OR a 、-OC(=O)R a 、-OC(=O)OR b 、-OC(=O)NR c R d , -SH, -SR a 、-S(=O)R a 、-S(=O)2R a 、-S(=O)2NR c R d 、-NR c R d 、-NR b C(=O)NR c R d 、-NR b C(=O)R a 、-NR b C(=O)OR b 、-NR b S(=O)2R a 、-C(=O)R a 、-C(=O)OR b 、-C(=O)NR c R d , C 1-12 Alkyl, C 1-12 Alkoxy, C 1-12 Alkylthio, halo 1-12 Alkyl, C 1-12 Hydroxyalkyl, C 1-12 Amine alkyl, C 2-12 Alkenyl, C 2-12 Alkynyl, cycloalkyl, heterocyclyl, aryl or heteroaryl, the C 1-12 Alkyl, C 1-12 Alkoxy, C 1-12 Alkylthio, halo 1-12 Alkyl, C 1-12 Hydroxyalkyl, C 1-12 Amine alkyl, C 2-12 Alkenyl, C 2-12 The alkynyl, cycloalkyl, heterocyclyl, aryl or heteroaryl group is optionally substituted with 1, 2 or more R; R a , R b , R c , R d are the same or different, independently selected from H, C 1-12 Alkyl, C 1-12 Alkoxy, C 1-12 Alkylthio, halo 1-12 Alkyl, C 1-12 Hydroxyalkyl, C 1-12 Amine alkyl, C 2-12 Alkenyl, C 2-12 Alkynyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, C 1-12 Alkyl-cycloalkyl, C 1-12 Alkyl-heterocyclyl, C 1-12 Alkyl-aryl or C 1-12 Alkyl-heteroaryl; said C 1-12 Alkyl, C 1-12 Alkoxy, C 1-12 Alkylthio, halo 1-12 Alkyl, C 1-12 Hydroxyalkyl, C 1-12 Amine alkyl, C 2-12 Alkenyl, C 2-12 Alkynyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, C 1-12 Alkyl-cycloalkyl, C 1-12 Alkyl-heterocyclyl, C 1-12 Alkyl-aryl or C 1-12 Alkyl-heteroaryl is optionally substituted with 1, 2 or more R; or R c and R d are linked together to form a heterocyclic group, which is optionally substituted by 1, 2 or more R; R is independently selected from halogen, -CN, -OH, -S(=O)CH3, -S(=O)2CH3, -S(=O)2NH2, -S(=O)2NHCH3, -S(=O)2N(CH3)2, -NH2, -NHCH3, -N(CH3)2, -C(=O)CH3, -C(=O)OH, -C(=O)OCH3, =C(R 1a 2. C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, halo 1-6 Alkyl, C 1-6 Hydroxyalkyl, C 1-6 Amine alkyl or C 3-6 Cycloalkyl; Or two R are substituted on the same carbon atom and are linked together to form =O, a cycloalkyl group or a heterocyclic group.

3. The compound according to claim 1 or 2, or a pharmaceutically acceptable salt or stereoisomer thereof, wherein: A is selected from H, =O, halogen, CN, OH, NH2, SO2NH2, CONH2, C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 Aryl or 5-12 membered heteroaryl, the C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 The aryl or 5-12 membered heteroaryl group is optionally substituted by 1, 2 or more R AA replace; R AA are independently selected from halogen, -CN, -NH2, -OH, -OR a 、-OC(=O)R a 、-OC(=O)OR b 、-OC(=O)NR c R d , -SH, -SR a 、-S(=O)R a 、-S(=O)2R a 、-S(=O)2NR c R d 、-NR c R d 、-NR b C(=O)NR c R d 、-NR b C(=O)R a 、-NR b C(=O)OR b 、-NR b S(=O)2R a 、-C(=O)R a 、-C(=O)OR b 、-C(=O)NR c R d , C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, halo 1-6 Alkyl, C 1-6 Hydroxyalkyl, C 1-6 Amine alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 Aryl or 5-12 membered heteroaryl, the C 1-6 Alkyl, C 1-6 Alkoxy, C 1- 6-alkylthio, halogenated C 1-6 Alkyl, C 1-6 Hydroxyalkyl, C 1-6 Amine alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 The aryl or 5-12 membered heteroaryl group is optionally substituted by 1, 2 or more R 1a replace; or two R AA Substituted on the same atom and connected together to form =O, =C(R 1a )2, =CHR 1a , cycloalkyl or heterocyclic group; the cycloalkyl or heterocyclic group is optionally substituted by 1, 2 or more R 1a Substitution; the number of the =O substituents is 1, 2 or 3; R 1a are independently selected from halogen, -CN, -OH, -OR a 、-OC(=O)R a 、-OC(=O)OR b 、-OC(=O)NR c R d , -SH, -SR a 、-S(=O)R a 、-S(=O)2R a 、-S(=O)2NR c R d 、-NR c R d 、-NR b C(=O)NR c R d 、-NR b C(=O)R a 、-NR b C(=O)OR b 、-NR b S(=O)2R a 、-C(=O)R a 、-C(=O)OR b 、-C(=O)NR c R d , C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, halo 1-6 Alkyl, C 1-6 Hydroxyalkyl, C 1-6 Amine alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 Aryl or 5-12 membered heteroaryl, the C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, halo 1-6 Alkyl, C 1-6 Hydroxyalkyl, C 1-6 Amine alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 Aryl or 5-12 membered heteroaryl is optionally substituted by 1, 2 or more R; Q is selected from N, NR 1 or CR 1 , R 1 Selected from H, halogen, -CN, -OH, -OR a , -SH, -SR a 、-NR c R d 、-C(=O)R a 、-C(=O)OR b 、-C(=O)NR c R d 、-NHCOR a 、-NH-C 1-6 Alkyl-R a , -C 1-6 Alkyl-OR a , C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 Aryl or 5-12 membered heteroaryl, the C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 The aryl or 5-12 membered heteroaryl group is optionally substituted by 1, 2 or more R Qa replace; R Qa are independently selected from halogen, =O, -CN, -OH, -OR a 、-OC(=O)R a 、-OC(=O)OR b 、-OC(=O)NR c R d , -SH, -SR a 、-S(=O)R a 、-S(=O)2R a 、-S(=O)2NR c R d 、-NR c R d 、-NR b C(=O)NR c R d 、-NR b C(=O)R a 、-NR b C(=O)OR b 、-NR b S(=O)2R a 、-C(=O)R a 、-C(=O)OR b 、-C(=O)NR c R d , =C(R 1a 2. C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, halo 1-6 Alkyl, C 1-6 Hydroxyalkyl, C 1-6 Amine alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 Aryl or 5-12 membered heteroaryl, the C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, halo 1-6 Alkyl, C 1-6 Hydroxyalkyl, C 1-6 Amine alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 Aryl or 5-12 membered heteroaryl is optionally substituted by 1, 2 or more R; R 2 Selected from H, C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, halo 1-6 Alkyl, C 1-6 Hydroxyalkyl, C 1-6 Amine alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-12 Cycloalkyl or 3-12 membered heterocyclic group; X is C (Rx) or N; Y is C (Ry) or N; Z is N or C (Rz); Rx, Ry, Rz, R 3 , R 4 , R 5 , R 6 are the same or different and are independently selected from H, halogen, -CN, -OH, -OR a 、-OC(=O)R a 、-OC(=O)OR b , -OC(=O)NR c R d , -SH, -SR a 、-S(=O)R a 、-S(=O)2R a 、-S(=O)2NR c R d 、-NR c R d 、-NR b C(=O)NR c R d 、-NR b C(=O)R a 、-NR b C(=O)OR b 、-NR b S(=O)2R a 、-C(=O)R a 、-C(=O)OR b 、-C(=O)NR c R d , C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, halo 1-6 Alkyl, C 1-6 Hydroxyalkyl, C 1-6 Amine alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 Aryl or 5-12 membered heteroaryl, the C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, halo 1-6 Alkyl, C 1-6 Hydroxyalkyl, C 1-6 Amine alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 Aryl or 5-12 membered heteroaryl is optionally substituted by 1, 2 or more R; R a , R b , R c , R d are the same or different, independently selected from H, C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, halo 1-6 Alkyl, C 1-6 Hydroxyalkyl, C 1-6 Amine alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 Aryl, 5-12 membered heteroaryl, C 1-6 Alkyl-C 3-12 Cycloalkyl, C 1-6 Alkyl-3-12 membered heterocyclic group, C 1-6 Alkyl-C 6-14 Aryl or C 1-6 Alkyl-5-12 membered heteroaryl; said C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, halo 1-6 Alkyl, C 1-6 Hydroxyalkyl, C 1-6 Amine alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group, C 6-14 Aryl, 5-12 membered heteroaryl, C 1-6 Alkyl-C 3-12 Cycloalkyl, C 1-6 Alkyl-3-12 membered heterocyclic group, C 1-6 Alkyl-C 6-14 Aryl or C 1-6 Alkyl-5-12 membered heteroaryl is optionally substituted by 1, 2 or more R; or R c and R d are linked together to form a 3-12 membered heterocyclic group, wherein the 3-12 membered heterocyclic group is optionally substituted by 1, 2 or more R; R is independently selected from halogen, -CN, -OH, -S(=O)CH3, -S(=O)2CH3, -S(=O)2NH2, -S(=O)2NHCH3, -S(=O)2N(CH3)2, -NH2, -NHCH3, -N(CH3)2, -C(=O)CH3, -C(=O)OH, -C(=O)OCH3, =C(R 1a 2. C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Alkylthio, halo 1-6 Alkyl, C 1-6 Hydroxyalkyl, C 1-6 Amine alkyl or C 3-12 Cycloalkyl; Or two Rs are on the same carbon atom and are linked together to form =O, C 3-12 Cycloalkyl or 3-12 membered heterocyclic group.

4. The compound according to any one of claims 1 to 3, or a pharmaceutically acceptable salt or stereoisomer thereof, wherein: A is H, halogen, CN, OH, NH2, -SO2NH2, -Ra1-Rb1, -C≡C-Rc1 or -CH=CH-Rc2; Ra1 is selected from 5-12 membered heteroaryl, C 6-14 Aryl, C 3-12 Cycloalkyl or 3-12 membered heterocyclic group; Rb1 is selected from H, NH2, OH, C 1-12 Alkyl, C 2-12 Alkenyl, C 2-12 Alkynyl, =0, unsubstituted or optionally substituted by one, two or more Rb': C 3-12 Cycloalkyl or 3-12 membered heterocyclic group; Rb' is selected from CN, OH, NH2, halogen, mercapto or -SO2NH2; the number of substituents Rb1 is 1, 2 or 3; when Rb1 is 2 or 3, the Rb1 is substituted on the same atom or different atoms of the group represented by Ra1; Rc1 and Rc2 are the same or different and are independently selected from the following groups which are unsubstituted or optionally substituted by one, two or more Rc': 1-12 Alkyl, C 2-12 Alkenyl, C 2-12 Alkynyl, 3-12 membered heterocyclic group, C 3-12 Cycloalkyl, 5-12 membered heteroaryl or C 6-14 Aryl; Rc' is selected from NH2, OH, CN, halogen, mercapto, -SO2NH2, C 1-12 Alkyl, C 1-12 Alkoxy, halogenated C 1-12 Alkyl or halogenated C 1-12 Alkoxy; Q is N or CR 1 , R 1 Selected from H, -LR 7 , C 1-12 Alkyl, C 2-12 Alkenyl or C 2-12 Alkynyl; Wherein, L is selected from -NHCO-, -NH-C 1-12 Alkyl-, -C≡C-, -CO-, -C 1-12 Alkyl-O-, -CONH-, -C 1-12 Alkyl- or -CH=CH-; R 7 The same or different, independently selected from H, unsubstituted or optionally substituted by one, two or more Rd1: 5-12 membered heteroaryl, C 6-14 Aryl, C 3-12 Cycloalkyl, 3-12 membered heterocyclic group or C 1-12 Alkyl; Rd1 is selected from OH, NH2, CN, halogen, mercapto, -SO2NH2, C 1-12 Alkyl, C 1-12 Alkoxy, halogenated C 1-12 Alkyl or halogenated C 1-12 Alkoxy; R 2 H, C 1-12 Alkyl or halogenated C 1-12 alkyl; X is C (Rx) or N; Y is C (Ry) or N; Z is N or C (Rz); Rx, Ry, Rz, R 3 , R 4 , R 5 , R 6 The same or different, independently selected from H, OH, NH2, CN, halogen, mercapto, -SO2NH2, unsubstituted or optionally substituted by one, two or more Rs: C 1-12 Alkyl, C 2-12 Alkenyl, C 2-12 Alkynyl, C 1-12 Alkoxy, halogenated C 1-12 Alkyl, halogenated C 1-12 Alkoxy, 3-12 membered heterocyclic group, C 3-12 Cycloalkyl, -COC 1-12 Alkyl, -COC 6-14 Aryl, -CO-5-12 membered heteroaryl, C 1-12 Alkylthio, -SO2C 1-12 Alkyl, C 6-14 Aryl, -OC 6-14 aryl, -O-5-12 membered heteroaryl or 5-12 membered heteroaryl; wherein Rs is selected from halogen, CN, OH, NH2, thiol, -SO2NH2, C 1-12 Alkyl, C 2-12 Alkenyl, C 2-12 Alkynyl, C 1-12 Alkoxy, halogenated C 1-12 Alkyl or halogenated C 1-12 Alkoxy.

5. The compound according to any one of claims 1 to 4, or a pharmaceutically acceptable salt or stereoisomer thereof, characterized in that: The compound represented by Formula I has the structure represented by Formula Ia or Ic below: Among them, A, Q, X, R 3 , R 4 , R 5 , R 6 Having the definition as described in any one of claims 1 to 4; Optionally, X is CH, C-CH3, C-Cl or C-CN; Optionally, the compound represented by Formula I has a structure represented by Formula Ia', Ib' or Ic': Wherein, A and Q have the definitions in any one of claims 1 to 4; Optionally, the compound represented by Formula I has a structure represented by Formula Ia", Ib" or Ic": Wherein, A and Q have the definitions described in any one of claims 1-4.

6. The compound according to any one of claims 1 to 5, or a pharmaceutically acceptable salt or stereoisomer thereof, wherein: A is selected from H, halogen, -5-12 membered heteroaryl-C 3-12 Cycloalkyl-CN, -C 6-14 Aryl-C 3-12 Cycloalkyl-CN, 5-12 membered heteroaryl, C 6-14 Aryl, -5-12 membered heteroaryl-NH2, -C 6-14 Aryl-NH2, -C 1-12 Alkyl -NH2, -C≡CC 1-12 Alkyl -NH2, -CH=CH-C 1-12 Alkyl-NH2, -C≡C-3-12 membered heterocyclyl-OH, -CH=CH-3-12 membered heterocyclyl-OH, -C≡CC 3-12 Cycloalkyl -OH, -CH=CH-C 3-12 Cycloalkyl-OH, 3-12 membered heterocyclyl, -5-12 membered heteroaryl-C 1-12 Alkyl, -C 6-14 Aryl-C 1-12 Alkyl, -C≡CC 3-12 Cycloalkyl, -CH=CH-C 3-12 Cycloalkyl, -C≡C-3-12 membered heterocyclic group, -CH=CH-3-12 membered heterocyclic group, -C≡CC 1- 12 Alkyl-OH, -CH=CH-C 1-12 Alkyl-OH, C 3-12 Cycloalkyl, -C 3-12 Cycloalkyl (C 1-12 alkyl)-NH2, 3-12 membered heterocyclic group substituted by =O, -C 3- 12 Cycloalkyl (C 1-12 Alkyl)-OH, -3-12 membered heterocyclic group (C 1-12 Alkyl)-OH, -3-12 membered heterocyclic group (C 1-12 Alkyl)-NH2, CN, =O, -C 3-12 Cycloalkyl = C (halogen) 2, -3-12 membered heterocyclic group = CH-halogen, -3-12 membered heterocyclic group = C (halogen) 2, -C 3-12 Cycloalkyl=CH-halogen, -CH=CH-3-12 membered heterocyclyl-C 1-12 Alkyl, -3-12 membered heterocyclic group -COC 1-12 Alkyl, -3-12 membered heterocyclic group-C 1-12 Alkyl, -C≡C-5-12 membered heteroaryl-C 1-12 Alkyl or -CH=CH-3-12 membered heterocyclic group C 1-12 alkyl; Optionally, Q is selected from N or CR 1 , R 1 Selected from H, -NHCO-5-12 membered heteroaryl, -NHCO-C 6-14 Aryl, -NH-C 1-12 Alkyl-5-12 membered heteroaryl-C 1-12 Alkyl, -NH-C 1-12 Alkyl-C 6-14 Aryl-C 1-12 Alkyl, -C≡C-5-12 membered heteroaryl-C 1-12 Alkyl, -CH=CH-5-12 membered heteroaryl-C 1-12 Alkyl, -C≡CC 6-14 Aryl-C 1-12 Alkyl, -CH=CH-C 6-14 Aryl-C 1-12 alkyl, -CONH-5-12 membered heteroaryl, -CONH-C 6-14 Aryl, -CONH2, -C 1- 12 Alkyl-OC 3-12 Cycloalkyl, -C 1-12 Alkyl-O-3-12-membered heterocyclic group, -CONH-C 3-12 Cycloalkyl, -CONH-3-12 membered heterocyclic group, -C 1-12 Alkyl-C 3-12 Cycloalkyl, -C 1-12 Alkyl-3-12 membered heterocyclic group, C 1-12 Alkyl, C 1-12 Alkoxy, -C≡CC 1-12 Alkyl-OH, -CH=CH-C 1-12 Alkyl-OH, -C≡CC 1-12 Alkyl -NH2, -CH=CH-C 1-12 Alkyl -NH2, -CH=CH-C 3-12 Cycloalkyl, -CH=CH-OC 3-12 Cycloalkyl, -CH=CH-3-12 membered heterocyclic group, -C≡CC 3-12 Cycloalkyl, -C≡C-3-12 membered heterocyclic group, -C 1-12 Alkyl-O-5-12 membered heteroaryl, -C 1-12 Alkyl-OC 6-14 Aryl, -5-12 membered heteroaryl-NH2, -5-12 membered heteroaryl [C 3-12 Cycloalkyl=C(halogen)2]-NH2, -5-12 membered heteroaryl-3-12 membered heterocyclic group, -5-12 membered heteroaryl-3-12 membered heterocyclic group (C 1-12 alkyl)-NH2, -5-12 membered heteroaryl-C 1-12 alkyl, 3-12 membered heterocyclic group substituted by =O, -C 3-12 Cycloalkyl=C(halogen)2, -C=C-3-12 membered heterocyclic group-C 1- 12 Alkyl, -C=CC 3-12 Cycloalkyl-OH, -3-12 membered heterocyclyl-C 1-12 Alkyl, C substituted by =O 3-12 Cycloalkyl, -C 3-12 Cycloalkyl = C(halogen)2 or -C 3- 12 Cycloalkyl=CC 1-12 Alkyl-OC 1-12 alkyl; Optionally, A is selected from H, =O, CN, F, Cl, Br, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, Optionally, Q is selected from N or CR 1 , R 1 is selected from H, -CH2-O-cyclopropyl, -CH2-cyclopropyl, -CH2-cyclobutyl, -CH2-cyclopentyl, -CH2-cyclohexyl, -C2H4-cyclopropyl, -C2H4-cyclobutyl, -C2H4-cyclopentyl, -C2H4-cyclohexyl, methyl, ethyl, propyl, -CH2-O-cyclobutyl, -CH2-O-cyclopentyl, -CH2-O-cyclohexyl, -C2H4-O-cyclopropyl, -C2H4-O-cyclobutyl, -C2H4-O-cyclopentyl, -C2H4-O-cyclohexyl, methoxy, ethoxy, propyloxy, -CH=CH-cyclopropyl, -CH=CH-cyclobutyl, -CH=CH-cyclopentyl, -CH=CH-cyclohexyl, 7. A compound according to any one of claims 1 to 6, or a pharmaceutically acceptable salt or stereoisomer thereof, wherein: The compound is selected from one of Compound 1 to Compound 62.

8. A pharmaceutical composition comprising the compound according to any one of claims 1 to 7, a pharmaceutically acceptable salt or stereoisomer thereof, and a pharmaceutically acceptable excipient.

9. Use of the compound according to any one of claims 1 to 7, or a pharmaceutically acceptable salt or stereoisomer thereof in the preparation of a Myt1 kinase inhibitor.

10. The use according to claim 9, wherein The Myt1 kinase inhibitor is used to treat tumors; Optionally, the tumor overexpresses CCNE1; Optionally, the tumor has an inactivating mutation in the FBXW7 gene; Optionally, the tumor is a solid tumor; Optionally, the tumor is breast cancer, colorectal cancer, endometrial cancer, esophageal cancer, glioblastoma, hepatocellular carcinoma, lung cancer, neuroblastoma, ovarian cancer, prostate cancer, gastric cancer or uterine cancer.

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