3H-imidazo [4, 5-b] pyridine compounds as non-covalent modifiers of AKT1 and uses thereof

Abstract

Provided herein are non-covalent modifiers of AKT1 of Formula (I), (II), (II-A), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (V-A), (V-B), (VI), (VI-A), or (VI-B), and pharmaceutical compositions thereof. In some embodiments, the disclosure provides methods of modulating wild-type AKT1 using a compound or salt of Formula (I), (II), (II-A), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (V-A), (V-B), (VI), (VI-A), or (VI-B), and pharmaceutical compositions thereof.

Description

[0001] Cross-referencing This application claims the benefit of U.S. Provisional Application No. 63 / 517,760, filed August 4, 2023, and U.S. Provisional Application No. 63 / 650,658, filed May 22, 2024, each of which is hereby incorporated by reference in its entirety. Background Technology

[0002] The AKT or protein kinase B (PKB) family of serine / threonine protein kinases consists of three highly homologous members: AKT1, AKT2, and AKT3. The AKT protein family is involved in signal transduction pathways that regulate cellular processes, including apoptosis, proliferation, differentiation, and metabolism. The AKT1 pathway is the most frequently dysregulated signal transduction pathway in human cancers. Enhanced activation of all isoforms is potentially associated with tumor development and progression, and has been demonstrated in breast cancer, ovarian cancer, pancreatic cancer, prostate cancer, and other cancers (Song et al., 2019). In cancer cells, AKT1 is involved in proliferation and growth, promotes tumor initiation, and inhibits apoptosis, while AKT2 regulates cytoskeleton dynamics, favoring local tissue invasion and metastasis. It is hypothesized that excessive AKT3 activation in cancer may be related to stimulating cell proliferation (Hinz et al., 2019). Cell Commun Signal 2019, 17(1), 154; Pascual et al., Ann. Oncol. 2019, 30(7), 1051-1060). The expression of these AKT family members is altered in many human malignancies, including gastric, breast, prostate, ovarian, and pancreatic cancers. However, AKT family members are rarely mutated, with the most common mutation being AKT1 E17K, which has been reported in 6%–8% of breast cancers, 2%–6% of colorectal cancers, and 6% of meningiomas in humans (Yu et al., 2019, 30(7), 1051–1060). PLoS One 2015, 10 (10), Issue e0140479). Therefore, there is a need to develop novel therapies to regulate AKT1 and its mutants. Summary of the Invention

[0003] In one aspect, this disclosure provides compounds represented by the structure of formula (I): (I), Or its pharmaceutically acceptable salt, wherein: Ring B is selected from: and ; R 1 Selected from hydrogen, halogens, -OR 10 -SR 10 -N(R) 10 2. -NO2 and -CN; and C1-6 Alkyl group, optionally substituted by one or more substituents independently selected from: halogen, C 3-8 The carbon ring (which is optionally substituted by one or more substituents independently selected from the following: halogen, C 1-4 Alkyl, C 1-4 Halogenated alkyl groups, -OR 20 -SR 20 -N(R) 20 )2、-C(O)R 20 -C(O)OR 20 -OC(O)R 20 -C(O)N(R) 20 )2、-N(R 20 )C(O)R 20 -N(R) 20 )C(O)N(R 20 )2、-N(R 20 )C(O)OR 20 -OC(O)N(R) 20 )2、-S(O)R 20 -S(O)2R 20 -N(R) 20 )S(O)2R 20 -S(O)2N(R) 20 )2, -NO2 and -CN), 4- to 8-membered heterocycles (which are optionally substituted by one or more substituents independently selected from the following: halogen, C 1-4 Alkyl, C 1-4 Halogenated alkyl groups, -OR 20 -SR 20 -N(R) 20 )2、-C(O)R 20 -C(O)OR 20 -OC(O)R 20 -C(O)N(R) 20 )2、-N(R 20 )C(O)R 20 -N(R) 20 )C(O)N(R 20 )2、-N(R 20 )C(O)OR 20 -OC(O)N(R) 20 )2、-S(O)R 20 -S(O)2R 20 -N(R) 20 )S(O)2R 20 -S(O)2N(R) 20 )2, -NO2 and -CN); A1 and A 2 Each is independently selected from (i), (ii), and (iii): (i) Hydrogen, halogens, C 1-4 Halogenated alkyl groups, -OR 11 -SR 11 -N(R) 11 )2、-C(O)N(R 11 )2、-N(R 11 )C(O)R 11 -C(O)OR 11 -OC(O)R 11 -N(R) 11 )C(O)OR 11 -OC(O)N(R) 11 )2、-N(R 11 )C(O)N(R 11 )2、-S(O)R 11 -S(O)2R 11 -N(R) 11 )S(O)2R 11 -S(O)2N(R) 11 2. -NO2 and -CN; (ii) C 1-6 Alkyl, C 2-6 alkenyl and C 2-6 The alkynyl group, wherein any one of them is optionally substituted by one or more substituents independently selected from the following: Halogen, -OR 11 -SR 11 -N(R) 11 )2、-C(O)N(R 11 )2、-N(R 11 )C(O)R 11 -C(O)OR 11 -OC(O)R 11 -N(R) 11 )C(O)OR 11 -OC(O)N(R) 11 )2、-N(R 11 )C(O)N(R 11 )2、-S(O)R 11 -S(O)2R 11 -N(R) 11 )S(O)2R 11 -S(O)2N(R) 11 )2、-NO2、=O、=S、=N(R 11 ) and -CN; and C 3-10A carbocyclic ring and a 4- to 10-membered heterocycle, either of which may optionally be substituted by one or more substituents independently selected from the following: Halogen, -OR 11A -N(R) 11A )2、-C(O)R 11A -C(O)N(R) 11A )2、-N(R 11A )C(O)R 11A -C(O)OR 11A -OC(O)R 11A -NO2, =O, =S, =N(R) 11A ), -CN; and C 1-6 Alkyl C 2-6 alkenyl and C 2-6 Alkyne group, wherein any of them may optionally be substituted by one or more substituents independently selected from: halogen, -OR 11A -SR 11A -N(R) 11A )2、-C(O)R 11A -C(O)N(R) 11A )2、-N(R 11A )C(O)R 11A -N(R) 11A )S(O)2R 11A -C(O)OR 11A -OC(O)R 11A -NO2, =O, =S, =N(R) 11A ) and -CN; and (iii) 5-10 yuan heterocyclic rings and C 3-10 The carbon ring, wherein any one of them is optionally substituted by one or more substituents independently selected from the following: Halogen, -OR 11 -SR 11 -N(R) 11 )2、-C(O)R 11 -C(O)N(R) 11 )2、-N(R 11 )C(O)R 11 -N(R) 11 )S(O)2R 11 -NS(O)2N(R) 11 )2、-C(O)OR 11 -OC(O)R 11 -N(R) 11 )C(O)OR 11 -OC(O)N(R) 11 )2、-N(R11 )C(O)N(R 11 )2、-S(O)R 11 -S(O)2R 11 -S(O)2N(R) 11 )2、-NO2、=O、=S、=N(R 11 ) and -CN; and C 1-6 Alkyl, C 2-6 alkenyl and C 3-6 Alkyne group, wherein any of them may optionally be substituted by one or more substituents independently selected from: halogen, -OR 11 -SR 11 -N(R) 11 )2、-C(O)R 11 -C(O)N(R) 11 )2、-N(R 11 )C(O)R 11 -C(O)OR 11 -OC(O)R 11 -N(R) 11 )C(O)OR 11 -OC(O)N(R) 11 )2、-N(R 11 )C(O)N(R 11 )2、-S(O)R 11 -S(O)2R 11 -N(R) 11 )S(O)2R 11 -S(O)2N(R) 11 )2、-NO2、=O、=S、=N(R 11 ) and -CN; and C 3-10 A carbocyclic ring and a 4- to 10-membered heterocycle, either of which may optionally be substituted by one or more substituents independently selected from the following: Halogen, -OR 11 -N(R) 11 )2、-C(O)R 11 -C(O)N(R) 11 )2、-N(R 11 )C(O)R 11 -C(O)OR 11 -OC(O)R 11 -NO2, =O, =S, =N(R) 11 ), -CN; and C 1-6 Alkyl, C 2-6 alkenyl, C 3-6 alkynyl group, C3-8 A carbocyclic or 4- to 8-membered heterocyclic ring, either of which may optionally be substituted by one or more substituents independently selected from the following: halogen, -OR 11 -SR 11 -N(R) 11 )2、-C(O)R 11 -C(O)N(R) 11 )2、-N(R 11 )C(O)R 11 -N(R) 11 )S(O)2R 11 -C(O)OR 11 -OC(O)R 11 -NO2, =O, =S, =N(R) 11 ) and -CN; q is selected from 1, 2, and 3; m and n are each independently selected from 0, 1, 2 and 3; R 2 In each case, it is independently selected from halogens, C 1-4 Alkyl, C 1-4 Halogenated alkyl groups, -OR 12 -SR 12 -N(R) 12 2. -NO2 and -CN; R 3 Select independently in each case: Halogen, -OR 13 -SR 13 -N(R) 13 )2、-C(O)R 13 -C(O)N(R) 13 )2、-N(R 13 )C(O)R 13 -C(O)OR 13 -OC(O)R 13 -NO2 and -CN; and C 1-6 Alkyl group, optionally substituted by one or more substituents independently selected from: halogen, -OR 13 -SR 13 -N(R) 13 )2、-C(O)R 13 -C(O)N(R) 13 )2、-N(R 13 )C(O)R 13 -C(O)OR 13 -OC(O)R 13 -NO2, =O, =S, =N(R) 13) and -CN; p is selected from 0, 1, 2, 3, 4, and 5; R 4 Select independently in each case: Halogen, -OR 14 -SR 14 -N(R) 14 )2、-C(O)R 14 -C(O)N(R) 14 )2、-N(R 14 )C(O)R 14 -C(O)OR 14 -OC(O)R 14 -NO2 and -CN; and C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, wherein any of them may optionally be substituted by one or more substituents independently selected from: halogen, -OR 14 -SR 14 -N(R) 14 )2、-C(O)R 14 -C(O)N(R) 14 )2、-N(R 14 )C(O)R 14 -C(O)OR 14 -OC(O)R 14 -NO2, =O, =S, =N(R) 14 ) and -CN; or Two R atoms connected to the same atom 4 Together they form a group selected from the following: =O, =S, and =N(R) 14 );or Two R atoms connected to the same or adjacent atoms 4 Together with the carbon atoms they are attached to, they form groups selected from the following: 4- to 8-membered heterocycles and C. 3-8 A carbon ring, wherein any of the carbon rings may optionally be substituted by one or more substituents independently selected from the following: halogen, C 1-4 Alkyl, C 1-4 Halogenated alkyl groups, -OR 14 -SR 14 -N(R) 14 2. -NO2 and -CN; L by -L 1 -L 2 -L 3 -L 4 - indicates that L 1 L 2 L3 and L 4 Each is independently selected from (a) and (b): (a) -O-、-N(R 15 )-, -S-, -S(O)-, -S(O)2-, -S(O)(NR 15 )-、-N(R 15 )C(O)-、-N(R 15 )C(O)O-、-N(R 15 )S(O)2-、-N(R 15 )S(O)2N(R 15 )-、-S(O)(NR 15 )N(R 15 )-、-N(R 15 )N(R 15 )-、-(R 15 )NC(O)N(R 15 )- and -(R 15 )NC(O)N(R 15 )N(R 15 )-;and (b) C 1-6 Alkylene, C 2-6 imidene group, C 2-6 Ethyne group, C 3-8 Carbocyclic and 4- to 8-membered heterocyclic groups, either of which may optionally be substituted by one or more substituents independently selected from: halogen, -OR 15 -SR 15 =O, =S, and -CN; Where L 1 L 2 L 3 and L 4 Each of the two optional locations does not exist; Where L 1 L 2 L 3 and L 4 No more than two are selected from (a), and the two selected are not adjacent; R 5 Selected from 4- to 10-membered heterocycles and C 3-10 The carbon ring, wherein any one of them is optionally substituted by one or more substituents independently selected from the following: Halogen, C 1-4 Halogenated alkyl groups, -OR 16 -SR 16 -N(R) 16 )2、-C(O)N(R 16 )2、-C(O)OR 16 -OC(O)R16 -N(R) 16 )C(O)R 16 -N(R) 16 )S(O)2R 16 -S(O)2N(R) 16 )2、-N(R 16 )C(O)N(R 16 )2、-N(R 16 )C(O)OR 16 -OC(O)N(R) 16 )2、-S(O)R 16 -S(O)2R 16 -NO2, =O, =S, =N(R) 16 ) and -CN; C 1-6 Alkyl, C 2-6 alkenyl and C 2-6 Alkyne group, wherein each of them is optionally substituted by one or more substituents independently selected from: halogen, -OR 16 -SR 16 -N(R) 16 2. -NO2 and -CN; and 4- to 6-membered heterocyclic rings and C 3-8 A carbon ring, wherein each of which is optionally substituted by one or more substituents independently selected from the following: halogen, C 1-4 Alkyl, C 1-4 Halogenated alkyl groups, -OR 16 -SR 16 -N(R) 16 2. -NO2 and -CN; R 10 R 11 R 11A R 12 R 13 R 14 and R 15 Each time it appears, it is independently selected from: hydrogen, C 1-4 Alkyl, C 3-8 Carbon rings, 3- to 8-membered heterocycles and C 1-4 Halogenated alkyl groups; R 16 Each time it appears, it is independently selected from (iv), (v), and (vi): (iv) Hydrogen; (v) C 1-4 Alkyl, wherein the C 1-4 The alkyl group is optionally substituted by one or more substituents independently selected from the following: Halogen, -OR 20 -SR20 -N(R) 20 )2、-C(O)R 20 -C(O)OR 20 -OC(O)R 20 -C(O)N(R) 20 )2、-N(R 20 )C(O)R 20 -N(R) 20 )C(O)N(R 20 )2、-N(R 20 )C(O)OR 20 -OC(O)N(R) 20 )2、-S(O)R 20 -S(O)2R 20 -N(R) 20 )S(O)2R 20 -S(O)2N(R) 20 2. -NO2 and -CN; and C 3-8 A carbocyclic ring and 3- to 8-membered heterocycles, any of which may optionally be substituted by one or more substituents independently selected from the following: halogen, C 1-4 Alkyl, C 1-4 Halogenated alkyl groups, -OR 20 -SR 20 -N(R) 20 )2、-C(O)R 20 -C(O)OR 20 -OC(O)R 20 -C(O)N(R) 20 )2、-N(R 20 )C(O)R 20 -N(R) 20 )C(O)N(R 20 )2、-N(R 20 )C(O)OR 20 -OC(O)N(R) 20 )2、-S(O)R 20 -S(O)2R 20 -N(R) 20 )S(O)2R 20 -S(O)2N(R) 20 2. -NO2 and -CN; and C 3-8 A carbocyclic ring and 4- to 8-membered heterocycles, any of which may optionally be substituted by one or more substituents independently selected from the following: halogen, C 1-4 Alkyl, C 1-4 Halogenated alkyl groups, -OR 20 -SR20 -N(R) 20 )2、-C(O)R 20 -C(O)N(R) 20 )2、-C(O)OR 20 -OC(O)R 20 -N(R) 20 )C(O)R 20 -N(R) 20 )S(O)2R 20 -N(R) 20 )C(O)N(R 20 )2、-N(R 20 )C(O)OR 20 -OC(O)N(R) 20 )2、-S(O)R 20 -S(O)2R 20 -NO2, -CN and C 3-8 Carbon rings or 4- to 8-membered heterocycles, this C 3-8 The carbocyclic ring or any of the 4- to 8-membered heterocycles may optionally be further substituted by one or more substituents independently selected from the following: halogen, C 1-4 Alkyl, C 1-4 Halogenated alkyl groups, -OR 20 -SR 20 -N(R) 20 )2、-C(O)R 20 -C(O)N(R) 20 )2、-C(O)OR 20 -OC(O)R 20 -N(R) 20 )C(O)R 20 -N(R) 20 )S(O)2R 20 -N(R) 20 )C(O)N(R 20 )2、-N(R 20 )C(O)OR 20 -OC(O)N(R) 20 )2、-S(O)R 20 -S(O)2R 20 -NO2 and -CN; and R 20 Each time it appears, it is independently selected from hydrogen, C 1-4 Alkyl, C 1-4 Haloalkyl, C 3-8 Carbon rings and 4- to 8-membered heterocycles.

[0004] On the other hand, this disclosure provides compounds represented by the structure of formula (II): (II), Or its pharmaceutically acceptable salt, wherein: R 1 Selected from hydrogen, halogens, -OR 10 -SR 10 -N(R) 10 )2, -NO2 and -CN; and C, optionally substituted by one or more substituents independently selected from the following 1-6 Alkyl groups: halogens, -OR 10 -SR 10 -N(R) 10 2. -NO2 and -CN; A 1 and A 2 Each is independently selected from (i), (ii), and (iii): (i) Hydrogen, halogens, C 1-4 Halogenated alkyl groups, -OR 11 -SR 11 -N(R) 11 )2、-C(O)N(R 11 )2、-N(R 11 )C(O)R 11 -C(O)OR 11 -OC(O)R 11 -N(R) 11 )C(O)OR 11 -OC(O)N(R) 11 )2、-N(R 11 )C(O)N(R 11 )2、-S(O)R 11 -S(O)2R 11 -N(R) 11 )S(O)2R 11 -S(O)2N(R) 11 2. -NO2 and -CN; (ii) C 1-6 Alkyl, C 2-6 alkenyl and C 2-6 Alkyne group, wherein any one of them is optionally selected independently from halogen, -OR 11 -SR 11 -N(R) 11 )2、-C(O)N(R 11 )2、-N(R 11 )C(O)R 11 -C(O)OR 11 -OC(O)R 11 -N(R) 11)C(O)OR 11 -OC(O)N(R) 11 )2、-N(R 11 )C(O)N(R 11 )2、-S(O)R 11 -S(O)2R 11 -N(R) 11 )S(O)2R 11 -S(O)2N(R) 11 )2、-NO2、=O、=S、=N(R 11 Substitution of ) and -CN; and (iii) 5-10 yuan heterocyclic rings and C 3-10 The carbon ring, wherein any one of them is optionally substituted by one or more substituents independently selected from the following: Halogen, -OR 11 -SR 11 -N(R) 11 )2、-C(O)R 11 -C(O)N(R) 11 )2、-N(R 11 )C(O)R 11 -N(R) 11 )S(O)2R 11 -C(O)OR 11 -OC(O)R 11 -N(R) 11 )C(O)OR 11 -OC(O)N(R) 11 )2、-N(R 11 )C(O)N(R 11 )2、-S(O)R 11 -S(O)2R 11 -S(O)2N(R) 11 )2、-NO2、=O、=S、=N(R 11 ) and -CN; and C 1-6 Alkyl, C 2-6 alkenyl and C 3-6 Alkyne group, wherein any of them may optionally be substituted by one or more substituents independently selected from: halogen, -OR 11 -SR 11 -N(R) 11 )2、-C(O)R 11 -C(O)N(R) 11 )2、-N(R 11 )C(O)R 11 -C(O)OR 11 -OC(O)R11 -N(R) 11 )C(O)OR 11 -OC(O)N(R) 11 )2、-N(R 11 )C(O)N(R 11 )2、-S(O)R 11 -S(O)2R 11 -N(R) 11 )S(O)2R 11 -S(O)2N(R) 11 )2、-NO2、=O、=S、=N(R 11 ) and -CN; and C 3-10 A carbocyclic ring and a 4- to 10-membered heterocycle, either of which may optionally be substituted by one or more substituents independently selected from the following: Halogen, -OR 11 -N(R) 11 )2、-C(O)R 11 -C(O)N(R) 11 )2、-N(R 11 )C(O)R 11 -C(O)OR 11 -OC(O)R 11 -NO2, =O, =S, =N(R) 11 ), -CN; and C 1-6 Alkyl C 2-6 alkenyl and C 3-6 Alkyne group, wherein any of them may optionally be substituted by one or more substituents independently selected from: halogen, -OR 11 -SR 11 -N(R) 11 )2、-C(O)R 11 -C(O)N(R) 11 )2、-N(R 11 )C(O)R 11 -N(R) 11 )S(O)2R 11 -C(O)OR 11 -OC(O)R 11 -NO2, =O, =S, =N(R) 11 ) and -CN; q is selected from 1, 2, and 3; m and n are each independently selected from 0, 1, 2 and 3; R 2 In each case, it is independently selected from halogens, C 1-4 Alkyl, C 1-4Halogenated alkyl groups, -OR 12 -SR 12 -N(R) 12 2. -NO2 and -CN; R 3 Select independently in each case: Halogen, -OR 13 -SR 13 -N(R) 13 )2、-C(O)R 13 -C(O)N(R) 13 )2、-N(R 13 )C(O)R 13 -C(O)OR 13 -OC(O)R 13 -NO2 and -CN; and C 1-6 Alkyl group, optionally substituted by one or more substituents independently selected from: halogen, -OR 13 -SR 13 -N(R) 13 )2、-C(O)R 13 -C(O)N(R) 13 )2、-N(R 13 )C(O)R 13 -C(O)OR 13 -OC(O)R 13 -NO2, =O, =S, =N(R) 13 ) and -CN; p is selected from 0, 1, 2, 3, 4, and 5; R 4 Select independently in each case: Halogen, -OR 14 -SR 14 -N(R) 14 )2、-C(O)R 14 -C(O)N(R) 14 )2、-N(R 14 )C(O)R 14 -C(O)OR 14 -OC(O)R 14 -NO2 and -CN; and C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, wherein any of them may optionally be substituted by one or more substituents independently selected from: halogen, -OR 14 -SR 14 -N(R) 14)2、-C(O)R 14 -C(O)N(R) 14 )2、-N(R 14 )C(O)R 14 -C(O)OR 14 -OC(O)R 14 -NO2, =O, =S, =N(R) 14 ) and -CN; or Two R atoms connected to the same atom 4 Together they form a group selected from the following: =O, =S, and =N(R) 14 );or Two R atoms connected to the same or adjacent atoms 4 Together with the carbon atoms they are attached to, they form groups selected from the following: 4- to 8-membered heterocycles and C. 3-8 A carbon ring, wherein any of the carbon rings may optionally be substituted by one or more substituents independently selected from the following: halogen, C 1-4 Alkyl, C 1-4 Halogenated alkyl groups, -OR 14 -SR 14 -N(R) 14 2. -NO2 and -CN; L by -L 1 -L 2 -L 3 -L 4 - indicates that L 1 L 2 L 3 and L 4 Each is independently selected from (a) and (b): (a) -O-、-N(R 15 )-, -S-, -S(O)-, -S(O)2-, -S(O)(NR 15 )-、-N(R 15 )C(O)-、-N(R 15 )C(O)O-、-N(R 15 )S(O)2-、-N(R 15 )S(O)2N(R 15 )-、-S(O)(NR 15 )N(R 15 )-、-N(R 15 )N(R 15 )-、-(R 15 )NC(O)N(R 15 )- and -(R 15 )NC(O)N(R 15 )N(R 15 )-;and (b) C 1-6 Alkylene, C 2-6 imidene group, C 2-6 Ethyne group, C 3-8 Carbocyclic and 4- to 8-membered heterocyclic groups, either of which may optionally be substituted by one or more substituents independently selected from: halogen, -OR 15 -SR 15 =O, =S, and -CN; Where L 2 L 3 and L 4 Each of the two optional locations does not exist; Where L 1 L 2 L 3 and L 4 No more than two are selected from (a), and the two selected are not adjacent; R 5 Selected from 4- to 10-membered heterocycles and C 3-10 The carbon ring, wherein any one of them is optionally substituted by one or more substituents independently selected from the following: Halogen, C 1-4 Halogenated alkyl groups, -OR 16 -SR 16 -N(R) 16 )2、-C(O)N(R 16 )2、-C(O)OR 16 -OC(O)R 16 -N(R) 16 )C(O)R 16 -N(R) 16 )S(O)2R 16 -S(O)2N(R) 16 )2、-N(R 16 )C(O)N(R 16 )2、-N(R 16 )C(O)OR 16 -OC(O)N(R) 16 )2、-S(O)R 16 -S(O)2R 16 -NO2, =O, =S, =N(R) 16 ) and -CN; C 1-4 Alkyl, C 2-6 alkenyl and C 2-6 Alkyne group, wherein each of them is optionally substituted by one or more substituents independently selected from: halogen, C 1-4 Alkyl, C 1-4 Halogenated alkyl groups, -OR 16 -SR16 -N(R) 16 2. -NO2 and -CN; and 4- to 6-membered heterocyclic rings and C 3-8 A carbon ring, wherein each of which is optionally substituted by one or more substituents independently selected from the following: halogen, C 1-4 Alkyl, C 1-4 Halogenated alkyl groups, -OR 16 -SR 16 -N(R) 16 2. -NO2 and -CN; R 10 R 11 R 12 R 13 R 14 and R 15 Each time it appears, it is independently selected from: hydrogen, C 1-4 Alkyl, C 3-8 Carbon rings, 4- to 8-membered heterocycles and C 1-4 Halogenated alkyl groups; R 16 Each time it appears, it is independently selected from (iv), (v), and (vi): (iv) Hydrogen; (v) C 1-4 Alkyl, wherein the C 1-4 The alkyl group is optionally substituted by one or more substituents independently selected from the following: Halogen, -OR 20 -SR 20 -N(R) 20 )2、-C(O)R 20 -C(O)OR 20 -OC(O)R 20 -C(O)N(R) 20 )2、-N(R 20 )C(O)R 20 -N(R) 20 )C(O)N(R 20 )2、-N(R 20 )C(O)OR 20 -OC(O)N(R) 20 )2、-S(O)R 20 -S(O)2R 20 -N(R) 20 )S(O)2R 20 -S(O)2N(R) 20 2. -NO2 and -CN; C 3-8A carbocyclic ring and 4- to 8-membered heterocycles, any of which may optionally be substituted by one or more substituents independently selected from the following: halogen, C 1-4 Alkyl, C 1-4 Halogenated alkyl groups, -OR 20 -SR 20 -N(R) 20 )2、-C(O)R 20 -C(O)OR 20 -OC(O)R 20 -C(O)N(R) 20 )2、-N(R 20 )C(O)R 20 -N(R) 20 )C(O)N(R 20 )2、-N(R 20 )C(O)OR 20 -OC(O)N(R) 20 )2、-S(O)R 20 -S(O)2R 20 -N(R) 20 )S(O)2R 20 -S(O)2N(R) 20 2. -NO2 and -CN; and (ⅵ) C 3-8 A carbocyclic ring and 4- to 8-membered heterocycles, any of which may optionally be substituted by one or more substituents independently selected from the following: halogen, C 1-4 Alkyl, C 1-4 Halogenated alkyl groups, -OR 20 -SR 20 -N(R) 20 )2、-C(O)R 20 -C(O)N(R) 20 )2、-C(O)OR 20 -OC(O)R 20 -N(R) 20 )C(O)R 20 -N(R) 20 )S(O)2R 20 -N(R) 20 )C(O)N(R 20 )2、-N(R 20 )C(O)OR 20 -OC(O)N(R) 20 )2、-S(O)R 20 -S(O)2R 20 -NO2 and -CN; and R 20 Each time it appears, it is independently selected from hydrogen, C1-4 Alkyl, C 1-4 Haloalkyl, C 3-8 Carbon rings and 4- to 8-membered heterocycles.

[0005] In some embodiments, the compound or salt of formula (II) is represented by the structure of formula (III): (III); Or its pharmaceutically acceptable salt.

[0006] In some embodiments, the compound or salt of formula (II) is represented by the structure of formula (III-A): (III-A); Or its pharmaceutically acceptable salt.

[0007] In some embodiments, the compound or salt of formula (II) is represented by the structure of formula (IV): (IV); Or its pharmaceutically acceptable salt.

[0008] In some embodiments, the compound or salt of formula (II) is represented by the structure of formula (IV-A): (IV-A); Or its pharmaceutically acceptable salt.

[0009] In some embodiments, the compound or salt of formula (II) is represented by the structure of formula (V): (V); Or its pharmaceutically acceptable salt.

[0010] In some embodiments, the compound or salt of formula (II) is represented by the structure of formula (VA): (VA); Or its pharmaceutically acceptable salt.

[0011] In one aspect, this disclosure provides a pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound of formula (I), (II), (III), (III-A), (IV), (IV-A), (V), (VA) or a pharmaceutically acceptable salt thereof.

[0012] In one aspect, this disclosure provides a method for modulating the activity of wild-type AKT1, comprising administering to a subject in need a compound of formula (I), (II), (III), (III-A), (IV), (IV-A), (V), (VA) or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition of this disclosure comprising a pharmaceutically acceptable excipient and a compound of formula (I), (II), (III), (III-A), (IV), (IV-A), (V), (VA) or a pharmaceutically acceptable salt thereof. In another aspect, this disclosure provides a method for modulating the activity of mutant AKT1, comprising administering to a subject in need a compound of formula (I), (II), (III), (III-A), (IV), (IV-A), (V), (VA) or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition of this disclosure comprising a pharmaceutically acceptable excipient and a compound of formula (I), (II), (III), (III-A), (IV), (IV-A), (V), (VA) or a pharmaceutically acceptable salt thereof. In some implementations, the mutant AKT1 is AKT1 E17K.

[0013] In one aspect, this disclosure provides a method for selectively modulating the activity of wild-type AKT1 relative to wild-type AKT2, comprising administering to a subject in need a compound of formula (I), (II), (III), (III-A), (IV), (IV-A), (V), (VA) or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition of this disclosure comprising a pharmaceutically acceptable excipient and a compound of formula (I), (II), (III), (III-A), (IV), (IV-A), (V), (VA) or a pharmaceutically acceptable salt thereof.

[0014] In one aspect, this disclosure provides a method for selectively regulating the activity of a mutant AKT1 relative to wild-type AKT2, comprising administering to a subject in need a compound of formula (I), (II), (III), (III-A), (IV), (IV-A), (V), (VA) or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition of this disclosure comprising a pharmaceutically acceptable excipient and a compound of formula (I), (II), (III), (III-A), (IV), (IV-A), (V), (VA) or a pharmaceutically acceptable salt thereof. In some embodiments, the mutant AKT1 is AKT1 E17K.

[0015] In one aspect, this disclosure provides a method of treating cancer in a subject of need, the method comprising administering to the subject a compound of formula (I), (II), (III), (III-A), (IV), (IV-A), (V), (VA) or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition of this disclosure comprising a pharmaceutically acceptable excipient and a compound of formula (I), (II), (III), (III-A), (IV), (IV-A), (V), (VA) or a pharmaceutically acceptable salt thereof. In some embodiments, the cancer is selected from breast cancer, colorectal cancer, and meningioma. In some embodiments, the action modulates the activity of wild-type AKT1. In some embodiments, the action modulates the activity of mutant AKT1. In some embodiments, the mutant AKT1 is AKT1 E17K.

[0016] Incorporation For the specific purposes identified herein, all publications, patents and patent applications mentioned in this specification are incorporated herein by reference. Detailed Implementation

[0017] The serine / threonine protein kinase family, AKT or protein kinase B (PKB), regulates a variety of key cellular functions, including apoptosis, proliferation, differentiation, and metabolism. The AKT family consists of three highly homologous members: AKT1, AKT2, and AKT3, each with a unique tissue distribution and performing a distinct set of biological functions. Aberrant expression and / or activation of all AKT isoforms are associated with tumor development, including breast, ovarian, pancreatic, and prostate cancers, as well as other cancers.

[0018] Inhibitors of the AKT protein have been developed for cancer treatment, including two main classes of small-molecule AKT inhibitors under clinical investigation: allosteric inhibitors and ATP-competitive inhibitors. First, allosteric inhibitors (such as miransertib (ARQ 092) and MK-2206) interfere with PH domain-mediated membrane recruitment (the first step in AKT activation) and inhibit AKT kinase activation and AKT phosphorylation. Second, ATP-competitive inhibitors of AKT (such as ipatasertib and capivasertib) bind to the active kinase, where the PH domain has shifted from the kinase domain and exposed the ATP-binding pocket site, thereby inhibiting ATP binding.

[0019] This document provides compounds for regulating (e.g., inhibiting) AKT1 function, as well as methods and compositions for treating cancer using the compounds disclosed herein. In some embodiments, the compound selectively inhibits (e.g., 2x, 5x, 10x, 50x, 100x, etc.) AKT1 protein relative to AKT2 and / or AKT3 proteins.

[0020] definition Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains. All patents and publications mentioned herein are incorporated herein by reference.

[0021] As used in the specification and claims, unless the context clearly indicates otherwise, the singular forms “a”, “an” and “the” include plural references.

[0022] "Alkyl" refers to a compound consisting only of carbon and hydrogen atoms, without any unsaturation, and preferably having one to twelve carbon atoms (i.e., C2H2O). 1-12 An alkyl group is a straight-chain or branched hydrocarbon chain monovalent group. The alkyl group is linked to the rest of the molecule by a single bond. The alkyl chain may optionally be substituted with one or more substituents (such as those described herein). In some embodiments, the alkyl group comprises one to twelve carbon atoms (i.e., C12). 1-12 Alkyl groups. In some embodiments, the alkyl group comprises one to eight carbon atoms (i.e., C64-C ... 1-8 Alkyl groups. In other embodiments, the alkyl group comprises one to five carbon atoms (i.e., C16-C56). 1-5 Alkyl groups. In other embodiments, the alkyl group comprises one to four carbon atoms (i.e., C14-C24). 1-4 Alkyl groups. In other embodiments, the alkyl group comprises one to three carbon atoms (i.e., C14-C24-C14). 1-3 Alkyl groups. In other embodiments, the alkyl group comprises one or two carbon atoms (i.e., C14-C24). 1-2 Alkyl group). In other embodiments, the alkyl group comprises one carbon atom (i.e., C1 alkyl). In other embodiments, the alkyl group comprises five to fifteen carbon atoms (i.e., C1 alkyl). 5-15 Alkyl groups. In other embodiments, the alkyl group comprises five to eight carbon atoms (i.e., C64-C ... 5-8 Alkyl groups. In other embodiments, the alkyl group comprises two to five carbon atoms (i.e., C14-C52). 2-5 Alkyl groups. In other embodiments, the alkyl group comprises three to five carbon atoms (i.e., C14-C52). 3-5Alkyl groups. For example, alkyl groups can be attached to the rest of the molecule by a single bond, such as methyl, ethyl, 1-propyl (n-propyl), 1-methylethyl (isopropyl), 1-butyl (n-butyl), 1-methylpropyl (sec-butyl), 2-methylpropyl (isobutyl), 1,1-dimethylethyl (tert-butyl), 1-pentyl (n-pentyl), etc.

[0023] "Alkenyl" refers to a compound consisting only of carbon and hydrogen atoms, containing at least one carbon-carbon double bond, and preferably having two to twelve carbon atoms (i.e., C2H2O). 2-12 An alkenyl group is a straight-chain or branched hydrocarbon chain group. The alkenyl chain may optionally be substituted with one or more substituents (such as those described herein). In some embodiments, the alkenyl group comprises two to eight carbon atoms (i.e., C64-C ... 2-8 Alkenyl group). In some embodiments, the alkenyl group comprises two to six carbon atoms (i.e., C64-C ... 2-6 Alkenyl group). In other embodiments, the alkenyl group comprises two to four carbon atoms (i.e., C46). 2-4 Alkenyl groups are attached to the rest of the molecule by a single bond. Examples include ethenyl (i.e., vinyl), propenyl (i.e., allyl), butenyl, pentenyl, pent-1,4-dienyl, etc.

[0024] "Alkyne" refers to a group consisting only of carbon and hydrogen atoms, containing at least one carbon-carbon triple bond, and preferably having two to twelve carbon atoms (i.e., C2H2O). 2-12 An alkynyl group is a straight-chain or branched hydrocarbon chain group. The alkynyl chain may optionally be substituted with one or more substituents (such as those described herein). In some embodiments, the alkynyl group comprises two to eight carbon atoms (i.e., C64-C ... 2-8 (Alynyl group). In other embodiments, the alkynyl group comprises two to six carbon atoms (i.e., C64-C ... 2-6 (Alynyl group). In other embodiments, the alkynyl group comprises two to four carbon atoms (i.e., C24-C42). 2-4 Alynyl group). Alynyl groups are attached to the rest of the molecule by a single bond, such as ethynyl, propynyl, butynyl, pentylyl, hexynyl, etc.

[0025] "Alkylene" refers to a straight-chain or branched divalent hydrocarbon chain consisting only of carbon and hydrogen, free of unsaturation, and preferably having one to twelve carbon atoms, with the remainder of the molecule connected to a group. Examples include methylene, ethylene, propylene, (methyl)ethylene, butylene, etc. The alkylene chain is connected to the remainder of the molecule by single bonds and to the group via single bonds. The alkylene chain may optionally be substituted with one or more substituents (such as those described herein). In some embodiments, the alkylene comprises one to ten carbon atoms (i.e., C1 to C2). 1-10 Alkylene). In some embodiments, the alkylene comprises one to eight carbon atoms (i.e., C64-C ... 1-8Alkylene). In other embodiments, the alkylene comprises one to five carbon atoms (i.e., C10-C50). 1-5 Alkylene). In other embodiments, the alkylene comprises one to four carbon atoms (i.e., C10-C20). 1-4 Alkylene). In other embodiments, the alkylene comprises one to three carbon atoms (i.e., C10-C20). 1-3 Alkylene). In other embodiments, the alkylene comprises one or two carbon atoms (i.e., C10). 1-2 Alkylene). In other embodiments, the alkylene comprises one carbon atom (i.e., C1 alkylene). In other embodiments, the alkylene comprises five to eight carbon atoms (i.e., C1 alkylene). 5-8 Alkylene). In other embodiments, the alkylene comprises two to five carbon atoms (i.e., C12-C52). 2-5 Alkylene). In other embodiments, the alkylene comprises three to five carbon atoms (i.e., C64-C ... 3-5 (alkylene).

[0026] "Alkenyl" refers to a straight-chain or branched divalent hydrocarbon chain in which the remainder of the molecule is connected to a group, consists only of carbon and hydrogen, contains at least one carbon-carbon double bond, and preferably has two to twelve carbon atoms. The alkenyl chain is connected to the remainder of the molecule by single bonds and to the group by single bonds. The alkenyl chain may optionally be substituted with one or more substituents (such as those described herein). In some embodiments, the alkenyl group contains two to ten carbon atoms (i.e., C64-C ... 2-10 (Alkenyl group). In some embodiments, the alkenyl group contains two to eight carbon atoms (i.e., C64-C ... 2-8 (Alkenyl group). In other embodiments, the alkenyl group comprises two to five carbon atoms (i.e., C64-C ... 2-5 (Alkenyl group). In other embodiments, the alkenyl group comprises two to four carbon atoms (i.e., C64-C ... 2-4 (Alkenyl group). In other embodiments, the alkenyl group comprises two to three carbon atoms (i.e., C64-C ... 2-3 (Alkenyl group). In other embodiments, the alkenyl group comprises two carbon atoms (i.e., C2 alkenyl group). In other embodiments, the alkenyl group comprises five to eight carbon atoms (i.e., C2 alkenyl group). 5-8 (Alkenyl group). In other embodiments, the alkenyl group comprises three to five carbon atoms (i.e., C64-C ... 3-5 (alkenyl group).

[0027] "Imyynyl" refers to a straight-chain or branched divalent hydrocarbon chain in which the remainder of the molecule is connected to a group, consists only of carbon and hydrogen, contains at least one carbon-carbon triple bond, and preferably has two to twelve carbon atoms. The ynylyl chain is connected to the remainder of the molecule by single bonds and to the group by single bonds. The ynylyl chain may optionally be substituted with one or more substituents (such as those described herein). In some embodiments, the ynylyl group contains two to ten carbon atoms (i.e., C64-C ... 2-10(Imyynyl group). In some embodiments, the ynyl group contains two to eight carbon atoms (i.e., C64-C ... 2-8 (Imyynyl group). In other embodiments, the ynyl group comprises two to five carbon atoms (i.e., C24-C24-C24-C24). 2-5 (Imyynyl group). In other embodiments, the ynyl group comprises two to four carbon atoms (i.e., C24-C42). 2-4 (Imyynyl group). In other embodiments, the ynyl group comprises two to three carbon atoms (i.e., C24-C32-C42 ... 2-3 (Alynyl group). In other embodiments, the alynyl group comprises two carbon atoms (i.e., C2 alynyl group). In other embodiments, the alynyl group comprises five to eight carbon atoms (i.e., C2 alynyl group). 5-8 (Imyynyl group). In other embodiments, the ynyl group comprises three to five carbon atoms (i.e., C364-C4 ... 3-5 (Imynyl group).

[0028] Term "C" x-y When used in conjunction with chemical moieties such as alkyl, alkenyl, or ynyl, it means to include groups containing x to y carbons in the chain. For example, the term "C 1-6 "Alkyl" refers to a saturated hydrocarbon group containing 1 to 6 carbons, including straight-chain alkyl and branched-chain alkyl groups. (Term -C) x-y Alkylene refers to an alkylene chain having x to y carbons. For example, -C 1-6 The alkylene group can be selected from methylene, ethylene, propylene, butylene, pentylene, and hexylene, any of which may be optionally substituted.

[0029] Term "C" x-y "Alkenyl" and "C" x-y "Alkyne" refers to an unsaturated aliphatic group with a similar length and possible substitution to the alkyl groups described above, but containing at least one double or triple bond. Term -C x-y An alkenyl group refers to an alkenyl chain having x to y carbons. For example, -C 2-6 Alkenyl group – optionally selected from vinylene, propenylene, butenylene, pentenylene, and hexenylene, any of which may be optionally substituted. The alkenyl chain may have one or more double bonds. Terminology – C x-y The term "alkynyl group" refers to an alkynyl chain having x to y carbons. For example, -C 2-6 The ynyl group can be selected from ethynyl, propynyl, butynyl, pentyynyl, and hexynyl, any of which may be optionally substituted. The ynyl chain has one or more triple bonds.

[0030] As used herein, the term "carbocyclic ring" refers to a saturated, unsaturated, or aromatic ring in which each atom in the ring is carbon. Carbocyclic rings include 3- to 10-membered monocyclic rings and polycyclic rings (e.g., 6- to 12-membered bicyclic rings). Each ring in a polycyclic carbocyclic ring may be self-saturated, unsaturated, or aromatic. Polycyclic carbocyclic rings may be fused, bridged, or spirocyclic systems. Each ring in a bicyclic carbocyclic ring may be self-saturated, unsaturated, or aromatic. Bicyclic carbocyclic rings may be fused, bridged, or spirocyclic systems. In some embodiments, the carbocyclic ring is aryl. In some embodiments, the carbocyclic ring is cycloalkyl. In some embodiments, the carbocyclic ring is cycloalkenyl. In an exemplary embodiment, an aromatic ring (e.g., phenyl) may be fused to a saturated or unsaturated ring, such as cyclohexane, cyclopentane, or cyclohexene. Any combination of saturated, unsaturated, and aromatic bicyclic rings is included in the definition of a carbocyclic ring where valence permits. Exemplary carbocyclic rings include cyclopentyl, cyclohexyl, cyclohexenyl, adamantyl, phenyl, dihydroindenyl, and naphthyl. The carbocyclic ring may optionally be substituted with one or more substituents (such as those described herein).

[0031] As used herein, the term "carbocyclic group" refers to a divalent saturated, unsaturated, or aromatic ring, wherein each atom in the ring is carbon. The carbocyclic group is connected to the remainder of the molecule by a single bond and also to a group by a single bond. The carbocyclic group may optionally be substituted with one or more substituents (such as those described herein). Carbocyclic groups include divalent 3- to 10-membered monocyclic rings and divalent polycyclic rings (e.g., 6- to 12-membered bicyclic rings). Each ring in a polycyclic carbocyclic group may be self-saturated, unsaturated, or aromatic. Polycyclic carbocyclic groups may be fused, bridged, or spirocyclic systems. The single bonds connecting the carbocyclic group to the remainder of the molecule and the single bonds connecting the carbocyclic group to a group may be located on the same or different rings of the polycyclic carbocyclic group. In some embodiments, the carbocyclic ring is an arylene, such as a phenylene. As used herein, "phenylene" refers to a divalent phenyl group. The phenylene group is connected to the remainder of the molecule by a single bond and also to a group by a single bond. The phenylene group may optionally be substituted with one or more substituents (such as those described herein).

[0032] "Cycloalkyl" refers to a stable, fully saturated monocyclic or polycyclic hydrocarbon group consisting only of carbon and hydrogen atoms, including fused, bridged, or spirocyclic systems, and preferably having three to twelve carbon atoms (i.e., C64-C ... 3-12 Cycloalkyl groups. In some embodiments, cycloalkyl groups contain three to ten carbon atoms (i.e., C646). 3-10 (Cycloalkyl). In other embodiments, the cycloalkyl group contains five to seven carbon atoms (i.e., C64-C72-C64 ... 5-7Cycloalkyl groups. A cycloalkyl group can be attached to the rest of the molecule via a single bond. Examples of monocyclic cycloalkyl groups include, for example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and cyclooctyl. Polycyclic cycloalkyl groups include, for example, adamantyl, norbornyl (i.e., bicyclic [2.2.1]heptyl), norbornenyl, decahydronaphthyl, 7,7-dimethyl-bicyclic [2.2.1]heptyl, etc. A cycloalkyl group may optionally be substituted with one or more substituents (such as those described herein).

[0033] "Aryl" refers to a group derived from an aromatic monocyclic or polycyclic aromatic hydrocarbon ring system by removing a hydrogen atom from a ring carbon atom. An aromatic monocyclic or polycyclic aromatic hydrocarbon ring system contains only hydrogen and carbon, and five to eighteen carbon atoms, wherein at least one ring in the ring system is aromatic, i.e., according to Hückel theory, it contains a cyclic, delocalized (4n+2) p-electron system. Ring systems that derive aryl groups include, but are not limited to, groups such as benzene, fluorene, indene, indene, tetrahydronaphthalene, and naphthalene. The aryl group may optionally be substituted with one or more substituents (such as those described herein).

[0034] “C x-y "Carbon ring" refers to a group containing x to y carbon atoms in the ring. For example, the term "C" 3-6 "Carbon ring" can be a saturated, unsaturated or aromatic ring system containing 3 to 6 carbon atoms (any of which may be optionally substituted as provided herein).

[0035] As used herein, the term "heterocycle" refers to a saturated, unsaturated, non-aromatic, or aromatic ring containing one or more heteroatoms. Exemplary heteroatoms include N, O, Si, P, B, and S atoms. Heterocycles include 3- to 10-membered monocyclic and polycyclic (e.g., 6- to 12-membered bicyclic) rings. Polycyclic heterocycles can be fused, bridged, or spirocyclic systems. Each ring in a polycyclic heterocycle can be selected from self-saturated, unsaturated, and aromatic rings. In some embodiments, the heterocycle contains at least one heteroatom selected from oxygen, nitrogen, sulfur, or any combination thereof. In some embodiments, the heterocycle contains at least one heteroatom selected from oxygen, nitrogen, or any combination thereof. In some embodiments, the heterocycle contains at least one heteroatom selected from oxygen, sulfur, or any combination thereof. In some embodiments, the heterocycle contains at least one heteroatom selected from nitrogen, sulfur, or any combination thereof. The heterocycle may be attached to the remainder of the molecule by any atom of the heterocycle (such as a carbon or nitrogen atom of the heterocycle) where the valence allows. In some embodiments, the heterocycle is a heteroaryl group. In some embodiments, the heterocycle is a heterocyclic alkyl group. Exemplary heterocycles include pyrrolidinyl, pyrrolithyl, imidazolyl, pyrazolyl, triazolyl, piperidinyl, pyridinyl, pyrimidinyl, pyridazinyl, thiophenyl, oxazolyl, thiazolyl, morpholinyl, indazole, indolyl, and quinolinyl. The heterocycle may optionally be substituted with one or more substituents (such as those described herein). Bicyclic heterocycles may be fused, bridged, or spirocyclic systems. In one exemplary embodiment, the heterocycle (e.g., pyridinyl) may be fused to a saturated or unsaturated ring, such as cyclohexane, cyclopentane, or cyclohexene. The heterocycle may optionally be substituted with one or more substituents (such as those described herein).

[0036] As used herein, the term "hypoheterocyclic group" refers to a divalent saturated, unsaturated, non-aromatic, or aromatic ring containing one or more heteroatoms. Exemplary heteroatoms include N, O, Si, P, B, and S atoms. The hypoheterocyclic group is connected to the remainder of the molecule by a single bond and to a group by a single bond. The single bonds connecting the hypoheterocyclic group to the remainder of the molecule and the single bonds connecting the hypoheterocyclic group to the group can be independently linked by any atom of the hypoheterocyclic group, including carbon atoms or heteroatoms in the hypoheterocyclic ring, where valence allows. The hypoheterocyclic group may optionally be substituted with one or more substituents (such as those described herein). Hypoheterocyclic groups include 3- to 10-membered monocyclic and polycyclic (e.g., 6- to 12-membered bicyclic) rings. Each ring in a polycyclic hypoheterocyclic group may be self-saturated, unsaturated, or aromatic. Polycyclic hypoheterocyclic groups may be fused, bridged, or spirocyclic systems. The single bonds connecting the heterocyclic group to the remainder of the molecule and the single bonds connecting the heterocyclic group to the functional group may be located on the same or different rings of the polycyclic heterocyclic group, and may be connected to the remainder of the molecule or the functional group through any atom of the heterocyclic group (such as a carbon or nitrogen atom of the heterocycle), subject to valence. In some embodiments, the heterocyclic group contains at least one heteroatom selected from oxygen, nitrogen, sulfur, or any combination thereof. In some embodiments, the heterocyclic group contains at least one heteroatom selected from oxygen, nitrogen, or any combination thereof. In some embodiments, the heterocyclic group contains at least one heteroatom selected from oxygen, sulfur, or any combination thereof. In some embodiments, the heterocyclic group contains at least one heteroatom selected from nitrogen, sulfur, or any combination thereof. In some embodiments, the heterocyclic group is a heteroaryl group. In some embodiments, the heterocyclic group is a heterocyclic alkyl group.

[0037] "Heterocyclic alkyl" refers to a stable 3- to 12-membered non-aromatic cyclic group comprising two to twelve carbon atoms and at least one heteroatom, wherein each heteroatom may be selected from N, O, Si, P, B, and S atoms. In some embodiments, the heterocyclic alkyl contains at least one heteroatom selected from oxygen, nitrogen, sulfur, or any combination thereof. In some embodiments, the heterocyclic alkyl contains at least one heteroatom selected from oxygen, nitrogen, or any combination thereof. In some embodiments, the heterocyclic alkyl contains at least one heteroatom selected from oxygen, sulfur, or any combination thereof. In some embodiments, the heterocyclic alkyl contains at least one heteroatom selected from nitrogen, sulfur, or any combination thereof. The heterocyclic alkyl can be selected from monocyclic or bicyclic and fused, bridged, or spirocyclic systems. The heteroatom in the heterocyclic alkyl is optionally oxidized. If one or more nitrogen atoms are present, they are optionally quaternized. The heterocyclic alkyl is partially or fully saturated. The heterocyclic alkyl is linked to the remainder of the molecule by any atom of the heterocyclic alkyl (such as any carbon or nitrogen atom of the heterocyclic alkyl) as permitted by valence. Examples of heterocyclic alkyl groups include, but are not limited to, dioxolanyl, thiophene[1,3]dithiaalkyl, decahydroisoquinolinyl, imidazolinyl, imidazoalkyl, isothiazolyl, isoxazolyl, morpholinyl, octahydroindolyl, octahydroisoindolyl, 2-oxopiperazinyl, 2-oxopiperidinyl, 2-oxopiperylalkyl, oxazolyl, piperidinyl, piperazinyl, 4-piperidinoneyl, pyrrolylalkyl, pyrazolylalkyl, quininecycloyl, thiazoalkyl, tetrahydrofuranyl, trithiaalkyl, tetrahydropyranyl, thiomorpholinyl, thiamorpholinyl, 1-oxothiomorpholinyl, and 1,1-dioxothiomorpholinyl. Heterocyclic alkyl groups may optionally be substituted with one or more substituents (such as those described herein).

[0038] The term "heteroaryl" refers to a group derived from a 5- to 12-membered aromatic ring group whose ring structure contains at least one heteroatom, preferably between one and four heteroatoms. In some embodiments, the heteroaryl contains at least one heteroatom selected from oxygen, nitrogen, sulfur, or any combination thereof. In some embodiments, the heteroaryl contains at least one heteroatom selected from oxygen, nitrogen, or any combination thereof. In some embodiments, the heteroaryl contains at least one heteroatom selected from oxygen, sulfur, or any combination thereof. In some embodiments, the heteroaryl contains at least one heteroatom selected from nitrogen, sulfur, or any combination thereof. As used herein, the heteroaryl ring may be selected from monocyclic or bicyclic and fused or bridged ring systems, wherein at least one ring in the ring system is aromatic, i.e., according to Hückel theory, it contains a cyclic, delocalized (4n+2) p-electron system. The heteroatom in the heteroaryl may optionally be oxidized. If one or more nitrogen atoms are present, they may optionally be quaternized. The heteroaryl may be linked to the remainder of the molecule via any atom of the heteroaryl (such as a carbon or nitrogen atom of the heteroaryl), provided the valence allows. Heteroaryl groups include aromatic monocyclic structures, preferably 5- to 6-membered rings, whose ring structure includes at least one heteroatom, preferably one to four heteroatoms, more preferably one or two heteroatoms. Heteroaryl groups include, for example, pyrrole, furan, thiophene, imidazole, oxazole, thiazole, pyrazole, pyridine, pyrazine, pyridazine, and pyrimidine. Heteroaryl groups may optionally be substituted with one or more substituents (such as those described herein). Heteroaryl groups also include polycyclic systems having two or more rings, wherein two or more atoms are common to two adjacent rings, wherein at least one ring is heteroaromatic, and the other rings may be aromatic or non-aromatic carbocyclic or heterocyclic. Heteroaryl groups may optionally be substituted with one or more substituents (such as those described herein).

[0039] "X-membered heterocyclic ring" refers to the number of inner ring atoms in the ring, i.e., X. For example, a 5-membered heteroaryl ring or a 5-membered aromatic heterocyclic ring has 5 inner ring atoms, such as triazole, oxazole, thiophene, etc.

[0040] "Alkoxy" refers to a group of the formula -O-alkyl that is bonded by an oxygen atom, wherein the alkyl group is an alkyl chain as defined above.

[0041] "Halogen" or "halogenated" refers to halogenated substituents, such as bromine, chlorine, fluorine, and iodine substituents.

[0042] As used herein, the term "haloalkyl" or "haloalkane" refers to an alkyl group as defined above that has been substituted with one or more halogen groups, such as trifluoromethyl, dichloromethyl, bromomethyl, 2,2,2-trifluoroethyl, 1-fluoromethyl-2-fluoroethyl, etc. In some embodiments, the alkyl portion of the fluoroalkyl group may optionally be further substituted. Examples of halogen-substituted alkanes (“haloalkanes”) include halomethanes (e.g., chloromethane, bromomethane, fluoromethane, iodomethane), dihalomethanes and trihalomethanes (e.g., chloroform, tribromomethane, trifluoromethane, triiodomethane), 1-haloethane, 2-haloethane, 1,2-dihaloethane, 1-halopropane, 2-halopropane, 3-halopropane, 1,2-dihalopropane, 1,3-dihalopropane, 2,3-dihalopropane, 1,2,3-trihalopropane, and any other suitable combination of alkanes (or substituted alkanes) with halogens (e.g., Cl, Br, F, and I). When the alkyl group is substituted with more than one halogen group, each halogen can be chosen independently, for example, 1-chloro,2-fluoroethane.

[0043] The term “substituted” refers to a portion of a compound having a substituent that replaces a hydrogen atom on one or more carbon atoms or substituted heteroatoms (e.g., NH or NH2). Unless otherwise specified (e.g., by using the terms “substituted” or “optionally substituted,” or by including a “-R” group), the chemical groups described herein are not substituted. It will be understood that “substituted” or “replaced by” includes implied limitations: such substitution is consistent with the permissible valence of the substituted atom and the substituent, and the substitution produces a stable compound, i.e., a compound that does not spontaneously undergo transformations such as by rearrangement, cyclization, elimination, etc. In some embodiments, substituted refers to a portion having a substituent that replaces two hydrogen atoms on the same carbon atom, such as replacing two hydrogen atoms on a single carbon atom with an oxo, imino, or thio group. As used herein, the term “substituted” is contemplated to include all permissible substituents of an organic compound. In a broad sense, permissible substituents include acyclic and cyclic, branched and unbranched, carbocyclic and heterocyclic, and aromatic and non-aromatic substituents of organic compounds. For appropriate organic compounds, it is permissible for substituents to be one or more and to be the same or different.

[0044] In some embodiments, the substituents may include any substituents described herein, such as: halogen, hydroxyl, oxo (=O), thio (=S), cyano (-CN), nitro (-NO2), imino (=NH), oxime (=N-OH), hydrazine (=N-NH2), -R b -OR a -R b -OC(O)R a -R b -OC(O)OR a -R b-OC(O)N(R a )2、-R b -N(R a )2、-R b -C(O)R a -R b -C(O)OR a -R b -C(O)N(R a )2、-R b -OR c -C(O)N(R a )2、-R b -N(R a )C(O)OR a -R b -N(R a )C(O)R a -R b -N(R a S(O) t R a (where t is 1 or 2), -R b -S(O) t R a (where t is 0, 1, or 2), -R b -S(O) t OR a (where t is 1 or 2), -R b -S(O) t N(R a )2 (where t is 1 or 2) and -P(O)(R a )2; and alkyl, alkenyl, alkynyl, aryl, aralkyl, arylenyl, arynyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, heterocycloalkylalkyl, heteroaryl and heteroarylalkyl, any of which may optionally be substituted by: alkyl, alkenyl, alkynyl, halogen, haloalkyl, haloalkenyl, haloalkynyl, oxo (=O), thio (=S), cyano (-CN), nitro (-NO2), imino (=NH), oxime (=N-OH), hydrazine (=N-NH2), -R b -OR a -R b -OC(O)R a -R b -OC(O)OR a -R b -OC(O)N(R a )2、-R b -N(R a )2、-R b -C(O)R a -R b-C(O)OR a -R b -C(O)N(R a )2、-R b -OR c -C(O)N(R a )2、-R b -N(R a )C(O)OR a -R b -N(R a )C(O)R a -R b -N(R a S(O) t R a (where t is 1 or 2), -R b -S(O) t R a (where t is 0, 1, or 2), -R b -S(O) t OR a (where t is 1 or 2), -R b -S(O) t N(R a )2 (where t is 1 or 2) and -P(O)(R a )2; where each R a Independently selected from hydrogen, alkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heterocycloalkyl, heterocycloalkylalkyl, heteroaryl, or heteroarylalkyl, wherein each R a Subject to permissible oxidation states, it may optionally be substituted with the following: alkyl, alkenyl, alkynyl, halogen, haloalkyl, haloalkenyl, haloalkynyl, oxo (=O), thio (=S), cyano (-CN), nitro (-NO2), imino (=NH), oxime (=N-OH), hydrazine (=N-NH2), -R b -OR a -R b -OC(O)-R a -R b -OC(O)-OR a -R b -OC(O)-N(R a )2、-R b -N(R a )2、-R b -C(O)R a -R b -C(O)OR a -R b -C(O)N(R a )2、-R b-OR c -C(O)N(R a )2、-R b -N(R a )C(O)OR a -R b -N(R a )C(O)R a -R b -N(R a S(O) t R a (where t is 1 or 2), -R b -S(O) t R a (where t is 0, 1, or 2), -R b -S(O) t OR a (where t is 1 or 2), -R b -S(O) t N(R a )2 (where t is 1 or 2) and -P(O)(R a )2; and each of R b Independently selected from direct-chain or straight-chain or branched alkylene, alkenyl, or ynylene chains, and each R c It is a branched or branched alkylene, alkenylene, or ynylene chain. Those skilled in the art will understand that, where appropriate, the substituent itself can be substituted.

[0045] The term "salt" or "pharmaceutically acceptable salt" refers to a salt derived from a variety of organic and inorganic counterions well known in the art. Pharmaceutically acceptable acid addition salts can be formed from inorganic and organic acids. Pharmaceutically acceptable base addition salts can be formed from inorganic and organic bases.

[0046] The phrase “pharmaceutically acceptable” is used in this document to refer to those compounds, materials, compositions, and / or dosage forms that, to the extent of reasonable medical judgment, are suitable for contact with human and animal tissues without excessive toxicity, irritation, allergic reactions, or other problems or complications, and in proportion to a reasonable benefit / risk ratio.

[0047] As used herein, the phrase “pharmaceuticalally acceptable excipient” or “pharmaceuticalally acceptable carrier” means a pharmaceutically acceptable material, composition, or medium, such as a liquid or solid filler, diluent, excipient, solvent, or encapsulating material. Each carrier must be “acceptable” in the sense that it is compatible with the other components of the formulation and is harmless to the patient.

[0048] The terms “object,” “individual,” or “patient” are used interchangeably and refer to humans as well as non-human mammals (e.g., non-human primates, canines, equines, felines, suidae, bovids, ungulates, lagos, etc.). In various implementations, the object may be a human being under the care of a physician or other healthcare worker in a hospital, as an outpatient, or in another clinical setting (e.g., adult males, adult females, adolescent males, adolescent females, boys, girls). In some implementations, the object may not be under the care or prescription of a physician or other healthcare worker.

[0049] As used herein, the phrase “objects in need” refers to those who have or are at risk of developing a disease that is preventively or therapeutically treated by the compounds or salts described herein, as described below.

[0050] The terms "administer," "administered," "administers," and "administering" are defined as providing a composition to a subject via routes known in the art, including but not limited to intravenous, intra-arterial, oral, parenteral, buccal, topical, percutaneous, rectal, intramuscular, subcutaneous, intraosseous, mucosal, or intraperitoneal administration. In some embodiments, the composition may be administered orally. The terms "administered," "administered," "administers," and "administering" should be understood as indicating an intention to provide an individual in need with a compound or salt of the invention, or a prodrug of a compound or salt of the invention.

[0051] As used herein, “treatment” or “treating” refers to a means of obtaining a beneficial or desired outcome (including, but not limited to, therapeutic and / or preventive benefits) with respect to a disease, condition, or medical condition. In some embodiments, treatment or treating involves administering a compound or composition disclosed herein to a subject. Therapeutic benefits may include eradicating or improving the underlying condition being treated. Moreover, therapeutic benefits may be achieved by eradicating or improving one or more physiological symptoms associated with the underlying condition, such as observing improvement in the subject, although the subject may still have the underlying condition. In some embodiments, for preventive benefits, the composition is administered to a subject at risk of developing a particular disease, or to a subject who reports one or more physiological symptoms of a disease, even if the disease may not yet be diagnosed. Treatment may include, for example, reducing or delaying one or more symptoms of a disease or condition or lessening their severity, or may include reducing the frequency with which a patient experiences symptoms of a disease, defect, condition, or adverse condition. Treatment may be used herein to refer to a method of treatment or improvement that causes a disease or condition to a certain extent, and may encompass a range of results for that purpose, including but not limited to complete prevention of the condition.

[0052] In some implementations, the terms “prevent” or “preventing”, when associated with a disease or condition, may refer to a compound reducing the incidence of a disease or condition in a treated sample relative to an untreated control sample, or delaying the onset or reducing the severity of one or more symptoms of a disease or condition relative to an untreated control sample.

[0053] As used herein, the term "therapeutic effect" encompasses the therapeutic and / or preventive benefits described above. Preventive effects include delaying or eliminating the onset of a disease or condition, delaying or eliminating the onset of symptoms of a disease or condition, slowing, preventing, or reversing the progression of a disease or condition, or any combination thereof.

[0054] compound In some aspects, this disclosure provides compounds represented by the structure of formula (I): (I), Or its pharmaceutically acceptable salt, wherein: Ring B is selected from: and ; R 1 Selected from hydrogen, halogens, -OR 10 -SR 10 -N(R) 10)2, -NO2 and -CN; and C, optionally substituted by one or more substituents independently selected from the following 1-6 Alkyl groups: halogens, -OR 10 -SR 10 -N(R) 10 2. -NO2 and -CN; A 1 and A 2 Each is independently selected from (i), (ii), and (iii): (i) Hydrogen, halogens, C 1-4 Halogenated alkyl groups, -OR 11 -SR 11 -N(R) 11 )2、-C(O)N(R 11 )2、-N(R 11 )C(O)R 11 -C(O)OR 11 -OC(O)R 11 -N(R) 11 )C(O)OR 11 -OC(O)N(R) 11 )2、-N(R 11 )C(O)N(R 11 )2、-S(O)R 11 -S(O)2R 11 -N(R) 11 )S(O)2R 11 -S(O)2N(R) 11 2. -NO2 and -CN; (ii) C 1-6 Alkyl, C 2-6 alkenyl and C 2-6 The alkynyl group, wherein any one of them is optionally substituted by one or more substituents independently selected from the following: Halogen, -OR 11 -SR 11 -N(R) 11 )2、-C(O)N(R 11 )2、-N(R 11 )C(O)R 11 -C(O)OR 11 -OC(O)R 11 -N(R) 11 )C(O)OR 11 -OC(O)N(R) 11 )2、-N(R 11 )C(O)N(R 11 )2、-S(O)R 11 -S(O)2R11 -N(R) 11 )S(O)2R 11 -S(O)2N(R) 11 )2、-NO2、=O、=S、=N(R 11 ) and -CN; and C 3-10 A carbocyclic ring and a 4- to 10-membered heterocycle, either of which may optionally be substituted by one or more substituents independently selected from the following: Halogen, -OR 11A -N(R) 11A )2、-C(O)R 11A -C(O)N(R) 11A )2、-N(R 11A )C(O)R 11A -C(O)OR 11A -OC(O)R 11A -NO2, =O, =S, =N(R) 11A ), -CN; and C 1-6 Alkyl C 2-6 alkenyl and C 2-6 Alkyne group, wherein any of them may optionally be substituted by one or more substituents independently selected from: halogen, -OR 11A -SR 11A -N(R) 11A )2、-C(O)R 11A -C(O)N(R) 11A )2、-N(R 11A )C(O)R 11A -N(R) 11A )S(O)2R 11A -C(O)OR 11A -OC(O)R 11A -NO2, =O, =S, =N(R) 11A ) and -CN; and (iii) 5-10 yuan heterocyclic rings and C 3-10 The carbon ring, wherein any one of them is optionally substituted by one or more substituents independently selected from the following: Halogen, -OR 11 -SR 11 -N(R) 11 )2、-C(O)R 11 -C(O)N(R) 11 )2、-N(R 11 )C(O)R 11 -N(R) 11 )S(O)2R 11-C(O)OR 11 -OC(O)R 11 -N(R) 11 )C(O)OR 11 -OC(O)N(R) 11 )2、-N(R 11 )C(O)N(R 11 )2、-S(O)R 11 -S(O)2R 11 -S(O)2N(R) 11 )2、-NO2、=O、=S、=N(R 11 ) and -CN; and C 1-6 Alkyl, C 2-6 alkenyl and C 3-6 Alkyne group, wherein any of them may optionally be substituted by one or more substituents independently selected from: halogen, -OR 11 -SR 11 -N(R) 11 )2、-C(O)R 11 -C(O)N(R) 11 )2、-N(R 11 )C(O)R 11 -C(O)OR 11 -OC(O)R 11 -N(R) 11 )C(O)OR 11 -OC(O)N(R) 11 )2、-N(R 11 )C(O)N(R 11 )2、-S(O)R 11 -S(O)2R 11 -N(R) 11 )S(O)2R 11 -S(O)2N(R) 11 )2、-NO2、=O、=S、=N(R 11 ) and -CN; and C 3-10 A carbocyclic ring and a 4- to 10-membered heterocycle, either of which may optionally be substituted by one or more substituents independently selected from the following: Halogen, -OR 11 -N(R) 11 )2、-C(O)R 11 -C(O)N(R) 11 )2、-N(R 11 )C(O)R 11 -C(O)OR 11 -OC(O)R11 -NO2, =O, =S, =N(R) 11 ), -CN; and C 1-6 Alkyl C 2-6 alkenyl and C 3-6 Alkyne group, wherein any of them may optionally be substituted by one or more substituents independently selected from: halogen, -OR 11 -SR 11 -N(R) 11 )2、-C(O)R 11 -C(O)N(R) 11 )2、-N(R 11 )C(O)R 11 -N(R) 11 )S(O)2R 11 -C(O)OR 11 -OC(O)R 11 -NO2, =O, =S, =N(R) 11 ) and -CN; q is selected from 1, 2, and 3; m and n are each independently selected from 0, 1, 2 and 3; R 2 In each case, it is independently selected from halogens, C 1-4 Alkyl, C 1-4 Halogenated alkyl groups, -OR 12 -SR 12 -N(R) 12 2. -NO2 and -CN; R 3 Select independently in each case: Halogen, -OR 13 -SR 13 -N(R) 13 )2、-C(O)R 13 -C(O)N(R) 13 )2、-N(R 13 )C(O)R 13 -C(O)OR 13 -OC(O)R 13 -NO2 and -CN; and C 1-6 Alkyl group, optionally substituted by one or more substituents independently selected from: halogen, -OR 13 -SR 13 -N(R) 13 )2、-C(O)R 13 -C(O)N(R) 13 )2、-N(R 13)C(O)R 13 -C(O)OR 13 -OC(O)R 13 -NO2, =O, =S, =N(R) 13 ) and -CN; p is selected from 0, 1, 2, 3, 4, and 5; R 4 Select independently in each case: Halogen, -OR 14 -SR 14 -N(R) 14 )2、-C(O)R 14 -C(O)N(R) 14 )2、-N(R 14 )C(O)R 14 -C(O)OR 14 -OC(O)R 14 -NO2 and -CN; and C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, wherein any of them may optionally be substituted by one or more substituents independently selected from: halogen, -OR 14 -SR 14 -N(R) 14 )2、-C(O)R 14 -C(O)N(R) 14 )2、-N(R 14 )C(O)R 14 -C(O)OR 14 -OC(O)R 14 -NO2, =O, =S, =N(R) 14 ) and -CN; or Two R atoms connected to the same atom 4 Together they form a group selected from the following: =O, =S, and =N(R) 14 );or Two R atoms connected to the same or adjacent atoms 4 Together with the carbon atoms they are attached to, they form groups selected from the following: 4- to 8-membered heterocycles and C. 3-8 A carbon ring, wherein any of the carbon rings may optionally be substituted by one or more substituents independently selected from the following: halogen, C 1-4 Alkyl, C 1-4 Halogenated alkyl groups, -OR 14 -SR 14 -N(R) 14 2. -NO2 and -CN; L by -L 1-L 2 -L 3 -L 4 - indicates that L 1 L 2 L 3 and L 4 Each is independently selected from (a) and (b): (a) -O-、-N(R 15 )-, -S-, -S(O)-, -S(O)2-, -S(O)(NR 15 )-、-N(R 15 )C(O)-、-N(R 15 )C(O)O-、-N(R 15 )S(O)2-、-N(R 15 )S(O)2N(R 15 )-、-S(O)(NR 15 )N(R 15 )-、-N(R 15 )N(R 15 )-、-(R 15 )NC(O)N(R 15 )- and -(R 15 )NC(O)N(R 15 )N(R 15 )-;and (b) C 1-6 Alkylene, C 2-6 imidene group, C 2-6 Ethyne group, C 3-8 Carbocyclic and 4- to 8-membered heterocyclic groups, either of which may optionally be substituted by one or more substituents independently selected from: halogen, -OR 15 -SR 15 =O, =S, and -CN; Where L 1 L 2 L 3 and L 4 Each of the two optional locations does not exist; Where L 1 L 2 L 3 and L 4 No more than two are selected from (a), and the two selected are not adjacent; R 5 Selected from 4- to 10-membered heterocycles and C 3-10 The carbon ring, wherein any one of them is optionally substituted by one or more substituents independently selected from the following: Halogen, C 1-4 Halogenated alkyl groups, -OR 16 -SR16 -N(R) 16 )2、-C(O)N(R 16 )2、-C(O)OR 16 -OC(O)R 16 -N(R) 16 )C(O)R 16 -N(R) 16 )S(O)2R 16 -S(O)2N(R) 16 )2、-N(R 16 )C(O)N(R 16 )2、-N(R 16 )C(O)OR 16 -OC(O)N(R) 16 )2、-S(O)R 16 -S(O)2R 16 -NO2, =O, =S, =N(R) 16 ) and -CN; C 1-6 Alkyl, C 2-6 alkenyl and C 2-6 Alkyne group, wherein each of them is optionally substituted by one or more substituents independently selected from: halogen, -OR 16 -SR 16 -N(R) 16 2. -NO2 and -CN; and 4- to 6-membered heterocyclic rings and C 3-8 A carbon ring, wherein each of which is optionally substituted by one or more substituents independently selected from the following: halogen, C 1-4 Alkyl, C 1-4 Halogenated alkyl groups, -OR 16 -SR 16 -N(R) 16 2. -NO2 and -CN; R 10 R 11 R 11A R 12 R 13 R 14 and R 15 Each time it appears, it is independently selected from: hydrogen, C 1-4 Alkyl, C 3-8 Carbon rings, 4- to 8-membered heterocycles and C 1-4 Halogenated alkyl groups; R 16 Each time it appears, it is independently selected from (iv), (v), and (vi): (iv) Hydrogen; (v) C 1-4Alkyl, wherein the C 1-4 The alkyl group is optionally substituted by one or more substituents independently selected from the following: Halogen, -OR 20 -SR 20 -N(R) 20 )2、-C(O)R 20 -C(O)OR 20 -OC(O)R 20 -C(O)N(R) 20 )2、-N(R 20 )C(O)R 20 -N(R) 20 )C(O)N(R 20 )2、-N(R 20 )C(O)OR 20 -OC(O)N(R) 20 )2、-S(O)R 20 -S(O)2R 20 -N(R) 20 )S(O)2R 20 -S(O)2N(R) 20 2. -NO2 and -CN; and C 3-8 A carbocyclic ring and 4- to 8-membered heterocycles, any of which may optionally be substituted by one or more substituents independently selected from the following: halogen, C 1-4 Alkyl, C 1-4 Halogenated alkyl groups, -OR 20 -SR 20 -N(R) 20 )2、-C(O)R 20 -C(O)OR 20 -OC(O)R 20 -C(O)N(R) 20 )2、-N(R 20 )C(O)R 20 -N(R) 20 )C(O)N(R 20 )2、-N(R 20 )C(O)OR 20 -OC(O)N(R) 20 )2、-S(O)R 20 -S(O)2R 20 -N(R) 20 )S(O)2R 20 -S(O)2N(R) 20 2. -NO2 and -CN; and (ⅵ) C 3-8A carbocyclic ring and 4- to 8-membered heterocycles, any of which may optionally be substituted by one or more substituents independently selected from the following: halogen, C 1-4 Alkyl, C 1-4 Halogenated alkyl groups, -OR 20 -SR 20 -N(R) 20 )2、-C(O)R 20 -C(O)N(R) 20 )2、-C(O)OR 20 -OC(O)R 20 -N(R) 20 )C(O)R 20 -N(R) 20 )S(O)2R 20 -N(R) 20 )C(O)N(R 20 )2、-N(R 20 )C(O)OR 20 -OC(O)N(R) 20 )2、-S(O)R 20 -S(O)2R 20 -NO2 and -CN; and R 20 Each time it appears, it is independently selected from hydrogen, C 1-4 Alkyl, C 1-4 Haloalkyl, C 3-8 Carbon rings and 4- to 8-membered heterocycles.

[0055] In some implementations, for compounds or salts of formula (II), A 2 Selected from C 1-6 Alkyl, C 2-6 alkenyl and C 2-6 The alkynyl group, wherein each of them is optionally substituted by one or more substituents independently selected from the following: Halogen, -OR 11 -N(R) 11 )2、-C(O)N(R 11 )2、-N(R 11 )C(O)R 11 -N(R) 11 )S(O)2R 11 -S(O)2N(R) 11 )2, =O and -NO2, -CN; and C 3-10 A carbocyclic ring and a 4- to 10-membered heterocycle, either of which may optionally be substituted by one or more substituents independently selected from the following: Halogen, -OR 11A -N(R) 11A)2、-C(O)R 11A -C(O)N(R) 11A )2、-N(R 11A )C(O)R 11A -NO2, =O and -CN; and C 1-6 Alkyl, C 2-6 alkenyl and C 3-6 Alkyne group, wherein any of them may optionally be substituted by one or more substituents independently selected from: halogen, -OR 11A -N(R) 11A )2、-C(O)R 11A -C(O)N(R) 11A )2、-N(R 11A )C(O)R 11A -N(R) 11A )S(O)2R 11A -NO2, =O, and -CN.

[0056] In some implementations, for compounds or salts of formula (I), A 2 Selected from C that is optionally substituted by one or more substituents independently selected from the following 2-6 alkynyl group: Halogen, -OR 11 -N(R) 11 )2、-C(O)N(R 11 )2、-N(R 11 )C(O)R 11 -N(R) 11 )S(O)2R 11 -S(O)2N(R) 11 2. -NO2 and -CN; and C 3-10 A carbocyclic ring and a 4- to 10-membered heterocycle, either of which may optionally be substituted by one or more substituents independently selected from the following: Halogen, -OR 11A -N(R) 11A )2、-C(O)R 11A -C(O)N(R) 11A )2、-N(R 11A )C(O)R 11A -NO2, =O and -CN; and C 1-6 Alkyl, C 2-6 alkenyl and C 3-6 Alkyne group, wherein any of them may optionally be substituted by one or more substituents independently selected from: halogen, -OR 11A -N(R) 11A)2、-C(O)R 11A -C(O)N(R) 11A )2、-N(R 11A )C(O)R 11A -N(R) 11A )S(O)2R 11A -NO2, =O, and -CN.

[0057] In some implementations, for compounds or salts of formula (I), A 2 C is optionally substituted by one or more substituents independently selected from the following 2-6 Alkyne group: halogen, -OR 11 -N(R) 11 )2、-NO2、-CN;C 3-10 Carbon rings and 4- to 10-membered heterocycles, this C 3-10 The carbocyclic ring and the 4- to 10-membered heterocycle are each optionally substituted by one or more substituents independently selected from the following: halogen, -OR 11A -N(R) 11A )2, -NO2, =O and -CN; and C 1-6 Alkyl group, optionally substituted by one or more substituents independently selected from: halogen, -OR 11A -N(R) 11A )2, -NO2, =O and -CN.

[0058] In some implementations, for compounds or salts of formula (I), A 2 C is optionally substituted by one or more substituents independently selected from the following 2-6 alkynyl group: C 3-6 A carbocyclic ring and 4- to 6-membered heterocycles, each optionally substituted by one or more substituents independently selected from: halogens, -OR 11A -N(R) 11A )2、-C(O)R 11A -C(O)N(R) 11A )2、-N(R 11A )C(O)R 11A -NO2, =O and -CN; and C 1-6 Alkyl group, optionally substituted by one or more substituents independently selected from: -OR 11A -N(R) 11A )2、-C(O)R 11A -C(O)N(R) 11A )2、-N(R 11A )C(O)R 11A -NO2, =O, and -CN.

[0059] In some implementations, for compounds or salts of formula (I), A 2 C is optionally substituted by one or more substituents independently selected from the following 2-6 alkynyl group: C 3-6 A carbocyclic ring and a 4- to 6-membered heterocycle, either of which may optionally be substituted by one or more substituents independently selected from the following: halogen, -OR 11A -N(R) 11A )2、-C(O)R 11A -C(O)N(R) 11A )2、-N(R 11A )C(O)R 11A -NO2, =O and -CN; and C 1-6 Alkyl group, optionally substituted by one or more substituents independently selected from: halogen, -OR 11A and -N(R) 11A )2.

[0060] In some implementations, for compounds or salts of formula (I), A 2 C is optionally substituted by one or more substituents independently selected from the following 2-6 alkynyl group: C 3-6 A carbocyclic ring and a 4- to 6-membered heterocycle, either of which may optionally be substituted by one or more substituents independently selected from the following: halogen, -OR 11A -N(R) 11A )2, -NO2, =O and -CN; and C 1-6 Alkyl group, optionally substituted by one or more substituents independently selected from: halogen, -OR 11A and -N(R) 11A )2.

[0061] In some implementations, for compounds or salts of formula (I), A 2 C is optionally substituted by one or more substituents independently selected from the following 2-6 alkynyl group: C 3-6 A carbocyclic ring and a 4- to 6-membered heterocycle, either of which may optionally be substituted by one or more substituents independently selected from the following: halogen, -OR 11A and -N(R) 11A )2; and C 1-6 Alkyl group, optionally substituted by one or more substituents independently selected from: halogen, -OR 11A and -N(R) 11A )2.

[0062] In some implementations, for compounds or salts of formula (I), A 2C is optionally substituted by one or more substituents independently selected from the following 2-6 alkynyl group: C 3-6 A carbocyclic ring and a 4- to 6-membered heterocycle, either of which may optionally be substituted by one or more substituents independently selected from the following: halogen, -OR 11A -N(R) 11A 2. C 1-6 Alkyl and C 1-6 Halogenated alkyl groups.

[0063] In some implementations, for compounds or salts of formula (I), A 2 C is optionally substituted by one or more substituents independently selected from the following 2-6 alkynyl group: C 3-6 A carbocyclic ring and 4- to 6-membered heterocycles, any of which may optionally be substituted by one or more substituents independently selected from the following: halogen, C 1-6 Alkyl and C 1-6 Halogenated alkyl groups.

[0064] In some implementations, for compounds or salts of formula (I), A 2 C is optionally replaced by the following 2-6 Alkyne group: cyclopropyl, cyclopentyl, oxetyl, aziryl, and oxazolyl, any of which may optionally be substituted by one or more substituents independently selected from: halogen, -OR 11A -N(R) 11A )2、-C(O)R 11A -C(O)N(R) 11A )2、-N(R 11A )C(O)R 11A -NO2, =O, -CN; and C 1-6 Alkyl group, optionally substituted by one or more substituents independently selected from: halogen, -OR 11A and -N(R) 11A )2.

[0065] In some implementations, for compounds or salts of formula (I), A 2 C is optionally replaced by the following 2-6 Alkyne group: cyclopropyl, cyclopentyl, oxetyl, aziryl, and oxazolyl, wherein each is optionally substituted by one or more substituents independently selected from: halogen, -OR 11A -N(R) 11A )2, -NO2, =O, -CN; and C 1-6 Alkyl group, optionally substituted by one or more substituents independently selected from: halogen, -OR 11A and -N(R) 11A)2.

[0066] In some implementations, for compounds or salts of formula (I), A 2 C is optionally replaced by the following 2-6 Alkyne group: cyclopropyl, cyclopentyl, oxetyl, aziryl, and oxazolyl, wherein each is optionally substituted by one or more substituents independently selected from: halogen, -OR 11A and -N(R) 11A )2; and C 1-6 Alkyl group, optionally substituted by one or more substituents independently selected from: halogen, -OR 11A and -N(R) 11A )2.

[0067] In some embodiments, for compounds or salts of formula (I), A2 is selected from... , , , , , and .

[0068] In some implementations, for compounds or salts of formula (I), A 2 yes Among them, ring B 1 It is C 3-8 A carbocyclic or 4- to 8-membered heterocyclic ring, any of which may optionally be substituted by one or more substituents independently selected from the following: halogen, C 1-4 Alkyl, C 1-4 Halogenated alkyl groups, -OR 20 -SR 20 -N(R) 20 )2、-C(O)R 20 -C(O)N(R) 20 )2、-C(O)OR 20 -OC(O)R 20 -N(R) 20 )C(O)R 20 -N(R) 20 )S(O)2R 20 -N(R) 20 )C(O)N(R 20 )2、-N(R 20 )C(O)OR 20 -OC(O)N(R) 20 )2、-S(O)R 20 -S(O)2R 20 -NO2 and -CN.

[0069] In some implementations, for compounds or salts of formula (I), L 1 L 2 L 3 and L 4 None of them exist.

[0070] In some implementations, for compounds or salts of formula (I), R 5 Selected from 4- to 10-membered heterocycles and C 3-10 The carbon ring, wherein any one of them is optionally substituted by one or more substituents independently selected from the following: Halogen, C 1-4 Halogenated alkyl groups, -OR 16 -SR 16 -N(R) 16 )2、-C(O)N(R 16 )2、-C(O)OR 16 -OC(O)R 16 -N(R) 16 )C(O)R 16 -N(R) 16 )S(O)2R 16 -S(O)2N(R) 16 )2、-N(R 16 )C(O)N(R 16 )2、-N(R 16 )C(O)OR 16 -OC(O)N(R) 16 )2、-S(O)R 16 -S(O)2R 16 -NO2, =O, =S, =N(R) 16 ) and -CN; C 1-6 Alkyl group, optionally substituted by one or more substituents independently selected from: halogen, -OR 16 -SR 16 -N(R) 16 2. -NO2 and -CN; and 4- to 6-membered heterocyclic rings and C 3-8 A carbon ring, wherein each of which is optionally substituted by one or more substituents independently selected from the following: halogen, C 1-4 Alkyl, C 1-4 Halogenated alkyl groups, -OR 16 -SR 16 -N(R) 16 2. -NO2 and -CN.

[0071] In some implementations, for compounds or salts of formula (I), R 5Selected from 4- to 10-membered heterocycles and C 3-10 The carbon ring, wherein any one of them is optionally substituted by one or more substituents independently selected from the following: Halogen, -OR 16 -SR 16 -N(R) 16 )2、-C(O)N(R 16 )2、-C(O)OR 16 -OC(O)R 16 -N(R) 16 )C(O)R 16 -N(R) 16 )S(O)2R 16 -S(O)2N(R) 16 )2、-N(R 16 )C(O)N(R 16 )2、-N(R 16 )C(O)OR 16 -OC(O)N(R) 16 )2、-S(O)R 16 -S(O)2R 16 -NO2, =O, =S, =N(R) 16 ) and -CN; C 1-4 Alkyl group, optionally substituted by one or more substituents independently selected from: halogen, C 1-4 Alkyl, C 1-4 Halogenated alkyl groups, -OR 16 -SR 16 -N(R) 16 2. -NO2 and -CN; and 4- to 6-membered heterocyclic rings and C 3-8 A carbon ring, wherein each of which is optionally substituted by one or more substituents independently selected from the following: halogen, C 1-4 Alkyl, C 1-4 Halogenated alkyl groups, -OR 16 -SR 16 -N(R) 16 2. -NO2 and -CN.

[0072] In some implementations, for compounds or salts of formula (I), R 5 Selected from 4- to 10-membered heterocycles and C 3-10 The carbon ring, wherein any one of them is optionally substituted by one or more substituents independently selected from the following: Halogen, -OR 16 -N(R) 16 )2、-C(O)N(R 16 )2、-C(O)OR16 -OC(O)R 16 -N(R) 16 )C(O)R 16 -NO2, =O, and -CN; C 1-4 Alkyl group, optionally substituted by one or more substituents independently selected from: halogen, -OR 16 -SR 16 -N(R) 16 2. -NO2 and -CN; and 4- to 6-membered heterocyclic rings and C 3-8 A carbon ring, wherein each of which is optionally substituted by one or more substituents independently selected from the following: halogen, C 1-4 Alkyl, C 1-4 Halogenated alkyl groups, -OR 16 -SR 16 -N(R) 16 2. -NO2 and -CN.

[0073] In some implementations, for compounds or salts of formula (I), R 5 Selected from 4- to 10-membered heterocycles and C 3-10 The carbon ring, wherein any one of them is optionally substituted by one or more substituents independently selected from the following: Halogen, -OR 16 -N(R) 16 2. -NO2, =O, and -CN; C 1-4 Alkyl group, optionally substituted by one or more substituents independently selected from: halogen, -OR 16 -N(R) 16 2. -NO2 and -CN; and 4- to 6-membered heterocyclic rings and C 3-8 A carbon ring, wherein each of which is optionally substituted by one or more substituents independently selected from the following: halogen, C 1-4 Alkyl, C 1-4 Halogenated alkyl groups, -OR 16 -N(R) 16 2. -NO2 and -CN.

[0074] In some implementations, for compounds or salts of formula (I), R 5 Selected from 4- to 10-membered heterocycles and C 3-10 The carbon ring, wherein any one of them is optionally substituted by one or more substituents independently selected from the following: Halogen, -OR 16 -N(R) 16 )2, -NO2, =O and -CN; and C 1-4 Alkyl group, optionally substituted by one or more substituents independently selected from: halogen, -OR 16 -N(R) 16 2. -NO2 and -CN.

[0075] In some implementations, for compounds or salts of formula (I), R 5 Selected from 4- to 10-membered heterocycles and C 3-10 The carbon ring, wherein any one of them is optionally substituted by one or more substituents independently selected from the following: Halogen, -OR 16 and -N(R) 16 )2; and C 1-4 Alkyl group, optionally substituted by one or more substituents independently selected from: halogen, -OR 16 and -N(R) 16 )2.

[0076] In some implementations, for compounds or salts of formula (I), R 5 It is a 4- to 10-membered heterocycle optionally substituted with one or more substituents independently selected from the following: Halogen, -OR 16 -SR 16 -N(R) 16 )2、-C(O)N(R 16 )2、-C(O)OR 16 -OC(O)R 16 -N(R) 16 )C(O)R 16 -N(R) 16 )S(O)2R 16 -S(O)2N(R) 16 )2、-N(R 16 )C(O)N(R 16 )2、-N(R 16 )C(O)OR 16 -OC(O)N(R) 16 )2、-S(O)R 16 -S(O)2R 16 -NO2, =O, =S, =N(R) 16 ) and -CN; C 1-4 Alkyl group, optionally substituted by one or more substituents independently selected from: halogen, C 1-4 Alkyl, C 1-4 Halogenated alkyl groups, -OR 16 -SR16 -N(R) 16 2. -NO2 and -CN; and 4- to 6-membered heterocyclic rings and C 3-8 A carbon ring, wherein each of which is optionally substituted by one or more substituents independently selected from the following: halogen, C 1-4 Alkyl, C 1-4 Halogenated alkyl groups, -OR 16 -SR 16 -N(R) 16 2. -NO2 and -CN.

[0077] In some implementations, for compounds or salts of formula (I), R 5 It is a 4- to 10-membered heterocycle optionally substituted with one or more substituents independently selected from the following: Halogen, -OR 16 -SR 16 -N(R) 16 )2、-C(O)N(R 16 )2、-C(O)OR 16 -OC(O)R 16 -N(R) 16 )C(O)R 16 -N(R) 16 )S(O)2R 16 -S(O)2N(R) 16 )2、-N(R 16 )C(O)N(R 16 )2、-N(R 16 )C(O)OR 16 -OC(O)N(R) 16 )2、-S(O)R 16 -S(O)2R 16 -NO2, =O, =S, =N(R) 16 ) and -CN; C 1-4 Alkyl group, optionally substituted by one or more substituents independently selected from: halogen, C 1-4 Alkyl, C 1-4 Halogenated alkyl groups, -OR 16 -SR 16 -N(R) 16 2. -NO2 and -CN.

[0078] In some implementations, for compounds or salts of formula (I), R 5 It is a 4- to 10-membered heterocycle optionally substituted with one or more substituents independently selected from the following: Halogen, -OR16 -N(R) 16 )2、-C(O)N(R 16 )2、-C(O)OR 16 -OC(O)R 16 -N(R) 16 )C(O)R 16 -NO2, =O, and -CN; C 1-4 Alkyl group, optionally substituted by one or more substituents independently selected from: halogen, -OR 16 -SR 16 -N(R) 16 2. -NO2 and -CN; and 4- to 6-membered heterocyclic rings and C 3-8 A carbon ring, wherein each of which is optionally substituted by one or more substituents independently selected from the following: halogen, C 1-4 Alkyl, C 1-4 Halogenated alkyl groups, -OR 16 -SR 16 -N(R) 16 2. -NO2 and -CN.

[0079] In some implementations, for compounds or salts of formula (I), R 5 It is a 4- to 10-membered heterocycle optionally substituted with one or more substituents independently selected from the following: Halogen, -OR 16 -N(R) 16 2. -NO2, =O, and -CN; C 1-4 Alkyl group, optionally substituted by one or more substituents independently selected from: halogen, -OR 16 -N(R) 16 2. -NO2 and -CN; and 4- to 6-membered heterocyclic rings and C 3-8 A carbon ring, wherein each of which is optionally substituted by one or more substituents independently selected from the following: halogen, C 1-4 Alkyl, C 1-4 Halogenated alkyl groups, -OR 16 -N(R) 16 2. -NO2 and -CN.

[0080] In some implementations, for compounds or salts of formula (I), R 5 It is a 4- to 10-membered heterocycle optionally substituted with one or more substituents independently selected from the following: Halogen, -OR 16 -N(R) 16)2, -NO2, =O and -CN; and C 1-4 Alkyl group, optionally substituted by one or more substituents independently selected from: halogen, -OR 16 -N(R) 16 2. -NO2 and -CN.

[0081] In some implementations, for compounds or salts of formula (I), R 5 It is a 4- to 10-membered heterocycle optionally substituted with one or more substituents independently selected from the following: Halogen, -OR 16 and -N(R) 16 )2; and C 1-4 Alkyl group, optionally substituted by one or more substituents independently selected from: halogen, -OR 16 and -N(R) 16 )2.

[0082] In some implementations, for compounds or salts of formula (I), R 5 The group is selected from azacyclobutane, cyclopentyl, cyclohexyl, imidazolyl, pyrazolyl, 1H-1,2,3-triazolyl, 4H-1,2,4-triazolyl, 1,4-dihydropyridinyl, 3,4-dihydropyridino[3,4-d]pyrimidinyl, 1H-benzo[d][1,2,3]triazolyl, wherein each is optionally substituted by one or more substituents independently selected from the following: Halogen, -OR 16 -SR 16 -N(R) 16 )2、-C(O)N(R 16 )2、-C(O)OR 16 -OC(O)R 16 -N(R) 16 )C(O)R 16 -N(R) 16 )S(O)2R 16 -S(O)2N(R) 16 )2、-N(R 16 )C(O)N(R 16 )2、-N(R 16 )C(O)OR 16 -OC(O)N(R) 16 )2、-S(O)R 16 -S(O)2R 16 -NO2, =O, =S, =N(R) 16 ) and -CN; C 1-4Alkyl group, optionally substituted by one or more substituents independently selected from: halogen, C 1-4 Alkyl, C 1-4 Halogenated alkyl groups, -OR 16 -SR 16 -N(R) 16 2. -NO2 and -CN.

[0083] In some implementations, for compounds or salts of formula (I), R 5 The group is selected from azacyclobutane, cyclopentyl, cyclohexyl, imidazolyl, pyrazolyl, 1H-1,2,3-triazolyl, 4H-1,2,4-triazolyl, 1,4-dihydropyridinyl, 3,4-dihydropyridino[3,4-d]pyrimidinyl, 1H-benzo[d][1,2,3]triazolyl, wherein each is optionally substituted by one or more substituents independently selected from the following: Halogen, -OR 16 -N(R) 16 )2、-C(O)N(R 16 )2、-C(O)OR 16 -OC(O)R 16 -N(R) 16 )C(O)R 16 -NO2, =O and -CN; and C 1-4 Alkyl group, optionally substituted by one or more substituents independently selected from: halogen, -OR 16 -N(R) 16 2. -NO2 and -CN.

[0084] In some implementations, for compounds or salts of formula (I), R 5 The group is selected from azacyclobutane, cyclopentyl, cyclohexyl, imidazolyl, pyrazolyl, 1H-1,2,3-triazolyl, 4H-1,2,4-triazolyl, 1,4-dihydropyridinyl, 3,4-dihydropyridino[3,4-d]pyrimidinyl, 1H-benzo[d][1,2,3]triazolyl, wherein each is optionally substituted by one or more substituents independently selected from the following: Halogen, -OR 16 -N(R) 16 )2 and =O; and C 1-4 Alkyl group, optionally substituted by one or more substituents independently selected from: halogen, -OR 16 and -N(R) 16 )2.

[0085] In some implementations, for compounds or salts of formula (I), R 5 Selected from .

[0086] In some implementations, for compounds or salts of formula (I), ring B is .

[0087] In some implementations, for compounds or salts of formula (I), R 2 In each case, it is independently selected from halogens, C 1-4 Alkyl, C 1-4 Halogenated alkyl groups. In some embodiments, R 2 It is a halogen. In some implementations, R 2 It's fluorine.

[0088] In some embodiments, for compounds or salts of formula (I), ring B is selected from... and .

[0089] In some implementations, for compounds or salts of formula (I), ring B is .

[0090] In some implementations, for compounds or salts of formula (I), ring B is Furthermore, the compounds or salts of formula (I) are represented by the structures of formula (II): .

[0091] In some aspects, this disclosure provides compounds represented by the structure of formula (II): (II), Or its pharmaceutically acceptable salt, wherein: R 1 Selected from hydrogen, halogens, -OR 10 -SR 10 -N(R) 10 )2, -NO2 and -CN; and C, optionally substituted by one or more substituents independently selected from the following 1-6 Alkyl groups: halogens, -OR 10 -SR 10 -N(R) 10 2. -NO2 and -CN; A 1 and A 2 Each is independently selected from (i), (ii), and (iii): (i) Hydrogen, halogens, C 1-4 Halogenated alkyl groups, -OR 11 -SR 11 -N(R) 11 )2、-C(O)N(R 11)2、-N(R 11 )C(O)R 11 -C(O)OR 11 -OC(O)R 11 -N(R) 11 )C(O)OR 11 -OC(O)N(R) 11 )2、-N(R 11 )C(O)N(R 11 )2、-S(O)R 11 -S(O)2R 11 -N(R) 11 )S(O)2R 11 -S(O)2N(R) 11 2. -NO2 and -CN; (ii) C 1-6 Alkyl, C 2-6 alkenyl and C 2-6 Alkyne group, wherein any one of them is optionally selected independently from halogen, -OR 11 -SR 11 -N(R) 11 )2、-C(O)N(R 11 )2、-N(R 11 )C(O)R 11 -C(O)OR 11 -OC(O)R 11 -N(R) 11 )C(O)OR 11 -OC(O)N(R) 11 )2、-N(R 11 )C(O)N(R 11 )2,-S(O)R 11 -S(O)2R 11 -N(R) 11 )S(O)2R 11 -S(O)2N(R) 11 )2、-NO2、=O、=S、=N(R 11 Substitution of ) and -CN; and (iii) 5-10 yuan heterocyclic rings and C 3-10 The carbon ring, wherein any one of them is optionally substituted by one or more substituents independently selected from the following: Halogen, -OR 11 -SR 11 -N(R) 11 )2、-C(O)R 11 -C(O)N(R) 11 )2、-N(R 11)C(O)R 11 -N(R) 11 )S(O)2R 11 -C(O)OR 11 -OC(O)R 11 -N(R) 11 )C(O)OR 11 -OC(O)N(R) 11 )2、-N(R 11 )C(O)N(R 11 )2、-S(O)R 11 -S(O)2R 11 -S(O)2N(R) 11 )2、-NO2、=O、=S、=N(R 11 ) and -CN; and C 1-6 Alkyl, C 2-6 alkenyl and C 3-6 Alkyne group, wherein any of them may optionally be substituted by one or more substituents independently selected from: halogen, -OR 11 -SR 11 -N(R) 11 )2、-C(O)R 11 -C(O)N(R) 11 )2、-N(R 11 )C(O)R 11 -C(O)OR 11 -OC(O)R 11 -N(R) 11 )C(O)OR 11 -OC(O)N(R) 11 )2、-N(R 11 )C(O)N(R 11 )2、-S(O)R 11 -S(O)2R 11 -N(R) 11 )S(O)2R 11 -S(O)2N(R) 11 )2、-NO2、=O、=S、=N(R 11 ) and -CN; and C 3-10 A carbocyclic ring and a 4- to 10-membered heterocycle, either of which may optionally be substituted by one or more substituents independently selected from the following: Halogen, -OR 11 -N(R) 11 )2、-C(O)R 11 -C(O)N(R) 11 )2、-N(R 11)C(O)R 11 -C(O)OR 11 -OC(O)R 11 -NO2, =O, =S, =N(R) 11 ), -CN; and C 1-6 Alkyl C 2-6 alkenyl and C 3-6 Alkyne group, wherein any of them may optionally be substituted by one or more substituents independently selected from: halogen, -OR 11 -SR 11 -N(R) 11 )2、-C(O)R 11 -C(O)N(R) 11 )2、-N(R 11 )C(O)R 11 -N(R) 11 )S(O)2R 11 -C(O)OR 11 -OC(O)R 11 -NO2, =O, =S, =N(R) 11 ) and -CN; q is selected from 1, 2, and 3; m and n are each independently selected from 0, 1, 2 and 3; R 2 In each case, it is independently selected from halogens, C 1-4 Alkyl, C 1-4 Halogenated alkyl groups, -OR 12 -SR 12 -N(R) 12 2. -NO2 and -CN; R 3 Select independently in each case: Halogen, -OR 13 -SR 13 -N(R) 13 )2、-C(O)R 13 -C(O)N(R) 13 )2、-N(R 13 )C(O)R 13 -C(O)OR 13 -OC(O)R 13 -NO2 and -CN; and C 1-6 Alkyl group, optionally substituted by one or more substituents independently selected from: halogen, -OR 13 -SR 13 -N(R) 13 )2、-C(O)R13 -C(O)N(R) 13 )2、-N(R 13 )C(O)R 13 -C(O)OR 13 -OC(O)R 13 -NO2, =O, =S, =N(R) 13 ) and -CN; p is selected from 0, 1, 2, 3, 4, and 5; R 4 Select independently in each case: Halogen, -OR 14 -SR 14 -N(R) 14 )2、-C(O)R 14 -C(O)N(R) 14 )2、-N(R 14 )C(O)R 14 -C(O)OR 14 -OC(O)R 14 -NO2 and -CN; and C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, wherein any of them may optionally be substituted by one or more substituents independently selected from: halogen, -OR 14 -SR 14 -N(R) 14 )2、-C(O)R 14 -C(O)N(R) 14 )2、-N(R 14 )C(O)R 14 -C(O)OR 14 -OC(O)R 14 -NO2, =O, =S, =N(R) 14 ) and -CN; or Two R atoms connected to the same atom 4 Together they form a group selected from the following: =O, =S, and =N(R) 14 );or Two R atoms connected to the same or adjacent atoms 4 Together with the carbon atoms they are attached to, they form groups selected from the following: 4- to 8-membered heterocycles and C. 3-8 A carbon ring, wherein any of the carbon rings may optionally be substituted by one or more substituents independently selected from the following: halogen, C 1-4 Alkyl, C 1-4 Halogenated alkyl groups, -OR 14 -SR 14 -N(R)14 2. -NO2 and -CN; L by -L 1 -L 2 -L 3 -L 4 - indicates that L 1 L 2 L 3 and L 4 Each is independently selected from (a) and (b): (a) -O-、-N(R 15 )-, -S-, -S(O)-, -S(O)2-, -S(O)(NR 15 )-、-N(R 15 )C(O)-、-N(R 15 )C(O)O-、-N(R 15 )S(O)2-、-N(R 15 )S(O)2N(R 15 )-、-S(O)(NR 15 )N(R 15 )-、-N(R 15 )N(R 15 )-、-(R 15 )NC(O)N(R 15 )- and -(R 15 )NC(O)N(R 15 )N(R 15 )-;and (b) C 1-6 Alkylene, C 2-6 imidene group, C 2-6 Ethyne group, C 3-8 Carbocyclic and 4- to 8-membered heterocyclic groups, either of which may optionally be substituted by one or more substituents independently selected from: halogen, -OR 15 -SR 15 =O, =S, and -CN; Where L 2 L 3 and L 4 Each of the two optional locations does not exist; Where L 1 L 2 L 3 and L 4 No more than two are selected from (a), and the two selected are not adjacent; R 5 Selected from 4- to 10-membered heterocycles and C 3-10 The carbon ring, wherein any one of them is optionally substituted by one or more substituents independently selected from the following: Halogen, C1-4 Halogenated alkyl groups, -OR 16 -SR 16 -N(R) 16 )2、-C(O)N(R 16 )2、-C(O)OR 16 -OC(O)R 16 -N(R) 16 )C(O)R 16 -N(R) 16 )S(O)2R 16 -S(O)2N(R) 16 )2、-N(R 16 )C(O)N(R 16 )2、-N(R 16 )C(O)OR 16 -OC(O)N(R) 16 )2、-S(O)R 16 -S(O)2R 16 -NO2, =O, =S, =N(R) 16 ) and -CN; C 1-4 Alkyl, C 2-6 alkenyl and C 2-6 Alkyne group, wherein each of them is optionally substituted by one or more substituents independently selected from: halogen, C 1-4 Alkyl, C 1-4 Halogenated alkyl groups, -OR 16 -SR 16 -N(R) 16 2. -NO2 and -CN; and 4- to 6-membered heterocyclic rings and C 3-8 A carbon ring, wherein each of which is optionally substituted by one or more substituents independently selected from the following: halogen, C 1-4 Alkyl, C 1-4 Halogenated alkyl groups, -OR 16 -SR 16 -N(R) 16 2. -NO2 and -CN; R 10 R 11 R 12 R 13 R 14 and R 15 Each time it appears, it is independently selected from: hydrogen, C 1-4 Alkyl, C 3-8 Carbon rings, 4- to 8-membered heterocycles and C 1-4 Halogenated alkyl groups; R 16Each time it appears, it is independently selected from (iv), (v), and (vi): (iv) Hydrogen; (v) C 1-4 Alkyl, wherein the C 1-4 The alkyl group is optionally substituted by one or more substituents independently selected from the following: Halogen, -OR 20 -SR 20 -N(R) 20 )2、-C(O)R 20 -C(O)OR 20 -OC(O)R 20 -C(O)N(R) 20 )2、-N(R 20 )C(O)R 20 -N(R) 20 )C(O)N(R 20 )2、-N(R 20 )C(O)OR 20 -OC(O)N(R) 20 )2、-S(O)R 20 -S(O)2R 20 -N(R) 20 )S(O)2R 20 -S(O)2N(R) 20 2. -NO2 and -CN; C 3-8 A carbocyclic ring and 4- to 8-membered heterocycles, any of which may optionally be substituted by one or more substituents independently selected from the following: halogen, C 1-4 Alkyl, C 1-4 Halogenated alkyl groups, -OR 20 -SR 20 -N(R) 20 )2、-C(O)R 20 -C(O)OR 20 -OC(O)R 20 -C(O)N(R) 20 )2、-N(R 20 )C(O)R 20 -N(R) 20 )C(O)N(R 20 )2、-N(R 20 )C(O)OR 20 -OC(O)N(R) 20 )2、-S(O)R 20 -S(O)2R 20 -N(R) 20 )S(O)2R 20 -S(O)2N(R)20 2. -NO2 and -CN; and (ⅵ) C 3-8 A carbocyclic ring and 4- to 8-membered heterocycles, any of which may optionally be substituted by one or more substituents independently selected from the following: halogen, C 1-4 Alkyl, C 1-4 Halogenated alkyl groups, -OR 20 -SR 20 -N(R) 20 )2、-C(O)R 20 -C(O)N(R) 20 )2、-C(O)OR 20 -OC(O)R 20 -N(R) 20 )C(O)R 20 -N(R) 20 )S(O)2R 20 -N(R) 20 )C(O)N(R 20 )2、-N(R 20 )C(O)OR 20 -OC(O)N(R) 20 )2、-S(O)R 20 -S(O)2R 20 -NO2 and -CN; and R 20 Each time it appears, it is independently selected from hydrogen, C 1-4 Alkyl, C 1-4 Haloalkyl, C 3-8 Carbon rings and 4- to 8-membered heterocycles.

[0092] In some embodiments, for compounds or salts of formula (I) or (II), q is selected from 1, 2, and 3. In some embodiments, q is selected from 1 and 2. In some embodiments, q is selected from 1 and 3. In some embodiments, q is selected from 2 and 3. In some embodiments, q is selected from 1 and 2. In some embodiments, q is 1.

[0093] In some embodiments, the compound or salt of formula (II) is represented by the structure of formula (II-A): (II-A), Or a pharmaceutically acceptable salt thereof, wherein A 1 A 2 R 1 R 2 R 3 R 4 R 5 , m, n, p and L are each defined as in equation (II).

[0094] In some embodiments, the compound or salt of formula (II) is represented by the structure of formula (III): (III); Or a pharmaceutically acceptable salt thereof, wherein A 1 A 2 R 1 R 2 R 3 R 4 R 5 , m, n, p and L are each defined as in equation (II).

[0095] In some embodiments, the compound or salt of formula (II) is represented by the structure of formula (III-A): (III-A); Or a pharmaceutically acceptable salt thereof, wherein A 1 A 2 R 1 R 2 R 3 R 4 R 5 , m, n, p and L are each defined as in equation (II).

[0096] In some embodiments, the compound or salt of formula (II) is represented by the structure of formula (III-B): (III-B); Or a pharmaceutically acceptable salt thereof, wherein A 1 A 2 R 1 R 2 R 3 R 4 R 5 , m, n, p and L are each defined as in equation (II).

[0097] In some embodiments, for compounds or salts of formula (I), (II), (II-A), (III), (III-A), or (III-B), m is selected from 0, 1, 2, and 3. In some embodiments, m is selected from 0, 1, and 2. In some embodiments, m is selected from 0 and 1. In some embodiments, m is 0.

[0098] In some embodiments, for compounds or salts of formula (I), (II), (II-A), (III), (III-A), or (III-B), n is selected from 0, 1, 2, and 3. In some embodiments, n is selected from 0, 1, and 2. In some embodiments, n is selected from 0 and 1. In some embodiments, n is 0.

[0099] In some embodiments, for compounds or salts of formula (I), (II), (II-A), (III), (III-A), or (III-B), p is selected from 0, 1, 2, 3, 4, and 5. In some embodiments, p is selected from 0, 1, 2, 3, and 4. In some embodiments, p is selected from 0, 1, 2, and 3. In some embodiments, p is selected from 0, 1, and 2. In some embodiments, p is selected from 0 and 1. In some embodiments, p is 0.

[0100] In some embodiments, for compounds or salts of formula (I), (II), (II-A), (III), (III-A), or (III-B), A 1 and A 2 Each of them is independently selected from (i), (ii), and (iii): (i) Hydrogen, halogens, C 1-4 Halogenated alkyl groups, -OR 11 -SR 11 -N(R) 11 )2、-C(O)N(R 11 )2、-N(R 11 )C(O)R 11 -C(O)OR 11 -OC(O)R 11 -N(R) 11 )C(O)OR 11 -OC(O)N(R) 11 )2、-N(R 11 )C(O)N(R 11 )2、-S(O)R 11 -S(O)2R 11 -N(R) 11 )S(O)2R 11 -S(O)2N(R) 11 2. -NO2 and -CN; (ii) C 1-6 Alkyl, C 2-6 alkenyl and C 2-6 Alkyne group, wherein any of them may optionally be substituted by one or more substituents independently selected from: halogen, -OR 11 -SR 11 -N(R) 11)2、-C(O)N(R 11 )2、-N(R 11 )C(O)R 11 -C(O)OR 11 -OC(O)R 11 -N(R) 11 )C(O)OR 11 -OC(O)N(R) 11 )2、-N(R 11 )C(O)N(R 11 )2、-S(O)R 11 -S(O)2R 11 -N(R) 11 )S(O)2R 11 -S(O)2N(R) 11 )2、-NO2、=O、=S、=N(R 11 ) and -CN; and (iii) 5-10 yuan heterocyclic rings and C 3-10 The carbon ring, wherein any one of them is optionally substituted by one or more substituents independently selected from the following: Halogen, -OR 11 -SR 11 -N(R) 11 )2、-C(O)R 11 -C(O)N(R) 11 )2、-N(R 11 )C(O)R 11 -N(R) 11 )S(O)2R 11 -C(O)OR 11 -OC(O)R 11 -N(R) 11 )C(O)OR 11 -OC(O)N(R) 11 )2、-N(R 11 )C(O)N(R 11 )2、-S(O)R 11 -S(O)2R 11 -S(O)2N(R) 11 )2、-NO2、=O、=S、=N(R 11 ) and -CN; C 1-6 Alkyl, C 2-6 alkenyl and C 3-6 Alkyne group, wherein any of them may optionally be substituted by one or more substituents independently selected from: halogen, -OR 11 -SR 11 -N(R) 11)2、-C(O)R 11 -C(O)N(R) 11 )2、-N(R 11 )C(O)R 11 -C(O)OR 11 -OC(O)R 11 -N(R) 11 )C(O)OR 11 -OC(O)N(R) 11 )2、-N(R 11 )C(O)N(R 11 )2、-S(O)R 11 -S(O)2R 11 -N(R) 11 )S(O)2R 11 -S(O)2N(R) 11 )2、-NO2、=O、=S、=N(R 11 ) and -CN; and C 3-10 Carbon rings and 4- to 10-membered heterocycles; wherein the C 3-10 The carbocyclic ring and the 4- to 10-membered heterocycle are each optionally substituted by one or more substituents independently selected from the following: Halogen, -OR 11 -N(R) 11 )2、-C(O)R 11 -C(O)N(R) 11 )2、-N(R 11 )C(O)R 11 -C(O)OR 11 -OC(O)R 11 -NO2, =O, =S, =N(R) 11 ) and -CN; C 1-6 Alkyl, C 2-6 alkenyl and C 3-6 Alkyne group, wherein any of them may optionally be substituted by one or more substituents independently selected from: halogen, -OR 11 -SR 11 -N(R) 11 )2、-C(O)R 11 -C(O)N(R) 11 )2、-N(R 11 )C(O)R 11 -N(R) 11 )S(O)2R 11 -C(O)OR 11 -OC(O)R 11 -NO2, =O, =S, =N(R)11 ) and -CN.

[0101] In some embodiments, for compounds or salts of formula (I), (II), (II-A), (III), (III-A), or (III-B), A 1 and A 2 Each of them is independently selected from (i), (ii), and (iii): (i) Hydrogen, halogens, C 1-4 Halogenated alkyl groups, -OR 11 -SR 11 -N(R) 11 )2、-C(O)N(R 11 )2、-N(R 11 )C(O)R 11 -C(O)OR 11 -OC(O)R 11 -N(R) 11 )C(O)OR 11 -OC(O)N(R) 11 )2、-N(R 11 )C(O)N(R 11 )2、-S(O)R 11 -S(O)2R 11 -N(R) 11 )S(O)2R 11 -S(O)2N(R) 11 2. -NO2 and -CN; (ii) C 1-6 Alkyl, C 2-6 alkenyl and C 2-6 Alkyne group, wherein any of them may optionally be substituted by one or more substituents independently selected from: halogen, -OR 11 -SR 11 -N(R) 11 )2、-C(O)N(R 11 )2、-N(R 11 )C(O)R 11 -C(O)OR 11 -OC(O)R 11 -N(R) 11 )C(O)OR 11 -OC(O)N(R) 11 )2、-N(R 11 )C(O)N(R 11 )2、-S(O)R 11 -S(O)2R 11 -N(R) 11 )S(O)2R 11-S(O)2N(R) 11 )2、-NO2、=O、=S、=N(R 11 ) and -CN; and (iii) 5-10 yuan heterocyclic rings and C 3-10 The carbon ring, wherein any one of them is optionally substituted by one or more substituents independently selected from the following: Halogen, -OR 11 -SR 11 -N(R) 11 )2、-C(O)R 11 -C(O)N(R) 11 )2、-N(R 11 )C(O)R 11 -N(R) 11 )S(O)2R 11 -C(O)OR 11 -OC(O)R 11 -N(R) 11 )C(O)OR 11 -OC(O)N(R) 11 )2、-N(R 11 )C(O)N(R 11 )2、-S(O)R 11 -S(O)2R 11 -S(O)2N(R) 11 )2、-NO2、=O、=S、=N(R 11 ) and -CN; C 1-6 Alkyl, C 2-6 alkenyl and C 3-6 Alkyne group, wherein any of them may optionally be substituted by one or more substituents independently selected from: halogen, -OR 11 -SR 11 -N(R) 11 )2、-C(O)R 11 -C(O)N(R) 11 )2、-N(R 11 )C(O)R 11 -C(O)OR 11 -OC(O)R 11 -N(R) 11 )C(O)OR 11 -OC(O)N(R) 11 )2、-N(R 11 )C(O)N(R 11 )2、-S(O)R 11 -S(O)2R 11 -N(R) 11)S(O)2R 11 -S(O)2N(R) 11 )2、-NO2、=O、=S、=N(R 11 ) and -CN; and C 3-10 Carbon rings and 4- to 10-membered heterocycles; wherein the C 3-10 The carbocyclic ring and the 4- to 10-membered heterocycle are each optionally substituted by one or more substituents independently selected from the following: Halogen, -OR 11 -N(R) 11 )2、-C(O)R 11 -C(O)N(R) 11 )2、-N(R 11 )C(O)R 11 -C(O)OR 11 -OC(O)R 11 -NO2, =O, =S, =N(R) 11 ) and -CN; C 1-6 Alkyl, C 2-6 alkenyl and C 3-6 Alkyne group, wherein any of them may optionally be substituted by one or more substituents independently selected from: halogen, -OR 11 -SR 11 -N(R) 11 )2、-C(O)R 11 -C(O)N(R) 11 )2、-N(R 11 )C(O)R 11 -N(R) 11 )S(O)2R 11 -C(O)OR 11 -OC(O)R 11 -NO2, =O, =S, =N(R) 11 ) and -CN; and R 11 Each time it appears, it is independently selected from hydrogen, C 1-4 Alkyl, C 3-8 Carbon rings, 4- to 8-membered heterocycles and C 1-4 Halogenated alkyl groups.

[0102] In some embodiments, for compounds or salts of formula (I), (II), (II-A), (III), (III-A), or (III-B), A 1 and A 2 Each is independently selected from (i), (ii), and (iii): (i) Hydrogen, halogens, C 1-4Halogenated alkyl groups, -OR 11 -N(R) 11 )2、-C(O)N(R 11 )2、-N(R 11 )C(O)R 11 and -CN; (ii) C 1-6 Alkyl, C 2-6 alkenyl and C 2-6 Alkyne group, wherein any of them may optionally be substituted by one or more substituents independently selected from: halogen, -OR 11 -N(R) 11 )2、-C(O)N(R 11 )2、-N(R 11 )C(O)R 11 =O and -CN; and (iii) 5-10 yuan heterocyclic rings and C 3-10 The carbon ring, wherein any one of them is optionally substituted by one or more substituents independently selected from the following: Halogen, -OR 11 -N(R) 11 )2、-C(O)R 11 -C(O)N(R) 11 )2、-N(R 11 )C(O)R 11 -N(R) 11 )S(O)2R 11 =O and -CN; C 1-6 Alkyl, C 2-6 alkenyl and C 3-6 Alkyne group, wherein any of them may optionally be substituted by one or more substituents independently selected from: halogen, -OR 11 、N(R 11 )2、-C(O)R 11 -C(O)N(R) 11 )2、-N(R 11 )C(O)R 11 -N(R) 11 )S(O)2R 11 -NO2, =O and -CN; and C 3-10 Carbon rings and 4- to 10-membered heterocycles; wherein the C 3-10 The carbocyclic ring and the 4- to 10-membered heterocycle are each optionally substituted by one or more substituents independently selected from the following: Halogen, -OR 11 -N(R) 11 )2、-C(O)R 11 -C(O)N(R)11 )2、-N(R 11 )C(O)R 11 =O and -CN; and C 1-6 Alkyl, C 2-6 alkenyl and C 3-6 Alkyne group, wherein any of them may optionally be substituted by one or more substituents independently selected from: halogen, -OR 11 -N(R) 11 )2、-C(O)R 11 -C(O)N(R) 11 )2、-N(R 11 )C(O)R 11 -N(R) 11 )S(O)2R 11 =O and -CN.

[0103] In some embodiments, for compounds or salts of formula (I), (II), (II-A), (III), (III-A), or (III-B), A 1 and A 2 Each is independently selected from (i), (ii), and (iii): (i) Hydrogen, halogens, C 1-4 Halogenated alkyl groups, -OR 11 -N(R) 11 )2 and -CN; (ii) C 1-6 Alkyl and C 2-6 Alkyne group, wherein any one of them is optionally substituted with one or more halogens; and (iii) 5-10 yuan heterocyclic rings and C 3-10 The carbon ring, wherein any one of them is optionally substituted by one or more substituents independently selected from the following: Halogen, -OR 11 C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-10 Carbon rings and 4- to 10-membered heterocycles; wherein the C 3-10 The carbon ring and the 4- to 10-membered heterocycle are each optionally separated by one or more C rings. 1-6 Alkyl substitution.

[0104] In some embodiments, for compounds or salts of formula (I), (II), (II-A), (III), (III-A), or (III-B), A 1 and A 2 Each is independently selected from (i) and (iii): (i) Hydrogen, halogens, -OR 11 C 1-6Alkyl and C 2-6 acetylenic group; and (iii) 5-10 yuan heterocyclic rings and C 3-10 The carbon ring, wherein any one of them is optionally substituted by one or more substituents independently selected from the following: Halogen, C 1-6 Alkyl, C 1-6 Halogenated alkyl groups and 4- to 10-membered heterocycles; wherein the 4- to 10-membered heterocycle is optionally separated by one or more C groups. 1-6 Alkyl substitution.

[0105] In some embodiments, for compounds or salts of formula (I), (II), (II-A), (III), (III-A), or (III-B), A 1 and A 2 Each is independently selected from: hydrogen, 5- to 10-membered heterocycles, and C. 3-10 A carbon ring, wherein any of the carbon rings may optionally be substituted by one or more substituents independently selected from the following: halogen, C 1-6 Alkyl and C 1-6 Halogenated alkyl groups.

[0106] In some embodiments, for compounds or salts of formula (I), (II), (II-A), (III), (III-A), or (III-B), A 1 and A 2 Each is independently selected from: hydrogen and 5- to 10-membered heterocycles, wherein any one of them is optionally substituted by one or more substituents independently selected from: halogen, C 1-6 Alkyl and C 1-6 Halogenated alkyl groups.

[0107] In some embodiments, for compounds or salts of formula (I), (II), (II-A), (III), (III-A), or (III-B), A 1 and A 2 Each is independently selected from: hydrogen and 5- to 10-membered heterocycles, wherein any one of them is optionally substituted by one or more substituents independently selected from: halogens.

[0108] In some embodiments, for compounds or salts of formula (I), (II), (II-A), (III), (III-A), or (III-B), A 1 Selected from (i), (ii) and (iii): (i) Hydrogen, halogens, C 1-4 Halogenated alkyl groups, -OR 11 -SR 11 -N(R) 11 )2、-C(O)N(R 11 )2、-N(R11 )C(O)R 11 -C(O)OR 11 -OC(O)R 11 -N(R) 11 )C(O)OR 11 -OC(O)N(R) 11 )2、-N(R 11 )C(O)N(R 11 )2、-S(O)R 11 -S(O)2R 11 -N(R) 11 )S(O)2R 11 -S(O)2N(R) 11 2. -NO2 and -CN; (ii) C 1-6 Alkyl, C 2-6 alkenyl and C 2-6 Alkyne group, wherein any of them may optionally be substituted by one or more substituents independently selected from: halogen, -OR 11 -SR 11 -N(R) 11 )2、-C(O)N(R 11 )2、-N(R 11 )C(O)R 11 -C(O)OR 11 -OC(O)R 11 -N(R) 11 )C(O)OR 11 -OC(O)N(R) 11 )2、-N(R 11 )C(O)N(R 11 )2、-S(O)R 11 -S(O)2R 11 -N(R) 11 )S(O)2R 11 -S(O)2N(R) 11 )2、-NO2、=O、=S、=N(R 11 ) and -CN; and (iii) 5-10 yuan heterocyclic rings and C 3-10 The carbon ring, wherein any one of them is optionally substituted by one or more substituents independently selected from the following: Halogen, -OR 11 -SR 11 -N(R) 11 )2、-C(O)R 11 -C(O)N(R) 11 )2、-N(R 11 )C(O)R11 -N(R) 11 )S(O)2R 11 -C(O)OR 11 -OC(O)R 11 -N(R) 11 )C(O)OR 11 -OC(O)N(R) 11 )2、-N(R 11 )C(O)N(R 11 )2、-S(O)R 11 -S(O)2R 11 -S(O)2N(R) 11 )2、-NO2、=O、=S、=N(R 11 ) and -CN; C 1-6 Alkyl, C 2-6 alkenyl and C 3-6 Alkyne group, wherein any of them may optionally be substituted by one or more substituents independently selected from: halogen, -OR 11 -SR 11 -N(R) 11 )2、-C(O)R 11 -C(O)N(R) 11 )2、-N(R 11 )C(O)R 11 -C(O)OR 11 -OC(O)R 11 -N(R) 11 )C(O)OR 11 -OC(O)N(R) 11 )2、-N(R 11 )C(O)N(R 11 )2、-S(O)R 11 -S(O)2R 11 -N(R) 11 )S(O)2R 11 -S(O)2N(R) 11 )2、-NO2、=O、=S、=N(R 11 ) and -CN; and C 3-10 Carbon rings and 4- to 10-membered heterocycles; wherein the C 3-10 The carbocyclic ring and the 4- to 10-membered heterocycle are each optionally substituted by one or more substituents independently selected from the following: Halogen, -OR 11 -N(R) 11 )2、-C(O)R 11 -C(O)N(R) 11)2、-N(R 11 )C(O)R 11 -C(O)OR 11 -OC(O)R 11 -NO2, =O, =S, =N(R) 11 ) and -CN; C 1-6 Alkyl, C 2-6 alkenyl and C 3-6 Alkyne group, wherein any of them may optionally be substituted by one or more substituents independently selected from: halogen, -OR 11 -SR 11 -N(R) 11 )2、-C(O)R 11 -C(O)N(R) 11 )2、-N(R 11 )C(O)R 11 -N(R) 11 )S(O)2R 11 -C(O)OR 11 -OC(O)R 11 -NO2, =O, =S, =N(R) 11 ) and -CN.

[0109] In some embodiments, for compounds or salts of formula (I), (II), (II-A), (III), (III-A), or (III-B), A 1 Selected from (i), (ii) and (iii): (i) Hydrogen, halogens, C 1-4 Halogenated alkyl groups, -OR 11 -SR 11 -N(R) 11 )2、-C(O)N(R 11 )2、-N(R 11 )C(O)R 11 -C(O)OR 11 -OC(O)R 11 -N(R) 11 )C(O)OR 11 -OC(O)N(R) 11 )2、-N(R 11 )C(O)N(R 11 )2、-S(O)R 11 -S(O)2R 11 -N(R) 11 )S(O)2R 11 -S(O)2N(R) 11 2. -NO2 and -CN; (ii) C 1-6 Alkyl, C 2-6 alkenyl and C 2-6 Alkyne group, wherein any of them may optionally be substituted by one or more substituents independently selected from: halogen, -OR 11 -SR 11 -N(R) 11 )2、-C(O)N(R 11 )2、-N(R 11 )C(O)R 11 -C(O)OR 11 -OC(O)R 11 -N(R) 11 )C(O)OR 11 -OC(O)N(R) 11 )2、-N(R 11 )C(O)N(R 11 )2、-S(O)R 11 -S(O)2R 11 -N(R) 11 )S(O)2R 11 -S(O)2N(R) 11 )2、-NO2、=O、=S、=N(R 11 ) and -CN; and (iii) 5-10 yuan heterocyclic rings and C 3-10 The carbon ring, wherein any one of them is optionally substituted by one or more substituents independently selected from the following: Halogen, -OR 11 -SR 11 -N(R) 11 )2、-C(O)R 11 -C(O)N(R) 11 )2、-N(R 11 )C(O)R 11 -N(R) 11 )S(O)2R 11 -C(O)OR 11 -OC(O)R 11 -N(R) 11 )C(O)OR 11 -OC(O)N(R) 11 )2、-N(R 11 )C(O)N(R 11 )2、-S(O)R 11 -S(O)2R 11 -S(O)2N(R) 11 )2、-NO2、=O、=S、=N(R 11 ) and -CN; C 1-6 Alkyl, C 2-6 alkenyl and C 3-6 Alkyne group, wherein any of them may optionally be substituted by one or more substituents independently selected from: halogen, -OR 11 -SR 11 -N(R) 11 )2、-C(O)R 11 -C(O)N(R) 11 )2、-N(R 11 )C(O)R 11 -C(O)OR 11 -OC(O)R 11 -N(R) 11 )C(O)OR 11 -OC(O)N(R) 11 )2、-N(R 11 )C(O)N(R 11 )2、-S(O)R 11 -S(O)2R 11 -N(R) 11 )S(O)2R 11 -S(O)2N(R) 11 )2、-NO2、=O、=S、=N(R 11 ) and -CN; and C 3-10 Carbon rings and 4- to 10-membered heterocycles; wherein the C 3-10 The carbocyclic ring and the 4- to 10-membered heterocycle are each optionally substituted by one or more substituents independently selected from the following: Halogen, -OR 11 -N(R) 11 )2、-C(O)R 11 -C(O)N(R) 11 )2、-N(R 11 )C(O)R 11 -C(O)OR 11 -OC(O)R 11 -NO2, =O, =S, =N(R) 11 ) and -CN; C 1-6 Alkyl, C 2-6 alkenyl and C 3-6 Alkyne group, wherein any of them may optionally be substituted by one or more substituents independently selected from: halogen, -OR 11 -SR 11 -N(R) 11 )2、-C(O)R 11 -C(O)N(R)11 )2、-N(R 11 )C(O)R 11 -N(R) 11 )S(O)2R 11 -C(O)OR 11 -OC(O)R 11 -NO2, =O, =S, =N(R) 11 ) and -CN; and R 11 Each time it appears, it is independently selected from hydrogen, C 1-4 Alkyl, C 3-8 Carbon rings, 4- to 8-membered heterocycles and C 1-4 Halogenated alkyl groups.

[0110] In some embodiments, for compounds or salts of formula (I), (II), (II-A), (III), (III-A), or (III-B), A 1 Selected from (i), (ii), and (iii): (i) Hydrogen, halogens, C 1-4 Halogenated alkyl groups, -OR 11 -N(R) 11 )2、-C(O)N(R 11 )2、-N(R 11 )C(O)R 11 and -CN; (ii) C 1-6 Alkyl, C 2-6 alkenyl and C 2-6 Alkyne group, wherein any of them may optionally be substituted by one or more substituents independently selected from: halogen, -OR 11 -N(R) 11 )2、-C(O)N(R 11 )2、-N(R 11 )C(O)R 11 =O and -CN; and (iii) 5-10 yuan heterocyclic rings and C 3-10 The carbon ring, wherein any one of them is optionally substituted by one or more substituents independently selected from the following: Halogen, -OR 11 -N(R) 11 )2、-C(O)R 11 -C(O)N(R) 11 )2、-N(R 11 )C(O)R 11 -N(R) 11 )S(O)2R 11 =O and -CN; C 1-6Alkyl, C 2-6 alkenyl and C 3-6 Alkyne group, wherein any of them may optionally be substituted by one or more substituents independently selected from: halogen, -OR 11 、N(R 11 )2、-C(O)R 11 -C(O)N(R) 11 )2、-N(R 11 )C(O)R 11 -N(R) 11 )S(O)2R 11 -NO2, =O and -CN; and C 3-10 Carbon rings and 4- to 10-membered heterocycles; wherein the C 3-10 The carbocyclic ring and the 4- to 10-membered heterocycle are each optionally substituted by one or more substituents independently selected from the following: Halogen, -OR 11 -N(R) 11 )2、-C(O)R 11 -C(O)N(R) 11 )2、-N(R 11 )C(O)R 11 =O and -CN; and C 1-6 Alkyl, C 2-6 alkenyl and C 3-6 Alkyne group, wherein any of them may optionally be substituted by one or more substituents independently selected from: halogen, -OR 11 -N(R) 11 )2、-C(O)R 11 -C(O)N(R) 11 )2、-N(R 11 )C(O)R 11 -N(R) 11 )S(O)2R 11 =O and -CN.

[0111] In some embodiments, for compounds or salts of formula (I), (II), (II-A), (III), (III-A), or (III-B), A 1 Selected from (i), (ii), and (iii): (i) Hydrogen, halogens, C 1-4 Halogenated alkyl groups, -OR 11 -N(R) 11 )2 and -CN; (ii) C 1-6 Alkyl and C 2-6 Alkyne group, wherein any one of them is optionally substituted with one or more halogens; and (iii) 5-10 yuan heterocyclic rings and C 3-10 The carbon ring, wherein any one of them is optionally substituted by one or more substituents independently selected from the following: Halogen, -OR 11 C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-10 Carbon rings and 4- to 10-membered heterocycles; wherein the C 3-10 The carbon ring and the 4- to 10-membered heterocycle are each optionally separated by one or more C rings. 1-6 Alkyl substitution.

[0112] In some embodiments, for compounds or salts of formula (I), (II), (II-A), (III), (III-A), or (III-B), A 1 Selected from (i) and (iii): (i) Hydrogen, halogens, -OR 11 C 1-6 Alkyl and C 2-6 acetylenic group; and (iii) 5-10 yuan heterocyclic rings and C 3-10 The carbon ring, wherein any one of them is optionally substituted by one or more substituents independently selected from the following: Halogen, C 1-6 Alkyl, C 1-6 Halogenated alkyl groups and 4- to 10-membered heterocycles; wherein the 4- to 10-membered heterocycle is optionally separated by one or more C groups. 1-6 Alkyl substitution.

[0113] In some embodiments, for compounds or salts of formula (I), (II), (II-A), (III), (III-A), or (III-B), A 1 Selected from: hydrogen, 5- to 10-membered heterocycles and C 3-10 A carbon ring, wherein any of the carbon rings may optionally be substituted by one or more substituents independently selected from the following: halogen, C 1-6 Alkyl and C 1-6 Halogenated alkyl groups. In some embodiments, A 1 Selected from: hydrogen and 5- to 10-membered heterocycles, any of which may optionally be substituted by one or more substituents independently selected from: halogens, C 1-6 Alkyl and C 1-6 Halogenated alkyl groups. In some embodiments, A 1 Selected from: hydrogen and 5- to 10-membered heterocycles, any of which may optionally be substituted by one or more substituents independently selected from: halogens. In some embodiments, A 1 It is hydrogen.

[0114] In some embodiments, for compounds or salts of formula (I), (II), (II-A), (III), (III-A), or (III-B), A 1 Selected from hydrogen, halogens, C 1-4 Alkyl, C 1-4 Halogenated alkyl groups, -OR 11 -N(R) 11 )2 and -CN. In some implementations, A 1 Selected from hydrogen, halogens, C 1-4 Alkyl and C 1-4 Halogenated alkyl groups. In some embodiments, A 1 Selected from hydrogen, fluorine, and methyl. In some embodiments, A 1 It is hydrogen.

[0115] In some embodiments, for compounds or salts of formula (I), (II), (II-A), (III), (III-A), or (III-B), R 2 In each case, it is independently selected from halogens, C 1-4 Alkyl, C 1-4 Halogenated alkyl groups, -OR 12 -SR 12 -N(R) 12 )2, -NO2, and -CN. In some implementations, R 2 In each case, it is independently selected from: halogen, C 1-4 Alkyl, C 1-4 Halogenated alkyl groups, -OR 12 -SR 12 -N(R) 12 )2, -NO2 and -CN; and R 12 Each time it appears, it is independently selected from hydrogen and C. 1-4 Alkyl group. In some embodiments, R 2 In each case, it is independently selected from halogens, C 1-4 Alkyl and C 1-4 Halogenated alkyl groups.

[0116] In some embodiments, for compounds or salts of formula (I), (II), (II-A), (III), (III-A), or (III-B), R 3 Select independently in each case: Halogen, -OR 13 -SR 13 -N(R) 13 )2、-C(O)R 13 -C(O)N(R) 13 )2、-N(R 13 )C(O)R 13-C(O)OR 13 -OC(O)R 13 -NO2 and -CN; and C 1-6 Alkyl group, optionally substituted by one or more substituents independently selected from: halogen, -OR 13 -SR 13 -N(R) 13 )2、-C(O)R 13 -C(O)N(R) 13 )2、-N(R 13 )C(O)R 13 -C(O)OR 13 -OC(O)R 13 -NO2, =O, =S, =N(R) 13 ) and -CN.

[0117] In some embodiments, for compounds or salts of formula (I), (II), (II-A), (III), (III-A), or (III-B), R 3 Select independently in each case: Halogen, -OR 13 -N(R) 13 )2、-C(O)R 13 -C(O)N(R) 13 )2、-N(R 13 )C(O)R 13 -C(O)OR 13 -OC(O)R 13 -NO2 and -CN; and C 1-6 Alkyl group, optionally substituted by one or more substituents independently selected from: halogen, -OR 13 -SR 13 -N(R) 13 )2、-C(O)R 13 -C(O)N(R) 13 )2、-N(R 13 )C(O)R 13 -C(O)OR 13 -OC(O)R 13 -NO2, =O, =S, =N(R) 13 ) and -CN.

[0118] In some embodiments, for compounds or salts of formula (I), (II), (II-A), (III), (III-A), or (III-B), R 3 Select independently in each case: Halogen, -OR 13 -N(R) 13 )2、-C(O)R 13 -C(O)N(R) 13 )2、-N(R 13 )C(O)R 13 -C(O)OR 13 -OC(O)R 13 -NO2 and -CN; and C 1-6 Alkyl group, optionally substituted by one or more substituents independently selected from: halogen, -OR 13 -SR 13 -N(R) 13 )2、-C(O)R 13 -C(O)N(R) 13 )2、-N(R 13 )C(O)R 13 -C(O)OR 13 -OC(O)R 13 -NO2, =O, =S, =N(R) 13 ) and -CN; and R 13 Each time it appears, it is independently selected from hydrogen and C. 1-4 Alkyl, C 3-8 Carbon rings, 4- to 8-membered heterocycles and C 1-4 Halogenated alkyl groups.

[0119] In some embodiments, for compounds or salts of formula (I), (II), (II-A), (III), (III-A), or (III-B), R 3 Select independently in each case: Halogen, -OR 13 -SR 13 -N(R) 13 )2、-C(O)R 13 -C(O)N(R) 13 )2、-N(R 13 )C(O)R 13 and -CN; and C 1-6 Alkyl group, optionally substituted by one or more substituents independently selected from: halogen, -OR 13 -N(R) 13 )2、-C(O)R 13 -C(O)N(R) 13 )2、-N(R 13 )C(O)R 13=O and -CN.

[0120] In some embodiments, for compounds or salts of formula (I), (II), (II-A), (III), (III-A), or (III-B), R 3 In each case, it is independently selected from halogen, -OR 13 -N(R) 13 )2、-CN、C 1-6 Alkyl and C 1-6 Halogenated alkyl groups. In some embodiments, R 3 In each case, it is independently selected from halogen, -OR 13 -N(R) 13 )2、-CN、C 1-6 Alkyl and C 1-6 Haloalkyl; and R 13 Each time it appears, it is independently selected from hydrogen and C. 1-4 Alkyl group. In some embodiments, R 3 In each case, it is independently selected from halogens, C 1-4 Alkyl, C 1-4 Halogenated alkyl groups and -CN.

[0121] In some embodiments, for compounds or salts of formula (I), (II), (II-A), (III), (III-A), or (III-B), R 4 Select independently in each case: Halogen, -OR 14 -SR 14 -N(R) 14 )2、-C(O)R 14 -C(O)N(R) 14 )2、-N(R 14 )C(O)R 14 -C(O)OR 14 -OC(O)R 14 -NO2 and -CN; and C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 The alkynyl group, wherein any one of them is optionally substituted by one or more substituents selected from: halogen, -OR 14 -SR 14 -N(R) 14 )2、-C(O)R 14 -C(O)N(R) 14 )2、-N(R 14 )C(O)R 14 -C(O)OR 14 -OC(O)R14 -NO2, =O, =S, =N(R) 14 ) and -CN; or Two R atoms connected to the same atom 4 Together they form a group selected from the following: =O, =S, and =N(R) 14 );or Two R atoms connected to the same or adjacent atoms 4 Together with the carbon atoms they are attached to, they form groups selected from the following: 4- to 8-membered heterocycles and C. 3-8 A carbon ring, wherein any of the carbon rings may optionally be substituted by one or more substituents independently selected from the following: halogen, C 1-4 Alkyl, C 1-4 Halogenated alkyl groups, -OR 14 -SR 14 -N(R) 14 2. -NO2 and -CN.

[0122] In some embodiments, for compounds or salts of formula (I), (II), (II-A), (III), (III-A), or (III-B), R 4 Select independently in each case: Halogen, -OR 14 -SR 14 -N(R) 14 )2、-C(O)R 14 -C(O)N(R) 14 )2、-N(R 14 )C(O)R 14 -C(O)OR 14 -OC(O)R 14 -NO2 and -CN; and C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 The alkynyl group, wherein any one of them is optionally substituted by one or more substituents selected from: halogen, -OR 14 -SR 14 -N(R) 14 )2、-C(O)R 14 -C(O)N(R) 14 )2、-N(R 14 )C(O)R 14 -C(O)OR 14 -OC(O)R 14 -NO2, =O, =S, =N(R) 14 ) and -CN; or Two R atoms connected to the same atom 4Together they form a group selected from the following: =O, =S, and =N(R) 14 );or Two R atoms connected to the same or adjacent atoms 4 Together with the carbon atoms they are attached to, they form groups selected from the following: 4- to 8-membered heterocycles and C. 3-8 A carbon ring, wherein any of the carbon rings may optionally be substituted by one or more substituents independently selected from the following: halogen, C 1-4 Alkyl, C 1-4 Halogenated alkyl groups, -OR 14 -SR 14 -N(R) 14 )2, -NO2 and -CN; and R 14 Each time it appears, it is independently selected from hydrogen, C 1-4 Alkyl, C 3-8 Carbon rings, 4- to 8-membered heterocycles and C 1-4 Halogenated alkyl groups.

[0123] In some embodiments, for compounds or salts of formula (I), (II), (II-A), (III), (III-A), or (III-B), R 4 Select independently in each case: Halogen, -OR 14 -N(R) 14 )2、-C(O)R 14 -C(O)N(R) 14 )2 and -CN; and C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 The alkynyl group, wherein any one of them is optionally substituted by one or more substituents selected from: halogen, -OR 14 -N(R) 14 )2、-C(O)R 14 -C(O)N(R) 14 )2、-N(R 14 )C(O)R 14 =O and -CN; or Two R atoms connected to the same atom 4 Together they form a group selected from the following: =O, =S, and =N(R) 14 );or Two R atoms connected to the same or adjacent atoms 4 Together with the carbon atoms they are attached to, they form groups selected from the following: 4- to 8-membered heterocycles and C. 3-8 A carbon ring, wherein any of the carbon rings may optionally be substituted by one or more substituents independently selected from the following: halogen, C 1-4Alkyl, C 1-4 Halogenated alkyl groups, -OR 14 -N(R) 14 )2 and -CN.

[0124] In some embodiments, for compounds or salts of formula (I), (II), (II-A), (III), (III-A), or (III-B), R 4 Select independently in each case: Halogen, -OR 14 -SR 14 -N(R) 14 )2、-CN、C 1-6 Alkyl, C 2-6 alkenyl and C 2-6 alkynyl group, wherein the C 1-6 Alkyl, C 2-6 alkenyl and C 2-6 Each of the alkynyl groups is optionally surrounded by one or more groups selected from halogens, -OR 14 -N(R) 14 )2. Substitution by =O and -CN substituents; or Two R atoms connected to the same atom 4 Together to form = O; or Two R atoms connected to the same or adjacent atoms 4 Together with the carbon atoms they are attached to, they form heterocycles selected from 4- to 8-membered rings and C. 3-8 The group of the carbon ring; and R 14 Selected from hydrogen and C 1-4 alkyl.

[0125] In some embodiments, for compounds or salts of formula (I), (II), (II-A), (III), (III-A), or (III-B), R 4 Select independently in each case: Halogen, -OR 14 C 1-6 Alkyl and C 2-6 alkynyl group; or Two R atoms connected to the same atom 4 Together to form = O; or Two R atoms connected to the same or adjacent atoms 4 Together with the carbon atoms they are attached to, they form heterocycles selected from 4- to 8-membered rings and C. 3-8 The group of the carbon ring; and R 14 Selected from hydrogen and C 1-4 alkyl.

[0126] In some embodiments, for compounds or salts of formula (I), (II), (II-A), (III), (III-A), or (III-B), R 4 Select independently in each case: Halogen, -OH, C 1-6 Alkyl and C 2-6 alkynyl group; or Two R atoms connected to the same atom 4 Together to form = O; or Two R atoms connected to the same or adjacent atoms 4 Together with the carbon they are attached to, they form C 3-8 Carbon ring.

[0127] In some embodiments, for compounds or salts of formula (I), (II), (II-A), (III), (III-A), or (III-B), R 4 Select independently in each case: Halogen, -OR 14 -SR 14 -N(R) 14 )2、-C(O)R 14 -C(O)N(R) 14 )2、-N(R 14 )C(O)R 14 -C(O)OR 14 -OC(O)R 14 -NO2 and -CN; and C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 The alkynyl group, wherein any one of them is optionally substituted by one or more substituents selected from: halogen, -OR 14 -SR 14 -N(R) 14 )2、-C(O)R 14 -C(O)N(R) 14 )2、-N(R 14 )C(O)R 14 -C(O)OR 14 -OC(O)R 14 -NO2, =O, =S, =N(R) 14 ) and -CN.

[0128] In some embodiments, for compounds or salts of formula (I), (II), (II-A), (III), (III-A), or (III-B), R 4 Select independently in each case: Halogen, -OR14 -N(R) 14 )2、-C(O)R 14 -C(O)N(R) 14 )2 and -CN; and C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 The alkynyl group, wherein any one of them is optionally substituted by one or more substituents selected from: halogen, -OR 14 -N(R) 14 )2、-C(O)R 14 -C(O)N(R) 14 )2、-N(R 14 )C(O)R 14 =O and -CN.

[0129] In some embodiments, for compounds or salts of formula (I), (II), (II-A), (III), (III-A), or (III-B), R 4 In each case, it is independently selected from halogen, -OR 14 -SR 14 -N(R) 14 )2、-CN、C 1-6 Alkyl, C 2-6 alkenyl and C 2-6 alkynyl group, wherein the C 1-6 Alkyl, C 2-6 alkenyl and C 2-6 Each of the alkynyl groups is optionally surrounded by one or more groups selected from halogens, -OR 14 -N(R) 14 )2. Substituent substitutions of =O and -CN. In some embodiments, R 4 In each case, it is independently selected from halogen, -OR 14 C 1-6 Alkyl and C 2-6 Alkyne group. In some embodiments, R 4 In each case, it is independently selected from halogen, -OH, C. 1-6 Alkyl and C 2-6 Alkyne group.

[0130] In some embodiments, for compounds or salts of formula (I), (II), (II-A), (III), (III-A), or (III-B), R 4 In each case, it is independently selected from halogen, -OR 14 -SR 14 -N(R) 14 )2、-C(O)R 14 -C(O)N(R)14 )2、-N(R 14 )C(O)R 14 -C(O)OR 14 -OC(O)R 14 -NO2 and -CN. In some implementations, R 4 In each case, it is independently selected from halogen, -OR 14 -N(R) 14 )2、-C(O)R 14 -C(O)N(R) 14 )2 and -CN. In some implementations, R 4 In each case, it is independently selected from halogen, -OR 14 -SR 14 -N(R) 14 )2 and -CN. In some implementations, R 4 In each case, the halogen and -OR are selected independently. 14 In some implementations, R 4 It is a halogen. In some implementations, R 4 In each case, the fluorine, chlorine, and bromine are selected independently.

[0131] In some implementations, compounds or salts of formula (II) are represented by the structure of formula (IV): (IV); Or a pharmaceutically acceptable salt thereof, wherein A 2 R 1 R 5 L and L are each defined as in equation (II).

[0132] In some embodiments, compounds or salts of formula (II) are represented by the structure of formula (IV-A): (IV-A); Or a pharmaceutically acceptable salt thereof, wherein A 2 R 1 R 5 L and L are each defined as in equation (II).

[0133] In some embodiments, compounds or salts of formula (II) are represented by the structure of formula (IV-B): (IV-B); Or a pharmaceutically acceptable salt thereof, wherein A 2 R 1 R 5 L and L are each defined as in equation (II).

[0134] In some embodiments, for compounds or salts of formula (I), (II), (II-A), (III), (III-A), (III-B), (IV), (IV-A), or (IV-B), R 1 Selected from hydrogen, halogens, -OR 10 -N(R) 10 )2, -NO2, -CN; and C 1-6 Alkyl group, optionally composed of one or more elements independently selected from halogens, -OR 10 and -N(R) 10 Substituents of )2. In some embodiments, R 1 Selected from hydrogen, halogens, -OR 10 -N(R) 10 )2, -CN; and C 1-6 Alkyl group, optionally composed of one or more elements independently selected from halogens, -OR 10 and -N(R) 10 Substituents of )2. In some embodiments, R 1 Selected from hydrogen, -OR 10 and -CN; and C 1-6 Alkyl groups, optionally surrounded by one or more -OR 10 Replacement. In some implementations, R 1 Selected from hydrogen, methoxy, -CN, methyl, ethyl, and (methoxy)methyl. In some embodiments, R 1 It is hydrogen. In some implementations, R 1 Selected from methoxy, -CN, methyl, ethyl and (methoxy)methyl.

[0135] In some embodiments, for compounds or salts of formula (I), (II), (II-A), (III), (III-A), (III-B), (IV), (IV-A), or (IV-B), R 1 Selected from hydrogen, halogens, -OR 10 -CN; and C 1-6 Alkyl group, optionally composed of one or more elements independently selected from halogens, -OR 10 Substituents are substituted. In some embodiments, R 1 Selected from hydrogen, fluorine, methoxy, -CN, methyl, ethyl, (methoxy)methyl and .

[0136] In some embodiments, compounds or salts of formula (II) are represented by the structure of formula (V): (V); Or a pharmaceutically acceptable salt thereof, wherein A 2R 5 L and L are each defined as in equation (II).

[0137] In some embodiments, compounds or salts of formula (II) are represented by the structure of formula (VA): (VA); Or a pharmaceutically acceptable salt thereof, wherein A 2 R 5 L and L are each defined as in equation (II).

[0138] In some implementations, compounds or salts of formula (II) are represented by the structure of formula (VB): (VB); Or a pharmaceutically acceptable salt thereof, wherein A 2 R 5 L and L are each defined as in equation (II).

[0139] In some embodiments, for compounds or salts of formula (I), (II), (II-A), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), or (VB), A 2 Selected from (i), (ii) and (iii): (i) Hydrogen, halogens, C 1-4 Halogenated alkyl groups, -OR 11 -SR 11 -N(R) 11 )2、-C(O)N(R 11 )2、-N(R 11 )C(O)R 11 -C(O)OR 11 -OC(O)R 11 -N(R) 11 )C(O)OR 11 -OC(O)N(R) 11 )2、-N(R 11 )C(O)N(R 11 )2、-S(O)R 11 -S(O)2R 11 -N(R) 11 )S(O)2R 11 -S(O)2N(R) 11 2. -NO2 and -CN; (ii) C 1-6 Alkyl, C 2-6 alkenyl and C 2-6Alkyne group, wherein any of them may optionally be substituted by one or more substituents independently selected from: halogen, -OR 11 -SR 11 -N(R) 11 )2、-C(O)N(R 11 )2、-N(R 11 )C(O)R 11 -C(O)OR 11 -OC(O)R 11 -N(R) 11 )C(O)OR 11 -OC(O)N(R) 11 )2、-N(R 11 )C(O)N(R 11 )2、-S(O)R 11 -S(O)2R 11 -N(R) 11 )S(O)2R 11 -S(O)2N(R) 11 )2、-NO2、=O、=S、=N(R 11 ) and -CN; and (iii) 5-10 yuan heterocyclic rings and C 3-10 The carbon ring, wherein any one of them is optionally substituted by one or more substituents independently selected from the following: Halogen, -OR 11 -SR 11 -N(R) 11 )2、-C(O)R 11 -C(O)N(R) 11 )2、-N(R 11 )C(O)R 11 -N(R) 11 )S(O)2R 11 -C(O)OR 11 -OC(O)R 11 -N(R) 11 )C(O)OR 11 -OC(O)N(R) 11 )2、-N(R 11 )C(O)N(R 11 )2、-S(O)R 11 -S(O)2R 11 -S(O)2N(R) 11 )2、-NO2、=O、=S、=N(R 11 ) and -CN; C 1-6 Alkyl, C 2-6 alkenyl and C 3-6Alkyne group, wherein any of them may optionally be substituted by one or more substituents independently selected from: halogen, -OR 11 -SR 11 -N(R) 11 )2、-C(O)R 11 -C(O)N(R) 11 )2、-N(R 11 )C(O)R 11 -C(O)OR 11 -OC(O)R 11 -N(R) 11 )C(O)OR 11 -OC(O)N(R) 11 )2、-N(R 11 )C(O)N(R 11 )2、-S(O)R 11 -S(O)2R 11 -N(R) 11 )S(O)2R 11 -S(O)2N(R) 11 )2、-NO2、=O、=S、=N(R 11 ) and -CN; and C 3-10 Carbon rings and 4- to 10-membered heterocycles; wherein the C 3-10 The carbocyclic ring and the 4- to 10-membered heterocycle are each optionally substituted by one or more substituents independently selected from the following: Halogen, -OR 11 -N(R) 11 )2、-C(O)R 11 -C(O)N(R) 11 )2、-N(R 11 )C(O)R 11 -C(O)OR 11 -OC(O)R 11 -NO2, =O, =S, =N(R) 11 ) and -CN; C 1-6 Alkyl, C 2-6 alkenyl and C 3-6 Alkyne group, wherein any of them may optionally be substituted by one or more substituents independently selected from: halogen, -OR 11 -SR 11 -N(R) 11 )2、-C(O)R 11 -C(O)N(R) 11 )2、-N(R 11 )C(O)R 11 -N(R)11 )S(O)2R 11 -C(O)OR 11 -OC(O)R 11 -NO2, =O, =S, =N(R) 11 ) and -CN.

[0140] In some embodiments, for compounds or salts of formula (I), (II), (II-A), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), or (VB), A 2 Selected from (i), (ii) and (iii): (i) Hydrogen, halogens, -OR 11 -N(R) 11 )2、-C(O)N(R 11 )2、-N(R 11 )C(O)R 11 -N(R) 11 )S(O)2R 11 -S(O)2N(R) 11 2. -NO2 and -CN; (ii) C 1-6 Alkyl, C 2-6 alkenyl and C 2-6 Alkyne group, wherein any of them may optionally be substituted by one or more substituents independently selected from: halogen, -OR 11 -N(R) 11 )2、-C(O)N(R 11 )2、-N(R 11 )C(O)R 11 -N(R) 11 )S(O)2R 11 -S(O)2N(R) 11 )2, -NO2, =O and -CN; and (iii) 5-10 yuan heterocyclic rings and C 3-10 The carbon ring, wherein any one of them is optionally substituted by one or more substituents independently selected from the following: Halogen, -OR 11 -N(R) 11 )2、-C(O)R 11 -C(O)N(R) 11 )2、-N(R 11 )C(O)R 11 -N(R) 11 )S(O)2R 11 -NO2, =O, and -CN; C 1-6Alkyl, C 2-6 alkenyl and C 3-6 Alkyne group, wherein any of them may optionally be substituted by one or more substituents independently selected from: halogen, -OR 11 -N(R) 11 )2、-C(O)R 11 -C(O)N(R) 11 )2、-N(R 11 )C(O)R 11 -N(R) 11 )S(O)2R 11 -NO2, -NO2, =O and -CN; and C 3-10 A carbocyclic ring and a 4- to 10-membered heterocycle, either of which may optionally be substituted by one or more substituents independently selected from the following: halogen, -OR 11 -N(R) 11 )2、-C(O)R 11 -C(O)N(R) 11 )2、-N(R 11 )C(O)R 11 -NO2, =O, -CN; C 1-6 Alkyl, C 2-6 alkenyl and C 2-6 alkynyl group, the C 1-6 Alkyl, C 2-6 alkenyl and C 3-6 Each alkynyl group may optionally be substituted by one or more substituents independently selected from the following: halogen, -OR 11 -N(R) 11 )2、-C(O)R 11 -C(O)N(R) 11 )2、-N(R 11 )C(O)R 11 -N(R) 11 )S(O)2R 11 -NO2, =O, and -CN.

[0141] In some embodiments, for compounds or salts of formula (I), (II), (II-A), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), or (VB), A 2 Selected from: C 1-6 Alkyl, C 2-6 alkenyl and C 2-6 Alkyne group, wherein any of them may optionally be substituted by one or more substituents independently selected from: halogen, -OR 11 -N(R)11 )2、-C(O)N(R 11 )2、-N(R 11 )C(O)R 11 -N(R) 11 )S(O)2R 11 -S(O)2N(R) 11 )2, -NO2, =O and -CN; and 5 to 10 yuan heterocyclic rings and C 3-10 The carbon ring, wherein any one of them is optionally substituted by one or more substituents independently selected from the following: Halogen, -OR 11 -N(R) 11 )2、-C(O)R 11 -C(O)N(R) 11 )2、-N(R 11 )C(O)R 11 -N(R) 11 )S(O)2R 11 -NO2, =O, and -CN; C 1-6 Alkyl, C 2-6 alkenyl and C 3-6 Alkyne group, wherein any of them may optionally be substituted by one or more substituents independently selected from: halogen, -OR 11 -N(R) 11 )2、-C(O)R 11 -C(O)N(R) 11 )2、-N(R 11 )C(O)R 11 -N(R) 11 )S(O)2R 11 -NO2, -NO2, =O and -CN; and C 3-10 A carbocyclic ring and 3- to 10-membered heterocycles, any of which may optionally be substituted by one or more substituents independently selected from the following: halogen, -OR 11 -N(R) 11 )2、-C(O)R 11 -C(O)N(R) 11 )2、-N(R 11 )C(O)R 11 -NO2, =O, -CN; C 1-6 Alkyl, C 2-6 alkenyl and C 2-6 alkynyl group, the C 1-6 Alkyl, C 2-6 alkenyl and C 3-6Each alkynyl group may optionally be substituted by one or more substituents independently selected from the following: halogen, -OR 11 -N(R) 11 )2、-C(O)R 11 -C(O)N(R) 11 )2、-N(R 11 )C(O)R 11 -N(R) 11 )S(O)2R 11 -NO2, =O, and -CN.

[0142] In some embodiments, for compounds or salts of formula (I), (II), (II-A), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), or (VB), A 2 Selected from: C 1-6 Alkyl and C 2-6 Alkyne groups, wherein each is optionally selected independently by one or more groups from halogens, -OR 11 -N(R) 11 )2、-C(O)N(R 11 )2、-N(R 11 )C(O)R 11 -N(R) 11 )S(O)2R 11 -S(O)2N(R) 11 Substitution by substituents of -NO2, =O, and -CN; and 5 to 10 yuan heterocyclic rings and C 3-10 The carbon ring, wherein any one of them is optionally substituted by one or more substituents independently selected from the following: Halogen, -OR 11 -N(R) 11 )2、-C(O)R 11 -C(O)N(R) 11 )2、-N(R 11 )C(O)R 11 -N(R) 11 )S(O)2R 11 -NO2, =O, and -CN; C 1-6 Alkyl, C 2-6 alkenyl and C 2-6 Alkyne group, wherein any of them may optionally be substituted by one or more substituents independently selected from: halogen, -OR 11 -N(R) 11 )2、-C(O)R 11 -C(O)N(R)11 )2、-N(R 11 )C(O)R 11 -N(R) 11 )S(O)2R 11 -NO2, =O and -CN; and C 3-8 A carbocyclic ring and a 4- to 10-membered heterocycle, either of which may optionally be substituted by one or more substituents independently selected from the following: halogen, -OR 11 -N(R) 11 )2、-C(O)R 11 -C(O)N(R) 11 )2、-N(R 11 )C(O)R 11 -NO2, =O, -CN; C 1-6 Alkyl, C 2-6 alkenyl and C 2-6 alkynyl group, the C 1-6 Alkyl, C 2-6 alkenyl and C 2-6 Each alkynyl group may optionally be substituted by one or more substituents independently selected from the following: halogen, -OR 11 -N(R) 11 )2、-C(O)R 11 -C(O)N(R) 11 )2、-N(R 11 )C(O)R 11 -N(R) 11 )S(O)2R 11 -NO2, =O, and -CN.

[0143] In some embodiments, for compounds or salts of formula (I), (II), (II-A), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), or (VB), A 2 Selected from C 1-6 Alkyl and C 2-6 Alkyne groups, wherein each is optionally selected independently by one or more groups from halogens, -OR 11 -N(R) 11 )2、-C(O)N(R 11 )2、-N(R 11 )C(O)R 11 -N(R) 11 )S(O)2R 11 -S(O)2N(R) 11 )2. Substituents of -NO2, =O, and -CN. In some embodiments, A 2 Selected from C1-6 Alkyl and C 2-6 Alkyne groups, wherein each is optionally selected independently by one or more groups from halogens, -OR 11 -N(R) 11 )2. Substituents of -NO2, =O, and -CN. In some embodiments, A 2 Selected from C 1-4 Alkyl and C 2-4 Alkyne groups, wherein each is optionally selected independently by one or more groups from halogens, -OR 11 -N(R) 11 )2. Substituents of -NO2, =O, and -CN. In some embodiments, A 2 Selected from C 1-4 Alkyl and C 2-4 Alkyne groups, wherein each is optionally selected independently by one or more groups from halogens, -OR 11 and -N(R) 11 Substituents of )2. In some embodiments, A 2 Selected from C 1-4 Alkyl and C 2-4 Alkyne groups, wherein each is optionally selected independently by one or more groups from -OR 11 and -N(R) 11 Substituents of )2. In some embodiments, A 2 Selected from methyl, ethyl, propyl, isopropyl, ethynyl, propynyl, and isopropynyl, wherein each is optionally selected independently by one or more elements selected from halogen, -OR 11 -N(R) 11 )2. Substituents of -NO2, =O, and -CN. In some embodiments, A 2 Selected from methyl, ethyl, propyl, isopropyl, ethynyl, propynyl, and isopropynyl, wherein each is optionally selected independently by one or more elements selected from halogen, -OR 11 and -N(R) 11 Substituents of )2.

[0144] In some embodiments, for compounds or salts of formula (I), (II), (II-A), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), or (VB), A 2 Selected from: -CH3、 , , , , and .

[0145] In some embodiments, for compounds or salts of formula (I), (II), (II-A), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), or (VB), A 2 Selected from 5- to 10-membered heteroaryl, 5- to 10-membered heterocycloalkyl, C 4-8 Aryl and C 3-10 Cycloalkyl groups, wherein each is optionally substituted by one or more substituents independently selected from the following: Halogen, -OR 11 -SR 11 -N(R) 11 )2、-C(O)R 11 -C(O)N(R) 11 )2、-N(R 11 )C(O)R 11 -N(R) 11 )S(O)2R 11 -C(O)OR 11 -OC(O)R 11 -N(R) 11 )C(O)OR 11 -OC(O)N(R) 11 )2、-N(R 11 )C(O)N(R 11 )2、-S(O)R 11 -S(O)2R 11 -S(O)2N(R) 11 )2、-NO2、=O、=S、=N(R 11 ) and -CN; C 1-6 Alkyl, C 2-6 alkenyl and C 3-6 Alkyne group, wherein any of them may optionally be substituted by one or more substituents independently selected from: halogen, -OR 11 -SR 11 -N(R) 11 )2、-C(O)R 11 -C(O)N(R) 11 )2、-N(R 11 )C(O)R 11 -C(O)OR 11 -OC(O)R 11 -N(R) 11 )C(O)OR 11 -OC(O)N(R) 11 )2、-N(R 11 )C(O)N(R 11)2、-S(O)R 11 -S(O)2R 11 -N(R) 11 )S(O)2R 11 -S(O)2N(R) 11 )2、-NO2、=O、=S、=N(R 11 ) and -CN; and C 3-10 Carbon rings and 4- to 10-membered heterocycles; wherein the C 3-10 The carbocyclic ring and the 4- to 10-membered heterocycle are each optionally substituted by one or more substituents independently selected from the following: halogen, -OR 11 -N(R) 11 )2、-C(O)R 11 -C(O)N(R) 11 )2、-N(R 11 )C(O)R 11 -C(O)OR 11 -OC(O)R 11 -NO2, =O, =S, =N(R) 11 ) and -CN;C 1-6 Alkyl, C 2-6 alkenyl and C 2-6 alkynyl group, the C 1-6 Alkyl, C 2-6 alkenyl and C 2-6 Each alkynyl group may optionally be substituted by one or more substituents independently selected from the following: halogen, -OR 11 -SR 11 -N(R) 11 )2、-C(O)R 11 -C(O)N(R) 11 )2、-N(R 11 )C(O)R 11 -N(R) 11 )S(O)2R 11 -C(O)OR 11 -OC(O)R 11 -NO2, =O, =S, =N(R) 11 ) and -CN.

[0146] In some embodiments, for compounds or salts of formula (I), (II), (II-A), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), or (VB), A 2 Selected from 5- to 10-membered heteroaryl, 5- to 10-membered heterocycloalkyl, C 4-8 Aryl and C 3-10Cycloalkyl groups, wherein each is optionally substituted by one or more substituents independently selected from the following: Halogen, -OR 11 -N(R) 11 )2、-C(O)R 11 -C(O)N(R) 11 )2、-N(R 11 )C(O)R 11 -N(R) 11 )S(O)2R 11 -NO2, =O, and -CN; C 1-6 Alkyl, C 2-6 alkenyl and C 3-6 Alkyne group, wherein any of them may optionally be substituted by one or more substituents independently selected from: halogen, -OR 11 -N(R) 11 )2、-C(O)R 11 -C(O)N(R) 11 )2、-N(R 11 )C(O)R 11 -N(R) 11 )S(O)2R 11 -NO2, -NO2, =O and -CN; and C 3-10 A carbocyclic ring and a 4- to 10-membered heterocycle, either of which may optionally be substituted by one or more substituents independently selected from the following: halogen, -OR 11 -N(R) 11 )2、-C(O)R 11 -C(O)N(R) 11 )2、-N(R 11 )C(O)R 11 -NO2, =O, -CN; C 1-6 Alkyl, C 2-6 alkenyl and C 2-6 alkynyl group, the C 1-6 Alkyl, C 2-6 alkenyl and C 3-6 Each alkynyl group may optionally be substituted by one or more substituents independently selected from the following: halogen, -OR 11 -N(R) 11 )2、-C(O)R 11 -C(O)N(R) 11 )2、-N(R 11 )C(O)R 11 -N(R) 11 )S(O)2R 11 -NO2, =O, and -CN.

[0147] In some embodiments, for compounds or salts of formula (I), (II), (II-A), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), or (VB), A 2 Selected from pyrazolyl, triazolyl, oxazolyl, thiazolyl, morpholinyl, phenyl, and cyclopropyl, wherein each is optionally substituted by one or more substituents independently selected from the following: Halogen, -OR 11 -N(R) 11 )2、-C(O)R 11 -C(O)N(R) 11 )2、-N(R 11 )C(O)R 11 -N(R) 11 )S(O)2R 11 -NO2, =O, and -CN; C 1-6 Alkyl, C 2-6 alkenyl and C 3-6 Alkyne group, wherein any of them may optionally be substituted by one or more substituents independently selected from: halogen, -OR 11 -N(R) 11 )2、-C(O)R 11 -C(O)N(R) 11 )2、-N(R 11 )C(O)R 11 -N(R) 11 )S(O)2R 11 -NO2, -NO2, =O and -CN; and C 3-10 A carbocyclic ring and a 4- to 10-membered heterocycle, either of which may optionally be substituted by one or more substituents independently selected from the following: halogen, -OR 11 -N(R) 11 )2、-C(O)R 11 -C(O)N(R) 11 )2、-N(R 11 )C(O)R 11 -NO2, =O, -CN; C 1-6 Alkyl, C 2-6 alkenyl and C 2-6 alkynyl group, the C 1-6 Alkyl, C 2-6 alkenyl and C 2-6 Each alkynyl group may optionally be substituted by one or more substituents independently selected from the following: halogen, -OR 11 -N(R) 11 )2、-C(O)R11 -C(O)N(R) 11 )2、-N(R 11 )C(O)R 11 -N(R) 11 )S(O)2R 11 -NO2, =O, and -CN.

[0148] In some embodiments, for compounds or salts of formula (I), (II), (II-A), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), or (VB), A 2 Selected from 5- to 10-membered heteroaryl, 5- to 10-membered heterocycloalkyl, C 4-8 Aryl and C 3-10 Cycloalkyl groups, wherein each is optionally substituted by one or more substituents independently selected from the following: Halogen, -OR 11 -N(R) 11 2. -NO2, =O, and -CN; C 1-6 Alkyl group, optionally substituted by one or more substituents independently selected from: halogen, -OR 11 -N(R) 11 )2, -NO2, =O and -CN; and C 3-10 Carbon rings and 4- to 10-membered heterocycles, any of which may optionally be selected independently by one or more halogens, -OR 11 -N(R) 11 )2、-NO2、=O、-CN、C 1-6 Alkyl (C) 1-6 alky) and C 1-6 Substitution of alkyl halogens.

[0149] In some embodiments, for compounds or salts of formula (I), (II), (II-A), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), or (VB), A 2 Selected from pyrazolyl, triazolyl, oxazolyl, thiazolyl, morpholinyl, phenyl, and cyclopropyl, wherein each is optionally substituted by one or more substituents independently selected from the following: Halogen, -OR 11 -N(R) 11 2. -NO2, =O, and -CN; C 1-6 Alkyl group, optionally substituted by one or more substituents independently selected from: halogen, -OR11 -N(R) 11 )2, -NO2, =O and -CN; and C 3-10 Carbon rings and 4- to 10-membered heterocycles, any of which may optionally be selected independently by one or more halogens, -OR 11 -N(R) 11 )2、-NO2、=O、-CN、C 1-6 Alkyl (C) 1-6 alky) and C 1-6 Substitution of alkyl halogens.

[0150] In some embodiments, for compounds or salts of formula (I), (II), (II-A), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), or (VB), A 2 Selected from: .

[0151] In some embodiments, for compounds or salts of formula (I), (II), (II-A), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), or (VB), A 2 Selected from: .

[0152] In some embodiments, for compounds or salts of formula (I), (II), (II-A), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), or (VB), A 2 It is a 5- to 10-membered heterocycle optionally substituted by one or more substituents independently selected from (i), (ii), and (iii): (i) Halogens, -OR 11 -N(R) 11 )2、-C(O)R 11 -C(O)N(R) 11 )2、-N(R 11 )C(O)R 11 -N(R) 11 )S(O)2R 11 =O and -CN; (ii) C 1-6 Alkyl, C 2-6 alkenyl and C 3-6Alkyne group, wherein any of them may optionally be substituted by one or more substituents independently selected from: halogen, -OR 11 -N(R) 11 )2、-C(O)R 11 -C(O)N(R) 11 )2、-N(R 11 )C(O)R 11 -N(R) 11 )S(O)2R 11 -NO2, =O and -CN; and (ⅲ) C 3-10 The carbon ring and 4- to 10-membered heterocycles, each of which may be optionally substituted by one or more substituents independently selected from the following: Halogen, -OR 11 -N(R) 11 )2、-C(O)R 11 -C(O)N(R) 11 )2、-N(R 11 )C(O)R 11 =O and -CN; and C 1-6 Alkyl, C 2-6 alkenyl and C 3-6 Alkyne group, wherein any of them may optionally be substituted by one or more substituents independently selected from: halogen, -OR 11 -N(R) 11 )2、-C(O)R 11 -C(O)N(R) 11 )2、-N(R 11 )C(O)R 11 -N(R) 11 )S(O)2R 11 =O and -CN.

[0153] In some embodiments, for compounds or salts of formula (I), (II), (II-A), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), or (VB), A 2 Selected from 5- to 10-membered heterocycles and C 3-10 The carbocyclic ring, wherein any one of them is optionally substituted by one or more substituents independently selected from (i), (ii) and (iii): (i) Halogens, -OR 11 -SR 11 -N(R) 11 )2、-C(O)R 11 -C(O)N(R) 11 )2、-N(R11 )C(O)R 11 -N(R) 11 )S(O)2R 11 -C(O)OR 11 -OC(O)R 11 -N(R) 11 )C(O)OR 11 -OC(O)N(R) 11 )2、-N(R 11 )C(O)N(R 11 )2、-S(O)R 11 -S(O)2R 11 -S(O)2N(R) 11 )2、-NO2、=O、=S、=N(R 11 ) and -CN; (ii) C 1-6 Alkyl, C 2-6 alkenyl and C 3-6 Alkyne group, wherein any of them may optionally be substituted by one or more substituents independently selected from: halogen, -OR 11 -SR 11 -N(R) 11 )2、-C(O)R 11 -C(O)N(R) 11 )2、-N(R 11 )C(O)R 11 -C(O)OR 11 -OC(O)R 11 -N(R) 11 )C(O)OR 11 -OC(O)N(R) 11 )2、-N(R 11 )C(O)N(R 11 )2、-S(O)R 11 -S(O)2R 11 -N(R) 11 )S(O)2R 11 -S(O)2N(R) 11 )2、-NO2、=O、=S、=N(R 11 ) and -CN; and (ⅲ) C 3-10 Carbon rings and 4- to 10-membered heterocycles; wherein the C 3-10 The carbocyclic ring and the 4- to 10-membered heterocycle are each optionally substituted by one or more substituents independently selected from the following: Halogen, -OR 11 -N(R) 11 )2、-C(O)R 11-C(O)N(R) 11 )2、-N(R 11 )C(O)R 11 -C(O)OR 11 -OC(O)R 11 -NO2, =O, =S, =N(R) 11 ) and -CN; C 1-6 Alkyl, C 2-6 alkenyl and C 3-6 Alkyne group, wherein any of them may optionally be substituted by one or more substituents independently selected from: halogen, -OR 11 -SR 11 -N(R) 11 )2、-C(O)R 11 -C(O)N(R) 11 )2、-N(R 11 )C(O)R 11 -N(R) 11 )S(O)2R 11 -C(O)OR 11 -OC(O)R 11 -NO2, =O, =S, =N(R) 11 ) and -CN; and R 11 Each time it appears, it is independently selected from hydrogen, C 1-4 Alkyl, C 3-8 Carbon rings, 4- to 8-membered heterocycles and C 1-4 Halogenated alkyl groups.

[0154] In some embodiments, for compounds or salts of formula (I), (II), (II-A), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), or (VB), A 2 Selected from 5- to 10-membered heterocycles and C 3-10 The carbocyclic ring, wherein any one of them is optionally substituted by one or more substituents independently selected from (i), (ii) and (iii): (i) Halogens, -OR 11 -N(R) 11 )2、-C(O)R 11 -C(O)N(R) 11 )2、-N(R 11 )C(O)R 11 -N(R) 11 )S(O)2R 11 =O and -CN; (ii) C 1-6 Alkyl, C2-6 alkenyl and C 3-6 Alkyne group, wherein any of them may optionally be substituted by one or more substituents independently selected from: halogen, -OR 11 、N(R 11 )2、-C(O)R 11 -C(O)N(R) 11 )2、-N(R 11 )C(O)R 11 -N(R) 11 )S(O)2R 11 -NO2, =O and -CN; and (ⅲ) C 3-10 Carbon rings and 4- to 10-membered heterocycles; wherein the C 3-10 The carbocyclic ring and the 4- to 10-membered heterocycle are each optionally substituted by one or more substituents independently selected from the following: Halogen, -OR 11 -N(R) 11 )2、-C(O)R 11 -C(O)N(R) 11 )2、-N(R 11 )C(O)R 11 =O and -CN; and C 1-6 Alkyl, C 2-6 alkenyl and C 3-6 Alkyne group, wherein any of them may optionally be substituted by one or more substituents independently selected from: halogen, -OR 11 -N(R) 11 )2、-C(O)R 11 -C(O)N(R) 11 )2、-N(R 11 )C(O)R 11 -N(R) 11 )S(O)2R 11 =O and -CN.

[0155] In some embodiments, for compounds or salts of formula (I), (II), (II-A), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), or (VB), A 2 Selected from 5- to 10-membered heterocycles optionally substituted by one or more substituents independently selected from (i), (ii), and (iii): (i) Halogens, -OR 11 -N(R) 11 )2、-C(O)R 11 -C(O)N(R) 11)2、-N(R 11 )C(O)R 11 =O and -CN; (ii) C 1-6 Alkyl group, optionally substituted by one or more substituents independently selected from: halogen, -OR 11 -N(R) 11 )2、-C(O)R 11 -C(O)N(R) 11 )2、-N(R 11 )C(O)R 11 and = O; and (ⅲ) C 3-10 Carbon rings and 4- to 10-membered heterocycles; wherein the C 3-10 The carbocyclic ring and the 4- to 10-membered heterocycle are each optionally substituted by one or more substituents independently selected from the following: halogen, -OR 11 -N(R) 11 )2、-C(O)R 11 -C(O)N(R) 11 )2、-N(R 11 )C(O)R 11 =O and -CN; and C 1-6 Alkyl, the C 1-6 The alkyl group is optionally substituted by one or more substituents independently selected from the following: halogen, -OR 11 -N(R) 11 )2、-C(O)R 11 -C(O)N(R) 11 )2、-N(R 11 )C(O)R 11 And = O.

[0156] In some embodiments, for compounds or salts of formula (I), (II), (II-A), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), or (VB), A 2 Selected from 5- to 10-membered heterocycles and C 3-10 Carbon rings, wherein any one of them is optionally selected independently from halogens, -OR 11 C 1-6 Alkyl, C 1-6 Haloalkyl, C 3-10 Substitution of the carbocyclic ring and 4- to 10-membered heterocycles; wherein the C 3-10 The carbon ring and the 3- to 10-membered heterocycle are each optionally separated by one or more C rings. 1-6 Alkyl substitution.

[0157] In some embodiments, for compounds or salts of formula (I), (II), (II-A), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), or (VB), A 2 It is a 5- to 10-membered heterocycle optionally substituted with one or more substituents independently selected from the following: halogen, -OR 11 -N(R) 11 )2、-C(O)R 11 -C(O)N(R) 11 )2、-N(R 11 )C(O)R 11 =O and -CN; and C 1-6 Alkyl group, optionally composed of one or more elements independently selected from halogens, -OR 11 -N(R) 11 )2、-C(O)R 11 -C(O)N(R) 11 )2、-N(R 11 )C(O)R 11 Substituents of =O are used. In some embodiments, A 2 Selected from 5- to 10-membered heterocycles and C 3-10 A carbon ring, wherein any of the carbon rings may optionally be substituted by one or more substituents independently selected from the following: halogen, C 1-6 Alkyl, C 1-6 Halogenated alkyl groups and 4- to 10-membered heterocycles; wherein the 4- to 10-membered heterocycle is optionally separated by one or more C groups. 1-6 Alkyl substitution. In some embodiments, A 2 It is a 5- to 10-membered heterocycle optionally substituted with one or more substituents independently selected from the following: halogen, -OR 11 -N(R) 11 )2、-C(O)R 11 -C(O)N(R) 11 )2、-N(R 11 )C(O)R 11 =O and -CN; and C 1-6 Alkyl group, optionally composed of one or more elements independently selected from halogens, -OR 11 and -N(R) 11 Substituents of )2. In some embodiments, A 2 Selected from 5- to 10-membered heterocycles and C 3-10 Carbon rings, wherein any one of them is optionally selected independently from halogens, C 1-6 Alkyl and C 1-6 Substituents of haloalkyl groups. In some embodiments, A 2It is a 5- to 10-membered heterocycle optionally substituted with one or more substituents independently selected from the following: halogens; and C 1-6 Alkyl group, optionally substituted by one or more substituents independently selected from halogens. In some embodiments, A 2 It is a 5- to 10-membered heterocycle optionally substituted with one or more substituents independently selected from the following: halogen, C 1-6 Alkyl and C 1-6 Halogenated alkyl groups. In some embodiments, A 2 It is a 5- to 10-membered heterocycle optionally substituted with one or more substituents independently selected from the following: halogen. In some embodiments, A 2 It is a 5- to 10-membered heterocycle optionally substituted with one or more substituents independently selected from the following: fluorine. In some embodiments, A 2 It is a 5- to 10-membered heteroaryl group that is optionally substituted. In some embodiments, A 2 It is an optionally substituted 5-membered heteroaryl group. In some embodiments, A 2 Selected from optionally substituted pyrazolyl groups and optionally substituted triazole groups. In some embodiments, A 2 Selected from , , and In some implementations, A2 is selected from... , and .

[0158] In some embodiments, for compounds or salts of formula (I), (II), (II-A), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), or (VB), A 2 Selected from , , and .

[0159] In some embodiments, for compounds or salts of formula (I), (II), (II-A), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), or (VB), L is derived from -L 1 -L 2 -L 3 -L 4 - indicates that L 1 L 2 L 3 and L 4Each is independently selected from (a) and (b): (a) -O-、-N(R 15 )-, -S-, -S(O)-, -S(O)2-, -S(O)(NR 15 )-、-N(R 15 )C(O)-、-N(R 15 )C(O)O-、-N(R 15 )S(O)2-、-N(R 15 )S(O)2N(R 15 )-、-S(O)(NR 15 )N(R 15 )-、-N(R 15 )N(R 15 )-、-(R 15 )NC(O)N(R 15 )- and -(R 15 )NC(O)N(R 15 )N(R 15 )-;and (b) C 1-6 Alkylene, C 2-6 imidene group, C 2-6 Ethyne group, C 3-8 Carbocyclic and 4- to 8-membered heterocyclic groups, either of which may optionally be substituted by one or more substituents independently selected from: halogen, -OR 15 -SR 15 =O, =S, and -CN; Where L 2 L 3 and L 4 Each of them arbitrarily does not exist; and Where L 1 L 2 L 3 and L 4 No more than two are selected from (a), and the two selected are not adjacent.

[0160] In some embodiments, for compounds or salts of formula (I), (II), (II-A), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), or (VB), L is derived from -L 1 -L 2 -L 3 -L 4 - indicates that L 1 L 2 L 3 and L 4 Each is independently selected from (a) and (b): (a) -O-、-N(R 15 )-, -S-, -S(O)-, -S(O)2-, -S(O)(NR 15 )-、-N(R 15 )C(O)-、-N(R 15 )C(O)O-、-N(R 15 )S(O)2-、-N(R 15 )S(O)2N(R 15 )-、-S(O)(NR 15 )N(R 15 )-、-N(R 15 )N(R 15 )-、-(R 15 )NC(O)N(R 15 )- and -(R 15 )NC(O)N(R 15 )N(R 15 )-;and (b) C 1-6 Alkylene, C 2-6 imidene group, C 2-6 Ethyne group, C 3-8 Carbocyclic and 4- to 8-membered heterocyclic groups, either of which may optionally be substituted by one or more substituents independently selected from: halogen, -OR 15 -SR 15 =O, =S, and -CN; and R 15 Each time it appears, it is independently selected from hydrogen and C. 1-4 Alkyl, C 3-8 Carbon rings, 4- to 8-membered heterocycles and C 1-4 Halogenated alkyl groups; Where L 2 L 3 and L 4 Each of them arbitrarily does not exist; and Where L 1 L 2 L 3 and L 4 No more than two are selected from (a), and the two selected are not adjacent.

[0161] In some embodiments, for compounds or salts of formula (I), (II), (II-A), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), or (VB), L is derived from -L 1 -L 2 -L 3 -L 4- indicates that L 1 L 2 L 3 and L 4 Each is independently selected from (a) and (b): (a) -O-、-N(R 15 )-、-S-、-N(R 15 )C(O)-、-N(R 15 )C(O)O-、-N(R 15 S(O)2、-N(R) 15 )N(R 15 )- and -(R 15 )NC(O)N(R 15 )-;and (b) C 1-6 Alkylene, C 2-6 imidene group, C 2-6 Ethyne group, C 3-6 Carbocyclic and 4- to 6-membered heterocyclic groups, either of which may optionally be independently selected from halogens, -OR 15 Substitution of =O and -CN groups; Where L 2 L 3 and L 4 Each of them arbitrarily does not exist; and Where L 1 L 2 L 3 and L 4 No more than two are selected from (a), and the two selected are not adjacent.

[0162] In some embodiments, for compounds or salts of formula (I), (II), (II-A), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), or (VB), L is derived from -L 1 -L 2 -L 3 -L 4 - indicates that L 1 L 2 L 3 and L 4 Each is independently selected from (a) and (b): (a) -O-、-N(R 15 - and -N(R) 15 )C(O)-; and (b) C 1-6 Alkylene, C 2-6 etyne and C 3-6 subcarbonyl cyclo group; Where L 2 L 3 and L 4 Each of the two optional locations does not exist; Where L 1 L 2 L 3 and L 4 No more than two are selected from (a), and the two selected are not adjacent; and R 15 Selected from hydrogen and C 1-4 alkyl.

[0163] In some embodiments, for compounds or salts of formula (I), (II), (II-A), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), or (VB), L is derived from -L 1 -L 2 -L 3 -L 4 - indicates that L 1 L 2 L 3 and L 4 Each is independently selected from (a) and (b): (a) -O-、-N(R 15 - and -N(R) 15 )C(O)-; and (b) C 1-6 Alkylene and C 3-6 subcarbonyl cyclo group; Where L 2 L 3 and L 4 Each of the two optional locations does not exist; Where L 1 L 2 L 3 and L 4 No more than two are selected from (a), and the two selected are not adjacent; and R 15 Selected from hydrogen and C 1-4 alkyl.

[0164] In some embodiments, for compounds or salts of formula (I), (II), (II-A), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), or (VB), L is derived from -L 1 -L 2 -L 3 -L 4 - indicates that L1 L 2 L 3 and L 4 Each is independently selected from (a) and (b): (a) -O-, -NH- and -N(H)C(O)-; and (b) Methylene; Where L 2 L 3 and L 4 Each of them arbitrarily does not exist; and Where L 1 L 2 L 3 and L 4 No more than two are selected from (a), and the two selected are not adjacent.

[0165] In some embodiments, for compounds or salts of formula (I), (II), (II-A), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), or (VB), L is derived from -L 1 -L 2 -L 3 -L 4 - indicates that L 2 L 3 and L 4 It does not exist; and L 1 Selected from: (a) -O-、-N(R 15 )-, -S-, -S(O)-, -S(O)2-, -S(O)(NR 15 )-、-N(R 15 )C(O)-、-N(R 15 )C(O)O-、-N(R 15 )S(O)2-、-N(R 15 )S(O)2N(R 15 )-、-S(O)(NR 15 )N(R 15 )-、-N(R 15 )N(R 15 )-、-(R 15 )NC(O)N(R 15 )- and -(R 15 )NC(O)N(R 15 )N(R 15 )-;and (b) C 1-6 Alkylene, C 2-6 imide and C 2-6 Alynyl group.

[0166] In some embodiments, for compounds or salts of formula (I), (II), (II-A), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), or (VB), L is derived from -L 1 -L 2 -L 3 -L 4 - indicates that L 2 L 3 and L 4 It does not exist; and L 1 Selected from: (a) -O-、-N(R 15 )-, -S-, -S(O)-, -S(O)2-, -S(O)(NR 15 )-、-N(R 15 )C(O)-、-N(R 15 )C(O)O-、-N(R 15 )S(O)2-、-N(R 15 )S(O)2N(R 15 )-、-S(O)(NR 15 )N(R 15 )-、-N(R 15 )N(R 15 )-、-(R 15 )NC(O)N(R 15 )- and -(R 15 )NC(O)N(R 15 )N(R 15 )-;and (b) C 1-6 Alkylene, C 2-6 imidene group, C 2-6 etyne group; and R 15 Selected from hydrogen and C 1-4 Alkyl and C 1-4 Halogenated alkyl groups.

[0167] In some embodiments, for compounds or salts of formula (I), (II), (II-A), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), or (VB), L is derived from -L 1 -L 2 -L 3 -L 4 - indicates that L 2 L 3 and L 4It does not exist; and L 1 Selected from -N(R) 15 - and -N(R) 15 )C(O)-. In some implementations, L is composed of -L 1 -L 2 -L 3 -L 4 - indicates that L 2 L 3 and L 4 It does not exist; and L 1 Selected from -N(R) 15 - and -N(R) 15 )C(O)-; and R 15 Selected from hydrogen and C 1-4 Alkyl group. In some embodiments, L is composed of -L 1 -L 2 -L 3 -L 4 - indicates that L 2 L 3 and L 4 It does not exist; and L 1 Selected from -N(R) 15 - and -N(R) 15 )C(O)-; and R 15 Selected from hydrogen and methyl. In some embodiments, L is composed of -L 1 -L 2 -L 3 -L 4 - indicates that L 2 L 3 and L 4 It does not exist; and L 1 Selected from -N(H)C(O)-.

[0168] In some embodiments, for compounds or salts of formula (I), (II), (II-A), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), or (VB), L is derived from -L 1 -L 2 -L 3 -L 4 - indicates that L 3 and L 4 It does not exist; and L 1 Selected from -O-, -N(R) 15 )-, -S-, -S(O)-, -S(O)2-, -S(O)(NR 15 )-、-N(R 15 )C(O)-、-N(R15 )C(O)O-、-N(R 15 )S(O)2-、-N(R 15 )S(O)2N(R 15 )-、-S(O)(NR 15 )N(R 15 )-、-N(R 15 )N(R 15 )-、-(R 15 )NC(O)N(R 15 )- and -(R 15 )NC(O)N(R 15 )N(R 15 )-;and L 2 Selected from C 1-6 Alkylene, C 2-6 imidene group, C 2-6 Ethyne group, C 3-8 Carbocyclic group and 4- to 8-membered heterocyclic group, any of which may optionally be independently selected from halogen, -OR 15 -SR 15 Substitution with =O, =S and -CN substituents.

[0169] In some embodiments, for compounds or salts of formula (I), (II), (II-A), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), or (VB), L is derived from -L 1 -L 2 -L 3 -L 4 - indicates that L 3 and L 4 It does not exist; and L 1 Selected from -O-, -N(R) 15 )-, -S-, -S(O)-, -S(O)2-, -S(O)(NR 15 )-、-N(R 15 )C(O)-、-N(R 15 )C(O)O-、-N(R 15 )S(O)2-、-N(R 15 )S(O)2N(R 15 )-、-S(O)(NR 15 )N(R 15 )-、-N(R 15 )N(R 15 )-、-(R 15 )NC(O)N(R 15)- and -(R 15 )NC(O)N(R 15 )N(R 15 )-;and L 2 Selected from C 1-6 Alkylene, C 2-6 imidene group, C 2-6 Ethyne group, C 3-8 Carbocyclic group and 4- to 8-membered heterocyclic group, any of which may optionally be independently selected from halogen, -OR 15 -SR 15 Substitution by =O, =S, and -CN substituents; and R 15 Each time it appears, it is independently selected from hydrogen and C. 1-4 Alkyl and C 1-4 Halogenated alkyl groups.

[0170] In some embodiments, for compounds or salts of formula (I), (II), (II-A), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), or (VB), L is derived from -L 1 -L 2 -L 3 -L 4 - indicates that L 3 and L 4 Does not exist; L 1 Selected from -N(R) 15 - and -N(R) 15 )C(O)-; and L 2 Selected from C 1-6 Alkylene, C 2-6 imidene group, C 3-8 Subcarbonyl cyclo group. In some embodiments, L is composed of -L 1 -L 2 -L 3 -L 4 - indicates that L 3 and L 4 Does not exist; L 1 Selected from -N(R) 15 - and -N(R) 15 )C(O)-; and L 2 Selected from C 1-6 Alkylene and C 3-6 Subcarbonyl cyclo group. In some embodiments, L is composed of -L 1 -L 2 -L 3 -L 4 - indicates that L 3 and L4 Does not exist; L 1 Selected from -N(R) 15 - and -N(R) 15 )C(O)-;L 2 Selected from C 1-6 Alkylene and C 3-6 subcarbocyclic group; and R 15 Selected from hydrogen and C 1-4 Alkyl group. In some embodiments, L is composed of -L 1 -L 2 -L 3 -L 4 - indicates that L 3 and L 4 Does not exist; L 1 Selected from -N(H)C(O)-; and L 2 Selected from methylene.

[0171] In some embodiments, for compounds or salts of formula (I), (II), (II-A), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), or (VB), L is derived from -L 1 -L 2 -L 3 -L 4 - indicates that L 4 It does not exist; and L 1 Selected from -O-, -N(R) 15 )-, -S-, -S(O)-, -S(O)2-, -S(O)(NR 15 )-、-N(R 15 )C(O)-、-N(R 15 )C(O)O-、-N(R 15 )S(O)2-、-N(R 15 )S(O)2N(R 15 )-、-S(O)(NR 15 )N(R 15 )-、-N(R 15 )N(R 15 )-、-(R 15 )NC(O)N(R 15 )- and -(R 15 )NC(O)N(R 15 )N(R 15 )-; L 2 Selected from C 1-6 Alkylene, C 2-6 imidene group, C 2-6Ethyne group, C 3-8 Carbocyclic group and 4- to 8-membered heterocyclic group, any of which may optionally be independently selected from halogen, -OR 15 -SR 15 Substitution by =O, =S, and -CN substituents; and L 3 Selected from -O-, -N(R) 15 )-, -S-, -S(O)-, -S(O)2-, -S(O)(NR 15 )-、-N(R 15 )C(O)-、-N(R 15 )C(O)O-、-N(R 15 )S(O)2-、-N(R 15 )S(O)2N(R 15 )-、-S(O)(NR 15 )N(R 15 )-、-N(R 15 )N(R 15 )-、-(R 15 )NC(O)N(R 15 )- and -(R 15 )NC(O)N(R 15 )N(R 15 )-.

[0172] In some embodiments, for compounds or salts of formula (I), (II), (II-A), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), or (VB), L is derived from -L 1 -L 2 -L 3 -L 4 - indicates that L 4 It does not exist; and L 1 Selected from -O-, -N(R) 15 )-, -S-, -S(O)-, -S(O)2-, -S(O)(NR 15 )-、-N(R 15 )C(O)-、-N(R 15 )C(O)O-、-N(R 15 )S(O)2-、-N(R 15 )S(O)2N(R 15 )-、-S(O)(NR 15 )N(R 15 )-、-N(R 15 )N(R 15 )-、-(R15 )NC(O)N(R 15 )- and -(R 15 )NC(O)N(R 15 )N(R 15 )-; L 2 Selected from C 1-6 Alkylene, C 2-6 imidene group, C 2-6 Ethyne group, C 3-8 Carbocyclic group and 4- to 8-membered heterocyclic group, any of which may optionally be independently selected from halogen, -OR 15 -SR 15 Substitution by =O, =S and -CN substituents; L 3 Selected from -O-, -N(R) 15 )-, -S-, -S(O)-, -S(O)2-, -S(O)(NR 15 )-、-N(R 15 )C(O)-、-N(R 15 )C(O)O-、-N(R 15 )S(O)2-、-N(R 15 )S(O)2N(R 15 )-、-S(O)(NR 15 )N(R 15 )-、-N(R 15 )N(R 15 )-、-(R 15 )NC(O)N(R 15 )- and -(R 15 )NC(O)N(R 15 )N(R 15 )-;and R 15 Each time it appears, it is independently selected from hydrogen and C. 1-4 Alkyl and C 1-4 Halogenated alkyl groups.

[0173] In some embodiments, for compounds or salts of formula (I), (II), (II-A), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), or (VB), L is derived from -L 1 -L 2 -L 3 -L 4 - indicates that L 4 Does not exist; L 1 Selected from -N(R) 15 - and -N(R) 15)C(O)-;L 2 Selected from C 1-6 Alkylene, C 2-6 imidene group, C 3-8 subcarbocyclic group; and L 3 It is -O-. In some implementations, L is -L 1 -L 2 -L 3 -L 4 - indicates that L 4 Does not exist; L 1 Selected from -N(R) 15 - and -N(R) 15 )C(O)-;L 2 Selected from C 1-6 Alkylene and C 3-6 subcarbocyclic group; and L 3 It is -O-. In some implementations, L is -L 1 -L 2 -L 3 -L 4 - indicates that L 4 Does not exist; L 1 Selected from -N(R) 15 - and -N(R) 15 )C(O)-;L 2 Selected from C 1-6 Alkylene and C 3-6 subcarbocyclic group; L 3 It is -O-; and R 15 Selected from hydrogen and C 1-4 Alkyl group. In some embodiments, L is composed of -L 1 -L 2 -L 3 -L 4 - indicates that L 4 Does not exist; L 1 It is -N(H)C(O)-; L 2 It is methylene; and L 3 Yes -O-.

[0174] In some embodiments, for compounds or salts of formula (I), (II), (II-A), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), or (VB), L is selected from -N(H)C(O)-. and .

[0175] In some embodiments, for compounds or salts of formula (I), (II), (II-A), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), or (VB), L is derived from -L 1 -L 2 -L 3 -L 4 - indicates. In some implementations, L 4 It does not exist. In some implementations, L 3 It is a methylene group that is absent, -O-, ethynyl, or substituted with =O. In some embodiments, L 3 It does not exist or is -O-. In some implementations, L 2 It is absent or methylene. In some implementations, L 2 It is absent, methylene, (methyl)methylene, ethylene, or -O-. In some embodiments, the compound or salt according to any one of claims 64-70, wherein L 1 It is -N(R) 15 )C(O)-. In some implementations, L 1 Selected from -N(R) 15 )C(O)-、-N(R 15 )-、-N(R 15 )S(O)-、-(R 15 )NC(O)N(R 15 )- and optionally substituted with one or more halogen atoms, comprising 4- to 6-membered heterocyclic groups. In some embodiments, R 15 It is hydrogen. In some implementations, R 15 Selected from hydrogen and -CH3.

[0176] In some embodiments, for compounds or salts of formula (I), (II), (II-A), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), or (VB), L is selected from... , , , , , , , , , , , , , , , , , , , , and .

[0177] In some embodiments, the compound or salt of formula (II) is represented by the structure of formula (VI): (VI); Or a pharmaceutically acceptable salt thereof, wherein A 2 and R 5 Each is as defined in equation (II).

[0178] In some embodiments, the compound or salt of formula (II) is represented by the structure of formula (VI-A): (VI-A); Or a pharmaceutically acceptable salt thereof, wherein A 2 and R 5 Each is as defined in equation (II).

[0179] In some embodiments, the compound or salt of formula (II) is represented by the structure of formula (VI-B): (VI-B); Or a pharmaceutically acceptable salt thereof, wherein A 2 and R 5 Each is as defined in equation (II).

[0180] In some embodiments, for compounds or salts of formula (I), (II), (II-A), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), (VB), (VI), (VI-A), or (VI-B), R 5 Selected from 4- to 10-membered heterocycles and C 3-10 The carbon ring, wherein any one of them is optionally substituted by one or more substituents independently selected from the following: Halogen, C 1-4 Halogenated alkyl groups, -OR 16 -SR 16 -N(R) 16 )2、-C(O)N(R 16 )2、-C(O)OR 16 -OC(O)R 16 -N(R) 16 )C(O)R 16 -N(R) 16 )S(O)2R 16 -S(O)2N(R)16 )2、-N(R 16 )C(O)N(R 16 )2、-N(R 16 )C(O)OR 16 -OC(O)N(R) 16 )2、-S(O)R 16 -S(O)2R 16 -NO2, =O, =S, =N(R) 16 ) and -CN; C 1-4 Alkyl, C 2-6 alkenyl and C 2-6 Alkyne group, wherein each of them is optionally substituted by one or more substituents independently selected from: halogen, C 1-4 Alkyl, C 1-4 Halogenated alkyl groups, -OR 16 -SR 16 -N(R) 16 2. -NO2 and -CN; and 4- to 6-membered heterocyclic rings and C 3-8 A carbon ring, wherein any of the carbon rings may optionally be substituted by one or more substituents independently selected from the following: halogen, C 1-4 Alkyl, C 1-4 Halogenated alkyl groups, -OR 16 -SR 16 -N(R) 16 2. -NO2 and -CN.

[0181] In some embodiments, for compounds or salts of formula (I), (II), (II-A), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), (VB), (VI), (VI-A), or (VI-B), R 5 Selected from 4- to 10-membered heterocycles and C 3-10 The carbon ring, wherein any one of them is optionally substituted by one or more substituents independently selected from the following: Halogen, C 1-4 Halogenated alkyl groups, -OR 16 -SR 16 -N(R) 16 )2、-C(O)N(R 16 )2、-N(R 16 )C(O)R 16 -N(R) 16 )S(O)2R 16 -S(O)2N(R) 16 )2、-N(R 16 )C(O)N(R16 2. =O and -CN; C 1-4 Alkyl, C 2-6 alkenyl and C 2-6 Alkyne group, wherein each of them is optionally substituted by one or more substituents independently selected from: halogen, C 1-4 Alkyl, C 1-4 Halogenated alkyl groups, -OR 16 -SR 16 -N(R) 16 2. -NO2 and -CN; and 4- to 6-membered heterocyclic rings and C 3-8 Carbon rings, wherein any one of them is optionally selected independently from halogens, C 1-4 Alkyl, C 1-4 Halogenated alkyl groups, -OR 16 -SR 16 -N(R) 16 2. Substitution of -NO2 and -CN groups.

[0182] In some embodiments, for compounds or salts of formula (I), (II), (II-A), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), (VB), (VI), (VI-A), or (VI-B), R 5 Selected from 4- to 10-membered heterocycles and C 3-10 The carbon ring, wherein any one of them is optionally substituted by one or more substituents independently selected from the following: Halogen, C 1-4 Halogenated alkyl groups, -OR 16 -N(R) 16 )2、-C(O)N(R 16 )2、-C(O)OR 16 -OC(O)R 16 -N(R) 16 )C(O)R 16 -N(R) 16 )S(O)2R 16 -S(O)2R 16 -S(O)2N(R) 16 2. -NO2, =O, and -CN; C 1-4 Alkyl, C 2-6 alkenyl and C 2-6 Alkyne group, wherein each of them is optionally substituted by one or more substituents independently selected from: halogen, C 1-4 Alkyl, C 1-4 Halogenated alkyl groups, -OR16 -SR 16 -N(R) 16 2. -NO2 and -CN; and 4- to 6-membered heterocyclic rings and C 3-8 A carbon ring, wherein each of which is optionally substituted by one or more substituents independently selected from the following: halogen, C 1-4 Alkyl, C 1-4 Halogenated alkyl groups, -OR 16 -N(R) 16 2. -NO2 and -CN.

[0183] In some embodiments, for compounds or salts of formula (I), (II), (II-A), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), (VB), (VI), (VI-A), or (VI-B), R 5 Selected from 4- to 10-membered heterocycles and C 3-10 The carbon ring, wherein any one of them is optionally substituted by one or more substituents independently selected from the following: Halogen, C 1-4 Halogenated alkyl groups, -OR 16 -N(R) 16 )2、-C(O)N(R 16 )2、-C(O)OR 16 -OC(O)R 16 -N(R) 16 )C(O)R 16 -NO2, =O, and -CN; C 1-4 Alkyl, C 2-6 alkenyl and C 2-6 Alkyne group, wherein each of them is optionally substituted by one or more substituents independently selected from: halogen, C 1-4 Alkyl, C 1-4 Halogenated alkyl groups, -OR 16 -SR 16 -N(R) 16 2. -NO2 and -CN; and 4- to 6-membered heterocyclic rings and C 3-8 A carbon ring, wherein each of which is optionally substituted by one or more substituents independently selected from the following: halogen, C 1-4 Alkyl, C 1-4 Halogenated alkyl groups, -OR 16 -N(R) 16 2. -NO2 and -CN.

[0184] In some embodiments, for compounds or salts of formula (I), (II), (II-A), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), (VB), (VI), (VI-A), or (VI-B), R 5 Selected from 4- to 10-membered heterocycles and C 3-10 The carbon ring, wherein any one of them is optionally substituted by one or more substituents independently selected from the following: Halogen, C 1-4 Halogenated alkyl groups, -OR 16 -N(R) 16 )2、-C(O)N(R 16 )2、-C(O)OR 16 -OC(O)R 16 -N(R) 16 )C(O)R 16 -NO2, =O, and -CN; C 1-4 Alkyl, C 2-6 alkenyl and C 2-6 The alkynyl group, wherein any one of them is optionally substituted by one or more substituents independently selected from: halogen, C 1-4 Alkyl, C 1-4 Halogenated alkyl groups, -OR 16 and -N(R) 16 )2; and 4- to 6-membered heterocyclic rings and C 3-8 A carbon ring, wherein each of which is optionally substituted by one or more substituents independently selected from the following: halogen, C 1-4 Alkyl, C 1-4 Halogenated alkyl groups, -OR 16 -N(R) 16 2. -NO2 and -CN.

[0185] In some embodiments, for compounds or salts of formula (I), (II), (II-A), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), (VB), (VI), (VI-A), or (VI-B), R 5 Selected from 4- to 10-membered heterocycles and C 3-10 The carbon ring, wherein any one of them is optionally substituted by one or more substituents independently selected from the following: Halogen, C 2-6 alkynyl group, C 1-4 Halogenated alkyl groups, -OR 16 -N(R) 16 2. =O and -CN; C 1-4 Alkyl group, optionally substituted by one or more substituents independently selected from the following: -N(R 16 )2; and 4- to 6-membered heterocyclic rings and C 3-8 A carbon ring, wherein each of which is optionally substituted by one or more substituents independently selected from the following: halogens.

[0186] In some embodiments, for compounds or salts of formula (I), (II), (II-A), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), (VB), (VI), (VI-A), or (VI-B), R 5 Selected from 4- to 10-membered heterocycles and C 3-10 A carbocyclic ring, wherein any of the carbocyclic rings may optionally be substituted by one or more substituents independently selected from the following: fluorine, chlorine, methyl, ethyl, ethynyl, difluoromethyl, hydroxyl, methoxy, trifluoromethoxy, dimethylamino, =O, -CN, cyclopropyl, and pyrazolyl.

[0187] In some embodiments, for compounds or salts of formula (I), (II), (II-A), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), (VB), (VI), (VI-A), or (VI-B), R 5 Selected from 4- to 10-membered heterocycles and C 3-10 Carbon rings, wherein any one of them is optionally selected independently from halogens, C 1-4 Alkyl, C 2-6 alkynyl group, C 1-4 Halogenated alkyl groups, -OR 16 -N(R) 16 )2, =O, -CN and C 3-8 Substituents on the carbide ring. In some embodiments, R 5 Selected from 4- to 10-membered heterocycles and C 3-10 A carbocyclic ring, wherein any of the carbocyclic rings may optionally be substituted by one or more substituents independently selected from the following: fluorine, chlorine, methyl, ethyl, ethynyl, difluoromethyl, hydroxyl, methoxy, trifluoromethoxy, dimethylamino, =O, -CN, cyclopropyl, and pyrazolyl.

[0188] In some embodiments, for compounds or salts of formula (I), (II), (II-A), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), (VB), (VI), (VI-A), or (VI-B), R 5Selected from 4- to 10-membered heterocycles and C 3-10 Carbon rings, wherein any one of them is optionally selected independently from halogens, C 1-4 Alkyl, C 2-6 alkynyl group, C 1-4 Halogenated alkyl groups, -OR 16 -N(R) 16 )2、-C(O)N(R 16 )2、=O、-CN、C 3-8 Substitution of the carbocyclic ring and 3- to 8-membered heterocycles, wherein the C 3-8 The carbon ring and the 4- to 8-membered heterocycle are each optionally surrounded by one or more elements selected from halogens, C 1-4 Alkyl and C 1-4 Substituents of the haloalkyl group. In some embodiments, R 5 Selected from 4- to 10-membered heterocycles and C 3-10 The carbocyclic ring, wherein any of the carbon rings may optionally be substituted by one or more substituents independently selected from the following: fluorine, chlorine, methyl, ethyl, ethynyl, propynyl, fluoromethyl, difluoromethyl, trifluoromethyl, hydroxyl, -CH2OH, methoxy, -CH2OCH3, , , , Difluoromethoxy, trifluoromethoxy, -NH2, dimethylamino, -CH2N(CH3)2, , , , , , , =O, -CN, cyclopropyl, phenyl, morpholino, pyrazolyl And pyridyl.

[0189] In some embodiments, for compounds or salts of formula (I), (II), (II-A), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), (VB), (VI), (VI-A), or (VI-B), R 5 It is a substituted 3- to 10-membered heteroaryl group. In some embodiments, R 5 It is an optional 5- to 10-membered heteroaryl group that is substituted. In some embodiments, R 5 It is an optionally substituted 5- to 6-membered heteroaryl group. In some embodiments, R 5Selected from: optionally substituted pyrazolyl, optionally substituted thiazolyl, optionally substituted oxazolyl, optionally substituted pyridyl, optionally substituted pyrimidinyl, optionally substituted pyrazinyl, optionally substituted pyridazinyl, optionally substituted benzo[d]isooxazolyl, optionally substituted imidazo[1,2-a]pyridinyl, optionally substituted 1H-benzo[d]imidazolyl, optionally substituted 1H-pyrazolo[3,4-b]pyridinyl, optionally substituted 2H-pyrrolo[3,4-c]pyridinyl, and optionally substituted isoquinolinyl. In some embodiments, R 5 Selected from: optionally substituted pyrazolyl, optionally substituted thiazolyl, optionally substituted oxazolyl, optionally substituted pyridyl, optionally substituted pyrimidinyl, optionally substituted pyrazinyl, optionally substituted pyridazinyl, optionally substituted benzo[d]isooxazolyl, optionally substituted imidazo[1,2-a]pyridinyl, optionally substituted 1H-benzo[d]imidazolyl, optionally substituted 1H-pyrazolo[3,4-b]pyridinyl, optionally substituted 2H-pyrrolo[3,4-c]pyridinyl, and optionally substituted isoquinolinyl. In some embodiments, R 5 Selected from: optionally substituted pyrazolyl, optionally substituted thiazolyl, optionally substituted oxazolyl, optionally substituted pyridyl, optionally substituted pyrimidinyl, optionally substituted pyrazinyl, optionally substituted pyridazinyl, optionally substituted benzo[d]isooxazolyl, optionally substituted imidazo[1,2-a]pyridyl, optionally substituted 1H-benzo[d]imidazolyl, optionally substituted 1H-pyrazolo[3,4-b]pyridyl, optionally substituted 2H-pyrrolo[3,4-c]pyridyl, and optionally substituted isoquinolinyl.

[0190] In some embodiments, for compounds or salts of formula (I), (II), (II-A), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), (VB), (VI), (VI-A), or (VI-B), R 5 These are optionally substituted 4- to 10-membered heterocyclic rings. In some implementations, R... 5 These are optional 4- to 10-membered heteroaryl groups.

[0191] In some embodiments, for compounds or salts of formula (I), (II), (II-A), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), (VB), (VI), (VI-A), or (VI-B), R 5It is an optionally substituted 3- to 8-membered heterocyclic alkyl group. In some embodiments, R 5 It is an optionally substituted 3- to 6-membered heterocyclic alkyl group. In some embodiments, R 5 It is an optionally substituted 4- to 6-membered heterocyclic alkyl group. In some embodiments, R 5 It is selected from optionally substituted oxecyclobutane, optionally substituted pyrrole, and optionally substituted morpholino.

[0192] In some embodiments, for compounds or salts of formula (I), (II), (II-A), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), (VB), (VI), (VI-A), or (VI-B), R 5 Selected from C which is arbitrarily replaced 3-6 Cycloalkyl groups and optionally substituted phenyl groups. In some embodiments, R 5 C is arbitrarily replaced 3-5 Cycloalkyl groups and optionally substituted phenyl groups. In some embodiments, R 5 Selected from optionally substituted cyclopropyl, optionally substituted cyclobutyl, and optionally substituted phenyl groups. In some embodiments, R 5 C is arbitrarily replaced 3-6 Cycloalkyl. In some embodiments, R 5 C is arbitrarily replaced 3-5 Cycloalkyl. In some embodiments, R 5 Selected from optionally substituted cyclopropyl and optionally substituted cyclobutyl groups. In some embodiments, R 5 It is a phenyl group that is optionally substituted.

[0193] In some embodiments, for compounds or salts of formula (I), (II), (II-A), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), (VB), (VI), (VI-A), or (VI-B), R 5 Selected from: .

[0194] In some embodiments, for compounds or salts of formula (I), (II), (II-A), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), (VB), (VI), (VI-A), or (VI-B), R 5 Selected from optionally substituted pyrazolyl, optionally substituted thiazolyl, optionally substituted oxazolyl, optionally substituted pyridyl, optionally substituted pyrimidinyl, optionally substituted pyrazinyl, optionally substituted pyridazinyl, optionally substituted benzo[d]isooxazolyl, optionally substituted imidazo[1,2-a]pyridyl, optionally substituted 1H-benzo[d]imidazolyl, optionally substituted 1H-pyrazolo[3,4-b]pyridyl, optionally substituted 2H-pyrrolo[3,4-c]pyridyl, and optionally substituted isoquinolinyl.

[0195] In some embodiments, for compounds or salts of formula (I), (II), (II-A), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), (VB), (VI), (VI-A), or (VI-B), R 5Selected from optionally substituted pyrazolyl, optionally substituted thiazolyl, optionally substituted oxazolyl, optionally substituted pyridyl, optionally substituted pyrimidinyl, optionally substituted pyrazinyl, optionally substituted pyridazinyl, optionally substituted benzo[d]isooxazolyl, optionally substituted imidazo[1,2-a]pyridinyl, optionally substituted 1H-benzo[d]imidazolyl, optionally substituted 1H-pyrazolo[3,4-b]pyridinyl, optionally substituted 2H-pyrrolo[3,4-c]pyridinyl and optionally substituted isoquinolinyl, optionally substituted isoxazolyl, optionally substituted isothiazole, optionally substituted 1,2,3-thiadiazolyl, optionally substituted Substituted 5,6-dihydro-4H-pyrrolo[1,2-b]pyrazolyl, optionally substituted 2,3-dihydropyrazolo[5,1-b]oxazolyl, optionally substituted 5,6-dihydro-3H-furano[2,3-d]imidazolyl, optionally substituted indazinyl, optionally substituted pyrazolo[1,5-a]pyridinyl, optionally substituted pyrrolo[1,2-a]pyrimidinyl, optionally substituted pyrazolo[1,5-a]pyrimidinyl, optionally substituted imidazo[1,2-a]pyrimidinyl, optionally substituted imidazo[1,2-b]pyridazinyl, optionally substituted [1,2,4]triazolo[1,5-a]pyridinyl, optionally substituted 6,7-di Hydro-5H-cyclopentadieno[b]pyridyl, optionally substituted 6,7-dihydro-5H-cyclopentadieno[c]pyridyl, optionally substituted 5,6,7,8-tetrahydroisoquinolinyl, optionally substituted 3,4-dihydro-2H-pyrano[2,3-b]pyridyl, optionally substituted 2,3-dihydro-[1,4]dioxane-hexeno[2,3-b]pyridyl, optionally substituted 5,7-dihydrofurano[3,4-b]pyridyl, optionally substituted 2,3-dihydrofurano[2,3-c]pyridyl, optionally substituted 2,3-dihydrofurano[2,3-b]pyridyl, optionally substituted [1,3]dioxane-penteno[4,5- [b]pyridyl, optionally substituted furano[2,3-b]pyridyl, optionally substituted thieno[2,3-b]pyridyl, optionally substituted 1,2-dihydro-3H-indazole-3-one, optionally substituted 1H-benzo[d][1,2,3]triazolyl, optionally substituted 1,3-dihydro-2H-benzo[d]imidazol-2-one, optionally substituted benzo[d]oxazol-2(3H)-one, optionally substituted benzo[d]thiazol-2(3H)-one, optionally substituted 1H-indazole, optionally substituted indololin-2-one, and optionally substituted 1,3-dihydro-2H-pyrrolo[2,3-b]pyridin-2-one.

[0196] In some embodiments, for compounds or salts of formula (I), (II), (II-A), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), (VB), (VI), (VI-A), or (VI-B), R 5 It is selected from the following optional substituted 6- to 10-member bicyclic heterocycles: optional substituted 6- to 10-member fused heterocycles, optional substituted 6- to 10-member bridging heterocycles, and optional substituted 6- to 10-member spirocyclic heterocycles.

[0197] In some embodiments, for compounds or salts of formula (I), (II), (II-A), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), (VB), (VI), (VI-A), or (VI-B), R 5 It is selected from the following optionally substituted 6- to 10-membered spirocyclic heterocycles: optionally substituted 2-azaspiro[3.3]heptyl, optionally substituted 6-azaspiro[3.4]octyl, optionally substituted 5-azaspiro[3.4]octyl, optionally substituted 2-azaspiro[3.5]nonyl, optionally substituted 7-azaspiro[3.5]nonyl and optionally substituted 6-azaspiro[3.5]nonyl.

[0198] In some embodiments, for compounds or salts of formula (I), (II), (II-A), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), (VB), (VI), (VI-A), or (VI-B), R 5 It is selected from optionally substituted oxecyclobutane, optionally substituted pyrrole, optionally substituted morpholino, optionally substituted azacyclobutane, optionally substituted pyrrole, optionally substituted tetrahydro-2H-thiaranyl, and optionally substituted piperidinyl.

[0199] In some embodiments, for compounds or salts of formula (I), (II), (II-A), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), (VB), (VI), (VI-A), or (VI-B), R 5 Selected from: .

[0200] In some embodiments, for compounds or salts of formula (I), (II), (II-A), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), (VB), (VI), (VI-A), or (VI-B), R 5 Selected from: .

[0201] In some embodiments, for compounds or salts of formula (I), (II), (II-A), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), (VB), (VI), (VI-A), or (VI-B), R 10 R 11 R 12 R 13 R 14 and R 15 Each time it appears, it is independently selected from: hydrogen, C 1-4 Alkyl, C 3-6 Carbon rings, 4- to 6-membered heterocycles and C 1-4 Halogenated alkyl groups. In some embodiments, R 10 R 11 R 12 R 13 R 14 and R 15 Each time it appears, it is independently selected from: hydrogen, C 1-4 Alkyl and C 1-4 Halogenated alkyl groups.

[0202] In some embodiments, for compounds or salts of formula (I), (II), (II-A), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), (VB), (VI), (VI-A), or (VI-B), R 16 Each time it appears, it is independently selected from (iv), (v), and (vi): (iv) Hydrogen; (v) C 1-4 Alkyl, wherein the C1-4 The alkyl group is optionally substituted by one or more substituents independently selected from the following: Halogen, -OR 20 -SR 20 -N(R) 20 )2、-C(O)R 20 -C(O)OR 20 -OC(O)R 20 -C(O)N(R) 20 )2、-N(R 20 )C(O)R 20 -N(R) 20 )C(O)N(R 20 )2、-N(R 20 )C(O)OR 20 -OC(O)N(R) 20 )2、-S(O)R 20 -S(O)2R 20 -N(R) 20 )S(O)2R 20 -S(O)2N(R) 20 2. -NO2 and -CN; and C 3-8 A carbocyclic ring and 4- to 8-membered heterocycles, any of which may optionally be substituted by one or more substituents independently selected from the following: halogen, C 1-4 Alkyl, C 1-4 Halogenated alkyl groups, -OR 20 -SR 20 -N(R) 20 )2、-C(O)R 20 -C(O)OR 20 -OC(O)R 20 -C(O)N(R) 20 )2、-N(R 20 )C(O)R 20 -N(R) 20 )C(O)N(R 20 )2、-N(R 20 )C(O)OR 20 -OC(O)N(R) 20 )2、-S(O)R 20 -S(O)2R 20 -N(R) 20 )S(O)2R 20 -S(O)2N(R) 20 2. -NO2 and -CN; and (ⅵ) C 3-8A carbocyclic ring and 4- to 8-membered heterocycles, any of which may optionally be substituted by one or more substituents independently selected from the following: halogen, C 1-4 Alkyl, C 1-4 Halogenated alkyl groups, -OR 20 -SR 20 -N(R) 20 )2、-C(O)R 20 -C(O)N(R) 20 )2、-C(O)OR 20 -OC(O)R 20 -N(R) 20 )C(O)R 20 -N(R) 20 )S(O)2R 20 -N(R) 20 )C(O)N(R 20 )2、-N(R 20 )C(O)OR 20 -OC(O)N(R) 20 )2、-S(O)R 20 -S(O)2R 20 -NO2 and -CN.

[0203] In some embodiments, for compounds or salts of formula (I), (II), (II-A), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), (VB), (VI), (VI-A), or (VI-B), R 16 Each time it appears, it is independently selected from hydrogen; and C. 3-8 A carbocyclic ring and 4- to 8-membered heterocycles, any of which may optionally be substituted by one or more substituents independently selected from the following: halogen, C 1-4 Alkyl, C 1-4 Halogenated alkyl groups, -OR 20 -SR 20 -N(R) 20 )2、-C(O)R 20 -C(O)N(R) 20 )2、-C(O)OR 20 -OC(O)R 20 -N(R) 20 )C(O)R 20 -N(R) 20 )S(O)2R 20 -N(R) 20 )C(O)N(R 20 )2、-N(R 20 )C(O)OR 20-OC(O)N(R) 20 )2、-S(O)R 20 -S(O)2R 20 -NO2 and -CN.

[0204] In some embodiments, for compounds or salts of formula (I), (II), (II-A), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), (VB), (VI), (VI-A), or (VI-B), R 16 Each time it appears, it is independently selected from (iv) and (v): (iv) Hydrogen; and (v) C 1-4 Alkyl, wherein the C 1-4 The alkyl group is optionally substituted by one or more substituents independently selected from the following: Halogen, -OR 20 -SR 20 -N(R) 20 )2、-C(O)R 20 -C(O)OR 20 -OC(O)R 20 -C(O)N(R) 20 )2、-N(R 20 )C(O)R 20 -N(R) 20 )C(O)N(R 20 )2、-N(R 20 )C(O)OR 20 -OC(O)N(R) 20 )2、-S(O)R 20 -S(O)2R 20 -N(R) 20 )S(O)2R 20 -S(O)2N(R) 20 2. -NO2 and -CN; and C 3-8 A carbocyclic ring and 4- to 8-membered heterocycles, any of which may optionally be substituted by one or more substituents independently selected from the following: halogen, C 1-4 Alkyl, C 1-4 Halogenated alkyl groups, -OR 20 -SR 20 -N(R) 20 )2、-C(O)R 20 -C(O)OR 20 -OC(O)R 20 -C(O)N(R) 20)2、-N(R 20 )C(O)R 20 -N(R) 20 )C(O)N(R 20 )2、-N(R 20 )C(O)OR 20 -OC(O)N(R) 20 )2、-S(O)R 20 -S(O)2R 20 -N(R) 20 )S(O)2R 20 -S(O)2N(R) 20 2. -NO2 and -CN.

[0205] In some embodiments, for compounds or salts of formula (I), (II), (II-A), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), (VB), (VI), (VI-A), or (VI-B), R 16 Each time it appears, it is independently selected from hydrogen; and C. 1-4 Alkyl, wherein the C 1-4 The alkyl group is optionally substituted by one or more substituents independently selected from the following: halogen, -OR 20 -SR 20 -N(R) 20 )2、-C(O)R 20 -C(O)OR 20 -OC(O)R 20 -C(O)N(R) 20 )2、-N(R 20 )C(O)R 20 -N(R) 20 )C(O)N(R 20 )2、-N(R 20 )C(O)OR 20 -OC(O)N(R) 20 )2、-S(O)R 20 -S(O)2R 20 -N(R) 20 )S(O)2R 20 -S(O)2N(R) 20 )2, -NO2, and -CN. In some implementations, R 16 Each time it appears, it is independently selected from hydrogen and C. 1-4 Alkyl, wherein the C 1-4 The alkyl group is optionally substituted with one or more substituents independently selected from halogens. In some embodiments, R 16Each time it appears, it is independently selected from hydrogen and C. 1-4 Alkyl, wherein the C 1-4 The alkyl group is optionally substituted with one or more substituents independently selected from fluorine. In some embodiments, R 16 Each time it appears, it is independently selected from hydrogen and methyl, wherein the methyl group is optionally substituted by one or more substituents independently selected from halogens. In some embodiments, R 16 Each time it appears, it is independently selected from hydrogen and methyl, wherein the methyl group is optionally substituted by one or more substituents independently selected from fluorine. In some embodiments, R 16 It is independently selected from hydrogen each time it appears. In some implementations, R 16 Each time it appears, it is independently selected from C. 1-4 Alkyl group. In some embodiments, R 16 Each time it appears, it is independently selected from methyl. In some embodiments, R 16 Each time it appears, it is independently selected from C. 1-4 Alkyl, the C 1-4 The alkyl group is optionally substituted by one or more substituents selected independently of halogens each time it appears. In some embodiments, R 16 Each time it appears, it is independently selected from C. 1-4 Alkyl, the C 1-4 The alkyl group is optionally substituted by one or more substituents selected independently of fluorine each time it appears. In some embodiments, R 16 Each time it appears, it is independently selected from methyl, which is optionally substituted by one or more substituents selected each time it appears, independently selected from fluorine. In some embodiments, R 16 Each time it appears, it is independently selected from trifluoromethyl. In some embodiments, R 16 Each time it appears, it is independently selected from hydrogen, methyl, and trifluoromethyl.

[0206] In some embodiments, for compounds or salts of formula (I), (II), (II-A), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), (VB), (VI), (VI-A), or (VI-B), R 20 Each time it appears, it is independently selected from hydrogen, C 1-4 Alkyl, C 1-4 Haloalkyl, C 3-6 Carbon rings and 4- to 6-membered heterocycles. In some embodiments, R 20 Each time it appears, it is independently selected from hydrogen, C 1-4 Alkyl and C 1-4 Halogenated alkyl groups.

[0207] In some embodiments, the compound or salt of formula (I) or formula (II) are the compounds in Table 1.

[0208] Table 1. Chemical structures of the selected compounds. * indicates a stereocenter with undetermined absolute stereochemistry in a single diastereomer. In some aspects, this disclosure provides a compound selected from the compounds in Table 2 or pharmaceutically acceptable salts thereof.

[0209] Table 2. Chemical structures of the selected compounds. While preferred embodiments of the invention have been shown and described herein, it will be apparent to those skilled in the art that such embodiments are provided by way of example only. Many variations, modifications, and substitutions will now occur to those skilled in the art without departing from the invention. It should be understood that various alternatives to the embodiments of the invention described herein may be employed in the practice of the invention. The following claims are intended to define the scope of the invention and therefore cover the methods and structures within the scope of these claims and their equivalents.

[0210] Chemical entities with carbon-carbon double bonds or carbon-nitrogen double bonds can be... Z -or E - It exists in the form (either cis or trans). Furthermore, some chemical entities can exist in various tautomeric forms. Unless otherwise specified, compounds or salts of formulas (I), (II), (II-A), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), (VB), (VI), (VI-A), or (VI-B) are also intended to include all Z -、 E - and tautomerism.

[0211] "Isomers" are different compounds having the same molecular formula. "Stereoisomers" are isomers that differ only in the spatial arrangement of atoms. "Enantiomers" are a pair of stereoisomers that are non-overlapping mirror images of each other. A 1:1 mixture of a pair of enantiomers is a "racemic" mixture. Where appropriate, the term "(±)" is used to designate racemic mixtures. "Diastereoisomer" or "diastereomer" is a stereoisomer having at least two asymmetric atoms that are not mirror images of each other. Absolute stereochemistry is specified according to the Cahn-Ingold-Prelog RS system. When the compound is a pure enantiomer, the stereochemistry at each chiral carbon may be specified by R or S. Resolved compounds with unknown absolute configuration may be designated as (+) or (-) according to the direction (dextrorotatory or levorotatory) of the plane-polarized light at the wavelength of the sodium D line. Some of the compounds described herein contain one or more asymmetric centers, and thus can produce enantiomers, diastereomers, and other stereoisomers, whose asymmetric centers can be defined by absolute stereochemistry as (R)- or (S)-. These chemical entities, pharmaceutical compositions, and methods are intended to include all such possible stereoisomers, including racemic mixtures, optically pure forms, mixtures of diastereomers, and mixtures of intermediates. Optically active (R)- and (S)- isomers can be prepared using chiral synthons or chiral reagents, or resolved using conventional techniques. The optical activity of the compounds can be analyzed by any suitable method, including but not limited to chiral chromatography and optical rotation determination, and can determine the degree of dominance of one stereoisomer over another.

[0212] Compounds or salts of formulas (I), (II), (II-A), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), (VB), (VI), (VI-A), or (VI-B) may, in some cases, be present in diastereomers, enantiomers, or other stereoisomers. The compounds presented herein include all diastereomers, enantiomers, and epimers, as well as racemates, mixtures of diastereomers, and other mixtures, to the extent that they can be prepared by those skilled in the art through routine experiments. Separation of stereoisomers may be performed by chromatography or by forming diastereomers and separating them by recrystallization or chromatography, or any combination thereof. (Jean Jacques, Andre Collet, Samuel H. Wilen, “Enantiomers, Racemates and Resolutions,” John Wiley AndSons, Inc., 1981, for which this disclosure is incorporated herein by reference). Stereoisomers can also be obtained through stereoselective synthesis. Furthermore, mixtures of two enantiomers enriched in one of them can be purified by recrystallization and / or grinding to provide other optically enriched forms of the primary enantiomer.

[0213] In some embodiments, the compound or salt of formula (I), (II), (II-A), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), (VB), (VI), (VI-A), or (VI-B) may comprise two or more enantiomers or diastereomers of the compound, wherein a single enantiomer or diastereomer comprises at least about 70% by weight, at least about 80% by weight, at least about 90% by weight, at least about 98% by weight, or at least about 99% by weight or more of the total weight of all stereoisomers. Methods for producing substantially pure enantiomers are well known to those skilled in the art. For example, a single stereoisomer (e.g., an enantiomer) substantially free of its stereoisomers can be obtained by resolving a racemic mixture using methods such as forming diastereomers using an optically active resolving agent (Stereochemistry of Carbon Compounds, (1962), EL Eliel, McGraw Hill; Lochmuller (1975)). J. Chromatogr., 113(3): 283-302). Racemic mixtures of chiral compounds can be separated / isolated by any suitable method, including but not limited to: (1) forming ionic diastereomeric salts with the chiral compound and separating them by fractional crystallization or other methods; (2) forming diastereomeric compounds with a chiral derivatizing agent, separating the diastereomeric isomers and converting them to pure stereoisomers; and (3) directly separating substantially pure or enriched stereoisomers under chiral conditions. Another method for separating enantiomers is to use a Diacel chiral column and elute with an organic mobile phase, such as by Chiral Technologies (www.chiraltech.com) on a charge-per-service basis.

[0214] A "tautomer" is a molecule in which a proton may translocate from one atom of the molecule to another atom of the same molecule. In some embodiments, compounds or salts of formulas (I), (II), (II-A), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), (VB), (VI), (VI-A), or (VI-B) exist as tautomers. A chemical equilibrium of tautomers can exist where tautomerization is possible. The precise ratio of tautomers depends on several factors, including physical state, temperature, solvent, and pH. Some non-limiting examples of tautomeric equilibria include: .

[0215] In some embodiments, the compounds disclosed herein are used in different enriched isotopic forms, such as enriched isotopes. 2 H, 3 H, 11 C 13 C and / or 14 The content of C. In one particular embodiment, the compound may be deuterated at at least one position. Such deuterated forms can be prepared by the procedures described in U.S. Patent Nos. 5,846,514 and 6,334,997. As described in U.S. Patent Nos. 5,846,514 and 6,334,997, deuteration can improve metabolic stability and / or efficacy, thus increasing the duration of drug action.

[0216] In some embodiments, some or all of the compounds disclosed herein 1 H atoms are 2 H atom substitution. Methods for synthesizing deuterium-containing compounds are known in the art and include (by way of non-limiting example only) the following synthetic methods.

[0217] Deuterium-substituted compounds are synthesized using various methods such as those described in: Dean, Dennis C.; ed. Recent Advances in the Synthesis and Applications of Radiolabeled Compounds for Drug Discovery and Development. [Published in: Curr., Pharm. Des., 2000; 6(10)] 2000, p. 110; George W.; Varma, Rajender S. The Synthesis of Radiolabeled Compounds via Organometallic Intermediates, Tetrahedron, 1989, 45(21), 6601-21; and Evans, E. Anthony. Synthesis of radiolabeled compounds, J. Radioanal. Chem., 1981, 64(1-2), 9-32.

[0218] Deuteration starting materials are readily available and can be synthesized using the methods described herein to provide materials for the synthesis of deuterium-containing compounds. A wide range of deuterium-containing reagents and structural units are commercially available from chemical suppliers such as Aldrich Chemical Co.

[0219] Unless otherwise stated, the compounds described herein are intended to include compounds that differ only in the presence of one or more isotopically enriched atoms. For example, compounds where hydrogen is replaced by deuterium or tritium, or carbon by... 13 C- or 14 C-enriched carbon substitutions and compounds having this structure are all within the scope of this disclosure.

[0220] The compounds disclosed herein optionally contain atomic isotopes in non-natural proportions at one or more atoms constituting such compounds. For example, the compounds may contain isotopes such as, for example, deuterium (… 2 H), tritium ( 3 H), Iodine-125 ( 125 I) or carbon-14 ( 14 C) Marking. (After) 2 H, 11 C 13 C 14 C 15 C 12 N、 13 N、 15 N、16 N、 16 O、 17 O、 14 F, 15 F, 16 F, 17 F, 18 F, 33 S, 34 S, 35 S, 36 S, 35 Cl、 37 Cl、 79 Br、 81 Br and 125 Isotope substitutions are all included. All isotopic variants of the compounds of this invention, whether or not they are radioactive, are covered within the scope of this invention.

[0221] Including in this disclosure are salts of compounds of formula (I), (II), (II-A), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), (VB), (VI), (VI-A), or (VI-B), especially pharmaceutically acceptable salts. The compounds of this disclosure may have sufficiently acidic functional groups, sufficiently basic functional groups, or both, and may react with a variety of inorganic bases and any of inorganic and organic acids to form salts. Alternatively, inherently charged compounds (such as those having quaternary nitrogen) may form salts with suitable counterions, such as halide ions, such as bromide, chloride, or fluoride ions, especially bromide ions.

[0222] Methods and compositions of formulas (I), (II), (II-A), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), (VB), (VI), (VI-A), or (VI-B) include the use of amorphous forms as well as crystalline forms (also known as polymorphs). The compounds described herein may be in pharmaceutically acceptable salt forms. In some embodiments, active metabolites of these compounds having the same type of activity are also included within the scope of this disclosure. Additionally, the compounds described herein may be present in unsolvable forms as well as in solvated forms formed with pharmaceutically acceptable solvents (such as water, ethanol, etc.). The solvated forms of the compounds presented herein are also considered to be disclosed herein.

[0223] Compounds of formula (I), (II), (II-A), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), (VB), (VI), (VI-A), or (VI-B) also include crystalline and amorphous forms of those compounds, pharmaceutically acceptable salts, and active metabolites of those compounds having the same type of activity, including, for example, polymorphs, pseudopolymorphs, solvates, hydrates, nonsolventized polymorphs (including anhydrous forms), conformational polymorphs, and amorphous forms of the compounds, as well as mixtures thereof.

[0224] Salts of compounds represented by formulas (I), (II), (II-A), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), (VB), (VI), (VI-A), or (VI-B) are included in this disclosure, especially pharmaceutically acceptable salts. Compounds of the present invention having sufficiently acidic, sufficiently basic, or both functional groups can react with a variety of inorganic bases and any of inorganic and organic acids to form salts. Alternatively, inherently charged compounds (such as those having quaternary nitrogen) can form salts with suitable counterions, such as halide ions, such as bromide, chloride, or fluoride ions, especially bromide ions.

[0225] In some embodiments, compounds or salts of formulas (I), (II), (II-A), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), (VB), (VI), (VI-A), or (VI-B) may be prodrugs, for example, wherein the hydroxyl group in the parent compound is presented as an ester or carbonate, or the carboxylic acid present in the parent compound is presented as an ester. The term "prodrug" is intended to cover compounds that are converted into pharmaceuticals of this disclosure under physiological conditions. A method for preparing a prodrug comprises hydrolyzing one or more selected portions under physiological conditions to produce the desired molecule. In other embodiments, the prodrug is converted by the enzymatic activity of a host animal, such as specific target cells in the host animal. For example, esters or carbonates (e.g., esters of alcohols or carboxylic acids or esters of carbonates and phosphonates) are preferred prodrugs of this disclosure.

[0226] pharmaceutical preparations In some aspects, this disclosure provides a pharmaceutical composition comprising a compound or salt of formula (I), (II), (II-A), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), (VB), (VI), (VI-A), or (VI-B) and at least one pharmaceutically acceptable excipient.

[0227] In some aspects, this disclosure provides a pharmaceutical composition comprising the compounds listed in Table 2.

[0228] Pharmaceutical compositions can be formulated using one or more physiologically acceptable carriers comprising excipients and adjuvants. The formulation may be modified according to the chosen route of administration. Pharmaceutical compositions comprising compounds, salts, or conjugates can be manufactured, for example, by lyophilizing the compound, salt, or conjugate, mixing, dissolving, emulsifying, encapsulating, or embedding the conjugate. Pharmaceutical compositions may also comprise compounds, salts, or conjugates in free base form or in pharmaceutically acceptable salt form.

[0229] Compounds or salts of formulas (I), (II), (II-A), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), (VB), (VI), (VI-A), or (VI-B) can be formulated in any suitable pharmaceutical formulation. Pharmaceutical formulations of this disclosure typically contain an active ingredient (e.g., a compound or salt of any of formulas (I), (II), (II-A), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), (VB), (VI), (VI-A), or (VI-B)) and one or more pharmaceutically acceptable excipients or carriers, including but not limited to: inert solid diluents and fillers, diluents, sterile aqueous solutions, and various organic solvents, penetration enhancers, antioxidants, solubilizers, and adjuvants.

[0230] The compounds or salts in Table 2 can be formulated in any suitable pharmaceutical formulation. Pharmaceutical formulations disclosed herein typically contain an active ingredient (such as the compounds or salts in Table 2) and one or more pharmaceutically acceptable excipients or carriers, including but not limited to: inert solid diluents and fillers, diluents, sterile aqueous solutions, and various organic solvents, penetration enhancers, antioxidants, solubilizers, and excipients.

[0231] Treatment The compounds described herein can be used to prepare medicaments for the prevention or treatment of diseases or conditions. Additionally, methods for treating any of the diseases or conditions described herein in a subject requiring such treatment involve administering a pharmaceutical composition to the subject in a therapeutically effective amount, the pharmaceutical composition containing at least one compound described herein or a pharmaceutically acceptable salt, pharmaceutically acceptable prodrug, or pharmaceutically acceptable solvate thereof.

[0232] Compositions containing one or more of the compounds described herein may be applied for preventative and / or therapeutic treatment. In therapeutic use, the composition is administered to a patient with the disease or condition in an amount sufficient to cure or at least partially suppress the symptoms of the disease or condition. The effective amount for this purpose will be determined based on the severity and course of the disease or condition, prior therapy, the patient's health status, weight and response to the drug, and the judgment of the treating physician.

[0233] In prophylactic use, a composition containing the compounds described herein is administered to a patient who is susceptible to a specific disease, condition, or illness, or otherwise at risk of such a disease, condition, or illness. Such amounts are defined as “preventative effective amounts or doses.” In this use, the precise amount is also determined based on the patient’s health condition, weight, etc. When used in a patient, the effective amount for this purpose will be determined based on the severity and course of the disease, condition, or illness, prior therapy, the patient’s health condition and response to the drug, and the judgment of the treating physician.

[0234] In some aspects, this disclosure provides a method of treatment comprising administering to a subject in need an effective amount of a compound or salt of formula (I), (II), (II-A), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), (VB), (VI), (VI-A), or (VI-B). In some aspects, this disclosure provides a method of treating cancer in a patient in need, comprising administering to the subject an effective amount of a compound or salt of formula (I), (II), (II-A), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), (VB), (VI), (VI-A), or (VI-B). In some embodiments, the cancer is selected from breast cancer, colorectal cancer, and meningioma. In some embodiments, the cancer is breast cancer. In some embodiments, the cancer is colorectal cancer. In some embodiments, the cancer is meningioma.

[0235] In some embodiments, this disclosure can be used as a method of inhibiting the AKT1 protein of a desired subject, comprising administering to the subject a compound or salt of formula (I), (II), (II-A), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), (VB), (VI), (VI-A), or (VI-B), or a pharmaceutical composition of formula (I), (II), (II-A), (III), (III-A), (III-B), (IV), (IV-A), (IV-B), (V), (VA), (VB), (VI), (VI-A), or (VI-B). In some embodiments, the AKT protein is wild-type AKT1. In some embodiments, the AKT protein is a mutant AKT1 protein. In some embodiments, the mutant AKT1 protein comprises an E17K mutant. In some embodiments, the activity of the mutant AKT1 is modulated. In some embodiments, the activity of the wild-type AKT1 is modulated.

[0236] In some aspects, this disclosure provides a method for treatment comprising administering an effective amount of a compound or salt from Table 2 to a subject in need. In some aspects, this disclosure provides a method for treating cancer in a patient in need, comprising administering an effective amount of a compound or salt from Table 2 to the subject. In some embodiments, the cancer is selected from breast cancer, colorectal cancer, and meningioma. In some embodiments, the cancer is breast cancer. In some embodiments, the cancer is colorectal cancer. In some embodiments, the cancer is meningioma.

[0237] In some embodiments, this disclosure can be used as a method of inhibiting the AKT1 protein of a desired subject, comprising administering to the subject a compound or salt of Table 2, or a pharmaceutical composition comprising a compound or salt of Table 2. In some embodiments, the AKT protein is wild-type AKT1. In some embodiments, the AKT protein is a mutant AKT1 protein. In some embodiments, the mutant AKT1 protein comprises an E17K mutant. In some embodiments, the application modulates the activity of the mutant AKT1. In some embodiments, the application modulates the activity of the wild-type AKT1.

[0238] Example The invention has now been generally described, and will be more readily understood by referring to the following embodiments, which are included for the purpose of illustrating certain aspects and embodiments of the invention and are not intended to limit the invention in any way.

[0239] Chemical synthesis The following examples illustrate various methods for preparing the compounds described herein. These examples are exemplary and not exhaustive. It should be understood that those skilled in the art can synthesize the compounds using similar methods.

[0240] Compound 1: (S)-N-(5-(2-(2-aminopyridin-3-yl)-5-(1H-pyrazol-1-yl)-3H-imidazo[4,5-b]pyridin-3-yl)-2,3-dihydro-1H-inden-1-yl)acetamide (Compound 1) Synthesis route: Step 1: Synthesis of (S)-N-(5-(2-(2-aminopyridin-3-yl)-5-(1H-pyrazol-1-yl)-3H-imidazo[4,5-b]pyridin-3-yl)-2,3-dihydro-1H-inden-1-yl)acetamide (compound 1) At room temperature and under N2, 1,4-dioxane (5 mL) was added to a mixture of (S)-N-(5-(2-(2-aminopyridin-3-yl)-5-chloro-3H-imidazo[4,5-b]pyridin-3-yl)-2,3-dihydro-1H-inden-1-yl)acetamide (intermediate 1-1) (200 mg, 0.477 mmol, 1 equivalent), pyrazole (39 mg, 0.57 mmol, 1.5 equivalent), t-BuBrettPhos Pd G3 (41 mg, 0.048 mmol, 0.1 equivalent), t-BuBrettPhos (23 mg, 0.048 mmol, 0.1 equivalent), and K3PO4 (304 mg, 1.43 mmol, 3 equivalent). The resulting mixture was stirred at 100 °C under a nitrogen atmosphere for 2 h. Brine was added, and the mixture was extracted with ethyl acetate. The combined organic layers were dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography using a gradient of methanol in ethyl acetate. The substance obtained at this stage was used for subsequent transformations, as described below. The substance was further purified by preparative HPLC on an XSelect CSH Prep C18 OBD column using a gradient of acetonitrile in water (+0.05% TFA) for characterization and determination to give (S)-N-(5-(2-(2-aminopyridin-3-yl)-5-(1H-pyrazol-1-yl)-3H-imidazo[4,5-b]pyridin-3-yl)-2,3-dihydro-1H-indene-1-yl)acetamide (TFA salt) (compound 1) (84 mg, 39%) as a white solid. 25 H 22The calculated MS (ESI) value for N8O is 450.19 m / z, and the measured value is 451.15 [M+H]. + . 1 H NMR (300 MHz, DMSO- d 6) δ (ppm): 8.40 - 8.50 (m,1H), 8.33 - 8.40 (m, 1H), 8.02 - 8.10 (m, 1H), 7.95 - 8.02 (m, 1H), 7.78 -7.88 (m, 1H), 7.72 - 7.78 (m, 1H), 7.40 - 7.51 (m, 1H), 7.26 - 7.40 (m, 2H), 6.78 - 6.90 (m, 1H), 6.55 - 6.65 (m, 1H), 5.22 - 5.40 (m, 1H), 2.80 - 3.10(m, 2H), 2.35 - 2.50 (m, 1H), 1.91 - 2.00 (m, 3H), 1.78 - 1.90 (m, 1H).

[0241] Intermediate 1-1: ( S )- N -(5-(2-(2-aminopyridin-3-yl)-5-chloro-3 H -imidazo[4,5- b ]pyridin-3-yl)-2,3-dihydro-1 H -indene-1-yl)acetamide Synthesis route: Step 1: ( S )- N -(5-bromo-2,3-dihydro-1 H Synthesis of 1-indene-1-yl)acetamide Acetic anhydride (55.2 g, 526 mmol, 1.5 equivalent) was added to a mixture of (S)-5-bromo-2,3-dihydro-1H-indene-1-amine (74 g, 350 mmol, 1 equivalent) and triethylamine (106 g, 1.05 mol, 3 equivalent) in dichloromethane (1.5 L) at 0 °C, and the mixture was stirred at 0 °C for 2 h. The reaction mixture was quenched by adding water and extracted three times with ethyl acetate. The combined organic layers were dried over anhydrous sodium sulfate and concentrated under reduced pressure. The crude product was recrystallized from petroleum ether to give (S)-N-(5-bromo-2,3-dihydro-1H-indene-1-yl)acetamide (90 g, 83% yield) as a white solid.11 H 12 MS (ESI) calculated value of BrNO: 253.01, measured value: 254.00 [M+H] + 256.00 [M+H+2] + .

[0242] Step 2: ( S )-(1-acetamido-2,3-dihydro-1 H Synthesis of tert-butyl indene-5-yl)carbamate Under a nitrogen atmosphere, towards N -[(1S)-5-bromo-2,3-dihydro-1 H [Indene-1-yl]acetamide (40 g, 157 mmol, 1 equivalent), tert-butyl carbamate (27.66 g, 236 mmol, 1.5 equivalent), XantPhos (9.11 g, 15.7 mmol, 10 mol%), palladium(II) acetate (3.54 g, 15.7 mmol, 10 mol%), and cesium carbonate (154 g, 472 mmol, 10 mol%) were mixed with 1,4-dioxane (300 mL). The resulting mixture was stirred at 100 °C for 3 h. The reaction mixture was quenched with water and extracted three times with ethyl acetate. The combined organic layers were dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography using petroleum ether / dichloromethane / methanol (70:27:3) as the eluent to obtain N -[(1S)-1-acetamido-2,3-dihydro-1 H [Indene-5-yl] tert-butyl carbamate (43.1 g, 48%). C 16 H 22 MS (ESI) calculated value of N2O3: 290.16 m / z, measured value: 289.05 [MH] - .

[0243] Step 3: (S)- N -(5-amino-2,3-dihydro-1 H Synthesis of 1-indene-1-yl)acetamide Towards N -[(1S)-1-acetamido-2,3-dihydro-1 H[Indene-5-yl]tert-butyl carbamate (43.1 g, 148 mmol, 1 equivalent) was added to a stirred solution of 1,4-dioxane in 4N hydrochloric acid (185 mL, 742 mmol, 5 equivalent) in dichloromethane (180 mL). The reaction mixture was stirred at room temperature for 1 h. The reaction mixture was concentrated under vacuum and recrystallized from ethyl acetate to give a white solid. N -[(1S)-5-amino-2,3-dihydro-1 H [Indene-1-yl]acetamide (hydrochloride) (23 g, 81%). C 11 H 14 MS (ESI) value of N₂O: 190.11 m / z, measured value: 191.15 [M+H] + .

[0244] Step 4: N -[(1S)-5-[(6-chloro-3-nitropyridin-2-yl)amino]-2,3-dihydro-1 H Synthesis of 1-indene-1-yl]acetamide Towards N -[(1S)-5-amino-2,3-dihydro-1 H [Indene-1-yl]acetamide (100 g, 526 mmol, 1 equivalent) was prepared in ethanol (2 L) solution with triethylamine (160 g, 1.58 mol, 3 equivalent) and 2,6-dichloro-3-nitropyridine (122 g, 631 mmol, 1.2 equivalent). The resulting mixture was stirred overnight at 60 °C. The mixture was then cooled to room temperature and quenched with water. The resulting precipitate was collected by filtration and washed with ethanol / water to give a red solid. N -[(1S)-5-[(6-chloro-3-nitropyridin-2-yl)amino]-2,3-dihydro-1 H [Indene-1-yl]acetamide (100 g, 49%). C 16 H 15 MS (ESI) calculated value of ClN4O3: 346.08 m / z, measured value: 345.00 [MH] - .

[0245] Step 5: N -[(1S)-5-[2-(2-aminopyridin-3-yl)-5-chloroimidozolo[4,5-b]pyridin-3-yl]-2,3-dihydro-1 H Synthesis of 1-indene-1-yl]acetamide (intermediate 1-1) Towards N -[(1S)-5-[(6-chloro-3-nitropyridin-2-yl)amino]-2,3-dihydro-1H [Indene-1-yl]acetamide (100 g, 288 mmol, 1 equivalent) was dissolved in dimethyl sulfoxide (1.8 L) and methanol (300 mL) with the addition of 2-aminopyridine-3-carboxaldehyde (38.74 g, 317.2 mmol, 1.1 equivalent) and sodium dithionite (110 g, 634 mmol, 2.2 equivalent). The resulting mixture was stirred overnight at 100 °C. Water was added, and the precipitated solid was collected by filtration and washed with water. The collected solid was purified by silica gel column chromatography with elution in dichloromethane / methanol (10:1) to give a yellow solid. N -[(1S)-5-[2-(2-aminopyridin-3-yl)-5-chloroimidozolo[4,5-b]pyridin-3-yl]-2,3-dihydro-1 H [Indene-1-yl]acetamide (intermediate 1-1) (43.2 g, 31%). C 22 H 19 MS (ESI) calculated value of ClN6O: 418.13 m / z, measured value: 419.10 [M+H] + .

[0246] Example 2: (S)-3-(3-(1-amino-2,3-dihydro-1H-inden-5-yl)-5-(1H-pyrazol-1-yl)-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine (Compound 2) Synthesis route: Step 1: Synthesis of (S)-3-(3-(1-amino-2,3-dihydro-1H-inden-5-yl)-5-(1H-pyrazol-1-yl)-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine (compound 2) To a stirred suspension of (S)-N-(5-(2-(2-aminopyridin-3-yl)-5-(1H-pyrazol-1-yl)-3H-imidazo[4,5-b]pyridin-3-yl)-2,3-dihydro-1H-indene-1-yl)acetamide (compound 1) (1.00 g, 2.22 mmol, 1 equivalent) in methanol (5 mL), HCl (5 mL, concentrated) was added, and the resulting solution was stirred overnight at 90 °C under a nitrogen atmosphere. The solution was cooled to room temperature and diluted with dichloromethane. The solution was concentrated to dryness under reduced pressure. The crude solid was dissolved in DMSO and pyrrolidine (395 mg, 5.55 mmol, 2.5 equivalents) was added. The solution was stirred for 2 min, followed by the addition of TFA (959 mg, 6.66 mmol, 3 equivalents). The solution was purified by preparative HPLC on a Phenomenex Gemini C18 column using a gradient of acetonitrile in water (+0.05% TFA) to give (S)-3-(3-(1-amino-2,3-dihydro-1H-inden-5-yl)-5-(1H-pyrazol-1-yl)-3H-imidazo[4,5-b]pyridin-2-yl)pyridine-2-amine (TFA salt) (compound 2) (869 mg, 75%) as a yellow solid. 23 H 20 The calculated MS (ESI) value for N8 is 408.08 m / z, while the measured value is 409.15 [M+H]. + . 1 H NMR (300 MHz, DMSO-) d 6) δ (ppm): 8.40 - 8.43 (m, 1H), 8.32 - 8.40 (m, 1H), 8.02 -8.10 (m, 1H), 7.95 - 8.02 (m, 1H), 7.78 - 7.85 (m, 1H), 7.61 - 7.75 (m, 2H),7.48 - 7.58 (m, 1H), 7.36 - 7.45 (m,1H), 6.72 - 6.82 (m, 1H), 6.51 - 6.69 (m,1H), 4.72 - 4.82 (m, 1H), 3.05 - 3.30 (m, 1H), 2.88 - 3.05 (m, 1H), 2.55 -2.68 (m, 1H), 2.01 - 2.18 (m, 1H).

[0247] Example 3: ( S )- N -(5-(2-(2-aminopyridin-3-yl)-5-(1 H -pyrazole-1-yl)-3H -imidazo[4,5- b ]pyridin-3-yl)-2,3-dihydro-1 H (-inden-1-yl)-3,4-difluoro-5-methoxybenzamide (compound 3) Synthesis route: Step 1: ( S )- N -(5-(2-(2-aminopyridin-3-yl)-5-(1 H -pyrazole-1-yl)-3 H -imidazo[4,5- b ]pyridin-3-yl)-2,3-dihydro-1 H Synthesis of (inden-1-yl)-3,4-difluoro-5-methoxybenzamide (compound 3) 3,4-Difluoro-5-anesic acid (37 mg, 0.20 mmol, 1 equivalent) was added to a dry vial under a nitrogen atmosphere. A solution of HATU (79 mg, 0.20 mmol, 1.05 equivalent) in N,N-dimethylformamide (0.8 mL) was added, and the solution was cooled to 0°C. N,N-Diisopropylethylamine (26 mg, 0.20 mmol, 1 equivalent) was added, and the solution was stirred at 0°C for 1 h. (Add...) S )-3-(3-(1-amino-2,3-dihydro-1 H -indene-5-yl)-5-(1 H -pyrazole-1-yl)-3 H -imidazo[4,5- b A solution of pyridin-2-yl)pyridin-2-amine (compound 2) (126 mg, 0.24 mmol, 1.2 equivalents) and N,N-diisopropylethylamine (64 mg, 0.5 mmol, 2.5 equivalents) in N,N-dimethylformamide (1.2 mL) was prepared and stirred overnight at room temperature. The reaction mixture was purified by preparative HPLC on a Phenomenex Gemini C18 column using a gradient of acetonitrile in water (+0.05% TFA (or formic acid for formate obtained using a similar procedure, or ammonium bicarbonate for free base obtained using a similar procedure)) to give ( S )- N -(5-(2-(2-aminopyridin-3-yl)-5-(1 H -pyrazole-1-yl)-3 H -imidazo[4,5- b ]pyridin-3-yl)-2,3-dihydro-1H (-indene-1-yl)-3,4-difluoro-5-methoxybenzamide (TFA salt) (compound 3) (78 mg, 69%). C 31 H 24 MS (ESI) calculated value of F2N8O2: 578.20 m / z, measured value: 579.25 [M+H] + . 1 H NMR (400 MHz, DMSO- d 6 ) δ (ppm) 9.00 (d, J = 8.2 Hz, 1H), 8.43 (d, J = 8.7Hz, 1H), 8.38 (dd, J = 2.6, 0.7 Hz, 1H), 8.09 (dd, J = 5.9, 1.7 Hz, 1H), 8.01(d, J = 8.6 Hz, 1H), 7.83 (dd, J = 1.8, 0.7 Hz, 1H), 7.76 (dd, J = 7.5, 1.7Hz, 1H), 7.62 – 7.57 (m, 2H), 7.49 – 7.46 (m, 1H), 7.42 – 7.35 (m, 2H), 6.79(dd, J = 7.6, 5.9 Hz, 1H), 6.57 (dd, J = 2.6, 1.7 Hz, 1H), 5.64 (dd, J = 8.2,8.2 Hz, 1H), 3.95 (s, 3H), 3.07 (ddd, J = 16.3, 8.9, 2.7 Hz, 1H), 2.93 (ddd,J = 16.2, 8.4, 8.4 Hz, 1H), 2.59 – 2.53 (m, 1H), 2.17 – 2.02 (m, 1H). 19 F NMR (376 MHz, DMSO- d 6 ) δ (ppm) -137.55 (d, J = 21.1 Hz), -156.31 (d, J = 21.3Hz).

[0248] The following compounds were prepared in a manner similar to the synthesis and preparation described in Example 3 (Compound 3).

[0249] Table 3. Characterization data of compounds prepared similar to compound 3. Example 4: ( S )- N -(5-(2-(2-aminopyridin-3-yl)-5-(1 H -pyrazole-1-yl)-3 H -imidazo[4,5- b ]pyridin-3-yl)-2,3-dihydro-1 H -indene-1-yl)-5-methyl-1 H-Pyrazole-3-carboxamide (compound 4) Compound 4 was prepared in a manner similar to that of compound 3 by using 5-methyl-3-pyrazolic acid instead of 3,4-difluoro-5-anisolic acid. 28 H 24 N 10 The calculated MS (ESI) value for O is 516.21 m / z, while the measured value is 517.30 [M+H]. + . 1 H NMR (400MHz, DMSO- d 6 ) (ppm) δ 8.45 - 8.40 (m, 2H), 8.39 (d, J = 2.6 Hz, 1H), 8.08(dd, J = 5.9, 1.7 Hz, 1H), 8.01 (d, J = 8.6 Hz, 1H), 7.83 (d, J = 1.6 Hz,1H), 7.73 (dd, J = 7.6, 1.7 Hz, 1H), 7.44 (s, 1H), 7.34 (s, 1H), 7.33 (s,1H), 6.80 (dd, J = 7.6, 5.9 Hz, 1H), 6.56 (dd, J = 2.6, 1.7 Hz, 1H), 6.49 (s,1H), 5.58 (dd, J = 8.4, 8.4 Hz, 1H), 3.03 (ddd, J = 16.3, 8.9, 2.7 Hz, 1H), 2.88 (ddd, J = 16.4, 8.5, 8.5 Hz, 1H), 2.48 - 2.41 (m, 1H), 2.26 (s, 3H), 2.14 (dddd, J = 12.3, 8.9, 8.9, 8.8 Hz, 1H). (TFA salt) Example 5: ( S )- N -(5-(2-(2-aminopyridin-3-yl)-5-(1 H -pyrazole-1-yl)-3 H -imidazo[4,5- b ]pyridin-3-yl)-2,3-dihydro-1 H -indene-1-yl)-2-(isoxazo-3-yloxy)acetamide (compound 5) Compound 5 was prepared in a manner similar to that of compound 3 by using potassium (3-isoxazolyloxy)acetate instead of 3,4-difluoro-5-anisolic acid and omitting the initial addition of N,N-diisopropylethylamine. 28 H 23 MS (ESI) calculated value of N9O3: 533.19 m / z, measured value: 534.25 [M+H] + . 1 H NMR (400 MHz, DMSO- d 6 ) δ (ppm) 8.67 - 8.63 (m, 2H), 8.42 (d, J = 8.6 Hz, 1H), 8.36 (d, J = 2.5 Hz, 1H), 8.07 (dd, J = 6.0, 1.7Hz, 1H), 8.01 (d, J = 8.7 Hz, 1H), 7.82 (d, J = 1.7 Hz, 1H), 7.77 (dd, J =7.5, 1.7 Hz, 1H), 7.44 (s, 1H), 7.34 (s, 1H), 7.33 (s, 1H), 6.81 (dd, J =7.6, 6.0 Hz, 1H), 6.56 (dd, J = 2.6, 1.7 Hz, 1H), 6.35 (d, J = 1.8 Hz, 1H), 5.42 (dd, J = 8.3, 8.3 Hz, 1H), 4.75 (s, 2H), 2.99 (ddd, J = 16.4, 8.9, 2.9Hz, 1H), 2.87 (ddd, J = 16.4, 8.5, 8.5 Hz, 1H), 2.47 - 2.41 (m, 1H), 1.96 (dddd, J = 12.4, 8.9, 8.9, 8.8 Hz, 1H). (TFA salt) Example 6: ( S )- N -(5-(2-(2-aminopyridin-3-yl)-5-(1 H -pyrazole-1-yl)-3 H -imidazo[4,5- b ]pyridin-3-yl)-2,3-dihydro-1 H -indene-1-yl)-5-methyl-4-oxo-4,5-dihydro-2 H -Pyrrolo[3,4-c]pyridine-1-carboxamide (compound 6) Compound 6 was prepared in a manner similar to that of compound 3 by using 5-methyl-4-oxo-2,5-dihydro-2,5-diaza-1-indolecarboxylic acid instead of 3,4-difluoro-5-anisolic acid. 32 H 26 N 10 The calculated MS (ESI) value for O2 is 582.22 m / z, while the measured value is 583.30 [M+H]. + . 1 H NMR (400 MHz, DMSO- d 6 ) δ (ppm) 12.51 (d, J = 3.4 Hz, 1H), 8.43 (d, J = 8.6 Hz, 1H), 8.39 (dd, J = 2.6, 0.7 Hz, 1H), 8.18 (d, J = 8.0Hz, 1H), 8.08 (dd, J = 5.8, 1.7 Hz, 1H), 8.01 (d, J = 8.6 Hz, 1H), 7.83 (dd,J = 1.7, 0.7 Hz, 1H), 7.72 - 7.66 (m, 2H), 7.49 - 7.42 (m, 2H), 7.36 (dd, J =8.1, 2.0 Hz, 1H), 7.10 (d, J = 7.4 Hz, 1H), 6.88 (dd, J = 7.4, 0.7 Hz, 1H), 6.76 (dd, J = 7.6, 5.8 Hz, 1H), 6.57 (dd, J = 2.6, 1.7 Hz, 1H), 5.61 (q, J =8.0 Hz, 1H), 3.39 (s, 3H), 3.06 (ddd, J = 16.7, 9.0, 3.3 Hz, 1H), 2.92 (ddd,J = 16.3, 8.4, 8.4 Hz, 1H), 2.57 (dddd, J = 12.4, 7.9, 7.9, 3.1 Hz, 1H), 2.05(dddd, J = 12.5, 8.7, 8.7, 8.7 Hz, 1H). (TFA salt) Example 7: N-{(S)-5-[2-(2-amino-3-pyridyl)-5-(1-pyrazolyl)-3H-1,3,4-triazainden-3-yl]-1-dihydroindenyl}5-(dimethylamino)-2-fluorobenzamide (Compound 7) Compound 7 was prepared in a manner similar to that of compound 3 by using 5-(dimethylamino)-2-fluorobenzoic acid instead of 3,4-difluoro-5-anisolic acid. 32 H 28 MS (ESI) calculated value for FN9O: 573.24 m / z, measured value: 574.30 [M+H] + . 1 HNMR (400 MHz, DMSO- d 6 ) δ (ppm): 8.63 (dd, J = 8.2, 1.6 Hz, 1H), 8.37 (d, J =8.7 Hz, 1H), 8.31 (dd, J = 2.6, 0.7 Hz, 1H), 8.04 (dd, J = 6.1, 1.7 Hz, 1H), 7.95 (d, J = 8.6 Hz, 1H), 7.76 - 7.75 (m, 1H), 7.73 (d, J = 1.7 Hz, 1H), 7.41(d, J = 1.9 Hz, 1H), 7.37 (d, J = 8.0 Hz, 1H), 7.31 (dd, J = 8.0, 1.9 Hz,1H), 7.09 – 7.02 (m, 1H), 6.89 (dd, J = 5.7, 3.2 Hz, 1H), 6.82 (ddd, J = 9.1,3.6, 3.6 Hz, 1H), 6.77 (dd, J = 7.5, 6.1 Hz, 1H), 6.49 (dd, J = 2.6, 1.7 Hz,1H), 5.52 (dd, J = 8.2, 8.2 Hz, 1H), 3.02 - 2.92 (m, 1H), 2.89 - 2.79 (m,7H), 2.50 - 2.45 (m, 1H), 2.07 - 1.91 (m, 1H). (TFA salt) Example 8: N-{(S)-5-[2-(2-amino-3-pyridinyl)-5-(1-pyrazolyl)-3H-1,3,4-triazainden-3-yl]-1-dihydroindenyl}-2-methyl-1-oxo-1,2-dihydro-3-isoquinoline carboxamide (Compound 8) Compound 8 was prepared in a manner similar to that of compound 3 by using 2-methyl-1-oxo-1,2-dihydro-3-isoquinolinecarboxylic acid instead of 3,4-difluoro-5-anisolic acid. 34 H 27MS (ESI) calculated value of N9O2: 593.23 m / z, measured value: 594.25 [M+H] + . 1 H NMR (400 MHz, DMSO- d 6 ) δ (ppm) 9.31 (d, J = 8.1 Hz, 1H), 8.37 (d, J =8.6 Hz, 1H), 8.32 (dd, J = 2.6, 0.7 Hz, 1H), 8.18 (dd, J = 8.1, 1.1 Hz, 1H), 8.03 (dd, J = 5.9, 1.7 Hz, 1H), 7.95 (d, J = 8.6 Hz, 1H), 7.76 (dd, J = 1.7,0.7 Hz, 1H), 7.72 - 7.65 (m, 3H), 7.51 (ddd, J = 8.2, 5.0, 3.4 Hz, 1H), 7.47(d, J = 8.0 Hz, 1H), 7.43 (d, J = 2.0 Hz, 1H), 7.33 (dd, J = 8.0, 2.0 Hz,1H), 6.83 (s, 1H), 6.72 (dd, J = 7.6, 5.9 Hz, 1H), 6.49 (dd, J = 2.6, 1.6 Hz,1H), 5.50 (dd, J = 8.0, 8.0 Hz, 1H), 3.48 (s, 3H), 3.00 (ddd, J = 16.4, 8.9,3.3 Hz, 1H), 2.87 (ddd, J = 16.3, 8.3, 8.3 Hz, 1H), 2.52 (dddd, J = 12.6,7.9, 7.9, 3.3 Hz, 1H), 2.07 - 1.96 (m, 1H). (TFA salt) Example 9: N-{(S)-5-[2-(2-amino-3-pyridinyl)-5-(1-pyrazolyl)-3H-1,3,4-triazainden-3-yl]-1-dihydroindenyl}(3-ethynyl-3-oxetanebutyloxy)acetamide (compound 9) Compound 9 was prepared in a manner similar to that of compound 3 by using (3-ethynyl-3-oxetanedioloxy)acetic acid instead of 3,4-difluoro-5-anisolic acid. 30 H 26MS (ESI) calculated value of N8O3: 546.21 m / z, measured value: 547.30 [M+H] + . 1 H NMR (400 MHz, DMSO- d 6 ) δ (ppm) 8.42 (d, J = 8.6 Hz, 1H), 8.40 – 8.36 (m,2H), 8.08 (dd, J = 5.8, 1.8 Hz, 1H), 8.01 (d, J = 8.6 Hz, 1H), 7.83 (dd, J =1.6, 0.7 Hz, 1H), 7.70 (dd, J = 7.6, 1.7 Hz, 1H), 7.44 (s, 1H), 7.34 (d, J =1.4 Hz, 2H), 6.76 (dd, J = 7.6, 5.8 Hz, 1H), 6.57 (dd, J = 2.6, 1.7 Hz, 1H),5.45 (dd, J = 8.4, 8.4 Hz, 1H), 4.69 (dd, J = 7.4, 2.3 Hz, 2H), 4.64 (d, J =6.8 Hz, 2H), 4.06 (d, J = 1.8 Hz, 2H), 3.99 (s, 1H), 3.01 (ddd, J = 16.3,8.9, 2.7 Hz, 1H), 2.88 (dddd, J = 16.4, 8.5, 8.5 Hz, 1H), 2.44 (dddd, J =12.4, 8.0, 7.9, 2.8 Hz, 1H), 2.04 (dddd, J = 12.4, 9.0, 9.0, 9.0 Hz, 1H). (TFA salt) Example 10: N-{(S)-5-[2-(2-amino-3-pyridinyl)-5-(1-pyrazolyl)-3H-1,3,4-triazainden-3-yl]-1-dihydroindenyl}3-(difluoromethyl)-3-methoxycyclobutaneformamide (Compound 10) Compound 10 was prepared in a manner similar to that of compound 3, using 3-(difluoromethyl)-3-methoxycyclobutanecarboxylic acid instead of 3,4-difluoro-5-anisolic acid. Note that a racemic acid was used, but a single unknown diastereomer was obtained. 30 H 28 MS(ESI) calculated value of F2N8O2: 570.23 m / z, measured value: 571.30 [M+H]+ . 1 H NMR (400 MHz, DMSO- d 6 ) (ppm)δ 8.42 (d, J = 8.6 Hz, 1H), 8.39 – 8.34 (m, 2H), 8.07 (dd, J = 5.8, 1.7 Hz,1H), 8.00 (d, J = 8.6 Hz, 1H), 7.83 (dd, J = 1.6, 0.7 Hz, 1H), 7.67 (dd, J =7.6, 1.7 Hz, 1H), 7.43 (s, 1H), 7.34 – 7.29 (m, 2H), 6.74 (dd, J = 7.6, 5.8Hz, 1H), 6.56 (dd, J = 2.6, 1.7 Hz, 1H), 6.15 (t, J = 55.4 Hz, 1H), 5.36 (dd,J = 8.1, 8.1 Hz, 1H), 3.27 (s, 3H), 2.97 (ddd, J = 16.3, 8.9, 3.0 Hz, 1H), 2.86 (ddd, J = 16.3, 8.4, 8.4 Hz, 1H), 2.74 (ddd, J = 8.7, 8.7, 8.7 Hz, 1H), 2.47 – 2.39 (m, 3H), 2.35 – 2.25 (m, 2H), 1.87 (dddd, J = 12.4, 8.9, 8.9, 8.9Hz, 1H). 19F NMR (376 MHz, DMSO) δ (ppm): -132.55. (TFA salt) Example 11: N-{(S)-5-[2-(2-amino-3-pyridinyl)-5-(1-pyrazolyl)-3H-1,3,4-triazainden-3-yl]-1-dihydroindenyl}(1-methyl-5-oxo-2-pyrrolidinyl)acetamide (Compound 11) Compound 11 was prepared in a manner similar to that of compound 3, using (1-methyl-5-oxo-2-pyrrolyl)acetic acid instead of 3,4-difluoro-5-anisolic acid. Note that a racemic acid was used and a mixture of diastereomers was obtained. C 30 H 29 MS (ESI) calculated value of N9O2: 547.24 m / z, measured value: 548.35 [M+H] + . 1H NMR (400 MHz, DMSO- d 6 ) δ (ppm):8.44 (dd, J = 8.1, 3.3 Hz, 1H), 8.37 (d, J = 8.6 Hz, 1H), 8.31 (dd, J = 2.6,0.7 Hz, 1H), 8.03 (dd, J = 6.0, 1.7 Hz, 1H), 7.95 (d, J = 8.6 Hz, 1H), 7.76(dd, J = 1.6, 0.7 Hz, 1H), 7.72 - 7.67 (m, 1H), 7.40 - 7.38 (m, 1H), 7.31 -7.23 (m, 2H), 6.76 - 6.71 (m, 1H), 6.51 - 6.48 (m, 1H), 5.35 - 5.26 (m, 1H),3.84 - 3.76 (m, 1H), 2.98 - 2.87 (m, 1H), 2.85 - 2.72 (m, 1H), 2.63 (s, 3H),2.58 - 2.51 (m, 1H), 2.42 - 2.34 (m, 1H), 2.24 -1.98 (m, 4H), 1.88 - 1.60 (m, 2H). (TFA salt) Example 12: (S)-N-(5-(2-(2-aminopyridin-3-yl)-5-(1H-pyrazol-1-yl)-3H-imidazo[4,5-b]pyridin-3-yl)-2,3-dihydro-1H-inden-1-yl)-4-methoxybenzamide (Compound 12) Compound 12 was prepared in a manner similar to that of compound 3 by using 4-methoxybenzoic acid instead of 3,4-difluoro-5-anisolic acid. 31 H 26 MS (ESI) calculated value of N8O2: 542.22 m / z, measured value: 543.30 [M+H] + . 1 H NMR (300 MHz, DMSO- d 6) δ (ppm): 8.40 - 8.50 (m, 2H), 8.02 - 8.10 (m, 2H), 7.90 - 7.95 (m,2H), 7.83 - 7.85 (m, 1H), 7.74 - 7.78 (m, 1H), 7.45 - 7.49 (m, 1H), 7.30 -7.40 (m, 2H), 7.01 - 7.09 (m, 2H), 6.78 - 6.90 (m, 1H), 6.60 - 6.62 (m, 1H),5.60 - 5.69 (m, 1H), 3.80 (s, 3H), 3.05 - 3.13 (m, 1H), 2.88 - 3.00 (m, 1H), 2.50 - 2.54 (m, 1H), 2.03 - 2.18 (m, 1H). (TFA salt) Example 13: (S)-N-(5-(2-(2-aminopyridin-3-yl)-5-(1H-pyrazol-1-yl)-3H-imidazo[4,5-b]pyridin-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazol-3-carboxamide (Compound 13) Using 1-methyl-1 H Compound 13 was prepared in a manner similar to that of compound 3 by replacing pyrazole-3-carboxylic acid with 3,4-difluoro-5-anisolic acid. 28 H 24 N 10 The calculated MS (ESI) value for O is 516.21 m / z, while the measured value is 517.20 [M+H]. + . 1 H NMR (300 MHz, DMSO-) d6) δ (ppm): 8.41 - 8.49 (m, 1H), 8.33 - 8.40 (m, 1H), 8.04 -8.11 (m, 1H), 7.97 - 8.03 (m, 1H), 7.73 - 7.88 (m, 3H), 7.44 (s, 1H), 7.27 -7.38 (m, 2H), 6.77 - 6.91 (m, 1H), 6.64 - 6.76 (m, 1H), 6.50 - 6.61 (m, 1H), 5.47 - 5.66 (m, 1H), 3.90 (s, 3H), 2.98 - 3.15 (m, 1H), 2.78 - 2.97 (m, 1H), 2.37 - 2.51 (m, 1H), 2.03 - 2.22 (m, 1H). (TFA salt) Example 14: (S)-N-(5-(2-(2-aminopyridin-3-yl)-5-(1H-pyrazol-1-yl)-3H-imidazo[4,5-b]pyridin-3-yl)-2,3-dihydro-1H-inden-1-yl)thiazolyl-5-carboxamide (Compound 14) Compound 14 was prepared in a manner similar to that of compound 3 by using thiazol-5-carboxylic acid instead of 3,4-difluoro-5-anisolic acid. 27 H 21 The calculated MS (ESI) value for N9OS is 519.16 m / z, while the measured value is 520.20 [M+H]. + . 1 H NMR (400 MHz, DMSO- d 6) δ (ppm): 9.21 - 9.27 (m, 1H), 8.55 - 8.59 (m, 1H), 8.32 - 8.39 (m,2H), 8.01 - 8.05 (m, 1H), 7.94 - 7.99 (m, 1H), 7.83 - 7.90 (m, 1H), 7.36 -7.40 (m, 2H), 7.26 - 7.31 (m, 2H), 6.56 - 6.60 (m, 1H), 6.45 - 6.52 (m, 1H),5.56 - 5.64 (m, 1H), 2.98 - 3.11 (m, 1H), 2.84 - 2.96 (m, 1H), 2.60 - 2.63 (m, 1H), 2.05 - 2.16 (m, 1H). (Formate) Example 15: (S)-N-(5-(2-(2-aminopyridin-3-yl)-5-(1H-pyrazol-1-yl)-3H-imidazo[4,5-b]pyridin-3-yl)-2,3-dihydro-1H-inden-1-yl)oxetane-3-carboxamide (Compound 15) Compound 15 was prepared in a manner similar to that of compound 3 by using oxetane-3-carboxylic acid instead of 3,4-difluoro-5-anisolic acid. 27 H 24 MS (ESI) calculated value of N8O2: 492.20 m / z, measured value: 493.20 [M+H] + . 1 H NMR (300MHz, DMSO- d 6) δ (ppm): 8.35 - 8.40 (m, 2H), 8.01 - 8.07 (m, 1H), 7.95 - 7.99(m, 1H), 7.83- 7.86 (m, 1H), 7.29 - 7.40 (m, 4H), 6.57 - 6.60 (m, 1H), 6.44 -6.49 (m, 1H), 5.37 - 5.48 (m, 1H), 4.65 - 4.71 (m, 4H), 3.79 - 3.90 (m, 1H), 2.85 - 3.03 (m, 2H), 2.55 - 2.62 (m, 1H), 1.85 - 1.93 (m, 1H).

[0250] Example 16: (S)-N-(5-(2-(2-aminopyridin-3-yl)-5-(1H-pyrazol-1-yl)-3H-imidazo[4,5-b]pyridin-3-yl)-2,3-dihydro-1H-inden-1-yl)-3-fluoro-4-hydroxybenzamide (Compound 16) Compound 16 was prepared in a manner similar to that of compound 3 by using 3-fluoro-4-hydroxybenzoic acid instead of 3,4-difluoro-5-anisolic acid. 30 H 23 MS (ESI) calculated value of FN8O2: 546.19 m / z, measured value: 547.25 [M+H] + . 1 H NMR (400MHz, DMSO- d6) δ (ppm): 8.35 - 8.40 (m, 2H), 8.01 - 8.07 (m, 1H), 7.92 - 7.97(m, 1H), 7.80 - 7.82 (m, 1H), 7.72 - 7.78 (m, 1H), 7.65 - 7.69 (m, 1H), 7.37- 7.40 (m, 1H), 7.31 - 7.35 (m, 1H), 7.25 - 7.30 (m, 2H), 6.97 - 7.05 (m,1H), 6.55 - 6.58 (m, 1H), 6.43 - 6.48 (m, 1H), 5.58 - 5.65 (m, 1H), 2.99 -3.07 (m, 1H), 2.82 - 2.94 (m, 1H), 2.54 - 2.57 (m, 1H), 2.01 - 2.10 (m, 1H). 19 F NMR (376 MHz, DMSO- d 6) δ (ppm): -136.43.

[0251] Example 17: (S)-N-(5-(2-(2-aminopyridin-3-yl)-5-(1H-pyrazol-1-yl)-3H-imidazo[4,5-b]pyridin-3-yl)-2,3-dihydro-1H-inden-1-yl)imidazo[1,2-a]pyridin-6-carboxamide (Compound 17) Use imidazo[1,2- a Compound 17 was prepared in a manner similar to that of compound 3 by replacing 3,4-difluoro-5-anisolic acid with pyridine-6-carboxylic acid. 31 H 24 N 10 The calculated MS (ESI) value for O is 552.21 m / z, while the measured value is 553.20 [M+H]. + . 1 H NMR (300 MHz, DMSO-) d6) δ (ppm): 9.12 - 9.22 (m, 1H), 8.29 - 8.41 (m, 2H), 8.06 -8.11 (m, 1H), 7.98 - 8.05 (m, 1H), 7.89 - 7.97 (m, 1H), 7.79 - 7.86 (m, 1H),7.70 - 7.78 (m, 1H), 7.58 - 7.69 (m, 2H), 7.36 - 7.48 (m, 2H), 7.22 - 7.35(m, 2H), 6.51 - 6.60 (m, 1H), 6.39 - 6.50 (m, 1H), 5.57 - 5.70 (m, 1H), 3.01- 3.17 (m, 1H), 2.85 - 3.00 (m, 1H), 2.53 - 2.69 (m, 1H), 2.01 - 2.21 (m, 1H).

[0252] Example 18: (S)-N-(5-(2-(2-aminopyridin-3-yl)-5-(1H-pyrazol-1-yl)-3H-imidazo[4,5-b]pyridin-3-yl)-2,3-dihydro-1H-inden-1-yl)-6-(difluoromethyl)nicotinamide (Compound 18) Compound 18 was prepared in a manner similar to that of compound 3 by using 6-(difluoromethyl)nicotinic acid instead of 3,4-difluoro-5-anesticic acid. 30 H 23 MS (ESI) calculated value of F2N9O: 563.20 m / z, measured value: 564.15 [M+H] + . 1 H NMR (300MHz, DMSO- d 6) δ (ppm): 9.06 - 8.25 (m, 1H), 8.23 ​​- 8.55 (m, 3H), 7.95 - 8.22(m, 2H), 7.60 - 7.90 (m, 3H), 7.28 - 7.60 (m, 3H), 6.72 - 7.25 (m, 2H), 6.40- 6.70 (m, 1H), 5.48 - 5.78 (m, 1H), 2.95 - 3.20 (m, 1H), 2.85 - 2.95 (m,1H), 2.51 - 2.60 (m, 1H), 1.98 - 2.20 (m, 1H). 19F NMR (282 MHz, DMSO- d 6 δ(ppm): -116.08.

[0253] Example 19: (S)-N-(5-(2-(2-aminopyridin-3-yl)-5-(1H-pyrazol-1-yl)-3H-imidazo[4,5-b]pyridin-3-yl)-2,3-dihydro-1H-inden-1-yl)pyrazin-2-carboxamide (Compound 19) Compound 19 was prepared in a manner similar to that of compound 3 by using pyrazine-2-carboxylic acid instead of 3,4-difluoro-5-anisolic acid. 28 H 22 N 10 The calculated MS (ESI) value for O is 514.20 m / z, while the measured value is 515.20 [M+H]. + . 1 H NMR (400 MHz, DMSO- d 6) δ (ppm): 9.23 - 9.26 (m, 1H), 8.87 - 8.92 (m, 1H), 8.75 - 8.79 (m,1H), 8.31 - 8.39 (m, 2H), 8.01 - 8.06 (m, 1H), 7.95 - 7.99 (m, 1H), 7.81-7.85 (m, 1H), 7.37 - 7.40 (m, 1H), 7.34 - 7.37 (m, 1H), 7.26 - 7.31 (m, 2H), 6.53 - 6.57 (m, 1H), 6.44 - 6.49 (m, 1H), 5.64 - 5.69 (m, 1H), 3.01 - 3.11 (m, 1H), 2.89 - 2.97 (m, 1H), 2.60 - 2.62 (m, 1H), 2.17 - 2.26 (m, 1H). (Formate) Example 20: (S)-N-(5-(2-(2-aminopyridin-3-yl)-5-(1H-pyrazol-1-yl)-3H-imidazo[4,5-b]pyridin-3-yl)-2,3-dihydro-1H-inden-1-yl)benzo[d]isoxazole-5-carboxamide (Compound 20) Use benzo[ d Compound 20 was prepared in a manner similar to that of compound 3 by replacing 3,4-difluoro-5-anisolic acid with isoxazol-5-carboxylic acid.31 H 23 MS (ESI) calculated value of N9O2: 553.20 m / z, measured value: 554.15 [M+H] + . 1 H NMR (400MHz, DMSO- d 6) δ (ppm): 8.83 - 8.91 (m, 1H), 8.31 - 8.39 (m, 2H), 8.21 - 8.28(m, 1H), 8.06 - 8.11 (m, 1H), 8.01 - 8.05 (m, 1H), 7.94 - 7.99 (m, 1H), 7.80- 7.89 (m, 1H), 7.33 - 7.43 (m, 2H), 7.26 - 7.31 (m, 2H), 7.06 - 7.15 (m,1H), 6.57 - 6.61 (m, 1H), 6.43 - 6.51 (m, 1H), 5.51 - 5.64 (m, 1H), 2.98 -3.11 (m, 1H), 2.84 - 2.96 (m, 1H), 2.56 - 2.61 (m, 1H), 2.05 - 2.18 (m, 1H). (Formate) Example 21: (S)-N-(5-(2-(2-aminopyridin-3-yl)-5-(1H-pyrazol-1-yl)-3H-imidazo[4,5-b]pyridin-3-yl)-2,3-dihydro-1H-inden-1-yl)-5-methoxynicotinamide (Compound 21) Compound 21 was prepared in a manner similar to that of compound 3 by using 5-methoxynicotinic acid instead of 3,4-difluoro-5-anisolic acid. 30 H 25 MS (ESI) calculated value of N9O2: 543.21 m / z, measured value: 544.20 [M+H] + . 1 H NMR (300 MHz, DMSO- d6) δ (ppm): 8.70 - 8.80 (m, 1H), 8.45 - 8.59 (m, 2H), 8.29 - 8.35 (m,1H), 8.09 - 8.19 (m, 1H), 8.01 - 8.08 (m, 1H), 7.76 - 7.91 (m, 3H), 7.31 -7.52 (m, 3H), 6.81 - 6.99 (m, 1H), 6.51 - 6.75 (m, 1H), 5.64 - 5.79 (m, 1H),3.89 (s, 3H), 3.01 - 3.18 (m, 1H), 2.82 - 2.99 (m, 1H), 2.59 - 2.61 (m, 1H), 2.01 - 2.26 (m, 1H). (TFA salt) Example 22: (S)-N-(5-(2-(2-aminopyridin-3-yl)-5-(1H-pyrazol-1-yl)-3H-imidazo[4,5-b]pyridin-3-yl)-2,3-dihydro-1H-inden-1-yl)-1H-benzo[d]imidazo-5-carboxamide (Compound 22) Use 1 H -benzo[ d Compound 22 was prepared in a manner similar to that of compound 3 by replacing 3,4-difluoro-5-anisolic acid with imidazole-5-carboxylic acid. 31 H 24 N 10 The calculated MS (ESI) value for O is 552.21 m / z, while the measured value is 553.20 [M+H]. + . 1 H NMR (300 MHz, DMSO-) d 6) δ (ppm): 9.26 (s, 1H), 8.25 - 8.46 (m, 3H), 7.95 - 8.12(m, 3H), 7.69 - 7.88 (m, 3H), 7.30 - 7.51 (m, 3H), 6.79 - 6.83 (m, 1H), 6.51- 6.60 (m, 1H), 5.55 - 5.68 (m, 1H), 3.09 - 3.21 (m, 1H), 2.88 - 3.02 (m,1H), 2.58 - 2.68 (m, 1H), 2.03 - 2.23 (m, 1H). (TFA salt) Example 23: (S)-N-(5-(2-(2-aminopyridin-3-yl)-5-(1H-pyrazol-1-yl)-3H-imidazo[4,5-b]pyridin-3-yl)-2,3-dihydro-1H-inden-1-yl)-2-methoxypyrimidine-5-carboxamide (Compound 23) Compound 23 was prepared in a manner similar to that of compound 3 by using 2-methoxypyrimidine-5-carboxylic acid instead of 3,4-difluoro-5-anisolic acid. 29 H 24 N 10 The calculated MS (ESI) value for O2 is 544.21 m / z, while the measured value is 545.20 [M+H]. + . 1 H NMR (400 MHz, DMSO-) d 6 ) δ (ppm): 9.08 (m, 3H), 8.35 - 8.37 (m, 2H), 8.01 - 8.02(m, 1H), 7.94 - 7.96 (m, 1H), 7.81 - 7.82 (m, 1H), 7.41 - 7.44 (m, 2H), 7.31- 7.33 (m, 2H), 6.88 - 6.89 (m, 2H), 6.55 - 6.56 (m, 1H), 6.46 - 6.47 (m,1H), 5.63 - 5.65 (m, 1H), 3.99 (s, 3H), 3.05 - 3.06 (m,1H), 2.93 - 2.95 (m,1H), 2.50 - 2.51 (m, 1H), 2.06 - 2.09 (m, 1H).

[0254] Example 24: (S)-N-(5-(2-(2-aminopyridin-3-yl)-5-(1H-pyrazol-1-yl)-3H-imidazo[4,5-b]pyridin-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-6-oxo-1,6-dihydropyridin-3-carboxamide (Compound 24) Compound 24 was prepared in a manner similar to that of compound 3 by using 1-methyl-6-oxo-1,6-dihydropyridine-3-carboxylic acid instead of 3,4-difluoro-5-anisolic acid. 30 H 25 MS (ESI) calculated value of N9O2: 543.21 m / z, measured value: 544.20 [M+H] + .1 H NMR (400 MHz, DMSO- d 6 ) δ (ppm): 8.63 - 8.65 (m, 1H), 8.45 - 8.46 (m,1H), 8.36 - 8.38 (m, 2H), 8.02 - 8.03 (m, 1H), 7.94 - 7.96 (m, 2H), 7.81 -7.82 (m, 1H), 7.35 - 7.37 (m, 1H), 7.29 - 7.31 (m, 1H), 7.28 - 7.29 (m, 2H), 6.92 - 6.93 (m, 2H), 6.47 - 6.56 (m, 1H), 6.41 - 6.43 (m, 2H), 5.56 - 5.63(m, 1H), 3.49 (s, 3H), 3.00 - 3.02 (m, 1H), 2.92 - 2.95 (m, 1H), 2.50 - 2.52(m, 1H), 2.00 - 2.01 (m, 1H).

[0255] Example 25: (S)-N-(5-(2-(2-aminopyridin-3-yl)-5-(1H-pyrazol-1-yl)-3H-imidazo[4,5-b]pyridin-3-yl)-2,3-dihydro-1H-inden-1-yl)-2-methoxyisonicotinamide (Compound 25) Compound 25 was prepared in a manner similar to that of compound 3 by using 2-methoxyisonicotinic acid instead of 3,4-difluoro-5-anisolic acid. 30 H 25 The calculated MS (ESI) value for N9O2 is 543.21 m / z, and the measured value is 544.15 [M+H]. + . 1 H NMR (400 MHz, DMSO- d 6) δ (ppm): 9.13 - 9.15 (m, 1H), 8.37 - 8.38 (m, 2H), 8.30 - 8.31 (m,1H), 8.01 - 8.02 (m, 1H), 7.94 - 7.96 (m, 1H), 7.81 - 7.82 (m, 1H), 7.39 -7.45 (m, 3H), 7.28 - 7.32 (m, 3H), 6.90 (s, 2H), 6.55 - 6.56 (m, 1H), 6.43 -6.45 (m, 1H), 5.62 - 5.64 (m, 1H), 3.90 (s, 3H), 2.96 - 3.05 (m, 2H), 2.50 -2.55 (m, 1H), 2.09 - 2.12 (m, 1H).

[0256] Example 26: (S)-N-(5-(2-(2-aminopyridin-3-yl)-5-(1H-pyrazol-1-yl)-3H-imidazo[4,5-b]pyridin-3-yl)-2,3-dihydro-1H-inden-1-yl)-6-methylnicotinamide (Compound 26) Compound 26 was prepared in a manner similar to that of compound 3 by using 6-methylnicotinic acid instead of 3,4-difluoro-5-anisolic acid. 30 H 25 The calculated MS (ESI) value for N9O is 527.22 m / z, while the measured value is 528.30 [M+H]. + . 1 H NMR (300 MHz, DMSO- d6) δ (ppm): 8.92 - 8.93 (m, 1H), 8.37 - 8.41 (m, 2H), 8.16 - 8.21 (m,1H), 8.00 - 8.05 (m, 1H), 7.95 - 7.99 (m, 1H), 7.79 - 7.81 (m, 1H), 7.38 -7.44 (m, 3H), 7.28 - 7.31 (m, 2H), 6.56 - 6.59 (m, 1H), 6.47 - 6.53 (m, 1H),5.60 - 5.67 (m, 1H), 3.00 - 3.10 (m, 1H), 2.88 - 2.98 (m, 1H), 2.59 - 2.61 (m, 1H), 2.54 (s, 3H), 2.03 - 2.18 (m, 1H). (TFA salt) Example 27: (S)-N-(5-(2-(2-aminopyridin-3-yl)-5-(1H-pyrazol-1-yl)-3H-imidazo[4,5-b]pyridin-3-yl)-2,3-dihydro-1H-inden-1-yl)morpholine-4-carboxamide (Compound 27) Synthesis route: Step 1: Synthesis of (S)-N-(5-(2-(2-aminopyridin-3-yl)-5-(1H-pyrazol-1-yl)-3H-imidazo[4,5-b]pyridin-3-yl)-2,3-dihydro-1H-inden-1-yl)morpholine-4-carboxamide (compound 27) A suspension of (S)-3-(3-(1-amino-2,3-dihydro-1H-inden-5-yl)-5-(1H-pyrazol-1-yl)-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine (compound 2) (200 mg, 0.490 mmol, 1.2 equivalents) in dichloromethane was treated with pyridine (484 mg, 6.12 mmol, 15 equivalents), and the resulting mixture was stirred at room temperature for 3 min, followed by dropwise addition of morpholine-4-formyl chloride (61 mg, 0.408 mmol, 1 equivalent) at room temperature. The resulting mixture was stirred at room temperature for 1 h. The reaction mixture was concentrated under reduced pressure, then dissolved in dichloromethane and concentrated to dryness under reduced pressure. The crude residue was purified by preparative HPLC on a YMC Triart C18 ExRs column using a gradient of acetonitrile in water (+10 mmol / L ammonium bicarbonate) to give (S)-N-(5-(2-(2-aminopyridin-3-yl)-5-(1H-pyrazol-1-yl)-3H-imidazo[4,5-b]pyridin-3-yl)-2,3-dihydro-1H-inden-1-yl)morpholine-4-carboxamide (compound 27) (17.5 mg, 8%) as a white solid. 28 H 27 MS (ESI) calculated value of N9O2: 521.23 m / z, measured value: 522.35 [M+H] + . 1 H NMR (300 MHz, DMSO- d 6) δ (ppm): 8.35 - 8.47 (m, 2H), 7.93 - 8.09 (m, 2H), 7.81 - 7.89 (s,1H), 7.29 - 7.48 (m, 4H), 6.52 - 6.64 (m, 2H), 5.21 - 5.33 (m, 1H), 2.55 -2.68 (m, 4H), 3.32 - 3.43 (m, 4H), 2.92 - 3.06 (m, 1H), 2.78 - 2.89 (m, 1H), 2.46 - 2.51 (m, 1H), 1.89 - 2.03 (m, 1H).

[0257] The following compounds were prepared in a manner similar to the synthesis in Example 27 (Compound 27).

[0258] Table 3A. Characterization data of compounds prepared similar to compound 27. Example 28: (S)-N-(5-(2-(2-aminopyridin-3-yl)-5-(1H-pyrazol-1-yl)-3H-imidazo[4,5-b]pyridin-3-yl)-2,3-dihydro-1H-inden-1-yl)-1-methyl-1H-pyrazol[3,4-b]pyridin-5-carboxamide (Compound 28) Using 1-methyl-1 H -pyrazolo[3,4- b Compound 28 was prepared in a manner similar to that of compound 3 by replacing 3,4-difluoro-5-anisolic acid with pyridine-5-carboxylic acid. 31 H 25 N 11 The calculated MS (ESI) value for O is 567.22 m / z, while the measured value is 568.15 [M+H]. + . 1 H NMR (300 MHz, DMSO- d 6) δ (ppm): 9.04 - 9.06 (m, 1H), 8.76 - 8.78 (m,1H), 8.28 - 8.41 (m, 3H), 8.00 - 8.02 (m, 1H), 7.93 - 7.95 (m, 1H), 7.80 -7.83 (m, 1H), 7.42 - 7.46 (m, 1H), 7.37 - 7.39 (m, 1H), 7.31 - 7.33 (m, 2H), 6.48 - 6.61 (m, 2H), 5.60 - 5.66 (m, 1H), 4.10 (s, 3H), 2.90 - 3.08 (m, 2H),2.50 - 2.54 (m, 1H), 2.10 - 2.13 (m, 1H).

[0259] Example 29: (S)-N-(5-(2-(2-aminopyridin-3-yl)-5-(1H-pyrazol-1-yl)-3H-imidazo[4,5-b]pyridin-3-yl)-2,3-dihydro-1H-inden-1-yl)-2-methylnicotinamide (Compound 29) Compound 29 was prepared in a manner similar to that of compound 3 by using 2-methylnicotinic acid instead of 3,4-difluoro-5-anisolic acid. 30 H 25 The calculated MS (ESI) value for N9O is 527.22 m / z, while the measured value is 528.15 [M+H]. + . 1H NMR (300 MHz, DMSO- d 6 ) δ (ppm): 8.50 - 8.52 (m, 1H), 8.32 - 8.40 (m, 2H), 8.00 - 8.02 (m,1H), 7.93 - 7.96 (m, 1H), 7.76 - 7.85 (m, 2H), 7.46 - 7.48 (m, 1H), 7.25 -7.42 (m, 4H), 6.54 - 6.57 (m, 1H), 6.50 - 6.52 (m, 1H), 5.54 - 5.58 (m, 1H), 2.83 - 3.11 (m, 2H), 2.58 - 2.60 (m, 1H), 2.55 - 3.57 (m, 3H),1.98 - 2.02 (m, 1H).

[0260] Example 30: (S)-N-(5-(2-(2-aminopyridin-3-yl)-5-(1H-pyrazol-1-yl)-3H-imidazo[4,5-b]pyridin-3-yl)-2,3-dihydro-1H-inden-1-yl)-5-methylnicotinamide (Compound 30) Compound 30 was prepared in a manner similar to that of compound 3 by using 5-methylnicotinic acid instead of 3,4-difluoro-5-anisolic acid. 30 H 25 The calculated MS (ESI) value for N9O is 527.22 m / z, while the measured value is 528.10 [M+H]. + . 1 H NMR (300 MHz, DMSO- d6) δ (ppm): 8.81 - 8.89 (m, 1H), 8.48 - 8.58 (m, 1H), 8.27 - 8.40 (m,2H), 8.05 - 8.14 (m, 1H), 7.98 - 8.04 (m, 1H), 7.89 - 7.97 (m, 1H), 7.76 -7.85 (m, 1H), 7.34 - 7.46 (m, 2H), 7.21 - 7.33 (m, 2H), 6.51 - 6.60 (m, 1H),6.40 - 6.50 (m, 1H), 5.57 - 5.73 (m, 1H), 2.99 - 3.13 (m, 1H), 2.83 - 2.98 (m, 1H), 2.57 - 2.61 (m, 1H), 2.36 (s, 3H), 1.98 - 2.21 (m, 1H).

[0261] Example 31: (S)-N-(5-(2-(2-aminopyridin-3-yl)-5-(1H-pyrazol-1-yl)-3H-imidazo[4,5-b]pyridin-3-yl)-2,3-dihydro-1H-inden-1-yl)-4-methylnicotinamide (Compound 31) Compound 31 was prepared in a manner similar to that of compound 3 by using 4-methylnicotinic acid instead of 3,4-difluoro-5-anisolic acid. 30 H 25 The calculated MS (ESI) value for N9O is 527.22 m / z, while the measured value is 528.15 [M+H]. + . 1 H NMR (400 MHz, DMSO- d6) δ (ppm): 8.54 - 8.55 (m, 1H), 8.48 - 8.49 (m, 1H), 8.35 - 8.36 (m,2H), 8.00 - 8.01 (m, 1H), 7.94 - 7.96 (m, 1H), 7.80 - 7.81 (m, 1H), 7.46 -7.48 (m, 1H), 7.39 - 7.40 (m, 1H), 7.31 - 7.32 (m, 2H), 7.26 - 7.27 (m, 1H),6.55 - 6.56 (m, 1H), 6.45 - 6.46 (m, 1H), 5.58 - 5.62 (m, 1H), 2.92 - 3.93 (m, 2H), 2.50 - 2.51 (m, 1H), 2.41 - 2.42 (m, 3H), 2.02 - 2.03 (m, 1H).

[0262] Example 32: (S)-N-(5-(2-(2-aminopyridin-3-yl)-5-(1H-pyrazol-1-yl)-3H-imidazo[4,5-b]pyridin-3-yl)-2,3-dihydro-1H-inden-1-yl)-5-fluoronicotinamide (Compound 32) Compound 32 was prepared in a manner similar to that of compound 3 by using 5-fluoronicotinic acid instead of 3,4-difluoro-5-anisolic acid. 29 H 22 The calculated MS (ESI) value for FN9O is 531.19 m / z, while the measured value is 532.30 [M+H]. + . 1 H NMR (300 MHz, DMSO- d6) δ (ppm): 9.15 - 9.23 (m, 1H), 8.89 - 8.96 (m, 1H), 8.68 - 8.75 (m,1H), 8.30 - 8.39 (m, 2H), 8.03 - 8.17 (m, 1H), 7.97 - 8.01 (m, 1H), 7.87 -7.96 (m, 1H), 7.73 - 7.79 (m, 1H), 7.32 - 7.41 (m, 2H), 7.19 - 7.31 (m, 2H), 6.50 - 6.56 (m, 1H), 6.38 - 6.48 (m, 1H), 5.53 - 5.66 (m, 1H), 2.86 - 3.09 (m, 2H), 2.56 - 2.61 (m, 1H), 2.01 - 2.16 (m, 1H). (Formate) Example 33: (S)-N-(5-(2-(2-aminopyridin-3-yl)-5-(1H-pyrazol-1-yl)-3H-imidazo[4,5-b]pyridin-3-yl)-2,3-dihydro-1H-inden-1-yl)pyridazine-4-carboxamide (Compound 33) Compound 33 was prepared in a manner similar to that of compound 3 by using pyridazine-4-carboxylic acid instead of 3,4-difluoro-5-anisolic acid. 28 H 22 N 10 The calculated MS (ESI) value for O is 514.20 m / z, while the measured value is 515.25 [M+H]. + . 1 H NMR (400 MHz, DMSO- d 6) δ (ppm): 9.58 - 9.64 (m, 1H), 9.41 - 9.48 (m, 1H), 8.33 - 8.41 (m,2H), 7.92 - 8.14 (m, 3H), 7.78 - 7.83 (m, 1H), 7.40 - 7.47 (m, 2H), 7.28 -7.39 (m, 2H), 6.48 - 6.58 (m, 2H), 5.59 - 5.68 (m, 1H), 2.93 - 3.05 (m, 2H),2.50 - 2.51 (m, 1H), 2.11 - 2.06 (m, 1H). (TFA salt) Example 34: N-[(1S)-5-[2-(2-aminopyridin-3-yl)-5-(pyrazol-1-yl)imidazo[4,5-b]pyridin-3-yl]-2,3-dihydro-1H-inden-1-yl]pyridin-3-carboxamide (compound 34) Compound 34 was prepared in a manner similar to that of compound 3 by using nicotinic acid instead of 3,4-difluoro-5-anisolic acid and PyBOP instead of HATU. 29 H 23 Calculated MS (ESI) value for N9O: 513.20 m / z, measured value: 514.25 [MH] + . 1 H NMR (400 MHz, DMSO-) d 6 ) δ 9.14 - 9.16 (m, 1H), 9.05 - 9.08 (m, 1H), 8.71 - 8.72(m, 1H), 8.33 - 8.36 (m, 2H), 8.25 - 8.28 (m, 1H), 8.16 (s, 1H), 7.93 - 8.02(m, 1H), 7.80 (s, 1H), 7.51 - 7.54 (m, 1H), 7.38 - 7.40 (m, 2H), 7.26 - 7.31(m, 2H), 6.54 - 6.55 (m, 1H), 6.44 - 6.47 (m, 1H), 5.62 - 5.68 (m, 1H), 2.87-3.08 (m, 2H), 2.53-2.58 (m, 1H), 2.09-2.14 (m, 1H).

[0263] Example 35: N-[(1S)-5-[2-(2-aminopyridin-3-yl)-5-(pyrazol-1-yl)imidazo[4,5-b]pyridin-3-yl]-2,3-dihydro-1H-inden-1-yl]pyridin-4-carboxamide (Compound 35) Compound 35 was prepared in a manner similar to that of compound 3 by using isonicotinic acid instead of 3,4-difluoro-5-anisolic acid. 29 H 23 The calculated MS (ESI) value for N9O is 513.57 m / z, while the measured value is 514.25 [M+H]. + . 1 H NMR (400 MHz, DMSO- d6 ) δ (ppm) 8.70- 8.72 (m, 2H), 8.32 - 8.34 (m, 2H), 7.99 -8.00 (m, 1H), 7.94- 7.98 (m, 1H), 7.78 - 7.82 (m, 3H), 7.35 - 7.37 (m, 2H), 7.25 - 7.27 (m,2H), 6.53 - 6.54 (m, 1H), 6.44 - 6.47 (m, 1H), 5.58 - 5.63 (m, 1H), 3.00 -3.05 (m, 1H), 2.85 - 2.94 (m, 1H), 2.51 - 2.52 (m, 1H), 2.07 - 2.13 (m, 1H).

[0264] Example 36: N-[(1S)-5-[2-(2-aminopyridin-3-yl)-5-(pyrazol-1-yl)imidazo[4,5-b]pyridin-3-yl]-2,3-dihydro-1H-inden-1-yl]pyridin-2-carboxamide (Compound 36) Compound 36 was prepared in a manner similar to that of compound 3 by using pyridinecarboxylic acid instead of 3,4-difluoro-5-anisolic acid and PyBOP instead of HATU. 29 H 23 The calculated MS (ESI) value for N9O is 513.20 m / z, and the measured value is 514.15 [M+H]. + . 1 HNMR (300 MHz, DMSO- d 6) δ (ppm): 8.64 - 8.66 (m, 1H), 8.35 - 8.37 (m, 2H), 8.02 - 8.13 (m, 1H), 7.96 - 8.05 (m, 2H), 7.94 - 7.96 (m, 1H), 7.80 - 7.81(m, 1H), 7.61 - 7.64 (m, 1H), 7.38 - 7.39 (m, 1H), 7.32 - 7.34 (m, 1H), 7.24- 7.28 (m, 2H), 6.54 - 6.55 (m, 1H), 6.44 - 6.47 (m, 1H), 5.63 - 5.65 (m,1H), 3.45 - 3.52 (m, 1H), 2.91 - 2.94 (m, 1H), 2.50 - 2.51 (m, 1H), 2.23 -2.33 (m, 1H).

[0265] Example 37: N-[(1S)-5-[2-(2-aminopyridin-3-yl)-5-(pyrazol-1-yl)imidazo[4,5-b]pyridin-3-yl]-2,3-dihydro-1H-inden-1-yl]cyclopropaneformamide (Compound 37) Compound 37 was prepared in a manner similar to that of compound 3 by using cyclopropanecarboxylic acid instead of 3,4-difluoro-5-anisolic acid. 27 H 24 MS (ESI) calculated value for N8O: 476.21 m / z, measured value: 477.05 [M+H] + . 1 HNMR (400 MHz, DMSO- d6) δ (ppm): 8.52 - 8.79 (m, 1H), 8.27 - 8.51 (m, 2H), 7.95 - 8.04 (m,1H), 7.90 - 7.99 (m, 1H), 7.78 - 7.90 (m, 1H), 7.32 - 7.48 (m, 1H), 7.24 -7.31 (m, 3H), 6.45 - 6.49 (m, 1H), 6.41 - 6.41 (m, 1H), 5.30 - 5.48 (m, 1H), 2.95 - 3.08 (m, 1H), 2.81 - 2.95 (m, 1H), 2.42 - 2.55 (m, 1H), 1.97 - 1.99 (m, 1H), 1.48 - 1.67 (m, 1H), 0.70 - 0.82 (m, 4H).

[0266] Example 38: N-[(1S)-5-[2-(2-aminopyridin-3-yl)-5-(pyrazol-1-yl)imidazo[4,5-b]pyridin-3-yl]-2,3-dihydro-1H-inden-1-yl]-6-methoxypyridin-3-carboxamide (Compound 38) Compound 38 was prepared in a manner similar to that of compound 3 by using 6-methoxynicotinic acid instead of 3,4-difluoro-5-anisolic acid. 30 H 25 MS (ESI) calculated value of N9O2: 543.21 m / z, measured value: 544.25 [M+H] + . 1 HNMR (400 MHz, DMSO- d6) δ (ppm): 8.85 - 9.09 (m, 1H), 8.61 - 9.85 (m, 1H), 8.42 - 8.49 (m,2H), 8.09 - 8.27 (m, 1H), 7.98 - 8.10 (m, 1H), 7.89 - 7.95 (m, 1H), 7.56 -7.89 (m, 1H), 7.14 - 7.44 (m, 4H), 6.85 - 6.92 (m, 1H), 6.55 - 6.70 (s, 1H), 6.35 - 6.55 (m, 1H), 5.55 - 5.70 (m, 1H), 3.85 - 3.99 (m, 3H), 3.08 - 3.14 (m, 1H), 2.81 - 2.99 (m, 1H), 2.52 - 2.61 (m, 1H), 2.01 - 2.15 (m, 1H).

[0267] Example 39: ( S )-N-(5-(2-(2-aminopyridin-3-yl)-5-(1 H -pyrazol-1-yl)-3H-imidazo[4,5- b ]pyridin-3-yl)-2,3-dihydro-1 H (indole-1-yl)-1-methyl-1H-pyrazole-4-carboxamide (compound 39) Using 1-methyl-1 H Compound 39 was prepared in a manner similar to that of compound 3, by substituting pyrazole-4-carboxylic acid for 3,4-difluoro-5-anisolic acid. 28 H 24 N 10 The calculated MS (ESI) value for O is 516.21 m / z, while the measured value is 517.15 [M+H]. + . 1 HNMR (400 MHz, DMSO- d6) δ (ppm): 8.55 - 8.75 (m, 1H), 8.30 - 8.45 (m, 2H), 8.15 -8.28 (m, 1H), 8.00 - 8.05 (m, 1H), 7.91 - 8.00 (m, 2H), 7.78 - 7.89 (m, 1H),7.20 -7.45 (m, 4H), 6.55 - 6.65 (m, 1H), 6.35 - 6.55 (m, 1H), 3.89 - 3.91 (m,3H), 2.90 - 3.15 (m, 1H), 2.80 - 2.90 (m, 1H), 2.50 - 2.51 (m, 1H), 1.90 -2.14 (m, 1H).

[0268] Example 40: N-[(1S)-5-[2-(2-aminopyridin-3-yl)-5-(pyrazol-1-yl)imidazo[4,5-b]pyridin-3-yl]-2,3-dihydro-1H-indene-1-yl]pyrimidine-5-carboxamide (Compound 40) Compound 40 was prepared in a manner similar to that of compound 3 by using pyrimidine-5-carboxylic acid instead of 3,4-difluoro-5-anisolic acid. 28 H 22 N 10 The calculated MS (ESI) value for O is 514.20 m / z, while the measured value is 515.15 [M+H]. + . 1 HNMR (400 MHz, DMSO- d 6) δ (ppm): 9.25 - 9.30 (m, 1H), 9.35 - 9.40 (m, 2H), 8.45 - 8.61 (m,2H), 7.98 - 8.10 (m, 2H), 7.80 - 7.82 (s, 1H), 7.50 - 7.60 (m, 2H), 7.30 -7.44 (m, 2H), 6.55 - 6.66 (m, 1H), 6.45 - 6.50 (m, 1H), 5.55 - 5.80 (m, 1H),2.80 - 3.20 (m, 2H), 2.45 - 2.52 (m, 1H), 2.01 - 2.15 (m, 1H).

[0269] Example 41: N-[(1S)-5-[2-(2-aminopyridin-3-yl)-5-(pyrazol-1-yl)imidazo[4,5-b]pyridin-3-yl]-2,3-dihydro-1H-inden-1-yl]-4-cyanobenzamide (Compound 41) Compound 41 was prepared in a manner similar to that of compound 3 by using 4-cyanobenzoic acid instead of 3,4-difluoro-5-anisolic acid. 31 H 23 MS (ESI) calculated value for N9O: 537.20 m / z, measured value: 538.20 [M+H] + . 1 HNMR (400 MHz, DMSO- d 6) δ (ppm): 8.30 - 8.60 (m, 2H), 7.90 - 8.30 (m, 6H), 7.65 - 7.90 (m,1H), 7.38 - 7.65 (m, 2H), 7.19 - 7.38 (m, 2H), 6.55 - 6.80 (m, 1H), 6.38 -6.55 (m, 1H), 5.50 - 5.88 (m, 1H), 2.89 - 3.30 (m, 2H), 2.58 - 2.70 (m, 1H), 1.95 - 2.30 (m, 1H).

[0270] Example 42: ( S )-N-(5-(2-(2-aminopyridin-3-yl)-5-(1 H -pyrazole-1-yl)-3 H -imidazo[4,5- b ]pyridin-3-yl)-2,3-dihydro-1 H (indene-1-yl)-4-hydroxybenzamide (compound 42) Compound 42 was prepared in a manner similar to that of compound 3 by using 4-hydroxybenzoic acid instead of 3,4-difluoro-5-anisolic acid. 30 H 24 MS (ESI) calculated value of N8O2: 528.20 m / z, measured value: 529.30 [M+H] + . 1 HNMR (400 MHz, DMSO- d6) δ (ppm): 8.35 - 8.37 (m, 2H), 8.01 - 8.02 (m, 1H), 7.94 - 8.00 (m,1H), 7.81 - 7.83 (m, 3H), 7.25 - 7.38 (m, 4H), 6.88 - 7.08 (m, 2H), 6.55 -6.58 (m, 1H), 6.44 - 6.46 (m, 1H), 5.60 - 5.64 (m, 1H), 2.87 - 3.03 (m, 2H),2.51 - 2.52 (m, 1H), 2.10 - 2.30 (m, 1H).

[0271] Example 43: ( S )-N-(5-(2-(2-aminopyridin-3-yl)-5-(1H-pyrazol-1-yl)-3 H -imidazo[4,5- b ]pyridin-3-yl)-2,3-dihydro-1 H (indene-1-yl)benzamide (compound 43) Compound 43 was prepared in a manner similar to that of compound 3 by using benzoic acid instead of 3,4-difluoro-5-anisolic acid and PyBOP instead of HATU. 30 H 24 The calculated MS (ESI) value for N8O is 512.21 m / z, and the measured value is 513.15 [M+H]. + . 1 HNMR (400 MHz, DMSO- d 6) δ (ppm): 8.94 (s, 1H), 8.36 - 8.38 (m, 2H), 8.04 (m, 1H), 7.94 - 7.97 (m, 3H), 7.81 7.82 (m, 1H), 7.48 - 7.51 (m, 3H), 7.41 (m, 2H),7.40 (m, 2H), 6.56 - 6.60 (m, 1H), 6.45 - 6.54 (m, 1H), 5.60 - 5.70 (m, 1H),2.96 - 3.12 (m, 1H), 2.85 - 2.95 (m, 1H), 2.50 - 2.52 (m, 1H), 2.01 - 2.22(m, 1H).

[0272] Example 44: (S)-N-(5-(2-(2-aminopyridin-3-yl)-5-(1H-pyrazol-1-yl)-3H-imidazo[4,5-b]pyridin-3-yl)-2,3-dihydro-1H-inden-1-yl)-2-(difluoromethyl)isonicotinamide (Compound 44) Compound 44 was prepared in a manner similar to that of compound 3 by using 2-(difluoromethyl)isonicotinic acid instead of 3,4-difluoro-5-anesticic acid. 30 H 23 MS (ESI) calculated value of F2N9O: 563.20 m / z, measured value: 564.25 [M+H] + . 1 H NMR (300MHz, DMSO- d 6) δ (ppm): 8.80 - 8.90 (m, 1H), 8.28 - 8.40 (m, 2H), 8.11 - 8.21(m, 1H), 8.00 - 8.09 (m, 2H), 7.88 - 7.99 (m, 1H), 7.76 - 7.85 (m, 1H), 7.36- 7.47 (m, 2H), 7.24 - 7.34 (m, 2H), 6.82 - 7.33 (m, 1H), 6.50 - 6.60 (m,1H), 6.39 - 6.49 (m, 1H), 5.57 - 5.71 (m, 1H), 2.82 - 3.15 (m, 2H), 2.51 -2.62 (m, 1H), 1.98 - 2.20 (m, 1H). 19 F NMR (282 MHz, DMSO- d 6) δ (ppm): -115.65.

[0273] Example 45: (S)-N-(5-(2-(2-aminopyridin-3-yl)-5-(1H-pyrazol-1-yl)-3H-imidazo[4,5-b]pyridin-3-yl)-2,3-dihydro-1H-inden-1-yl)-6-chloronicotinamide (Compound 45) Compound 45 was prepared in a manner similar to that of compound 3 by using 6-chloronicotinic acid instead of 3,4-difluoro-5-anisolic acid. 29 H 22 The MS (ESI) value for ClN9O is 547.16 m / z, and the measured value is 548.20 [M+H]. + .1 H NMR (300 MHz, DMSO- d 6) δ (ppm): 8.78 - 8.84 (m, 1H), 8.22 - 8.43 (m, 3H), 7.89 - 8.06 (m,2H), 7.82 - 7.87 (m, 1H), 7.62 - 7.68 (m, 1H), 7.23 - 7.49 (m, 4H), 6.54 -6.62 (m, 2H), 5.57 - 5.64 (m, 1H), 2.85 - 3.11 (m, 2H), 2.61 - 2.69 (m, 1H), 2.04 - 2.16 (m, 1H).

[0274] Example 46: N-[(1S)-5-[2-(2-aminopyridin-3-yl)-5-(pyrazol-1-yl)imidazo[4,5-b]pyridin-3-yl]-2,3-dihydro-1H-inden-1-yl]-6-cyclopropylpyridin-3-carboxamide (Compound 46) Compound 46 was prepared in a manner similar to that of compound 3 by using 6-cyclopropylnicotinic acid instead of 3,4-difluoro-5-anisolic acid. 32 H 27 The calculated MS (ESI) value for N9O is 553.23 m / z, while the measured value is 554.15 [M+H]. + . 1 H NMR (300 MHz, DMSO- d 6) δ (ppm): 8.96 - 9.06 (m, 1H), 8.85 - 8.95 (m, 1H), 8.28 - 8.43 (m,2H), 8.08 - 8.18 (m, 1H), 7.98 - 8.07 (m, 1H), 7.89 - 7.97 (m, 1H), 7.75 -7.85 (m, 1H), 7.34 - 7.46 (m, 3H), 7.22 - 7.33 (m, 2H), 6.50 - 6.60 (m, 1H),6.39 - 6.49 (m, 1H), 5.54 - 5.72 (m, 1H), 2.79 - 3.13 (m, 2H), 2.52 - 2.60 (m, 1H), 1.95 - 2.23 (m, 2H), 0.89 - 1.10 (m, 4H).

[0275] Example 47: N-((S)-5-(2-(2-aminopyridin-3-yl)-5-(1H-pyrazol-1-yl)-3H-imidazo[4,5-b]pyridin-3-yl)-2,3-dihydro-1H-inden-1-yl)-2-(5-oxopyrrolidine-2-yl)acetamide (Compound 47) Compound 47 was prepared in a manner similar to that of compound 3 by using 2-(5-oxopyrrolidone-2-yl)acetic acid instead of 3,4-difluoro-5-anisolic acid. 29 H 27 MS (ESI) calculated value of N9O2: 533.23 m / z, measured value: 534.30 [M+H] + . 1 HNMR (300 MHz, DMSO- d 6 δ (ppm): 8.31 - 8.40 (m, 2H), 7.95 - 8.03 (m, 2H), 7.98 - 7.82 (m, 1H), 7.25 - 7.50 (m, 4H), 6.50 - 6.60 (m, 2H), 5.33 - 5.41 (m, 1H), 3.88 - 3.93 (m, 1H), 2.79 - 3.02 (m, 2H), 2.45 - 2.65 (m, 2H), 2.29 - 2.35 (m, 1H), 2.09 - 2.25 (m, 3H), 1.80 - 1.92 (m, 1H), 1.65 - 1.78 (m, 1H). (Formate) Example 48: (S)-N-(5-(2-(2-aminopyridin-3-yl)-5-(1H-pyrazol-1-yl)-3H-imidazo[4,5-b]pyridin-3-yl)-2,3-dihydro-1H-inden-1-yl)-2-(pyridin-3-yl)acetamide (Compound 48) Compound 48 was prepared in a manner similar to that of compound 3 by using 2-(pyridin-3-yl)acetic acid (HCl salt) instead of 3,4-difluoro-5-anisolic acid and by using an additional equivalent of N,N-diisopropylethylamine. 30 H 25 The calculated MS (ESI) value for N9O is 527.22 m / z, while the measured value is 528.30 [M+H]. + . 1 H NMR (400 MHz, DMSO- d6) δ (ppm): 8.30 - 8.39 (m,3H), 8.21 - 8.26 (m, 1H), 7.90 - 7.95 (m, 1H), 7.78 - 7.83 (m, 1H), 7.70 -7.76 (m, 2H), 7.28 - 7.39 (m, 3H), 7.10 - 7.19 (m, 2H), 6.50 - 6.57 (m, 2H),5.19 - 5.25 (m, 1H), 3.53 (s, 2H), 2.90 - 2.98 (m, 1H), 2.72 - 2.81 (m, 1H),2.37 - 2.40 (m, 1H), 1.79 - 1.91 (m, 1H).

[0276] Example 49: N-[(1S)-5-[2-(2-aminopyridin-3-yl)-5-(pyrazol-1-yl)imidazo[4,5-b]pyridin-3-yl]-2,3-dihydro-1H-inden-1-yl]-2-(pyridin-4-yl)acetamide (compound 49) Compound 49 was prepared in a manner similar to that of compound 3 by using 2-(pyridin-4-yl)acetic acid (HCl salt) instead of 3,4-difluoro-5-anisolic acid and by using an additional equivalent of N,N-diisopropylethylamine. 30 H 25 The calculated MS (ESI) value for N9O is 527.22 m / z, while the measured value is 528.25 [M+H]. + . 1 H-NMR (400 MHz, DMSO- d 6) δ (ppm): 8.73 - 8.75 (m,1H), 8.48 - 8.50 (m, 2H), 8.34 - 8.36 (m, 2H), 8.00 - 8.01 (m, 1H), 7.93 -7.96 (m, 1H), 7.80 - 7.81 (m, 1H), 7.32 - 7.37 (m, 3H), 7.24 - 7.28 (m, 3H), 6.55 - 6.56 (m, 1H), 6.43 - 6.46 (m, 1H), 5.32 - 5.34 (m, 1H), 3.55 (s, 2H), 2.94 - 2.96 (m, 1H), 2.85 - 2.87 (m, 1H), 2.50 - 2.51 (m, 1H), 1.88 - 1.90 (m, 1H).

[0277] Example 50: (S)-N-(5-(2-(2-aminopyridin-3-yl)-5-(1H-pyrazol-1-yl)-3H-imidazo[4,5-b]pyridin-3-yl)-2,3-dihydro-1H-inden-1-yl)-2-(pyridin-2-yl)acetamide (Compound 50) Compound 50 was prepared in a manner similar to that of compound 3 by using 2-(pyridin-2-yl)acetic acid (HCl salt) instead of 3,4-difluoro-5-anisolic acid and by using an additional equivalent of N,N-diisopropylethylamine. 30 H 25 The calculated MS (ESI) value for N9O is 527.22 m / z, while the measured value is 528.30 [M+H]. + . 1 H NMR (300 MHz, DMSO- d 6) δ (ppm): 8.42 - 8.56 (m, 1H), 8.32 - 8.41 (m, 2H), 7.88 - 8.06 (m, 2H), 7.72 - 7.88 (m, 2H), 7.19 - 7.43 (m, 6H), 6.53 - 6.59 (m, 1H), 6.45 - 6.51 (m, 1H), 5.31 - 5.42 (m, 1H), 3.81 - 3.96 (m, 1H), 3.69 - 3.76 (m, 1H), 2.81 - 3.04 (m, 2H), 2.46 - 2.51 (m, 1H), 1.83 - 2.01 (m, 1H). (Formate) Example 51: (S)-N-(5-(2-(2-aminopyridin-3-yl)-5-(1H-pyrazol-1-yl)-3H-imidazo[4,5-b]pyridin-3-yl)-2,3-dihydro-1H-inden-1-yl)-2-(1H-pyrazol-5-yl)acetamide (Compound 51) Compound 51 was prepared in a manner similar to that of compound 3 by using 2-(1H-pyrazol-5-yl)acetic acid (HCl salt) instead of 3,4-difluoro-5-anisolic acid and by using an additional equivalent of N,N-diisopropylethylamine. 28 H 24 N 10 The calculated MS (ESI) value for O is 516.21 m / z, while the measured value is 517.15 [M+H]. + . 1H NMR (300 MHz, DMSO-d 6 ) δ (ppm): 8.32 - 8.41(m, 2H), 8.00 - 8.02 (m, 1H), 7.92 - 7.96 (m, 1H), 7.81 - 7.83 (m, 1H), 7.60- 7.62 (m, 1H), 7.21 - 7.35 (m, 4H), 6.52 - 6.56 (m, 1H), 6.42 - 6.46 (m,1H), 6.18 (s, 1H), 5.33 - 5.35 (m, 1H), 3.57 - 3.59 (m, 1H), 3.55 - 5.57 (m,1H), 2.78 - 3.05 (m, 2H), 2.44 - 2.47 (m, 1H), 1.90 - 1.92 (m, 1H).

[0278] Example 52: (S)-N-(5-(2-(2-aminopyridin-3-yl)-5-(3-fluoro-1H-pyrazol-1-yl)-3H-imidazo[4,5-b]pyridin-3-yl)-2,3-dihydro-1H-inden-1-yl)-6-methylnicotinamide (Compound 52) Compound 52 was prepared in a manner similar to that of compound 3, using 6-methylnicotinic acid instead of 3,4-difluoro-5-anesticic acid, intermediate 52-1 instead of compound 2, and PyBOP instead of HATU. 30 H 24 The calculated MS (ESI) value for FON9 is 545.21, while the measured value is 546.15 [M+H]. + . 1 H NMR (400 MHz, DMSO- d6) δ (ppm): 9.02 - 9.07 (m,1H), 8.42 - 8.49 (m, 2H), 8.30 - 8.36 (m, 1H), 8.04 - 8.11 (m, 1H), 7.81 -7.88 (m, 2H), 7.63 - 7.69 (m, 1H), 7.46 - 7.51 (m, 1H), 7.40 - 7.45 (m, 1H), 7.32 - 7.39 (m, 1H), 6.82 - 6.89 (m, 1H), 6.35 - 6.41 (m, 1H), 5. 59 - 5.68(m, 1H), 3.03 - 3.13 (m, 1H), 2.88 - 3.00 (m, 1H), 2.64 (s, 3H), 2.53 - 2.62 (m, 1H), 2.04 - 2.17 (m, 1H). 19 F NMR (376 MHz, DMSO- d 6) δ (ppm): -126.82. (TFA salt) Intermediate 52-1: ( S )-3-(3-(1-amino-2,3-dihydro-1 H -indene-5-yl)-5-(3-fluoro-1 H -pyrazole-1-yl)-3 H -imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine Intermediate 52-1 was prepared in a manner similar to that of compound 1 by using 3-fluoropyrazole instead of pyrazole. 23 H 19 The calculated MS (ESI) value for FN8 is 426.17 m / z, while the measured value is 427.10 [M+H]. + .

[0279] Example 53: (S)-N-(5-(2-(2-aminopyridin-3-yl)-5-(3-fluoro-1H-pyrazol-1-yl)-3H-imidazo[4,5-b]pyridin-3-yl)-2,3-dihydro-1H-inden-1-yl)-6-(difluoromethyl)nicotinamide (Compound 53) Compound 53 was prepared in a manner similar to that of compound 3 by using 6-(difluoromethyl)nicotinic acid instead of 3,4-difluoro-5-anesticic acid and intermediate 52-1 instead of compound 2. 30 H 22MS (ESI) calculated value for F3N9O: 581.19 m / z, measured value: 582.25 [M+H] + . 1 H NMR (300 MHz, DMSO- d 6) δ (ppm): 9.13 - 9.14 (m, 1H), 8.40 -8.46 (m, 1H), 8.30 - 8.36 (m, 1H), 8.28 - 8.29 (m, 1H), 8.01 - 8.03 (m, 1H),7.84 - 7.86 (m, 1H), 7.76 - 7.79 (m, 1H), 7.38 - 7.44 (m, 2H), 7.19 - 7.31(m, 2H), 6.83 - 7.20 (m, 1H), 6.45 - 6.55 (m, 1H), 6.30 - 6.35 (m, 1H), 5.83- 5.88 (m, 1H), 2.80 - 3.15 (m, 2H), 2.51 - 2.53 (m, 1H), 2.15 - 2.18 (m, 1H). 19 F NMR (300 MHz, DMSO- d 6) δ (ppm): -116.08, -127.28.

[0280] Example 54: (S)-N-(5-(2-(2-aminopyridin-3-yl)-5-(1H-pyrazol-1-yl)-3H-imidazo[4,5-b]pyridin-3-yl)-2,3-dihydro-1H-inden-1-yl)-6-(1H-pyrazol-1-yl)nicotinamide (Compound 54) Compound 54 was prepared in a manner similar to that of compound 3 by using 6-(1H-pyrazol-1-yl)nicotinic acid instead of 3,4-difluoro-5-anisolic acid. 32 H 25 N 11 The calculated MS (ESI) value for O is 579.22 m / z, while the measured value is 580.30 [M+H]. + . 1 H NMR (300MHz, DMSO- d6) δ (ppm): 8.91 - 8.99 (m, 1H), 8.62 - 8.69 (m, 1H), 8.34 - 8.48(m, 3H), 7.96 - 8.11 (m, 3H), 7.89 - 7.95 (m, 1H), 7.81 - 7.87 (m, 1H), 7.29- 7.51 (m, 4H), 6.69 - 6.72 (m, 1H), 6.57 - 6.65 (m, 2H), 5.63 - 5.72 (m,1H), 3.05 - 3.17 (m, 1H), 2.82 - 3.04 (m, 1H), 2.61 - 2.69 (m, 1H), 2.07 -2.21 (m, 1H).

[0281] Example 55: (S)-N-(5-(2-(2-aminopyridin-3-yl)-5-(1H-pyrazol-1-yl)-3H-imidazo[4,5-b]pyridin-3-yl)-2,3-dihydro-1H-inden-1-yl)-6-ethynylnicotinamide (Compound 55) Compound 55 was prepared in a manner similar to that of compound 3 by using 6-ethynylpyridin-3-carboxylic acid instead of 3,4-difluoro-5-anisolic acid. 31 H 23 The calculated MS (ESI) value for N9O is 537.20 m / z, while the measured value is 538.30 [M+H]. + . 1 H NMR (300MHz, DMSO- d6) δ (ppm): 8.93 - 8.99 (m, 1H), 8.40 - 8.48 (m, 1H), 8.31 - 8.39(m, 1H), 8.23 ​​- 8.29 (m, 1H), 8.01 - 8.08 (m, 1H), 7.89 - 7.96 (m, 1H), 7.81- 7.88 (m, 1H), 7.72 - 7.78 (m, 1H), 7.39 - 7.47 (m, 3H), 7.24 - 7.31 (m,1H), 6.56 - 6.67 (m, 2H), 5.52 - 5.64 (m, 1H), 4.16 - 4.21 (m, 1H), 3.07 -3.18 (m, 1H), 2.83 - 3.06 (m, 1H), 2.61 - 2.69 (m, 1H), 2.05 - 2.21 (m, 1H). (Formate) Example 56: (S)-N-(5-(2-(2-aminopyridin-3-yl)-5-(1H-pyrazol-1-yl)-3H-imidazo[4,5-b]pyridin-3-yl)-2,3-dihydro-1H-inden-1-yl)-6-(difluoromethyl)-4-methylnicotinamide (Compound 56) Synthesis route: Step 2: Synthesis of (S)-N-(5-(2-(2-aminopyridin-3-yl)-5-(1H-pyrazol-1-yl)-3H-imidazo[4,5-b]pyridin-3-yl)-2,3-dihydro-1H-inden-1-yl)-6-(difluoromethyl)-4-methylnicotinamide (compound 56) XPhos (6.3 mg, 0.013 mmol, 1 equivalent) and XPhos Pd G3 (11 mg, 0.013 mmol, 0.1 equivalent) were added to a solution of (S)-N-(5-(2-(2-aminopyridin-3-yl)-5-(1H-pyrazol-1-yl)-3H-imidazo[4,5-b]pyridin-3-yl)-2,3-dihydro-1H-indene-1-yl)-6-bromo-4-methylnicotinamide (intermediate 56-1) (80 mg, 0.13 mmol, 1 equivalent) and [1,3-bis[2,6-bis(isopropyl)phenyl]-2-imidazolidinedimethylsilver]difluoromethylsilver(I) (94 mg, 0.17 mmol, 1.3 equivalent) in toluene (6 mL), and the resulting mixture was stirred at 100 °C under a nitrogen atmosphere for 6 h. The reaction was quenched with water at room temperature. The resulting mixture was extracted three times with ethyl acetate. The combined organic layers were washed with brine and dried over anhydrous Na₂SO₄. After filtration, the filtrate was concentrated under reduced pressure. The crude product was purified by preparative HPLC on an XSelect CSH fluorophenyl column using a gradient of acetonitrile in water (+ 0.1% formic acid) to give (S)-N-(5-(2-(2-aminopyridin-3-yl)-5-(1H-pyrazol-1-yl)-3H-imidazo[4,5-b]pyridin-3-yl)-2,3-dihydro-1H-inden-1-yl)-6-(difluoromethyl)-4-methylnicotinamide (compound 56) (6.4 mg, 8%) as a white solid. 31 H 25 MS (ESI) calculated value of F2N9O: 577.22 m / z, measured value: 578.20 [M+H] + . 1 H NMR (300 MHz, DMSO- d 6) δ(ppm): 8.64 (s, 1H), 8.35 - 8.37 (m, 2H), 7.94 - 8.03 (m, 2H), 7.94 - 7.97(m, 1H), 7.66 (s, 1H), 7.49 - 7.51 (m, 1H), 7.33 - 7.39 (m, 1H), 7.26 - 7.29(m, 2H), 6.57 - 7.12 (m, 1H), 6.56 - 7.57 (m, 1H), 6.45 - 6.49 (m, 1H), 5.57- 5.62 (m, 1H), 2.89 - 3.15 (m, 2H), 2.51 - 2.53 (m, 1H), 2.41 - 2.48 (m,3H), 1.95 - 2.18 (m, 1H).19 F NMR (300 MHz, DMSO- d 6) δ (ppm): -115.64.

[0282] Intermediate 56-1: ( S )- N -(5-(2-(2-aminopyridin-3-yl)-5-(1 H -pyrazole-1-yl)-3 H -imidazo[4,5-b]pyridin-3-yl)-2,3-dihydro-1 H (indene-1-yl)-6-bromo-4-methylnicotinamide Intermediate 56-1 was prepared in a manner similar to that of compound 3 by using 6-bromo-4-methylnicotinic acid instead of 3,4-difluoro-5-anesticic acid. 30 H 24 MS (ESI) value of BrN9O: 605.13 m / z, measured values: 605.95, 607.95 [M+H, M+H+2] + .

[0283] The following compounds were prepared in a manner similar to the synthesis in Example 56 (Compound 56).

[0284] Table 4. Characterization data of compounds prepared similar to compound 56. Example 57: (S)-N-(5-(2-(2-aminopyridin-3-yl)-5-(1H-pyrazol-1-yl)-3H-imidazo[4,5-b]pyridin-3-yl)-2,3-dihydro-1H-inden-1-yl)-4-ethyloxazol-2-carboxamide (Compound 57) Synthesis route: Step 1: Synthesis of (S)-N-(5-(2-(2-aminopyridin-3-yl)-5-(1H-pyrazol-1-yl)-3H-imidazo[4,5-b]pyridin-3-yl)-2,3-dihydro-1H-inden-1-yl)-4-bromooxazol-2-carboxamide AlMe3 (1.15 mL, 2.21 mmol, 2 M in toluene, 5 equivalents) was added to a solution of (S)-3-(3-(1-amino-2,3-dihydro-1H-inden-5-yl)-5-(1H-pyrazol-1-yl)-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine (compound 2) (180 mg, 0.441 mmol, 1 equivalent) in DCE (5 mL). Then, methyl 4-bromooxazol-2-carboxylate (107 mg, 0.485 mmol, 1.1 equivalents) was added. The resulting mixture was maintained under nitrogen and stirred at 60 °C for 16 h. After cooling to room temperature, the reaction was quenched with water. The resulting mixture was extracted three times with ethyl acetate. The organic layers were combined, dried over anhydrous Na2SO4, filtered, and concentrated. The crude product was purified by reversed-phase rapid column chromatography on C18 silica gel using a gradient of acetonitrile in water (+ 0.05% TFA) to give (S)-N-(5-(2-(2-aminopyridin-3-yl)-5-(1H-pyrazol-1-yl)-3H-imidazo[4,5-b]pyridin-3-yl)-2,3-dihydro-1H-inden-1-yl)-4-bromooxazol-2-carboxamide (80 mg, 31%) as a yellow solid. 27 H 20 MS (ESI) calculated value of BrN9O2: 581.09 m / z, measured value: 582.00 [M+H] + .

[0285] Step 2: Synthesis of (S)-N-(5-(2-(2-aminopyridin-3-yl)-5-(1H-pyrazol-1-yl)-3H-imidazo[4,5-b]pyridin-3-yl)-2,3-dihydro-1H-inden-1-yl)-4-vinyloxazol-2-carboxamide To a solution of (S)-N-(5-(2-(2-aminopyridin-3-yl)-5-(1H-pyrazol-1-yl)-3H-imidazo[4,5-b]pyridin-3-yl)-2,3-dihydro-1H-indene-1-yl)-4-bromooxazol-2-carboxamide (60 mg, 0.103 mmol, 1 equivalent) in 1,4-dioxane (1.6 mL) and water (0.4 mL), 4,4,5,5-tetramethyl-2-vinyl-1,3,2-dioxaborhecyclopentane (159 mg, 1.03 mmol, 1 equivalent), Pd(PPh3)4 (12 mg, 0.010 mmol, 0.1 equivalent), and Na2CO3 (55 mg, 0.52 mmol, 5 equivalent) were added. The resulting mixture was maintained under a nitrogen atmosphere and stirred at 100 °C for 5 h. After cooling to room temperature, the reaction was quenched with water. The resulting mixture was extracted three times with ethyl acetate. The organic layers were combined, dried over anhydrous Na₂SO₄, filtered, and concentrated. The crude product was purified by reversed-phase rapid column chromatography on C18 silica gel using a gradient of acetonitrile in water (+0.05% TFA) to give (S)-N-(5-(2-(2-aminopyridin-3-yl)-5-(1H-pyrazol-1-yl)-3H-imidazo[4,5-b]pyridin-3-yl)-2,3-dihydro-1H-inden-1-yl)-4-vinyloxazol-2-carboxamide (40 mg, 73%) as a yellow solid. 29 H 23 MS (ESI) calculated value of N9O2: 529.20 m / z, measured value: 530.10 [M+H] + .

[0286] Step 3: Synthesis of (S)-N-(5-(2-(2-aminopyridin-3-yl)-5-(1H-pyrazol-1-yl)-3H-imidazo[4,5-b]pyridin-3-yl)-2,3-dihydro-1H-inden-1-yl)-4-ethyloxazol-2-carboxamide (compound 57) A mixture of (S)-N-(5-(2-(2-aminopyridin-3-yl)-5-(1H-pyrazol-1-yl)-3H-imidazo[4,5-b]pyridin-3-yl)-2,3-dihydro-1H-inden-1-yl)-4-vinyloxazol-2-carboxamide (30 mg, 0.057 mmol, 1 equivalent) and 10% Pd / C (30 mg, 0.026 mmol, 0.5 equivalent) in THF (5 mL) was stirred at room temperature under H2 atmosphere for 1 h. The mixture was filtered and concentrated. The crude product was purified by preparative HPLC on an XSelect CSH Prep C18 OBD column using a gradient of acetonitrile in water (+ 0.05% TFA) to give (S)-N-(5-(2-(2-aminopyridin-3-yl)-5-(1H-pyrazol-1-yl)-3H-imidazo[4,5-b]pyridin-3-yl)-2,3-dihydro-1H-inden-1-yl)-4-ethyloxazol-2-carboxamide (trifluoroacetate) (compound 57) (5.9 mg, 16%) as a grayish-white solid. 29 H 25 MS (ESI) calculated value of N9O2: 531.21 m / z, measured value: 532.15 [M+H] + . 1 H NMR (300 MHz, DMSO- d 6) δ (ppm): 8.31 -8.52 (m, 2H), 7.93 - 8.12 (m, 3H), 7.75 - 7.90 (m, 1H), 7.65 - 7.74 (m, 1H),7.40 - 7.51 (m, 1H), 7.25 - 7.39 (m, 2H), 6.68 - 6.89 (m, 1H), 6.48 - 6.64(m, 1H), 5.47 - 5.64 (m, 1H), 2.98 - 3.18 (m, 1H), 2.80 - 2.97 (m, 1H), 2.56- 2.68 (m, 3H), 2.08 - 2.27 (m, 1H), 1.10 - 1.30 (m, 3H).

[0287] Example 58: (S)-N-(5-(2-(2-aminopyridin-3-yl)-5-(2H-1,2,3-triazol-2-yl)-3H-imidazo[4,5-b]pyridin-3-yl)-2,3-dihydro-1H-inden-1-yl)nicotinamide (compound 58) Compound 58 was prepared in a manner similar to that of compound 3 by using nicotinic acid instead of 3,4-difluoro-5-anisolic acid and intermediate 58-1 instead of compound 2. 28 H 22 N 10 The calculated MS (ESI) value for O is 514.20 m / z, while the measured value is 515.15 [M+H]. + . 1 H-NMR (400 MHz, DMSO- d 6) δ (ppm): 9.10 - 9.11 (m, 1H), 8.76 - 8.77 (m,1H), 8.50 - 8.52 (m, 1H), 8.37 - 8.38 (m, 1H), 8.05 - 8.11 (m, 4H), 7.85 -7.87 (m, 1H), 7.61 - 7.63 (m, 1H), 7.45 - 7.48 (m, 2H), 7.36 - 7.38 (m, 1H), 6.85 - 6.87 (m, 1H), 5.63 - 5.67 (m, 1H), 3.03 - 3.05 (m, 1H), 2.94 - 2.96(m, 1H), 2.50 - 2.51 (m, 1H), 2.10 - 2.12 (m, 1H). (TFA salt) Intermediate 58-1: ( S )-3-(3-(1-amino-2,3-dihydro-1 H -indene-5-yl)-5-(2 H -1,2,3-triazol-2-yl)-3 H -imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine Synthesis route: Step 1: ( S )- N -(5-bromo-2,3-dihydro-1 H Synthesis of 1-indene-1-yl)acetamide Acetic anhydride (55.2 g, 526 mmol, 1.5 equivalent) was added to a mixture of (S)-5-bromo-2,3-dihydro-1H-indene-1-amine (74 g, 350 mmol, 1 equivalent) and triethylamine (106 g, 1.05 mol, 3 equivalent) in dichloromethane (1.5 L) at 0 °C, and the mixture was stirred at 0 °C for 2 h. The reaction mixture was quenched by adding water and extracted three times with ethyl acetate. The combined organic layers were dried over anhydrous sodium sulfate and concentrated under reduced pressure. The crude product was recrystallized from petroleum ether to give (S)-N-(5-bromo-2,3-dihydro-1H-indene-1-yl)acetamide (90 g, 83% yield) as a white solid. 11 H 12 MS (ESI) calculated value of BrNO: 253.01, measured value: 254.00 [M+H] + 256.00 [M+H+2] + .

[0288] Step 2: ( S )-(1-acetamido-2,3-dihydro-1 H Synthesis of tert-butyl indene-5-yl)carbamate Under a nitrogen atmosphere, towards N -[(1S)-5-bromo-2,3-dihydro-1 H [Indene-1-yl]acetamide (40 g, 157 mmol, 1 equivalent), tert-butyl carbamate (27.66 g, 236 mmol, 1.5 equivalent), XantPhos (9.11 g, 15.7 mmol, 10 mol%), palladium(II) acetate (3.54 g, 15.7 mmol, 10 mol%), and cesium carbonate (154 g, 472 mmol, 10 mol%) were mixed with 1,4-dioxane (300 mL). The resulting mixture was stirred at 100 °C for 3 h. The reaction mixture was quenched with water and extracted three times with ethyl acetate. The combined organic layers were dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography using petroleum ether / dichloromethane / methanol (70:27:3) as the eluent to obtain N -[(1S)-1-acetamido-2,3-dihydro-1 H [Indene-5-yl] tert-butyl carbamate (43.1 g, 48%). C 16 H 22 MS (ESI) calculated value of N2O3: 290.16 m / z, measured value: 289.05 [MH] - .

[0289] Step 3: (S)-N -(5-amino-2,3-dihydro-1 H Synthesis of 1-indene-1-yl)acetamide Towards N -[(1S)-1-acetamido-2,3-dihydro-1 H [Indene-5-yl]tert-butyl carbamate (43.1 g, 148 mmol, 1 equivalent) was added to a stirred solution of 1,4-dioxane in 4N hydrochloric acid (185 mL, 742 mmol, 5 equivalent) in dichloromethane (180 mL). The reaction mixture was stirred at room temperature for 1 h. The reaction mixture was concentrated under vacuum and recrystallized from ethyl acetate to give a white solid. N -[(1S)-5-amino-2,3-dihydro-1 H [Indene-1-yl]acetamide (hydrochloride) (23 g, 81%). C 11 H 14 MS (ESI) value of N₂O: 190.11 m / z, measured value: 191.15 [M+H] + .

[0290] Step 4: Synthesis of (S)-N-(5-((6-bromo-3-nitropyridin-2-yl)amino)-2,3-dihydro-1H-inden-1-yl)acetamide A solution of (S)-N-(5-amino-2,3-dihydro-1H-indene-1-yl)acetamide (17 g, 89 mmol), 2,6-dibromo-3-nitropyridine (25.19 g, 89.36 mmol), and triethylamine (45.21 g, 446.8 mmol) in EtOH (200 mL) was stirred at room temperature for 2 h. The reaction was quenched with water, and the precipitated solid was collected by filtration and washed with EtOH / H₂O = 1:1 to give (S)-N-(5-((6-bromo-3-nitropyridine-2-yl)amino)-2,3-dihydro-1H-indene-1-yl)acetamide (26 g, 74.37% yield) as an orange solid. 16 H 15 MS (ESI) calculated value of BrN4O3: 390.03, measured value: 413.00 [M+Na] + 415.00 [M+Na+2] + .

[0291] Step 5: Synthesis of (S)-N-(5-((3-nitro-6-(2H-1,2,3-triazol-2-yl)pyridin-2-yl)amino)-2,3-dihydro-1H-inden-1-yl)acetamide K₂CO₃ (52.99 g, 383.4 mmol) and 1H-1,2,3-triazole (17.65 g, 255.6 mmol) were added to a solution of (S)-N-(5-(((6-bromo-3-nitropyridin-2-yl)amino)-2,3-dihydro-1H-indene-1-yl)acetamide (50.0 g, 128 mmol) in DMF (1.5 L). The resulting mixture was stirred overnight at room temperature. The product was precipitated by adding H₂O. The precipitated solid was collected by filtration and washed with water. The crude product was recrystallized from petroleum ether to give (S)-N-(5-((3-nitro-6-(2H-1,2,3-triazol-2-yl)pyridin-2-yl)amino)-2,3-dihydro-1H-indene-1-yl)acetamide (45 g, 93%) as a yellow solid. 18 H 17 MS (ESI) calculated value of N7O3: 379.14 m / z, measured value: 380.15 [M+H] + . 1 H NMR (400 MHz, DMSO- d 6 ) δ (ppm): 7.98 (s, 2H), 7.79 (d, J = 2.1 Hz, 1H), 7.68 (dd, J = 8.3, 2.1 Hz, 1H), 7.17 (d, J = 8.1 Hz, 1H), 7.13 - 7.04 (m,2H), 5.18 (t, J = 7.4 Hz, 1H), 2.93 - 2.85 (m, 1H), 2.80 - 2.70 (m, 1H), 2.43- 2.31 (m, 1H), 1.87 (s, 3H), 1.82 - 1.71 (m, 1H).

[0292] Step 6: Synthesis of (S)-N-(5-((3-amino-6-(2H-1,2,3-triazol-2-yl)pyridin-2-yl)amino)-2,3-dihydro-1H-inden-1-yl)acetamide Add B2(OH)4 (0.92 g, 10 mmol) to a cooled (0 °C) solution of (S)-N-(5-((3-nitro-6-(2H-1,2,3-triazol-2-yl)pyridin-2-yl)amino)-2,3-dihydro-1H-indene-1-yl)acetamide (1.3 g, 3.4 mmol) and 4,4-bipyridine (27 mg, 0.17 mmol) in DMF (25 mL). Stir the resulting mixture at room temperature for 2 h. Quench the reaction with H2O. Extract the resulting mixture three times with ethyl acetate. Combine the organic layers, dry over Na2SO4, filter, and concentrate. The resulting residue was purified by silica gel column chromatography using a gradient of ethyl acetate in petroleum ether to give (S)-N-(5-((3-amino-6-(2H-1,2,3-triazol-2-yl)pyridin-2-yl)amino)-2,3-dihydro-1H-indene-1-yl)acetamide (800 mg, 67%) as a yellow solid. 18 H 19 The calculated MS (ESI) value for N7O is 349.17 m / z, and the measured value is 350.15 [M+H]. + .

[0293] Step 7: Synthesis of (S)-N-(5-(2-(2-aminopyridin-3-yl)-5-(2H-1,2,3-triazol-2-yl)-3H-imidazo[4,5-b]pyridin-3-yl)-2,3-dihydro-1H-inden-1-yl)acetamide 2-Aminonicotinaldehyde (269 mg, 2.20 mmol) and sodium perborate (328 mg, 4.00 mmol) were added to a solution of (S)-N-(5-((3-amino-6-(2H-1,2,3-triazol-2-yl)pyridin-2-yl)amino)-2,3-dihydro-1H-indene-1-yl)acetamide (700 mg, 2.00 mmol) in AcOH (10 mL) and MeOH (2 mL). The resulting mixture was stirred at 70 °C for 3 h. The solvent was removed by vacuum distillation. The resulting mixture was purified by reversed-phase rapid column chromatography on C18 silica gel using a gradient of acetonitrile in water (+ 0.05% ammonium bicarbonate) to give (S)-N-(5-(2-(2-aminopyridin-3-yl)-5-(2H-1,2,3-triazol-2-yl)-3H-imidazo[4,5-b]pyridin-3-yl)-2,3-dihydro-1H-indene-1-yl)acetamide (520 mg, 57%) as a pale reddish-brown solid. 24 H 21 The calculated MS (ESI) value for N9O is 451.19 m / z, while the measured value is 452.20 [M+H]. + .

[0294] Step 8: Synthesis of (S)-3-(3-(1-amino-2,3-dihydro-1H-inden-5-yl)-5-(2H-1,2,3-triazol-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine (intermediate 58-1) A solution of (S)-N-(5-(2-(2-aminopyridin-3-yl)-5-(2H-1,2,3-triazol-2-yl)-3H-imidazo[4,5-b]pyridin-3-yl)-2,3-dihydro-1H-indene-1-yl)acetamide (520 mg, 1.152 mmol) in HCl (20 mL, concentrated) and MeOH (20 mL) was stirred overnight at 90 °C. The solvent was removed by distillation under vacuum to give crude (S)-3-(3-(1-amino-2,3-dihydro-1H-indene-5-yl)-5-(2H-1,2,3-triazol-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine (intermediate 58-1) (400 mg, 85%) as a yellow solid. 22 H 19 The calculated MS (ESI) value for N9 is 409.18 m / z, while the measured value is 410.20 [M+H]. + .

[0295] Example 59: (S)-N-(5-(2-(2-aminopyridin-3-yl)-5-(2H-1,2,3-triazol-2-yl)-3H-imidazo[4,5-b]pyridin-3-yl)-2,3-dihydro-1H-inden-1-yl)pyrimidin-5-carboxamide (Compound 59) Compound 59 was prepared in a manner similar to that of compound 3, using pyrimidine-5-carboxylic acid instead of 3,4-difluoro-5-anisolic acid, intermediate 58-1 instead of compound 2, and PyBOP instead of HATU. 27 H 21 N 11 The calculated MS (ESI) value for O is 515.19 m / z, while the measured value is 516.10 [M+H]. + . 1 H NMR (300 MHz, DMSO- d6) δ (ppm): 9.23 - 9.33(m, 3H), 8.49 - 8.52 (m, 1H), 8.04 - 8.15 (m, 4H), 7.80 - 7.83 (m, 1H), 7.37- 7.51 (m, 3H), 6.80 - 6.84 (m, 1H), 5.62 - 5.67 (m, 1H), 2.89 - 3.15 (m, 2H), 2.51 - 2.53 (m, 1H), 2.06 - 2.13 (m, 1H). (TFA salt) Example 60: (S)-N-(5-(2-(2-aminopyridin-3-yl)-5-(1H-pyrazol-1-yl)-3H-imidazo[4,5-b]pyridin-3-yl)-2,3-dihydro-1H-inden-1-yl)-6-(difluoromethyl)-5-methylnicotinamide (Compound 60) Compound 60 was prepared in a manner similar to that of compound 56 (via intermediate 56-1) by using 6-bromo-5-methylnicotinic acid instead of 6-bromo-4-methylnicotinic acid. 31 H 25 MS (ESI) calculated value of F2N9O: 577.22 m / z, measured value: 578.10 [M+H] + . 1 H NMR (300 MHz, DMSO- d 6) δ (ppm): 8.88 (s, 1H), 8.24 - 8.40 (m, 2H), 8.19 (s, 1H), 7.95 - 8.02 (m, 1H), 7.82 - 7.94 (m, 1H), 7.67 - 7.81 (m, 1H), 7.31- 7.45 (m, 2H), 7.12 - 7.30 (m, 2H), 6.65 - 7.11 (m, 1H), 6.47 - 6.56 (m,1H), 6.37 - 6.46 (m, 1H), 5.48 - 5.68 (m, 1H), 2.77 - 3.13 (m, 2H), 2.52 -2.61 (m, 1H), 2.38 - 2.48 (m, 3H), 1.90 - 2.15 (m, 1H). 19 F NMR (282 MHz, DMSO- d 6) δ (ppm): -116.07.

[0296] Example 61: (S )- N -(5-(2-(2-aminopyridin-3-yl)-5-(1 H -pyrazole-1-yl)-3 H -Imidazolo[4,5-b]pyridin-3-yl)-2,3-dihydro-1H-inden-1-yl)-4-(difluoromethyl)benzamide (compound 61) Compound 61 was prepared in a manner similar to that of compound 3 by using 4-(difluoromethyl)benzoic acid instead of 3,4-difluoro-5-anisolic acid. 31 H 24 MS (ESI) calculation value for F2N8O: 562.20 m / z, measured value: 563.25 [M+H] + . 1 H NMR (400MHz, DMSO- d 6) δ (ppm): 8.42 - 8.44 (m, 1H), 8.37 - 8.38 (m, 1H), 8.05 - 8.07(m, 4H), 7.93 - 7.96 (m, 2H), 7.79 - 7.82 (m, 2H), 7.67 - 7.69 (m, 1H), 7.40- 7.46 (m, 2H), 7.22 - 7.38 (m, 1H), 6.85 - 6.94 (m, 1H), 6.56 - 6.57 (m,1H), 5.61 - 5.65 (m, 1H), 3.03 - 3.05 (m, 1H), 2.94 - 2.96 (m, 1H), 2.50 -2.51 (m, 1H), 2.10 - 2.12 (m, 1H). 19 F NMR (376 MHz, DMSO- d 6) δ (ppm): -110.38. (TFA salt) Example 62: (S)-N-(5-(2-(2-aminopyridin-3-yl)-5-(1H-pyrazol-1-yl)-3H-imidazo[4,5-b]pyridin-3-yl)-2,3-dihydro-1H-inden-1-yl)-6-(difluoromethyl)-5-fluoronicotinamide (Compound 62) Compound 62 was prepared in a manner similar to that of compound 60 (via intermediate 56-1) by using TCFH instead of HATU, N-methylimidazolium instead of N,N-diisopropylethylamine, acetonitrile instead of N,N-dimethylformamide, and 6-bromo-5-fluoronicotinic acid instead of 6-bromo-5-methylnicotinic acid. 30 H 22 MS (ESI) calculated value for F3N9O: 581.19 m / z, measured value: 582.25 [M+H] + . 1 H NMR (300 MHz, DMSO- d 6) δ (ppm): 9.33 - 9.36 (m, 1H), 9.01 (s,1H), 8.34 - 8.58 (m, 3H), 8.00 - 8.15 (m, 2H), 7.82 - 7.83 (m, 1H), 7.73 -7.76 (m, 1H), 7.45 - 7.48 (m, 2H), 7.04 - 7.39 (m, 2H), 6.77 - 6.81 (m, 1H), 6.58 - 6.59 (m, 1H), 5.61 - 5.68 (m, 1H), 2.89 - 3.12 (m, 2H), 2.51 - 2.53(m, 1H), 2.07 - 2.18 (m, 1H). 19 F NMR (300 MHz, DMSO- d 6) δ (ppm): -117.82, -126.49. (TFA salt) Example 63: (S)-N-(5-(2-(2-aminopyridin-3-yl)-5-(1H-pyrazol-1-yl)-3H-imidazo[4,5-b]pyridin-3-yl)-2,3-dihydro-1H-inden-1-yl)-2-(dimethylamino)isonicotinamide (Compound 63) Compound 63 was prepared in a manner similar to that of compound 3 by using 2-(dimethylamino)isonicotinic acid instead of 3,4-difluoro-5-anesticic acid. 31 H 28 N 10 The calculated MS (ESI) value for O is 556.24 m / z, while the measured value is 557.25 [M+H]. + . 1 H NMR (300MHz, DMSO- d6) δ (ppm): 8.31 - 8.39 (m, 2H), 8.13 - 8.18 (m, 1H), 7.96 - 8.07(m, 2H), 7.79 - 7.87 (m, 1H), 7.31 - 7.49 (m, 4H), 6.97 - 7.05 (m, 2H), 6.43- 6.58 (m, 2H), 5.57 - 5.69 (m, 1H), 2.98 - 3.13 (m, 6H), 2.81 - 2.97 (m,2H), 2.53 - 2.59 (m, 1H), 2.07 - 2.13 (m, 1H).

[0297] Example 64: (S)-N-(5-(2-(2-aminopyridin-3-yl)-5-(1H-pyrazol-1-yl)-3H-imidazo[4,5-b]pyridin-3-yl)-2,3-dihydro-1H-inden-1-yl)-2-(trifluoromethoxy)isonicotinamide (Compound 64) Compound 64 was prepared in a manner similar to that of compound 3 by using 2-(trifluoromethoxy)isonicotinic acid instead of 3,4-difluoro-5-anesticic acid and PyBOP instead of HATU. 30 H 22 The calculated MS (ESI) value for F3N9O2 is 597.18 m / z, and the measured value is 598.10 [M+H]. + . 1 H NMR (300 MHz, DMSO- d 6 ) δ (ppm): 8.48 - 8.55 (m, 1H), 8.30 -8.40 (m, 2H), 7.97 - 8.05 (m, 1H), 7.89 - 7.97 (m, 1H), 7.80 - 7.89 (m, 1H),7.75 - 80 (m, 1H), 7.67 (s, 1H), 7.36 - 7.42 (m, 2H), 7.22 - 7.33 (m, 2H), 6.51 - 6.58 (m, 1H), 6.41 - 6.50 (m, 1H), 5.55 - 5.66 (m, 1H), 2.82 - 3.11(m, 2H), 2.53 - 2.61 (m, 1H), 2.00 - 2.17 (m, 1H). 19 F NMR (282 MHz, DMSO- d6 δ (ppm): -55.18. (Formate) Example 65: (S)-N-(5-(2-(2-aminopyridin-3-yl)-5-(2H-1,2,3-triazol-2-yl)-3H-imidazo[4,5-b]pyridin-3-yl)-2,3-dihydro-1H-inden-1-yl)-6-(difluoromethyl)nicotinamide (Compound 65) Compound 65 was prepared in a manner similar to that of compound 3 by using 6-(difluoromethyl)nicotinic acid instead of 3,4-difluoro-5-anesticic acid, PyBOP instead of HATU, and intermediate 58-1 instead of compound 2. 29 H 22 F2N 10 The calculated MS (ESI) value for O is 564.19 m / z, while the measured value is 565.25 [M+H]. + . 1 H NMR (300 MHz, DMSO- d 6 ) δ (ppm): 9.15 -9.25 (m, 1H), 8.38 - 8.52 (m, 2H), 8.13 (s, 2H), 7.97 - 8.08 (m, 2H), 7.78 -7.85 (m, 1H), 7.39 - 7.48 (m, 2H), 7.24 - 7.35 (m, 2H), 7.85 - 7.03 (m, 1H), 6.40 - 6.50 (m, 1H), 5.61 - 5.72 (m, 1H), 2.85 - 3.15 (m, 2H), 2.52 - 2.64(m, 1H), 2.00 - 2.19 (m, 1H). 19 F NMR (282 MHz, DMSO- d 6 δ (ppm): -116.04 (formate).

[0298] Example 66: (S)-3-(5-(2-(2-aminopyridin-3-yl)-5-(1H-pyrazol-1-yl)-3H-imidazo[4,5-b]pyridin-3-yl)-2,3-dihydro-1H-inden-1-yl)-6-methylpyrido[3,4-d]pyrimidin-4(3H)-one (Compound 81) Synthesis route: Step 1: Synthesis of (S)-5-amino-N-(5-(2-(2-aminopyridin-3-yl)-5-(1H-pyrazol-1-yl)-3H-imidazo[4,5-b]pyridin-3-yl)-2,3-dihydro-1H-inden-1-yl)-2-methylisonicotinamide To a solution of 5-amino-2-methylpyridine-4-carboxylate (41.6 mg, 0.220 mmol) in DMF (1 mL), DIEA (85.4 mg, 0.660 mmol), 3-{3-[(1S)-1-amino-2,3-dihydro-1H-inden-5-yl]-5-(pyrazol-1-yl)imidazo[4,5-b]pyridin-2-yl}pyridine-2-amine (compound 2) (90 mg, 0.22 mmol), and HATU (101 mg, 0.264 mmol) were added. The resulting mixture was maintained under nitrogen and stirred at room temperature for 3 h. The reaction was quenched with water (100 mL). The resulting mixture was extracted with ethyl acetate (3 × 100 mL). The organic layers were combined, dried over anhydrous Na2SO4, filtered, and concentrated. The crude product was purified by reversed-phase rapid column chromatography on C18 silica gel using a gradient of acetonitrile in water (+ 0.05% TFA) to give (S)-5-amino-N-(5-(2-(2-aminopyridin-3-yl)-5-(1H-pyrazol-1-yl)-3H-imidazo[4,5-b]pyridin-3-yl)-2,3-dihydro-1H-inden-1-yl)-2-methylisonicotinamide (90 mg, 75% yield) as a yellow solid. 30 H 26 N 10 The calculated MS (ESI) value for O is 542.23 m / z, while the measured value is 543.15 [M+H]. + .

[0299] Step 2: Synthesis of (S)-3-(5-(2-(2-aminopyridin-3-yl)-5-(1H-pyrazol-1-yl)-3H-imidazo[4,5-b]pyridin-3-yl)-2,3-dihydro-1H-inden-1-yl)-6-methylpyrido[3,4-d]pyrimidin-4(3H)-one (compound 81) A solution of 5-amino-N-[(1S)-5-[2-(2-aminopyridin-3-yl)-5-(pyrazol-1-yl)imidazo[4,5-b]pyridin-3-yl]-2,3-dihydro-1H-indene-1-yl]-2-methylpyridin-4-carboxamide (80 mg, 0.15 mmol) in formic acid (2 mL) was stirred at 100 °C for 16 h. The reaction mixture was cooled to room temperature and purified by preparative HPLC on an XBridgePrep OBD C18 column using a gradient of acetonitrile in water (+ 0.05% TFA) to give (S)-3-(5-(2-(2-aminopyridin-3-yl)-5-(1H-pyrazol-1-yl)-3H-imidazo[4,5-b]pyridin-3-yl)-2,3-dihydro-1H-inden-1-yl)-6-methylpyrido[3,4-d]pyrimidin-4(3H)-one (compound 81) (TFA salt) (16.2 mg, 16% yield). 31 H 24 N 10 The calculated MS (ESI) value for O is 552.21 m / z, and the measured value is 553.15 [M+H]. + . 1 H NMR (300MHz, DMSO- d 6+D2O) δ (ppm): 8.96 - 9.04 (m, 1H), 8.37 - 8.52 (m, 2H), 8.15 -8.25 (m, 1H), 8.04 - 8.12 (m, 1H), 8.00 - 8.03 (m, 1H), 7.88 - 7.95 (m, 1H),7.80 - 7.87 (m, 1H), 7.74 - 7.86 (m, 1H), 7.53 - 7.64 (m, 1H), 7.28 - 7.42(m, 2H), 6.80 - 6.93 (m, 1H), 6.53 - 6.62 (m, 1H), 6.26 - 6.40 (m, 1H), 3.19- 3.37 (m, 1H), 2.98 -...

Claims

1. A compound represented by the structure of formula (I): (I)， Or its pharmaceutically acceptable salt, wherein: Ring B is selected from: and ; R 1 Selected from hydrogen, halogens, -OR 10 -SR 10 -N(R) 10 )2, -NO2, -CN, C that is optionally substituted 3-8 Carbon rings, optionally substituted 4- to 8-membered heterocycles, and optionally substituted C rings 1-6 Alkyl groups, wherein each is optionally substituted by one or more substituents independently selected from: halogen, -OR 10 -SR 10 -N(R) 10 2. -NO2 and -CN; A 1 and A 2 Each is independently selected from (i), (ii), and (iii): (i) Hydrogen, halogens, C 1-4 Halogenated alkyl groups, -OR 11 -SR 11 -N(R) 11 )2、-C(O)N(R 11 )2、-N(R 11 )C(O)R 11 -C(O)OR 11 -OC(O)R 11 -N(R) 11 )C(O)OR 11 -OC(O)N(R) 11 )2、-N(R 11 )C(O)N(R 11 )2、-S(O)R 11 -S(O)2R 11 -N(R) 11 )S(O)2R 11 -S(O)2N(R) 11 2. -NO2 and -CN; (ii) C 1-6 Alkyl, C 2-6 alkenyl and C 2-6 The alkynyl group, wherein any one of them is optionally substituted by one or more substituents independently selected from the following: Halogen, -OR 11 , -SR 11 , -N(R 11 )2, -C(O)N(R 11 )2, -N(R 11 )C(O)R 11 , -C(O)OR 11 , -OC(O)R 11 , -N(R 11 )C(O)OR 11 , -OC(O)N(R 11 )2, -N(R 11 )C(O)N(R 11 )2, -S(O)R 11 , -S(O)2R 11 , -N(R 11 )S(O)2R 11 , -S(O)2N(R 11 )2, -NO2, =O, =S, =N(R 11 ) and -CN; and C 3-10 A carbocyclic ring and a 4- to 10-membered heterocycle, either of which may optionally be substituted by one or more substituents independently selected from the following: halogen, -OR 11A , -N(R 11A )2, -C(O)R 11A , -C(O)N(R 11A )2, -N(R 11A )C(O)R 11A , -C(O)OR 11A , -OC(O)R 11A , -NO2, =O, =S, =N(R 11A ), -CN; and C 1-6 Alkyl C 2-6 alkenyl and C 2-6 Alkyne group, wherein any of them may optionally be substituted by one or more substituents independently selected from: halogen, -OR 11A -SR 11A -N(R) 11A )2、-C(O)R 11A -C(O)N(R) 11A )2、-N(R 11A )C(O)R 11A -N(R) 11A )S(O)2R 11A -C(O)OR 11A -OC(O)R 11A -NO2, =O, =S, =N(R) 11A ) and -CN; and (iii) 5-10 yuan heterocyclic rings and C 3-10 The carbon ring, wherein any one of them is optionally substituted by one or more substituents independently selected from the following: halogen, -OR 11 , -SR 11 , -N(R 11 )2, -C(O)R 11 , -C(O)N(R 11 )2, -N(R 11 )C(O)R 11 , -N(R 11 )S(O)2R 11 , -NS(O)2N(R 11 )2, -C(O)OR 11 , -OC(O)R 11 , -N(R 11 )C(O)OR 11 , -OC(O)N(R 11 )2, -N(R 11 )C(O)N(R 11 )2, -S(O)R 11 , -S(O)2R 11 , -S(O)2N(R 11 )2, -NO2, =O, =S, =N(R 11 ) and -CN; and C 1-6 Alkyl, C 2-6 alkenyl and C 2-6 Alkyne group, wherein any of them may optionally be substituted by one or more substituents independently selected from: halogen, -OR 11 -SR 11 -N(R) 11 )2、-C(O)R 11 -C(O)N(R) 11 )2、-N(R 11 )C(O)R 11 -C(O)OR 11 -OC(O)R 11 -N(R) 11 )C(O)OR 11 -OC(O)N(R) 11 )2、-N(R 11 )C(O)N(R 11 )2、-S(O)R 11 -S(O)2R 11 -N(R) 11 )S(O)2R 11 -S(O)2N(R) 11 )2、-NO2、=O、=S、=N(R 11 ) and -CN; and C 3-10 A carbocyclic ring and a 4- to 10-membered heterocycle, either of which may optionally be substituted by one or more substituents independently selected from the following: halogen, -OR 11 , -N(R 11 )2, -C(O)R 11 , -C(O)N(R 11 )2, -N(R 11 )C(O)R 11 , -C(O)OR 11 , -OC(O)R 11 , -NO2, =O, =S, =N(R 11 ), -CN; and C 1-6 Alkyl, C 2-6 alkenyl, C 3-6 alkynyl group, C 3-8 A carbocyclic or 4- to 8-membered heterocyclic ring, any of which may optionally be substituted by one or more substituents independently selected from the following: halogen, -OR 11 -SR 11 -N(R) 11 )2、-C(O)R 11 -C(O)N(R) 11 )2、-N(R 11 )C(O)R 11 -N(R) 11 )S(O)2R 11 -C(O)OR 11 -OC(O)R 11 -NO2, =O, =S, =N(R) 11 ) and -CN; q is selected from 1, 2, and 3; m and n are each independently selected from 0, 1, 2 and 3; R 2 In each case, it is independently selected from halogens, C 1-4 Alkyl, C 1-4 Halogenated alkyl groups, -OR 12 -SR 12 -N(R) 12 2. -NO2 and -CN; R 3 Select independently in each case: Halogen, -OR 13 -SR 13 -N(R) 13 )2、-C(O)R 13 -C(O)N(R) 13 )2、-N(R 13 )C(O)R 13 -C(O)OR 13 -OC(O)R 13 -NO2 and -CN; and C 1-6 Alkyl group, optionally substituted by one or more substituents independently selected from: halogen, -OR 13 -SR 13 -N(R) 13 )2、-C(O)R 13 -C(O)N(R) 13 )2、-N(R 13 )C(O)R 13 -C(O)OR 13 -OC(O)R 13 -NO2, =O, =S, =N(R) 13 ) and -CN; p is selected from 0, 1, 2, 3, 4, and 5; R 4 Select independently in each case: Halogen, -OR 14 -SR 14 -N(R) 14 )2、-C(O)R 14 -C(O)N(R) 14 )2、-N(R 14 )C(O)R 14 -C(O)OR 14 -OC(O)R 14 -NO2 and -CN; and C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, wherein any of them may optionally be substituted by one or more substituents independently selected from: halogen, -OR 14 -SR 14 -N(R) 14 )2、-C(O)R 14 -C(O)N(R) 14 )2、-N(R 14 )C(O)R 14 -C(O)OR 14 -OC(O)R 14 -NO2, =O, =S, =N(R) 14 ) and -CN; or Two R atoms connected to the same atom 4 Together they form a group selected from the following: =O, =S, and =N(R) 14 );or Two R atoms connected to the same or adjacent atoms 4 Together with the carbon atoms they are attached to, they form groups selected from the following: 4- to 8-membered heterocycles and C. 3-8 A carbon ring, wherein any of the carbon rings may optionally be substituted by one or more substituents independently selected from the following: halogen, C 1-4 Alkyl, C 1-4 Halogenated alkyl groups, -OR 14 -SR 14 -N(R) 14 2. -NO2 and -CN; L by -L 1 -L 2 -L 3 -L 4 - indicates that L 1 L 2 L 3 and L 4 Each is independently selected from (a) and (b): (a) -O-, -N(R 15 )-, -S-, -S(O)-, -S(O)2-, -S(O)(NR 15 )-, -N(R 15 )C(O)-, -N(R 15 )C(O)O-, -N(R 15 )S(O)2-, -N(R 15 )S(O)2N(R 15 )-, -S(O)(NR 15 )N(R 15 )-, -N(R 15 )N(R 15 )-, -(R 15 )NC(O)N(R 15 )- and -(R 15 )NC(O)N(R 15 )N(R 15 )-; and (b) C 1-6 Alkylene, C 2-6 imidene group, C 2-6 Ethyne group, C 3-8 Carbocyclic and 4- to 8-membered heterocyclic groups, either of which may optionally be substituted by one or more substituents independently selected from: halogen, -OR 15 -SR 15 =O, =S, and -CN; Where L 1 L 2 L 3 and L 4 Each of the two optional locations does not exist; Where L 1 L 2 L 3 and L 4 No more than two are selected from (a), and the two selected are not adjacent; R 5 Selected from 4- to 10-membered heterocycles and C 3-10 The carbon ring, wherein any one of them is optionally substituted by one or more substituents independently selected from the following: Halogen, C 1-4 Halogenated alkyl, -OR 16 , -SR 16 , -N(R 16 )2, -C(O)N(R 16 )2, -C(O)OR 16 , -OC(O)R 16 , -N(R 16 )C(O)R 16 , -N(R 16 )S(O)2R 16 , -S(O)2N(R 16 )2, -N(R 16 )C(O)N(R 16 )2, -N(R 16 )C(O)OR 16 , -OC(O)N(R 16 )2, -S(O)R 16 , -S(O)2R 16 , -NO2, =O, =S, =N(R 16 ) and -CN; C 1-6 Alkyl, C 2-6 alkenyl and C 2-6 Alkyne group, wherein each of them is optionally substituted by one or more substituents independently selected from: halogen, -OR 16 -SR 16 -N(R) 16 2. -NO2 and -CN; as well as 4- to 6-membered heterocyclic rings and C 3-8 A carbon ring, wherein each of which is optionally substituted by one or more substituents independently selected from the following: halogen, C 1-4 Alkyl, C 1-4 Halogenated alkyl groups, -OR 16 -SR 16 -N(R) 16 2. -NO2 and -CN; R 10 R 11 R 11A R 12 R 13 R 14 and R 15 Each time it appears, it is independently selected from: hydrogen, C 1-4 Alkyl, C 3-8 Carbon rings, 4- to 8-membered heterocycles and C 1-4 Halogenated alkyl groups; R 16 Each time it appears, it is independently selected from (iv), (v), and (vi): (iv) Hydrogen; (v) C 1-4 Alkyl, wherein the C 1-4 The alkyl group is optionally substituted by one or more substituents independently selected from the following: halogen, -OR 20 , -SR 20 , -N(R 20 )2, -C(O)R 20 , -C(O)OR 20 , -OC(O)R 20 , -C(O)N(R 20 )2, -N(R 20 )C(O)R 20 , -N(R 20 )C(O)N(R 20 )2, -N(R 20 )C(O)OR 20 , -OC(O)N(R 20 )2, -S(O)R 20 , -S(O)2R 20 , -N(R 20 )S(O)2R 20 , -S(O)2N(R 20 ), -NO2 and -CN; and C 3-8 A carbocyclic ring and 4- to 8-membered heterocycles, any of which may optionally be substituted by one or more substituents independently selected from the following: halogen, C 1-4 Alkyl, C 1-4 Halogenated alkyl groups, -OR 20 -SR 20 -N(R) 20 )2、-C(O)R 20 -C(O)OR 20 -OC(O)R 20 -C(O)N(R) 20 )2、-N(R 20 )C(O)R 20 -N(R) 20 )C(O)N(R 20 )2、-N(R 20 )C(O)OR 20 -OC(O)N(R) 20 )2、-S(O)R 20 -S(O)2R 20 -N(R) 20 )S(O)2R 20 -S(O)2N(R) 20 2. -NO2 and -CN; and (ⅵ) C 3-8 A carbocyclic ring and 4- to 8-membered heterocycles, any of which may optionally be substituted by one or more substituents independently selected from the following: halogen, C 1-4 Alkyl, C 1-4 Halogenated alkyl groups, -OR 20 -SR 20 -N(R) 20 )2、-C(O)R 20 -C(O)N(R) 20 )2、-C(O)OR 20 -OC(O)R 20 -N(R) 20 )C(O)R 20 -N(R) 20 )S(O)2R 20 -N(R) 20 )C(O)N(R 20 )2、-N(R 20 )C(O)OR 20 -OC(O)N(R) 20 )2、-S(O)R 20 -S(O)2R 20 -NO2, -CN and C 3-8 Carbon rings or 4- to 8-membered heterocyclic rings, wherein the C 3-8 The carbocyclic ring or any of the 4- to 8-membered heterocycles may optionally be further substituted by one or more substituents independently selected from the following: halogen, C 1-4 Alkyl, C 1-4 Halogenated alkyl groups, -OR 20 -SR 20 -N(R) 20 )2、-C(O)R 20 -C(O)N(R) 20 )2、-C(O)OR 20 -OC(O)R 20 -N(R) 20 )C(O)R 20 -N(R) 20 )S(O)2R 20 -N(R) 20 )C(O)N(R 20 )2、-N(R 20 )C(O)OR 20 -OC(O)N(R) 20 )2、-S(O)R 20 -S(O)2R 20 -NO2 and -CN; and R 20 Each time it appears, it is independently selected from hydrogen, C 1-4 Alkyl, C 1-4 Haloalkyl, C 3-8 Carbon rings and 4- to 8-membered heterocycles.

2. The compound or salt according to claim 1, wherein A 2 Selected from C 1-6 Alkyl, C 2-6 alkenyl and C 2-6 The alkynyl group, wherein each of them is optionally substituted by one or more substituents independently selected from the following: Halogen, -OR 11 -N(R) 11 )2、-C(O)N(R 11 )2、-N(R 11 )C(O)R 11 -N(R) 11 )S(O)2R 11 -S(O)2N(R) 11 )2, =O and -NO2, -CN; and C 3-10 A carbocyclic ring and a 4- to 10-membered heterocycle, either of which may optionally be substituted by one or more substituents independently selected from the following: Halogen, -OR 11A -N(R) 11A )2、-C(O)R 11A -C(O)N(R) 11A )2、-N(R 11A )C(O)R 11A -NO2, =O and -CN; and C 1-6 Alkyl, C 2-6 alkenyl and C 3-6 Alkyne group, wherein any of them may optionally be substituted by one or more substituents independently selected from: halogen, -OR 11A -N(R) 11A )2、-C(O)R 11A -C(O)N(R) 11A )2、-N(R 11A )C(O)R 11A -N(R) 11A )S(O)2R 11A -NO2, =O, and -CN.

3. The compound or salt according to claim 1 or claim 2, wherein A 2 Selected from C that is optionally substituted by one or more substituents independently selected from the following 2-6 alkynyl group: Halogen, -OR 11 -N(R) 11 )2、-C(O)N(R 11 )2、-N(R 11 )C(O)R 11 -N(R) 11 )S(O)2R 11 -S(O)2N(R) 11 2. -NO2 and -CN; and C 3-10 A carbocyclic ring and a 4- to 10-membered heterocycle, either of which may optionally be substituted by one or more substituents independently selected from the following: Halogen, -OR 11A -N(R) 11A )2、-C(O)R 11A -C(O)N(R) 11A )2、-N(R 11A )C(O)R 11A -NO2, =O and -CN; and C 1-6 Alkyl, C 2-6 alkenyl and C 3-6 Alkyne group, wherein any of them may optionally be substituted by one or more substituents independently selected from: halogen, -OR 11A -N(R) 11A )2、-C(O)R 11A -C(O)N(R) 11A )2、-N(R 11A )C(O)R 11A -N(R) 11A )S(O)2R 11A -NO2, =O, and -CN.

4. The compound or salt according to any one of claims 1-3, wherein A 2 C is optionally substituted by one or more substituents independently selected from the following 2-6 Alkyne group: halogen, -OR 11 -N(R) 11 )2、-NO2、-CN;C 3-10 Carbon rings and 4- to 10-membered heterocycles, wherein the C 3-10 The carbocyclic ring and the 3- to 10-membered heterocycle are each optionally substituted by one or more substituents independently selected from the following: halogen, -OR 11A -N(R) 11A )2, -NO2, =O and -CN; and C 1-6 Alkyl group, optionally substituted by one or more substituents independently selected from: halogen, -OR 11A -N(R) 11A )2, -NO2, =O and -CN.

5. The compound or salt according to claim 4, wherein A 2 C is optionally substituted by one or more substituents independently selected from the following 2-6 alkynyl group: C 3-6 A carbocyclic ring and 4- to 6-membered heterocycles, each optionally substituted by one or more substituents independently selected from: halogens, -OR 11A -N(R) 11A )2、-C(O)R 11A -C(O)N(R) 11A )2、-N(R 11A )C(O)R 11A -NO2, =O and -CN; and C 1-6 Alkyl group, optionally substituted by one or more substituents independently selected from: -OR 11A -N(R) 11A )2、-C(O)R 11A -C(O)N(R) 11A )2、-N(R 11A )C(O)R 11A -NO2, =O, and -CN.

6. The compound or salt according to claim 4, wherein A 2 C is optionally substituted by one or more substituents independently selected from the following 2-6 alkynyl group: C 3-6 A carbocyclic ring and a 4- to 6-membered heterocycle, either of which may optionally be substituted by one or more substituents independently selected from the following: halogen, -OR 11A -N(R) 11A )2、-C(O)R 11A -C(O)N(R) 11A )2、-N(R 11A )C(O)R 11A -NO2, =O and -CN; and C 1-6 Alkyl group, optionally substituted by one or more substituents independently selected from: halogen, -OR 11A and -N(R) 11A )2.

7. The compound or salt according to claim 6, wherein A 2 C is optionally replaced by the following 2-6 Alkyne group: cyclopropyl, cyclopentyl, oxetyl, aziryl, and oxazolyl, any of which may optionally be substituted by one or more substituents independently selected from: halogen, -OR 11A -N(R) 11A )2、-C(O)R 11A -C(O)N(R) 11A )2、-N(R 11A )C(O)R 11A -NO2, =O, -CN; and C 1-6 Alkyl group, optionally substituted by one or more substituents independently selected from: halogen, -OR 11A and -N(R) 11A )2.

8. The compound or salt according to claim 7, wherein A 2 Selected from , , , , , and .

9. The compound or salt according to any one of claims 1-8, wherein L 1 L 2 L 3 and L 4 None of them exist.

10. The compound or salt according to any one of claims 1-9, wherein A 2 yes Among them, ring B 1 It is C 3-8 A carbocyclic or 4- to 8-membered heterocyclic ring, any of which may optionally be substituted by one or more substituents independently selected from the following: halogen, C 1-4 Alkyl, C 1-4 Halogenated alkyl groups, -OR 20 -SR 20 -N(R) 20 )2、-C(O)R 20 -C(O)N(R) 20 )2、-C(O)OR 20 -OC(O)R 20 -N(R) 20 )C(O)R 20 -N(R) 20 )S(O)2R 20 -N(R) 20 )C(O)N(R 20 )2、-N(R 20 )C(O)OR 20 -OC(O)N(R) 20 )2、-S(O)R 20 -S(O)2R 20 -NO2 and -CN.

11. The compound or salt according to any one of claims 1-10, wherein R 5 Selected from 4- to 10-membered heterocycles and C 3-10 The carbon ring, wherein any one of them is optionally substituted by one or more substituents independently selected from the following: halogen, -OR 16 , -SR 16 , -N(R 16 )2, -C(O)N(R 16 )2, -C(O)OR 16 , -OC(O)R 16 , -N(R 16 )C(O)R 16 , -N(R 16 )S(O)2R 16 , -S(O)2N(R 16 )2, -N(R 16 )C(O)N(R 16 )2, -N(R 16 )C(O)OR 16 , -OC(O)N(R 16 )2, -S(O)R 16 , -S(O)2R 16 , -NO2, =O, =S, =N(R 16 ) and -CN; C 1-4 Alkyl group, optionally substituted by one or more substituents independently selected from: halogen, C 1-4 Alkyl, C 1-4 Halogenated alkyl groups, -OR 16 -SR 16 -N(R) 16 2. -NO2 and -CN; and 4- to 6-membered heterocyclic rings and C 3-8 A carbon ring, wherein each of which is optionally substituted by one or more substituents independently selected from the following: halogen, C 1-4 Alkyl, C 1-4 Halogenated alkyl groups, -OR 16 -SR 16 -N(R) 16 2. -NO2 and -CN.

12. The compound or salt according to claim 11, wherein R 5 It is a 4- to 10-membered heterocycle optionally substituted with one or more substituents independently selected from the following: halogen, -OR 16 , -SR 16 , -N(R 16 )2, -C(O)N(R 16 )2, -C(O)OR 16 , -OC(O)R 16 , -N(R 16 )C(O)R 16 , -N(R 16 )S(O)2R 16 , -S(O)2N(R 16 )2, -N(R 16 )C(O)N(R 16 )2, -N(R 16 )C(O)OR 16 , -OC(O)N(R 16 )2, -S(O)R 16 , -S(O)2R 16 , -NO2, =O, =S, =N(R 16 ) and -CN; C 1-4 Alkyl group, optionally substituted by one or more substituents independently selected from: halogen, C 1-4 Alkyl, C 1-4 Halogenated alkyl groups, -OR 16 -SR 16 -N(R) 16 2. -NO2 and -CN; and 4- to 6-membered heterocyclic rings and C 3-8 A carbon ring, wherein each of which is optionally substituted by one or more substituents independently selected from the following: halogen, C 1-4 Alkyl, C 1-4 Halogenated alkyl groups, -OR 16 -SR 16 -N(R) 16 2. -NO2 and -CN.

13. The compound or salt according to claim 12, wherein R 5 It is a 4- to 10-membered heterocycle optionally substituted with one or more substituents independently selected from the following: Halogen, -OR 16 , -SR 16 , -N(R 16 )2, -C(O)N(R 16 )2, -C(O)OR 16 , -OC(O)R 16 , -N(R 16 )C(O)R 16 , -N(R 16 )S(O)2R 16 , -S(O)2N(R 16 )2, -N(R 16 )C(O)N(R 16 )2, -N(R 16 )C(O)OR[[ID=2,9]] 16 , -OC(O)N(R 16 )2, -S(O)R[[ID=,33]] 16 , -S(O)2R 16 , -NO2, =O, =S, =N(R 16 ) and -CN; C 1-4 Alkyl group, optionally substituted by one or more substituents independently selected from: halogen, C 1-4 Alkyl, C 1-4 Halogenated alkyl groups, -OR 16 -SR 16 -N(R) 16 2. -NO2 and -CN.

14. The compound or salt according to claim 13, wherein R 5 The group is selected from azacyclobutane, cyclopentyl, cyclohexyl, imidazolyl, pyrazolyl, 1H-1,2,3-triazolyl, 4H-1,2,4-triazolyl, 1,4-dihydropyridinyl, 3,4-dihydropyridino[3,4-d]pyrimidinyl, 1H-benzo[d][1,2,3]triazolyl, wherein each is optionally substituted by one or more substituents independently selected from the following: halogen, -OR 16 , -SR 16 , -N(R 16 )2, -C(O)N(R 16 )2, -C(O)OR 16 , -OC(O)R 16 , -N(R 16 )C(O)R 16 , -N(R 16 )S(O)2R 16 , -S(O)2N(R 16 ) - N(R 16 )C(O)N(R 16 )2, -N(R 16 )C(O)OR 16 , -OC(O)N(R 16 )2, -S(O)R 16 , -S(O)2R 16 , -NO2, =O, =S, =N(R 16 ) and -CN; C 1-4 Alkyl group, optionally substituted by one or more substituents independently selected from: halogen, C 1-4 Alkyl, C 1-4 Halogenated alkyl groups, -OR 16 -SR 16 -N(R) 16 2. -NO2 and -CN.

15. The compound or salt according to claim 14, wherein R 5 Selected from , , , , , , , , , , , , , , , , and .

16. The compound or salt according to any one of claims 1-15, wherein ring B is .

17. The compound or salt according to claim 16, wherein ring B is selected from... and .

18. The compound or salt according to any one of claims 1-15, wherein ring B is .

19. The compound or salt according to claim 1, wherein the structure of formula (I) is represented by the structure of formula (II): (II), Or its pharmaceutically acceptable salt, wherein: R 1 Selected from hydrogen, halogens, -OR 10 -SR 10 -N(R) 10 )2, -NO2 and -CN; and C, optionally substituted by one or more substituents independently selected from the following 1-6 Alkyl groups: halogens, -OR 10 -SR 10 -N(R) 10 2. -NO2 and -CN; A 1 and A 2 Each is independently selected from (i), (ii), and (iii): (i) Hydrogen, halogens, C 1-4 Halogenated alkyl groups, -OR 11 -SR 11 -N(R) 11 )2、-C(O)N(R 11 )2、-N(R 11 )C(O)R 11 -C(O)OR 11 -OC(O)R 11 -N(R) 11 )C(O)OR 11 -OC(O)N(R) 11 )2、-N(R 11 )C(O)N(R 11 )2、-S(O)R 11 -S(O)2R 11 -N(R) 11 )S(O)2R 11 -S(O)2N(R) 11 2. -NO2 and -CN; (ii) C 1-6 Alkyl, C 2-6 alkenyl and C 2-6 Alkyne group, wherein any one of them is optionally selected independently from halogen, -OR 11 -SR 11 -N(R) 11 )2、-C(O)N(R 11 )2、-N(R 11 )C(O)R 11 -C(O)OR 11 -OC(O)R 11 -N(R) 11 )C(O)OR 11 -OC(O)N(R) 11 )2、-N(R 11 )C(O)N(R 11 )2、-S(O)R 11 -S(O)2R 11 -N(R) 11 )S(O)2R 11 -S(O)2N(R) 11 )2、-NO2、=O、=S、=N(R 11 Substitution of ) and -CN; and (iii) 5-10 yuan heterocyclic rings and C 3-10 The carbon ring, wherein any one of them is optionally substituted by one or more substituents independently selected from the following: halogen, -OR 11 , -SR 11 , -N(R 11 )2, -C(O)R 11 , -C(O)N(R 11 )2, -N(R 11 )C(O)R 11 , -N(R 11 )S(O)2R 11 , -C(O)OR 11 , -OC(O)R 11 , -N(R 11 )C(O)OR 11 , -OC(O)N(R 11 )2, -N(R 11 )C(O)N(R 11 )2, -S(O)R 11 , -S(O)2R 11 , -S(O)2N(R 11 )2, -NO2, =O, =S, =N(R 11 ) and -CN; and C 1-6 Alkyl, C 2-6 alkenyl and C 2-6 Alkyne group, wherein any of them may optionally be substituted by one or more substituents independently selected from: halogen, -OR 11 -SR 11 -N(R) 11 )2、-C(O)R 11 -C(O)N(R) 11 )2、-N(R 11 )C(O)R 11 -C(O)OR 11 -OC(O)R 11 -N(R) 11 )C(O)OR 11 -OC(O)N(R) 11 )2、-N(R 11 )C(O)N(R 11 )2、-S(O)R 11 -S(O)2R 11 -N(R) 11 )S(O)2R 11 -S(O)2N(R) 11 )2、-NO2、=O、=S、=N(R 11 ) and -CN; and C 3-10 A carbocyclic ring and a 4- to 10-membered heterocycle, either of which may optionally be substituted by one or more substituents independently selected from the following: halogen, -OR 11 , -N(R 11 )2, -C(O)R 11 , -C(O)N(R 11 )2, -N(R 11 )C(O)R 11 , -C(O)OR 11 , -OC(O)R 11 , -NO2, =O, =S, =N(R 11 ), -CN; and C 1-6 Alkyl C 2-6 alkenyl and C 3-6 Alkyne group, wherein any of them may optionally be substituted by one or more substituents independently selected from: halogen, -OR 11 -SR 11 -N(R) 11 )2、-C(O)R 11 -C(O)N(R) 11 )2、-N(R 11 )C(O)R 11 -N(R) 11 )S(O)2R 11 -C(O)OR 11 -OC(O)R 11 -NO2, =O, =S, =N(R) 11 ) and -CN; q is selected from 1, 2, and 3; m and n are each independently selected from 0, 1, 2 and 3; R 2 In each case, it is independently selected from halogens, C 1-4 Alkyl, C 1-4 Halogenated alkyl groups, -OR 12 -SR 12 -N(R) 12 2. -NO2 and -CN; R 3 Select independently in each case: Halogen, -OR 13 -SR 13 -N(R) 13 )2、-C(O)R 13 -C(O)N(R) 13 )2、-N(R 13 )C(O)R 13 -C(O)OR 13 -OC(O)R 13 -NO2 and -CN; and C 1-6 Alkyl group, optionally substituted by one or more substituents independently selected from: halogen, -OR 13 -SR 13 -N(R) 13 )2、-C(O)R 13 -C(O)N(R) 13 )2、-N(R 13 )C(O)R 13 -C(O)OR 13 -OC(O)R 13 -NO2, =O, =S, =N(R) 13 ) and -CN; p is selected from 0, 1, 2, 3, 4, and 5; R 4 Select independently in each case: Halogen, -OR 14 -SR 14 -N(R) 14 )2、-C(O)R 14 -C(O)N(R) 14 )2、-N(R 14 )C(O)R 14 -C(O)OR 14 -OC(O)R 14 -NO2 and -CN; and C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, wherein any of them may optionally be substituted by one or more substituents independently selected from: halogen, -OR 14 -SR 14 -N(R) 14 )2、-C(O)R 14 -C(O)N(R) 14 )2、-N(R 14 )C(O)R 14 -C(O)OR 14 -OC(O)R 14 -NO2, =O, =S, =N(R) 14 ) and -CN; or Two R atoms connected to the same atom 4 Together they form a group selected from the following: =O, =S, and =N(R) 14 );or Two R atoms connected to the same or adjacent atoms 4 Together with the carbon atoms they are attached to, they form groups selected from the following: 4- to 8-membered heterocycles and C. 3-8 A carbon ring, wherein any of the carbon rings may optionally be substituted by one or more substituents independently selected from the following: halogen, C 1-4 Alkyl, C 1-4 Halogenated alkyl groups, -OR 14 -SR 14 -N(R) 14 2. -NO2 and -CN; L by -L 1 -L 2 -L 3 -L 4 - indicates that L 1 L 2 L 3 and L 4 Each is independently selected from (a) and (b): (a) -O-, -N(R 15 )-, -S-, -S(O)-, -S(O)2-, -S(O)(NR 15 )-, -N(R 15 )C(O)-, -N(R 15 )C(O)O-, -N(R 15 )S(O)2-, -N(R 15 )S(O)2N(R 15 )-, -S(O)(NR 15 )N(R 15 )-, -N(R 15 )N(R 15 )-, -(R 15 )NC(O)N(R 15 )-, and -(R 15 )NC(O)N(R 15 )N(R 15 )-; and (b) C 1-6 Alkylene, C 2-6 imidene group, C 2-6 Ethyne group, C 3-8 Carbocyclic and 4- to 8-membered heterocyclic groups, either of which may optionally be substituted by one or more substituents independently selected from: halogen, -OR 15 -SR 15 =O, =S, and -CN; Where L 2 L 3 and L 4 Each of the two optional locations does not exist; Where L 1 L 2 L 3 and L 4 No more than two are selected from (a), and the two selected are not adjacent; R 5 Selected from 4- to 10-membered heterocycles and C 3-10 The carbon ring, wherein any one of them is optionally substituted by one or more substituents independently selected from the following: Halogen, C 1-4 Halogenated alkyl, -OR 16 , -SR 16 , -N(R 16 )2, -C(O)N(R 16 )2, -C(O)OR 16 , -OC(O)R 16 , -N(R 16 )C(O)R 16 , -N(R 16 )S(O)2R 16 , -S(O)2N(R 16 )2, -N(R 16 )C(O)N(R 16 )2, -N(R 16 )C(O)OR 16 , -OC(O)N(R 16 )2, -S(O)R 16 , -S(O)2R 16 , -NO2, =O, =S, =N(R 16 ) and -CN; C 1-4 Alkyl, C 2-6 alkenyl and C 2-6 Alkyne group, wherein each of them is optionally substituted by one or more substituents independently selected from: halogen, C 1-4 Alkyl, C 1-4 Halogenated alkyl groups, -OR 16 -SR 16 -N(R) 16 2. -NO2 and -CN; as well as 4- to 6-membered heterocyclic rings and C 3-8 A carbon ring, wherein each of which is optionally substituted by one or more substituents independently selected from the following: halogen, C 1-4 Alkyl, C 1-4 Halogenated alkyl groups, -OR 16 -SR 16 -N(R) 16 2. -NO2 and -CN; R 10 R 11 R 12 R 13 R 14 and R 15 Each time it appears, it is independently selected from: hydrogen, C 1-4 Alkyl, C 3-8 Carbon rings, 4- to 8-membered heterocycles and C 1-4 Halogenated alkyl groups; R 16 Each time it appears, it is independently selected from (iv), (v), and (vi): (iv) Hydrogen; (v) C 1-4 Alkyl, wherein the C 1-4 The alkyl group is optionally substituted by one or more substituents independently selected from the following: Halogen, -OR 20 , -SR 20 , -N(R 20 )2, -C(O)R 20 , -C(O)OR 20 , -OC(O)R 20 , -C(O)N(R 20 )2, -N(R 20 )C(O)R 20 , -N(R 20 )C(O)N(R 20 )2, -N(R 20 )C(O)OR 20 , -OC(O)N(R 20 )2, -S(O)R 20 , -S(O)2R 20 , -N(R 20 )S(O)2R 20 , -S(O)2N(R 20 )2, -NO2 and -CN; and C 3-8 A carbocyclic ring and 4- to 8-membered heterocycles, any of which may optionally be substituted by one or more substituents independently selected from the following: halogen, C 1-4 Alkyl, C 1-4 Halogenated alkyl groups, -OR 20 -SR 20 -N(R) 20 )2、-C(O)R 20 -C(O)OR 20 -OC(O)R 20 -C(O)N(R) 20 )2、-N(R 20 )C(O)R 20 -N(R) 20 )C(O)N(R 20 )2、-N(R 20 )C(O)OR 20 -OC(O)N(R) 20 )2、-S(O)R 20 -S(O)2R 20 -N(R) 20 )S(O)2R 20 -S(O)2N(R) 20 2. -NO2 and -CN; and (ⅵ) C 3-8 A carbocyclic ring and 4- to 8-membered heterocycles, any of which may optionally be substituted by one or more substituents independently selected from the following: halogen, C 1-4 Alkyl, C 1-4 Halogenated alkyl groups, -OR 20 -SR 20 -N(R) 20 )2、-C(O)R 20 -C(O)N(R) 20 )2、-C(O)OR 20 -OC(O)R 20 -N(R) 20 )C(O)R 20 -N(R) 20 )S(O)2R 20 -N(R) 20 )C(O)N(R 20 )2、-N(R 20 )C(O)OR 20 -OC(O)N(R) 20 )2、-S(O)R 20 -S(O)2R 20 -NO2 and -CN; and R 20 Each time it appears, it is independently selected from hydrogen, C 1-4 Alkyl, C 1-4 Haloalkyl, C 3-8 Carbon rings and 4- to 8-membered heterocycles.

20. The compound or salt according to claim 19, wherein q is 1.

21. The compound or salt according to claim 19 or claim 20, wherein the structure is represented by formula (III): (III); Or its pharmaceutically acceptable salt.

22. The compound or salt according to any one of claims 19-21, wherein the structure is represented by formula (III-A): (III-A); Or its pharmaceutically acceptable salt.

23. The compound or salt according to any one of claims 19-22, wherein m is 0.

24. The compound or salt according to any one of claims 19-23, wherein n is 0.

25. The compound or salt according to any one of claims 19-24, wherein p is selected from 0, 1 and 2.

26. The compound or salt according to any one of claims 19-25, wherein R 4 In each case, it is independently selected from: halogen, -OR 14 -SR 14 -N(R) 14 )2、-C(O)R 14 -C(O)N(R) 14 )2、-N(R 14 )C(O)R 14 -C(O)OR 14 -OC(O)R 14 -NO2 and -CN.

27. The compound or salt according to claim 26, wherein R 4 Fluorine, chlorine, and bromine are chosen independently in each case.

28. The compound or salt according to claim 25, wherein p is 0.

29. The compound or salt according to any one of claims 19-28, wherein A 1 Selected from hydrogen, halogens, C 1-4 Alkyl, C 1-4 Halogenated alkyl groups, -OR 11 -N(R) 11 )2 and -CN.

30. The compound or salt according to claim 29, wherein A 1 Selected from hydrogen, halogens, C 1-4 Alkyl and C 1-4 Halogenated alkyl groups.

31. The compound or salt according to claim 29 or claim 30, wherein A 1 Selected from hydrogen, fluorine, and methyl.

32. The compound or salt according to any one of claims 29-31, wherein A 1 It is hydrogen.

33. The compound or salt according to any one of claims 19-32, wherein the structure is represented by formula (IV): (IV); Or its pharmaceutically acceptable salt.

34. The compound or salt according to any one of claims 19-33, wherein the structure is represented by formula (IV-A): (IV-A); Or its pharmaceutically acceptable salt.

35. The compound or salt according to any one of claims 19-34, wherein R 1 Selected from hydrogen, halogens, -OR 10 -N(R) 10 )2, -NO2, -CN; and C 1-6 Alkyl group, optionally composed of one or more elements independently selected from halogens, -OR 10 and -N(R) 10 Substituents of )2.

36. The compound or salt according to claim 35, wherein R 1 Selected from hydrogen, -OR 10 and -CN; and C 1-6 Alkyl groups, optionally surrounded by one or more -OR 10 replace.

37. The compound or salt according to claim 35 or claim 36, wherein R 1 Selected from hydrogen, methoxy, -CN, methyl, ethyl and (methoxy)methyl.

38. The compound or salt according to claim 35 or claim 36, wherein R 1 Selected from hydrogen, fluorine, methoxy, -CN, methyl, ethyl, (methoxy)methyl and .

39. The compound or salt according to any one of claims 35-38, wherein R 1 It is hydrogen.

40. The compound or salt according to any one of claims 19-39, wherein the structure is represented by formula (V): (V)； Or its pharmaceutically acceptable salt.

41. The compound or salt according to any one of claims 19-40, wherein the structure is represented by formula (VA): (VA); Or its pharmaceutically acceptable salt.

42. The compound or salt according to any one of claims 19-41, wherein A 2 Selected from: C 1-6 Alkyl, C 2-6 alkenyl and C 2-6 Alkyne group, wherein any of them may optionally be substituted by one or more substituents independently selected from: halogen, -OR 11 -N(R) 11 )2、-C(O)N(R 11 )2、-N(R 11 )C(O)R 11 -N(R) 11 )S(O)2R 11 -S(O)2N(R) 11 )2, -NO2, =O and -CN; and 5 to 10 yuan heterocyclic rings and C 3-10 The carbon ring, wherein any one of them is optionally substituted by one or more substituents independently selected from the following: Halogen, -OR 11 -N(R) 11 )2、-C(O)R 11 -C(O)N(R) 11 )2、-N(R 11 )C(O)R 11 -N(R) 11 )S(O)2R 11 -NO2, =O, and -CN; C 1-6 Alkyl, C 2-6 alkenyl and C 3-6 Alkyne group, wherein any of them may optionally be substituted by one or more substituents independently selected from: halogen, -OR 11 -N(R) 11 )2、-C(O)R 11 -C(O)N(R) 11 )2、-N(R 11 )C(O)R 11 -N(R) 11 )S(O)2R 11 -NO2, =O and -CN; and C 3-10 A carbocyclic ring and a 4- to 10-membered heterocycle, either of which may optionally be substituted by one or more substituents independently selected from the following: halogen, -OR 11 -N(R) 11 )2、-C(O)R 11 -C(O)N(R) 11 )2、-N(R 11 )C(O)R 11 -NO2, =O, -CN; C 1-6 Alkyl, C 2-6 alkenyl and C 2-6 alkynyl group, the C 1-6 Alkyl, C 2-6 alkenyl and C 3-6 Each alkynyl group may optionally be substituted by one or more substituents independently selected from the following: halogen, -OR 11 -N(R) 11 )2、-C(O)R 11 -C(O)N(R) 11 )2、-N(R 11 )C(O)R 11 -N(R) 11 )S(O)2R 11 -NO2, =O, and -CN.

43. The compound or salt according to claim 42, wherein A 2 Selected from: C 1-6 Alkyl and C 2-6 Alkyne groups, wherein each is optionally selected independently by one or more groups from halogens, -OR 11 -N(R) 11 )2、-C(O)N(R 11 )2、-N(R 11 )C(O)R 11 -N(R) 11 )S(O)2R 11 -S(O)2N(R) 11 Substitution by substituents of -NO2, =O, and -CN; and 5 to 10 yuan heterocyclic rings and C 3-10 The carbon ring, wherein any one of them is optionally substituted by one or more substituents independently selected from the following: Halogen, -OR 11 -N(R) 11 )2、-C(O)R 11 -C(O)N(R) 11 )2、-N(R 11 )C(O)R 11 -N(R) 11 )S(O)2R 11 -NO2, =O, and -CN; C 1-6 Alkyl, C 2-6 alkenyl and C 2-6 Alkyne group, wherein any of them may optionally be substituted by one or more substituents independently selected from: halogen, -OR 11 -N(R) 11 )2、-C(O)R 11 -C(O)N(R) 11 )2、-N(R 11 )C(O)R 11 -N(R) 11 )S(O)2R 11 -NO2, =O and -CN; and C 3-8 A carbocyclic ring and a 4- to 10-membered heterocycle, either of which may optionally be substituted by one or more substituents independently selected from the following: halogen, -OR 11 -N(R) 11 )2、-C(O)R 11 -C(O)N(R) 11 )2、-N(R 11 )C(O)R 11 -NO2, =O, -CN; C 1-6 Alkyl, C 2-6 alkenyl and C 2-6 alkynyl group, the C 1-6 Alkyl, C 2-6 alkenyl and C 2-6 Each alkynyl group may optionally be substituted by one or more substituents independently selected from the following: halogen, -OR 11 -N(R) 11 )2、-C(O)R 11 -C(O)N(R) 11 )2、-N(R 11 )C(O)R 11 -N(R) 11 )S(O)2R 11 -NO2, =O, and -CN.

44. The compound or salt according to claim 42 or claim 43, wherein A 2 Selected from C 1-6 Alkyl and C 2-6 Alkyne groups, wherein each is optionally selected independently by one or more groups from halogens, -OR 11 -N(R) 11 Substitution with substituents such as -NO2, =O, and -CN.

45. The compound or salt according to claim 44, wherein A 2 Selected from methyl, ethyl, propyl, isopropyl, ethynyl, propynyl, and isopropynyl, wherein each is optionally selected independently by one or more halogens, -OR 11 -N(R) 11 Substitution with substituents such as -NO2, =O, and -CN.

46. ​​The compound or salt according to claim 45, wherein A 2 Selected from: -CH3、 , , , , and .

47. The compound or salt according to claim 42 or claim 43, wherein A 2 Selected from 5- to 10-membered heteroaryl, 5- to 10-membered heterocycloalkyl, C 4-8 Aryl and C 3-10 Cycloalkyl groups, wherein each is optionally substituted by one or more substituents independently selected from the following: Halogen, -OR 11 -N(R) 11 )2、-C(O)R 11 -C(O)N(R) 11 )2、-N(R 11 )C(O)R 11 -N(R) 11 )S(O)2R 11 -NO2, =O, and -CN; C 1-6 Alkyl, C 2-6 alkenyl and C 3-6 Alkyne group, wherein any of them may optionally be substituted by one or more substituents independently selected from: halogen, -OR 11 -N(R) 11 )2、-C(O)R 11 -C(O)N(R) 11 )2、-N(R 11 )C(O)R 11 -N(R) 11 )S(O)2R 11 -NO2, =O and -CN; and C 3-10 A carbocyclic ring and a 4- to 10-membered heterocycle, either of which may optionally be substituted by one or more substituents independently selected from the following: halogen, -OR 11 -N(R) 11 )2、-C(O)R 11 -C(O)N(R) 11 )2、-N(R 11 )C(O)R 11 -NO2, =O, -CN; C 1-6 Alkyl, C 2-6 alkenyl and C 2-6 alkynyl group, the C 1-6 Alkyl, C 2-6 alkenyl and C 3-6 Each alkynyl group may optionally be substituted by one or more substituents independently selected from the following: halogen, -OR 11 -N(R) 11 )2、-C(O)R 11 -C(O)N(R) 11 )2、-N(R 11 )C(O)R 11 -N(R) 11 )S(O)2R 11 -NO2, =O, and -CN.

48. The compound or salt according to claim 47, wherein A 2 Selected from pyrazolyl, triazolyl, oxazolyl, thiazolyl, morpholinyl, phenyl, and cyclopropyl, wherein each is optionally substituted by one or more substituents independently selected from the following: Halogen, -OR 11 -N(R) 11 )2、-C(O)R 11 -C(O)N(R) 11 )2、-N(R 11 )C(O)R 11 -N(R) 11 )S(O)2R 11 -NO2, =O, and -CN; C 1-6 Alkyl, C 2-6 alkenyl and C 3-6 Alkyne group, wherein any of them may optionally be substituted by one or more substituents independently selected from: halogen, -OR 11 -N(R) 11 )2、-C(O)R 11 -C(O)N(R) 11 )2、-N(R 11 )C(O)R 11 -N(R) 11 )S(O)2R 11 -NO2, =O and -CN; and C 3-10 A carbocyclic ring and a 4- to 10-membered heterocycle, either of which may optionally be substituted by one or more substituents independently selected from the following: halogen, -OR 11 -N(R) 11 )2、-C(O)R 11 -C(O)N(R) 11 )2、-N(R 11 )C(O)R 11 -NO2, =O, -CN; C 1-6 Alkyl, C 2-6 alkenyl and C 2-6 alkynyl group, the C 1-6 Alkyl, C 2-6 alkenyl and C 3-6 Each alkynyl group may optionally be substituted by one or more substituents independently selected from the following: halogen, -OR 11 -N(R) 11 )2、-C(O)R 11 -C(O)N(R) 11 )2、-N(R 11 )C(O)R 11 -N(R) 11 )S(O)2R 11 -NO2, =O, and -CN.

49. The compound or salt according to claim 42, wherein A 2 Selected from: 。 50. The compound or salt according to claim 42, wherein A 2 Selected from: 。 51. The compound or salt according to any one of claims 19-41, wherein A 2 Selected from 5- to 10-membered heterocycles and C 3-10 The carbon ring, wherein any one of them is optionally substituted by one or more substituents independently selected from the following: chlorine, -OR 11 , -N(R 11 )2, -C(O)R 11 ,-C(O)N(R 11 )2, -N(R 11 )C(O)R 11 , -N(R 11 )S(O)2R 11 , = O sum - CN; C 1-6 Alkyl, C 2-6 alkenyl and C 3-6 Alkyne group, wherein any of them may optionally be substituted by one or more substituents independently selected from: halogen, -OR 11 -N(R) 11 )2、-C(O)R 11 -C(O)N(R) 11 )2、-N(R 11 )C(O)R 11 -N(R) 11 )S(O)2R 11 -NO2, =O and -CN; and C 3-10 A carbocyclic ring and a 4- to 10-membered heterocycle, either of which may optionally be substituted by one or more substituents independently selected from the following: Halogen, -OR 11 -N(R) 11 )2、-C(O)R 11 -C(O)N(R) 11 )2、-N(R 11 )C(O)R 11 =O and -CN; and C 1-6 Alkyl, C 2-6 alkenyl and C 3-6 Alkyne group, wherein any of them may optionally be substituted by one or more substituents independently selected from: halogen, -OR 11 -N(R) 11 )2、-C(O)R 11 -C(O)N(R) 11 )2、-N(R 11 )C(O)R 11 -N(R) 11 )S(O)2R 11 =O and -CN.

52. The compound or salt according to claim 51, wherein A 2 It is a 5- to 10-membered heterocycle optionally substituted with one or more substituents independently selected from the following: chlorine, -OR 11 , -N(R 11 )2, -C(O)R 11 ,-C(O)N(R 11 )2, -N(R 11 )C(O)R 11 , -N(R 11 )S(O)2R 11 , = O sum - CN; C 1-6 Alkyl, C 2-6 alkenyl and C 3-6 Alkyne group, wherein any of them may optionally be substituted by one or more substituents independently selected from: halogen, -OR 11 -N(R) 11 )2、-C(O)R 11 -C(O)N(R) 11 )2、-N(R 11 )C(O)R 11 -N(R) 11 )S(O)2R 11 -NO2, =O and -CN; and C 3-10 The carbocyclic ring and 4- to 10-membered heterocycles, each of which may be optionally substituted by one or more substituents independently selected from the following: Halogen, -OR 11 -N(R) 11 )2、-C(O)R 11 -C(O)N(R) 11 )2、-N(R 11 )C(O)R 11 =O and -CN; and C 1-6 Alkyl, C 2-6 alkenyl and C 3-6 Alkyne group, wherein any of them may optionally be substituted by one or more substituents independently selected from: halogen, -OR 11 -N(R) 11 )2、-C(O)R 11 -C(O)N(R) 11 )2、-N(R 11 )C(O)R 11 -N(R) 11 )S(O)2R 11 =O and -CN.

53. The compound or salt according to claim 51 or claim 52, wherein A 2 It is a 5- to 10-membered heterocycle optionally substituted with one or more substituents independently selected from the following: chlorine, -OR 11 , -N(R 11 )2, -C(O)R 11 ,-C(O)N(R 11 )2, -N(R 11 )C(O)R 11 , = O sum - CN; C 1-6 Alkyl group, optionally substituted by one or more substituents independently selected from: halogen, -OR 11 -N(R) 11 )2、-C(O)R 11 -C(O)N(R) 11 )2、-N(R 11 )C(O)R 11 and = O; and C 3-10 Carbon rings and 4- to 10-membered heterocycles; wherein the C 3-10 The carbocyclic ring and the 4- to 10-membered heterocycle are each optionally substituted by one or more substituents independently selected from the following: halogen, -OR 11 -N(R) 11 )2、-C(O)R 11 -C(O)N(R) 11 )2、-N(R 11 )C(O)R 11 =O and -CN; and C 1-6 Alkyl, the C 1-6 The alkyl group is optionally substituted by one or more substituents independently selected from the following: halogen, -OR 11 -N(R) 11 )2、-C(O)R 11 -C(O)N(R) 11 )2、-N(R 11 )C(O)R 11 And = O.

54. The compound or salt according to any one of claims 51-53, wherein A 2 It is a 5- to 10-membered heterocycle optionally substituted with one or more substituents independently selected from the following: halogen, -OR 11 -N(R) 11 )2、-C(O)R 11 -C(O)N(R) 11 )2、-N(R 11 )C(O)R 11 =O and -CN; and C 1-6 Alkyl group, optionally composed of one or more elements independently selected from halogens, -OR 11 -N(R) 11 )2、-C(O)R 11 -C(O)N(R) 11 )2、-N(R 11 )C(O)R 11 Substitution with =O and substituents.

55. The compound or salt according to any one of claims 51-54, wherein A 2 It is a 5- to 10-membered heterocycle optionally substituted with one or more substituents independently selected from the following: halogen, -OR 11 -N(R) 11 )2、-C(O)R 11 -C(O)N(R) 11 )2、-N(R 11 )C(O)R 11 =O and -CN; and C 1-6 Alkyl group, optionally composed of one or more elements independently selected from halogens, -OR 11 and -N(R) 11 Substituents of )2.

56. The compound or salt according to any one of claims 51-55, wherein A 2 It is a 5- to 10-membered heterocycle optionally substituted with one or more substituents independently selected from halogens.

57. The compound or salt according to any one of claims 51-56, wherein A 2 It is a 5- to 10-membered heterocycle optionally substituted with one or more substituents independently selected from fluorine.

58. The compound or salt according to any one of claims 51-57, wherein the optionally substituted 5- to 10-membered heterocycle is an optionally substituted 5- to 10-membered heteroaryl group.

59. The compound or salt according to any one of claims 51-58, wherein the optionally substituted 5- to 10-membered heterocycle is an optionally substituted 5-membered heteroaryl group.

60. The compound or salt according to any one of claims 51-59, wherein the optionally substituted 5-membered heteroaryl group is selected from optionally substituted pyrazolyl and optionally substituted triazolyl.

61. The compound or salt according to any one of claims 51-58, wherein A 2 Selected from , , and .

62. The compound or salt according to any one of claims 51-58, wherein A 2 Selected from , , and .

63. The compound or salt according to any one of claims 51-62, wherein A 2 Selected from , and .

64. The compound or salt according to any one of claims 19-63, wherein L 1 L 2 L 3 and L 4 Each is independently selected from (a) and (b): (a) -O-, -N(R 15 )-, -S-, -N(R 15 )C(O)-, -N(R 15 )C(O)O-, -N(R 15 )S(O)2, -N(R 15 )N(R 15 )- and -(R 15 )NC(O)N(R 15 )-; and (b) C 1-6 Alkylene, C 2-6 imidene group, C 2-6 Ethyne group, C 3-6 Carbocyclic and 4- to 6-membered heterocyclic groups, either of which may optionally be independently selected from halogens, -OR 15 Substitution of =O and -CN groups; Where L 2 L 3 and L 4 Each of the two optional locations does not exist; Where L 1 L 2 L 3 and L 4 No more than two are selected from (a), and the two selected are not adjacent; R 15 Selected from hydrogen and C 1-4 alkyl.

65. The compound or salt according to claim 64, wherein L 1 L 2 L 3 and L 4 Each is independently selected from (a) and (b): (a) -O-、-N(R 15 - and -N(R) 15 )C(O)-; and (b) C 1-6 Alkylene; Where L 2 L 3 and L 4 Each of the two optional locations does not exist; Where L 1 L 2 L 3 and L 4 No more than two are selected from (a), and the two selected are not adjacent; and R 15 Selected from hydrogen and C 1-4 alkyl.

66. The compound or salt according to claim 64 or claim 65, wherein L 4 It does not exist.

67. The compound or salt according to any one of claims 64-66, wherein L 3 It does not exist or is -O-.

68. The compound or salt according to any one of claims 64-66, wherein L 3 It is a methylene group that does not exist, is -O-, ethynyl, or is substituted with =O.

69. The compound or salt according to any one of claims 64-68, wherein L 2 It is either non-existent or methylene.

70. The compound or salt according to any one of claims 64-68, wherein L 2 It is non-existent, methylene, (methyl)methylene, ethylene, or -O-.

71. The compound or salt according to any one of claims 64-70, wherein L 1 It is -N(R) 15 )C(O)-.

72. The compound or salt according to any one of claims 64-70, wherein L 1 Selected from -N(R) 15 )C(O)-、-N(R 15 )-、-N(R 15 )S(O)-、-(R 15 )NC(O)N(R 15 )- and 4- to 6-membered heterocyclic groups optionally substituted with one or more halogen atoms.

73. The compound or salt according to any one of claims 64-72, wherein R 15 It is hydrogen.

74. The compound or salt according to any one of claims 64-72, wherein R 15 Selected from hydrogen and -CH3.

75. The compound or salt according to claim 64 or claim 65, wherein L is selected from... , and .

76. The compound or salt according to claim 64 or claim 65, wherein L is selected from... 。 77. The compound or salt according to any one of claims 19-76, wherein R 5 Selected from 4- to 10-membered heterocycles and C 3-10 The carbon ring, wherein any one of them is optionally substituted by one or more substituents independently selected from the following: Halogen, C 1-4 Halogenated alkyl groups, -OR 16 -N(R) 16 )2、-C(O)N(R 16 )2、-C(O)OR 16 -OC(O)R 16 -N(R) 16 )C(O)R 16 -NO2, =O, and -CN; C 1-4 Alkyl, C 2-6 alkenyl and C 2-6 Alkyne group, wherein each of them is optionally substituted by one or more substituents independently selected from: halogen, C 1-4 Alkyl, C 1-4 Halogenated alkyl groups, -OR 16 -SR 16 -N(R) 16 2. -NO2 and -CN; and 4- to 6-membered heterocyclic rings and C 3-8 A carbon ring, wherein each of which is optionally substituted by one or more substituents independently selected from the following: halogen, C 1-4 Alkyl, C 1-4 Halogenated alkyl groups, -OR 16 -N(R) 16 2. -NO2 and -CN.

78. The compound or salt according to any one of claims 19-76, wherein R 5 Selected from 4- to 10-membered heterocycles and C 3-10 The carbon ring, wherein any one of them is optionally substituted by one or more substituents independently selected from the following: Halogen, C 1-4 Halogenated alkyl groups, -OR 16 -N(R) 16 )2、-C(O)N(R 16 )2、-C(O)OR 16 -OC(O)R 16 -N(R) 16 )C(O)R 16 -N(R) 16 )S(O)2R 16 -S(O)2R 16 -S(O)2N(R) 16 2. -NO2, =O, and -CN; C 1-4 Alkyl, C 2-6 alkenyl and C 2-6 Alkyne group, wherein each of them is optionally substituted by one or more substituents independently selected from: halogen, C 1-4 Alkyl, C 1-4 Halogenated alkyl groups, -OR 16 -SR 16 -N(R) 16 2. -NO2 and -CN; and 4- to 6-membered heterocyclic rings and C 3-8 A carbon ring, wherein each of which is optionally substituted by one or more substituents independently selected from the following: halogen, C 1-4 Alkyl, C 1-4 Halogenated alkyl groups, -OR 16 -N(R) 16 2. -NO2 and -CN.

79. The compound or salt according to claim 77, wherein R 5 Selected from 4- to 10-membered heterocycles and C 3-10 The carbon ring, wherein any one of them is optionally substituted by one or more substituents independently selected from the following: Halogen, C 1-4 Halogenated alkyl groups, -OR 16 -N(R) 16 )2、-C(O)N(R 16 )2、-C(O)OR 16 -OC(O)R 16 -N(R) 16 )C(O)R 16 -NO2, =O, and -CN; C 1-4 Alkyl, C 2-6 alkenyl and C 2-6 The alkynyl group, wherein any one of them is optionally substituted by one or more substituents independently selected from: halogen, C 1-4 Alkyl, C 1-4 Halogenated alkyl groups, -OR 16 -SR 16 -N(R) 16 2. -NO2 and -CN; and C 3-8 A carbon ring, optionally substituted by one or more substituents independently selected from: halogens, C 1-4 Alkyl, C 1-4 Halogenated alkyl groups, -OR 16 -N(R) 16 2. -NO2 and -CN.

80. The compound or salt according to claim 77 or claim 78, wherein R 5 Selected from 4- to 10-membered heterocycles and C 3-10 The carbon ring, wherein any one of them is optionally substituted by one or more substituents independently selected from the following: Halogen, C 2-6 alkynyl group, C 1-4 Halogenated alkyl groups, -OR 16 -N(R) 16 )2, =O and -CN; C 1-4 Alkyl group, optionally substituted by one or more substituents independently selected from the following: -N(R 16 )2; and C 3-8 A carbon ring, which is optionally substituted by one or more substituents independently selected from the following: halogens.

81. The compound or salt according to any one of claims 77-80, wherein R 5 Selected from 4- to 10-membered heterocycles and C 3-10 A carbocyclic ring, wherein any of the carbocyclic rings may optionally be substituted by one or more substituents independently selected from the following: fluorine, chlorine, methyl, ethyl, ethynyl, difluoromethyl, hydroxyl, methoxy, trifluoromethoxy, dimethylamino, =O, -CN, cyclopropyl, and pyrazolyl.

82. The compound or salt according to any one of claims 77-80, wherein R 5 Selected from 4- to 10-membered heterocycles and C 3-10 The carbocyclic ring, wherein any of the carbon rings may optionally be substituted by one or more substituents independently selected from the following: fluorine, chlorine, methyl, ethyl, ethynyl, propynyl, fluoromethyl, difluoromethyl, trifluoromethyl, hydroxyl, -CH2OH, methoxy, -CH2OCH3, , , , Difluoromethoxy, trifluoromethoxy, -NH2, dimethylamino, -CH2N(CH3)2, , , , , , , =O, -CN, cyclopropyl, phenyl, morpholino, pyrazolyl And pyridyl.

83. The compound or salt according to any one of claims 77-82, wherein R 5 These are optional 4- to 10-membered heterocycles that can be replaced.

84. The compound or salt according to any one of claims 77-83, wherein R 5 These are optional 4- to 10-membered heteroaryl groups.

85. The compound or salt according to claim 84, wherein R 5 Selected from: optionally substituted pyrazolyl, optionally substituted thiazolyl, optionally substituted oxazolyl, optionally substituted pyridyl, optionally substituted pyrimidinyl, optionally substituted pyrazinyl, optionally substituted pyridazinyl, optionally substituted benzo[d]isooxazolyl, optionally substituted imidazo[1,2-a]pyridyl, optionally substituted 1H-benzo[d]imidazolyl, optionally substituted 1H-pyrazolo[3,4-b]pyridyl, optionally substituted 2H-pyrrolo[3,4-c]pyridyl, and optionally substituted isoquinolinyl.

86. The compound or salt according to claim 84, wherein R 5 Selected from: optionally substituted pyrazolyl, optionally substituted thiazolyl, optionally substituted oxazolyl, optionally substituted pyridyl, optionally substituted pyrimidinyl, optionally substituted pyrazinyl, optionally substituted pyridazinyl, optionally substituted benzo[d]isoxazolyl, optionally substituted imidazo[1,2-a]pyridinyl, optionally substituted 1H-benzo[d]imidazolyl, optionally substituted 1H-pyrazolo[3,4-b]pyridinyl, optionally substituted 2H-pyrrolo[3,4-c]pyridinyl and optionally substituted isoquinolinyl, optionally substituted isoxazolyl, optionally substituted isothiazole, optionally substituted 1,2,3-thiadiazolyl, optionally Substituted 5,6-dihydro-4H-pyrrolo[1,2-b]pyrazolyl, optionally substituted 2,3-dihydropyrazolo[5,1-b]oxazolyl, optionally substituted 5,6-dihydro-3H-furano[2,3-d]imidazolyl, optionally substituted indazinyl, optionally substituted pyrazolo[1,5-a]pyridyl, optionally substituted pyrrolo[1,2-a]pyrimidinyl, optionally substituted pyrazolo[1,5-a]pyrimidinyl, optionally substituted imidazo[1,2-a]pyrimidinyl, optionally substituted imidazo[1,2-b]pyridazinyl, optionally substituted [1,2,4]triazolo[1,5-a]pyridyl, optionally substituted 6,7-di Hydro-5H-cyclopentadieno[b]pyridyl, optionally substituted 6,7-dihydro-5H-cyclopentadieno[c]pyridyl, optionally substituted 5,6,7,8-tetrahydroisoquinolinyl, optionally substituted 3,4-dihydro-2H-pyrano[2,3-b]pyridyl, optionally substituted 2,3-dihydro-[1,4]dioxane-hexeno[2,3-b]pyridyl, optionally substituted 5,7-dihydrofurano[3,4-b]pyridyl, optionally substituted 2,3-dihydrofurano[2,3-c]pyridyl, optionally substituted 2,3-dihydrofurano[2,3-b]pyridyl, optionally substituted [1,3]dioxane-penteno[4,5- [b]pyridyl, optionally substituted furano[2,3-b]pyridyl, optionally substituted thieno[2,3-b]pyridyl, optionally substituted 1,2-dihydro-3H-indazole-3-one, optionally substituted 1H-benzo[d][1,2,3]triazolyl, optionally substituted 1,3-dihydro-2H-benzo[d]imidazol-2-one, optionally substituted benzo[d]oxazol-2(3H)-one, optionally substituted benzo[d]thiazol-2(3H)-one, optionally substituted 1H-indazole, optionally substituted indololin-2-one, and optionally substituted 1,3-dihydro-2H-pyrrolo[2,3-b]pyridin-2-one.

87. The compound or salt according to claims 77-83, wherein R 5 It is selected from the following optional substituted 6- to 10-member bicyclic heterocycles: optional substituted 6- to 10-member fused heterocycles, optional substituted 6- to 10-member bridging heterocycles, and optional substituted 6- to 10-member spirocyclic heterocycles.

88. The compound or salt according to claim 87, wherein R 5 It is selected from the following optionally substituted 6- to 10-membered spirocyclic heterocycles: optionally substituted 2-azaspiro[3.3]heptyl, optionally substituted 6-azaspiro[3.4]octyl, optionally substituted 5-azaspiro[3.4]octyl, optionally substituted 2-azaspiro[3.5]nonyl, optionally substituted 7-azaspiro[3.5]nonyl and optionally substituted 6-azaspiro[3.5]nonyl.

89. The compound or salt according to any one of claims 77-83, wherein R 5 It is a 3- to 8-membered heterocyclic alkyl group that is optionally substituted.

90. The compound or salt according to claim 89, wherein R 5 It is selected from optionally substituted oxecyclobutane, optionally substituted pyrrole, and optionally substituted morpholino.

91. The compound or salt according to claim 89, wherein R 5 It is selected from optionally substituted oxecyclobutane, optionally substituted pyrrole, optionally substituted morpholino, optionally substituted azacyclobutane, optionally substituted pyrrole, optionally substituted tetrahydro-2H-thiaranyl, and optionally substituted piperidinyl.

92. The compound or salt according to any one of claims 77-81, wherein R 5 Selected from C which is arbitrarily replaced 3-6 Cycloalkyl groups and optionally substituted phenyl groups.

93. The compound or salt according to claim 92, wherein R 5 Selected from optionally substituted cyclopropyl, optionally substituted cyclobutyl, and optionally substituted phenyl.

94. The compound or salt according to claim 77 or claim 78, wherein R 5 Selected from: 。 95. The compound or salt according to claim 77 or claim 78, wherein R 5 Selected from: 。 96. The compound or salt according to any one of claims 1 to 95, wherein the compound is selected from the compounds in Table 1 or pharmaceutically acceptable salts thereof.

97. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound or salt according to any one of claims 1-96.

98. A method for modulating the activity of wild-type AKT1, comprising administering to a subject in need a compound or salt according to any one of claims 1-96 or a pharmaceutical composition according to claim 97.

99. A method for modulating the activity of mutant AKT1, comprising administering to a subject in need a compound or salt according to any one of claims 1-96, or a pharmaceutical composition according to claim 97.

100. A method for selectively modulating the activity of wild-type AKT1 relative to wild-type AKT2, comprising administering to a subject in need a compound or salt according to any one of claims 1-96, or a pharmaceutical composition according to claim 97.

101. A method for selectively regulating the activity of a mutant AKT1 relative to wild-type AKT2, comprising administering to a subject in need a compound or salt according to any one of claims 1-96, or a pharmaceutical composition according to claim 97.

102. A method of treating cancer in a subject of need, the method comprising administering to the subject a compound or salt according to any one of claims 1-96, or a pharmaceutical composition according to claim 97.

103. The method of claim 102, wherein the cancer is selected from breast cancer, colorectal cancer, and meningioma.

104. The method of claim 103, wherein the application modulates the activity of the mutant AKT1.

105. The method according to claim 98, 101 or 104, wherein the mutant AKT1 is AKT1 E17K.

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