Heterocyclic compound as well as pharmaceutical composition and application thereof

Abstract

The invention discloses a heterocyclic compound as well as a pharmaceutical composition and application thereof. Specifically, the present invention discloses a heterocyclic compound represented by formula (I), a pharmaceutically acceptable salt thereof, a solvate thereof or a solvate of the pharmaceutically acceptable salt thereof. The compound provided by the invention has inhibitory activity on proliferation of one or more of stably transfected cells Ba / F3 KRAS G12C, Ba / F3 KRAS G12D, Ba / F3 KRAS G12V, human pancreatic cancer cells Capan-1, human non-small cell lung cancer cells NCI-H358 (KRAS G12C mutation) and human metastatic pancreatic adenocarcinoma cells AsPC-1 (KRAS G12D mutation) containing KRAS mutation, or the compound provided by the invention has relatively weak inhibitory activity on proliferation of wild PC-9 cells of KRAS. # imgabs0 #

Description

Heterocyclic compounds, pharmaceutical compositions and uses thereof

[0001] This application claims priority from the following Chinese patent applications:

[0002] Chinese patent application 2023100863077, filed on January 18, 2023;

[0003] Chinese patent application 2023105402255, filed on May 12, 2023;

[0004] Chinese patent application 2023109896663, filed on August 7, 2023;

[0005] Chinese patent application 2023116215125 with an application date of November 29, 2023.

[0006] This application cites the full text of the above-mentioned Chinese patent application. Technical Field

[0007] The present invention relates to heterocyclic compounds, pharmaceutical compositions and uses thereof. Background Art

[0008] RAS proteins are 21kDa guanine trinucleotide phosphate (GTP)-binding proteins located on the cell membrane, composed of 188 or 189 amino acids. The activity of RAS proteins influences cell growth, differentiation, the cytoskeleton, protein trafficking, and secretion. Their activity is regulated by binding to GTP or guanine dinucleotide phosphate (GDP). When bound to GDP, RAS proteins are in an "inactive" state. Upon stimulation by specific upstream growth factors, guanine nucleotide exchange factors (GEFs) catalyze the release of GDP from RAS proteins, allowing them to bind to GTP and enter an "activated" state. GTP-bound RAS proteins can activate downstream proteins and signaling pathways. RAS proteins possess weak GTPase activity, hydrolyzing GTP to GDP, thereby transitioning from an active to an inactive state. This hydrolysis process also requires the participation of GTPase-activating proteins (GAPs), which interact with RAS proteins and significantly enhance their ability to hydrolyze GTP to GDP. Any mutation in a RAS protein that affects its GTPase activity, its interaction with GAPs, or its ability to hydrolyze GTP to GDP will result in a prolonged activation of the RAS protein. This prolonged activation of the RAS protein continues to provide growth signals to downstream proteins, leading to continued cell growth and differentiation, and ultimately cancer. The RAS gene family consists of three members: KRAS, NRAS, and HRAS.

[0009] KRAS mutation is the most common oncogenic driver, present in a variety of tumors: lung adenocarcinoma (32%), colorectal cancer (41%), and pancreatic cancer (86%). KRAS mutation is most common with the G12 mutation at codon 12. For example, in KRAS-mutated lung adenocarcinoma, colorectal cancer, and pancreatic cancer, G12 mutations account for 85%, 68%, and 91%, respectively; G12 mutations include G12C, G12D, G12V, G12R and other mutation forms. Among patients with KRAS G12 mutations in lung adenocarcinoma, colorectal cancer, and pancreatic cancer, patients with KRAS G12D mutations accounted for 17%, 45%, and 45%, respectively, and patients with KRAS G12V mutations accounted for 23%, 30%, and 35%, respectively (for example, see Moore, AR et al. Nat Rev Drug Discov 19, 533 (2020)).

[0010] Currently, only inhibitors targeting KRAS G12C mutations are on the market, and inhibitors targeting KRAS G12D mutations are about to enter clinical research. However, the patient population that benefits from KRAS G12C inhibitors only accounts for a small part of the population carrying KRAS mutations. More than 85% of KRAS mutation cancers still lack effective treatments (see Marco, HHet al. Cancer Discov 12, 924 (2022)), and patients still need therapies targeting other KRAS mutations (such as G12V, G12R, and G12A).

[0011] Pan-KRAS inhibitors can inhibit multiple KRAS mutants and have the potential to treat a wider range of patient groups, where there is a huge unmet clinical need.

[0012] Summary of the Invention

[0013] The present invention addresses the problem of the single structure of KRAS mutant inhibitors in the prior art. The present invention provides a heterocyclic compound, a pharmaceutical composition thereof, and uses thereof. The compounds of the present invention have inhibitory activity against the proliferation of one or more of the following KRAS mutation-bearing cells: Ba / F3 KRAS G12C, Ba / F3 KRAS G12D, Ba / F3 KRAS G12V, Capan-1, human non-small cell lung cancer cells NCI-H358 (KRAS G12C mutation), and human metastatic pancreatic adenocarcinoma cells AsPC-1 (KRAS G12D mutation). Alternatively, the compounds of the present invention have weak inhibitory activity against the proliferation of KRAS wild-type PC-9 cells.

[0014] The present invention solves the above technical problems through the following methods.

[0015] The present invention provides a heterocyclic compound represented by Formula I, a pharmaceutically acceptable salt thereof, a solvate thereof, or a solvate of a pharmaceutically acceptable salt thereof.

[0016] Wherein, n is 1, 2 or 3;

[0017] X is independently -C(R 7 )2-、-NR 7 -、-O-、-S-、-CR 7 =CR 7 -, -N=N- or -CR 7 =N-;

[0018] R 7 are independently hydrogen, deuterium, halogen, cyano, hydroxy, amino, C1-C6 alkyl, C1-C6 alkyl-O-, C2-C6 alkenyl, C2-C6 alkynyl, 7a Substituted C1-C6 alkyl, one or more R 7b Substituted C1-C6 alkyl-O-, one or more R 7c Substituted C2-C6 alkenyl or one or more R 7d substituted C2-C6 alkynyl;

[0019] R 7a 、R 7b 、R 7c and R 7d are each independently deuterium, -CN, halogen or -OH;

[0020] Y is -NR 4 -、-O-、-S-、-C(R 4 )2- or -(CH2) p NR 4 -;

[0021] p is 1, 2, or 3;

[0022] R 4 are independently hydrogen, C1-C6 alkyl, C3-C 10 Cycloalkyl, 3-10 membered heterocycloalkyl, C3-C 10 Cycloalkenyl, 3-10 membered heterocycloalkenyl, 5-10 membered heteroaryl, C6-C 10 Aryl, -SO2R h , by one or more R 4a Substituted C1-C6 alkyl, one or more R 4b Substituted C3-C 10 Cycloalkyl, one or more R 4c substituted 3-10 membered heterocycloalkyl, substituted by one or more R 4dsubstituted 3-10 membered heterocycloalkenyl, substituted by one or more R 4e substituted 5-10 membered heteroaryl, 5-10 membered heteroaryl ring and 3-10 membered heterocycloalkyl, substituted by one or more R 4f Substituted C3-C 10 Cycloalkenyl, one or more R 4g Substituted C6-C 10 Aryl or one or more R 4k substituted 5-10 membered heteroaromatic ring and 3-10 membered heterocycloalkyl; the 3-10 membered heterocycloalkyl, 3-10 membered heterocycloalkenyl, 5-10 membered heteroaryl, 5-10 membered heteroaromatic ring and 3-10 membered heterocycloalkyl in 5-10 membered heteroaromatic ring and 3-10 membered heterocycloalkyl in 3-10 membered heterocycloalkyl, 3-10 membered heterocycloalkyl in 5-10 membered heteroaromatic ring and 3-10 membered heterocycloalkyl, substituted one or more R 4k substituted 5-10 membered heteroaromatic ring and 5-10 membered heteroaromatic ring in 3-10 membered heterocycloalkyl, replaced by one or more R 4k substituted 5-10 membered heteroaromatic ring and 3-10 membered heterocycloalkyl in 3-10 membered heterocycloalkyl, replaced by one or more R 4c The 3-10 membered heterocycloalkyl in the substituted 3-10 membered heterocycloalkyl is replaced by one or more R 4d The 3-10 membered heterocycloalkenyl in the substituted 3-10 membered heterocycloalkenyl and the 3-10 membered heterocycloalkenyl replaced by one or more R 4e The heteroatoms in the 5-10 membered heteroaryl group of the substituted 5-10 membered heteroaryl group are each independently selected from one or more of N, O and S, and the number of heteroatoms is each independently 1, 2 or 3;

[0023] R 4a 、R 4b 、R 4c 、R 4d 、R 4e 、R 4f 、R 4g 、R 4k and R h are independently halogen, =O, cyano, -OR 10 、-N(R 8 )2、-SR 11 、-SO2R 11 、-C(O)N(R 10 )2、-C(O)R 10 、-C(O)OR 10 、 C1-C6 alkyl, C3-C 10 Cycloalkyl, 3-10 membered heterocycloalkenyl, 5-10 membered heteroaryl, 3-10 membered heterocycloalkyl, C3-C 10 Cycloalkenyl, C6-C 10 Aryl, carboxyl, one or more R4-a Substituted C1-C6 alkyl, one or more R 4-b Substituted C3-C 10 Cycloalkyl, one or more R 4- c substituted 3-10 membered heterocycloalkyl, substituted by one or more R 4-d substituted 3-10 membered heterocycloalkenyl, substituted by one or more R 4-e substituted 5-10 membered heteroaryl, substituted by one or more R 4-f Substituted C3-C 10 Cycloalkenyl or one or more R 4-g Substituted C6-C 10 Aryl; the 3-10 membered heterocycloalkyl, 3-10 membered heterocycloalkenyl, 5-10 membered heteroaryl, one or more R 4-c The 3-10 membered heterocycloalkyl in the substituted 3-10 membered heterocycloalkyl is replaced by one or more R 4-d The 3-10 membered heterocycloalkenyl in the substituted 3-10 membered heterocycloalkenyl and the 3-10 membered heterocycloalkenyl replaced by one or more R 4-e The heteroatoms in the 5-10 membered heteroaryl group of the substituted 5-10 membered heteroaryl group are each independently selected from one or more of N, O and S, and the number of heteroatoms is each independently 1, 2 or 3;

[0024] R 4-a 、R 4-b 、R 4-c 、R 4-d 、R 4-e 、R 4-f and R 4-g are independently halogen, =O, cyano, -OR 10 、-N(R 8 )2、-SR 11 、-SO2R 11 、-C(O)N(R 10 )2、-C(O)R 10 , C1-C6 alkyl, C3-C 10 Cycloalkyl, 3-10 membered heterocycloalkenyl, 3-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-C 10 Cycloalkenyl, C6-C 10 Aryl, one or more R 4-a-1 Substituted C1-C6 alkyl, one or more R 4- a-2 Substituted C3-C 10 Cycloalkyl, one or more R 4-a-3 substituted 3-10 membered heterocycloalkyl, substituted by one or more R 4-a-4 substituted 3-10 membered heterocycloalkenyl, substituted by one or more R4-a-5 substituted 5-10 membered heteroaryl, substituted by one or more R 4-a-6 Substituted C3-C 10 Cycloalkenyl or one or more R 4-a-7 Substituted C6-C 10 Aryl; the 3-10 membered heterocycloalkyl, 3-10 membered heterocycloalkenyl, 5-10 membered heteroaryl, one or more R 4-a-3 The 3-10 membered heterocycloalkyl in the substituted 3-10 membered heterocycloalkyl is replaced by one or more R 4-a-4 The 3-10 membered heterocycloalkenyl in the substituted 3-10 membered heterocycloalkenyl and the 3-10 membered heterocycloalkenyl replaced by one or more R 4-a-5 The heteroatoms in the 5-10 membered heteroaryl group of the substituted 5-10 membered heteroaryl group are each independently selected from one or more of N, O and S, and the number of heteroatoms is each independently 1, 2 or 3;

[0025] R 4-i Each is independently hydrogen or C1-C6 alkyl;

[0026] R 4-a-1 、R 4-a-2 、R 4-a-3 、R 4-a-4 、R 4-a-5 、R 4-a-6 and R 4-a-7 Each is independently halogen, =O, cyano, -C(O)CH3, -C(O)NH2, -OH, halogenated C1-C6 alkyl, -N(R 8 )2, -SCH3, -SO2CH3, C1-C6 alkyl, C3-C 10 Cycloalkyl, 3-10 membered heterocycloalkyl or 3-10 membered heterocycloalkenyl; the heteroatoms in the 3-10 membered heterocycloalkyl and 3-10 membered heterocycloalkenyl are each independently selected from one or more of N, O and S, and the number of heteroatoms is each independently 1, 2 or 3;

[0027] R 8 are independently hydrogen, -C(O)N(R 10 )2、-C(O)R 10 , C1-C6 alkyl, C3-C 10 Cycloalkyl, 3-10 membered heterocycloalkyl, 3-10 membered heterocycloalkenyl, 5-10 membered heteroaryl, substituted by one or more R 8a Substituted C1-C6 alkyl, one or more R 8b Substituted C3-C 10 Cycloalkyl, one or more R 8c substituted 3-10 membered heterocycloalkyl, substituted by one or more R 8d substituted 3-10 membered heterocycloalkenyl or one or more R8e substituted 5-10 membered heteroaryl; the 3-10 membered heterocycloalkyl, 3-10 membered heterocycloalkenyl, 5-10 membered heteroaryl, substituted by one or more R 8c The 3-10 membered heterocycloalkyl in the substituted 3-10 membered heterocycloalkyl is replaced by one or more R 8d The 3-10 membered heterocycloalkenyl in the substituted 3-10 membered heterocycloalkenyl and the 3-10 membered heterocycloalkenyl replaced by one or more R 8e The heteroatoms in the 5-10 membered heteroaryl group of the substituted 5-10 membered heteroaryl group are each independently selected from one or more of N, O and S, and the number of heteroatoms is each independently 1, 2 or 3;

[0028] R 8a 、R 8b 、R 8c 、R 8d and R 8e are independently halogen, cyano, -C(O)R 10 、-C(O)N(R 10 )2、-OH、C1-C6 alkyl-O-、-N(R 10 )2、-SO2N(R 10 )2, -SO2R 10 , C1-C6 alkyl, C3-C 10 Cycloalkyl, 3-10 membered heterocycloalkyl, 3-10 membered heterocycloalkenyl, 5-10 membered heteroaryl, substituted by one or more R 8-a Substituted C1-C6 alkyl, one or more R 8-b Substituted C3-C 10 Cycloalkyl, one or more R 8-c substituted 3-10 membered heterocycloalkyl, substituted by one or more R 8-d substituted 3-10 membered heterocycloalkenyl or one or more R 8-e substituted 5-10 membered heteroaryl; the 3-10 membered heterocycloalkyl, 3-10 membered heterocycloalkenyl, 5-10 membered heteroaryl, substituted by one or more R 8-c The 3-10 membered heterocycloalkyl in the substituted 3-10 membered heterocycloalkyl is replaced by one or more R 8-d The 3-10 membered heterocycloalkenyl in the substituted 3-10 membered heterocycloalkenyl and the 3-10 membered heterocycloalkenyl replaced by one or more R 8-e The heteroatoms in the 5-10 membered heteroaryl group of the substituted 5-10 membered heteroaryl group are each independently selected from one or more of N, O and S, and the number of heteroatoms is each independently 1, 2 or 3;

[0029] R 8-a 、R 8-b 、R 8-c 、R 8-d and R 8-eare independently halogen, cyano, -C(O)R 10 、-C(O)N(R 10 )2、-OH、C1-C6 alkyl-O-、-N(R 10 )2、-SO2N(R 10 )2、-SO2(R 10 ), C1-C6 alkyl, C3-C 10 Cycloalkyl, 3-10 membered heterocycloalkyl, 3-10 membered heterocycloalkenyl, 5-10 membered heteroaryl, substituted by one or more R 8-a-1 Substituted C1-C6 alkyl, one or more R 8-a-2 Substituted C3-C 10 Cycloalkyl, one or more R 8-a-3 substituted 3-10 membered heterocycloalkyl, substituted by one or more R 8-a-4 substituted 3-10 membered heterocycloalkenyl or one or more R 8-a-5 substituted 5-10 membered heteroaryl; the 3-10 membered heterocycloalkyl, 3-10 membered heterocycloalkenyl, 5-10 membered heteroaryl, substituted by one or more R 8-a-3 The 3-10 membered heterocycloalkyl in the substituted 3-10 membered heterocycloalkyl is replaced by one or more R 8-a-4 The 3-10 membered heterocycloalkenyl in the substituted 3-10 membered heterocycloalkenyl and the 3-10 membered heterocycloalkenyl replaced by one or more R 8-a-5 The heteroatoms in the 5-10 membered heteroaryl group of the substituted 5-10 membered heteroaryl group are each independently selected from one or more of N, O and S, and the number of heteroatoms is each independently 1, 2 or 3;

[0030] R 8-a-1 、R 8-a-2 、R 8-a-3 、R 8-a-4 and R 8-a-5 are independently halogen, cyano, -C(O)R 10 、-C(O)N(R 10 )2、-OH、-OCH3、-N(R 10 )2、-SO2N(R 10 )2, -SO2R 10 , C1-C6 alkyl or halogenated C1-C6 alkyl;

[0031] R 10 are independently hydrogen, C1-C6 alkyl, halogenated C1-C6 alkyl, C3-C 10 Cycloalkyl or 3-10 membered heterocycloalkyl;

[0032] R 11 are independently -NH2 or C1-C6 alkyl;

[0033] R5 and R 6 are independently hydrogen, halogen, -N(R 8 )2, 3-10 membered heterocycloalkyl, C1-C6 alkyl, 3-10 membered heterocycloalkenyl, C3-C 10 Cycloalkyl, C3-C 10 Cycloalkenyl, 5-10 membered heteroaryl, C6-C 10 Aryl, one or more R 5a Substituted C1-C6 alkyl, one or more R 5b substituted 3-10 membered heterocycloalkyl, substituted by one or more R 5c substituted 3-10 membered heterocycloalkenyl, substituted by one or more R 5d Substituted C3-C 10 Cycloalkyl, one or more R 5e Substituted C3-C 10 Cycloalkenyl, one or more R 5f substituted 5-10 membered heteroaryl or one or more R 5g Substituted C6-C 10 Aryl; the 3-10 membered heterocycloalkyl, 3-10 membered heterocycloalkenyl, 5-10 membered heteroaryl, one or more R 5b The 3-10 membered heterocycloalkyl in the substituted 3-10 membered heterocycloalkyl is replaced by one or more R 5c The 3-10 membered heterocycloalkenyl in the substituted 3-10 membered heterocycloalkenyl and the 3-10 membered heterocycloalkenyl replaced by one or more R 5f The heteroatoms in the 5-10 membered heteroaryl group of the substituted 5-10 membered heteroaryl group are each independently selected from one or more of N, O and S, and the number of heteroatoms is each independently 1, 2 or 3;

[0034] R 5a 、R 5b 、R 5c 、R 5d 、R 5e 、R 5f and R 5g Each is independently halogen, =O, cyano, -OH, C1-C6 alkyl-O-, C1-C6 alkyl or halogenated C1-C6 alkyl;

[0035] R 4 and R 5 It can also form a 3-10 membered saturated heterocyclic ring, a 5-10 membered heteroaromatic ring, a 3-10 membered heterocyclic alkene, or one or more R 4h substituted 3-10 membered saturated heterocyclic ring, replaced by one or more R 4i Substituted 3-10 membered heterocyclic olefins or one or more R 4jsubstituted 5-10 membered heteroaromatic ring; the 3-10 membered saturated heterocyclic ring, 3-10 membered heterocyclic alkene, 5-10 membered heteroaromatic ring, substituted by one or more R 4h The 3-10 membered saturated heterocyclic ring in the substituted 3-10 membered saturated heterocyclic ring is replaced by one or more R 4i The 3-10 membered heterocyclic olefin in the substituted 3-10 membered heterocyclic olefin and the substituted 3-10 membered heterocyclic olefin are replaced by one or more R 4j The heteroatoms in the 5-10 membered heteroaromatic ring of the substituted 5-10 membered heteroaromatic ring are each independently selected from one or more of N, O and S, and the number of heteroatoms is each independently 1, 2 or 3;

[0036] R 4h 、R 4i and R 4j are each independently halogen, =O, cyano, -OH, -N(R 8 )2、-SR 11 、-SO2R 11 、-C(O)N(R 10 )2、-C(O)R 10 , C1-C6 alkyl or one or more R 4-h Substituted C1-C6 alkyl;

[0037] Or two adjacent R 4h Together with the atoms to which they are attached, they form a 5-10 membered heteroaromatic ring, wherein the 5-10 membered heteroaromatic ring is optionally substituted by one or more of the following groups: halogen, =O, cyano, -OH, -N(R 8 )2、-SR 11 、-SO2R 11 、-C(O)N(R 10 )2、-C(O)R 10 , C1-C6 alkyl or one or more R 4-h substituted C1-C6 alkyl; the heteroatoms in the 5-10 membered heteroaromatic ring are each independently selected from one or more of N, O and S, and the number of heteroatoms is each independently 1, 2 or 3; R 4-h are independently halogen, =O, cyano or -N(R 8 )2;

[0038] R 1 C6-C 10 Aryl, 5-10 membered heteroaryl, 3-10 membered heterocycloalkyl, 1a Substituted C6-C 10 Aryl, one or more R 1b substituted 5-10 membered heteroaryl or one or more R 1csubstituted 3-10 membered heterocycloalkyl; said 5-10 membered heteroaryl, 3-10 membered heterocycloalkyl, substituted by one or more R 1b The 5-10 membered heteroaryl in the substituted 5-10 membered heteroaryl and the 5-10 membered heteroaryl replaced by one or more R 1c The heteroatoms in the 3-10 membered heterocycloalkyl group in the substituted 3-10 membered heterocycloalkyl group are each independently selected from one or more of N, O and S, and the number of heteroatoms is each independently 1, 2 or 3;

[0039] R 1a 、R 1b and R 1c Each is independently deuterium, halogen, -OH, -CN, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, 5-10 membered heteroaryl, C1-C6 alkyl-O-, C1-C6 alkyl-S-, -N(R 8 )2、-(CH2)-C(=O)N(R 8 )2. C3-C 10 Cycloalkyl, one or more R 1-a Substituted C1-C6 alkyl, one or more R 1-b Substituted C1-C6 alkyl-O-, one or more R 1-c Substituted C1-C6 alkyl-S-, one or more R 1-d Substituted C2-C6 alkenyl, one or more R 1-e Substituted C2-C6 alkynyl, one or more R 1- f Substituted C3-C 10 Cycloalkyl or one or more R 1-g substituted 5-10 membered heteroaryl; said 5-10 membered heteroaryl and one or more R 1-g The heteroatoms in the 5-10 membered heteroaryl group of the substituted 5-10 membered heteroaryl group are each independently selected from one or more of N, O and S, and the number of heteroatoms is each independently 1, 2 or 3;

[0040] Or two adjacent R 1c Together with the atoms to which they are attached, they form a 5-10 membered heteroaromatic ring, wherein the 5-10 membered heteroaromatic ring is optionally substituted by one or more of the following groups: deuterium, halogen, -OH, -CN, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, 5-10 membered heteroaryl, C1-C6 alkyl-O-, C1-C6 alkyl-S-, -N(R 8 )2、-(CH2)-C(=O)N(R 8 )2. C3-C 10 Cycloalkyl, one or more R 1- aSubstituted C1-C6 alkyl, one or more R 1-b Substituted C1-C6 alkyl-O-, one or more R 1-c Substituted C1-C6 alkyl-S-, one or more R 1-d Substituted C2-C6 alkenyl, one or more R 1-e Substituted C2-C6 alkynyl, one or more R 1-f Substituted C3-C 10 Cycloalkyl or one or more R 1-g substituted 5-10 membered heteroaryl; the 5-10 membered heteroaryl ring, the 5-10 membered heteroaryl and the substituted one or more R 1-g The heteroatoms in the 5-10 membered heteroaryl group of the substituted 5-10 membered heteroaryl group are independently selected from one or more of N, O and S, and the number of heteroatoms is independently 1, 2 or 3;

[0041] R 1-a 、R 1-b 、R 1-c 、R 1-d 、R 1-e 、R 1-f and R 1-g are each independently deuterium, halogen, -CN, -OH, C1-C4 alkyl, C1-C4 alkyl-O- or C3-C 10 Cycloalkyl;

[0042] L is absent, -O-(CR 9 R 9 ) n1 -、-S-(CR 9 R 9 ) n2 -、-N(R 8 )-(CR 9 R 9 ) n3 -、-SO-(CR 9 R 9 ) n4 -or-SO2-(CR 9 R 9 ) n5 -;

[0043] R 9 are independently hydrogen, halogen, -CN, C1-C6 alkyl, C1-C6 alkyl-O-, deuterated C1-C6 alkyl, or 5-10 membered heteroaryl;

[0044] n1, n2, n3, n4 and n5 are each independently 0, 1, 2 or 3; (when 0, it represents a connecting bond);

[0045] R 2is hydrogen, -COOH, C1-C6 alkyl, C1-C6 alkyl-O-, C3-C 10 Cycloalkyl, C3-C 10 Cycloalkenyl, 4-10 membered heterocycloalkyl, C6-C 10 Aryl, 5-10 membered heteroaryl, -NHC(=NH)NH2, -C(O)N(R 8 )2、-(CH2OR 10 )(CH2) n6 OR 10 、-NR 8 C(=O)-C6-C 10 Aryl, -C(=O)O-C1-C6 alkyl, one or more R 2a Substituted C3-C 10 Cycloalkyl, one or more R 2b Substituted C3-C 10 Cycloalkenyl, one or more R 2c substituted 4-10 membered heterocycloalkyl, substituted by one or more R 2d Substituted C6-C 10 Aryl or one or more R 2e substituted 5-10 membered heteroaryl; said 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, substituted by one or more R 2c The 4-10 membered heterocycloalkyl in the substituted 4-10 membered heterocycloalkyl and the substituted 4-10 membered heterocycloalkyl 2e The heteroatoms in the 5-10 membered heteroaryl group of the substituted 5-10 membered heteroaryl group are each independently selected from one or more of N, O and S, and the number of heteroatoms is each independently 1, 2 or 3;

[0046] n6 is 0, 1, 2, or 3;

[0047] R 2a 、R 2b 、R 2c 、R 2d and R 2e are independently halogen, -OH, deuterium, -CN, -C(=O)H, =CR 2-c R 2-c , C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 alkyl-O-, -N(R 8 )2、(C l -C4 alkyl)-C(=O)-, oxo(=O), -SO2F, (C l -C4 alkyl)-SO2-, (C l -C4 alkyl)-O-(C l -C4 alkyl)-, (C l -C4 alkyl)-O-(Cl -C4 alkyl)-O-, -CH2OC(=O)N(R 8 )2、(C l -C4 alkyl)-OC(=O)-NHCH2-, -CH2NHC(=O)N(R 8 )2、(C l -C4 alkyl)-C(=O)NHCH2-, (pyrazolyl)-CH2-, (C l -C4 alkyl)-SO2-NHCH2-, (4-10 membered heterocycloalkyl)-C(=O)-OCH2-, (R 8 )2N-C(=O)-O-、(C l -C4 alkyl)-O-(C l -C4 alkyl)-NH-C(=O)-O-, phenyl-C(=O)NH-, phenyl-(C l -C4 alkyl)-NH-C(=O)-O-, (4-10 membered heterocycloalkyl)-C(=O)-O-, (4-10 membered heterocycloalkyl)-CH2-, 4-10 membered heterocycloalkyl, 2-a Substituted C1-C4 alkyl, one or more R 2-b Substituted C1-C4 alkyl-O- or one or more R 2-d Substituted 4-10 membered heterocycloalkyl; the phenyl-C(=O)NH- and phenyl-(C l -C4 alkyl)-NH-C(=O)-O-phenyl is optionally substituted by -C(=O)H, halogen, -CN or -OH; the 4-10 membered heterocycloalkyl in the (4-10 membered heterocycloalkyl)-C(=O)-OCH2-, (4-10 membered heterocycloalkyl)-C(=O)-O- and (4-10 membered heterocycloalkyl)-CH2- is optionally substituted by =O, halogen, -CN, -OH or C l -C6 alkyl substituted; the 4-10 membered heterocycloalkyl, by one or more R 2-d The heteroatoms in the 4-10 membered heterocycloalkyl in the substituted 4-10 membered heterocycloalkyl, (4-10 membered heterocycloalkyl)-C(═O)-OCH2-, (4-10 membered heterocycloalkyl)-C(═O)-O- and the 4-10 membered heterocycloalkyl in (4-10 membered heterocycloalkyl)-CH2- are each independently selected from one or more of N, O and S, and the number of heteroatoms is each independently 1, 2 or 3;

[0048] R 2-a 、R 2-b 、R 2-c and R 2-d are each independently deuterium, -CN, halogen or -OH;

[0049] R3 H, deuterium, -N(R 8 )2, halogen, -OH, C1-C6 alkyl, -CN, halo-C1-C6 alkyl, deuterated C1-C6 alkyl, C1-C6 alkyl-O-, deuterated C1-C6 alkyl-O-, C2-C6 alkenyl or C2-C6 alkynyl.

[0050] The present invention provides a heterocyclic compound represented by Formula I, a pharmaceutically acceptable salt thereof, a solvate thereof, or a solvate of a pharmaceutically acceptable salt thereof.

[0051] Wherein, n is 1, 2 or 3;

[0052] X is independently -C(R 7 )2-、-NR 7 -、-O-、-S-、-CR 7 =CR 7 -, -N=N- or -CR 7 =N-;

[0053] R 7 are independently hydrogen, deuterium, halogen, cyano, hydroxy, amino, C1-C6 alkyl, C1-C6 alkyl-O-, C2-C6 alkenyl, C2-C6 alkynyl, 7a Substituted C1-C6 alkyl, one or more R 7b Substituted C1-C6 alkyl-O-, one or more R 7c Substituted C2-C6 alkenyl or one or more R 7d substituted C2-C6 alkynyl;

[0054] R 7a 、R 7b 、R 7c and R 7d are each independently deuterium, -CN, halogen or -OH;

[0055] Y is -NR 4 -、-O-、-S-、-C(R 4 )2- or -(CH2) p NR 4 -;

[0056] p is 1, 2, or 3;

[0057] R 4 are independently hydrogen, C1-C6 alkyl, C3-C 10 Cycloalkyl, 3-10 membered heterocycloalkyl, C3-C 10 Cycloalkenyl, 3-10 membered heterocycloalkenyl, 5-10 membered heteroaryl, C6-C 10 Aryl, -SO2Rh , by one or more R 4a Substituted C1-C6 alkyl, one or more R 4b Substituted C3-C 10 Cycloalkyl, one or more R 4c substituted 3-10 membered heterocycloalkyl, substituted by one or more R 4d substituted 3-10 membered heterocycloalkenyl, substituted by one or more R 4e substituted 5-10 membered heteroaryl, 5-10 membered heteroaryl ring and 3-10 membered heterocycloalkyl, substituted by one or more R 4f Substituted C3-C 10 Cycloalkenyl, one or more R 4g Substituted C6-C 10 Aryl or one or more R 4k substituted 5-10 membered heteroaromatic ring and 3-10 membered heterocycloalkyl; the 3-10 membered heterocycloalkyl, 3-10 membered heterocycloalkenyl, 5-10 membered heteroaryl, 5-10 membered heteroaromatic ring and 3-10 membered heterocycloalkyl in 5-10 membered heteroaromatic ring and 3-10 membered heterocycloalkyl in 3-10 membered heterocycloalkyl, 3-10 membered heterocycloalkyl in 5-10 membered heteroaromatic ring and 3-10 membered heterocycloalkyl, substituted one or more R 4k substituted 5-10 membered heteroaromatic ring and 5-10 membered heteroaromatic ring in 3-10 membered heterocycloalkyl, replaced by one or more R 4k substituted 5-10 membered heteroaromatic ring and 3-10 membered heterocycloalkyl in 3-10 membered heterocycloalkyl, replaced by one or more R 4c The 3-10 membered heterocycloalkyl in the substituted 3-10 membered heterocycloalkyl is replaced by one or more R 4d The 3-10 membered heterocycloalkenyl in the substituted 3-10 membered heterocycloalkenyl and the 3-10 membered heterocycloalkenyl replaced by one or more R 4e The heteroatoms in the 5-10 membered heteroaryl group of the substituted 5-10 membered heteroaryl group are each independently selected from one or more of N, O and S, and the number of heteroatoms is each independently 1, 2 or 3;

[0058] R 4a 、R 4b 、R 4c 、R 4d 、R 4e 、R 4f 、R 4g 、R 4k and R h are independently halogen, =O, cyano, -OR 10 、-N(R 8 )2、-SR 11 、-SO2R 11 、-C(O)N(R 10 )2、-C(O)R 10, C1-C6 alkyl, C3-C 10 Cycloalkyl, 3-10 membered heterocycloalkenyl, 5-10 membered heteroaryl, 3-10 membered heterocycloalkyl, C3-C 10 Cycloalkenyl, C6-C 10 Aryl, carboxyl, one or more R 4-a Substituted C1-C6 alkyl, one or more R 4-b Substituted C3-C 10 Cycloalkyl, one or more R 4-c substituted 3-10 membered heterocycloalkyl, substituted by one or more R 4- d substituted 3-10 membered heterocycloalkenyl, substituted by one or more R 4-e substituted 5-10 membered heteroaryl, substituted by one or more R 4-f Substituted C3-C 10 Cycloalkenyl or one or more R 4-g Substituted C6-C 10 Aryl; the 3-10 membered heterocycloalkyl, 3-10 membered heterocycloalkenyl, 5-10 membered heteroaryl, one or more R 4-c The 3-10 membered heterocycloalkyl in the substituted 3-10 membered heterocycloalkyl is replaced by one or more R 4-d The 3-10 membered heterocycloalkenyl in the substituted 3-10 membered heterocycloalkenyl and the 3-10 membered heterocycloalkenyl replaced by one or more R 4-e The heteroatoms in the 5-10 membered heteroaryl group of the substituted 5-10 membered heteroaryl group are each independently selected from one or more of N, O and S, and the number of heteroatoms is each independently 1, 2 or 3;

[0059] R 4-a 、R 4-b 、R 4-c 、R 4-d 、R 4-e 、R 4-f and R 4-g are independently halogen, =O, cyano, -OR 10 、-N(R 8 )2、-SR 11 、-SO2R 11 、-C(O)N(R 10 )2、-C(O)R 10 , C1-C6 alkyl, C3-C 10 Cycloalkyl, 3-10 membered heterocycloalkenyl, 3-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-C 10 Cycloalkenyl, C6-C 10 Aryl, one or more R 4-a-1 Substituted C1-C6 alkyl, one or more R 4-a - 2 Substituted C3-C 10 Cycloalkyl, one or more R 4-a-3 substituted 3-10 membered heterocycloalkyl, substituted by one or more R 4-a-4 substituted 3-10 membered heterocycloalkenyl, substituted by one or more R 4-a-5 substituted 5-10 membered heteroaryl, substituted by one or more R 4-a-6 Substituted C3-C 10 Cycloalkenyl or one or more R 4-a-7 Substituted C6-C 10 Aryl; the 3-10 membered heterocycloalkyl, 3-10 membered heterocycloalkenyl, 5-10 membered heteroaryl, one or more R 4-a-3 The 3-10 membered heterocycloalkyl in the substituted 3-10 membered heterocycloalkyl is replaced by one or more R 4-a-4 The 3-10 membered heterocycloalkenyl in the substituted 3-10 membered heterocycloalkenyl and the 3-10 membered heterocycloalkenyl replaced by one or more R 4-a-5 The heteroatoms in the 5-10 membered heteroaryl group of the substituted 5-10 membered heteroaryl group are each independently selected from one or more of N, O and S, and the number of heteroatoms is each independently 1, 2 or 3;

[0060] R 4-a-1 、R 4-a-2 、R 4-a-3 、R 4-a-4 、R 4-a-5 、R 4-a-6 and R 4-a-7 Each is independently halogen, =O, cyano, -C(O)CH3, -C(O)NH2, -OH, halogenated C1-C6 alkyl, -N(R 8 )2, -SCH3, -SO2CH3, C1-C6 alkyl, C3-C 10 Cycloalkyl, 3-10 membered heterocycloalkyl or 3-10 membered heterocycloalkenyl; the heteroatoms in the 3-10 membered heterocycloalkyl and 3-10 membered heterocycloalkenyl are each independently selected from one or more of N, O and S, and the number of heteroatoms is each independently 1, 2 or 3;

[0061] R 8 are independently hydrogen, -C(O)N(R 10 )2、-C(O)R 10 , C1-C6 alkyl, C3-C 10 Cycloalkyl, 3-10 membered heterocycloalkyl, 3-10 membered heterocycloalkenyl, 5-10 membered heteroaryl, substituted by one or more R 8a Substituted C1-C6 alkyl, one or more R 8b Substituted C3-C 10Cycloalkyl, one or more R 8c substituted 3-10 membered heterocycloalkyl, substituted by one or more R 8d substituted 3-10 membered heterocycloalkenyl or one or more R 8e substituted 5-10 membered heteroaryl; the 3-10 membered heterocycloalkyl, 3-10 membered heterocycloalkenyl, 5-10 membered heteroaryl, substituted by one or more R 8c The 3-10 membered heterocycloalkyl in the substituted 3-10 membered heterocycloalkyl is replaced by one or more R 8d The 3-10 membered heterocycloalkenyl in the substituted 3-10 membered heterocycloalkenyl and the 3-10 membered heterocycloalkenyl replaced by one or more R 8e The heteroatoms in the 5-10 membered heteroaryl group of the substituted 5-10 membered heteroaryl group are each independently selected from one or more of N, O and S, and the number of heteroatoms is each independently 1, 2 or 3;

[0062] R 8a 、R 8b 、R 8c 、R 8d and R 8e are independently halogen, cyano, -C(O)R 10 、-C(O)N(R 10 )2、-OH、C1-C6 alkyl-O-、-N(R 10 )2、-SO2N(R 10 )2, -SO2R 10 , C1-C6 alkyl, C3-C 10 Cycloalkyl, 3-10 membered heterocycloalkyl, 3-10 membered heterocycloalkenyl, 5-10 membered heteroaryl, substituted by one or more R 8-a Substituted C1-C6 alkyl, one or more R 8-b Substituted C3-C 10 Cycloalkyl, one or more R 8-c substituted 3-10 membered heterocycloalkyl, substituted by one or more R 8-d substituted 3-10 membered heterocycloalkenyl or one or more R 8-e substituted 5-10 membered heteroaryl; the 3-10 membered heterocycloalkyl, 3-10 membered heterocycloalkenyl, 5-10 membered heteroaryl, substituted by one or more R 8-c The 3-10 membered heterocycloalkyl in the substituted 3-10 membered heterocycloalkyl is replaced by one or more R 8-d The 3-10 membered heterocycloalkenyl in the substituted 3-10 membered heterocycloalkenyl and the 3-10 membered heterocycloalkenyl replaced by one or more R 8-e The heteroatoms in the 5-10 membered heteroaryl group of the substituted 5-10 membered heteroaryl group are each independently selected from one or more of N, O and S, and the number of heteroatoms is each independently 1, 2 or 3;

[0063] R 8-a 、R 8-b 、R 8-c 、R 8-d and R 8-e are independently halogen, cyano, -C(O)R 10 、-C(O)N(R 10 )2、-OH、C1-C6 alkyl-O-、-N(R 10 )2、-SO2N(R 10 )2、-SO2(R 10 ), C1-C6 alkyl, C3-C 10 Cycloalkyl, 3-10 membered heterocycloalkyl, 3-10 membered heterocycloalkenyl, 5-10 membered heteroaryl, substituted by one or more R 8-a-1 Substituted C1-C6 alkyl, one or more R 8-a-2 Substituted C3-C 10 Cycloalkyl, one or more R 8-a-3 substituted 3-10 membered heterocycloalkyl, substituted by one or more R 8-a-4 substituted 3-10 membered heterocycloalkenyl or one or more R 8-a-5 substituted 5-10 membered heteroaryl; the 3-10 membered heterocycloalkyl, 3-10 membered heterocycloalkenyl, 5-10 membered heteroaryl, substituted by one or more R 8-a-3 The 3-10 membered heterocycloalkyl in the substituted 3-10 membered heterocycloalkyl is replaced by one or more R 8-a-4 The 3-10 membered heterocycloalkenyl in the substituted 3-10 membered heterocycloalkenyl and the 3-10 membered heterocycloalkenyl replaced by one or more R 8-a-5 The heteroatoms in the 5-10 membered heteroaryl group of the substituted 5-10 membered heteroaryl group are each independently selected from one or more of N, O and S, and the number of heteroatoms is each independently 1, 2 or 3;

[0064] R 8-a-1 、R 8-a-2 、R 8-a-3 、R 8-a-4 and R 8-a-5 are independently halogen, cyano, -C(O)R 10 、-C(O)N(R 10 )2、-OH、-OCH3、-N(R 10 )2、-SO2N(R 10 )2, -SO2R 10 , C1-C6 alkyl or halogenated C1-C6 alkyl;

[0065] R 10 are independently hydrogen, C1-C6 alkyl, halogenated C1-C6 alkyl, C3-C 10 Cycloalkyl or 3-10 membered heterocycloalkyl;

[0066] R 11 are independently -NH2 or C1-C6 alkyl;

[0067] R 5 and R 6 are independently hydrogen, halogen, -N(R 8 )2, 3-10 membered heterocycloalkyl, C1-C6 alkyl, 3-10 membered heterocycloalkenyl, C3-C 10 Cycloalkyl, C3-C 10 Cycloalkenyl, 5-10 membered heteroaryl, C6-C 10 Aryl, one or more R 5a Substituted C1-C6 alkyl, one or more R 5b substituted 3-10 membered heterocycloalkyl, substituted by one or more R 5c substituted 3-10 membered heterocycloalkenyl, substituted by one or more R 5d Substituted C3-C 10 Cycloalkyl, one or more R 5e Substituted C3-C 10 Cycloalkenyl, one or more R 5f substituted 5-10 membered heteroaryl or one or more R 5g Substituted C6-C 10 Aryl; the 3-10 membered heterocycloalkyl, 3-10 membered heterocycloalkenyl, 5-10 membered heteroaryl, one or more R 5b The 3-10 membered heterocycloalkyl in the substituted 3-10 membered heterocycloalkyl is replaced by one or more R 5c The 3-10 membered heterocycloalkenyl in the substituted 3-10 membered heterocycloalkenyl and the 3-10 membered heterocycloalkenyl replaced by one or more R 5f The heteroatoms in the 5-10 membered heteroaryl group of the substituted 5-10 membered heteroaryl group are each independently selected from one or more of N, O and S, and the number of heteroatoms is each independently 1, 2 or 3;

[0068] R 5a 、R 5b 、R 5c 、R 5d 、R 5e 、R 5f and R 5g Each is independently halogen, =O, cyano, -OH, C1-C6 alkyl-O-, C1-C6 alkyl or halogenated C1-C6 alkyl;

[0069] R 4 and R 5 It can also form a 3-10 membered saturated heterocyclic ring, a 5-10 membered heteroaromatic ring, a 3-10 membered heterocyclic alkene, or one or more R 4hsubstituted 3-10 membered saturated heterocyclic ring, replaced by one or more R 4i Substituted 3-10 membered heterocyclic olefins or one or more R 4j substituted 5-10 membered heteroaromatic ring; the 3-10 membered saturated heterocyclic ring, 3-10 membered heterocyclic alkene, 5-10 membered heteroaromatic ring, substituted by one or more R 4h The 3-10 membered saturated heterocyclic ring in the substituted 3-10 membered saturated heterocyclic ring is replaced by one or more R 4i The 3-10 membered heterocyclic olefin in the substituted 3-10 membered heterocyclic olefin and the substituted 3-10 membered heterocyclic olefin are replaced by one or more R 4j The heteroatoms in the 5-10 membered heteroaromatic ring of the substituted 5-10 membered heteroaromatic ring are each independently selected from one or more of N, O and S, and the number of heteroatoms is each independently 1, 2 or 3;

[0070] R 4h 、R 4i and R 4j are each independently halogen, =O, cyano, -OH, -N(R 8 )2、-SR 11 、-SO2R 11 、-C(O)N(R 10 )2、-C(O)R 10 , C1-C6 alkyl or one or more R 4-h Substituted C1-C6 alkyl;

[0071] Or two adjacent R 4h Together with the atoms to which they are attached, they form a 5-10 membered heteroaromatic ring, wherein the 5-10 membered heteroaromatic ring is optionally substituted by one or more of the following groups: halogen, =O, cyano, -OH, -N(R 8 )2、-SR 11 、-SO2R 11 、-C(O)N(R 10 )2、-C(O)R 10 , C1-C6 alkyl or one or more R 4-h substituted C1-C6 alkyl; the heteroatoms in the 5-10 membered heteroaromatic ring are each independently selected from one or more of N, O and S, and the number of heteroatoms is each independently 1, 2 or 3; R 4-h are independently halogen, =O, cyano or -N(R 8 )2;

[0072] R 1 C6-C 10 Aryl, 5-10 membered heteroaryl, 3-10 membered heterocycloalkyl, 1a Substituted C6-C 10 Aryl, one or more R 1bsubstituted 5-10 membered heteroaryl or one or more R 1c substituted 3-10 membered heterocycloalkyl; said 5-10 membered heteroaryl, 3-10 membered heterocycloalkyl, substituted by one or more R 1b The 5-10 membered heteroaryl in the substituted 5-10 membered heteroaryl and the 5-10 membered heteroaryl replaced by one or more R 1c The heteroatoms in the 3-10 membered heterocycloalkyl group in the substituted 3-10 membered heterocycloalkyl group are each independently selected from one or more of N, O and S, and the number of heteroatoms is each independently 1, 2 or 3;

[0073] R 1a 、R 1b and R 1c Each is independently deuterium, halogen, -OH, -CN, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, 5-10 membered heteroaryl, C1-C6 alkyl-O-, C1-C6 alkyl-S-, -N(R 8 )2、-(CH2)-C(=O)N(R 8 )2. C3-C 10 Cycloalkyl, one or more R 1-a Substituted C1-C6 alkyl, one or more R 1-b Substituted C1-C6 alkyl-O-, one or more R 1-c Substituted C1-C6 alkyl-S-, one or more R 1-d Substituted C2-C6 alkenyl, one or more R 1-e Substituted C2-C6 alkynyl, one or more R 1- f Substituted C3-C 10 Cycloalkyl or one or more R 1-g substituted 5-10 membered heteroaryl; said 5-10 membered heteroaryl and one or more R 1-g The heteroatoms in the 5-10 membered heteroaryl group of the substituted 5-10 membered heteroaryl group are each independently selected from one or more of N, O and S, and the number of heteroatoms is each independently 1, 2 or 3;

[0074] Or two adjacent R 1c Together with the atoms to which they are attached, they form a 5-10 membered heteroaromatic ring, wherein the 5-10 membered heteroaromatic ring is optionally substituted by one or more of the following groups: deuterium, halogen, -OH, -CN, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, 5-10 membered heteroaryl, C1-C6 alkyl-O-, C1-C6 alkyl-S-, -N(R 8 )2、-(CH2)-C(=O)N(R 8 )2. C3-C 10Cycloalkyl, one or more R 1- a Substituted C1-C6 alkyl, one or more R 1-b Substituted C1-C6 alkyl-O-, one or more R 1-c Substituted C1-C6 alkyl-S-, one or more R 1-d Substituted C2-C6 alkenyl, one or more R 1-e Substituted C2-C6 alkynyl, one or more R 1-f Substituted C3-C 10 Cycloalkyl or one or more R 1-g substituted 5-10 membered heteroaryl; the 5-10 membered heteroaryl ring, the 5-10 membered heteroaryl and the substituted one or more R 1-g The heteroatoms in the 5-10 membered heteroaryl group of the substituted 5-10 membered heteroaryl group are independently selected from one or more of N, O and S, and the number of heteroatoms is independently 1, 2 or 3;

[0075] R 1-a 、R 1-b 、R 1-c 、R 1-d 、R 1-e 、R 1-f and R 1-g Each is independently deuterium, halogen, -CN, -OH, C1-C4 alkyl, C1-C4 alkyl-O- or C3-C 10 Cycloalkyl;

[0076] L is absent, -O-(CR 9 R 9 ) n1 -、-S-(CR 9 R 9 ) n2 -、-N(R 8 )-(CR 9 R 9 ) n3 -、-SO-(CR 9 R 9 ) n4 -or-SO2-(CR 9 R 9 ) n5 -;

[0077] R 9 are independently hydrogen, halogen, -CN, C1-C6 alkyl, C1-C6 alkyl-O-, deuterated C1-C6 alkyl, or 5-10 membered heteroaryl;

[0078] n1, n2, n3, n4 and n5 are each independently 0, 1, 2 or 3; (when 0, it represents a connecting bond);

[0079] R 2 is hydrogen, -COOH, C1-C6 alkyl, C1-C6 alkyl-O-, C3-C 10 Cycloalkyl, C3-C 10 Cycloalkenyl, 4-10 membered heterocycloalkyl, C6-C 10 Aryl, 5-10 membered heteroaryl, -NHC(=NH)NH2, -C(O)N(R 8 )2、-(CH2OR 10 )(CH2) n6 OR 10 、-NR 8 C(=O)-C6-C 10 Aryl, -C(=O)O-C1-C6 alkyl, one or more R 2a Substituted C3-C 10 Cycloalkyl, one or more R 2b Substituted C3-C 10 Cycloalkenyl, one or more R 2c substituted 4-10 membered heterocycloalkyl, substituted by one or more R 2d Substituted C6-C 10 Aryl or one or more R 2e substituted 5-10 membered heteroaryl; said 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, substituted by one or more R 2c The 4-10 membered heterocycloalkyl in the substituted 4-10 membered heterocycloalkyl and the substituted 4-10 membered heterocycloalkyl 2e The heteroatoms in the 5-10 membered heteroaryl group of the substituted 5-10 membered heteroaryl group are each independently selected from one or more of N, O and S, and the number of heteroatoms is each independently 1, 2 or 3;

[0080] n6 is 0, 1, 2, or 3;

[0081] R 2a 、R 2b 、R 2c 、R 2d and R 2e are independently halogen, -OH, deuterium, -CN, -C(=O)H, =CR 2-c R 2-c , C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 alkyl-O-, -N(R 8 )2、(C l -C4 alkyl)-C(=O)-, oxo(=O), -SO2F, (C l -C4 alkyl)-SO2-, (C l -C4 alkyl)-O-(C l-C4 alkyl)-, (C l -C4 alkyl)-O-(C l -C4 alkyl)-O-, -CH2OC(=O)N(R 8 )2、(C l -C4 alkyl)-OC(=O)-NHCH2-, -CH2NHC(=O)N(R 8 )2、(C l -C4 alkyl)-C(=O)NHCH2-, (pyrazolyl)-CH2-, (C l -C4 alkyl)-SO2-NHCH2-, (4-10 membered heterocycloalkyl)-C(=O)-OCH2-, (R 8 )2N-C(=O)-O-、(C l -C4 alkyl)-O-(C l -C4 alkyl)-NH- C(=O)-O-, phenyl-C(=O)NH-, phenyl-(C l -C4 alkyl)-NH-C(=O)-O-, (4-10 membered heterocycloalkyl)-C(=O)-O-, (4-10 membered heterocycloalkyl)-CH2-, 4-10 membered heterocycloalkyl, 2-a Substituted C1-C4 alkyl, one or more R 2-b Substituted C1-C4 alkyl-O- or one or more R 2-d Substituted 4-10 membered heterocycloalkyl; the phenyl-C(=O)NH- and phenyl-(C l -C4 alkyl)-NH-C(=O)-O-phenyl is optionally substituted by -C(=O)H, halogen, -CN or -OH; the 4-10 membered heterocycloalkyl in the (4-10 membered heterocycloalkyl)-C(=O)-OCH2-, (4-10 membered heterocycloalkyl)-C(=O)-O- and (4-10 membered heterocycloalkyl)-CH2- is optionally substituted by =O, halogen, -CN, -OH or C l -C6 alkyl substituted; the 4-10 membered heterocycloalkyl, by one or more R 2-d The heteroatoms in the 4-10 membered heterocycloalkyl in the substituted 4-10 membered heterocycloalkyl, (4-10 membered heterocycloalkyl)-C(═O)-OCH2-, (4-10 membered heterocycloalkyl)-C(═O)-O- and the 4-10 membered heterocycloalkyl in (4-10 membered heterocycloalkyl)-CH2- are each independently selected from one or more of N, O and S, and the number of heteroatoms is each independently 1, 2 or 3;

[0082] R 2-a 、R 2-b 、R 2-c and R 2-dare each independently deuterium, -CN, halogen or -OH;

[0083] R 3 H, deuterium, -N(R 8 )2, halogen, -OH, C1-C6 alkyl, -CN, halo-C1-C6 alkyl, deuterated C1-C6 alkyl, C1-C6 alkyl-O-, deuterated C1-C6 alkyl-O-, C2-C6 alkenyl or C2-C6 alkynyl.

[0084] The present invention provides a heterocyclic compound represented by Formula I, a pharmaceutically acceptable salt thereof, a solvate thereof, or a solvate of a pharmaceutically acceptable salt thereof.

[0085] Wherein, n is 1, 2 or 3;

[0086] X is independently -C(R 7 )2-、-NR 7 -、-O-、-S-、-CR 7 =CR 7 -, -N=N- or -CR 7 =N-;

[0087] R 7 are independently hydrogen, deuterium, halogen, cyano, hydroxy, amino, C1-C6 alkyl, C1-C6 alkyl-O-, C2-C6 alkenyl, C2-C6 alkynyl, 7a Substituted C1-C6 alkyl, one or more R 7b Substituted C1-C6 alkyl-O-, one or more R 7c Substituted C2-C6 alkenyl or one or more R 7d substituted C2-C6 alkynyl;

[0088] R 7a 、R 7b 、R 7c and R 7d are each independently deuterium, -CN, halogen or -OH;

[0089] Y is -NR 4 -、-O-、-S-、-C(R 4 )2- or -(CH2) p NR 4 -;

[0090] p is 1, 2, or 3;

[0091] R 4 are independently hydrogen, C1-C6 alkyl, C3-C 10 Cycloalkyl, 3-10 membered heterocycloalkyl, C3-C 10Cycloalkenyl, 3-10 membered heterocycloalkenyl, 5-10 membered heteroaryl, C6-C 10 Aryl, -SO2R h , by one or more R 4a Substituted C1-C6 alkyl, one or more R 4b Substituted C3-C 10 Cycloalkyl, one or more R 4c substituted 3-10 membered heterocycloalkyl, substituted by one or more R 4d substituted 3-10 membered heterocycloalkenyl, substituted by one or more R 4e substituted 5-10 membered heteroaryl, substituted by one or more R 4f Substituted C3-C 10 Cycloalkenyl or one or more R 4g Substituted C6-C 10 Aryl; the 3-10 membered heterocycloalkyl, 3-10 membered heterocycloalkenyl, 5-10 membered heteroaryl, one or more R 4c The 3-10 membered heterocycloalkyl in the substituted 3-10 membered heterocycloalkyl is replaced by one or more R 4d The 3-10 membered heterocycloalkenyl in the substituted 3-10 membered heterocycloalkenyl and the 3-10 membered heterocycloalkenyl replaced by one or more R 4e The heteroatoms in the 5-10 membered heteroaryl group of the substituted 5-10 membered heteroaryl group are each independently selected from one or more of N, O and S, and the number of heteroatoms is each independently 1, 2 or 3;

[0092] R 4a 、R 4b 、R 4c 、R 4d 、R 4e 、R 4f 、R 4g and R h are independently halogen, =O, cyano, -OR 10 、-N(R 8 )2、-SR 11 、-SO2R 11 、-C(O)N(R 10 )2、-C(O)R 10 , C1-C6 alkyl, C3-C 10 Cycloalkyl, 3-10 membered heterocycloalkenyl, 5-10 membered heteroaryl, 3-10 membered heterocycloalkyl, C3-C 10 Cycloalkenyl, C6-C 10 Aryl, one or more R 4-a Substituted C1-C6 alkyl, one or more R 4- b Substituted C3-C 10 Cycloalkyl, one or more R4-c substituted 3-10 membered heterocycloalkyl, substituted by one or more R 4-d substituted 3-10 membered heterocycloalkenyl, substituted by one or more R 4-e substituted 5-10 membered heteroaryl, substituted by one or more R 4-f Substituted C3-C 10 Cycloalkenyl or one or more R 4-g Substituted C6-C 10 Aryl; the 3-10 membered heterocycloalkyl, 3-10 membered heterocycloalkenyl, 5-10 membered heteroaryl, one or more R 4-c The 3-10 membered heterocycloalkyl in the substituted 3-10 membered heterocycloalkyl is replaced by one or more R 4-d The 3-10 membered heterocycloalkenyl in the substituted 3-10 membered heterocycloalkenyl and the 3-10 membered heterocycloalkenyl replaced by one or more R 4-e The heteroatoms in the 5-10 membered heteroaryl group of the substituted 5-10 membered heteroaryl group are each independently selected from one or more of N, O and S, and the number of heteroatoms is each independently 1, 2 or 3;

[0093] R 4-a 、R 4-b 、R 4-c 、R 4-d 、R 4-e 、R 4-f and R 4-g are independently halogen, =O, cyano, -OR 10 、-N(R 8 )2、-SR 11 、-SO2R 11 、-C(O)N(R 10 )2、-C(O)R 10 , C1-C6 alkyl, C3-C 10 Cycloalkyl, 3-10 membered heterocycloalkenyl, 3-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-C 10 Cycloalkenyl, C6-C 10 Aryl, one or more R 4-a-1 Substituted C1-C6 alkyl, one or more R 4- a - 2 Substituted C3-C 10 Cycloalkyl, one or more R 4-a-3 substituted 3-10 membered heterocycloalkyl, substituted by one or more R 4-a-4 substituted 3-10 membered heterocycloalkenyl, substituted by one or more R 4-a-5 substituted 5-10 membered heteroaryl, substituted by one or more R 4-a-6 Substituted C3-C 10Cycloalkenyl or one or more R 4-a-7 Substituted C6-C 10 Aryl; the 3-10 membered heterocycloalkyl, 3-10 membered heterocycloalkenyl, 5-10 membered heteroaryl, one or more R 4-a-3 The 3-10 membered heterocycloalkyl in the substituted 3-10 membered heterocycloalkyl is replaced by one or more R 4-a-4 The 3-10 membered heterocycloalkenyl in the substituted 3-10 membered heterocycloalkenyl and the 3-10 membered heterocycloalkenyl replaced by one or more R 4-a-5 The heteroatoms in the 5-10 membered heteroaryl group of the substituted 5-10 membered heteroaryl group are each independently selected from one or more of N, O and S, and the number of heteroatoms is each independently 1, 2 or 3;

[0094] R 4-a-1 、R 4-a-2 、R 4-a-3 、R 4-a-4 、R 4-a-5 、R 4-a-6 and R 4-a-7 Each is independently halogen, =O, cyano, -C(O)CH3, -C(O)NH2, -OH, halogenated C1-C6 alkyl, -N(R 8 )2, -SCH3, -SO2CH3, C1-C6 alkyl, C3-C 10 Cycloalkyl, 3-10 membered heterocycloalkyl or 3-10 membered heterocycloalkenyl; the heteroatoms in the 3-10 membered heterocycloalkyl and 3-10 membered heterocycloalkenyl are each independently selected from one or more of N, O and S, and the number of heteroatoms is each independently 1, 2 or 3;

[0095] R 8 are independently hydrogen, -C(O)N(R 10 )2、-C(O)R 10 , C1-C6 alkyl, C3-C 10 Cycloalkyl, 3-10 membered heterocycloalkyl, 3-10 membered heterocycloalkenyl, 5-10 membered heteroaryl, substituted by one or more R 8a Substituted C1-C6 alkyl, one or more R 8b Substituted C3-C 10 Cycloalkyl, one or more R 8c substituted 3-10 membered heterocycloalkyl, substituted by one or more R 8d substituted 3-10 membered heterocycloalkenyl or one or more R 8e substituted 5-10 membered heteroaryl; the 3-10 membered heterocycloalkyl, 3-10 membered heterocycloalkenyl, 5-10 membered heteroaryl, substituted by one or more R 8c The 3-10 membered heterocycloalkyl in the substituted 3-10 membered heterocycloalkyl is replaced by one or more R 8dThe 3-10 membered heterocycloalkenyl in the substituted 3-10 membered heterocycloalkenyl and the 3-10 membered heterocycloalkenyl replaced by one or more R 8e The heteroatoms in the 5-10 membered heteroaryl group of the substituted 5-10 membered heteroaryl group are each independently selected from one or more of N, O and S, and the number of heteroatoms is each independently 1, 2 or 3;

[0096] R 8a 、R 8b 、R 8c 、R 8d and R 8e are independently halogen, cyano, -C(O)R 10 、-C(O)N(R 10 )2、-OH、C1-C6 alkyl-O-、-N(R 10 )2、-SO2N(R 10 )2, -SO2R 10 , C1-C6 alkyl, C3-C 10 Cycloalkyl, 3-10 membered heterocycloalkyl, 3-10 membered heterocycloalkenyl, 5-10 membered heteroaryl, substituted by one or more R 8-a Substituted C1-C6 alkyl, one or more R 8-b Substituted C3-C 10 Cycloalkyl, one or more R 8-c substituted 3-10 membered heterocycloalkyl, substituted by one or more R 8-d substituted 3-10 membered heterocycloalkenyl or one or more R 8-e substituted 5-10 membered heteroaryl; the 3-10 membered heterocycloalkyl, 3-10 membered heterocycloalkenyl, 5-10 membered heteroaryl, substituted by one or more R 8-c The 3-10 membered heterocycloalkyl in the substituted 3-10 membered heterocycloalkyl is replaced by one or more R 8-d The 3-10 membered heterocycloalkenyl in the substituted 3-10 membered heterocycloalkenyl and the 3-10 membered heterocycloalkenyl replaced by one or more R 8-e The heteroatoms in the 5-10 membered heteroaryl group of the substituted 5-10 membered heteroaryl group are each independently selected from one or more of N, O and S, and the number of heteroatoms is each independently 1, 2 or 3;

[0097] R 8-a 、R 8-b 、R 8-c 、R 8-d and R 8-e are independently halogen, cyano, -C(O)R 10 、-C(O)N(R 10 )2、-OH、C1-C6 alkyl-O-、-N(R 10 )2、-SO2N(R 10 )2、-SO2(R10 ), C1-C6 alkyl, C3-C 10 Cycloalkyl, 3-10 membered heterocycloalkyl, 3-10 membered heterocycloalkenyl, 5-10 membered heteroaryl, substituted by one or more R 8-a-1 Substituted C1-C6 alkyl, one or more R 8-a-2 Substituted C3-C 10 Cycloalkyl, one or more R 8-a-3 substituted 3-10 membered heterocycloalkyl, substituted by one or more R 8-a-4 substituted 3-10 membered heterocycloalkenyl or one or more R 8-a-5 substituted 5-10 membered heteroaryl; the 3-10 membered heterocycloalkyl, 3-10 membered heterocycloalkenyl, 5-10 membered heteroaryl, substituted by one or more R 8-a-3 The 3-10 membered heterocycloalkyl in the substituted 3-10 membered heterocycloalkyl is replaced by one or more R 8-a-4 The 3-10 membered heterocycloalkenyl in the substituted 3-10 membered heterocycloalkenyl and the 3-10 membered heterocycloalkenyl replaced by one or more R 8-a-5 The heteroatoms in the 5-10 membered heteroaryl group of the substituted 5-10 membered heteroaryl group are each independently selected from one or more of N, O and S, and the number of heteroatoms is each independently 1, 2 or 3;

[0098] R 8-a-1 、R 8-a-2 、R 8-a-3 、R 8-a-4 and R 8-a-5 are independently halogen, cyano, -C(O)R 10 、-C(O)N(R 10 )2、-OH、-OCH3、-N(R 10 )2、-SO2N(R 10 )2, -SO2R 10 , C1-C6 alkyl or halogenated C1-C6 alkyl;

[0099] R 10 are independently hydrogen, C1-C6 alkyl, halogenated C1-C6 alkyl, C3-C 10 Cycloalkyl or 3-10 membered heterocycloalkyl;

[0100] R 11 are independently -NH2 or C1-C6 alkyl;

[0101] R 5 and R 6 are independently hydrogen, halogen, -N(R 8 )2, 3-10 membered heterocycloalkyl, C1-C6 alkyl, 3-10 membered heterocycloalkenyl, C3-C 10 Cycloalkyl, C3-C 10Cycloalkenyl, 5-10 membered heteroaryl, C6-C 10 Aryl, one or more R 5a Substituted C1-C6 alkyl, one or more R 5b substituted 3-10 membered heterocycloalkyl, substituted by one or more R 5c substituted 3-10 membered heterocycloalkenyl, substituted by one or more R 5d Substituted C3-C 10 Cycloalkyl, one or more R 5e Substituted C3-C 10 Cycloalkenyl, one or more R 5f substituted 5-10 membered heteroaryl or one or more R 5g Substituted C6-C 10 Aryl; the 3-10 membered heterocycloalkyl, 3-10 membered heterocycloalkenyl, 5-10 membered heteroaryl, one or more R 5b The 3-10 membered heterocycloalkyl in the substituted 3-10 membered heterocycloalkyl is replaced by one or more R 5c The 3-10 membered heterocycloalkenyl in the substituted 3-10 membered heterocycloalkenyl and the 3-10 membered heterocycloalkenyl replaced by one or more R 5f The heteroatoms in the 5-10 membered heteroaryl group of the substituted 5-10 membered heteroaryl group are each independently selected from one or more of N, O and S, and the number of heteroatoms is each independently 1, 2 or 3;

[0102] R 5a 、R 5b 、R 5c 、R 5d 、R 5e 、R 5f and R 5g Each is independently halogen, =O, cyano, -OH, C1-C6 alkyl-O-, C1-C6 alkyl or halogenated C1-C6 alkyl;

[0103] R 4 and R 5 It can also form a 3-10 membered saturated heterocyclic ring, a 5-10 membered heteroaromatic ring, a 3-10 membered heterocyclic alkene, or one or more R 4h substituted 3-10 membered saturated heterocyclic ring, replaced by one or more R 4i Substituted 3-10 membered heterocyclic olefins or one or more R 4j substituted 5-10 membered heteroaromatic ring; the 3-10 membered saturated heterocyclic ring, 3-10 membered heterocyclic alkene, 5-10 membered heteroaromatic ring, substituted by one or more R 4h The 3-10 membered saturated heterocyclic ring in the substituted 3-10 membered saturated heterocyclic ring is replaced by one or more R 4i The 3-10 membered heterocyclic olefin in the substituted 3-10 membered heterocyclic olefin and the substituted 3-10 membered heterocyclic olefin are replaced by one or more R4j The heteroatoms in the 5-10 membered heteroaromatic ring of the substituted 5-10 membered heteroaromatic ring are each independently selected from one or more of N, O and S, and the number of heteroatoms is each independently 1, 2 or 3;

[0104] R 4h 、R 4i and R 4j are each independently halogen, =O, cyano, -OH, -N(R 8 )2、-SR 11 、-SO2R 11 、-C(O)N(R 10 )2、-C(O)R 10 , C1-C6 alkyl or one or more R 4-h Substituted C1-C6 alkyl;

[0105] Or two adjacent R 4h Together with the atoms to which they are attached, they form a 5-10 membered heteroaromatic ring, wherein the 5-10 membered heteroaromatic ring is optionally substituted by one or more of the following groups: halogen, =O, cyano, -OH, -N(R 8 )2、-SR 11 、-SO2R 11 、-C(O)N(R 10 )2、-C(O)R 10 , C1-C6 alkyl or one or more R 4-h substituted C1-C6 alkyl; the heteroatoms in the 5-10 membered heteroaromatic ring are each independently selected from one or more of N, O and S, and the number of heteroatoms is each independently 1, 2 or 3; R 4-h are independently halogen, =O, cyano or -N(R 8 )2;

[0106] R 1 C6-C 10 Aryl, 5-10 membered heteroaryl, 3-10 membered heterocycloalkyl, 1a Substituted C6-C 10 Aryl, one or more R 1b substituted 5-10 membered heteroaryl or one or more R 1c substituted 3-10 membered heterocycloalkyl; said 5-10 membered heteroaryl, 3-10 membered heterocycloalkyl, substituted by one or more R 1b The 5-10 membered heteroaryl in the substituted 5-10 membered heteroaryl and the 5-10 membered heteroaryl replaced by one or more R 1c The heteroatoms in the 3-10 membered heterocycloalkyl group in the substituted 3-10 membered heterocycloalkyl group are each independently selected from one or more of N, O and S, and the number of heteroatoms is each independently 1, 2 or 3;

[0107] R 1a 、R 1b and R 1c Each is independently deuterium, halogen, -OH, -CN, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, 5-10 membered heteroaryl, C1-C6 alkyl-O-, C1-C6 alkyl-S-, -N(R 8 )2、-(CH2)-C(=O)N(R 8 )2. C3-C 10 Cycloalkyl, one or more R 1-a Substituted C1-C6 alkyl, one or more R 1-b Substituted C1-C6 alkyl-O-, one or more R 1-c Substituted C1-C6 alkyl-S-, one or more R 1-d Substituted C2-C6 alkenyl, one or more R 1-e Substituted C2-C6 alkynyl, one or more R 1- f Substituted C3-C 10 Cycloalkyl or one or more R 1-g substituted 5-10 membered heteroaryl; said 5-10 membered heteroaryl and one or more R 1-g The heteroatoms in the 5-10 membered heteroaryl group of the substituted 5-10 membered heteroaryl group are each independently selected from one or more of N, O and S, and the number of heteroatoms is each independently 1, 2 or 3;

[0108] Or two adjacent R 1c Together with the atoms to which they are attached, they form a 5-10 membered heteroaromatic ring, wherein the 5-10 membered heteroaromatic ring is optionally substituted by one or more of the following groups: deuterium, halogen, -OH, -CN, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, 5-10 membered heteroaryl, C1-C6 alkyl-O-, C1-C6 alkyl-S-, -N(R 8 )2、-(CH2)-C(=O)N(R 8 )2. C3-C 10 Cycloalkyl, one or more R 1- a Substituted C1-C6 alkyl, one or more R 1-b Substituted C1-C6 alkyl-O-, one or more R 1-c Substituted C1-C6 alkyl-S-, one or more R 1-d Substituted C2-C6 alkenyl, one or more R 1-e Substituted C2-C6 alkynyl, one or more R 1-f Substituted C3-C10 Cycloalkyl or one or more R 1-g substituted 5-10 membered heteroaryl; the 5-10 membered heteroaryl ring, the 5-10 membered heteroaryl and the substituted one or more R 1-g The heteroatoms in the 5-10 membered heteroaryl group of the substituted 5-10 membered heteroaryl group are independently selected from one or more of N, O and S, and the number of heteroatoms is independently 1, 2 or 3;

[0109] R 1-a 、R 1-b 、R 1-c 、R 1-d 、R 1-e 、R 1-f and R 1-g Each is independently deuterium, halogen, -CN, -OH, C1-C4 alkyl, C1-C4 alkyl-O- or C3-C 10 Cycloalkyl;

[0110] L is -O-(CR 9 R 9 ) n1 -、-S-(CR 9 R 9 ) n2 -、-N(R 8 )-(CR 9 R 9 ) n3 -、-SO-(CR 9 R 9 ) n4 -or-SO2-(CR 9 R 9 ) n5 -;

[0111] R 9 are independently hydrogen, halogen, -CN, C1-C6 alkyl, C1-C6 alkyl-O-, deuterated C1-C6 alkyl, or 5-10 membered heteroaryl;

[0112] n1, n2, n3, n4 and n5 are each independently 0, 1, 2 or 3; (when 0, it represents a connecting bond);

[0113] R 2 is hydrogen, -COOH, C1-C6 alkyl, C1-C6 alkyl-O-, C3-C 10 Cycloalkyl, C3-C 10 Cycloalkenyl, 4-10 membered heterocycloalkyl, C6-C 10 Aryl, 5-10 membered heteroaryl, -NHC(=NH)NH2, -C(O)N(R 8 )2、-(CH2OR 10 )(CH2)n6 OR 10 、-NR 8 C(=O)-C6- C 10 Aryl, -C(=O)O-C1-C6 alkyl, one or more R 2a Substituted C3-C 10 Cycloalkyl, one or more R 2b Substituted C3-C 10 Cycloalkenyl, one or more R 2c substituted 4-10 membered heterocycloalkyl, substituted by one or more R 2d Substituted C6-C 10 Aryl or one or more R 2e substituted 5-10 membered heteroaryl; said 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, substituted by one or more R 2c The 4-10 membered heterocycloalkyl in the substituted 4-10 membered heterocycloalkyl and the substituted 4-10 membered heterocycloalkyl 2e The heteroatoms in the 5-10 membered heteroaryl group of the substituted 5-10 membered heteroaryl group are each independently selected from one or more of N, O and S, and the number of heteroatoms is each independently 1, 2 or 3;

[0114] n6 is 0, 1, 2, or 3;

[0115] R 2a 、R 2b 、R 2c 、R 2d and R 2e are independently halogen, -OH, deuterium, -CN, -C(=O)H, =CR 2-c R 2-c , C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 alkyl-O-, -N(R 8 )2、(C l -C4 alkyl)-C(=O)-, oxo(=O), -SO2F, (C l -C4 alkyl)-SO2-, (C l -C4 alkyl)-O-(C l -C4 alkyl)-, (C l -C4 alkyl)-O-(C l -C4 alkyl)-O-, -CH2OC(=O)N(R 8 )2、(C l -C4 alkyl)-OC(=O)-NHCH2-, -CH2NHC(=O)N(R 8 )2、(C l -C4 alkyl)-C(=O)NHCH2-, (pyrazolyl)-CH2-, (Cl -C4 alkyl)-SO2-NHCH2-, (4-10 membered heterocycloalkyl)-C(=O)-OCH2-, (R 8 )2N-C(=O)-O-、(C l -C4 alkyl)-O-(C l -C4 alkyl)-NH-C(=O)-O-, phenyl-C(=O)NH-, phenyl-(C l -C4 alkyl)-NH-C(=O)-O-, (4-10 membered heterocycloalkyl)-C(=O)-O-, (4-10 membered heterocycloalkyl)-CH2-, 2-a Substituted C1-C4 alkyl or one or more R 2-b Substituted C1-C4 alkyl-O-; the phenyl-C(=O)NH- and phenyl-(C l -C4 alkyl)-NH-C(=O)-O-phenyl is optionally substituted by -C(=O)H, halogen, -CN or -OH; the 4-10 membered heterocycloalkyl in the (4-10 membered heterocycloalkyl)-C(=O)-OCH2-, (4-10 membered heterocycloalkyl)-C(=O)-O- and (4-10 membered heterocycloalkyl)-CH2- is optionally substituted by =O, halogen, -CN, -OH or C l -C6 alkyl substitution; the heteroatoms in the 4-10 membered heterocycloalkyl in (4-10 membered heterocycloalkyl)-C(=O)-OCH2-, (4-10 membered heterocycloalkyl)-C(=O)-O- and (4-10 membered heterocycloalkyl)-CH2- are each independently selected from one or more of N, O and S, and the number of heteroatoms is each independently 1, 2 or 3;

[0116] R 2-a 、R 2-b and R 2-c are each independently deuterium, -CN, halogen or -OH;

[0117] R 3 H, deuterium, -N(R 8 )2, halogen, -OH, C1-C6 alkyl, -CN, halo-C1-C6 alkyl, deuterated C1-C6 alkyl, C1-C6 alkyl-O-, deuterated C1-C6 alkyl-O-, C2-C6 alkenyl or C2-C6 alkynyl.

[0118] In one embodiment of the present invention, n is 1, 2 or 3;

[0119] X is independently -C(R 7 )2-、-NR 7 -、-O-、-S-、-CR 7 =CR 7 -, -N=N- or -CR7 =N-;

[0120] R 7 are independently hydrogen, deuterium, halogen, cyano, hydroxy, amino, C1-C6 alkyl, C1-C6 alkyl-O-, C2-C6 alkenyl, C2-C6 alkynyl, 7a Substituted C1-C6 alkyl, one or more R 7b Substituted C1-C6 alkyl-O-, one or more R 7c Substituted C2-C6 alkenyl or one or more R 7d substituted C2-C6 alkynyl;

[0121] R 7a 、R 7b 、R 7c and R 7d are each independently deuterium, -CN, halogen or -OH;

[0122] Y is -NR 4 -, -O-, -S- or -C(R 4 )2-;

[0123] R 4 are independently hydrogen, C1-C6 alkyl, C3-C 10 Cycloalkyl, 3-10 membered heterocycloalkyl, C3-C 10 Cycloalkenyl, 3-10 membered heterocycloalkenyl, 5-10 membered heteroaryl, C6-C 10 Aryl, one or more R 4a Substituted C1-C6 alkyl, one or more R 4b Substituted C3-C 10 Cycloalkyl, one or more R 4c substituted 3-10 membered heterocycloalkyl, substituted by one or more R 4d substituted 3-10 membered heterocycloalkenyl, substituted by one or more R 4e substituted 5-10 membered heteroaryl, substituted by one or more R 4f Substituted C3-C 10 Cycloalkenyl or one or more R 4g Substituted C6-C 10 Aryl; the 3-10 membered heterocycloalkyl, 3-10 membered heterocycloalkenyl, 5-10 membered heteroaryl, one or more R 4c The 3-10 membered heterocycloalkyl in the substituted 3-10 membered heterocycloalkyl is replaced by one or more R 4d The 3-10 membered heterocycloalkenyl in the substituted 3-10 membered heterocycloalkenyl and the 3-10 membered heterocycloalkenyl replaced by one or more R 4eThe heteroatoms in the 5-10 membered heteroaryl group of the substituted 5-10 membered heteroaryl group are each independently selected from one or more of N, O and S, and the number of heteroatoms is each independently 1, 2 or 3;

[0124] R 4a 、R 4b 、R 4c 、R 4d 、R 4e 、R 4f and R 4g are independently halogen, =O, cyano, -OR 10 、-N(R 8 )2、-SR 11 、-SO2R 11 、-C(O)N(R 10 )2、-C(O)R 10 , C1-C6 alkyl, C3-C 10 Cycloalkyl, 3-10 membered heterocycloalkenyl, 5-10 membered heteroaryl, 3-10 membered heterocycloalkyl, C3-C 10 Cycloalkenyl, C6-C 10 Aryl, one or more R 4-a Substituted C1-C6 alkyl, one or more R 4-b Substituted C3-C 10 Cycloalkyl, one or more R 4-c substituted 3-10 membered heterocycloalkyl, substituted by one or more R 4-d substituted 3-10 membered heterocycloalkenyl, substituted by one or more R 4-e substituted 5-10 membered heteroaryl, substituted by one or more R 4-f Substituted C3-C 10 Cycloalkenyl or one or more R 4-g Substituted C6-C 10 Aryl; the 3-10 membered heterocycloalkyl, 3-10 membered heterocycloalkenyl, 5-10 membered heteroaryl, one or more R 4-c The 3-10 membered heterocycloalkyl in the substituted 3-10 membered heterocycloalkyl is replaced by one or more R 4-d The 3-10 membered heterocycloalkenyl in the substituted 3-10 membered heterocycloalkenyl and the 3-10 membered heterocycloalkenyl replaced by one or more R 4-e The heteroatoms in the 5-10 membered heteroaryl group of the substituted 5-10 membered heteroaryl group are each independently selected from one or more of N, O and S, and the number of heteroatoms is each independently 1, 2 or 3;

[0125] R 4-a 、R 4-b 、R 4-c 、R 4-d 、R 4-e 、R4-f and R 4-g are independently halogen, =O, cyano, -OR 10 、-N(R 8 )2、-SR 11 、-SO2R 11 、-C(O)N(R 10 )2、-C(O)R 10 , C1-C6 alkyl, C3-C 10 Cycloalkyl, 3-10 membered heterocycloalkenyl, 3-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-C 10 Cycloalkenyl, C6-C 10 Aryl, one or more R 4-a-1 Substituted C1-C6 alkyl, one or more R 4- a-2 Substituted C3-C 10 Cycloalkyl, one or more R 4-a-3 substituted 3-10 membered heterocycloalkyl, substituted by one or more R 4-a-4 substituted 3-10 membered heterocycloalkenyl, substituted by one or more R 4-a-5 substituted 5-10 membered heteroaryl, substituted by one or more R 4-a-6 Substituted C3-C 10 Cycloalkenyl or one or more R 4-a-7 Substituted C6-C 10 Aryl; the 3-10 membered heterocycloalkyl, 3-10 membered heterocycloalkenyl, 5-10 membered heteroaryl, one or more R 4-a-3 The 3-10 membered heterocycloalkyl in the substituted 3-10 membered heterocycloalkyl is replaced by one or more R 4-a-4 The 3-10 membered heterocycloalkenyl in the substituted 3-10 membered heterocycloalkenyl and the 3-10 membered heterocycloalkenyl replaced by one or more R 4-a-5 The heteroatoms in the 5-10 membered heteroaryl group of the substituted 5-10 membered heteroaryl group are each independently selected from one or more of N, O and S, and the number of heteroatoms is each independently 1, 2 or 3;

[0126] R 4-a-1 、R 4-a-2 、R 4-a-3 、R 4-a-4 、R 4-a-5 、R 4-a-6 and R 4-a-7 Each is independently halogen, =O, cyano, -C(O)CH3, -C(O)NH2, -OH, halogenated C1-C6 alkyl, -N(R 8 )2, -SCH3, -SO2CH3, C1-C6 alkyl, C3-C 10Cycloalkyl, 3-10 membered heterocycloalkyl or 3-10 membered heterocycloalkenyl; the heteroatoms in the 3-10 membered heterocycloalkyl and 3-10 membered heterocycloalkenyl are each independently selected from one or more of N, O and S, and the number of heteroatoms is each independently 1, 2 or 3;

[0127] R 8 are independently hydrogen, -C(O)N(R 10 )2、-C(O)R 10 , C1-C6 alkyl, C3-C 10 Cycloalkyl, 3-10 membered heterocycloalkyl, 3-10 membered heterocycloalkenyl, 5-10 membered heteroaryl, substituted by one or more R 8a Substituted C1-C6 alkyl, one or more R 8b Substituted C3-C 10 Cycloalkyl, one or more R 8c substituted 3-10 membered heterocycloalkyl, substituted by one or more R 8d substituted 3-10 membered heterocycloalkenyl or one or more R 8e substituted 5-10 membered heteroaryl; the 3-10 membered heterocycloalkyl, 3-10 membered heterocycloalkenyl, 5-10 membered heteroaryl, substituted by one or more R 8c The 3-10 membered heterocycloalkyl in the substituted 3-10 membered heterocycloalkyl is replaced by one or more R 8d The 3-10 membered heterocycloalkenyl in the substituted 3-10 membered heterocycloalkenyl and the 3-10 membered heterocycloalkenyl replaced by one or more R 8e The heteroatoms in the 5-10 membered heteroaryl group of the substituted 5-10 membered heteroaryl group are each independently selected from one or more of N, O and S, and the number of heteroatoms is each independently 1, 2 or 3;

[0128] R 8a 、R 8b 、R 8c 、R 8d and R 8e are independently halogen, cyano, -C(O)R 10 、-C(O)N(R 10 )2、-OH、C1-C6 alkyl-O-、-N(R 10 )2、-SO2N(R 10 )2, -SO2R 10 , C1-C6 alkyl, C3-C 10 Cycloalkyl, 3-10 membered heterocycloalkyl, 3-10 membered heterocycloalkenyl, 5-10 membered heteroaryl, substituted by one or more R 8-a Substituted C1-C6 alkyl, one or more R 8-b Substituted C3-C 10 Cycloalkyl, one or more R 8-csubstituted 3-10 membered heterocycloalkyl, substituted by one or more R 8-d substituted 3-10 membered heterocycloalkenyl or one or more R 8-e substituted 5-10 membered heteroaryl; the 3-10 membered heterocycloalkyl, 3-10 membered heterocycloalkenyl, 5-10 membered heteroaryl, substituted by one or more R 8-c The 3-10 membered heterocycloalkyl in the substituted 3-10 membered heterocycloalkyl is replaced by one or more R 8-d The 3-10 membered heterocycloalkenyl in the substituted 3-10 membered heterocycloalkenyl and the 3-10 membered heterocycloalkenyl replaced by one or more R 8-e The heteroatoms in the 5-10 membered heteroaryl group of the substituted 5-10 membered heteroaryl group are each independently selected from one or more of N, O and S, and the number of heteroatoms is each independently 1, 2 or 3;

[0129] R 8-a 、R 8-b 、R 8-c 、R 8-d and R 8-e are independently halogen, cyano, -C(O)R 10 、-C(O)N(R 10 )2、-OH、C1-C6 alkyl-O-、-N(R 10 )2、-SO2N(R 10 )2、-SO2(R 10 ), C1-C6 alkyl, C3-C 10 Cycloalkyl, 3-10 membered heterocycloalkyl, 3-10 membered heterocycloalkenyl, 5-10 membered heteroaryl, substituted by one or more R 8-a-1 Substituted C1-C6 alkyl, one or more R 8-a-2 Substituted C3-C 10 Cycloalkyl, one or more R 8-a-3 substituted 3-10 membered heterocycloalkyl, substituted by one or more R 8-a-4 substituted 3-10 membered heterocycloalkenyl or one or more R 8-a-5 substituted 5-10 membered heteroaryl; the 3-10 membered heterocycloalkyl, 3-10 membered heterocycloalkenyl, 5-10 membered heteroaryl, substituted by one or more R 8-a-3 The 3-10 membered heterocycloalkyl in the substituted 3-10 membered heterocycloalkyl is replaced by one or more R 8-a-4 The 3-10 membered heterocycloalkenyl in the substituted 3-10 membered heterocycloalkenyl and the 3-10 membered heterocycloalkenyl replaced by one or more R 8-a-5 The heteroatoms in the 5-10 membered heteroaryl group of the substituted 5-10 membered heteroaryl group are each independently selected from one or more of N, O and S, and the number of heteroatoms is each independently 1, 2 or 3;

[0130] R 8-a-1 、R8-a-2 、R 8-a-3 、R 8-a-4 and R 8-a-5 are independently halogen, cyano, -C(O)R 10 、-C(O)N(R 10 )2、-OH、-OCH3、-N(R 10 )2、-SO2N(R 10 )2, -SO2R 10 , C1-C6 alkyl or halogenated C1-C6 alkyl;

[0131] R 10 are independently hydrogen, C1-C6 alkyl, halogenated C1-C6 alkyl, C3-C 10 Cycloalkyl or 3-10 membered heterocycloalkyl;

[0132] R 11 are independently -NH2 or C1-C6 alkyl;

[0133] R 5 and R 6 are independently hydrogen, halogen, -N(R 8 )2, 3-10 membered heterocycloalkyl, C1-C6 alkyl, 3-10 membered heterocycloalkenyl, C3-C 10 Cycloalkyl, C3-C 10 Cycloalkenyl, 5-10 membered heteroaryl, C6-C 10 Aryl, one or more R 5a Substituted C1-C6 alkyl, one or more R 5b substituted 3-10 membered heterocycloalkyl, substituted by one or more R 5c substituted 3-10 membered heterocycloalkenyl, substituted by one or more R 5d Substituted C3-C 10 Cycloalkyl, one or more R 5e Substituted C3-C 10 Cycloalkenyl, one or more R 5f substituted 5-10 membered heteroaryl or one or more R 5g Substituted C6-C 10 Aryl; the 3-10 membered heterocycloalkyl, 3-10 membered heterocycloalkenyl, 5-10 membered heteroaryl, one or more R 5b The 3-10 membered heterocycloalkyl in the substituted 3-10 membered heterocycloalkyl is replaced by one or more R 5c The 3-10 membered heterocycloalkenyl in the substituted 3-10 membered heterocycloalkenyl and the 3-10 membered heterocycloalkenyl replaced by one or more R 5fThe heteroatoms in the 5-10 membered heteroaryl group of the substituted 5-10 membered heteroaryl group are each independently selected from one or more of N, O and S, and the number of heteroatoms is each independently 1, 2 or 3;

[0134] R 5a 、R 5b 、R 5c 、R 5d 、R 5e 、R 5f and R 5g Each is independently halogen, =O, cyano, -OH, C1-C6 alkyl-O-, C1-C6 alkyl or halogenated C1-C6 alkyl;

[0135] R 4 and R 5 It can also form a 3-10 membered saturated heterocyclic ring, a 5-10 membered heteroaromatic ring, a 3-10 membered heterocyclic alkene, or one or more R 4h substituted 3-10 membered saturated heterocyclic ring, replaced by one or more R 4i Substituted 3-10 membered heterocyclic olefins or one or more R 4j substituted 5-10 membered heteroaromatic ring; the 3-10 membered saturated heterocyclic ring, 3-10 membered heterocyclic alkene, 5-10 membered heteroaromatic ring, substituted by one or more R 4h The 3-10 membered saturated heterocyclic ring in the substituted 3-10 membered saturated heterocyclic ring is replaced by one or more R 4i The 3-10 membered heterocyclic olefin in the substituted 3-10 membered heterocyclic olefin and the substituted 3-10 membered heterocyclic olefin are replaced by one or more R 4j The heteroatoms in the 5-10 membered heteroaromatic ring of the substituted 5-10 membered heteroaromatic ring are each independently selected from one or more of N, O and S, and the number of heteroatoms is each independently 1, 2 or 3;

[0136] R 4h 、R 4i and R 4j are each independently halogen, =O, cyano, -OH, -N(R 8 )2、-SR 11 、-SO2R 11 、-C(O)N(R 10 )2, - C(O)R 10 , C1-C6 alkyl or one or more R 4-h Substituted C1-C6 alkyl;

[0137] R 4-h are independently halogen, =O, cyano or -N(R 8 )2;

[0138] R 1 C6-C 10Aryl, 5-10 membered heteroaryl, substituted by one or more R 1a Substituted C6-C 10 Aryl or one or more R 1b substituted 5-10 membered heteroaryl; said 5-10 membered heteroaryl and one or more R 1b The heteroatoms in the 5-10 membered heteroaryl group of the substituted 5-10 membered heteroaryl group are each independently selected from one or more of N, O and S, and the number of heteroatoms is each independently 1, 2 or 3;

[0139] R 1a and R 1b Each is independently deuterium, halogen, -OH, -CN, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, 5-10 membered heteroaryl, C1-C6 alkyl-O-, C1-C6 alkyl-S-, -N(R 8 )2、-(CH2)-C(=O)N(R 8 )2. C3-C 10 Cycloalkyl, one or more R 1-a Substituted C1-C6 alkyl, one or more R 1-b Substituted C1-C6 alkyl-O-, one or more R 1-c Substituted C1-C6 alkyl-S-, one or more R 1-d Substituted C2-C6 alkenyl, one or more R 1-e Substituted C2-C6 alkynyl, one or more R 1-f Substituted C3-C 10 Cycloalkyl or one or more R 1-g substituted 5-10 membered heteroaryl; said 5-10 membered heteroaryl and one or more R 1-g The heteroatoms in the 5-10 membered heteroaryl group of the substituted 5-10 membered heteroaryl group are each independently selected from one or more of N, O and S, and the number of heteroatoms is each independently 1, 2 or 3;

[0140] R 1-a 、R 1-b 、R 1-c 、R 1-d 、R 1-e 、R 1-f and R 1-g Each is independently deuterium, halogen, -CN, -OH, C1-C4 alkyl, C1-C4 alkyl-O- or C3-C 10 Cycloalkyl;

[0141] L is -O-(CR 9 R 9 ) n1 -、-S-(CR9 R 9 ) n2 -、-N(R 8 )-(CR 9 R 9 ) n3 -、-SO-(CR 9 R 9 ) n4 -or-SO2-(CR 9 R 9 ) n5 -;

[0142] R 9 are independently hydrogen, halogen, -CN, C1-C6 alkyl, C1-C6 alkyl-O-, deuterated C1-C6 alkyl, or 5-10 membered heteroaryl;

[0143] n1, n2, n3, n4 and n5 are each independently 0, 1, 2 or 3; (when 0, it represents a connecting bond);

[0144] R 2 is hydrogen, -COOH, C1-C6 alkyl, C1-C6 alkyl-O-, C3-C 10 Cycloalkyl, C3-C 10 Cycloalkenyl, 4-10 membered heterocycloalkyl, C6-C 10 Aryl, 5-10 membered heteroaryl, -NHC(=NH)NH2, -C(O)N(R 8 )2、-(CH2OR 10 )(CH2) n6 OR 10 、-NR 8 C(=O)-C6-C 10 Aryl, -C(=O)O-C1-C6 alkyl, one or more R 2a Substituted C3-C 10 Cycloalkyl, one or more R 2b Substituted C3-C 10 Cycloalkenyl, one or more R 2c substituted 4-10 membered heterocycloalkyl, substituted by one or more R 2d Substituted C6-C 10 Aryl or one or more R 2e substituted 5-10 membered heteroaryl; said 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, substituted by one or more R 2c The 4-10 membered heterocycloalkyl in the substituted 4-10 membered heterocycloalkyl and the substituted 4-10 membered heterocycloalkyl 2eThe heteroatoms in the 5-10 membered heteroaryl group of the substituted 5-10 membered heteroaryl group are each independently selected from one or more of N, O and S, and the number of heteroatoms is each independently 1, 2 or 3;

[0145] n6 is 0, 1, 2, or 3;

[0146] R 2a 、R 2b 、R 2c 、R 2d and R 2e Each is independently halogen, -OH, deuterium, -CN, -C(=O)H, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 alkyl-O-, -N(R 8 )2、(C l -C4 alkyl)-C(=O)-, oxo(=O), -SO2F, (C l -C4 alkyl)-SO2-, (C l -C4 alkyl)-O-(C l -C4 alkyl)-O-, -CH2OC(=O)N(R 8 )2、(C l -C4 alkyl)-OC(=O)-NHCH2-, -CH2NHC(=O)N(R 8 )2、(C l -C4 alkyl)-C(=O)NHCH2-, (pyrazolyl)-CH2-, (C l -C4 alkyl)-SO2-NHCH2-, (4-10 membered heterocycloalkyl)-C(=O)-OCH2-, (R 8 )2N-C(=O)-O-、(C l -C4 alkyl)-O-(C l -C4 alkyl)-NH-C(=O)-O-, phenyl-C(=O)NH-, phenyl-(C l -C4 alkyl)-NH-C(=O)-O-, (4-10 membered heterocycloalkyl)-C(=O)-O-, (4-10 membered heterocycloalkyl)-CH2-, 2-a Substituted C1-C4 alkyl or one or more R 2-b Substituted C1-C4 alkyl-O-; the phenyl-C(=O)NH- and phenyl-(C lwherein the phenyl group in the (4-10 membered heterocycloalkyl)-C(=O)-OCH2-, (4-10 membered heterocycloalkyl)-C(=O)-O- and (4-10 membered heterocycloalkyl)-CH2- is optionally substituted with ═O, halogen, -CN or -OH; the heteroatoms in the 4-10 membered heterocycloalkyl group in the (4-10 membered heterocycloalkyl)-C(=O)-OCH2-, (4-10 membered heterocycloalkyl)-C(=O)-O- and (4-10 membered heterocycloalkyl)-CH2- are each independently selected from one or more of N, O and S, and the number of heteroatoms is each independently 1, 2 or 3;

[0147] R 2-a and R 2-b are each independently deuterium, -CN, halogen or -OH;

[0148] R 3 H, deuterium, -N(R 8 )2, halogen, -OH, C1-C6 alkyl, -CN, halo-C1-C6 alkyl, deuterated C1-C6 alkyl, C1-C6 alkyl-O-, deuterated C1-C6 alkyl-O-, C2-C6 alkenyl or C2-C6 alkynyl.

[0149] In certain preferred embodiments of the present invention, certain groups in the heterocyclic compound represented by Formula I, its pharmaceutically acceptable salt, its solvate or the solvate of its pharmaceutically acceptable salt are defined as follows. The unmentioned groups are the same as those described in any embodiment of the present invention (referred to as "in a certain embodiment of the present invention").

[0150] In one embodiment of the present invention, each "C1-C6 alkyl" can independently be methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, n-pentyl, For example, methyl, ethyl, isopropyl,

[0151] In one embodiment of the present invention, each "C2-C6 alkenyl" may independently be a C2-C4 alkenyl, such as vinyl, allyl or propenyl.

[0152] In a certain embodiment of the present invention, each "C2-C6 alkynyl" may independently be a C2-C4 alkynyl, such as ethynyl, propargyl or propynyl.

[0153] In one embodiment of the present invention, each "halogen" can independently be F, Cl, Br or I, such as F, Cl or Br, further such as F or Cl, and further such as F.

[0154] In one embodiment of the present invention, each "C3-C 10 "Cycloalkyl" may independently be cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl, for example cyclopropyl, cyclobutyl or cyclopentyl.

[0155] In one embodiment of the present invention, each "3-10 membered heterocycloalkyl" may independently be a 4-, 5- or 6-membered heterocycloalkyl group having one or two heteroatoms selected from N and O, such as azetidinyl, oxetanyl, tetrahydropyrrolyl, tetrahydrofuranyl, piperidinyl, tetrahydropyranyl, tetrahydroimidazolyl, morpholinyl or piperazinyl, more preferably oxetanyl, tetrahydropyranyl or morpholinyl, preferably More preferably More preferably

[0156] In one embodiment of the present invention, each "C3-C 10 The "cycloalkenyl" group may independently be cyclopropenyl, cyclobutenyl, cyclobutadienyl, cyclopentenyl, cyclopentadienyl, cyclohexenyl or cyclohexadienyl.

[0157] In one embodiment of the present invention, each "3-10 membered heterocycloalkenyl" may be independently a heteroatom selected from one or both of N and O, and the number of heteroatoms is independently 1 or 2 5-10 membered heterocycloalkenyl, such as a 5-membered heterocycloalkenyl or a 6-membered heterocycloalkenyl, more such as a dihydropyrrolyl, a dihydrofuranyl, a dihydropyranyl, a dihydropyridinyl, a tetrahydropyridinyl, Preferred

[0158] In one embodiment of the present invention, each "3-10 membered heterocycloalkenyl" may be independently a heteroatom selected from one or both of N and O, and the number of heteroatoms is independently 1 or 2 5-10 membered heterocycloalkenyl, such as a 5-membered heterocycloalkenyl or a 6-membered heterocycloalkenyl, more preferably a dihydropyrrolyl, dihydrofuranyl, dihydropyranyl, dihydropyridinyl or tetrahydropyridinyl, preferably

[0159] In one embodiment of the present invention, each "5-10 membered heteroaryl" can independently be a heteroatom selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3 5-6 membered monocyclic heteroaryl or 8-10 membered bicyclic heteroaryl, such as 5-6 membered monocyclic heteroaryl or 9 membered bicyclic heteroaryl, further such as pyrrolyl, furyl, thienyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl , imidazolyl, 1,2,3-triazolyl, 1,2,4-triazolyl, 1,2,3-triazinyl, 1,3,5-s-triazinyl, 1,3,4-triazinyl (1,2,4-triazinyl), quinolyl, isoquinolyl, 1H-pyrazolo[4,3-c]pyridinyl, 1H-pyrrolo[3,2-c]pyridinyl, 7H-pyrrolo[2,3-d]pyrimidinyl, indolyl, isoindolyl, indazolyl, benzothiophenyl or benzothiazolyl, preferably Further optimization

[0160] In one embodiment of the present invention, each "5-10 membered heteroaryl" can independently be a heteroatom selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3 5-6 membered monocyclic heteroaryl or 8-10 membered bicyclic heteroaryl, such as 5-6 membered monocyclic heteroaryl or 9 membered bicyclic heteroaryl, further such as pyrrolyl, furyl, thienyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, pyridyl, pyridazinyl, pyrimidin ... pyridyl, pyrazinyl, imidazolyl, 1,2,3-triazolyl, 1,2,4-triazolyl, 1,2,3-triazinyl, 1,3,5-s-triazinyl, 1,3,4-triazinyl, quinolyl, isoquinolyl, 1H-pyrazolo[4,3-c]pyridinyl, 1H-pyrrolo[3,2-c]pyridinyl, 7H-pyrrolo[2,3-d]pyrimidinyl, indolyl, isoindolyl, indazolyl, benzothiophenyl or benzothiazolyl, preferably

[0161] In one embodiment of the present invention, each "5-10 membered heteroaryl" can independently be one or more heteroatoms selected from N, O and S, and the number of heteroatoms is 1 or 2 5-10 membered heteroaryl, such as pyrrolyl, furyl, thienyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, quinolyl or isoquinolyl, preferably pyridinyl, for example

[0162] In one embodiment of the present invention, each "C6-C 10 "Aryl" may independently be phenyl or naphthyl, for example phenyl.

[0163] In one embodiment of the present invention, each "3-10 membered saturated heterocycle" can independently be a 3-6 membered saturated heterocycle having one or two heteroatoms selected from N and O, and having 1, 2 or 3 heteroatoms, such as azetidine, oxetane, tetrahydropyrrole ring, tetrahydrofuran ring, piperidine ring, tetrahydropyran ring, morpholine ring or piperazine ring, and more preferably

[0164] In one embodiment of the present invention, each "3-10 membered saturated heterocycle" can independently be a 3-6 membered saturated heterocycle having one or two heteroatoms selected from N and O, and having 1, 2 or 3 heteroatoms, such as azetidine, oxetane, tetrahydropyrrole ring, tetrahydrofuran ring, piperidine ring, tetrahydropyran ring, morpholine ring, piperazine ring or 1,4-oxazaalkane ring, more such as Preferred

[0165] In one embodiment of the present invention, each "5-10 membered heteroaromatic ring" can independently be a heteroatom selected from one or more of N, O and S, and the number of heteroatoms is 1 or 2 5-10 membered heteroaromatic rings, such as pyrrole ring, furan ring, thiophene ring, pyrazole ring, oxazole ring, isoxazole ring, thiazole ring, isothiazole ring, pyridine ring, pyridazine ring, pyrimidine ring, pyrazine ring, quinoline ring or isoquinoline ring, further such as Preferred

[0166] In one embodiment of the present invention, each "3-10 membered heterocyclic alkene" may independently be a 5-10 membered heterocyclic alkene having one or both heteroatoms selected from N and O, and the number of heteroatoms is independently 1 or 2, such as a 5-membered heterocyclic alkene or a 6-membered heterocyclic alkene, and more preferably dihydropyrrole, dihydrofuran, dihydropyran, dihydropyridine or tetrahydropyridine.

[0167] In a certain embodiment of the present invention, each "4-10 membered heterocycloalkyl" can be independently a heteroatom selected from one or both of N and O, and the number of heteroatoms is 1 or 2, a 4-6 membered monocyclic or 8-10 membered bicyclic heterocycloalkyl, such as a 4-6 membered monocyclic heterocycloalkyl, an 8-10 membered cyclic heterocycloalkyl, an 8-10 membered bridged heterocycloalkyl or an 8-10 membered spirocyclic heterocycloalkyl, further such as azetidinyl, oxetane, tetrahydropyrrole yl, tetrahydroimidazolyl, tetrahydrofuranyl, piperidinyl, tetrahydropyranyl, morpholinyl, piperazinyl, hexahydro-1H-pyrrolizinyl, 1-azabicyclo[2.2.2]octyl or azaspiro[3.4]octyl, preferably hexahydro-1H-pyrrolizinyl, tetrahydropyrrolyl, morpholinyl, tetrahydrofuranyl, piperidinyl, piperazinyl, 1-azabicyclo[2.2.2]octyl, azaspiro[3.4]octyl or azetidinyl, for example

[0168] In a certain embodiment of the present invention, each "4-10 membered heterocycloalkyl" can independently be a heteroatom selected from one or both of N and O, and the number of heteroatoms is 1 or 2 4-6 membered monocyclic or 8-10 membered bicyclic heterocycloalkyl, such as 4-6 membered monocyclic heterocycloalkyl, 8-10 membered bicyclic heterocycloalkyl, 8-10 membered bridged heterocycloalkyl or 8-10 membered spirocyclic heterocycloalkyl, further such as azetidinyl, oxetanyl, tetrahydropyrrolyl, tetrahydroimidazolyl, tetrahydrofuranyl, piperidinyl, tetrahydropyranyl, morpholinyl, piperazinyl, hexahydro-1H-pyrrolizinyl or 1-azabicyclo[2.2.2]octyl, preferably hexahydro-1H-pyrrolizinyl, tetrahydropyrrolyl, morpholinyl, tetrahydrofuranyl, piperidinyl, piperazinyl or 1-azabicyclo[2.2.2]octyl, such as

[0169] In one embodiment of the present invention, each "4-10 membered heterocycloalkyl" may independently be a 4-6 membered monocyclic or 8-10 membered bicyclic heterocycloalkyl group having one or two heteroatoms selected from N and O, such as azetidinyl, oxetanyl, tetrahydropyrrolyl, tetrahydrofuranyl, piperidinyl, tetrahydropyranyl, morpholinyl, piperazinyl, hexahydro-1H-pyrrolizinyl, preferably hexahydro-1H-pyrrolizinyl, tetrahydropyrrolyl or morpholinyl, for example

[0170] In one embodiment of the present invention, each "4-10 membered heterocycloalkyl" may independently be a 4-6 membered monocyclic or 8-10 membered bicyclic heterocycloalkyl group having one or two heteroatoms selected from N and O, such as azetidinyl, oxetanyl, tetrahydropyrrolyl, tetrahydrofuranyl, piperidinyl, tetrahydropyranyl, morpholinyl, piperazinyl, hexahydro-1H-pyrrolizinyl, preferably hexahydro-1H-pyrrolizinyl, tetrahydropyrrolyl or morpholinyl, for example

[0171] In one embodiment of the present invention, the 5-10 membered heteroaromatic ring in each "5-10 membered heteroaromatic ring and 3-10 membered heterocycloalkyl" can independently be a heteroatom selected from one or more of N, O and S, and the number of heteroatoms is 1 or 2 5-10 membered heteroaromatic rings, such as a pyrrole ring, a furan ring, a thiophene ring, a pyrazole ring, an oxazole ring, an isoxazole ring, a thiazole ring, an isothiazole ring, a pyridine ring, a pyridazine ring, a pyrimidine ring, a pyrazine ring, a quinoline ring or an isoquinoline ring, preferably a pyridine ring.

[0172] In one embodiment of the present invention, the 3-10 membered heterocycloalkyl in each "5-10 membered heteroaromatic ring and 3-10 membered heterocycloalkyl" can be independently a 4-membered, 5-membered or 6-membered heterocycloalkyl with one or two heteroatoms selected from N and O, such as azetidinyl, oxetanyl, tetrahydropyrrolyl, tetrahydrofuranyl, piperidinyl, tetrahydropyranyl, tetrahydroimidazolyl, morpholinyl, piperazinyl or More example is piperazinyl or Preferably

[0173] In one embodiment of the present invention, each "5-10 membered heteroaromatic ring and 3-10 membered heterocycloalkyl" is For example

[0174] In one embodiment of the present invention, each "C l "-C4 alkyl" may independently be methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl or tert-butyl, for example methyl, ethyl or n-propyl.

[0175] In one embodiment of the present invention, each "C2-C4 alkenyl" may independently be ethenyl, propenyl or allyl.

[0176] In one embodiment of the present invention, each "C2-C4 alkynyl" may independently be ethynyl, propynyl or propargyl.

[0177] In one embodiment of the present invention, each "halo" can be independently substituted by F, Cl, Br or I.

[0178] In one embodiment of the present invention, X is independently -C(R 7 )2-、-CR 7 =CR 7 -, -N=N- and -CR 7 =N-,R 7 are independently hydrogen or C1-C6 alkyl, n is 1, 2 or 3; preferably, when n is 2 or 3, X is independently a -C(R 7 )2-, when n is 1, X is a -CR 7 =CR 7 -、 a -N=N-, a -CR 7 =N- or a -N=CR 7 -, R 7 are independently hydrogen or C1-C6 alkyl, wherein a side and The N atoms in the .

[0179] In one embodiment of the present invention, X is independently -C(R 7 )2-、-CR 7 =CR 7 -or-CR 7 =N-,R 7 are independently hydrogen or C1-C6 alkyl, n is 1, 2 or 3; preferably, when n is 2 or 3, X is independently a -C(R 7 )2-, when n is 1, X is independently -CR 7 =CR 7 -or a - N=CR 7 -, R 7 are independently hydrogen or C1-C6 alkyl, wherein a side and The N atoms in the .

[0180] In one embodiment of the present invention, X is independently -C(R 7 )2-、-CR 7 =CR 7 -, -N=N- and -CR 7 =N-,R 7 are independently hydrogen, n is 1, 2 or 3; preferably, when n is 2 or 3, X is independently a -C(R 7 )2-, when n is 1, X is a -CR 7 =CR 7 -、 a -N=N-,a -CR 7 =N- or a -N=CR 7 -, R 7 are independently hydrogen, wherein a side and More preferably, when n is 2 or 3, X is independently a -C(R 7 )2-, when n is 1, X is a -CR 7 =CR 7 -、 a -N=N- and a -CR 7 =N-, where side a and The N atoms in R 7 are independently hydrogen.

[0181] In one embodiment of the present invention, L is absent, -O-(CR 9 R 9 ) n1 -、-S-(CR 9 R 9 ) n2 -or-N(R 8 )-(CR 9 R 9 ) n3 -, R 8 are independently hydrogen, R 9 are independently hydrogen or C1-C6 alkyl, n1, n2 and n3 are each independently 0 or 1; preferably, L is absent or -O-(CR 9 R 9 ) n1 -, R 9 are independently hydrogen or C1-C6 alkyl, and n1 is 0 or 1.

[0182] In one embodiment of the present invention, L is -O-(CR 9 R 9 ) n1 -、-S-(CR 9 R 9 ) n2 -or-N(R 8 )-(CR 9 R 9 ) n3 -, R 8 are independently hydrogen, R 9 are independently hydrogen or C1-C6 alkyl, n1, n2 and n3 are each independently 0 or 1; preferably, L is -O-(CR 9 R 9 ) n1-, R 9 are independently hydrogen or C1-C6 alkyl, n1 is 0 or 1; more preferably, L is -O-(CR 9 R 9 ) n1 - b , R 9 is independently hydrogen or C1-C6 alkyl, n1 is 0 or 1, wherein the b side is connected to R 2 connected.

[0183] In one embodiment of the present invention, L is -O-(CR 9 R 9 ) n1 -、-S-(CR 9 R 9 ) n2 -or-N(R 8 )-(CR 9 R 9 ) n3 -, R 8 are independently hydrogen, R 9 are independently hydrogen, n1, n2 and n3 are each independently 0 or 1; preferably, L is -O-(CR 9 R 9 ) n1 -, R 9 are independently hydrogen, and n1 is 0 or 1.

[0184] In one embodiment of the present invention, R 2 For hydrogen, C3-C 10 Cycloalkyl, 4-10 membered heterocycloalkyl, 2a Substituted C3-C 10 Cycloalkyl or one or more R 2c Substituted 4-10 membered heterocycloalkyl, R 2a is independently (4-10 membered heterocycloalkyl)-CH2-, wherein the 4-10 membered heterocycloalkyl in the (4-10 membered heterocycloalkyl)-CH2- is optionally replaced by C l -C6 alkyl substituted, R 2c are independently halogen, C1-C4 alkyl, ═CR 2-c R 2-c 、C1-C4 alkyl-O-、-N(R 8 )2、(C l -C4 alkyl)-O-(C l -C4 alkyl)-, 4-10 membered heterocycloalkyl or one or more R 2- d Substituted 4-10 membered heterocycloalkyl, R 8 independently H, R 2-c and R 2-dare independently halogen;

[0185] Preferably, R 2 is hydrogen, 4-10 membered heterocycloalkyl, 2a Substituted C3-C 10 Cycloalkyl or one or more R 2c Substituted 4-10 membered heterocycloalkyl, R 2a is independently (4-10 membered heterocycloalkyl)-CH2-, wherein the 4-10 membered heterocycloalkyl in the (4-10 membered heterocycloalkyl)-CH2- is optionally replaced by C l -C6 alkyl substituted, R 2c are independently halogen, C1-C4 alkyl, ═CR 2-c R 2-c 、C1-C4 alkyl-O-、-N(R 8 )2、(C l -C4 alkyl)-O-(C l -C4 alkyl)- or 4-10 membered heterocycloalkyl, R 8 independently H, R 2-c are independently halogen;

[0186] More preferably, R 2 is a 4-10 membered heterocycloalkyl group, 2a Substituted C3-C 10 Cycloalkyl or one or more R 2c Substituted 4-10 membered heterocycloalkyl, R 2a is independently (4-10 membered heterocycloalkyl)-CH2-, wherein the 4-10 membered heterocycloalkyl in the (4-10 membered heterocycloalkyl)-CH2- is optionally replaced by C l -C6 alkyl substituted, R 2c are independently halogen, C1-C4 alkyl, C1-C4 alkyl-O-, -N(R 8 )2、(C l -C4 alkyl)-O-(C l -C4 alkyl)- or 4-10 membered heterocycloalkyl, R 8 independently H, R 2-c are independently halogen.

[0187] In one embodiment of the present invention, R 2 is a 4-10 membered heterocycloalkyl group, 2a Substituted C3-C 10 Cycloalkyl or one or more R 2c Substituted 4-10 membered heterocycloalkyl; R 2ais independently (4-10 membered heterocycloalkyl)-CH2-, wherein the 4-10 membered heterocycloalkyl in the (4-10 membered heterocycloalkyl)-CH2- is optionally replaced by C l -C6 alkyl substituted; R 2c are independently halogen, ═CR 2-c R 2-c 、C1-C4 alkyl、C1-C4 alkyl-O-、-N(R 8 )2 or (C l -C4 alkyl)-O-(C l -C4 alkyl)-, R 8 independently H, R 2-c are independently halogen.

[0188] In one embodiment of the present invention, R 2 For hydrogen, C3-C 10 Cycloalkyl, 4-10 membered heterocycloalkyl, 2a Substituted C3-C 10 Cycloalkyl or one or more R 2c Substituted 4-10 membered heterocycloalkyl, R 2a is independently (4-10 membered heterocycloalkyl)-CH2-, wherein the 4-10 membered heterocycloalkyl in the (4-10 membered heterocycloalkyl)-CH2- is optionally replaced by C l -C6 alkyl substituted, R 2c are independently halogen, C1-C4 alkyl, ═CR 2-c R 2-c 、C1-C4 alkyl-O-、-N(R 8 )2 or (C l -C4 alkyl)-O-(C l -C4 alkyl)-, R 8 independently H, R 2-c are independently halogen;

[0189] Preferably, R 2 is hydrogen, 4-10 membered heterocycloalkyl, 2a Substituted C3-C 10 Cycloalkyl or one or more R 2c Substituted 4-10 membered heterocycloalkyl, R 2a is independently (4-10 membered heterocycloalkyl)-CH2-, wherein the 4-10 membered heterocycloalkyl in the (4-10 membered heterocycloalkyl)-CH2- is optionally replaced by C l -C6 alkyl substituted, R 2c are independently halogen, C1-C4 alkyl, ═CR 2-c R 2-c 、C1-C4 alkyl-O-、-N(R 8 )2 or (Cl -C4 alkyl)-O-(C l -C4 alkyl)-, R 8 independently H, R 2-c are independently halogen;

[0190] More preferably, R 2 is a 4-10 membered heterocycloalkyl group, 2a Substituted C3-C 10 Cycloalkyl or one or more R 2c Substituted 4-10 membered heterocycloalkyl, R 2a is independently (4-10 membered heterocycloalkyl)-CH2-, wherein the 4-10 membered heterocycloalkyl in the (4-10 membered heterocycloalkyl)-CH2- is optionally replaced by C l -C6 alkyl substituted, R 2c are independently halogen, C1-C4 alkyl, C1-C4 alkyl-O-, -N(R 8 )2 or (C l -C4 alkyl)-O-(C l -C4 alkyl)-, R 8 are independently H.

[0191] In one embodiment of the present invention, R 2 For hydrogen, C3-C 10 Cycloalkyl, one or more R 2a Substituted C3-C 10 Cycloalkyl, 4-10 membered heterocycloalkyl or one or more R 2c Substituted 4-10 membered heterocycloalkyl, R 2a are independently (4-10 membered heterocycloalkyl)-CH2-, R 2c are independently halogen or C1-C4 alkyl;

[0192] Preferably, R 2 is hydrogen, one or more R 2a Substituted C3-C 10 Cycloalkyl or one or more R 2c Substituted 4-10 membered heterocycloalkyl, R 2a are independently (4-10 membered heterocycloalkyl)-CH2-, R 2c are independently halogen or C1-C4 alkyl.

[0193] In one embodiment of the present invention, R 2 For hydrogen, C3-C 10 Cycloalkyl, one or more R 2a Substituted C3-C 10 Cycloalkyl, 4-10 membered heterocycloalkyl or one or more R 2cSubstituted 4-10 membered heterocycloalkyl, R 2a are independently (4-10 membered heterocycloalkyl)-CH2-, R 2c are independently halogen;

[0194] Preferably, R 2 is hydrogen, one or more R 2a Substituted C3-C 10 Cycloalkyl or one or more R 2c Substituted 4-10 membered heterocycloalkyl, R 2a are independently (4-10 membered heterocycloalkyl)-CH2-, R 2c are independently halogen.

[0195] In one embodiment of the present invention, L is absent; R 2 is a 4-10 membered heterocycloalkyl group or is replaced by one or more R 2c Substituted 4-10 membered heterocycloalkyl; R 2c are independently C1-C4 alkyl, 4-10 membered heterocycloalkyl or substituted by one or more R 2-d Substituted 4-10 membered heterocycloalkyl, R 2- d are independently halogen; preferably, R 2 For one or more R 2c Substituted 4-10 membered heterocycloalkyl; R 2c are independently C1-C4 alkyl, 4-10 membered heterocycloalkyl or substituted by one or more R 2-d Substituted 4-10 membered heterocycloalkyl, R 2-d are independently halogen; more preferably, R 2 For one or more R 2c Substituted 4-10 membered heterocycloalkyl; R 2c are independently C1-C4 alkyl or 4-10 membered heterocycloalkyl.

[0196] In one embodiment of the present invention, L is -O-(CR 9 R 9 ) n1 -, R 2 For hydrogen, C3-C 10 Cycloalkyl, 4-10 membered heterocycloalkyl, 2a Substituted C3-C 10 Cycloalkyl or one or more R 2c Substituted 4-10 membered heterocycloalkyl, R 2a is independently (4-10 membered heterocycloalkyl)-CH2-, wherein the 4-10 membered heterocycloalkyl in the (4-10 membered heterocycloalkyl)-CH2- is optionally replaced by C l -C6 alkyl substituted, R 2care independently halogen, C1-C4 alkyl, ═CR 2-c R 2-c 、C1-C4 alkyl-O-、-N(R 8 )2 or (C l -C4 alkyl)-O-(C l -C4 alkyl)-, R 8 independently H, R 2-c are independently halogen;

[0197] Preferably, R 2 is hydrogen, 4-10 membered heterocycloalkyl, 2a Substituted C3-C 10 Cycloalkyl or one or more R 2c Substituted 4-10 membered heterocycloalkyl, R 2a is independently (4-10 membered heterocycloalkyl)-CH2-, wherein the 4-10 membered heterocycloalkyl in the (4-10 membered heterocycloalkyl)-CH2- is optionally replaced by C l -C6 alkyl substituted, R 2c are independently halogen, C1-C4 alkyl, ═CR 2-c R 2-c 、C1-C4 alkyl-O-、-N(R 8 )2 or (C l -C4 alkyl)-O-(C l -C4 alkyl)-, R 8 independently H, R 2-c are independently halogen;

[0198] More preferably, R 2 is a 4-10 membered heterocycloalkyl group, 2a Substituted C3-C 10 Cycloalkyl or one or more R 2c Substituted 4-10 membered heterocycloalkyl, R 2a is independently (4-10 membered heterocycloalkyl)-CH2-, wherein the 4-10 membered heterocycloalkyl in the (4-10 membered heterocycloalkyl)-CH2- is optionally replaced by C l -C6 alkyl substituted, R 2c are independently halogen, C1-C4 alkyl, C1-C4 alkyl-O-, -N(R 8 )2 or (C l -C4 alkyl)-O-(C l -C4 alkyl)-, R 8 independently H;

[0199] Optimally, R 2 For one or more R 2a Substituted C3-C 10Cycloalkyl or one or more R 2c Substituted 4-10 membered heterocycloalkyl, R 2a are independently (4-10 membered heterocycloalkyl)-CH2-, R 2c are independently halogen or C1-C4 alkyl.

[0200] In one embodiment of the present invention, R 1 C6-C 10 Aryl, 5-10 membered heteroaryl, 3-10 membered heterocycloalkyl, 1a Substituted C6-C 10 Aryl, one or more R 1b substituted 5-10 membered heteroaryl or one or more R 1c Substituted 3-10 membered heterocycloalkyl, R 1a are independently halogen, -OH or -N(R 8 )2,R 1b are independently halogen, -CN, -OH, C1-C6 alkyl, -N(R 8 )2 or by one or more R 1-a Substituted C1-C6 alkyl, R 1-a are independently halogen, R 8 is hydrogen, R 1c are independently C1-C6 alkyl, -CN or -N(R 8 )2, or two adjacent R 1c Together with the atoms to which they are attached, they form a 5-10 membered heteroaromatic ring, wherein the 5-10 membered heteroaromatic ring is optionally substituted by one or more of the following groups: -CN, -N(R 8 )2 or C1-C6 alkyl;

[0201] Preferably, R 1 For one or more R 1a Substituted C6-C 10 Aryl, one or more R 1b substituted 5-10 membered heteroaryl or one or more R 1c Substituted 3-10 membered heterocycloalkyl, R 1a are independently halogen, -OH or -N(R 8 )2,R 1b are independently halogen, -CN, -OH, C1-C6 alkyl, -N(R 8 )2 or by one or more R 1-a Substituted C1-C6 alkyl, R 1-a are independently halogen, R 8 is hydrogen, R 1c are independently C1-C6 alkyl, or two adjacent R 1cTogether with the atoms to which they are attached, they form a 5-10 membered heteroaromatic ring, wherein the 5-10 membered heteroaromatic ring is optionally substituted by one or more of the following groups: -CN or -N(R 8 )2;

[0202] More preferably, R 1 For one or more R 1a Substituted C6-C 10 Aryl or one or more R 1b Substituted 5-10 membered heteroaryl; R 1a are independently halogen, -OH or -N(R 8 )2,R 1b are independently halogen, -CN, C1-C6 alkyl, -N(R 8 )2 or by one or more R 1- a Substituted C1-C6 alkyl, R 1-a are independently halogen, R 8 is hydrogen;

[0203] Optimally, R 1 For one or more R 1b Substituted 5-10 membered heteroaryl; R 1b are independently halogen, -CN, C1-C6 alkyl, -N(R 8 )2 or by one or more R 1-a Substituted C1-C6 alkyl, R 1-a are independently halogen, R 8 For hydrogen.

[0204] In one embodiment of the present invention, R 1 is a 5-10 membered heteroaryl group or is replaced by one or more R 1b Substituted 5-10 membered heteroaryl, R 1b are independently halogen, -OH, C1-C6 alkyl, -N(R 8 )2 or by one or more R 1-a Substituted C1-C6 alkyl, R 1-a are independently halogen, R 8 is hydrogen;

[0205] Preferably, R 1 For one or more R 1b Substituted 5-10 membered heteroaryl, R 1b are independently C1-C6 alkyl, -N(R 8 )2 or by one or more R 1-a Substituted C1-C6 alkyl, R 1-a are independently halogen, R 8 For hydrogen.

[0206] In one embodiment of the present invention, R 3 is hydrogen, -N(R 8 )2, halogen, -OH, R 8 is hydrogen; preferably, R 3 It is a halogen.

[0207] In one embodiment of the present invention, Y is -NR 4 -, O, S or -(CH2) p NR 4 -, p is 1; preferably, Y is -NR 4 -, O or -(CH2) p NR 4 -, p is 1; more preferably, Y is -NR 4 -, O, or c -(CH2) p NR 4 -, p is 1, c side is -CHR 5 - connected; optimally, Y is -NR 4 -or c -(CH2) p NR 4 -, p is 1, c side is -CHR 5 - connected.

[0208] In one embodiment of the present invention, Y is -NR 4 -, O or S; preferably, Y is -NR 4 - or O.

[0209] In one embodiment of the present invention, R 4 are independently hydrogen, C1-C6 alkyl, C3-C 10 Cycloalkyl, 3-10 membered heterocycloalkyl, 5-10 membered heteroaryl, -SO2R h , 5-10 membered heteroaromatic ring and 3-10 membered heterocycloalkyl, one or more R 4a Substituted C1-C6 alkyl, one or more R 4b Substituted C3-C 10 Cycloalkyl, one or more R 4c substituted 3-10 membered heterocycloalkyl, substituted by one or more R 4e substituted 5-10 membered heteroaryl or one or more R 4k substituted 5-10 membered heteroaromatic ring and 3-10 membered heterocycloalkyl,

[0210] R h are independently 3-10 membered heterocycloalkenyl, 5-10 membered heteroaryl, substituted by one or more R 4-d substituted 3-10 membered heterocycloalkenyl or one or more R 4-esubstituted 5-10 membered heteroaryl,

[0211] R 4a are independently =O, -N(R 8 )2、-OR 10 、-C(O)N(R 10 )2、-C(O)OR 10 、 C3-C 10 Cycloalkyl, 3-10 membered heterocycloalkyl, 3-10 membered heterocycloalkenyl, 5-10 membered heteroaryl, C6-C 10 Aryl, carboxyl, one or more R 4-b Substituted C3-C 10 Cycloalkyl, one or more R 4-c substituted 3-10 membered heterocycloalkyl, substituted by one or more R 4-e substituted 5-10 membered heteroaryl or one or more R 4-d substituted 3-10 membered heterocycloalkenyl,

[0212] R 4-i are each independently hydrogen or C1-C6 alkyl,

[0213] R 4-b and R 4-c Each is independently -C(O)N(R 10 )2,

[0214] R 4-e are independently -N(R 8 )2, halogen, C1-C6 alkyl, -OR 10 、-C(O)R 10 、-C(O)N(R 10 )2 or by one or more R 4-a-1 Substituted C1-C6 alkyl,

[0215] R 4-d are independently ═O or —N(R 8 )2,

[0216] R 4b and R 4c Each is independently -C(O)N(R 10 )2,

[0217] R 4e is independently a 5-10 membered heteroaryl or is replaced by one or more R 4-e substituted 5-10 membered heteroaryl,

[0218] R 4k are independently ═O or —N(R 8 )2,

[0219] R 8 are independently hydrogen, C1-C6 alkyl or -C(O)R 10 ,

[0220] R 10 are independently hydrogen, C1-C6 alkyl or 3-10 membered heterocycloalkyl,

[0221] R 4-a-1 are independently -OH or -N(R 8 )2,

[0222] Preferably, R 4 are independently hydrogen, C1-C6 alkyl, 3-10 membered heterocycloalkyl, -SO2R h , by one or more R 4a Substituted C1-C6 alkyl, one or more R 4b Substituted C3-C 10 Cycloalkyl, one or more R 4e substituted 5-10 membered heteroaryl or one or more R 4k substituted 5-10 membered heteroaromatic ring and 3-10 membered heterocycloalkyl,

[0223] R h are independently 5-10 membered heteroaryl, substituted by one or more R 4-d substituted 3-10 membered heterocycloalkenyl or one or more R 4-e substituted 5-10 membered heteroaryl,

[0224] R 4a are independently =O, -N(R 8 )2、-OR 10 、-C(O)N(R 10 )2、-C(O)OR 10 、 C3-C 10 Cycloalkyl, 3-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C6-C 10 Aryl, carboxyl, one or more R 4-b Substituted C3-C 10 Cycloalkyl, one or more R 4-c substituted 3-10 membered heterocycloalkyl, substituted by one or more R 4-e substituted 5-10 membered heteroaryl or one or more R 4-d substituted 3-10 membered heterocycloalkenyl,

[0225] R 4-i are independently hydrogen or C1-C6 alkyl,

[0226] R 4-b and R 4-cEach is independently -C(O)N(R 10 )2,

[0227] R 4-e are independently -N(R 8 )2, halogen, C1-C6 alkyl, -OR 10 、-C(O)N(R 10 )2、-C(O)R 10 or by one or more R 4-a-1 Substituted C1-C6 alkyl,

[0228] R 4-d are independently ═O or —N(R 8 )2,

[0229] R 4b are independently -C(O)N(R 10 )2,

[0230] R 4e Independently by one or more R 4-e substituted 5-10 membered heteroaryl,

[0231] R 4k are independently ═O or —N(R 8 )2,

[0232] R 8 are independently hydrogen, C1-C6 alkyl or -C(O)R 10 ,

[0233] R 10 are independently hydrogen, C1-C6 alkyl or 3-10 membered heterocycloalkyl,

[0234] R 4-a-1 are independently -OH or -N(R 8 )2,

[0235] More preferably, R 4 independently hydrogen, -SO2R h , by one or more R 4a Substituted C1-C6 alkyl or one or more R 4k substituted 5-10 membered heteroaromatic ring and 3-10 membered heterocycloalkyl,

[0236] R h Independently for one or more R 4-d substituted 3-10 membered heterocycloalkenyl or one or more R 4-e substituted 5-10 membered heteroaryl,

[0237] R 4a are independently =O, -OR 10、-C(O)OR 10 、 C3-C 10 Cycloalkyl, 3-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C6-C 10 Aryl, carboxyl, one or more R 4-b Substituted C3-C 10 Cycloalkyl, one or more R 4-e substituted 5-10 membered heteroaryl or one or more R 4-d substituted 3-10 membered heterocycloalkenyl,

[0238] R 4-i are independently hydrogen or C1-C6 alkyl,

[0239] R 4-b are independently -C(O)N(R 10 )2,

[0240] R 4-e are independently -N(R 8 )2. Halogen, -OR 10 、-C(O)N(R 10 )2、-C(O)R 10 or by one or more R 4-a-1 Substituted C1-C6 alkyl,

[0241] R 4-d are independently ═O or —N(R 8 )2,

[0242] R 4k are independently =O,

[0243] R 8 are independently hydrogen or -C(O)R 10 ,

[0244] R 10 are independently hydrogen, C1-C6 alkyl or 3-10 membered heterocycloalkyl,

[0245] R 4-a-1 are independently -OH or -N(R 8 )2,

[0246] For example, R 4 independently hydrogen, -SO2R h , by one or more R 4a Substituted C1-C6 alkyl or one or more R 4k substituted 5-10 membered heteroaromatic ring and 3-10 membered heterocycloalkyl,

[0247] R h Independently for one or more R4-d substituted 3-10 membered heterocycloalkenyl or one or more R 4-e substituted 5-10 membered heteroaryl,

[0248] R 4a are independently =O, -OR 10 、-C(O)OR 10 、 Carboxyl, 5-10 membered heteroaryl, 3-10 membered heterocycloalkyl, 4-b Substituted C3-C 10 Cycloalkyl, one or more R 4-e substituted 5-10 membered heteroaryl or one or more R 4-d substituted 3-10 membered heterocycloalkenyl,

[0249] R 4-i are each independently hydrogen or C1-C6 alkyl,

[0250] R 4-b are independently -C(O)N(R 10 )2,

[0251] R 4-e are independently -N(R 8 )2. Halogen, -OR 10 、-C(O)N(R 10 )2 or by one or more R 4-a-1 Substituted C1-C6 alkyl,

[0252] R 4-d are independently ═O or —N(R 8 )2,

[0253] R 4k are independently =O,

[0254] R 8 are independently hydrogen,

[0255] R 10 are independently hydrogen or C1-C6 alkyl,

[0256] R 4-a-1 are independently -OH or -N(R 8 )2.

[0257] In one embodiment of the present invention, R 4 are independently hydrogen, C1-C6 alkyl, C3-C 10 Cycloalkyl, 3-10 membered heterocycloalkyl, 5-10 membered heteroaryl, -SO2R h , 5-10 membered heteroaromatic ring and 3-10 membered heterocycloalkyl, one or more R 4aSubstituted C1-C6 alkyl, one or more R 4b Substituted C3-C 10 Cycloalkyl, one or more R 4c substituted 3-10 membered heterocycloalkyl, substituted by one or more R 4e substituted 5-10 membered heteroaryl or one or more R 4k substituted 5-10 membered heteroaromatic ring and 3-10 membered heterocycloalkyl,

[0258] R h are independently 3-10 membered heterocycloalkenyl, 5-10 membered heteroaryl, substituted by one or more R 4-d substituted 3-10 membered heterocycloalkenyl or one or more R 4-e substituted 5-10 membered heteroaryl,

[0259] R 4a are independently =O, -N(R 8 )2、-OR 10 、-C(O)N(R 10 )2. C3-C 10 Cycloalkyl, 3-10 membered heterocycloalkyl, 3-10 membered heterocycloalkenyl, 5-10 membered heteroaryl, carboxyl, one or more R 4-b Substituted C3-C 10 Cycloalkyl, one or more R 4-c substituted 3-10 membered heterocycloalkyl, substituted by one or more R 4-e substituted 5-10 membered heteroaryl or one or more R 4-d substituted 3-10 membered heterocycloalkenyl,

[0260] R 4k are independently ═O or —N(R 8 )2,

[0261] R 4-b and R 4-c Each is independently -C(O)N(R 10 )2,

[0262] R 4-e are independently -N(R 8 )2, halogen, C1-C6 alkyl, -OR 10 、-C(O)N(R 10 )2 or by one or more R 4-a-1 Substituted C1-C6 alkyl,

[0263] R 4-d are independently ═O or —N(R 8 )2,

[0264] R 4b and R4c Each is independently -C(O)N(R 10 )2,

[0265] R 4e is independently a 5-10 membered heteroaryl or is replaced by one or more R 4-e substituted 5-10 membered heteroaryl,

[0266] R 8 and R 10 are each independently hydrogen or C1-C6 alkyl,

[0267] R 4-a-1 are independently -OH or -N(R 8 )2,

[0268] Preferably, R 4 are independently hydrogen, C1-C6 alkyl, 3-10 membered heterocycloalkyl, -SO2R h , by one or more R 4a Substituted C1-C6 alkyl, one or more R 4b Substituted C3-C 10 Cycloalkyl, one or more R 4e substituted 5-10 membered heteroaryl or one or more R 4k substituted 5-10 membered heteroaromatic ring and 3-10 membered heterocycloalkyl,

[0269] R h are independently 5-10 membered heteroaryl, substituted by one or more R 4-d substituted 3-10 membered heterocycloalkenyl or one or more R 4-e substituted 5-10 membered heteroaryl,

[0270] R 4a are independently =O, -N(R 8 )2、-OR 10 、-C(O)N(R 10 )2. C3-C 10 Cycloalkyl, 3-10 membered heterocycloalkyl, 5-10 membered heteroaryl, carboxyl, one or more R 4-b Substituted C3-C 10 Cycloalkyl, one or more R 4-c substituted 3-10 membered heterocycloalkyl, substituted by one or more R 4-e substituted 5-10 membered heteroaryl or one or more R 4-d substituted 3-10 membered heterocycloalkenyl,

[0271] R 4k are independently ═O or —N(R 8 )2,

[0272] R 4-b and R 4-c Each is independently -C(O)N(R 10 )2,

[0273] R 4-e are independently -N(R 8 )2, halogen, C1-C6 alkyl, -OR 10 、-C(O)N(R 10 )2 or by one or more R 4-a-1 Substituted C1-C6 alkyl,

[0274] R 4-d are independently ═O or —N(R 8 )2,

[0275] R 4b are independently -C(O)N(R 10 )2,

[0276] R 4e Independently for one or more R 4-e substituted 5-10 membered heteroaryl,

[0277] R 8 are independently hydrogen or C1-C6 alkyl,

[0278] R 10 are independently hydrogen or C1-C6 alkyl,

[0279] R 4-a-1 are independently -OH or -N(R 8 )2,

[0280] More preferably, R 4 independently hydrogen, -SO2R h or by one or more R 4a Substituted C1-C6 alkyl,

[0281] R h Independently for one or more R 4-d substituted 3-10 membered heterocycloalkenyl or one or more R 4-e substituted 5-10 membered heteroaryl,

[0282] R 4a are independently =O, -OR 10 , 5-10 membered heteroaryl, one or more R 4-b Substituted C3-C 10 Cycloalkyl, one or more R 4-e substituted 5-10 membered heteroaryl or one or more R 4-d substituted 3-10 membered heterocycloalkenyl,

[0283] R 4-b are independently -C(O)N(R 10 )2,

[0284] R 4-e are independently -N(R 8 )2. Halogen, -OR 10 、-C(O)N(R 10 )2 or by one or more R 4-a-1 Substituted C1-C6 alkyl,

[0285] R 4-d are independently ═O or —N(R 8 )2,

[0286] R 8 are independently hydrogen,

[0287] R 10 are independently hydrogen or C1-C6 alkyl,

[0288] R 4-a-1 are independently -OH or -N(R 8 )2.

[0289] In one embodiment of the present invention, R 4 are independently hydrogen, C1-C6 alkyl, C3-C 10 Cycloalkyl, 3-10 membered heterocycloalkyl, 5-10 membered heteroaryl, -SO2R h , by one or more R 4a Substituted C1-C6 alkyl, one or more R 4b Substituted C3-C 10 Cycloalkyl, one or more R 4c substituted 3-10 membered heterocycloalkyl or one or more R 4e Substituted 5-10 membered heteroaryl, R h is independently a 5-10 membered heteroaryl or is replaced by one or more R 4-e Substituted 5-10 membered heteroaryl, R 4a are independently =O, -N(R 8 )2、-C(O)N(R 10 )2. C3-C 10 Cycloalkyl, 3-10 membered heterocycloalkyl, 3-10 membered heterocycloalkenyl, 5-10 membered heteroaryl, substituted by one or more R 4-b Substituted C3-C 10 Cycloalkyl, one or more R 4-c substituted 3-10 membered heterocycloalkyl, substituted by one or more R 4-e substituted 5-10 membered heteroaryl or one or more R4- d Substituted 3-10 membered heterocycloalkenyl, R 4-b and R 4-c Each is independently -C(O)N(R 10 )2,R 4-e are independently -N(R 8 )2,R 4-d are independently =O, R 4b and R 4c Each is independently -C(O)N(R 10 )2,R 4e is independently a 5-10 membered heteroaryl or is replaced by one or more R 4-e Substituted 5-10 membered heteroaryl, R 8 and R 10 Each is independently hydrogen or C1-C6 alkyl;

[0290] Preferably, R 4 are independently hydrogen, C1-C6 alkyl, 3-10 membered heterocycloalkyl, -SO2R h , by one or more R 4a Substituted C1-C6 alkyl, one or more R 4b Substituted C3-C 10 Cycloalkyl or one or more R 4e Substituted 5-10 membered heteroaryl, R h is independently a 5-10 membered heteroaryl or is replaced by one or more R 4-e Substituted 5-10 membered heteroaryl, R 4a are independently =O, -N(R 8 )2、-C(O)N(R 10 )2. C3-C 10 Cycloalkyl, 3-10 membered heterocycloalkyl, 5-10 membered heteroaryl, one or more R 4-b Substituted C3-C 10 Cycloalkyl, one or more R 4-c substituted 3-10 membered heterocycloalkyl, substituted by one or more R 4-e substituted 5-10 membered heteroaryl or one or more R 4-d Substituted 3-10 membered heterocycloalkenyl, R 4-b and R 4-c Each is independently -C(O)N(R 10 )2,R 4-e are independently -N(R 8 )2,R 4-d are independently =O, R 4b are independently -C(O)N(R 10 )2,R 4eIndependently for one or more R 4-e Substituted 5-10 membered heteroaryl, R 8 are independently hydrogen or C1-C6 alkyl, R 10 are independently hydrogen.

[0291] In one embodiment of the present invention, R 4 are independently hydrogen, C1-C6 alkyl, C3-C 10 Cycloalkyl, 3-10 membered heterocycloalkyl, 4a Substituted C1-C6 alkyl, one or more R 4b Substituted C3-C 10 Cycloalkyl or one or more R 4c Substituted 3-10 membered heterocycloalkyl, R 4a are independently -N(R 8 )2、-C(O)N(R 10 )2. C3-C 10 Cycloalkyl, 3-10 membered heterocycloalkyl, 5-10 membered heteroaryl, one or more R 4-b Substituted C3-C 10 Cycloalkyl, one or more R 4-c substituted 3-10 membered heterocycloalkyl or one or more R 4-e Substituted 5-10 membered heteroaryl, R 4-b and R 4-c Each is independently -C(O)N(R 10 )2,R 4-e are independently -N(R 8 )2,R 4b and R 4c Each is independently -C(O)N(R 10 )2,R 8 and R 10 Each is independently hydrogen or C1-C6 alkyl;

[0292] Preferably, R 4 are independently hydrogen, C1-C6 alkyl, 3-10 membered heterocycloalkyl, 4a Substituted C1-C6 alkyl or one or more R 4b Substituted C3-C 10 Cycloalkyl, R 4a are independently -N(R 8 )2、-C(O)N(R 10 )2. C3-C 10 Cycloalkyl, one or more R 4-b Substituted C3-C 10 Cycloalkyl, 3-10 membered heterocycloalkyl, 4-csubstituted 3-10 membered heterocycloalkyl, substituted by one or more R 4-e Substituted 5-10 membered heteroaryl, R 4-b and R 4-c Each is independently -C(O)N(R 10 )2,R 4-e are independently -N(R 8 )2,R 4b are independently -C(O)N(R 10 )2,R 8 are independently hydrogen or C1-C6 alkyl, R 10 are independently hydrogen.

[0293] In one embodiment of the present invention, R 5 is hydrogen, 3-10 membered heterocycloalkyl, C1-C6 alkyl, 5a Substituted C1-C6 alkyl or one or more R 5b Substituted 3-10 membered heterocycloalkyl, R 5a -OH, R 5b =O;

[0294] Preferably, R 5 is hydrogen, one or more R 5a Substituted C1-C6 alkyl or one or more R 5b Substituted 3-10 membered heterocycloalkyl, R 5a -OH, R 5b =O.

[0295] In one embodiment of the present invention, R 5 is hydrogen or is replaced by one or more R 5a Substituted C1-C6 alkyl, R 5a is -OH; preferably, R 5 For hydrogen.

[0296] In one embodiment of the present invention, R 4 and R 5 It can also form a 3-10 membered saturated heterocyclic ring, a 5-10 membered heteroaromatic ring, a 3-10 membered heterocyclic alkene, or one or more R 4h substituted 3-10 membered saturated heterocyclic ring, replaced by one or more R 4j substituted 5-10 membered heteroaromatic ring or one or more R 4i Substituted 3-10 membered heterocyclic olefins, R 4h are independently -OH, -N(R 8 )2, C1-C6 alkyl or one or more R 4-h Substituted C1-C6 alkyl, R 4-h are independently -N(R 8)2, or two adjacent R 4h Together with the atoms to which they are attached, they form a 5-10 membered heteroaromatic ring, R 8 are independently hydrogen or C1-C6 alkyl, R 4i and R 4j Each is independently -C(O)N(R 10 )2,R 10 are independently hydrogen;

[0297] Preferably, R 4 and R 5 It can also form a 3-10 membered saturated heterocyclic ring with the atoms to which it is connected, or be surrounded by one or more R 4h substituted 3-10 membered saturated heterocyclic ring or one or more R 4j Substituted 5-10 membered heteroaromatic ring, R 4h are independently -OH, -N(R 8 )2, C1-C6 alkyl or one or more R 4-h Substituted C1-C6 alkyl, R 4-h are independently -N(R 8 )2, or two adjacent R 4h Together with the atoms to which they are attached, they form a 5-10 membered heteroaromatic ring, R 8 are independently hydrogen or C1-C6 alkyl, R 4j are independently -C(O)N(R 10 )2,R 10 are independently hydrogen.

[0298] In one embodiment of the present invention, R 4 and R 5 It can also form a 3-10 membered saturated heterocyclic ring together with the atoms to which it is connected or be replaced by one or more R 4h Substituted 3-10 membered saturated heterocycle; two adjacent R 4h Together with the atoms to which they are attached, they form a 5-10 membered heteroaromatic ring; preferably, R 4 and R 5 They may also be taken together with the atoms to which they are attached to form a 3-10 membered saturated heterocyclic ring.

[0299] In one embodiment of the present invention, R 4 and R 5 It can also form a 3-10 membered saturated heterocyclic ring together with the atoms to which it is connected or be replaced by one or more R 4h Substituted 3-10 membered saturated heterocyclic ring, R 4h are independently -OH, -N(R 8 )2, C1-C6 alkyl or one or more R 4-h Substituted C1-C6 alkyl, R 4-h are independently -N(R8 )2,R 8 are independently hydrogen or C1-C6 alkyl;

[0300] Preferably, R 4 and R 5 It can also form together with the atoms to which it is attached one or more R 4h Substituted 3-10 membered saturated heterocyclic ring, R 4h are independently -OH, -N(R 8 )2, C1-C6 alkyl or one or more R 4-h Substituted C1-C6 alkyl, R 4-h are independently N(R 8 )2,R 8 are independently hydrogen or C1-C6 alkyl.

[0301] In one embodiment of the present invention, R 6 For hydrogen.

[0302] In one embodiment of the present invention,

[0303] When n is 2 or 3, X is independently a -C(R 7 )2-, when n is 1, X is a -CR 7 =CR 7 -、 a -N=N-, a -CR 7 =N- or a -N=CR 7 -, where side a is The N atoms in are connected;

[0304] R 7 are independently hydrogen or C1-C6 alkyl;

[0305] L and R 2 The definition of satisfies one of the following conditions:

[0306] Case (1): L is -O-(CR 9 R 9 ) n1 - b , where side b is connected to R 2 connected;

[0307] R 9 are independently hydrogen or C1-C6 alkyl;

[0308] n1 is 0 or 1;

[0309] R 2 is hydrogen, 4-10 membered heterocycloalkyl,2a Substituted C3-C 10 Cycloalkyl or one or more R 2c substituted 4- to 10-membered heterocycloalkyl;

[0310] R 2a is independently (4-10 membered heterocycloalkyl)-CH2-, wherein the 4-10 membered heterocycloalkyl in the (4-10 membered heterocycloalkyl)-CH2- is optionally replaced by C l -C6 alkyl substitution;

[0311] R 2c are independently halogen, C1-C4 alkyl, ═CR 2-c R 2-c 、C1-C4 alkyl-O-、-N(R 8 )2 or (C l -C4 alkyl)-O-(C l -C4 alkyl)-;

[0312] R 2-c are independently halogen;

[0313] Case (2): L does not exist;

[0314] R 2 For one or more R 2c Substituted 4-10 membered heterocycloalkyl; R 2c are independently C1-C4 alkyl or 4-10 membered heterocycloalkyl;

[0315] R 1 For one or more R 1a Substituted C6-C 10 Aryl, one or more R 1b substituted 5-10 membered heteroaryl or one or more R 1c substituted 3-10 membered heterocycloalkyl;

[0316] R 1a are independently halogen, -OH or -N(R 8 )2;

[0317] R 1b are independently halogen, -CN, -OH, C1-C6 alkyl, -N(R 8 )2 or by one or more R 1-a Substituted C1-C6 alkyl;

[0318] R 1-a are independently halogen;

[0319] R 1c are independently C1-C6 alkyl;

[0320] Or two adjacent R 1c Together with the atoms to which they are attached, they form a 5-10 membered heteroaromatic ring, wherein the 5-10 membered heteroaromatic ring is optionally substituted by one or more of the following groups: -CN or -N(R 8 )2;

[0321] R 3 is a halogen;

[0322] Y is -NR 4 -, O, or c -(CH2) p NR 4 -, p is 1, c side is -CHR 5 - connected;

[0323] R 4 is hydrogen, C1-C6 alkyl, 3-10 membered heterocycloalkyl, -SO2R h , by one or more R 4a Substituted C1-C6 alkyl, one or more R 4b Substituted C3-C 10 Cycloalkyl, one or more R 4e substituted 5-10 membered heteroaryl or one or more R 4k substituted 5-10 membered heteroaryl ring and 3-10 membered heterocycloalkyl;

[0324] R h are independently 5-10 membered heteroaryl, substituted by one or more R 4-d substituted 3-10 membered heterocycloalkenyl or one or more R 4-e substituted 5-10 membered heteroaryl;

[0325] R 4a are independently =O, -N(R 8 )2、-OR 10 、-C(O)OR 10 , 5-10 membered heteroaryl, -C(O)N(R 10 )2. C3-C 10 Cycloalkyl, 3-10 membered heterocycloalkyl, carboxyl, C6-C 10 Aryl, one or more R 4-b Substituted C3-C 10 Cycloalkyl, one or more R 4-c substituted 3-10 membered heterocycloalkyl, substituted by one or more R 4-e substituted 5-10 membered heteroaryl or one or more R 4-d substituted 3-10 membered heterocycloalkenyl;

[0326] R4-i Each is independently hydrogen or C1-C6 alkyl;

[0327] R 4-b and R 4-c Each is independently -C(O)N(R 10 )2;

[0328] R 4-e are independently -N(R 8 )2, halogen, C1-C6 alkyl, -OR 10 、-C(O)N(R 10 )2、-C(O)R 10 or by one or more R 4-a-1 Substituted C1-C6 alkyl;

[0329] R 4-d are independently ═O or —N(R 8 )2;

[0330] R 4b are independently -C(O)N(R 10 )2;

[0331] R 4e Independently for one or more R 4-e substituted 5-10 membered heteroaryl;

[0332] R 4k are independently ═O or —N(R 8 )2;

[0333] R 8 are independently hydrogen, C1-C6 alkyl or -C(O)R 10 ;

[0334] R 10 are independently hydrogen, C1-C6 alkyl or 3-10 membered heterocycloalkyl;

[0335] R 4-a-1 are independently -OH or -N(R 8 )2;

[0336] R 5 is hydrogen, one or more R 5a Substituted C1-C6 alkyl or one or more R 5b substituted 3-10 membered heterocycloalkyl;

[0337] R 5a is -OH;

[0338] R 5b =O;

[0339] R 4and R 5 It can also form a 3-10 membered saturated heterocyclic ring with the atoms to which it is connected, or be surrounded by one or more R 4h substituted 3-10 membered saturated heterocyclic ring or one or more R 4j substituted 5-10 membered heteroaromatic ring;

[0340] R 4h are independently -OH, -N(R 8 )2, C1-C6 alkyl or one or more R 4-h Substituted C1-C6 alkyl; or two adjacent R 4h Together with the atoms to which they are attached, they form a 5-10 membered heteroaromatic ring;

[0341] R 4-h are independently -N(R 8 )2;

[0342] R 4j are independently -C(O)N(R 10 )2;

[0343] R 6 For hydrogen.

[0344] In one embodiment of the present invention,

[0345] When n is 2 or 3, X is independently a -C(R 7 )2-, when n is 1, X is a -CR 7 =CR 7 -or a -N=CR 7 -, where side a is The N atoms in are connected;

[0346] R 7 are independently hydrogen or C1-C6 alkyl;

[0347] L and R 2 The definition of satisfies one of the following conditions:

[0348] Case (1): L is -O-(CR 9 R 9 ) n1 - b , where side b is connected to R 2 connected;

[0349] R 9 are independently hydrogen or C1-C6 alkyl;

[0350] n1 is 0 or 1;

[0351] R2 is a 4-10 membered heterocycloalkyl group, 2a Substituted C3-C 10 Cycloalkyl or one or more R 2c substituted 4-10 membered heterocycloalkyl;

[0352] R 2a is independently (4-10 membered heterocycloalkyl)-CH2-, wherein the 4-10 membered heterocycloalkyl in the (4-10 membered heterocycloalkyl)-CH2- is optionally replaced by C l -C6 alkyl substitution;

[0353] R 2c are independently halogen, ═CR 2-c R 2-c 、C1-C4 alkyl、C1-C4 alkyl-O-、-N(R 8 )2 or (C l -C4 alkyl)-O-(C l -C4 alkyl)-;

[0354] R 2-c are independently halogen;

[0355] Case (2): L does not exist;

[0356] R 2 For one or more R 2c Substituted 4-10 membered heterocycloalkyl; R 2c are independently C1-C4 alkyl or 4-10 membered heterocycloalkyl;

[0357] R 1 For one or more R 1a Substituted C6-C 10 Aryl or one or more R 1b substituted 5-10 membered heteroaryl;

[0358] R 1a are independently halogen, -OH or -N(R 8 )2;

[0359] R 1b are independently halogen, -CN, C1-C6 alkyl, -N(R 8 )2 or by one or more R 1-a Substituted C1-C6 alkyl;

[0360] R 1-a are independently halogen;

[0361] R 3 is a halogen;

[0362] Y is -NR4 -, O, or c -(CH2) p NR 4 -, p is 1, c side is -CHR 5 - connected;

[0363] R 4 independently hydrogen, -SO2R h , by one or more R 4a Substituted C1-C6 alkyl or one or more R 4k substituted 5-10 membered heteroaryl ring and 3-10 membered heterocycloalkyl;

[0364] R h Independently for one or more R 4-d substituted 3-10 membered heterocycloalkenyl or one or more R 4-e substituted 5-10 membered heteroaryl;

[0365] R 4a are independently =O, -OR 10 、-C(O)OR 10 、 C3-C 10 Cycloalkyl, 3-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C6-C 10 Aryl, carboxyl, one or more R 4-b Substituted C3-C 10 Cycloalkyl, one or more R 4-e substituted 5-10 membered heteroaryl or one or more R 4-d substituted 3-10 membered heterocycloalkenyl;

[0366] R 4-i Each is independently hydrogen or C1-C6 alkyl;

[0367] R 4-b are independently -C(O)N(R 10 )2;

[0368] R 4-e are independently -N(R 8 )2. Halogen, -OR 10 、-C(O)N(R 10 )2、-C(O)R 10 or by one or more R 4-a-1 Substituted C1-C6 alkyl;

[0369] R 4-d are independently ═O or —N(R 8 )2;

[0370] R 4kindependently =0;

[0371] R 8 are independently hydrogen or -C(O)R 10 ;

[0372] R 10 are independently hydrogen, C1-C6 alkyl or 3-10 membered heterocycloalkyl;

[0373] R 4-a-1 are independently -OH or -N(R 8 )2;

[0374] R 5 is hydrogen or is replaced by one or more R 5a Substituted C1-C6 alkyl;

[0375] R 5a is -OH;

[0376] R 4 and R 5 It can also form a 3-10 membered saturated heterocyclic ring together with the atoms to which it is connected or be replaced by one or more R 4h Substituted 3-10 membered saturated heterocycle; two adjacent R 4h Together with the atoms to which they are attached, they form a 5-10 membered heteroaromatic ring;

[0377] R 6 For hydrogen.

[0378] In one embodiment of the present invention,

[0379] When n is 2 or 3, X is independently a -C(R 7 )2-, when n is 1, X is a -CR 7 =CR 7 -、 a -N=N-, a -CR 7 =N- or a -N=CR 7 -, where side a is The N atoms in are connected;

[0380] R 7 are independently hydrogen or C1-C6 alkyl;

[0381] L and R 2 The definition of satisfies one of the following conditions:

[0382] Case (1): L is -O-(CR 9 R 9 ) n1 - b, where side b is connected to R 2 connected;

[0383] R 9 are independently hydrogen or C1-C6 alkyl;

[0384] n1 is 0 or 1;

[0385] R 2 is hydrogen, 4-10 membered heterocycloalkyl, 2a Substituted C3-C 10 Cycloalkyl or one or more R 2c substituted 4-10 membered heterocycloalkyl;

[0386] R 2a is independently (4-10 membered heterocycloalkyl)-CH2-, wherein the 4-10 membered heterocycloalkyl in the (4-10 membered heterocycloalkyl)-CH2- is optionally replaced by C l -C6 alkyl substitution;

[0387] R 2c are independently halogen, C1-C4 alkyl, ═CR 2-c R 2-c 、C1-C4 alkyl-O-、-N(R 8 )2 or (C l -C4 alkyl)-O-(C l -C4 alkyl)-;

[0388] R 2-c are independently halogen;

[0389] Case (2): L does not exist;

[0390] R 2 For one or more R 2c Substituted 4-10 membered heterocycloalkyl; R 2c are independently C1-C4 alkyl or 4-10 membered heterocycloalkyl;

[0391] R 1 For one or more R 1a Substituted C6-C 10 Aryl, one or more R 1b substituted 5-10 membered heteroaryl or one or more R 1c substituted 3-10 membered heterocycloalkyl;

[0392] R 1a are independently halogen, -OH or -N(R 8 )2;

[0393] R 1b are independently halogen, -CN, -OH, C1-C6 alkyl, -N(R8 )2 or by one or more R 1-a Substituted C1-C6 alkyl;

[0394] R 1-a are independently halogen;

[0395] R 1c are independently C1-C6 alkyl;

[0396] Or two adjacent R 1c Together with the atoms to which they are attached, they form a 5-10 membered heteroaromatic ring, wherein the 5-10 membered heteroaromatic ring is optionally substituted by one or more of the following groups: -CN or -N(R 8 )2;

[0397] R 3 is a halogen;

[0398] Y is -NR 4 -, O, or c -(CH2) p NR 4 -, p is 1, c side is -CHR 5 - connected;

[0399] R 4 is hydrogen, C1-C6 alkyl, 3-10 membered heterocycloalkyl, -SO2R h , by one or more R 4a Substituted C1-C6 alkyl, one or more R 4b Substituted C3-C 10 Cycloalkyl, one or more R 4e substituted 5-10 membered heteroaryl or one or more R 4k substituted 5-10 membered heteroaryl ring and 3-10 membered heterocycloalkyl;

[0400] R h are independently 5-10 membered heteroaryl, substituted by one or more R 4-d substituted 3-10 membered heterocycloalkenyl or one or more R 4-e substituted 5-10 membered heteroaryl;

[0401] R 4a are independently =O, -N(R 8 )2、-OR 10 , 5-10 membered heteroaryl, -C(O)N(R 10 )2. C3-C 10 Cycloalkyl, 3-10 membered heterocycloalkyl, carboxyl, one or more R 4-b Substituted C3-C 10 Cycloalkyl, one or more R 4-csubstituted 3-10 membered heterocycloalkyl, substituted by one or more R 4-e substituted 5-10 membered heteroaryl or one or more R 4-d substituted 3-10 membered heterocycloalkenyl;

[0402] R 4k are independently ═O or —N(R 8 )2;

[0403] R 4-b and R 4-c Each is independently -C(O)N(R 10 )2;

[0404] R 4-e are independently -N(R 8 )2, halogen, C1-C6 alkyl, -OR 10 、-C(O)N(R 10 )2 or by one or more R 4-a-1 Substituted C1-C6 alkyl;

[0405] R 4-d are independently ═O or —N(R 8 )2;

[0406] R 4b are independently -C(O)N(R 10 )2;

[0407] R 4e Independently for one or more R 4-e substituted 5-10 membered heteroaryl;

[0408] R 8 are independently H or C1-C6 alkyl;

[0409] R 10 are independently hydrogen or C1-C6 alkyl;

[0410] R 4-a-1 are independently -OH or -N(R 8 )2;

[0411] R 5 is hydrogen, one or more R 5a Substituted C1-C6 alkyl or one or more R 5b substituted 3-10 membered heterocycloalkyl;

[0412] R 5a is -OH;

[0413] R 5b =O;

[0414] R 4and R 5 It can also form a 3-10 membered saturated heterocyclic ring with the atoms to which it is connected, or be surrounded by one or more R 4h substituted 3-10 membered saturated heterocyclic ring or one or more R 4j substituted 5-10 membered heteroaromatic ring;

[0415] R 4h are independently -OH, -N(R 8 )2, C1-C6 alkyl or one or more R 4-h Substituted C1-C6 alkyl; or two adjacent R 4h Together with the atoms to which they are attached, they form a 5-10 membered heteroaromatic ring;

[0416] R 4-h are independently -N(R 8 )2;

[0417] R 4j are independently -C(O)N(R 10 )2;

[0418] R 6 For hydrogen.

[0419] In one embodiment of the present invention,

[0420] When n is 2 or 3, X is independently a -C(R 7 )2-, when n is 1, X is a -CR 7 =CR 7 -or a -N=CR 7 -, where side a is The N atoms in are connected;

[0421] R 7 are independently hydrogen or C1-C6 alkyl;

[0422] L and R 2 The definition of satisfies one of the following conditions:

[0423] Case (1): L is -O-(CR 9 R 9 ) n1 - b , where side b is connected to R 2 connected;

[0424] R 9 are independently hydrogen or C1-C6 alkyl;

[0425] n1 is 0 or 1;

[0426] R2 is a 4-10 membered heterocycloalkyl group, 2a Substituted C3-C 10 Cycloalkyl or one or more R 2c substituted 4-10 membered heterocycloalkyl;

[0427] R 2a is independently (4-10 membered heterocycloalkyl)-CH2-, wherein the 4-10 membered heterocycloalkyl in the (4-10 membered heterocycloalkyl)-CH2- is optionally replaced by C l -C6 alkyl substitution;

[0428] R 2c are independently halogen, C1-C4 alkyl, C1-C4 alkyl-O-, -N(R 8 )2 or (C l -C4 alkyl)-O-(C l -C4 alkyl)-;

[0429] Case (2): L does not exist;

[0430] R 2 For one or more R 2c Substituted 4-10 membered heterocycloalkyl; R 2c are independently C1-C4 alkyl or 4-10 membered heterocycloalkyl;

[0431] R 1 For one or more R 1a Substituted C6-C 10 Aryl or one or more R 1b substituted 5-10 membered heteroaryl;

[0432] R 1a are independently halogen, -OH or -N(R 8 )2;

[0433] R 1b are independently halogen, -CN, C1-C6 alkyl, -N(R 8 )2 or by one or more R 1-a Substituted C1-C6 alkyl;

[0434] R 1-a are independently halogen;

[0435] R 3 is a halogen;

[0436] Y is -NR 4 -, O, or c -(CH2) p NR 4 -, p is 1, c side is -CHR5 - connected;

[0437] R 4 independently hydrogen, -SO2R h or by one or more R 4a Substituted C1-C6 alkyl;

[0438] R h Independently for one or more R 4-d substituted 3-10 membered heterocycloalkenyl or one or more R 4-e substituted 5-10 membered heteroaryl;

[0439] R 4a are independently =O, -OR 10 , 5-10 membered heteroaryl, one or more R 4-b Substituted C3-C 10 Cycloalkyl, one or more R 4-e substituted 5-10 membered heteroaryl or one or more R 4-d substituted 3-10 membered heterocycloalkenyl;

[0440] R 4-b are independently -C(O)N(R 10 )2;

[0441] R 4-e are independently -N(R 8 )2. Halogen, -OR 10 、-C(O)N(R 10 )2 or by one or more R 4-a-1 Substituted C1-C6 alkyl;

[0442] R 4-d are independently ═O or —N(R 8 )2;

[0443] R 8 are independently hydrogen;

[0444] R 10 are independently hydrogen or C1-C6 alkyl;

[0445] R 4-a-1 are independently -OH or -N(R 8 )2;

[0446] R 5 is hydrogen or is replaced by one or more R 5a Substituted C1-C6 alkyl;

[0447] R 5a is -OH;

[0448] R 4and R 5 It can also form a 3-10 membered saturated heterocyclic ring together with the atoms to which it is connected or be replaced by one or more R 4h Substituted 3-10 membered saturated heterocycle; two adjacent R 4h Together with the atoms to which they are attached, they form a 5-10 membered heteroaromatic ring;

[0449] R 6 For hydrogen.

[0450] In one embodiment of the present invention,

[0451] When n is 2 or 3, X is independently a -C(R 7 )2-, when n is 1, X is a -CR 7 =CR 7 -、 a -N=N-, a -CR 7 =N- or a -N=CR 7 -, where side a is The N atoms in are connected;

[0452] R 7 are independently hydrogen or C1-C6 alkyl;

[0453] L is -O-(CR 9 R 9 ) n1 - b , where side b is connected to R 2 connected;

[0454] R 9 are independently hydrogen or C1-C6 alkyl;

[0455] n1 is 0 or 1;

[0456] R 2 is hydrogen, 4-10 membered heterocycloalkyl, 2a Substituted C3-C 10 Cycloalkyl or one or more R 2c substituted 4-10 membered heterocycloalkyl;

[0457] R 2a is independently (4-10 membered heterocycloalkyl)-CH2-, wherein the 4-10 membered heterocycloalkyl in the (4-10 membered heterocycloalkyl)-CH2- is optionally replaced by C l -C6 alkyl substitution;

[0458] R 2c are independently halogen, C1-C4 alkyl, ═CR 2-c R2-c 、C1-C4 alkyl-O-、-N(R 8 )2 or (C l -C4 alkyl)-O-(C l -C4 alkyl)-;

[0459] R 8 are independently H or C1-C6 alkyl;

[0460] R 2-c are independently halogen;

[0461] R 1 For one or more R 1a Substituted C6-C 10 Aryl, one or more R 1b substituted 5-10 membered heteroaryl or one or more R 1c substituted 3-10 membered heterocycloalkyl;

[0462] R 1a are independently halogen, -OH or -N(R 8 )2;

[0463] R 1b are independently halogen, -CN, -OH, C1-C6 alkyl, -N(R 8 )2 or by one or more R 1-a Substituted C1-C6 alkyl;

[0464] R 1-a are independently halogen;

[0465] R 1c are independently C1-C6 alkyl;

[0466] Or two adjacent R 1c Together with the atoms to which they are attached, they form a 5-10 membered heteroaromatic ring, wherein the 5-10 membered heteroaromatic ring is optionally substituted by one or more of the following groups: -CN or -N(R 8 )2;

[0467] R 3 is a halogen;

[0468] Y is -NR 4 -, O, or c -(CH2) p NR 4 -, p is 1, c side is -CHR 5 - connected;

[0469] R 4 is hydrogen, C1-C6 alkyl, 3-10 membered heterocycloalkyl, -SO2R h , by one or more R4a Substituted C1-C6 alkyl, one or more R 4b Substituted C3-C 10 Cycloalkyl or one or more R 4e substituted 5-10 membered heteroaryl;

[0470] R h is independently a 5-10 membered heteroaryl or is replaced by one or more R 4-e substituted 5-10 membered heteroaryl;

[0471] R 4a are independently =O, -N(R 8 )2、-C(O)N(R 10 )2. C3-C 10 Cycloalkyl, 3-10 membered heterocycloalkyl, 4-b Substituted C3-C 10 Cycloalkyl, one or more R 4-c substituted 3-10 membered heterocycloalkyl, substituted by one or more R 4-e substituted 5-10 membered heteroaryl or one or more R 4-d substituted 3-10 membered heterocycloalkenyl;

[0472] R 4-b and R 4-c Each is independently -C(O)N(R 10 )2;

[0473] R 4-e are independently -N(R 8 )2;

[0474] R 4-d independently =0;

[0475] R 4b are independently -C(O)N(R 10 )2;

[0476] R 4e Independently for one or more R 4-e substituted 5-10 membered heteroaryl;

[0477] R 10 are independently hydrogen;

[0478] R 5 is hydrogen, one or more R 5a Substituted C1-C6 alkyl or one or more R 5b substituted 3-10 membered heterocycloalkyl;

[0479] R 5a is -OH;

[0480] R 5b =O;

[0481] R 4 and R 5 It can also form a 3-10 membered saturated heterocyclic ring with the atoms to which it is connected, or be surrounded by one or more R 4h substituted 3-10 membered saturated heterocyclic ring or one or more R 4j substituted 5-10 membered heteroaromatic ring;

[0482] R 4h are independently -OH, -N(R 8 )2, C1-C6 alkyl or one or more R 4-h Substituted C1-C6 alkyl;

[0483] Or two adjacent R 4h Together with the atoms to which they are attached, they form a 5-10 membered heteroaromatic ring;

[0484] R 4-h are independently -N(R 8 )2;

[0485] R 4j are independently -C(O)N(R 10 )2;

[0486] R 6 For hydrogen.

[0487] In one embodiment of the present invention,

[0488] When n is 2 or 3, X is independently a -C(R 7 )2-, when n is 1, X is a -CR 7 =CR 7 -、 a -N=N-, a -CR 7 =N- or a -N=CR 7 -, where side a is The N atoms in are connected;

[0489] R 7 are independently hydrogen;

[0490] L is -O-(CR 9 R 9 ) n1 - b , where side b is connected to R 2 connected;

[0491] R 9 are independently hydrogen;

[0492] n1 is 0 or 1;

[0493] R 2 is hydrogen, one or more R 2a Substituted C3-C 10 Cycloalkyl or one or more R 2c substituted 4-10 membered heterocycloalkyl;

[0494] R 2a are independently (4-10 membered heterocycloalkyl)-CH2-;

[0495] R 2c are independently halogen or C1-C4 alkyl;

[0496] R 1 For one or more R 1b substituted 5-10 membered heteroaryl;

[0497] R 1b are independently C1-C6 alkyl, -N(R 8 )2 or by one or more R 1-a Substituted C1-C6 alkyl;

[0498] R 1-a are independently halogen;

[0499] R 3 is a halogen;

[0500] Y is -NR 4 - or O;

[0501] R 4 is hydrogen, C1-C6 alkyl, 3-10 membered heterocycloalkyl, 4a Substituted C1-C6 alkyl or one or more R 4b Substituted C3-C 10 Cycloalkyl;

[0502] R 4a are independently -N(R 8 )2、-C(O)N(R 10 )2. C3-C 10 Cycloalkyl, 3-10 membered heterocycloalkyl, 4-b Substituted C3-C 10 Cycloalkyl, one or more R 4-c substituted 3-10 membered heterocycloalkyl or one or more R 4-e substituted 5-10 membered heteroaryl;

[0503] R 4b are independently -C(O)N(R10 )2;

[0504] R 4-b are independently -C(O)N(R 10 )2;

[0505] R 4-c are independently -C(O)N(R 10 )2;

[0506] R 4-e are independently -N(R 8 )2;

[0507] R 8 are independently hydrogen or C1-C6 alkyl;

[0508] R 10 are independently hydrogen;

[0509] R 5 is hydrogen, one or more R 5a Substituted C1-C6 alkyl or one or more R 5b substituted 3-10 membered heterocycloalkyl;

[0510] R 5a is -OH;

[0511] R 5b =O;

[0512] R 4 and R 5 It can also form a 3-10 membered saturated heterocyclic ring together with the atoms to which it is connected or be replaced by one or more R 4h substituted 3-10 membered saturated heterocycle;

[0513] R 4h are independently -OH, -N(R 8 )2, C1-C6 alkyl or one or more R 4-h Substituted C1-C6 alkyl;

[0514] R 4-h are independently -N(R 8 )2;

[0515] R 6 For hydrogen.

[0516] In one embodiment of the present invention,

[0517] When n is 2 or 3, X is independently a -C(R 7 )2-, when n is 1, X is a -CR 7 =CR 7 -、a -N=N- and a -CR 7 =N-, where side a and The N atoms in are connected;

[0518] R 7 are independently hydrogen;

[0519] L is -O-(CR 9 R 9 ) n1 - b , where side b is connected to R 2 connected;

[0520] R 9 are independently hydrogen;

[0521] n1 is 0 or 1;

[0522] R 2 is hydrogen, one or more R 2a Substituted C3-C 10 Cycloalkyl or one or more R 2c substituted 4-10 membered heterocycloalkyl;

[0523] R 2a are independently (4-10 membered heterocycloalkyl)-CH2-;

[0524] R 2c are independently halogen;

[0525] R 1 For one or more R 1b substituted 5-10 membered heteroaryl;

[0526] R 1b are independently C1-C6 alkyl, -N(R 8 )2 or by one or more R 1-a Substituted C1-C6 alkyl;

[0527] R 1-a are independently halogen;

[0528] R 3 is a halogen;

[0529] Y is -NR 4 - or O;

[0530] R 4 is hydrogen, C1-C6 alkyl, 3-10 membered heterocycloalkyl, 4a Substituted C1-C6 alkyl or one or more R 4b Substituted C3-C 10 Cycloalkyl;

[0531] R 4a are independently -N(R 8 )2、-C(O)N(R 10 )2. C3-C 10 Cycloalkyl, 3-10 membered heterocycloalkyl, 4-b Substituted C3-C 10 Cycloalkyl, one or more R 4-c substituted 3-10 membered heterocycloalkyl or one or more R 4-e substituted 5-10 membered heteroaryl;

[0532] R 4b are independently -C(O)N(R 10 )2;

[0533] R 4-b are independently -C(O)N(R 10 )2;

[0534] R 4-c are independently -C(O)N(R 10 )2;

[0535] R 4-e are independently -N(R 8 )2;

[0536] R 8 are independently hydrogen or C1-C6 alkyl;

[0537] R 10 are independently hydrogen;

[0538] R 5 is hydrogen, one or more R 5a Substituted C1-C6 alkyl or one or more R 5b substituted 3-10 membered heterocycloalkyl;

[0539] R 5a is -OH;

[0540] R 5b =O;

[0541] R 4 and R 5 It can also form together with the atoms to which it is attached one or more R 4h substituted 3-10 membered saturated heterocycle;

[0542] R 4h are independently -OH, -N(R 8 )2, C1-C6 alkyl or one or more R 4-h Substituted C1-C6 alkyl;

[0543] R 4-h are independently -N(R 8 )2;

[0544] R 6 For hydrogen.

[0545] In one embodiment of the present invention, X is independently -C(R 7 )2-、-CR 7 =CR 7 -or a -N=CR 7 -, n is 1, 2 or 3, R 7 are independently hydrogen or C1-C6 alkyl, wherein a side and The N atoms in the .

[0546] In one embodiment of the present invention, X is independently -C(R 7 )2-、-CR 7 =CR 7 -or a -N=CR 7 -, n is 1, 2 or 3, R 7 are independently hydrogen, wherein a side and The N atoms in the .

[0547] In one embodiment of the present invention, X is independently -C(R 7 )2-, n is 2 or 3, or X is independently -CR 7 =CR 7 -or a -N=CR 7 -, n is 1, R 7 are independently hydrogen or C1-C6 alkyl, wherein a side and The N atoms in the .

[0548] In one embodiment of the present invention, X is independently -C(R 7 )2-, n is 2 or 3, or X is independently -CR 7 =CR 7 -or a -N=CR 7 -, n is 1, R 7 are independently hydrogen, wherein a side and The N atoms in the .

[0549] In one embodiment of the present invention, R 1 For one or more R 1a Substituted C6-C 10 Aryl or one or more R 1bSubstituted 5-10 membered heteroaryl, R 1a are independently halogen, -OH or -N(R 8 )2,R 8 is hydrogen, R 1b are independently halogen, -CN, C1-C6 alkyl, -N(R 8 )2 or by one or more R 1-a Substituted C1-C6 alkyl, R 1-a are independently halogen.

[0550] In one embodiment of the present invention, R 2 is a 4-10 membered heterocycloalkyl group, 2a Substituted C3-C 10 Cycloalkyl or one or more R 2c Substituted 4-10 membered heterocycloalkyl; R 2a is independently (4-10 membered heterocycloalkyl)-CH2-, wherein the 4-10 membered heterocycloalkyl in the (4-10 membered heterocycloalkyl)-CH2- is optionally replaced by C l -C6 alkyl substituted; R 2c are independently halogen, C1-C4 alkyl or (C l -C4 alkyl)-O-(C l -C4 alkyl)-.

[0551] In one embodiment of the present invention, R 2 For one or more R 2c Substituted 4-10 membered heterocycloalkyl; R 2c are independently halogen or C1-C4 alkyl.

[0552] In one embodiment of the present invention, R 4 are independently hydrogen or replaced by one or more R 4a Substituted C1-C6 alkyl;

[0553] R 4a Independently C3-C 10 Cycloalkyl, 3-10 membered heterocycloalkyl, 4-b Substituted C3-C 10 Cycloalkyl or one or more R 4-e substituted 5-10 membered heteroaryl; preferably, R 4a Independently for one or more R 4-b Substituted C3-C 10 Cycloalkyl or one or more R 4-e substituted 5-10 membered heteroaryl;

[0554] R 4-b are independently -C(O)N(R 10 )2;

[0555] R 4-e are independently -N(R 8 )2;

[0556] R 8 are independently hydrogen;

[0557] R 10 are independently hydrogen.

[0558] In one embodiment of the present invention, R 5 is hydrogen or is replaced by one or more R 5a Substituted C1-C6 alkyl, R 5a is independently -OH.

[0559] In one embodiment of the present invention, R 4 and R 5 It can also form a 3-10 membered saturated heterocyclic ring or two R 4h Substituted 3-10 membered saturated heterocyclic ring, two R 4h Adjacent, and two R 4h Together with the atoms to which they are attached, they form a 5-10 membered heteroaryl ring.

[0560] In one embodiment of the present invention, R 4 and R 5 They may also be taken together with the atoms to which they are attached to form a 3-10 membered saturated heterocyclic ring.

[0561] In one embodiment of the present invention,

[0562] X is -C(R 7 )2-, n is 2 or 3, or X is -CR 7 =CR 7 -or a -N=CR 7 -, n is 1, where a side is The N atoms in are connected;

[0563] R 7 are independently hydrogen or C1-C6 alkyl;

[0564] L is -O- b 、-O-CH2- b or -O-CH(CH3)- b , where side b is connected to R 2 connected;

[0565] R 2 is a 4-10 membered heterocycloalkyl group, 2a Substituted C3-C 10 Cycloalkyl or one or more R 2csubstituted 4-10 membered heterocycloalkyl;

[0566] R 2a is independently (4-10 membered heterocycloalkyl)-CH2-, wherein the 4-10 membered heterocycloalkyl in the (4-10 membered heterocycloalkyl)-CH2- is optionally replaced by C l -C6 alkyl substitution;

[0567] R 2c are independently halogen, C1-C4 alkyl or (C l -C4 alkyl)-O-(C l -C4 alkyl)-;

[0568] R 1 For one or more R 1a Substituted C6-C 10 Aryl or one or more R 1b substituted 5-10 membered heteroaryl;

[0569] R 1a are independently halogen, -OH or -N(R 8 )2;

[0570] R 1b are independently halogen, -CN, C1-C6 alkyl, -N(R 8 )2 or by one or more R 1-a Substituted C1-C6 alkyl;

[0571] R 1-a are independently halogen;

[0572] R 3 is a halogen;

[0573] Y is -NR 4 -, O, or c -(CH2) p NR 4 -, p is 1, c side is -CHR 5 - connected;

[0574] R 4 are independently hydrogen or replaced by one or more R 4a Substituted C1-C6 alkyl;

[0575] R 4a Independently C3-C 10 Cycloalkyl, 3-10 membered heterocycloalkyl, 4-b Substituted C3-C 10 Cycloalkyl or one or more R 4-e substituted 5-10 membered heteroaryl; preferably, R 4a Independently for one or more R4-b Substituted C3-C 10 Cycloalkyl or one or more R 4-e substituted 5-10 membered heteroaryl;

[0576] R 4-b are independently -C(O)N(R 10 )2;

[0577] R 4-e are independently -N(R 8 )2;

[0578] R 8 are independently hydrogen;

[0579] R 10 are independently hydrogen;

[0580] R 5 is hydrogen or is replaced by one or more R 5a Substituted C1-C6 alkyl, R 5a are independently -OH;

[0581] Or, R 4 and R 5 It can also form a 3-10 membered saturated heterocyclic ring or two R 4h Substituted 3-10 membered saturated heterocyclic ring, two R 4h Adjacent, and two R 4h Together with the atoms to which they are attached, they form a 5-10 membered heteroaromatic ring;

[0582] R 6 For hydrogen.

[0583] In one embodiment of the present invention,

[0584] X is -C(R 7 )2-, n is 2 or 3, or X is -CR 7 =CR 7 -or a -N=CR 7 -, n is 1; where a side and The N atoms in are connected;

[0585] R 7 are independently hydrogen;

[0586] L is -O-CH2-;

[0587] R 2 For one or more R 2c substituted 4-10 membered heterocycloalkyl;

[0588] R 2care independently halogen or C1-C4 alkyl;

[0589] R 1 For one or more R 1b substituted 5-10 membered heteroaryl;

[0590] R 1b are independently C1-C6 alkyl, -N(R 8 )2 or by one or more R 1-a Substituted C1-C6 alkyl;

[0591] R 1-a are independently halogen;

[0592] R 3 is a halogen;

[0593] R 4 are independently hydrogen or replaced by one or more R 4a Substituted C1-C6 alkyl;

[0594] R 4a Independently C3-C 10 Cycloalkyl, 3-10 membered heterocycloalkyl, 4-b Substituted C3-C 10 Cycloalkyl or one or more R 4-e substituted 5-10 membered heteroaryl; preferably, R 4a Independently for one or more R 4-b Substituted C3-C 10 Cycloalkyl or one or more R 4-e substituted 5-10 membered heteroaryl;

[0595] R 4-b are independently -C(O)N(R 10 )2;

[0596] R 4-e are independently -N(R 8 )2;

[0597] R 8 are independently hydrogen;

[0598] R 10 are independently hydrogen;

[0599] R 5 is hydrogen or is replaced by one or more R 5a Substituted C1-C6 alkyl, R 5a are independently -OH;

[0600] Or, R 4 and R 5It can also form a 3-10 membered saturated heterocyclic ring together with the atoms to which it is attached;

[0601] R 6 For hydrogen.

[0602] In one embodiment of the present invention,

[0603] X is -C(R 7 )2- or -CR 7 =CR 7 -, n is 1, 2 or 3, R 7 is hydrogen;

[0604] Preferably, X is -CR 7 =CR 7 -, n is 1, R 7 is hydrogen;

[0605] L is -O-CH2-;

[0606] R 2 For one or more R 2c substituted 4-10 membered heterocycloalkyl;

[0607] R 2c are independently halogen;

[0608] R 1 For one or more R 1b substituted 5-10 membered heteroaryl;

[0609] R 1b are independently C1-C6 alkyl, -N(R 8 )2 or by one or more R 1-a Substituted C1-C6 alkyl;

[0610] R 1-a are independently halogen;

[0611] R 3 is a halogen;

[0612] Y is -NR 4 ;

[0613] R 4 For one or more R 4a Substituted C1-C6 alkyl;

[0614] R 4a Independently C3-C 10 Cycloalkyl, 3-10 membered heterocycloalkyl or one or more R 4-e substituted 5-10 membered heteroaryl; preferably, R 4a Independently for one or more R 4-e substituted 5-10 membered heteroaryl;

[0615] R 4-e are independently -N(R 8 )2;

[0616] R 5 is hydrogen;

[0617] R 6 is hydrogen;

[0618] R 8 are independently hydrogen.

[0619] In one embodiment of the present invention, -(X) n - is -CH2-CH2-, -CH2-CH2-CH2-, -CH=CH-, -N=N-, -C(CH3)=N-, or -CH=N-; preferably, -(X) n -for a -CH2-CH2-, a -CH2-CH2-CH2-, a -CH=CH-, a -N=N-、-C(CH3)=N- a 、 a -N=CH- or a -CH=N-, a side and More preferably, (X) n -for a -CH2-CH2-CH2-, a -CH=CH-, -C(CH3)=N- a or a -N=CH-, a side and The N atoms in the -(X) n -for a -CH=CH- or a - N=CH-, where a side is The N atoms in the .

[0620] In one embodiment of the present invention, -(X) n - is -CH2-CH2-, -CH2-CH2-CH2-, -CH=CH-, -N=N- or -CH=N-; preferably, -(X) n -for a -CH2-CH2-, a -CH2-CH2-CH2-, a -CH=CH-, a -N=N- or a -CH=N-, a side and More preferably, -(X) n -for a -CH=CH-, where a side and The N atoms in the .

[0621] In one embodiment of the present invention, -(X) n -for a -CH2-CH2-, a -CH2-CH2-CH2-, a -CH=CH-, a -N=N-, a -CH=N- or a -N=CH-, a side and More preferably, -(X) n -for a -CH2-CH2-, a -CH2-CH2-CH2-, a -CH=CH- or a -N=CN-, where a side is The N atoms in the .

[0622] In one embodiment of the present invention, L is absent, -O-, For example, L does not exist, -O- b 、 The b side is connected to R 2 For example, L does not exist or The b side is connected to R 2 connected.

[0623] In one embodiment of the present invention, L is -O-, For example -O- b 、 The b side is connected to R 2 connected.

[0624] In one embodiment of the present invention, L is -O- or For example -O- b or The b side is connected to R 2 Preferably, L is The b side is connected to R 2 connected.

[0625] In one embodiment of the present invention, R 2 For hydrogen, Preferably, R 2 for More preferably, R 2 for

[0626] Optimally, R 2 for

[0627] In one embodiment of the present invention, R 2 for

[0628] Preferably, R 2 for

[0629] In one embodiment of the present invention, R 2 For hydrogen, Preferably, R 2 for

[0630] In one embodiment of the present invention, R 2 For hydrogen, Preferably, R 2 for

[0631] In one embodiment of the present invention, R 2 For hydrogen, Preferably, R 2 for

[0632] In one embodiment of the present invention, R 1 for Preferably, R 1 for More preferably, R 1 for Optimally, R 1 for

[0633] In one embodiment of the present invention, R 1 for Preferably, R 1 for

[0634] In one embodiment of the present invention, R 1 for Preferably, R 1 for

[0635] In one embodiment of the present invention, R 1 for Preferably, R 1 for

[0636] In one embodiment of the present invention, R 3 is a halogen, such as F.

[0637] In one embodiment of the present invention, Y is -NR 4 or O; preferably Y is -NR 4 .

[0638] In one embodiment of the present invention, R 4 For hydrogen, -CH3,

[0639] Preferably, R 4 For hydrogen,

[0640] More preferably, R 4 For hydrogen, Optimally, R 4 for

[0641] Or, R 4 for

[0642] In one embodiment of the present invention, R 4 For hydrogen, -CH3,

[0643] Preferably, R 4 For hydrogen,

[0644] More preferably, R 4 For hydrogen, Optimally, R 4 for

[0645] Or, R 4 for

[0646] In one embodiment of the present invention, R 4 For hydrogen, -CH3,

[0647] Preferably, R 4 For hydrogen,

[0648] In one embodiment of the present invention, R 4 For hydrogen, -CH3, Preferably, R 4 For hydrogen, More preferably, R 4 for

[0649] In one embodiment of the present invention, R 5 For hydrogen, Preferably, R 5 For hydrogen or More preferably, R 5 For hydrogen.

[0650] In one embodiment of the present invention, R 4 and R 5 It can also form together with the atoms to which it is connected Preferably, R 4 and R 5 It can also form together with the atoms to which it is connected

[0651] In one embodiment of the present invention, R 4 and R 5 It can also form together with the atoms to which it is connected Preferably, R 4 and R 5 It can also form together with the atoms to which it is connected

[0652] In one embodiment of the present invention, R 4 and R 5 It can also form together with the atoms to which it is connected

[0653] In one embodiment of the present invention, the heterocyclic compound represented by formula I is a compound represented by formula I-1-1, I-1-2, I-1-3, I-1-4, I-1-5, I-1-6, I-1-7, I-1-8 or I-1-9:

[0654] m is 1, 2, or 3;

[0655] X, n, Y, R 2 、R 3 、R 5 、R 6 and R 1b The definition of is as described in the previous scheme.

[0656] Preferably, in the compound represented by formula I-1-1, I-1-2, I-1-3, I-1-4, I-1-5, I-1-6, I-1-7, I-1-8 or I-1-9, Y is -NR 4 -, R 4 The definition of is as described in the previous scheme.

[0657] More preferably, in the compound represented by formula I-1-1, I-1-2, I-1-3, I-1-4, I-1-5, I-1-6, I-1-7, I-1-8 or I-1-9, Y is -NR 4 -, R 4 for mixture of R 4a The definition of is as described in the previous scheme.

[0658] In one embodiment of the present invention, the heterocyclic compound represented by formula I is a compound represented by formula I-4-1, I-4-2 or I-4-3:

[0659] in, represents a single bond or a double bond;

[0660] m is 1, 2, or 3;

[0661] R 4For one or more R 4b Substituted C3-C 10 Cycloalkyl, "Mixture of"; preferably one or more R 4b Substituted C3-C 10 Cycloalkyl, mixture of";

[0662] R 4a Independently for one or more R 4-e substituted 5-10 membered heteroaryl, substituted by one or more R 4-b substituted cyclopropane;

[0663] Among them, when R 4 For one or more R 4b Substituted C3-C 10 When cycloalkyl, the C3-C 10 In the cycloalkyl group, The configuration of the carbon atom connected to N in is R configuration, and the R 4b In the C3-C 10 The carbon atom configuration of the connection site on the cycloalkyl group is also R configuration;

[0664] R 3 、R 4b 、R 4-e 、R 4-b 、R 6 and R 1b The definition of is as described in the previous scheme.

[0665] In one embodiment of the present invention, the heterocyclic compound represented by formula I is a compound represented by formula I-5:

[0666] Wherein, m is 1, 2 or 3;

[0667] The carbon atom with "*" is chiral carbon, and its configuration is R configuration;

[0668] R 4 for Or 3-10 membered heterocycloalkyl, wherein the 3-10 membered heterocycloalkyl The configuration of the carbon atom connected to the nitrogen in the is R configuration;

[0669] R 4a C3-C 10 Cycloalkyl or 4-membered heterocycloalkyl;

[0670] R 5 For one or more R 5a Substituted C1-C6 alkyl or one or more R 5bSubstituted 3-10 membered heterocycloalkyl, wherein the 3-10 membered heterocycloalkyl The configuration of the connected carbon atoms is R configuration;

[0671] R 3 、R 5a 、R 5b 、R 6 and R 1b The definition of is as described in the previous scheme.

[0672] In one embodiment of the present invention, the heterocyclic compound represented by formula I is a compound represented by formula I-6:

[0673] L, Y, R 1 、R 2 、R 3 and R 7 The definition of is as described in any embodiment of the present invention;

[0674] Preferably, L and R 3 The definition of R is as described in the previous scheme. 7 is hydrogen, Y is -NR 4 -or c -(CH2) p NR 4 -, p is 1, c side is -CHR 5 - connected, R 5 is hydrogen, R 1 、R 2 and R 4 is defined as any of the following:

[0675] Case 1: R 1 For one or more R 1b Replaced R 1b are independently halogen, -CN or -N(R 8 )2,R 8 is hydrogen;

[0676] R 2 For one or more R 2a Substituted C3-C 10 Cycloalkyl or one or more R 2c Substituted 4-10 membered heterocycloalkyl, R 2a are independently (4-10 membered heterocycloalkyl)-CH2-, R 2c are independently halogen, C1-C4 alkyl or 4-10 membered heterocycloalkyl;

[0677] R 4 -SO2R h or by one or more R4a Substituted C1-C6 alkyl; R 4a Independently -OR 10 or by one or more R 4-e Substituted 5-10 membered heteroaryl; R 4-e are independently -N(R 8 )2 or halogen; R h Independently for one or more R 4-e Substituted 5-10 membered heteroaryl; R 10 is hydrogen;

[0678] Case 2: R 1 For one or more R 1b Replaced R 1b are independently C1-C6 alkyl, -N(R 8 )2 or by one or more R 1-a Substituted C1-C6 alkyl; R 8 is hydrogen; R 1-a are independently halogen;

[0679] R 2 For one or more R 2a Substituted C3-C 10 Cycloalkyl or one or more R 2c Substituted 8-10 membered heterocyclic alkyl, R 2a are independently (4-10 membered heterocycloalkyl)-CH2-, R 2c are independently halogen;

[0680] R 4 For one or more R 4a Substituted C1-C6 alkyl; R 4a Independently for one or more R 4-e Substituted 5-10 membered heteroaryl, R 4-e are independently -N(R 8 )2;

[0681] Case 3: R 1 For one or more R 1b Replaced R 1b are independently halogen, -CN or -N(R 8 )2,R 8 is hydrogen;

[0682] R 2 For one or more R 2c Substituted 4-10 membered heterocycloalkyl, R 2c are independently halogen;

[0683] R4 For one or more R 4a Substituted C1-C6 alkyl; R 4a Independently for one or more R 4-e Substituted 5-10 membered heteroaryl, R 4-e are independently halogen, -N(R 8 )2OR-OR 10 ; R 10 are independently C1-C6 alkyl;

[0684] Case 4: R 1 For one or more R 1b Replaced R 1b are independently halogen, -CN or -N(R 8 )2,R 8 is hydrogen;

[0685] R 2 For one or more R 2a Substituted C3-C 10 Cycloalkyl or one or more R 2c Substituted 4-10 membered heterocycloalkyl, R 2a are independently (4-10 membered heterocycloalkyl)-CH2-, R 2c are independently halogen, ═CR 2-c R 2-c , C1-C4 alkyl or 4-10 membered heterocycloalkyl, R 2-c are independently halogen;

[0686] R 4 -SO2R h or by one or more R 4a Substituted C1-C6 alkyl; R 4a Independently -OR 10 , 3-10 membered heterocycloalkyl or one or more R 4-e Substituted 5-10 membered heteroaryl; R 4-e are independently -N(R 8 )2 or halogen; R h Independently for one or more R 4-e Substituted 5-10 membered heteroaryl; R 10 is hydrogen or C1-C6 alkyl;

[0687] Case 5: R 1 For one or more R 1b Replaced R 1b are independently halogen, -CN or -N(R 8 )2,R 8 is hydrogen;

[0688] R 2 For one or more R 2c Substituted 4-10 membered heterocycloalkyl, R 2c are independently halogen or C1-C4 alkyl;

[0689] R 4 For one or more R 4a Substituted C1-C6 alkyl; R 4a Independently -OR 10 , 3-10 membered heterocycloalkyl or one or more R 4-e Substituted 5-10 membered heteroaryl, R 4-e are independently halogen, -N(R 8 )2OR-OR 10 ; R 10 are independently hydrogen or C1-C6 alkyl;

[0690] R 4-i Each is independently a C1-C6 alkyl group.

[0691] In one embodiment of the present invention, the heterocyclic compound represented by formula I is a compound represented by formula I-6:

[0692] L, Y, R 1 、R 2 、R 3 and R 7 The definition of is as described in any embodiment of the present invention;

[0693] Preferably, L and R 3 The definition of R is as described in the previous scheme. 7 is hydrogen, Y is -NR 4 -or c -(CH2) p NR 4 -, p is 1, c side is -CHR 5 - connected, R 5 is hydrogen, R 1 、R 2 and R 4 is defined as any of the following:

[0694] Case 1: R 1 For one or more R 1b Replaced R 1b are independently halogen, -CN or -N(R 8 )2,R 8 is hydrogen;

[0695] R2 For one or more R 2a Substituted C3-C 10 Cycloalkyl or one or more R 2c Substituted 4-10 membered heterocycloalkyl, R 2a are independently (4-10 membered heterocycloalkyl)-CH2-, R 2c are independently halogen or C1-C4 alkyl;

[0696] R 4 For one or more R 4a Substituted C1-C6 alkyl; R 4a Independently for one or more R 4-e Substituted 5-10 membered heteroaryl, R 4-e are independently -N(R 8 )2;

[0697] Case 2: R 1 For one or more R 1b Replaced R 1b are independently C1-C6 alkyl, -N(R 8 )2 or by one or more R 1-a Substituted C1-C6 alkyl; R 8 is hydrogen; R 1-a are independently halogen;

[0698] R 2 For one or more R 2a Substituted C3-C 10 Cycloalkyl or one or more R 2c Substituted 8-10 membered heterocyclic alkyl, R 2a are independently (4-10 membered heterocycloalkyl)-CH2-, R 2c are independently halogen;

[0699] R 4 For one or more R 4a Substituted C1-C6 alkyl; R 4a Independently for one or more R 4-e Substituted 5-10 membered heteroaryl, R 4-e are independently -N(R 8 )2.

[0700] In one embodiment of the present invention, the heterocyclic compound represented by formula I is any one of the following compounds:

[0701] In one embodiment of the present invention, the pharmaceutically acceptable salt of the heterocyclic compound represented by Formula I is:

[0702] In one embodiment of the present invention, the compound represented by formula I is any of the following compounds:

[0703] The compound that elutes first under the following conditions: the stationary phase is C18, the mobile phase is a mixture of A and B, wherein A is 0.1% (v / v) ammonia water, B is acetonitrile, the volume percentage of B in the mobile phase is 19%, isocratic elution, and the flow rate is 25 mL / min; the conditions are preferably: column model: C18 OBD TM 19*250mm*5μM, the mobile phase is a mixture of A and B, wherein A is 0.1% (v / v) ammonia water, B is acetonitrile, the volume percentage of B in the mobile phase is 19%, isocratic elution, and the flow rate is 25mL / min; preferably, under the said conditions, the retention time of the said first-eluting compound is 6.42min;

[0704] Compounds that elute under the following conditions: C18 stationary phase, a mixture of A and B mobile phase, wherein A is 0.1% (v / v) ammonia water, B is acetonitrile, the volume percentage of B in the mobile phase is 19%, isocratic elution, flow rate 25 mL / min; the conditions are preferably: column model: C18 OBD TM 19*250mm*5μM, the mobile phase is a mixture of A and B, wherein A is 0.1% (v / v) ammonia water, B is acetonitrile, the volume percentage of B in the mobile phase is 19%, isocratic elution, and the flow rate is 25mL / min; preferably, under the said conditions, the retention time of the said late peak compound is 8.08min;

[0705] The compound that elutes first under the following conditions: the stationary phase is C18, the mobile phase is a mixture of A and B, wherein A is 0.1% (v / v) ammonia water, B is acetonitrile, the volume percentage of B in the mobile phase is 19%, isocratic elution, and the flow rate is 25 mL / min; the conditions are preferably: column model: C18 OBD TM 19*250mm*5μM, the mobile phase is a mixture of A and B, wherein A is 0.1% (v / v) ammonia water, B is acetonitrile, the volume percentage of B in the mobile phase is 19%, isocratic elution, and the flow rate is 25mL / min; preferably, under the said conditions, the retention time of the said first peak compound is 6.45min;

[0706] The compound that elutes later under the following conditions: the stationary phase is C18, the mobile phase is a mixture of A and B, wherein A is 0.1% (v / v) ammonia water, B is acetonitrile, the volume percentage of B in the mobile phase is 19%, isocratic elution, and the flow rate is 25 mL / min; the conditions are preferably: column model: C18 OBD TM 19*250mm*5μM, the mobile phase is a mixture of A and B, wherein A is 0.1% (v / v) ammonia water, B is acetonitrile, the volume percentage of B in the mobile phase is 19%, isocratic elution, and the flow rate is 25mL / min; preferably, under the said conditions, the retention time of the said late peak compound is 7.63min;

[0707] The compound that elutes first under the following conditions: the stationary phase is C18, the mobile phase is a mixture of A and B, wherein A is 0.1% (v / v) ammonia water, B is acetonitrile, the volume percentage of B in the mobile phase is 19%, isocratic elution, and the flow rate is 25 mL / min; the conditions are preferably: column model: C18 OBD TM 19*250mm*5μM, the mobile phase is a mixture of A and B, wherein A is 0.1% (v / v) ammonia water, B is acetonitrile, the volume percentage of B in the mobile phase is 19%, isocratic elution, and the flow rate is 25mL / min; preferably, under the said conditions, the retention time of the said first peak compound is 6.15min;

[0708] The compound that elutes later under the following conditions: the stationary phase is C18, the mobile phase is a mixture of A and B, wherein A is 0.1% (v / v) ammonia water, B is acetonitrile, the volume percentage of B in the mobile phase is 19%, isocratic elution, and the flow rate is 25 mL / min; the conditions are preferably: column model: C18 OBDTM 19*250mm*5μM, the mobile phase is a mixture of A and B, wherein A is 0.1% (v / v) ammonia water, B is acetonitrile, the volume percentage of B in the mobile phase is 19%, isocratic elution, and the flow rate is 25mL / min; preferably, under the said conditions, the retention time of the said later eluting compound is 6.95min;

[0709] Under the following conditions, the retention time is 2.53 min. Stereoisomers: Column model: AcquityUPLC@BEH C18 OBD TM 2.1*50mm*1.7μM, mobile phase is a mixture of A and B, where A is 0.1% (v / v) formic acid in water, B is acetonitrile, the volume percentage of B in the mobile phase is 5-95%, flow rate is 0.5mL / min, and analysis time is 8min;

[0710] Under the following conditions, the retention time is 3.81 min. Stereoisomers: Column model: AcquityUPLC@BEH C18 OBD TM 2.1*50mm*1.7μM, mobile phase is a mixture of A and B, where A is 0.1% (v / v) formic acid in water, B is acetonitrile, the volume percentage of B in the mobile phase is 5-95%, flow rate is 0.5mL / min, and analysis time is 8min;

[0711] The compound that elutes first under the following conditions: the stationary phase is C18, the mobile phase is a mixture of A and B, wherein A is 0.1% (v / v) ammonia water, B is acetonitrile, the volume percentage of B in the mobile phase is 35-50%, and the flow rate is 25 mL / min; the conditions are preferably: column model: C18 OBD TM 19*250mm*5μM, the mobile phase is a mixture of A and B, wherein A is 0.1% (v / v) ammonia water, B is acetonitrile, the volume percentage of B in the mobile phase is 35-50%, the flow rate is 25mL / min, and the analysis time is 13min; preferably, under the said conditions, the retention time of the said first peak compound is 8.2min;

[0712] The compound that elutes later under the following conditions: the stationary phase is C18, the mobile phase is a mixture of A and B, wherein A is 0.1% (v / v) ammonia water, B is acetonitrile, the volume percentage of B in the mobile phase is 35-50%, and the flow rate is 25 mL / min; the conditions are preferably: column model: C18 OBD TM19*250mm*5μM, the mobile phase is a mixture of A and B, wherein A is 0.1% (v / v) ammonia water, B is acetonitrile, the volume percentage of B in the mobile phase is 35-50%, the flow rate is 25mL / min, and the analysis time is 13min; preferably, under the said conditions, the retention time of the said late peak compound is 8.5min;

[0713] The compound that elutes first under the following conditions: the stationary phase is C18, the mobile phase is a mixture of A and B, wherein A is a 0.1% (v / v) formic acid aqueous solution, B is acetonitrile, the volume percentage of B in the mobile phase is 5-95%, and the flow rate is 0.5 mL / min; the conditions are preferably: column model: AcquityUPLC@BEH C18 OBD TM 2.1*50mm*1.7μM, the mobile phase is a mixture of A and B, wherein A is a 0.1% (v / v) formic acid aqueous solution, B is acetonitrile, the volume percentage of B in the mobile phase is 5-95%, the flow rate is 0.5mL / min, and the analysis time is 8min; preferably, under the said conditions, the retention time of the said first-eluting compound is 3.80-4.10min;

[0714] Compounds that elute later under the following conditions: C18 stationary phase, a mixture of A and B mobile phase, wherein A is 0.1% (v / v) formic acid aqueous solution, B is acetonitrile, the volume percentage of B in the mobile phase is 5-95%, and the flow rate is 0.5 mL / min; the conditions are preferably: Column model: AcquityUPLC@BEH C18 OBD TM 2.1*50mm*1.7μM, the mobile phase is a mixture of A and B, wherein A is a 0.1% (v / v) formic acid aqueous solution, B is acetonitrile, the volume percentage of B in the mobile phase is 5-95%, the flow rate is 0.5mL / min, and the analysis time is 8min; preferably, under the said conditions, the retention time of the said later eluting compound is 4.30-4.55min; The compound that elutes first under the following conditions: the stationary phase is C18, the mobile phase is a mixture of A and B, wherein A is a 0.1% (v / v) formic acid aqueous solution, B is acetonitrile, the volume percentage of B in the mobile phase is 5-95%, and the flow rate is 0.5 mL / min; the conditions are preferably: column model: AcquityUPLC@BEH C18 OBD TM2.1*50mm*1.7μM, the mobile phase is a mixture of A and B, wherein A is a 0.1% (v / v) formic acid aqueous solution, B is acetonitrile, the volume percentage of B in the mobile phase is 5-95%, the flow rate is 0.5mL / min, and the analysis time is 8min; preferably, under the said conditions, the retention time of the said first-eluting compound is 3.67-3.87min; Compounds that elute later under the following conditions: C18 stationary phase, a mixture of A and B mobile phase, wherein A is 0.1% (v / v) formic acid aqueous solution, B is acetonitrile, the volume percentage of B in the mobile phase is 5-95%, and the flow rate is 0.5 mL / min; the conditions are preferably: Column model: AcquityUPLC@BEH C18 OBD TM 2.1*50mm*1.7μM, the mobile phase is a mixture of A and B, wherein A is a 0.1% (v / v) formic acid aqueous solution, B is acetonitrile, the volume percentage of B in the mobile phase is 5-95%, the flow rate is 0.5mL / min, and the analysis time is 8min; preferably, under the said conditions, the retention time of the said later eluting compound is 3.89-3.98min;

[0715] The compound that elutes first under the following conditions: the stationary phase is C18, the mobile phase is a mixture of A and B, wherein A is 0.1% (v / v) ammonia water, B is acetonitrile, the volume percentage of B in the mobile phase is 45-55%, and the flow rate is 25 mL / min; the conditions are preferably: column model: C18 OBD TM 19*250mm*5μM, the mobile phase is a mixture of A and B, wherein A is 0.1% (v / v) ammonia water, B is acetonitrile, the volume percentage of B in the mobile phase is 45-55%, the flow rate is 25mL / min, and the analysis time is 13.2min; preferably, under the said conditions, the retention time of the said first peak compound is 7.25min;

[0716] The compound that elutes later under the following conditions: the stationary phase is C18, the mobile phase is a mixture of A and B, wherein A is 0.1% (v / v) ammonia water, B is acetonitrile, the volume percentage of B in the mobile phase is 45-55%, and the flow rate is 25 mL / min; the conditions are preferably: column model: C18 OBD TM19*250mm*5μM, the mobile phase is a mixture of A and B, wherein A is 0.1% (v / v) ammonia water, B is acetonitrile, the volume percentage of B in the mobile phase is 45-55%, the flow rate is 25mL / min, and the analysis time is 13.2min; preferably, under the said conditions, the retention time of the said late-eluting compound is 8.3min;

[0717] The compound that elutes first under the following conditions: the stationary phase is C18, the mobile phase is a mixture of A and B, wherein A is a 0.1% (v / v) formic acid aqueous solution, B is acetonitrile, the volume percentage of B in the mobile phase is 5-95%, and the flow rate is 0.5 mL / min; the conditions are preferably: column model: AcquityUPLC@BEH C18 OBD TM 2.1*50mm*1.7μM, mobile phase is a mixture of A and B, wherein A is 0.1% (v / v) formic acid in water and B is acetonitrile; the volume percentage of B in the mobile phase is 5-95%; flow rate is 0.5mL / min; analysis time is 8min; preferably, under the above conditions, the retention time of the first-eluting compound is 3.65-3.85min;

[0718] Compounds that elute later under the following conditions: C18 stationary phase, a mixture of A and B mobile phase, wherein A is 0.1% (v / v) formic acid in water, B is acetonitrile, the volume percentage of B in the mobile phase is 5-95%, and the flow rate is 0.5 mL / min; the conditions are preferably: Column model: AcquityUPLC@BEH C18 OBD TM 2.1*50mm*1.7μM, mobile phase is a mixture of A and B, wherein A is 0.1% (v / v) formic acid in water and B is acetonitrile; the volume percentage of B in the mobile phase is 5-95%; flow rate is 0.5mL / min; analysis time is 8min; preferably, under the above conditions, the retention time of the late-eluting compound is 3.87-3.95min;

[0719] The compound that elutes first under the following conditions: the stationary phase is C18, the mobile phase is a mixture of A and B, wherein A is a 0.1% (v / v) formic acid aqueous solution, B is acetonitrile, the volume percentage of B in the mobile phase is 5-95%, and the flow rate is 0.5 mL / min; the conditions are preferably: column model: AcquityUPLC@BEH C18 OBD TM2.1*50mm*1.7μM, mobile phase consisting of a mixture of A and B, wherein A is 0.1% (v / v) formic acid in water and B is acetonitrile; the volume percentage of B in the mobile phase is 5-95%; flow rate is 0.5mL / min; analysis time is 8min; preferably, under the described conditions, the retention time of the first-eluting compound is 3.64-3.84min;

[0720] Compounds that elute later under the following conditions: C18 stationary phase, a mixture of A and B mobile phase, wherein A is 0.1% (v / v) formic acid aqueous solution, B is acetonitrile, the volume percentage of B in the mobile phase is 5-95%, and the flow rate is 0.5 mL / min; the conditions are preferably: Column model: AcquityUPLC@BEH C18 OBD TM 2.1*50mm*1.7μM, mobile phase is a mixture of A and B, wherein A is 0.1% (v / v) formic acid in water and B is acetonitrile; the volume percentage of B in the mobile phase is 5-95%; flow rate is 0.5mL / min; analysis time is 8min; preferably, under the above conditions, the retention time of the compound eluting later is 3.84-3.93min;

[0721] Under the following conditions, the retention time is 3.60-3.69 min Stereoisomers, column: AcquityUPLC@BEH C18 OBD TM 2.1*50mm*1.7μM, mobile phase is a mixture of A and B, where A is 0.1% (v / v) formic acid in water and B is acetonitrile; the volume percentage of B in the mobile phase is 5-95%; flow rate is 0.5mL / min; analysis time is 8min;

[0722] Under the following conditions, the retention time is 3.69-3.77min Stereoisomers, column: AcquityUPLC@BEH C18 OBD TM 2.1*50mm*1.7μM, mobile phase is a mixture of A and B, where A is 0.1% (v / v) formic acid in water and B is acetonitrile; the volume percentage of B in the mobile phase is 5-95%; flow rate is 0.5mL / min; analysis time is 8min;

[0723] Under the following conditions, the retention time is 3.88-3.97min Stereoisomers, column: AcquityUPLC@BEH C18 OBD TM2.1*50mm*1.7μM, mobile phase is a mixture of A and B, where A is 0.1% (v / v) formic acid in water and B is acetonitrile; the volume percentage of B in the mobile phase is 5-95%; flow rate is 0.5mL / min; analysis time is 8min;

[0724] The compound that elutes first under the following conditions: the stationary phase is C18, the mobile phase is a mixture of A and B, wherein A is a 0.1% (v / v) formic acid aqueous solution, B is acetonitrile, the volume percentage of B in the mobile phase is 5-95%, and the flow rate is 0.5 mL / min; the conditions are preferably: column model: AcquityUPLC@BEH C18 OBD TM 2.1*50mm*1.7μM, mobile phase is a mixture of A and B, wherein A is 0.1% (v / v) formic acid in water and B is acetonitrile; the volume percentage of B in the mobile phase is 5-95%; flow rate is 0.5mL / min; analysis time is 8min; preferably, under the above conditions, the retention time of the first-eluting compound is 3.67-3.87min;

[0725] Compounds that elute later under the following conditions: C18 stationary phase, a mixture of A and B mobile phase, wherein A is 0.1% (v / v) formic acid aqueous solution, B is acetonitrile, the volume percentage of B in the mobile phase is 5-95%, and the flow rate is 0.5 mL / min; the conditions are preferably: Column model: AcquityUPLC@BEH C18 OBD TM 2.1*50mm*1.7μM, mobile phase is a mixture of A and B, wherein A is 0.1% (v / v) formic acid in water and B is acetonitrile; the volume percentage of B in the mobile phase is 5-95%; flow rate is 0.5mL / min; analysis time is 8min; preferably, under the above conditions, the retention time of the compound eluting later is 3.89-3.98min;

[0726] The compound that elutes first under the following conditions: the stationary phase is C18, the mobile phase is a mixture of A and B, wherein A is a 0.1% (v / v) formic acid aqueous solution, B is acetonitrile, the volume percentage of B in the mobile phase is 5-95%, and the flow rate is 0.5 mL / min; the conditions are preferably: column model: AcquityUPLC@BEH C18 OBD TM2.1*50mm*1.7μM, mobile phase is a mixture of A and B, wherein A is 0.1% (v / v) formic acid in water and B is acetonitrile; the volume percentage of B in the mobile phase is 5-95%; flow rate is 0.5mL / min; analysis time is 8min; preferably, under the above conditions, the retention time of the first-eluting compound is 3.65-3.74min;

[0727] Compounds that elute later under the following conditions: C18 stationary phase, a mixture of A and B mobile phase, wherein A is 0.1% (v / v) formic acid aqueous solution, B is acetonitrile, the volume percentage of B in the mobile phase is 5-95%, and the flow rate is 0.5 mL / min; the conditions are preferably: Column model: AcquityUPLC@BEH C18 OBD TM 2.1*50mm*1.7μM, mobile phase is a mixture of A and B, wherein A is 0.1% (v / v) formic acid in water and B is acetonitrile; the volume percentage of B in the mobile phase is 5-95%; flow rate is 0.5mL / min; analysis time is 8min; preferably, under the above conditions, the retention time of the late-eluting compound is 3.86-3.95min;

[0728] The compound that elutes first under the following conditions: the stationary phase is C18, the mobile phase is a mixture of A and B, wherein A is a 0.1% (v / v) formic acid aqueous solution, B is acetonitrile, the volume percentage of B in the mobile phase is 5-95%, and the flow rate is 0.5 mL / min; the conditions are preferably: column model: AcquityUPLC@BEH C18 OBD TM 2.1*50mm*1.7μM, mobile phase is a mixture of A and B, wherein A is 0.1% (v / v) formic acid in water and B is acetonitrile; the volume percentage of B in the mobile phase is 5-95%; flow rate is 0.5mL / min; analysis time is 8min; preferably, under the above conditions, the retention time of the first-eluting compound is 3.66-3.75min;

[0729] Compounds that elute later under the following conditions: C18 stationary phase, a mixture of A and B mobile phase, wherein A is 0.1% (v / v) formic acid aqueous solution, B is acetonitrile, the volume percentage of B in the mobile phase is 5-95%, and the flow rate is 0.5 mL / min; the conditions are preferably: Column model: AcquityUPLC@BEH C18 OBD TM2.1*50mm*1.7μM, mobile phase is a mixture of A and B, wherein A is 0.1% (v / v) formic acid in water and B is acetonitrile; the volume percentage of B in the mobile phase is 5-95%; flow rate is 0.5mL / min; analysis time is 8min; preferably, under the above conditions, the retention time of the late-eluting compound is 3.86-3.95min;

[0730] The compound that elutes first under the following conditions: the stationary phase is C18, the mobile phase is a mixture of A and B, wherein A is a 0.1% (v / v) formic acid aqueous solution, B is acetonitrile, the volume percentage of B in the mobile phase is 5-95%, and the flow rate is 0.5 mL / min; the conditions are preferably: column model: AcquityUPLC@BEH C18 OBD TM 2.1*50mm*1.7μM, mobile phase is a mixture of A and B, wherein A is 0.1% (v / v) formic acid in water and B is acetonitrile; the volume percentage of B in the mobile phase is 5-95%; flow rate is 0.5mL / min; analysis time is 8min; preferably, under the above conditions, the retention time of the first-eluting compound is 3.67-3.76min;

[0731] Compounds that elute later under the following conditions: C18 stationary phase, a mixture of A and B mobile phase, wherein A is 0.1% (v / v) formic acid aqueous solution, B is acetonitrile, the volume percentage of B in the mobile phase is 5-95%, and the flow rate is 0.5 mL / min; the conditions are preferably: Column model: AcquityUPLC@BEH C18 OBD TM 2.1*50mm*1.7μM, the mobile phase is a mixture of A and B, wherein A is a 0.1% (v / v) formic acid aqueous solution and B is acetonitrile; the volume percentage of B in the mobile phase is 5-95%; the flow rate is 0.5mL / min; the analysis time is 8min; preferably, under the said conditions, the retention time of the said late-eluting compound is 3.85-3.94min.

[0732] The above retention time test conditions do not limit the compounds. As long as the retention time obtained by the above test conditions is the same as that recorded above or is within the error range, and the compound is a stereoisomer of the compound defined by the retention time, it falls within the scope of protection of the present invention.

[0733] The present invention also provides a pharmaceutical composition comprising a substance X and a pharmaceutically acceptable excipient, wherein the substance X is a heterocyclic compound represented by Formula I described in any of the above schemes, a pharmaceutically acceptable salt thereof, a solvate thereof, or a solvate of a pharmaceutically acceptable salt thereof.

[0734] The present invention also provides a use of a heterocyclic compound represented by Formula I according to any of the above schemes, a pharmaceutically acceptable salt thereof, a solvate thereof, or a solvate of a pharmaceutically acceptable salt thereof in the preparation of a KRAS mutant inhibitor; preferably, the KRAS mutant is KRAS G12C, KRAS G12D, KRAS G12V, KRAS G12A, KRAS G12R, KRAS G12S, KRAS G13C, KRAS G13D, KRAS Q61H, KRAS Q61K or KRAS Q61R, such as KRAS G12C, KRAS G12V or KRAS G12D.

[0735] The present invention also provides a use of a heterocyclic compound represented by formula I according to any of the above schemes, a pharmaceutically acceptable salt thereof, a solvate thereof, or a solvate of a pharmaceutically acceptable salt thereof in the preparation of a medicament for treating and / or preventing a disease associated with a KRAS mutation; preferably, the KRAS mutation is KRAS G12C, KRAS G12D, KRAS G12V, KRAS G12A, KRAS G12R, KRAS G12S, KRAS G13C, KRAS G13D, KRAS Q61H, KRAS Q61K or KRAS Q61R, for example, KRAS G12C, KRAS G12V or KRAS G12D; preferably, the disease associated with KRAS mutation can be selected from one or more of breast cancer, prostate cancer, lung cancer, brain cancer, ovarian cancer, cervical cancer, kidney cancer, head and neck cancer, bone cancer, skin cancer, liver cancer, colorectal cancer, esophageal cancer, gastric cancer, thyroid cancer, bladder cancer, lymphoma, leukemia, melanoma and pancreatic cancer, preferably lung cancer, pancreatic cancer or colorectal cancer; preferably, the lung cancer is non-small cell lung cancer or small cell lung cancer; preferably, the colorectal cancer is colon cancer and rectal cancer.

[0736] The present invention also provides a use of a heterocyclic compound represented by Formula I according to any of the above schemes, a pharmaceutically acceptable salt thereof, a solvate thereof, or a solvate of a pharmaceutically acceptable salt thereof in the preparation of a medicament for treating and / or preventing cancer, wherein the cancer may be selected from one or more of breast cancer, prostate cancer, lung cancer, brain cancer, ovarian cancer, cervical cancer, kidney cancer, head cancer, neck cancer, bone cancer, skin cancer, liver cancer, colorectal cancer, esophageal cancer, gastric cancer, thyroid cancer, bladder cancer, lymphoma, leukemia, melanoma, and pancreatic cancer, preferably lung cancer, pancreatic cancer, or colorectal cancer; preferably, the lung cancer is non-small cell lung cancer or small cell lung cancer; preferably, the colorectal cancer is colon cancer and rectal cancer.

[0737] The present invention also provides a method for preventing and / or treating a disease, comprising administering to a patient a therapeutically effective amount of a heterocyclic compound represented by Formula I, a pharmaceutically acceptable salt thereof, a solvate thereof, or a solvate of a pharmaceutically acceptable salt thereof, as described in any of the above schemes, wherein the disease is a disease or cancer associated with KRAS mutation.

[0738] In one embodiment of the present invention, the cancer is selected from one or more of breast cancer, prostate cancer, lung cancer, brain cancer, ovarian cancer, cervical cancer, kidney cancer, head and neck cancer, bone cancer, skin cancer, liver cancer, colorectal cancer, esophageal cancer, gastric cancer, thyroid cancer, bladder cancer, lymphoma, leukemia, melanoma and pancreatic cancer, preferably lung cancer, pancreatic cancer or colorectal cancer; preferably, the lung cancer is non-small cell lung cancer or small cell lung cancer; preferably, the colorectal cancer is colon cancer and rectal cancer.

[0739] In one embodiment of the present invention, the KRAS mutation is KRAS G12C, KRAS G12D, KRAS G12V, KRAS G12A, KRAS G12R, KRAS G12S, KRAS G13C, KRAS G13D, KRAS Q61H, KRAS Q61K or KRAS Q61R, for example, KRAS G12C, KRAS G12V or KRAS G12D; preferably, the disease associated with KRAS mutation can be selected from one or more of breast cancer, prostate cancer, lung cancer, brain cancer, ovarian cancer, cervical cancer, kidney cancer, head and neck cancer, bone cancer, skin cancer, liver cancer, colorectal cancer, esophageal cancer, gastric cancer, thyroid cancer, bladder cancer, lymphoma, leukemia, melanoma and pancreatic cancer, preferably lung cancer, pancreatic cancer or colorectal cancer; preferably, the lung cancer is non-small cell lung cancer or small cell lung cancer; preferably, the colorectal cancer is colon cancer and rectal cancer.

[0740] The present invention also provides a compound represented by formula (II-1), (II-2), (II-3), (II-4), (II-5), (II-6), (II-7), (II-8) or (II-9):

[0741] In the above formulas, PG is independently an amino protecting group or a hydroxy protecting group, R d and R b are each independently hydrogen or C1-C6 alkyl, R c are independently hydrogen or an amino protecting group, X1 and X2 are each independently halogen, p1 is 0 or 1, X, n, R 5 、R 6 、R 3 and R 4The definition of is as described in any embodiment of the present invention;

[0742] The carbon atom with "*" is a chiral carbon, and its configuration is R configuration, S configuration or a mixture thereof;

[0743] Preferably, p1 is 0;

[0744] Preferably, the amino protecting group or hydroxy protecting group is p-methoxybenzyl.

[0745] The present invention also provides any one of the following compounds:

[0746] Without violating the common sense in the art, the above-mentioned preferred conditions can be arbitrarily combined to obtain preferred embodiments of the present invention.

[0747] The reagents and raw materials used in the present invention are commercially available.

[0748] Unless otherwise specified, the terms used in this invention have the following meanings:

[0749] It will be understood by those skilled in the art that the structural formulas used in the present invention to describe groups are based on the conventions used in the art. It means that the corresponding group is connected to other fragments and groups in the compound through this site.

[0750] As used herein, a substituent may be preceded by a single dash "-" to indicate that the named substituent is bonded to the parent moiety through a single bond.

[0751] The term "plurality" refers to 2, 3, 4 or 5.

[0752] The term "aryl" refers to a group having the specified number of carbon atoms (e.g., C6-C 10 ) is a cyclic, unsaturated, monovalent hydrocarbon group, which is monocyclic or polycyclic. If it is monocyclic, it is aromatic; if it is polycyclic, each monocyclic ring sharing two atoms and one chemical bond, and each ring is aromatic. Examples of aryl groups include, but are not limited to, phenyl or naphthyl.

[0753] The term "heteroaryl" refers to a cyclic, unsaturated, monovalent group having a specified number of ring atoms (e.g., 5-10, 5-6, 8-10, or 9 members), a specified number of heteroatoms (e.g., 1, 2, or 3), a specified type of heteroatom (one or more of N, O, and S), which is monocyclic or polycyclic, with two atoms and one bond shared between the monocyclic rings, and each ring having aromaticity. Examples of heteroaryl include, but are not limited to, pyridyl, pyrrolyl, furyl, thienyl, pyrazolyl, oxazolyl, , isoxazolyl, thiazolyl, isothiazolyl, pyridazinyl, pyrimidinyl, pyrazinyl, imidazolyl, 1,2,3-triazolyl, 1,2,4-triazolyl, 1,2,3-triazinyl, 1,3,5-s-triazinyl or 1,3,4-triazinyl, quinolyl, isoquinolyl, 1H-pyrazolo[4,3-c]pyridinyl, 1H-pyrrolo[3,2-c]pyridinyl, 7H-pyrrolo[2,3-d]pyrimidinyl, indolyl, isoindolyl, indazolyl, benzothiophenyl or benzothiazolyl, preferably Further optimization More preferred

[0754] The term "halogen" refers to F, Cl, Br or I.

[0755] The term "alkyl" refers to a straight or branched chain alkyl group having a specified number of carbon atoms (e.g., C1-C6, C1-C4). Examples of alkyl groups include methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, isobutyl, sec-butyl, n-pentyl, n-hexyl, (like ) and similar alkyl groups.

[0756] The term "alkenyl" refers to a straight or branched chain alkene having a specified number of carbon atoms (e.g., C2-C6) containing one or more carbon-carbon double bonds, which may be internal or terminal, and no carbon-carbon triple bonds.

[0757] The term "alkynyl" refers to a straight or branched hydrocarbon group having one or more triple bonds with a specified number of carbon atoms (e.g., C2-C6). The one or more carbon-carbon triple bonds can be internal or terminal.

[0758] The term "cycloalkyl" refers to a saturated cyclic group having a specified number of ring carbon atoms (e.g., 3-10 members) and the ring atoms consisting only of carbon atoms. Examples of cycloalkyl include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and the like.

[0759] The term "heterocycloalkyl" refers to a saturated cyclic group having a specified number of ring atoms (e.g., 3-10, 4-10, 4-6, 8-10 members), a specified number of heteroatoms (e.g., 1, 2, or 3), and a specified type of heteroatoms (1, 2, or 3 of N, O, and S). Examples of heterocycloalkyl include, but are not limited to, azetidinyl, tetrahydropyranyl, oxetanyl, tetrahydropyrrolyl, tetrahydroimidazolyl, morpholinyl, piperazinyl, hexahydro-1H-pyrrolizinyl, tetrahydrofuranyl, 1-azabicyclo[2.2.2]octyl, or piperidinyl, preferably hexahydro-1H-pyrrolizinyl, tetrahydropyrrolyl, tetrahydroimidazolyl, morpholinyl, tetrahydrofuranyl, piperidinyl, piperazinyl, or 1-azabicyclo[2.2.2]octyl, for example etc.; further example etc.; for example

[0760] The term "heterocycloalkenyl" refers to an unsaturated monovalent cyclic group having a specified number of ring atoms (e.g., 3-10, 5-10, 5-membered, or 6-membered), a specified number of heteroatoms (e.g., 1, 2, or 3), a specified type of heteroatom (one or more of N, O, and S), one or more (e.g., 1, 2, or 3) double bonds, and no aromaticity. A (monocyclic) heterocycloalkenyl group is attached to the rest of the molecule via a carbon atom or a heteroatom, e.g. For example

[0761] The term "cycloalkenyl" refers to a cycloalkenyl group having the specified number of carbon atoms (e.g., C3-C 10 A monovalent unsaturated cyclic group having one or more (e.g., 1, 2, or 3) carbon-carbon sp 2 Double bond, not aromatic.

[0762] The term "saturated heterocycle" satisfies any of the following conditions, and the rest of the definition is the same as the term "heterocycloalkyl": 1. It is connected to the rest of the molecule through two or more single bonds; 2. It shares two atoms and one bond with the rest of the molecule. For example, azetidine, oxetane, tetrahydropyrrole ring, tetrahydrofuran ring, piperidine ring, tetrahydropyran ring, morpholine ring, piperazine ring or 1,4-oxazaalkane ring, more for example Preferred

[0763] The term "heterocyclene" satisfies any of the following conditions, and the rest of the definition is the same as the term "heterocyclenyl": 1. It is connected to the rest of the molecule through two or more single bonds; 2. It shares two atoms and one bond with the rest of the molecule.

[0764] The term "heteroaromatic ring" satisfies any of the following conditions, and the rest of the definition is the same as the term "heteroaryl": 1. It is connected to the rest of the molecule through two or more single bonds; 2. It shares two atoms and one bond with the rest of the molecule. For example, a pyrrole ring, a furan ring, a thiophene ring, a pyrazole ring, an oxazole ring, an isoxazole ring, a thiazole ring, an isothiazole ring, a pyridine ring, a pyridazine ring, a pyrimidine ring, a pyrazine ring, a quinoline ring or an isoquinoline ring, and further for example Preferred

[0765] The "heteroaromatic ring" in the term "heteroaromatic and heterocycloalkyl" satisfies any of the following conditions, and the rest of the definitions are the same as the term "heteroaryl": 1. It is connected to the heterocycloalkyl in the "heteroaromatic and heterocycloalkyl" through two or more single bonds; 2. It shares two atoms and one bond with the heterocycloalkyl in the "heteroaromatic and heterocycloalkyl". The "heterocycloalkyl" in the "heteroaromatic and heterocycloalkyl" is defined the same as the term "heterocycloalkyl" as described above; for example, "5-10 membered heteroaromatic ring and 3-10 membered heterocycloalkyl" is Preferred

[0766] The terms "optional" or "optionally" mean that the subsequently described event or circumstance may but need not occur, and that the description includes instances where said event or circumstance occurs and instances where it does not.

[0767] When any variable (such as R 1a ) appears multiple times in the definition of a compound, the definition of each position of the variable is independent of the definition of the other positions, and their meanings are independent of each other and do not affect each other. Therefore, if a group is replaced by one or more R 1a group substituted, that is, the group may be replaced by up to 3 R 1a Replace, the position R 1a Definition and other positions R 1a The definitions are independent of each other.

[0768] The term "pharmaceutically acceptable salt" refers to salts prepared from compounds of the present invention with relatively nontoxic, pharmaceutically acceptable acids or bases. When the compounds of the present invention contain relatively acidic functional groups, base addition salts can be obtained by contacting the neutral form of such compounds with a sufficient amount of a pharmaceutically acceptable base in neat solution or in a suitable inert solvent. When the compounds of the present invention contain relatively basic functional groups, acid addition salts can be obtained by contacting the neutral form of such compounds with a sufficient amount of a pharmaceutically acceptable acid in neat solution or in a suitable inert solvent.

[0769] The term "solvate" refers to a compound of the present invention combined with a stoichiometric or non-stoichiometric amount of a solvent. The solvent molecules in the solvate may be present in an ordered or non-ordered arrangement. Such solvents include, but are not limited to, water, methanol, and ethanol.

[0770] The term "pharmaceutically acceptable salt" and "solvate" in the term "pharmaceutically acceptable salt solvate" as described above refer to substances prepared by the compounds of the present invention with relatively non-toxic, pharmaceutically acceptable acids or bases; and formed in combination with stoichiometric or non-stoichiometric solvents.

[0771] The term "pharmaceutically acceptable excipients" refers to excipients and additives used in the production of pharmaceuticals and the preparation of prescriptions. These excipients are all substances, other than the active ingredient, contained in a pharmaceutical preparation. For a complete list, see Part IV of the Pharmacopoeia of the People's Republic of China (2015 edition) or the Handbook of Pharmaceutical Excipients (Raymond C. Rowe, 2009, Sixth Edition).

[0772] In the present invention, the "inhibitor" can be used in mammalian organisms; it can also be used in vitro, mainly for experimental purposes, for example: as a standard sample or control sample for comparison, or prepared into a kit according to conventional methods in the art.

[0773] The term "treat" refers to therapeutic treatment. When referring to a specific condition, treatment means: (1) alleviating the disease or one or more biological manifestations of the condition, (2) interfering with (a) one or more points in the biological cascade that leads to or causes the condition or (b) one or more biological manifestations of the condition, (3) ameliorating one or more symptoms, effects, or side effects associated with the condition or one or more symptoms, effects, or side effects associated with the condition or its treatment, or (4) slowing the progression of the condition or one or more biological manifestations of the condition.

[0774] The term "prevent" refers to the reduction of the risk of acquiring or developing a disease or disorder.

[0775] The positive progressive effects of the present invention are that the compounds of the present invention have inhibitory activity on the proliferation of one or more cells selected from Ba / F3 KRAS G12C, Ba / F3 KRAS G12D, Ba / F3 KRAS G12V, Capan-1, human non-small cell lung cancer cells NCI-H358 (KRAS G12C mutation) and human metastatic pancreatic adenocarcinoma cells AsPC-1 (KRAS G12D mutation) containing KRAS mutations, or the compounds of the present invention have weak inhibitory activity on the proliferation of KRAS wild-type PC-9 cells. DETAILED DESCRIPTION

[0776] The present invention is further illustrated by way of examples below, but the present invention is not limited to the scope of the examples. Experimental methods in the following examples where specific conditions are not specified were performed according to conventional methods and conditions, or selected according to the product specifications.

[0777] The compound represented by formula I of the present invention can be prepared by various synthetic methods well known to those skilled in the art, without particular limitation. For example, it can be prepared by the following schemes 1, 2, 3, 4 or 5 provided by the present invention. It should be understood that the synthetic method of the compound represented by formula (I) of the present invention is not limited to this scheme, and those skilled in the art can make conventional substitutions and improvements.

[0778] Option 1:

[0779] Wherein, X is -C(R 7 )2- or -CR 7 =CR 7 -, R 7 is hydrogen, Y, L, R 1 、R 2 、R 3 、R 5 and R 6 As defined above. P1, P2, P3, P4, P5 and P6 are amino, hydroxyl, ester or thiol protecting groups, including but not limited to benzyl (Bn-), 4-methoxybenzyl (PMB-), bis (4-methoxybenzyl), benzyloxycarbonyl (Cbz-), tert-butyloxycarbonyl (Boc-), tert-butyl, methoxymethyl ether (MOM-), tert-butyldimethylsiloxy ether (TBS-), tert-butyldiphenylsiloxy ether (TBDPS-), phthaloyl, etc., P1 and R 1 The amino, hydroxyl, ester or thiol groups in the 5 The amino, hydroxyl, ester or thiol groups in the 6The amino, hydroxyl, ester, or thiol groups in the alkylene group are connected. P1, P2, P3, P4, P5, and P6 may be the same or different. If no protecting group is required, P1 to P6 may not be present. n is 1, 2, or 3.

[0780] Compound a-1 is iodinated to obtain compound a-2; a-2 and a-3 are subjected to a metal-catalyzed Heck reaction to obtain compound a-4; a-4 is subjected to hydrogenation to reduce the double bond and selectively remove the protecting group P2 on the ester group to obtain compound a-5, which is further subjected to functional group transformation (n=2: a-5 is converted into an amino compound with one less carbon by Curtius rearrangement reaction; n=3: a-5 is converted into the corresponding amino compound by a series of reactions such as reduction of carboxylic acid, nucleophilic substitution, and amination) to obtain a-6; a-6 is subjected to water The compound a-7 is converted into a-7 by decomposition and condensation reaction, and then a-8 is obtained by ring closure via triphosgene; the protecting group P3 on the amino group of a-8 is selectively removed to obtain compound a-9; a-9 and a-10 are subjected to reductive amination reaction to obtain a-11; a-11 is ring-closed under alkaline conditions to obtain a-12; a-12 is selectively subjected to removal of the protecting group P4 on Y to obtain compound a-13, and then a-14 is obtained by chlorination and ring closure in the presence of phosphorus oxychloride; a-14 is reacted with a-15 to obtain a-16; and finally, all protecting groups are removed to obtain the compound of formula I.

[0781] Option 2:

[0782] Among them, X, Y, L, R 1 、R 2 、R 3 、R 5 、R 6 and R 7 P1, P2, P3, P4, P5 and P6 are amino, hydroxyl, ester or thiol protecting groups, as defined in Scheme 1. n is 1, 2 or 3.

[0783] Compound b-1 (a byproduct obtained during the synthesis of a-4, which can also be obtained by hydrolysis of a-4) undergoes a condensation reaction to obtain b-2, which is further cyclized with triphosgene to obtain b-3; b-3 is converted to b-4 through an oxidation reaction (including but not limited to potassium osmate / sodium periodate conditions), which is further cyclized with hydrazine hydrate to obtain b-5; b-5 undergoes functional group transformation (including but not limited to halogenation, oxidation, coupling, etc.). If R 7 is hydrogen, no further operation is required in this step) to obtain b-6; b-6 is reacted with phosphorus oxychloride to obtain b-7, which is further reacted with b-8 to obtain b-9; b-9 is cyclized (including but not limited to Mitsunobu reaction) to obtain b-10, and b-10 is reacted with a-15 to obtain a-16; finally, all protecting groups are removed to obtain the compound of formula IA.

[0784] Option 3:

[0785] Among them, X, Y, L, R 1 、R 2 、R 3 、R 5 、R 6 and R 7 P1, P2, P3, P4, P5 and P6 are amino, hydroxyl, ester or thiol protecting groups, as defined in Scheme 1. n is 1, 2 or 3. is an organometallic group, including but not limited to wait.

[0786] Compound c-1 is iodinated to give c-2, which is then cyclized to give c-3 via triphosgene; c-3 and c-4 are converted to c-5 via metal-catalyzed coupling reactions (including but not limited to Suzuki reaction, Stille reaction, Negishi reaction, Kumada reaction, etc.), which are then oxidized (R 7 =H, including but not limited to potassium osmate / sodium periodate conditions, etc.) or other functional group transformation reactions to obtain c-6; c-6 reacts with hydrazine hydrate to close the ring to obtain c-7, and further reacts with phosphorus oxychloride to obtain c-8; c-8 reacts with b-8 to obtain c-9; c-9 closes the ring (including but not limited to by Mitsunobu reaction) to obtain c-10, and c-10 reacts with a-15 to obtain c-11; c-11 and c-12 are converted to a-16 by a metal-catalyzed coupling reaction (including but not limited to Suzuki reaction, Stille reaction, Negishi reaction, Kumada reaction, etc.), and finally all protecting groups are removed to obtain the compound shown in formula IA.

[0787] Option 4:

[0788] Among them, L, R 1 、R 2 、R 3 、R 4 、R 5 、R 6 and R 7 As defined above. P1, P2, P3, P4 and P 4’ is an amino, hydroxyl, ester or thiol protecting group (if no protecting group is required, P1 to P6 may not exist), as defined in Scheme 1. 4’ Same as R 4 , is R 4 The precursor of the structure can be converted into R by functional group conversion reaction (including but not limited to substitution reaction, oxidation reaction, reduction reaction, etc.)4 LG is a suitable leaving group (including but not limited to halogen, etc.). The preparation method of compound d-1 is the same as that of compound c-11 in Scheme 3 (ie, R in c-11 is 5 、R 6 (no protecting group, Y = N-P4).

[0789] Compound d-1 is deprotected to obtain compound d-2; compound d-2 reacts with compound d-3 (including but not limited to alkylation reaction, acylation reaction, sulfonylation reaction, metal-catalyzed coupling reaction, etc.) to directly obtain compound d-5; or compound d-2 is first reacted with compound d-3' (including but not limited to alkylation reaction, acylation reaction, sulfonylation reaction, metal-catalyzed coupling reaction, etc.) to obtain compound d-4, and compound d-4 is further subjected to a functional group transformation reaction (including but not limited to substitution reaction, oxidation reaction, reduction reaction, etc.) to obtain compound d-5; compound d-5 and compound c-12 are converted into compound d-6 through a metal-catalyzed coupling reaction (including but not limited to Suzuki reaction, Stille reaction, Negishi reaction, Kumada reaction, etc.), and finally all protecting groups are removed to obtain the compound represented by formula IA.

[0790] Option 5:

[0791] Among them, L, R 1 、R 2 、R 3 、R 4 、R 5 、R 6 and R 7 As defined above. P1, P2, P3, P4 and P 4’ is an amino, hydroxyl, ester or thiol protecting group (if no protecting group is required, P1 to P6 may not exist), as defined in Scheme 1. 4’ As defined in Option 4.

[0792] Compound d-2 and compound c-12 are subjected to a metal-catalyzed coupling reaction (including but not limited to Suzuki reaction, Stille reaction, Negishi reaction, Kumada reaction, etc.) to obtain compound e-1; compound e-1 is reacted with compound d-3 (including but not limited to alkylation reaction, acylation reaction, sulfonylation reaction, metal-catalyzed coupling reaction, etc.) to directly obtain compound d-6; or e-1 is first reacted with d-3' (including but not limited to alkylation reaction, acylation reaction, sulfonylation reaction, metal-catalyzed coupling reaction, etc.) to obtain compound e-2, and compound e-2 is further subjected to a functional group transformation reaction (including but not limited to substitution reaction, oxidation reaction, reduction reaction, etc.) to obtain compound d-6; all protecting groups of d-6 are removed to obtain the compound represented by formula IA.

[0793] I. Preparation Examples of Compounds of the Invention

[0794] The structures of the compounds of the present invention are determined by nuclear magnetic resonance (NMR) and / or liquid chromatography-mass spectrometry (LC-MS). NMR chemical shifts (δ) are given in parts per million (ppm). NMR measurements were performed using a Bruker AVANCE-400 NMR spectrometer, using deuterated dimethyl sulfoxide (DMSO-d6) and deuterated chloroform (CDCl3) as solvents, and tetramethylsilane (TMS) as the internal standard.

[0795] Liquid chromatography-mass spectrometry (LC-MS) was performed using an Agilent 6410 Triple Quad LC / MS.

[0796] Thin-layer chromatography silica gel plates are Yantai Huanghai HSGF254 or Qingdao GF254 silica gel plates. The specifications used for TLC are 0.15mm-0.20mm, and the specifications used for thin-layer chromatography separation and purification products are 0.4mm-0.5mm. Column chromatography generally uses Yantai Huanghai 200-300 mesh silica gel as the carrier.

[0797] Example 1:

[0798] Compound 1-1: 6-(5-(1-(2-aminopyridin-3-yl)ethyl)-9-fluoro-7-(((2R,7aS)-2-fluorotetrahydro-1H-pyrrolazin-7a(5H)-yl)methoxy)-4,5-dihydro-3H-2a,5,6,8-tetraazanaphtho[2,1,8-cde]azulen-10-yl)-4-methyl-5-(trifluoromethyl)pyridin-2-amine monocarboxylate

[0799] Step 1: Methyl 2-amino-4-(6-(bis(4-methoxybenzyl)amino)-4-methyl-3-(trifluoromethyl)pyridin-2-yl)-3,6-difluoro-5-iodobenzoate

[0800] 2-Amino-4-(6-(bis(4-methoxybenzyl)amino)-4-methyl-3-(trifluoromethyl)pyridin-2-yl)-3,6-difluorobenzoic acid methyl ester (10 g, 16.62 mmol, prepared according to the method of intermediate 37, steps 1 to 7 of document WO2022173678) was dissolved in N,N-dimethylformamide (100 mL) and acetic acid (25 mL), and N-iodosuccinimide (7.48 g, 33.24 mmol) was added and reacted at 70 ° C for 3 hours. Saturated sodium sulfite solution (300 mL) was added to the reaction solution to quench the reaction and extracted with ethyl acetate (100 mL x 3). The obtained organic phase was washed with saturated sodium chloride solution (200 mL), dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was chromatographed on a silica gel column (petroleum ether / tetrahydrofuran = 7:1, volume ratio) to give the product as a yellow solid (10.6 g, yield 88%). ESI-MS m / z:728.1[M+1] + . 1 H NMR(400MHz, CDCl3) δ7.15(d,J=8.4Hz,4H),6.84(d,J=8.4Hz,4H),6.39(s,1H),5.92(brs, 2H), 4.81 (d, J=16.0Hz, 2H), 4.51 (d, J=16.0Hz, 2H), 3.93 (s, 3H), 3.79 (s, 6H), 2.41 (s, 3H).

[0801] Step 2: Methyl (E)-2-amino-5-(3-(benzyloxy)-3-oxopropyl-1-en-1-yl)-4-(6-(bis(4-methoxybenzyl)amino)-4-methyl-3-(trifluoromethyl)pyridin-2-yl)-3,6-difluorobenzoate

[0802] Methyl 2-amino-4-(6-(bis(4-methoxybenzyl)amino)-4-methyl-3-(trifluoromethyl)pyridin-2-yl)-3,6-difluoro-5-iodobenzoate (5.6 g, 7.7 mmol) was dissolved in N,N-dimethylacetamide (60 mL). Benzyl acrylate (4.37 g, 26.95 mmol), palladium(II) acetate (345.7 mg, 1.54 mmol), N,N-diisopropylethylamine (2.98 g, 23.1 mmol), and tri(o-methylphenyl)phosphine (937.5 mg, 3.08 mmol) were added. The reaction mixture was purged with nitrogen and reacted at 135°C for 5 hours. Water (200 mL) was added to the reaction mixture, and the mixture was extracted with ethyl acetate (80 mL x 3). The resulting organic phase was washed with saturated sodium chloride solution (200 mL), dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (petroleum ether / tetrahydrofuran = 7:1, volume ratio) to obtain the product as a yellow liquid (3.9 g, yield 66%). ESI-MS m / z: 762.3 [M+1] + . 1 H NMR (400MHz, CDCl3) δ7.36-7.20(m,6H),7.12-7.05(m,4H),6.86-6.77(m,4H),6.43-6.35(m,2H),6.11(brs,2H ),5.18(s,2H),4.78(d,J=16.0Hz,2H),4.45(d,J=16.0Hz,2H),3.94(s,3H),3.76(s,6H),2.38(d,J=2.0Hz,3H).

[0803] 19 F NMR (376MHz, CDCl3) δ-65.62--54.73,-106.63,-142.02.

[0804] Step 3: Methyl 2-amino-5-(3-(benzyloxy)-3-oxopropyl)-4-(6-(bis(4-methoxybenzyl)amino)-4-methyl-3-(trifluoromethyl)pyridin-2-yl)-3,6-difluorobenzoate

[0805] Methyl (E)-2-amino-5-(3-(benzyloxy)-3-oxopropyl-1-en-1-yl)-4-(6-(bis(4-methoxybenzyl)amino)-4-methyl-3-(trifluoromethyl)pyridin-2-yl)-3,6-difluorobenzoate (3.4 g, 4.46 mmol) was dissolved in tetrahydrofuran (10 mL) and methanol (40 mL). Phenylmethylsulfonylhydrazide (8.31 g, 44.63 mmol) and sodium acetate (3.66 g, 44.63 mmol) were added and refluxed for 5 hours. Water (200 mL) was added to the reaction solution, and the mixture was extracted with ethyl acetate (80 mL x 3). The resulting organic phase was washed with saturated sodium chloride solution (200 mL), dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (petroleum ether / tetrahydrofuran = 5:1, volume ratio) to obtain the product as a yellow liquid (3.25 g, yield 95%). ESI-MS m / z: 764.3 [M+1] + . 1 H NMR (400MHz, CDCl3) δ7.34-7.27(m,5H),7.09-7.04(m,4H),6.85-6.79(m,4H),6.37(s,1H) ,5.13-4.99(m,2H),4.71-4.58(m,4H),3.91(s,3H),3.76(s,6H),2.57-2.42(m,4H),2.38(d J=2.0Hz,3H).

[0806] Step 4: 3-(4-amino-2-(6-(bis(4-methoxybenzyl)amino)-4-methyl-3-(trifluoromethyl)pyridin-2-yl)-3,6-difluoro-5-(methoxycarbonyl)phenyl)propanoic acid

[0807] Methyl 2-amino-5-(3-(benzyloxy)-3-oxopropyl)-4-(6-(bis(4-methoxybenzyl)amino)-4-methyl-3-(trifluoromethyl)pyridin-2-yl)-3,6-difluorobenzoate (3.25 g, 4.26 mmol) was dissolved in tetrahydrofuran (10 mL) and methanol (40 mL). Wet palladium on carbon (400 mg, 10%) and palladium hydroxide (400 mg, 20%) were added. The reaction mixture was reacted at 45°C under a hydrogen atmosphere (15 psi) for 40 hours. The reaction mixture was filtered through celite and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (petroleum ether / tetrahydrofuran = 4:1, volume ratio) to afford the product as a white solid (2.06 g, 72% yield). ESI-MS m / z: 674.2 [M+1] + . 1H NMR (400MHz, CDCl3) δ7.11-7.05(m,4H),6.86-6.80(m,4H),6.39(s,1H),4.67(q,J=16.0Hz, 4H), 3.93 (s, 3H), 3.76 (s, 6H), 2.81-2.69 (m, 1H), 2.54-2.42 (m, 3H), 2.39 (d, J = 2.0Hz, 3H).

[0808] Step 5: Methyl 2-amino-4-(6-(bis(4-methoxybenzyl)amino)-4-methyl-3-(trifluoromethyl)pyridin-2-yl)-5-(2-((tert-butoxycarbonyl)amino)ethyl)-3,6-difluorobenzoate

[0809] 3-(4-amino-2-(6-(bis(4-methoxybenzyl)amino)-4-methyl-3-(trifluoromethyl)pyridin-2-yl)-3,6-difluoro-5-(methoxycarbonyl)phenyl)propanoic acid (500 mg, 0.742 mmol) was dissolved in toluene (15 mL), and triethylamine (225 mg, 2.23 mmol) and diphenylphosphoryl azide (204 mg, 0.742 mmol) were added. The reaction was stirred at room temperature for 4 hours. Tert-butyl alcohol (15 mL) was added, and the reaction temperature was raised to 90°C and stirred for 16 hours. The mixture was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (petroleum ether / tetrahydrofuran = 8:1, volume ratio) to obtain the product as a colorless oil (350 mg, yield 63%). ESI-MS m / z: 745.3 [M+1] + . 1 H NMR (400MHz, CDCl3) δ7.13(d,J=8.4Hz,4H),6.87(d,J=8.4Hz,4H),6.41(s,1H),5.70(brs,2H),4.82-4.62(m,4H),4.5 2(s,1H),3.94(s,3H),3.82(s,6H),3.23-2.92(m,2H),2.84-2.61(m,1H),2.41(s,3H),2.37-2.29(m,1H),1.42(s,9H).

[0810] Step 6: 2-amino-4-(6-(bis(4-methoxybenzyl)amino)-4-methyl-3-(trifluoromethyl)pyridin-2-yl)-5-(2-((tert-butoxycarbonyl)amino)ethyl)-3,6-difluorobenzoic acid

[0811] Methyl 2-amino-4-(6-(bis(4-methoxybenzyl)amino)-4-methyl-3-(trifluoromethyl)pyridin-2-yl)-5-(2-((tert-butoxycarbonyl)amino)ethyl)-3,6-difluorobenzoate (350 mg, 0.470 mmol) was dissolved in tetrahydrofuran (9 mL), and water (3 mL), methanol (3 mL), and sodium hydroxide (282 mg, 7.05 mmol) were added. The reaction was stirred at room temperature for 4 hours. Saturated aqueous citric acid was added to adjust the pH to 5, and the solution was diluted with saturated aqueous sodium chloride (100 mL). The product was extracted with ethyl acetate (100 mL x 2). The organic phase was dried over anhydrous sodium sulfate and concentrated under reduced pressure to obtain the product as a colorless oil (340 mg, crude product). ESI-MS m / z: 731.3 [M+1] + .

[0812] Step 7: tert-Butyl (4-amino-2-(6-(bis(4-methoxybenzyl)amino)-4-methyl-3-(trifluoromethyl)pyridin-2-yl)-5-carbamoyl-3,6-difluorophenylethyl)carbamate

[0813] 2-Amino-4-(6-(bis(4-methoxybenzyl)amino)-4-methyl-3-(trifluoromethyl)pyridin-2-yl)-5-(2-((tert-butoxycarbonyl)amino)ethyl)-3,6-difluorobenzoic acid (340 mg, 0.470 mmol, crude) was dissolved in N,N-dimethylformamide (5 mL), and N,N-diisopropylethylamine (243 mg, 1.88 mmol), N,N,N′,N′-tetramethyl-O-(7-azabenzotriazol-1-yl)uronium hexafluorophosphate (357 mg, 0.94 mmol) and ammonium chloride (76 mg, 1.41 mmol) were added. The reaction was stirred at 35° C. for 16 hours. Water (100 mL) was added for dilution, and the mixture was extracted with ethyl acetate (70 mL x 2). The organic phase was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (petroleum ether / tetrahydrofuran = 3:1, volume ratio) to afford the product as a colorless oil (250 mg, yield 73%). ESI-MS m / z: 730.3 [M+1] + .

[0814] Step 8: tert-Butyl (2-(7-(6-(bis(4-methoxybenzyl)amino)-4-methyl-3-(trifluoromethyl)pyridin-2-yl)-5,8-difluoro-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-yl)ethyl)carbamate

[0815] Tert-butyl (4-amino-2-(6-(bis(4-methoxybenzyl)amino)-4-methyl-3-(trifluoromethyl)pyridin-2-yl)-5-carbamoyl-3,6-difluorophenethyl)carbamate (500 mg, 0.686 mmol) was dissolved in tetrahydrofuran (25 mL). Triphosgene (102 mg, 0.343 mmol) was added under nitrogen protection in an ice bath, and the mixture was then warmed to room temperature and stirred for 30 minutes. Saturated aqueous sodium bicarbonate solution (10 mL) was added under ice bath to quench the mixture, and the mixture was stirred for 5 minutes. Ethyl acetate (20 mL x 2) was added for extraction. The organic phase was washed with saturated brine (20 mL), dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was chromatographed on a silica gel column (petroleum ether / tetrahydrofuran = 3:1, volume ratio) to obtain the product as a yellow oil (370 mg, yield 71%). ESI-MS m / z: 756.1 [M+1] + .

[0816] Step 9: 6-(2-aminoethyl)-7-(6-(bis(4-methoxybenzyl)amino)-4-methyl-3-trifluoromethylpyridin-2-yl)-5,8-difluoroquinazoline-2,4(1H,3H)-dione

[0817] Tert-butyl (2-(7-(6-(bis(4-methoxybenzyl)amino)-4-methyl-3-(trifluoromethyl)pyridin-2-yl)-5,8-difluoro-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-yl)ethyl)carbamate (370 mg, 0.49 mmol) was dissolved in 1,4-dioxane (10 mL), and then a dioxane hydrochloride solution (10 mL, 4.9 mmol, 4.0 M in dioxane solution) was added and stirred at room temperature for 3 hours. The reaction solution was poured into a saturated aqueous sodium bicarbonate solution (20 mL) and extracted with ethyl acetate (20 mL x 2). The resulting organic phase was washed with saturated brine (20 mL) and dried over anhydrous sodium sulfate. The product was concentrated under reduced pressure to give a yellow foamy solid (330 g, crude product). ESI-MS m / z: 656.1[M+1] + .

[0818] Step 12: 3-Bromo-N,N-bis(4-methoxybenzyl)pyridin-2-amine

[0819] 3-Bromopyridin-2-amine (5.0 g, 29.1 mmol) was dissolved in N,N-dimethylformamide (100 mL). Sodium hydride (4.0 g, 101.8 mmol, 60% dispersion in mineral oil) was added at 0°C, followed by 4-methoxybenzyl chloride (18.0 g, 116.4 mmol). The reaction was stirred at room temperature for 12 hours. Water (50 mL) was slowly added to quench the mixture under ice-bath conditions, and the mixture was extracted with ethyl acetate (50 mL x 2). The organic phase was washed with saturated brine (50 mL), dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was chromatographed on a silica gel column (petroleum ether / tetrahydrofuran = 4:1, volume ratio) to obtain the product as a yellow oil (9.5 g, yield 79.2%). ESI-MS m / z: 413.1 [M+1] + .

[0820] Step 13: 3-(1-ethoxyvinyl)-N,N-bis(4-methoxybenzyl)pyridin-2-amine

[0821] 3-Bromo-N,N-bis(4-methoxybenzyl)pyridin-2-amine (8.0 g, 9.42 mmol) and tributyl(1-ethoxyvinyl)stannane (21.0 g, 9.42 mmol) were dissolved in N,N-dimethylformamide (80 mL). Bis(triphenylphosphine)palladium dichloride (1.3 g, 0.94 mmol) was added under nitrogen, and the reaction was stirred at 80°C for 12 hours. The reaction solution was cooled to room temperature, diluted with water (80 mL), and extracted with ethyl acetate (100 mL x 2). The organic phase was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (petroleum ether / tetrahydrofuran = 5:1, volume ratio) to obtain the product as a yellow oil (6.0 g, 77% yield). ESI-MS m / z: 405.1 [M+1] + .

[0822] Step 14: 1-(2-(bis(4-methoxybenzyl)amino)pyridin-3-yl)ethan-1-one

[0823] 3-(1-Ethoxyvinyl)-N,N-bis(4-methoxybenzyl)pyridin-2-amine (6.0 g, 14.9 mmol) was dissolved in acetone (100 mL), followed by the addition of 0.5 N aqueous hydrochloric acid (20 mL). The reaction was stirred at room temperature for 3 hours. The mixture was diluted with saturated aqueous sodium bicarbonate (40 mL) and extracted with ethyl acetate (50 mL x 2). The organic phase was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (petroleum ether / tetrahydrofuran = 4:1, volume ratio) to afford the product as a yellow oil (4.0 g, 72% yield). ESI-MS m / z: 377.1 [M+1] + .

[0824] Step 15: 2-(1-(2-(bis(4-methoxybenzyl)amino)pyridin-3-ethyl)amino)ethyl-1-ol

[0825] 1-(2-(bis(4-methoxybenzyl)amino)pyridin-3-yl)ethane-1-one (4.0 g, 10.6 mmol) was dissolved in anhydrous methanol (80 mL), and ethanolamine (1.9 g, 31.8 mmol) and tetraisopropyl titanate (12.0 g, 42.4 mmol) were added. The mixture was stirred at 80 ° C for 16 hours under nitrogen protection. The reaction solution was cooled to room temperature, and then sodium borohydride (1.6 g, 42.4 mmol) was added and the reaction was continued at room temperature for 2 hours. Water (2 mL) was added dropwise to quench the mixture, and a white solid precipitated. The mixture was filtered through celite and the filtrate was concentrated under reduced pressure. The residue was chromatographed on a silica gel column (petroleum ether / tetrahydrofuran = 3: 1, volume ratio) to give the product as a yellow oil (2.5 g, yield 56%). ESI-MS m / z: 422.1[M+1] + .

[0826] Step 16: tert-Butyl (1-(2-(bis(4-methoxybenzyl)amino)pyridin-3-yl)ethyl)(2-hydroxyethyl)carbamate

[0827] 2-(1-(2-(bis(4-methoxybenzyl)amino)pyridin-3-ethyl)amino)ethyl-1-ol (2.5 g, 5.9 mmol) was dissolved in dichloromethane (50 mL), and triethylamine (1.5 g, 14.8 mmol) and di-tert-butyl dicarbonate (2.6 g, 11.8 mmol) were added. The reaction was stirred at room temperature for 16 hours. Saturated aqueous ammonium chloride solution (20 mL) was added for dilution, and the organic phase was separated and extracted with dichloromethane (20 mL x 2). The organic phase was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was chromatographed on a silica gel column (petroleum ether / tetrahydrofuran = 4:1, volume ratio) to obtain the product as a yellow oil (2.4 g, yield 80%). ESI-MS m / z: 522.1 [M+1] + .

[0828] Step 17: tert-Butyl (1-(2-(bis(4-methoxybenzyl)amino)pyridin-3-yl)ethyl)(2-oxoethyl)carbamate

[0829] Tert-butyl (1-(2-(bis(4-methoxybenzyl)amino)pyridin-3-yl)ethyl)(2-hydroxyethyl)carbamate (700 mg, 1.34 mmol) was dissolved in dichloromethane (20 mL) and Dess-Martin periodinane (1.1 g, 2.68 mmol) was added. Stirring was continued at room temperature under nitrogen for 2 hours. Saturated aqueous sodium bicarbonate (10 mL) was added and stirring was continued for 30 minutes. The mixture was extracted with dichloromethane (20 mL x 2). The organic phase was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (petroleum ether / tetrahydrofuran = 4:1, volume ratio) to obtain the product as a yellow oil (500 mg, 72% yield). ESI-MS m / z: 520.1 [M+1] + . 1 H NMR(400MHz, CDCl3)δ9.13(s,1H),8.38(s,1H),7.55(s,1H),7.20-7.12(m,4H),7.09-7.02(m,1H), 6.82-6.79(m,4H),4.29-4.12(m,5H),3.79(s,6H),3.51(s,2H),1.50(s,9H),1.38(d,J=7.0Hz,3H).

[0830] Step 18: 2-(2-(7-(6-(bis(4-methoxybenzyl)amino)-4-methyl-3-trifluoromethylpyridin-2-yl)-5,8-difluoro-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-yl)ethyl)amino)ethyl)(1-(2-(2-(bis(4-methoxybenzyl)amino)pyridin-3-yl)ethylcarbamate

[0831] 6-(2-aminoethyl)-7-(6-(bis(4-methoxybenzyl)amino)-4-methyl-3-trifluoromethylpyridin-2-yl)-5,8-difluoroquinazoline-2,4(1H,3H)-dione (100 mg, 0.15 mmol) was dissolved in anhydrous methanol (10 mL), and tert-butyl (1-(2-(bis(4-methoxybenzyl)amino)pyridin-3-yl)ethyl)(2-oxoethyl)carbamate (158 mg, 0.3 mmol) and tetraisopropyl titanate (151 mg, 0.6 mmol) were added. The mixture was stirred at 80°C under nitrogen for 6 hours. The reaction solution was cooled to room temperature, and then sodium borohydride (24 mg, 0.6 mmol) was added, and the reaction was continued at room temperature for 1 hour. Water (2 mL) was added dropwise to quench the reaction, and a white solid precipitated. The solid was filtered through Celite and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (petroleum ether / tetrahydrofuran = 3:1, volume ratio) to afford the product as a yellow oil (120 mg, yield 68%). ESI-MS m / z: 1039.5 [M-119] + .1 H NMR (400MHz, CDCl3) δ8.36-8.24 (m, 1H), 7.58 (d, J = 8.0Hz, 1H), 7.12-7.05 (m,8H),6.97-6.91(m,1H),6.86(d,J=8.4Hz,4H),6.80-6.75(m,4H),6.42( d,J=4.8Hz,1H),4.77-4.50(m,4H),4.22-4.01(m,6H),3.81-3.75(m,12H), 3.18-2.93(m,2H),2.71-2.20(m,11H),1.43(s,9H),1.37(d,J=7.2Hz,3H). 19 F NMR (376MHz, CDCl3) δ-54.02-,-54.36,-117.81--118.43,-139.34--139.99.

[0832] Step 19: 2-(4-(6-(bis(4-methoxybenzyl)amino)-4-methyl-3-(trifluoromethyl)pyridin-2-yl)-5-fluoro-7,9-dioxo-2,3,6,7,8,9-hexahydro-1H-pyrrolo[2,3-f]quinazolin-1-yl)ethyl)(1-(2-(2-(bis(4-methoxybenzyl)amino)pyridin-3-yl)ethyl)carbamate

[0833] 2-(2-(7-(6-(bis(4-methoxybenzyl)amino)-4-methyl-3-trifluoromethylpyridin-2-yl)-5,8-difluoro-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-yl)ethyl)amino)ethyl)(1-(2-(2-(bis(4-methoxybenzyl)amino)pyridin-3-yl)ethylcarbamate (120 mg, 0.104 mmol) was dissolved in dimethyl sulfoxide (10 mL), and diisopropylethylamine (53.5 mg, 0.416 mmol) was added. The reaction mixture was heated to 60°C and stirred for 16 hours. Water (10 mL) was added to dilute the mixture, and ethyl acetate (10 mL x 10 mL) was added to the mixture. 2) Extraction. The organic phase was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was chromatographed on a silica gel column (petroleum ether / tetrahydrofuran ester = 2:1, volume ratio) to obtain the product as a yellow oil (100 mg, yield 85%). ESI-MS m / z: 1019.5 [M-119] + .

[0834] Step 20: 4-(6-(bis(4-methoxybenzyl)amino)-4-methyl-3-trifluoromethylpyridin-2-yl)-5-fluoro-1-(2-((1-(2-(4-methoxybenzyl)amino)pyridin-3-yl)ethyl)amino)ethyl)-1,2,3,6-tetrahydro-7H-pyrrolo[2,3-f]quinazoline-7,9(8H)-dione

[0835] 2-(4-(6-(bis(4-methoxybenzyl)amino)-4-methyl-3-(trifluoromethyl)pyridin-2-yl)-5-fluoro-7,9-dioxo-2,3,6,7,8,9-hexahydro-1H-pyrrolo[2,3-f]quinazolin-1-yl)ethyl)(1-(2-(2-(bis(4-methoxybenzyl)amino)pyridin-3-yl)ethyl)carbamate (100 mg, 0.09 mmol) was dissolved in 1,4-dioxane (10 mL), and then a dioxane hydrochloric acid solution (10 mL, 0.9 mmol, 4.0 M in dioxane solution) was added and stirred at room temperature for 3 hours. The reaction solution was poured into a saturated sodium bicarbonate aqueous solution (20 mL) and washed with ethyl acetate (20 mL x 40 mL). 2) Extraction, the organic phase was washed with saturated brine (20 mL), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain the product as a yellow foamy solid (80 mg, crude product). ESI-MS m / z: 919.5 [M+1] + .

[0836] Step 21: 6-(7-Chloro-9-fluoro-5-(1-(2-(4-methoxybenzyl)amino)pyridin-3-yl)ethyl)-4,5-dihydro-3H-2a,5,6,8-tetraazanaphtho[2,1,8-cde]azul-10-yl)-N,N-bis(4-methoxybenzyl)-4-methyl-5-trifluoromethylpyridin-2-amine

[0837] 4-(6-(bis(4-methoxybenzyl)amino)-4-methyl-3-trifluoromethylpyridin-2-yl)-5-fluoro-1-(2-((1-(2-(4-methoxybenzyl)amino)pyridin-3-yl)ethyl)amino)ethyl)-1,2,3,6-tetrahydro-7H-pyrrolo[2,3-f]quinazoline-7,9(8H)-dione (80 mg, 0.09 mmol) was dissolved in anhydrous toluene (4 mL), and phosphorus oxychloride (133 mg, 0.9 mmol) and diisopropylethylamine (45 mg, 0.36 mmol) were added. Under nitrogen protection, the reaction was stirred at 100°C for 16 hours. After cooling to room temperature, the reaction was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (dichloromethane / methanol = 15:1, volume ratio) to obtain the product as a yellow solid (70 mg, yield 88%). ESI-MS m / z: 917.5[M+1]+ .

[0838] Step 22: 6-(9-Fluoro-7-(2R,7aS)-2-fluorotetrahydro-1H-pyrrolizine-7a(5H)methoxy)-5-(1-(2-(4-methoxybenzyl)amino)pyridin-3-yl)ethyl)-4,5-dihydro-3H-2a,5,6,8-tetraaza[2,1,8-cde]azulen-10-yl)-N,N-bis(4-methoxybenzyl)-4-methyl-5-trifluoromethylpyridin-2-amine

[0839] 6-(7-Chloro-9-fluoro-5-(1-(2-(4-methoxybenzyl)amino)pyridin-3-yl)ethyl)-4,5-dihydro-3H-2a,5,6,8-tetraazanaphtho[2,1,8-cde]azul-10-yl)-N,N-bis(4-methoxybenzyl)-4-methyl-5-trifluoromethylpyridin-2-amine (19 mg, 0.002 mmol) was dissolved in dichloromethane (1 mL). (2R,7aS)-2-fluorotetrahydro-1H-pyrrolidine-7a(5H)methanol (6.2 mg, 0.004 mmol) and potassium tert-butoxide (4.4 mg, 0.004 mmol) were added, and the mixture was stirred at room temperature for 12 hours. The mixture was concentrated under reduced pressure, and the residue was chromatographed on silica gel (dichloromethane / methanol = 15:1, volume ratio) to afford the product as a yellow solid (9 mg, 45% yield). ESI-MS m / z: 1040.5[M+1] + .

[0840] Step 23: 6-(5-(1-(2-aminopyridin-3-yl)ethyl)-9-fluoro-7-(((2R,7aS)-2-fluorotetrahydro-1H-pyrrolazin-7a(5H)-yl)methoxy)-4,5-dihydro-3H-2a,5,6,8-tetraazanaphtho[2,1,8-cde]azul-10-yl)-4-methyl-5-(trifluoromethyl)pyridin-2-amine monocarboxylate

[0841] 6-(9-fluoro-7-(2R,7aS)-2-fluorotetrahydro-1H-pyrrolizine-7a(5H)methoxy)-5-(1-(2-(4-methoxybenzyl)amino)pyridin-3-yl)ethyl)-4,5-dihydro-3H-2a,5,6,8-tetraaza[2,1,8-cde]azulene-10-yl)-N,N-bis(4-methoxybenzyl)-4-methyl-5-trifluoromethylpyridin-2-amine (9 mg, 0.001 mmol) was dissolved in dichloromethane (0.5 mL), trifluoroacetic acid (1 mL) and trifluoromethanesulfonic acid (0.2 mL) were added, and the mixture was stirred at room temperature for 4 hours. The reaction solution was neutralized with saturated sodium bicarbonate aqueous solution to pH = 7, concentrated under reduced pressure, and purified by preparative high performance liquid chromatography. The product was lyophilized to obtain a white solid (1 mg). Preparative high performance liquid chromatography separation conditions: Column: C18 OBD TM 19*250mm*5μM, flow rate 25mL / min; mobile phase: A: water (0.1% formic acid, v / v) B: acetonitrile; mobile phase B%: 19-19%, 8min; detection wavelength: 214 / 254nm. ESI-MS m / z: 680.5[M+1] + . 1 H NMR (400MHz, DMSO-d6) δ11.00 (brs, 1H), 8.40-7.95 (m, 3H), 7.48 (d, J = 3.2Hz, 1H), 7. 03(d,J=6.8Hz,1H),6.77(brs,2H),6.52(s,1H),6.28(d,J=6.0Hz,1H),6.18(d,J=3. 2Hz,1H),5.60(d,J=52.4Hz,1H),4.71-4.30(m,3H),4.20-3.45(m,5H),3.40-3.27(m ,1H),2.70-2.55(m,1H),2.50-2.29(m,5H),2.27-1.95(m,4H),1.70(d,J=7.2Hz,3H). 19 F NMR (376MHz, DMSO-d6) δ-53.05--53.27,-141.12--141.50,-172.86--173.03.

[0842] Example 2:

[0843] Compound 2-1: 6-(6-(1-(2-aminopyridin-3-yl)ethyl)-10-fluoro-8-(((2R,7aS)-2-fluorotetrahydro-1H-pyrrolazin-7a(5H)-yl)methoxy)-1,2,3,4,5,6-hexahydro-3a,6,7,9-tetraazacycloheptane[def]phenanthrene-11-yl)-4-methyl-5-(trifluoromethyl)pyridin-2-amine formate

[0844] Step 1: Methyl 2-amino-4-(6-(bis(4-methoxybenzyl)amino)-4-methyl-3-(trifluoromethyl)pyridin-2-yl)-3,6-difluoro-5-(3-hydroxypropyl)benzoate

[0845] 3-(4-amino-2-(6-(bis(4-methoxybenzyl)amino)-4-methyl-3-(trifluoromethyl)pyridin-2-yl)-3,6-difluoro-5-(methoxycarbonyl)phenyl)propanoic acid (1.0 g, 1.48 mmol) was dissolved in tetrahydrofuran (20 mL). Borane dimethyl sulfide complex (0.45 ml, 4.45 mmol, 10.0 M dimethyl sulfide solution) was added at 0°C under N2 protection. The reaction was stirred at 0°C for 8 hours. The solution was diluted with saturated aqueous ammonium chloride (25 mL) and extracted with ethyl acetate (40 mL x 2). The organic phase was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (petroleum ether / tetrahydrofuran = 3:1, volume ratio) to afford the product as a white solid (480 mg, 49% yield). ESI-MS m / z: 660.3 [M+1] + . 1 H NMR (400MHz, CDCl3) δ7.82(d,J=8.0Hz,1H),7.39(d,J=8.0Hz,1H),7.12(d,J=8.4Hz,4H),6.87(d,J=8.4Hz,4H),6.43(s,1H),4.7 1(s,4H),3.95(s,3H),3.81(s,6H),3.48(t,J=6.4Hz,2H),2.61-2.52(m,1H),2.41(s,3H),2.27-2.14(m,1H),1.75-1.60(m,2H).

[0846] Step 2: Methyl 2-amino-4-(6-(bis(4-methoxybenzyl)amino)-4-methyl-3-(trifluoromethyl)pyridin-2-yl)-5-(3-(1,3-dioxoisoindol-2-yl)propyl)-3,6-difluorobenzoate

[0847] Methyl 2-amino-4-(6-(bis(4-methoxybenzyl)amino)-4-methyl-3-(trifluoromethyl)pyridin-2-yl)-3,6-difluoro-5-(3-hydroxypropyl)benzoate (480 mg, 0.727 mmol) was dissolved in tetrahydrofuran (15 mL). Phthalimide (214 mg, 1.45 mmol), triphenylphosphine (381 mg, 1.45 mmol), and diisopropyl azodicarboxylate (294 mg, 1.45 mmol) were added at 0°C under N2 protection. The reaction was allowed to warm to room temperature and stirred for 16 hours. Saturated aqueous sodium chloride solution (40 mL) was added for dilution, and the mixture was extracted with ethyl acetate (40 mL x 2). The organic phase was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (petroleum ether / tetrahydrofuran = 5:1, volume ratio) to obtain the product as a white solid (750 mg, crude product). ESI-MS m / z: 789.3[M+1] + .

[0848] Step 3: Methyl 2-amino-4-(6-(bis(4-methoxybenzyl)amino)-4-methyl-3-(trifluoromethyl)pyridin-2-yl)-5-(3-((tert-butoxycarbonyl)amino)propyl)-3,6-difluorobenzoate

[0849] Methyl 2-amino-4-(6-(bis(4-methoxybenzyl)amino)-4-methyl-3-(trifluoromethyl)pyridin-2-yl)-5-(3-(1,3-dioxoisoindol-2-yl)propyl)-3,6-difluorobenzoate (750 mg, 0.727 mmol, crude) was dissolved in ethanol (15 mL) and hydrazine hydrate (0.5 mL, 85% aqueous solution) was added. The reaction was heated to 80°C and stirred for 1 hour. The mixture was filtered, the filtrate was concentrated under reduced pressure, redissolved in ethanol (15 mL), and di-tert-butyl dicarbonate (316 mg, 1.45 mmol) was added. The reaction was stirred at room temperature for 16 hours. The residue was concentrated under reduced pressure and purified by silica gel column chromatography (petroleum ether / tetrahydrofuran = 7:1, volume ratio) to afford the product as a colorless oil (370 mg, 67% yield). ESI-MS m / z: 759.3 [M+1] + . 1H NMR (400MHz, CDCl3) δ7.11(d,J=8.4Hz,4H),6.87(d,J=8.4Hz,4H),6.43(s,1H),4.77(d,J=16.0Hz,2H),4.65(d,J=16.0Hz,2H),4.40( brs,1H),3.95(s,3H),3.82(s,6H),2.97(brs,2H),2.50-2.42(m,1H),2.42(s,3H),2.21-2.13(m,1H),1.58-1.51(m,2H),1.42(s,9H).

[0850] Step 4: 2-amino-4-(6-(bis(4-methoxybenzyl)amino)-4-methyl-3-(trifluoromethyl)pyridin-2-yl)-5-(3-((tert-butoxycarbonyl)amino)propyl)-3,6-difluorobenzoic acid

[0851] Methyl 2-amino-4-(6-(bis(4-methoxybenzyl)amino)-4-methyl-3-(trifluoromethyl)pyridin-2-yl)-5-(3-((tert-butoxycarbonyl)amino)propyl)-3,6-difluorobenzoate (370 mg, 0.487 mmol) was dissolved in tetrahydrofuran (6 mL). Water (3 mL), methanol (3 mL), and sodium hydroxide (195 mg, 4.87 mmol) were added and stirred at room temperature for 4 hours. Saturated aqueous citric acid was added to adjust the pH to 5, and the solution was diluted with saturated aqueous sodium chloride (50 mL). The product was extracted with ethyl acetate (50 mL x 2). The organic phase was dried over anhydrous sodium sulfate and concentrated under reduced pressure to obtain the product as a colorless oil (370 mg, crude product). ESI-MS m / z: 745.3 [M+1] + .

[0852] Step 5: tert-Butyl (3-(4-amino-2-(6-(bis(4-methoxybenzyl)amino)-4-methyl-3-(trifluoromethyl)pyridin-2-yl)-5-carbamoyl-3,6-difluorophenyl)propyl)carbamate

[0853] 2-Amino-4-(6-(bis(4-methoxybenzyl)amino)-4-methyl-3-(trifluoromethyl)pyridin-2-yl)-5-(3-((tert-butoxycarbonyl)amino)propyl)-3,6-difluorobenzoic acid (370 mg, 0.487 mmol, crude) was dissolved in N,N-dimethylformamide (5 mL), and N,N-diisopropylethylamine (189 mg, 1.46 mmol), N,N,N′,N′-tetramethyl-O-(7-azabenzotriazol-1-yl)uronium hexafluorophosphate (278 mg, 0.731 mmol), and ammonium chloride (75 mg, 1.46 mmol) were added. The reaction was stirred at 35° C. for 16 hours. Water (50 mL) was added for dilution, and the mixture was extracted with ethyl acetate (50 mL x 2). The organic phase was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (petroleum ether / tetrahydrofuran = 3:1, volume ratio) to afford the product as a colorless oil (340 mg, yield 93%). ESI-MS m / z: 744.3 [M+1] + . 1 H NMR (400MHz, CDCl3) δ7.12(d,J=8.4Hz,4H),6.87(d,J=8.4Hz,4H),6.77(d,J=13.6Hz,1H),6.46(s,1H),5.70(s,1H),4.80(d,J=16.0Hz,2H),4.65 (d,J=16.0Hz,2H),4.39(brs,1H),3.82(s,6H),2.99(brs,2H),2.49-2.4 3(m,1H),2.42(s,3H),2.23-2.14(m,1H),1.58-1.49(m,2H),1.44(s,9H).

[0854] Step 6: tert-Butyl (3-(7-(6-(bis(4-methoxybenzyl)amino)-4-methyl-3-(trifluoromethyl)pyridin-2-yl)-5,8-difluoro-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-yl)propyl)carbamate

[0855] Tert-butyl (3-(4-amino-2-(6-(bis(4-methoxybenzyl)amino)-4-methyl-3-(trifluoromethyl)pyridin-2-yl)-5-carbamoyl-3,6-difluorophenyl)propyl)carbamate (340 mg, 0.457 mmol) was dissolved in tetrahydrofuran (15 mL). Triphosgene (48 mg, 0.160 mmol) was added under nitrogen protection in an ice bath, and then the mixture was warmed to room temperature and stirred for 10 minutes. Saturated aqueous sodium bicarbonate solution (10 mL) was added under ice bath to quench the mixture, and the mixture was stirred for 5 minutes. Ethyl acetate (20 mL x 2) was added for extraction. The organic phase was washed with saturated brine (50 mL), dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was chromatographed on a silica gel column (petroleum ether / tetrahydrofuran = 3:1, volume ratio) to obtain the product as a white solid (270 mg, yield 76%). ESI-MS m / z: 770.3 [M+1] + . 1 H NMR (400MHz, CDCl3) δ8.09(s,1H),8.04(s,1H),7.10(d,J=8.4Hz,4H),6.88(d,J=8.4Hz,4H),6.49(s,1H),4.71(q,J=16 .0Hz,4H),4.41(s,1H),3.82(s,6H),3.04-2.91(m,2H),2.59-2.50(m,2H),2.44(s,3H),2.35-2.24(m,2H),1.43(s,9H).

[0856] Step 7: 6-(3-aminopropyl)-7-(6-(bis(4-methoxybenzyl)amino)-4-methyl-3-(trifluoromethyl)pyridin-2-yl)-5,8-difluoroquinazoline-2,4(1H,3H)-dione

[0857] Tert-butyl (3-(7-(6-(bis(4-methoxybenzyl)amino)-4-methyl-3-(trifluoromethyl)pyridin-2-yl)-5,8-difluoro-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-yl)propyl)carbamate (270 mg, 0.351 mmol) was dissolved in 1,4-dioxane (2 mL), followed by addition of a dioxane hydrochloride solution (2 mL, 4.0 M in dioxane) and stirring at room temperature for 1.5 hours. The reaction mixture was poured into a saturated aqueous sodium bicarbonate solution (20 mL) and extracted with ethyl acetate (20 mL x 2). The resulting organic phase was washed with saturated brine (40 mL) and dried over anhydrous sodium sulfate. The product was concentrated under reduced pressure to give a yellow foamy solid (220 mg, crude product). ESI-MS m / z: 670.2 [M+1] + .

[0858] Step 8: tert-Butyl(2-(3-(7-(6-(bis(4-methoxybenzyl)amino)-4-methyl-3-(trifluoromethyl)pyridin-2-yl)-5,8-difluoro-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-yl)propyl)amino)ethyl)(1-(2-(bis(-4-methoxybenzyl)amino)pyridin-3-yl)ethyl)carbamate

[0859] 6-(3-Aminopropyl)-7-(6-(bis(4-methoxybenzyl)amino)-4-methyl-3-(trifluoromethyl)pyridin-2-yl)-5,8-difluoroquinazoline-2,4(1H,3H)-dione (170 mg, 0.254 mmol) was dissolved in anhydrous methanol (15 mL), and tert-butyl (1-(2-(bis(4-methoxybenzyl)amino)pyridin-3-yl)ethyl)(2-oxoethyl)carbamate (264 mg, 0.507 mmol) and acetic acid (0.15 mL) were added. The mixture was stirred at 40°C under nitrogen for 2 hours. The reaction solution was cooled to room temperature, and sodium borohydride (58 mg, 1.52 mmol) was added in three batches over 3 hours. The reaction was continued at room temperature for 1 hour. Water (2 mL) was added dropwise to quench the reaction, and a white solid precipitated. The mixture was filtered through Celite and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (dichloromethane / methanol = 50:1, volume ratio) to afford the product as a yellow solid (140 mg, 47% yield). ESI-MS m / z: 1053.5 [M-119] + . 1 H NMR (400MHz, CDCl3) δ8.39-8.27(m,1H),8.14-7.91(m,1H),7.70-7.60(m,1H),7.16-6.98(m, 9H),6.92-6.82(m,4H),6.85-6.70(m,4H),6.50-6.38(m,1H),5.92-5.54(m,1H ),4.80-4.54(m,4H),4.26-4.08(m,5H),3.84-3.78(m,6H),3.78-3.73(m,6H),3 .33-2.91(m,3H),2.54(s,3H),2.41(s,3H),2.38-2.30(m,1H),2.30-2.14(m,1 H),1.73-1.69(m,1H),1.67-1.57(m,1H),1.53-1.41(m,9H),1.45-1.30(m,3H).

[0860] Step 9: Tert-butyl (2-(5-(6-(bis(4-methoxybenzyl)amino)-4-methyl-3-(trifluoromethyl)pyridin-2-yl)-6-fluoro-8,10-dioxo-3,4,7,8,9,10-hexahydropyridin[2,3-f]quinazolin-1(2H)-yl)ethyl)(1-(2-(bis(-4-methoxybenzyl)amino)pyridin-3-yl)ethyl

[0861] Tert-butyl (2-(3-(7-(6-(bis(4-methoxybenzyl)amino)-4-methyl-3-(trifluoromethyl)pyridin-2-yl)-5,8-difluoro-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-yl)propyl)amino)ethyl)(1-(2-(bis(-4-methoxybenzyl)amino)pyridin-3-yl)ethyl)carbamate (140 mg, 0.119 mmol) was dissolved in dimethyl sulfoxide (3 mL), and N,N-diisopropylethylamine (62 mg, 0.477 mmol) was added. The reaction mixture was heated to 60°C and stirred for 3 hours. Water (20 mL) was added for dilution, and the mixture was extracted with ethyl acetate (20 mL x 2). The organic phase was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (petroleum ether / tetrahydrofuran = 3:1, volume ratio) to afford the product as a yellow oil (120 mg, yield 87%). ESI-MS m / z: 1033.5 [M-119] + .

[0862] Step 10: 5-(6-(bis(4-methoxybenzyl)amino)-4-methyl-3-(trifluoromethyl)pyridin-2-yl)-6-fluoro-1-(2-((1-(2-(4-methylbenzyl)amino)pyridin-3-yl)ethyl)amino)ethyl)-2,3,4,7-tetrahydropyrido[2,3-f]quinazoline-8,10(1H,9H)-dione

[0863] Tert-butyl (2- (5- (6- (bis (4-methoxybenzyl) amino) -4-methyl-3- (trifluoromethyl) pyridin-2-yl) -6-fluoro-8,10-dioxo-3,4,7,8,9,10- hexahydropyridine [2,3-f] quinazolin-1 (2H) -yl) ethyl) (1- (2- (bis (-4-methoxybenzyl) amino) pyridin-3-yl) ethyl (120 mg, 0.104 mmol) was dissolved in 1,4-dioxane (2 mL), and then a dioxane hydrochloric acid solution (2 mL, 4.0 M dioxane solution) was added and stirred at room temperature for 3 hours. The reaction solution was poured into a saturated sodium bicarbonate aqueous solution (40 mL) and washed with ethyl acetate (30 mL x 4). 2) Extraction, the organic phase was washed with saturated brine (40 mL), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain the product as a yellow foamy solid (110 mg, crude product). ESI-MS m / z: 933.5 [M+1] + .

[0864] Step 11: 6-(8-chloro-10-fluoro-6-(1-(2-((4-methoxybenzyl)amino)pyridin-3-yl)ethyl)-1,2,3,4,5,6-hexahydro-3a,6,7,9-tetraazacycloheptan[definition]phenanthren-11yl)-N,N-bis(4-methylbenzyl)-4-methyl-5-(trifluoromethyl)pyridin-2-amine

[0865] 5-(6-(bis(4-methoxybenzyl)amino)-4-methyl-3-(trifluoromethyl)pyridin-2-yl)-6-fluoro-1-(2-((1-(2-(4-methylbenzyl)amino)pyridin-3-yl)ethyl)amino)ethyl)-2,3,4,7-tetrahydropyridine[2,3-f]quinazoline-8,10(1H,9H)-dione (110 mg, 0.104 mmol, crude) was dissolved in anhydrous toluene (5 mL), and phosphorus oxychloride (159 mg, 1.04 mmol) and N,N-diisopropylethylamine (54 mg, 0.416 mmol) were added. Under nitrogen protection, the reaction was stirred at 100°C for 16 hours. After cooling to room temperature, the mixture was concentrated under reduced pressure, and the residue was purified by preparative thin-layer chromatography (petroleum ether / tetrahydrofuran = 2:1, volume ratio) to obtain the product as a yellow solid (60 mg, 62% yield). ESI-MS m / z: 933.4[M+1] + .

[0866] Step 12: 6-(10-fluoro-8-(((2R,7aS)-2-fluorotetrahydro-1H-pyrrolazin-7a(5H)-yl)methoxy)-6-(1-(2-((4-methoxybenzyl)amino)pyridin-3-yl)ethyl)-1,2,3,4,5,6-hexahydro-3a,6,7,9-tetraazacycloheptan[definition]phenanthren-11yl)-N,N-bis(4-methylbenzyl)-4-methyl-5-(trifluoromethyl)pyridin-2-amine

[0867] 6-(8-Chloro-10-fluoro-6-(1-(2-((4-methoxybenzyl)amino)pyridin-3-yl)ethyl)-1,2,3,4,5,6-hexahydro-3a,6,7,9-tetraazacyclohepta[def]phenanthrene-11yl)-N,N-bis(4-methylbenzyl)-4-methyl-5-(trifluoromethyl)pyridin-2-amine (20 mg, 0.021 mmol) was dissolved in tetrahydrofuran (5 mL), and (2R,7aS)-2-fluorotetrahydro-1H-pyrrolidine-7a(5H)methanol (34 mg, 0.214 mmol) and sodium hydride (8 mg, 0.214 mmol, 60% dispersion in mineral oil) were added at 0°C, and the reaction mixture was heated to 60°C and stirred for 6 hours. The mixture was concentrated under reduced pressure, and the residue was subjected to preparative thin-layer chromatography (petroleum ether / tetrahydrofuran = 1:1, volume ratio) to obtain the product as a yellow oil (24 mg, crude product). ESI-MS m / z: 1056.5 [M+1] + .

[0868] Step 13: 6-(6-(1-(2-aminopyridin-3-yl)ethyl)-10-fluoro-8-(((2R,7aS)-2-fluorotetrahydro-1H-pyrrolazin-7a(5H)-yl)methoxy)-1,2,3,4,5,6-hexahydro-3a,6,7,9-tetraazacycloheptane[def]phenanthren-11-yl)-4-methyl-5-(trifluoromethyl)pyridin-2-amine formate

[0869] 6-(10-Fluoro-8-(((2R,7aS)-2-fluorotetrahydro-1H-pyrrolazin-7a(5H)-yl)methoxy)-6-(1-(2-((4-methoxybenzyl)amino)pyridin-3-yl)ethyl)-1,2,3,4,5,6-hexahydro-3a,6,7,9-tetraazacyclohepta[def]phenanthrene-11yl)-N,N-bis(4-methylbenzyl)-4-methyl-5-(trifluoromethyl)pyridin-2-amine (24 mg, 0.021 mmol, crude) was dissolved in trifluoroacetic acid (0.5 mL), and trifluoromethanesulfonic acid (0.1 mL) was added. The mixture was stirred at room temperature for 1.5 hours. The reaction mixture was neutralized with saturated aqueous sodium bicarbonate to pH 7, concentrated under reduced pressure, and purified by preparative HPLC. The product was lyophilized to obtain a yellow solid (3 mg, 20% yield).

[0870] Preparative HPLC separation conditions:

[0871] Pillar: C18 OBD TM 19*250mm*5μM, flow rate 25mL / min.

[0872] Mobile phase: A: water (0.1% formic acid, v / v); B: acetonitrile; Mobile phase B%: 19-19%, 8 min; Detection wavelength: 214 / 254 nm.

[0873] ESI-MS m / z: 696.4[M+1] + . 1 H NMR (400MHz, DMSO-d6) δ8.45(1H,brs),7.95(t,J=6.0Hz,1H),7.63(d,J=7.6Hz,1H),7.44-7.17(m,2H),6.80-6.61(m,2H),6.43(s,1H),6.12-5. 99(m,1H),5.87(d,J=60.4Hz,1H),5.42-5.21(m,2H),4.23-3.88(m,4H) ,3.15-2.78(m,4H),2.35(s,3H),2.20-1.92(m,4H),1.87-1.20(m,11H). 19 F NMR(377MHz,DMSO-d6)δ-53.37,-142.12,-171.96.

[0874] Example 3:

[0875] Step 1: (R)-3-((4-methoxybenzyl)oxy)propane-1,2-diol

[0876] (S)-(2,2-Dimethyl-1,3-dioxolan-4-yl)methanol (1, 26.4 g, 20 mmol) was dissolved in anhydrous tetrahydrofuran (520 mL). The temperature was cooled to 0°C, and sodium hydroxide (12 g, 30 mmol, 60% purity) was added portionwise. Tetrabutylammonium iodide (738 mg, 2.0 mmol) and p-methoxybenzyl chloride (47 g, 30 mmol) were added. The mixture was stirred at 70°C under nitrogen for 2 h. The reaction mixture was slowly poured into ice water (500 mL) to quench the mixture. The mixture was extracted three times with ethyl acetate (500 mL). The combined organic phases were washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated. Silica gel column chromatography (petroleum ether / ethyl acetate = 1:1, volume ratio) afforded a colorless oil (30 g, 71% yield). 1 H NMR (400MHz, CDCl3) δ7.29-7.27 (m, 2H), 6.91 (d, J = 7.7Hz, 2H), 4.51 (s, 2H), 3.91(s,1H),3.83(s,3H),3.79-3.62(m,2H),3.60-3.54(m,2H),2.29(s,2H).

[0877] Step 2: (S)-1-((tert-Butyldimethylsilyl)oxy)-3-((4-methoxybenzyl)oxy)propan-2-ol

[0878] (R)-3-((4-methoxybenzyl)oxy)propane-1,2-diol (15 g, 6.2 mmol) was dissolved in dichloromethane (150 mL), and imidazole (6.3 g, 9.3 mmol) and tert-butyldimethylsilyl chloride (9.3 g, 6.2 mmol) were added. The mixture was stirred at 25°C for 2 h. The reaction mixture was slowly poured into an aqueous ammonium chloride solution (200 mL) and extracted twice with dichloromethane (100 mL). The combined organic phases were washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated to obtain a colorless oil (20 g, crude product).

[0879] Step 3: (S)-5-(((4-methoxybenzyl)oxy)methyl)-2,2,8,8,9-hexamethyl-3,3-diphenyl-4,7-dioxa-3,8-disilapropane

[0880] (S)-1-((tert-butyldimethylsilyl)oxy)-3-((4-methoxybenzyl)oxy)propan-2-ol (20 g, 61.3 mmol) was dissolved in dichloromethane (200 mL), and imidazole (8.3 g, 122.6 mmol), tert-butyldiphenylsilyl chloride (20 g, 73.6 mmol), and 4,4-dimethylaminopyridine (1.5 g, 12.3 mmol) were added. The mixture was stirred at 25°C for 16 h. The reaction mixture was slowly poured into an aqueous ammonium chloride solution (200 mL) and extracted twice with dichloromethane (100 mL). The combined organic phases were washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated to obtain a colorless oil (30 g, crude product).

[0881] Step 4: (R)-2-((tert-Butyldiphenylsilyl)oxy)-3-((4-methoxybenzyl)oxy)-propan-1-ol

[0882] (S)-5-(((4-methoxybenzyl)oxy)methyl)-2,2,8,8,9-hexamethyl-3,3-diphenyl-4,7-dioxa-3,8-disilapropane (15 g, 26.5 mmol) was dissolved in tetrahydrofuran (150 mL), and aqueous trifluoroacetic acid (176 mL, 265 mmol, 1.5 mol / L) was added. The mixture was stirred at 25°C for 6 h. The reaction mixture was slowly poured into aqueous sodium bicarbonate (200 mL) and extracted twice with ethyl acetate (200 mL). The combined organic phases were washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated. Silica gel column chromatography (petroleum ether / ethyl acetate = 3:1, volume ratio) afforded a colorless oil (5.2 g, 43% yield). 1 H NMR (400MHz, CDCl3) δ7.68-7.61(m,4H),7.47-7.29(m,6H),7.11(d,J=6.6Hz,2H),6.82(d,J=8.6Hz,2H),4.35-4.21(m, 2H),3.97-3.86(m,1H),3.80(s,3H),3.63(d,J=4.3Hz,2H),3.53-3.45(m,1H),3.41(dd,J=9.6,4.8Hz,1H),1.06(s,9H).

[0883] Step 5: (S)-2-((tert-Butyldiphenylsilyl)oxy)-3-((4-methoxybenzyl)oxy)propanal

[0884] (R)-2-((tert-Butyldiphenylsilyl)oxy)-3-((4-methoxybenzyl)oxy)-propan-1-ol (5.2 g, 11.5 mmol) was dissolved in dichloromethane (52 mL), and Dess-Martin periodinane (9.8 g, 23 mmol) was added. The mixture was stirred at 25°C for 1 h. The reaction mixture was slowly poured into aqueous sodium bicarbonate (50 mL) and extracted twice with ethyl acetate (200 mL). The combined organic phases were washed twice with saturated aqueous sodium thiosulfate (50 mL), washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated. Silica gel column chromatography (petroleum ether / ethyl acetate = 3:1, volume ratio) afforded a colorless oil (2.3 g, 45% yield). 1 H NMR (400MHz, CDCl3) δ9.68 (s, 1H), 7.74-7.62 (m, 4H), 7.49-7.32 (m, 6H), 7.18 (d, J = 4.6Hz, 2H), 6.8 7(d,J=8.4Hz,2H),4.40(s,2H),4.16(d,J=4.4Hz,1H),3.83(s,3H),3.70-3.52(m,2H),1.14(s,9H).

[0885] Step 6: 7-(6-(bis(4-methoxybenzyl)amino)-4-methyl-3-(trifluoromethyl)pyridin-2-yl)-6-(2-(((R)-2-((tert-butyldiphenylsilyl)oxy)-3-((4-methoxybenzyl)oxy)propyl)amino)ethyl)-5,8-difluoroquinazoline-2,4(1H,3H)-dione

[0886] 6-(2-aminoethyl)-7-(6-(bis(4-methoxybenzyl)amino)-4-methyl-3-(trifluoromethyl)pyridin-2-yl)-5,8-difluoroquinazoline-2,4(1H,3H)-dione (840 mg, 1.28 mmol) was dissolved in anhydrous 1,2-dichloroethane (17 mL), and (S)-2-((tert-butyldiphenylsilyl)oxy)-3-((4-methoxybenzyl)oxy)propanal (574 mg, 1.28 mmol) and AcOH (3.84 mg, 0.064 mmol) were added. The mixture was stirred at 25°C under nitrogen for 5 minutes. The reaction solution became clear, and then sodium cyanoborohydride (804 mg, 12.8 mmol) was added, and the reaction was continued at room temperature for 2 hours. Water (20 mL) was added dropwise to quench the reaction, and the mixture was extracted three times with dichloromethane (20 mL). The combined organic phases were washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated. Silica gel column chromatography (petroleum ether / tetrahydrofuran = 3:1, volume ratio) afforded a yellow oil (780 mg, 55% yield). ESI-MS m / z: 1088.4 [M+1] + .1 H NMR (400MHz, CDCl3) δ7.74-7.52(m,5H),7.47-7.34(m,5H),7.20-7.03(m,6H),6.91-6.77(m,6H),6.54-6.41(m,1H),4.86-4.45(m,6H) ),4.39-3.87(m,6H),3.83-3.76(m,9H),3.32(d,J=10.4Hz,1H),2.99-2.75(m,1H),2.60-2.53(m,1H),2.45-2.40(m,3H),1.00(s,9H).

[0887] Step 7: 4-(6-(bis(4-methoxybenzyl)amino)-4-methyl-3-(trifluoromethyl)pyridin-2-yl)-1-((R)-2-((tert-butyldiphenylsilyl)oxy)-3-((4-methoxybenzyl)oxy)propyl)-5-fluoro-1,2,3,6-tetrahydro-7H-pyrrolo[2,3-f]quinazoline-7,9(8H)-dione

[0888] 7-(6-(bis(4-methoxybenzyl)amino)-4-methyl-3-(trifluoromethyl)pyridin-2-yl)-6-(2-(((R)-2-((tert-butyldiphenylsilyl)oxy)-3-((4-methoxybenzyl)oxy)propyl)amino)ethyl)-5,8-difluoroquinazoline-2,4(1H,3H)-dione (780 mg, 0.72 mmol) was dissolved in dimethyl sulfoxide (20 mL), and diisopropylethylamine (365 mg, 2.88 mmol) was added. The reaction mixture was heated to 60°C and stirred for 16 hours. Water (30 mL) was added for dilution, and the mixture was extracted with ethyl acetate (30 mL x 2). The organic phase was dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (petroleum ether / tetrahydrofuran ester = 2:1, volume ratio) to afford a yellow oil (700 mg, 91% yield). ESI-MS m / z:1068.5[M+1] + . 1H NMR (400MHz, CDCl3) δ7.72-7.66(m,5H),7.45-7.29(m,5H),7.15-7.09(m,6H),6.88-6.79(m,6H),6.49-6.40(m,1H),4.86-4.60(m,4H),4.4 0(s,1H),4.25-4.20(m,2H),3.99-3.95(m,3H),3.85-3.78(m,9H),3.6 3(t,J=9.9Hz,2H),3.54-3.40(m,3H),2.48-2.43(m,3H),1.01(s,9H).

[0889] Step 8: 4-(6-(bis(4-methoxybenzyl)amino)-4-methyl-3-(trifluoromethyl)pyridin-2-yl)-5-fluoro-1-((R)-2-hydroxy-3-((4-methoxybenzyl)oxy)propyl)-1,2,3,6-tetrahydro-7H-pyrrolo[2,3-f]quinazoline-7,9(8H)-dione

[0890] 4-(6-(bis(4-methoxybenzyl)amino)-4-methyl-3-(trifluoromethyl)pyridin-2-yl)-1-((R)-2-((tert-butyldiphenylsilyl)oxy)-3-((4-methoxybenzyl)oxy)propyl)-5-fluoro-1,2,3,6-tetrahydro-7H-pyrrolo[2,3-f]quinazoline-7,9(8H)-dione (700 mg, 0.66 mmol) was dissolved in tetrahydrofuran (20 mL). Tetrabutylammonium fluoride (3.3 mL, 3.3 mmol, 1 mol / L in THF) was added, and the reaction mixture was heated to 70°C and stirred for 16 hours. The mixture was diluted with water (30 mL) and extracted with ethyl acetate (30 mL x 2). The organic phase was dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (dichloromethane / methanol = 20:1, volume ratio) to give a yellow solid (310 mg, yield 56%). ESI-MS m / z: 830.4 [M+1] + . 1H NMR (400MHz, CDCl3) δ8.00 (s, 1H), 7.79 (d, J = 12.3Hz, 1H), 7.11 (d, J = 16.5 Hz,6H),6.92-6.76(m,6H),6.40(s,1H),4.84-4.54(m,4H),4.33-4.09(m, 4H),4.08-3.89(m,1H),3.79(d,J=16.7Hz,9H),3.73-3.66(m,1H),3.56(d d,J=14.4,7.0Hz,1H),3.50-3.23(m,3H),2.67-2.56(m,1H),2.41(s,3H).

[0891] Step 9: (9S)-3-(6-(bis(4-methoxybenzyl)amino)-4-methyl-3-(trifluoromethyl)pyridin-2-yl)-4-fluoro-9-(((4-methoxybenzyl)oxy)methyl)-2,5,9,10-tetrahydro-8-oxa-5,7,10a-triazinaphin[2,1,8-cde]azulene-6(1H)-one

[0892] Dissolve 4-(6-(bis(4-methoxybenzyl)amino)-4-methyl-3-(trifluoromethyl)pyridin-2-yl)-5-fluoro-1-((R)-2-hydroxy-3-((4-methoxybenzyl)oxy)propyl)-1,2,3,6-tetrahydro-7H-pyrrolo[2,3-f]quinazoline-7,9(8H)-dione (180 mg, 0.217 mmol) in tetrahydrofuran (20 mL). Add triphenylphosphine (142 mg, 0.543 mmol). Replace the nitrogen atmosphere three times. Cool the reaction mixture to 0°C, then slowly add diisopropyl azodicarboxylate (109 mg, 0.543 mmol) dropwise. Stir at room temperature for 2 hours. Add ammonium chloride aqueous solution (30 mL), and extract with ethyl acetate (30 mL x 2). The organic phase was dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (dichloromethane / methanol = 20:1, volume ratio) to give a yellow solid (150 mg, yield 85%). ESI-MS m / z: 812.4 [M+1] + . 1 H NMR (400MHz, CDCl3) δ7.18-7.00(m,6H),6.95-6.85(m,6H),6.43(s,1H),4.86-4.54(m,8H),3.93(d,J=14.9 Hz,1H),3.83-3.81(m,9H),3.72(d,J=13.8Hz,2H),3.53(d,J=12.4Hz,3H),2.82-2.59(m,1H),2.42(s,3H).

[0893] Step 10: 6-((S)-4-Fluoro-9-((4-methoxybenzyl)oxy)methyl)-6-(methylthio)-1,2,9,10-tetrahydro-8-oxo-5,7,10a-triazinaphin[2,1,8-cde]azul-3-yl)-N,N-bis(4-methoxybenzyl)-4-methyl-5-(trifluoromethyl)pyridin-2-amine

[0894] (9S)-3-(6-(bis(4-methoxybenzyl)amino)-4-methyl-3-(trifluoromethyl)pyridin-2-yl)-4-fluoro-9-(((4-methoxybenzyl)oxy)methyl)-2,5,9,10-tetrahydro-8-oxa-5,7,10a-triazanaphtho[2,1,8-cde]azulene-6(1H)-one (120 mg, 0.148 mmol) was dissolved in acetonitrile (12 mL). 1,8-diazabicyclo[5.4.0]undec-7-ene (45 mg, 0.296 mmol) was added. The atmosphere was purged with nitrogen three times, and Carter's condensation agent BOP (85 mg, 0.192 mmol) was added. The mixture was stirred at room temperature for 1 hour. Methyl mercaptan (1.42 g, 2.96 mmol, 10% propylene glycol solution) was added. The mixture was stirred at room temperature for 2 hours. Aqueous ammonium chloride (30 mL) was added, and the mixture was extracted with ethyl acetate (30 mL x 2). The organic phase was dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (petroleum ether / tetrahydrofuran = 2:1, volume ratio) to afford a yellow solid (120 mg, 96% yield). ESI-MS m / z: 842.3 [M+1] + . 1 H NMR (400MHz, CDCl3) δ7.23-7.00(m,6H),6.95-6.79(m,6H),6.47-6.35(m,1H),4.87-4.48(m,8H),4.00-3. 85(m,2H),3.84-3.80(m,9H),3.78-3.59(m,3H),3.48-3.42(m,2H),2.72-2.65(m,3H),2.46-2.42(m,3H).

[0895] Step 11: 6-((9S)-4-Fluoro-9-((4-methoxybenzyl)oxy)methyl)-6-(methylsulfinyl)-1,2,9,10-tetrahydro-8-oxo-5,7,10a-triazanaphtho[2,1,8-cde]azul-3-yl)-N,N-bis(4-methoxybenzyl)-4-methyl-5-(trifluoromethyl)pyridin-2-amine

[0896] 6-((S)-4-Fluoro-9-((4-methoxybenzyl)oxy)methyl)-6-(methylthio)-1,2,9,10-tetrahydro-8-oxo-5,7,10a-triazinap[2,1,8-cde]azul-3-yl)-N,N-bis(4-methoxybenzyl)-4-methyl-5-(trifluoromethyl)pyridin-2-amine (100 mg, 0.12 mmol) was dissolved in dichloromethane (20 mL), and m-chloroperbenzoic acid (26.6 mg, 0.13 mmol, 85% purity) was added. The mixture was stirred at room temperature for 2 hours. A mixed aqueous solution of sodium bicarbonate and sodium thiosulfate (30 mL, 1:1) was added, and the product was extracted with dichloromethane (30 mL x 2). The product was washed twice with a mixed aqueous solution of sodium bicarbonate and sodium thiosulfate (30 mL, 1:1). The organic phase was dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to give a crude product (130 mg). ESI-MS m / z: 858.3 [M+1] + .

[0897] Step 12: 6-((9S)-4-fluoro-6-(((2R,7aS)-2-fluorotetrahydro-1H-pyrrolizin-7a(5H)-yl)methoxy)-9-(((4-methoxybenzyl)oxy)methyl)-1,2,9,10-tetrahydro-8-oxy-5,7,10a-triazanaphtho[2,1,8-cde]azul-3-yl)-N,N-bis(4-methoxybenzyl)-4-methyl-5-(trifluoromethyl)pyrrolidone Pyridin-2-amine and 6-((4S)-9-fluoro-7-(((2R,7aS)-2-fluorotetrahydro-1H-pyrrolidin-7a(5H)-yl)methoxy)-4-(((4-methoxybenzyl)oxy)methyl)-3,4-dihydro-5-oxa-2a,6,8-triazanaphtho[2,1,8-cde]azul-10-yl)-N,N-bis(4-methoxybenzyl)-4-methyl-5-(trifluoromethyl)pyridin-2-amine

[0898] ((2R,7aS)-2-Fluorotetrahydro-1H-pyrrolazin-7a(5H)-yl)methanol (241 mg, 1.52 mmol) was dissolved in tetrahydrofuran (40 mL), the atmosphere was replaced with nitrogen three times, the temperature was lowered to 0°C, and lithium tert-butoxide (1.52 mL, 1.52 mmol, 1 mol / L) was slowly added dropwise. The mixture was stirred for 5 minutes. A solution of 6-((9S)-4-fluoro-9-((4-methoxybenzyl)oxy)methyl)-6-(methylsulfinyl)-1,2,9,10-tetrahydro-8-oxo-5,7,10a-triazanaphtho[2,1,8-cde]azulene-3-yl)-N,N-bis(4-methoxybenzyl)-4-methyl-5-(trifluoromethyl)pyridin-2-amine (130 mg, 0.152 mmol) in tetrahydrofuran was added dropwise, and the mixture was stirred at 0°C for 1 hour. The reaction mixture was slowly poured into an aqueous ammonium chloride solution (80 mL), extracted with ethyl acetate (40 mL x 2), and washed with saturated brine (80 mL). The organic phase was dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (dichloromethane / methanol = 20:1, volume ratio) to give the product 6-((9S)-4-fluoro-6-(((2R,7aS)-2-fluorotetrahydro-1H-pyrrolazin-7a(5H)-yl)methoxy)-9-(((4-methoxybenzyl)oxy)methyl)-1,2,9,10-tetrahydro-8-oxy-5,7,10a-triazanaphtho[2,1,8-cde]azul-3-yl)-N,N-bis(4-methoxybenzyl)-4-methyl-5-(trifluoromethyl)pyridin-2-amine (40 mg, yield 28%), yellow solid, ESI-MS m / z: 951.4 [M+1]. + And the product 6-((4S)-9-fluoro-7-(((2R,7aS)-2-fluorotetrahydro-1H-pyrrolazin-7a(5H)-yl)methoxy)-4-(((4-methoxybenzyl)oxy)methyl)-3,4-dihydro-5-oxa-2a,6,8-triazanaphtho[2,1,8-cde]azulen-10-yl)-N,N-bis(4-methoxybenzyl)-4-methyl-5-(trifluoromethyl)pyridin-2-amine (27 mg, yield 19%, yellow solid), ESI-MS m / z: 953.4 [M+1] + .

[0899] Step 13: ((4S,10S)-10-(6-amino-4-methyl-3-(trifluoromethyl)pyridin-2-yl)-9-fluoro-7-(((2R,7aS)-2-fluorotetrahydro-1H- ((4S,10R)-10-(6-amino-4-methyl-3-(trifluoromethyl)pyridin-2-yl)-9-fluoro-7-(((2R,7aS)-2-fluorotetrahydro-1H-pyrrolidin-7a(5H)-yl)methoxy)-3,4-dihydro-5-oxa-2a,6,8-triazanaphtho[2,1,8-cde]azulen-4-yl)methanol and ((4S,10R)-10-(6-amino-4-methyl-3-(trifluoromethyl)pyridin-2-yl)-9-fluoro-7-(((2R,7aS)-2-fluorotetrahydro-1H-pyrrolidin-7a(5H)-yl)methoxy)-3,4-dihydro-5-oxa-2a,6,8-triazanaphtho[2,1,8-cde]azulen-4-yl)methanol

[0900] 6-((4S)-9-fluoro-7-(((2R,7aS)-2-fluorotetrahydro-1H-pyrrolazin-7a(5H)-yl)methoxy)-4-(((4-methoxybenzyl)oxy)methyl)-3,4-dihydro-5-oxa-2a,6,8-triazanaphtho[2,1,8-cde]azulen-10-yl)-N,N-bis(4-methoxybenzyl)-4-methyl-5-(trifluoromethyl)pyridin-2-amine (27 mg, 0.0284 mmol) was dissolved in dichloromethane (5 mL), trifluoromethanesulfonic acid (42.6 mg, 0.284 mmol) was added, and the mixture was stirred at 25°C for 15 minutes. The reaction mixture was slowly poured into aqueous sodium bicarbonate solution (20 mL), and dichloromethane (20 mL x 10) was added. 2) Extraction, the combined organic phases were washed with saturated brine (40 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by preparative HPLC (column: C18 OBD TM 19*250mm*5μM, flow rate 25mL / min, mobile phase: A: water (0.1% ammonia water, v / v) B: acetonitrile; mobile phase B%: 19-19%, 8min; detection wavelength: 214 / 254nm) to separate and obtain compound 3-1 (2.10mg, yield 12.5%, white solid, retention time 6.42min) and compound 3-2 (1.75mg, yield 10.4%, white solid, retention time 8.08min).

[0901] Compound 3-1 (retention time 6.42 min):

[0902] ESI-MS m / z:591.2[M+1] + . 1H NMR(400MHz,DMSO-d6)δ7.51(d,J=3.0Hz,1H),6.78(s,2H),6.54(s,1H),6.1 9(d,J=3.1Hz,1H),5.47(s,1H),5.29(d,J=53.6Hz,1H),4.97-4.77(m,2H),4 .64-4.47(m,1H),4.21-4.02(m,2H),3.96-3.72(m,2H),3.16-3.03(m,3H),2 .84(q,J=5.5,3.6Hz,1H),2.39(s,3H),2.21-1.96(m,3H),1.95-1.70(m,3H). 19 F NMR (377MHz, DMSO-d6) δ-53.16 (d, J=58.8Hz), -141.09, -171.99.

[0903] Compound 3-2 (retention time 8.08 min):

[0904] ESI-MS m / z:591.2[M+1] + . 1 H NMR (400MHz, DMSO-d6) δ7.50(s,1H),6.77(s,2H),6.54(s,1H),6.17(d,J=3.1Hz,1 H),5.44(t,J=3.8Hz,1H),5.29(d,J=54.4Hz,1H),4.91(d,J=14.7Hz,1H),4.81-4.7 0(m,1H),4.60-4.45(m,1H),4.07(d,J=10.3Hz,2H),3.97-3.75(m,2H),3.18-2.99( m,3H),2.84(s,1H),2.39(s,3H),2.20-1.94(m,3H),1.85(dd,J=35.0,12.5Hz,3H). 19 F NMR(377MHz,DMSO-d6)δ-53.24,-141.33,-172.02.

[0905] Step 14: ((3S,9S)-3-(6-amino-4-methyl-3-(trifluoromethyl)pyridin-2-yl)-4-fluoro-6-(((2R,7aS)-2-fluorotetrahydro-1H-pyrrolazin-7a(5H)-yl)methoxy)-1,2,9,10-tetrahydro-8-oxa-5,7,10a-triazinaphin[2,1,8-cde]azulen-9-yl) Methanol and ((3R,9S)-3-(6-amino-4-methyl-3-(trifluoromethyl)pyridin-2-yl)-4-fluoro-6-(((2R,7aS)-2-fluorotetrahydro-1H-pyrrolizin-7a(5H)-yl)methoxy)-1,2,9,10-tetrahydro-8-oxa-5,7,10a-triazanaphtho[2,1,8-cde]azulen-9-yl)methanol

[0906] 6-((9S)-4-fluoro-6-(((2R,7aS)-2-fluorotetrahydro-1H-pyrrolazin-7a(5H)-yl)methoxy)-9-(((4-methoxybenzyl)oxy)methyl)-1,2,9,10-tetrahydro-8-oxy-5,7,10a-triazanaphtho[2,1,8-cde]azulen-3-yl)-N,N-bis(4-methoxybenzyl)-4-methyl-5-(trifluoromethyl)pyridin-2-amine (40 mg, 0.0419 mmol) was dissolved in dichloromethane (5 mL), trifluoromethanesulfonic acid (62.9 mg, 0.419 mmol) was added, and the mixture was stirred at 25°C for 15 minutes. The reaction mixture was slowly poured into aqueous sodium bicarbonate solution (20 mL), and dichloromethane (20 mL) was added. x2) extraction, the combined organic phases were washed with saturated brine (40 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by preparative HPLC (column: C18 OBD TM 19*250mm*5μM, flow rate 25mL / min. Mobile phase: A: water (0.1% ammonia water, v / v) B: acetonitrile; mobile phase B%: 19-19%, 8min; detection wavelength: 214 / 254nm.) Compound 3-3 (3.5mg, yield 14%, white solid, retention time 6.45min) and compound 3-4 (2.6mg, yield 17.5%, white solid, retention time 7.63min) were separated.

[0907] Compound 3-3 (retention time 6.45 min):

[0908] ESI-MS m / z:593.4[M+1] + . 1H NMR (400MHz, DMSO-d6) δ6.80 (s, 2H), 6.45 (s, 1H), 5.42-5.13 (m, 2H), 4.59 (q, J = 5.9Hz, 1H), 4.12-3.93 (m, 2H), 3.83-3.5 6(m,4H),3.46(q,J=9.8Hz,2H),3.18-2.93(m,3H),2.92-2.62(m,3H),2.36(s,3H),2.17-1.93(m,3H),1.86-1.70(m,3H). 19 F NMR(377MHz,DMSO-d6)δ-53.19,-145.08,-172.00.

[0909] Compound 3-4 (retention time 7.63 min):

[0910] ESI-MS m / z:593.4[M+1] + . 1 H NMR (400MHz, DMSO-d6) δ6.79 (s, 2H), 6.45 (s, 1H), 5.28 (dd, J = 30.0, 24.3Hz, 2H), 4 .56(q,J=6.0Hz,1H),4.11-3.91(m,2H),3.77(dt,J=10.4,5.0Hz,1H),3.74-3.60(m ,3H),3.51(q,J=9.7Hz,1H),3.42(dd,J=14.1,7.6Hz,1H),3.20-2.95(m,3H),2.95- 2.74(m,2H),2.74-2.56(m,1H),2.37(s,3H),2.24-1.96(m,3H),1.92-1.69(m,3H). 19 F NMR(377MHz,DMSO-d6)δ-53.34,-145.67,-172.03.

[0911] Embodiment 4:

[0912] Compound 4-1, compound 4-2 and compound 4-3 were obtained by a similar synthesis method to Example 3 using (R)-(2,2-dimethyl-1,3-dioxolane-4-yl)methanol as the starting material.

[0913] Compound 4-1 and compound 4-2 were prepared by HPLC (column: C18 OBD TM19*250mm*5μM, flow rate 25mL / min, mobile phase: A: water (0.1% ammonia, v / v) B: acetonitrile; mobile phase B%: 19-19%, 8min; detection wavelength: 214 / 254nm) for separation. Compound 4-1 had a retention time of 6.15min, and compound 4-2 had a retention time of 6.95min.

[0914] Compound 4-1 (retention time 6.15 min):

[0915] ESI-MS m / z:591.2[M+1] + . 1 H NMR (400MHz, DMSO-d6) δ7.51(s,1H),6.78(s,2H),6.51(s,1H),6.19(s,1H),5.59-5.13(m,2H),4.89(dd,J=27.3,10.9Hz,2H),4.62-4.42( m,1H),4.25-4.02(m,2H),3.96-3.70(m,2H),3.18-2.92(m,3H),2.84(d,J=9.9Hz,1H),2.41(s,3H),2.23-1.94(m,3H),1.88-1.80(m,3H). 19 F NMR(377MHz,DMSO-d6)δ-53.08,-141.09,-171.99.

[0916] Compound 4-2 (retention time 6.95 min):

[0917] ESI-MS m / z:591.2[M+1] + . 1 H NMR(400MHz,DMSO-d6)δ7.51(d,J=3.1Hz,1H),6.78(s,2H),6.51(s,1H),6.18(d ,J=3.1Hz,1H),5.51(s,1H),5.30(d,J=55.2Hz,1H),4.90(s,1H),4.84-4.71(m, 1H),4.63-4.42(m,1H),4.23-3.99(m,2H),3.99-3.72(m,2H),3.20-2.98(m,3H) ,2.84(q,J=9.5,8.4Hz,1H),2.41(s,3H),2.23-1.98(m,3H),1.94-1.67(m,3H). 19 F NMR(377MHz,DMSO-d6)δ-53.24,-141.34,-171.95.

[0918] Compound 4-3:

[0919] ESI-MS m / z:593.4[M+1] + . 1 H NMR (400MHz, DMSO-d6) δ6.79(d,J=6.8Hz,2H),6.45(s,1H),5.41-5.13(m,2H),4.57(dq,J=13.4,6.2Hz,1H),4.12-3.91(m,2H),3.81 -3.58(m,4H),3.56-3.39(m,2H),3.17-2.98(m,3H),2.78(dd,J=33.7,8.8Hz,3H),2.36(s,3H),2.19-1.93(m,3H),1.83-1.74(m,3H). 19 F NMR (377MHz, DMSO-d6)δ-53.20,-53.34,-145.09,-145.68,-171.99(d,J=22.3Hz).

[0920] Example 5:

[0921] Compound 5-1: 6-(9-fluoro-7-((2R,7aS)-2-fluorotetrahydro-1H-pyrrolizin-7a(5H)-yl)methoxy)-4,5-dihydro-3H-2a,5,6,8-tetraazanaphtho[2,1,8-cde]azulen-10-yl)-4-methyl-5-(trifluoromethyl)pyridin-2-amine

[0922] Step 1: 7-(6-(bis(4-methoxybenzyl)amino)-4-methyl-3-(trifluoromethyl)pyridin-2-yl)-6-(2-((2-(1,3-dioxoisoindol-2-yl)ethyl)amino)ethyl)-5,8-difluoroquinazoline-2,4(1H,3H)-dione

[0923] 6-(2-Aminoethyl)-7-(6-(bis(4-methoxybenzyl)amino)-4-methyl-3-(trifluoromethyl)pyridin-2-yl)-5,8-difluoroquinazoline-2,4(1H,3H)-dione (105 mg, 0.16 mmol) was dissolved in a mixed solvent of methanol (4 mL) and tetrahydrofuran (1 mL), 2-(1,3-dioxoisoindolin-2-yl)acetaldehyde (106 mg, 0.56 mmol) and a drop of acetic acid were added, and the mixture was stirred at room temperature. The reaction was stirred at room temperature for half an hour, and sodium cyanoborohydride (20 mg, 0.32 mmol) was slowly added. LCMS was performed every half an hour, and sodium cyanoborohydride (20 mg, 0.32 mmol) was added until most of the raw material 6-(2-aminoethyl)-7-(6-(bis(4-methoxybenzyl)amino)-4-methyl-3-(trifluoromethyl)pyridin-2-yl)-5,8-difluoroquinazoline-2,4(1H,3H)-dione was converted into the desired product. Pure water (30 mL) was added to the reaction solution to quench the reaction, and the mixture was extracted with ethyl acetate (30 mL x 3). The resulting organic phase was washed with saturated sodium chloride solution (30 mL), dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was chromatographed on a silica gel column (methanol / dichloromethane = 1:35, volume ratio) to obtain the product as a yellow solid (93 mg, yield 70%). ESI-MS m / z: 829.1 [M+1] + .

[0924] Step 2: 4-(6-(bis(4-methoxybenzyl)amino)-4-methyl-3-(trifluoromethyl)pyridin-2-yl)-1-(2-(1,3-dioxoisoindol-2-yl)ethyl)-5-fluoro-1,2,3,6-tetrahydro-7H-pyrrolo[2,3-f]quinazoline-7,9(8H)-dione

[0925] 7-(6-(bis(4-methoxybenzyl)amino)-4-methyl-3-(trifluoromethyl)pyridin-2-yl)-6-(2-((2-(1,3-dioxoisoindol-2-yl)ethyl)amino)ethyl)-5,8-difluoroquinazoline-2,4(1H,3H)-dione (93 mg, 0.11 mmol) was dissolved in dimethyl sulfoxide (5 mL), and diisopropylethylamine (45 mg, 0.33 mmol) was added. Under nitrogen protection, the reaction was stirred at 80°C for 16 hours. After cooling to room temperature, the mixture was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (dichloromethane / methanol = 60:1, volume ratio) to obtain the product as a yellow solid (71 mg, yield 78%). ESI-MS m / z: 809.1 [M+1] + .

[0926] Step 3: 3-(6-(bis(4-methoxybenzyl)amino)-4-methyl-3-(trifluoromethyl)pyridin-2-yl)-4-fluoro-2,5,9,10-tetrahydro-1H-5,7,8,10a-tetraazanaphtho[2,1,8-cde]azulene-6(8H)-one

[0927] 4-(6-(bis(4-methoxybenzyl)amino)-4-methyl-3-(trifluoromethyl)pyridin-2-yl)-1-(2-(1,3-dioxoisoindol-2-yl)ethyl)-5-fluoro-1,2,3,6-tetrahydro-7H-pyrrolo[2,3-f]quinazoline-7,9(8H)-dione (71 mg, 0.08 mmol) was added to ethanol (20 mL), followed by hydrazine hydrate (85%) (1 mL) and reflux for 5 hours. The reaction solution was cooled to room temperature and then placed in an ice-water bath to cool thoroughly. A large amount of solid precipitated, which was filtered, the filter cake washed with ethanol, and the solid was air-dried to obtain the product as a yellow-green solid (35 mg, 60% yield). ESI-MS m / z: 661.2 [M+1] + . 1 H NMR (400MHz, CDCl3) δ7.13(d,J=8.0Hz,4H),6.87(d,J=8.0Hz,4H),6.43(s,1H),4.81(d, J=16.0Hz,2H),4.62(d,J=8.0Hz,2H),3.89(bs,1H),3.82(s,6H),3.61-3.53(m,2H),3.47 (brs,2H),2.77-2.68(m,2H),2.42(s,3H). 19 F NMR (400MHz, CDCl3) δ-54.86,-153.05.

[0928] Step 4: Di-tert-butyl 3-(6-(bis(4-methoxybenzyl)amino)-4-methyl-3-(trifluoromethyl)pyridin-2-yl)-4-fluoro-6-oxo-1,2,9,10-tetrahydro-5H-5,7,8,10a-tetraazanaphtho[2,1,8-cde]azulene-5,8(6H)-dicarboxylate and tert-butyl 3-(6-(bis(4-methoxybenzyl)amino)-4-methyl-3-(trifluoromethyl)pyridin-2-yl)-4-fluoro-6-oxo-1,2,5,6,9,10-hexahydro-8H-5,7,8,10a-tetraazanaphtho[2,1,8-cde]azulene-8-carboxylate

[0929] 3-(6-(bis(4-methoxybenzyl)amino)-4-methyl-3-(trifluoromethyl)pyridin-2-yl)-4-fluoro-2,5,9,10-tetrahydro-1H-5,7,8,10a-tetraazanaphtho[2,1,8-cde]azulene-6(8H)-one (80 mg, 0.12 mmol) was added to dichloromethane (6 mL), followed by triethylamine (37 mg, 0.36 mmol), di-tert-butyl dicarbonate (52 mg, 0.24 mmol) and N,N-dimethylpyridin-4-amine (5 mg, 0.04 mmol), and the reaction was stirred at room temperature for 4 hours. The reaction solution was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (dichloromethane / methanol = 60:1, volume ratio) to give 3-(6-(bis(4-methoxybenzyl)amino)-4-methyl-3-(trifluoromethyl)pyridin-2-yl)-4-fluoro-6-oxo-1,2,9,10-tetrahydro-5H-5,7,8,10a-tetraazanaphtho[2,1,8-cde]azulene-5,8(6H)-dicarboxylic acid ditert-butyl ester Butyl ester (42 mg, yield 40%, orange-yellow solid) and tert-butyl 3-(6-(bis(4-methoxybenzyl)amino)-4-methyl-3-(trifluoromethyl)pyridin-2-yl)-4-fluoro-6-oxo-1,2,5,6,9,10-hexahydro-8H-5,7,8,10a-tetraazanaphtho[2,1,8-cde]azulene-8-carboxylate (50 mg, yield 54%, yellow solid).

[0930] Di-tert-butyl 3-(6-(bis(4-methoxybenzyl)amino)-4-methyl-3-(trifluoromethyl)pyridin-2-yl)-4-fluoro-6-oxo-1,2,9,10-tetrahydro-5H-5,7,8,10a-tetraazanaphtho[2,1,8-cde]azulene-5,8(6H)-dicarboxylate: 1 H NMR (400MHz, DMSO-d6) δ7.15(d,J=8.0Hz,4H),6.89(d,J=8.0Hz,4H),6.83(s,1H),4.78(d,J=16.0Hz,2H),4.62(d,J=8.0H z,2H),4.23-4.05(m,3H),3.73(s,6H),3.70-3.47(m,2H),2.67-2.64(m,2H),2.44-2.39(m,4H),1.54(s,9H),1.46(s,9H).

[0931] tert-Butyl 3-(6-(bis(4-methoxybenzyl)amino)-4-methyl-3-(trifluoromethyl)pyridin-2-yl)-4-fluoro-6-oxo-1,2,5,6,9,10-hexahydro-8H-5,7,8,10a-tetraazanaphtho[2,1,8-cde]azulene-8-carboxylate: ESI-MS m / z: 705.2 [M-55]+ . 1 H NMR (400MHz, DMSO-d6) δ11.07(s,1H),7.15(d,J=8.0Hz,4H),6.89(d,J=8.0Hz,4H),6.79(s,1H),4.96(d,J=16.0Hz,2H),4. 50(d,J=8.0Hz,2H),4.00-3.89(m,3H),3.73(s,6H),3.64-3.57(m,2H),3.51-3.42(m,2H),2.38-2.33(m,4H),1.45(s,9H).

[0932] Step 5: tert-Butyl 3-(6-(bis(4-methoxybenzyl)amino)-4-methyl-3-(trifluoromethyl)pyridin-2-yl)-4-fluoro-6-(methylthio)-1,2,9,10-tetrahydro-8H-5,7,8,10a-tetraazanaphtho[2,1,8-cde]azulene-8-carboxylate

[0933] tert-Butyl 3-(6-(bis(4-methoxybenzyl)amino)-4-methyl-3-(trifluoromethyl)pyridin-2-yl)-4-fluoro-6-oxo-1,2,5,6,9,10-hexahydro-8H-5,7,8,10a-tetraazanaphtho[2,1,8-cde]azulene-8-carboxylate (30 mg, 0.04 mmol) was dissolved in dry acetonitrile (5 mL), and ((1H-benzo[d][1,2,3]triazol-1-yl)oxy)tris(dimethylamino)phosphonium(V)hexafluorophosphate (35 mg, 0.08 mmol) and 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine (18 mg, 0.12 mmol) were added. The mixture was stirred at room temperature under nitrogen protection for 4 hours. LCMS monitoring showed that the raw material was basically converted to the intermediate state. Methyl mercaptan (10%, 1 mL) was added and stirring continued at room temperature for 16 hours. The mixture was concentrated under reduced pressure and the residue was chromatographed on a silica gel column (dichloromethane / methanol = 120:1, volume ratio) to afford the product as a yellow solid (24 mg, 77% yield). ESI-MS m / z: 396.1 [M / 2+1] + . 1H NMR (400MHz, CDCl3) δ7.13(d,J=8.4Hz,4H),6.87(d,J=8.4Hz,4H),6.42(s,1H),4.82-4.62(m,4H),4.15-4.00(m, 3H),3.82(s,6H),3.23-2.92(m,2H),2.84-2.61(m,1H),2.66(s,3H),2.41(s,3H),2.37-2.29(m,2H),1.42(s,9H).

[0934] Step 6: 6-(4-Fluoro-6-(((2R,7aS)-2-fluorotetrahydro-1H-pyrrolazin-7a(5H)-yl)methoxy)-2,8,9-10-tetrahydro-1H-5,7,8,10a-tetraazanaphtho[2,1,8-cde]azulene-3-yl)-N,N-bis(4-methoxybenzyl)-4-methyl-5-(trifluoromethyl)pyridin-2-amine

[0935] ((2R,7aS)-2-Fluorotetrahydro-1H-pyrrolazin-7a(5H)-yl)methanol (16 mg, 0.1 mmol) was dissolved in anhydrous tetrahydrofuran (2 mL). Sodium hydride (16 mg, 0.4 mmol) was added in an ice-water bath. The reaction was stirred for 0.5 h under nitrogen protection. Then, a solution of tert-butyl 3-(6-(bis(4-methoxybenzyl)amino)-4-methyl-3-(trifluoromethyl)pyridin-2-yl)-4-fluoro-6-(methylthio)-1,2,9,10-tetrahydro-8H-5,7,8,10a-tetraazanaphtho[2,1,8-cde]azulene-8-carboxylate (24 mg, 0.035 mmol) in tetrahydrofuran (2 mL) was added dropwise. The reaction was stirred at 50 ° C for 6 h under nitrogen protection. Saturated aqueous citric acid was added to adjust the pH to 5, and the mixture was diluted with saturated aqueous sodium chloride (100 mL). Extraction was then performed with ethyl acetate (100 mL x 2). The organic phase was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (dichloromethane / methanol = 12:1, volume ratio) to afford the product as a white solid (12 mg, 40% yield). ESI-MS m / z: 802.4 [M+1] + .

[0936] Step 7: 6-(9-fluoro-7-((2R,7aS)-2-fluorotetrahydro-1H-pyrrolizin-7a(5H)-yl)methoxy)-4,5-dihydro-3H-2a,5,6,8-tetraazanaphtho[2,1,8-cde]azulen-10-yl)-4-methyl-5-(trifluoromethyl)pyridin-2-amine

[0937] 6-(9-Fluoro-7-(((2R,7aS)-2-fluorotetrahydro-1H-pyrrolazin-7a(5H)-yl)methoxy)-4,5-dihydro-3H-2a,5,6,8-tetraazanaphtho[2,1,8-cde]azulene-10-yl)-N,N-bis(4-methoxybenzyl)-4-methyl-5-(trifluoromethyl)pyridin-2-amine (12 mg, 0.015 mmol) was dissolved in trifluoroacetic acid (2.5 mL) and trifluoromethanesulfonic acid (0.5 mL) and stirred at room temperature for 1 hour. The reaction mixture was neutralized with saturated aqueous potassium carbonate to pH = 9, concentrated under reduced pressure, and purified by preparative HPLC. The product was lyophilized to obtain a yellow solid (4 mg).

[0938] Preparative HPLC separation conditions:

[0939] Pillar: C18 OBD TM 19*250mm*5μM, flow rate 25mL / min.

[0940] Mobile phase: A: water (0.1% ammonia, v / v); B: acetonitrile; Mobile phase B%: 25-65%, 9 min; Detection wavelength: 214 / 254 nm.

[0941] ESI-MS m / z:559.9[M+1] + . 1 H NMR(400MHz,DMSO-d6)δ8.60-8.45(m,1H),7.30-7.15(m,1H),6.80-6.56(m,2H),6.50-6.35(m,1H),5.40-5.20(m,2H ),4.56-4.30(m,2H),4.15-3.60(m,4H),2.85-2.55(m,2H),2.50-2.30(m,3H),2.10-1.80(m,2H),1.50-1.15(m,6H). 19 F NMR(377MHz,DMSO-d6)δ-53.15,-145.23,-171.95,-172.00.

[0942] Example 6:

[0943] Compound 6-1: 1-(10-(6-amino-4-methyl-3-trifluoromethylpyridin-2-yl)-9-fluoro-7-(2R,7aS)-2-fluorotetrahydro-1H-pyrrolidine-7a(5H)-methoxy)-3,4-dihydro-5H-2a,5,6,8-tetraaza[2,1,8-cde]azulen-5-yl)ethyl)cyclopropane-1-carboxamide

[0944] Step 1: Methyl 1-(1-((2-hydroxyethyl)amino)ethyl)cyclopropane-1-carboxylate

[0945] Dissolve methyl 1-acetylcyclopropane-1-carboxylate (4.2 g, 30 mmol) in dichloromethane (100 mL), add 2-aminoethane-1-ol (2.2 g, 36 mmol) and acetic acid (0.5 mL), and stir at room temperature under nitrogen for 1 h. Then slowly add sodium acetate borohydride (14 g, 66 mmol) and react at room temperature overnight. Filter and wash the filter cake twice with dichloromethane (50 mL x 2). Dry the organic phase over anhydrous sodium sulfate and concentrate under reduced pressure to obtain the crude product as a white solid (10 g, crude product). ESI-MS m / z: 188.1 [M+1] + .

[0946] Step 2: Methyl 1-(1-((benzyloxy)carbonyl)(2-hydroxyethyl)amino)ethyl)cyclopropane-1-carboxylate

[0947] Methyl 1-(1-((2-hydroxyethyl)amino)ethyl)cyclopropane-1-carboxylate (10 g, crude product) was dissolved in dichloromethane (60 mL), and a saturated aqueous solution of sodium bicarbonate (120 mL) was added. In an ice-water bath, benzyl chloride (6.1 g, 36 mmol) was added dropwise. The reaction solution was naturally warmed to room temperature and stirred for 2 hours. Water (200 mL) was added to the reaction solution, and the mixture was extracted with dichloromethane (100 mL x 3). The resulting organic phase was washed with saturated sodium chloride solution (200 mL), dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (petroleum ether / tetrahydrofuran = 3:1, volume ratio) to obtain the product as a colorless viscous liquid (3.2 g, two-step yield 34%). ESI-MS m / z: 322.1 [M+1] + . 1 H NMR (400MHz, DMSO-d6) δ7.37-7.32(m,5H),5.10-5.07(m,2H),4.66-4.52(m,2H),3.52(s,3H),3.43-3.33(m,2H),3.21(brs,2H),1.36-0.93(m,7H).

[0948] Step 3: Methyl 1-(benzyloxy)carbonyl)(2-oxoethyl)amino)ethyl)cyclopropane-1-carboxylate

[0949] Methyl 1-(benzyloxy)carbonyl)(2-hydroxyethyl)amino)ethyl)cyclopropane-1-carboxylate (1 g, 3.12 mmol) was dissolved in dichloromethane (20 mL) and Dess-Martin periodinane (2.6 g, 6.13 mmol) was added. Stirring was continued at room temperature under nitrogen for 2 hours. Saturated aqueous sodium bicarbonate (10 mL) was added and stirring was continued for 30 minutes. The mixture was extracted with dichloromethane (20 mL x 2). The organic phase was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (petroleum ether / tetrahydrofuran = 4:1, volume ratio) to obtain the product as a yellow oil (500 mg, 51% yield). ESI-MS m / z: 320.1 [M+1] + . 1 H NMR (400MHz, CDCl3) δ9.51 (d, J = 14.0Hz, 1H), 7.43-7.29 (m, 5H), 5.15 (s, 2H), 4.30-4.08 (m, 3H), 3.59 (s, 3H), 1.38-1.14 (m, 7H).

[0950] Step 4: Methyl 1-(1-((benzyloxy)carbonyl)(2-(2-(7-(6-(bis(4-methoxybenzyl)amino)-4-methyl-3-trifluoromethylpyridin-2-yl)-5,8-difluoro-2,4-dioxo-1,2,3,4-tetrahydroquinazoline-6-ethyl)amino)ethyl)cyclopropane-1-carboxylate

[0951] 6-(2-aminoethyl)-7-(6-(bis(4-methoxybenzyl)amino)-4-methyl-3-trifluoromethylpyridin-2-yl)-5,8-difluoroquinazoline-2,4(1H,3H)-dione (250 mg, 0.38 mmol) was dissolved in anhydrous methanol (50 mL), and methyl 1-(benzyloxy)carbonyl)(2-oxoethyl)amino)ethyl)cyclopropane-1-carboxylate (244 mg, 0.76 mmol) and tetraisopropyl titanate (434 mg, 1.53 mmol) were added. The mixture was stirred at 80° C. under nitrogen protection for 6 hours. The reaction solution was cooled to room temperature, and then sodium borohydride (48 mg, 0.76 mmol) was added in an ice bath, and the reaction was continued at room temperature for 1 hour. Water (2 mL) was added dropwise to quench the reaction, and a white solid precipitated. The solid was filtered through Celite and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (petroleum ether / tetrahydrofuran = 3:1, volume ratio) to afford the product as a yellow oil (350 mg, crude product). ESI-MS m / z: 958.9 [M+1] + .

[0952] Step 5: Methyl 1-(1-(((benzyloxy)carbonyl)(2-(4-(6-(bis(4-methoxybenzyl)amino)-4-methyl-3-trifluoromethylpyridin-2-yl)-5-fluoro-7,9-dioxo-2,3,6,7,8,9-hexahydropyrrolo[2,3-f]quinazolin-1-yl)ethyl)amino)ethyl)cyclopropane-1-carboxylate

[0953] Methyl 1-(1-(benzyloxy)carbonyl)(2-(2-(7-(6-(bis(4-methoxybenzyl)amino)-4-methyl-3-trifluoromethylpyridin-2-yl)-5,8-difluoro-2,4-dioxo-1,2,3,4-tetrahydroquinazoline-6-ethyl)amino)ethyl)cyclopropane-1-carboxylate (350 mg, 0.36 mmol) was dissolved in dimethyl sulfoxide (20 mL), and diisopropylethylamine (136 mg, 1.46 mmol) was added. The reaction mixture was heated to 100°C and stirred for 4 hours. Water (20 mL) was added for dilution, and the mixture was extracted with ethyl acetate (20 mL x 2). The organic phase was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (petroleum ether / tetrahydrofuran ester = 2:1, volume ratio) to afford the product as a yellow oil (300 mg, 88% yield). ESI-MS m / z:938.9[M+1] + . 1 H NMR(400MHz, CDCl3)δ8.99(s,1H),8.52(s,1H),7.48-7.30(m,5H),7.17-7.04(m,4H),6.8 7(dd,J=8.7,2.1Hz,4H),6.50(d,J=13.4Hz,1H),5.20(s,2H),4.79-4.64(m,4H),4.09(br s,1H),3.85-3.72(m,7H),3.51(s,2H),3.16(br s,2H),2.78(br s,1H),2.44(s,3H),1.94-1.82(m,1H),1.66(br s,4H),1.28(d,J=2.7Hz,3H),1.23-1.19(m,2H),0.92-0.85(m,2H).

[0954] Step 6: Methyl 1-(2-(2-(4-(6-(bis(4-methoxybenzyl)amino)-4-methyl-3-trifluoromethylpyridin-2-yl)-5-fluoro-7,9-dioxo-2,3,6,7,8,9-hexahydro-1H-pyrrolo[2,3-f]quinazoline-1-ethyl)amino)ethyl)cyclopropane-1-carboxylate

[0955] Methyl 1-(1-(((benzyloxy)carbonyl)(2-(4-(6-(bis(4-methoxybenzyl)amino)-4-methyl-3-trifluoromethylpyridin-2-yl)-5-fluoro-7,9-dioxo-2,3,6,7,8,9-hexahydropyrrolo[2,3-f]quinazolin-1-yl)ethyl)amino)ethyl)cyclopropane-1-carboxylate (300 mg, 0.32 mmol) was dissolved in methanol (50 mL), and palladium hydroxide / carbon (150 mg, 1.1 mmol) was added. The atmosphere was replaced with hydrogen three times, and then stirred at room temperature for 2 hours. The reaction solution was filtered through celite, and the filtrate was concentrated under reduced pressure to obtain the product as a yellow oil (200 mg, 78% yield). ESI-MS m / z: 805.1 [M+1] + .

[0956] Step 7: Methyl 1-(3-(6-amino-4-methyl-3-trifluoromethylpyridin-2-yl)-6-chloro-4-fluoro-1,2,9,10-tetrahydro-8H-5,7,8,10a-tetraaza[2,1,8-cde]azulen-8-yl)ethyl)cyclopropane-1-carboxylate

[0957] Methyl 1-(2-(2-(4-(6-(bis(4-methoxybenzyl)amino)-4-methyl-3-trifluoromethylpyridin-2-yl)-5-fluoro-7,9-dioxo-2,3,6,7,8,9-hexahydro-1H-pyrrolo[2,3-f]quinazoline-1-ethyl)amino)ethyl)cyclopropane-1-carboxylate (100 mg, 0.12 mmol) was dissolved in anhydrous acetonitrile (4 mL), and phosphorus oxychloride (380 mg, 2.48 mmol) and diisopropylethylamine (32 mg, 0.24 mmol) were added. Under nitrogen protection, the reaction was stirred at 85°C for 16 hours. After cooling to room temperature, the mixture was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (dichloromethane / methanol = 10:1, volume ratio) to obtain the product as a yellow solid (50 mg, yield 71%). ESI-MS m / z: 563.1 [M+1] + .

[0958] Step 8: 1-(10-(6-amino-4-methyl-3-trifluoromethylpyridin-2-yl)-9-fluoro-7-(2R,7aS)-2-fluorotetrahydro-1H-pyrrolidin-7a(5H)-methoxy)-3,4-dihydro-5H-2a,5,6,8-tetraaza[2,1,8-cde]azulene-5-yl)ethyl)cyclopropane-1-carboxylic acid

[0959] Methyl 1-(3-(6-amino-4-methyl-3-trifluoromethylpyridin-2-yl)-6-chloro-4-fluoro-1,2,9,10-tetrahydro-8H-5,7,8,10a-tetraaza[2,1,8-CDE]azulen-8-yl)ethyl)cyclopropane-1-carboxylate (50 mg, 0.09 mmol) and (2R,7aS)-2-fluorotetrahydro-1H-pyrrolidine-7a(5H)methanol (57 mg, 0.36 mmol) were dissolved in anhydrous tetrahydrofuran (10 mL), and potassium tert-butoxide (100 mg, 8.9 mmol) was added. After stirring at room temperature for 4 hours, water (5 mL) and methanol (5 mL) were added, and the reaction was stirred at 50° C. for 12 hours. Most of the methanol and tetrahydrofuran were then concentrated under reduced pressure, and the mixture was acidified with 1N HCl (5 mL) until pH = 3, and then concentrated under reduced pressure. The residue was diluted with acetonitrile and filtered, and the filtrate was concentrated under reduced pressure to obtain the product as a yellow solid (50 mg, crude product). ESI-MS m / z: 671.9 [M+1] + .

[0960] Step 9: 1-(10-(6-amino-4-methyl-3-trifluoromethylpyridin-2-yl)-9-fluoro-7-(2R,7aS)-2-fluorotetrahydro-1H-pyrrolidin-7a(5H)-methoxy)-3,4-dihydro-5H-2a,5,6,8-tetraaza[2,1,8-cde]azulen-5-yl)ethyl)cyclopropane-1-carboxamide

[0961] 1-(10-(6-amino-4-methyl-3-trifluoromethylpyridin-2-yl)-9-fluoro-7-(2R,7aS)-2-fluorotetrahydro-1H-pyrrolidine-7a(5H)-methoxy)-3,4-dihydro-5H-2a,5,6,8-tetraaza[2,1,8-cde]azulen-5-yl)ethyl)cyclopropane-1-carboxylic acid (50 mg, 0.07 mmol) was dissolved in N,N-dimethylformamide (5 mL). N,N-diisopropylethylamine (38 mg, 0.28 mmol) and HATU (57 mg, 0.14 mmol) were added, and the mixture was stirred at room temperature for 1 hour. The mixture was concentrated under reduced pressure and purified by preparative high-performance liquid chromatography. The product was lyophilized to obtain a white solid (1.2 mg).

[0962] Preparative HPLC separation conditions:

[0963] Pillar: C18 OBD TM 19*250mm*5μM, flow rate 25mL / min.

[0964] Mobile phase: A: water (0.1% ammonia, v / v); B: acetonitrile; Mobile phase B%: 45-55%, 8 min; Detection wavelength: 214 / 254 nm.

[0965] ESI-MS m / z: 670.9[M+1] + . 1 H NMR (400MHz, CDCl3) δ7.05 (s, 1H), 6.48 (s, 1H), 6.27 (d, J = 5.3 Hz,1H),5.56-5.21(m,4H),4.85-4.65(m,2H),4.52-4.35(m,2H),3.60-3.40(m, 4H),3.10-2.95(m,2H),2.61-2.15(m,6H),1.75-1.56(m,3H),1.26-0.86(m,9H). 19 F NMR(377MHz,DMSO-d6)δ-55.26,-139.38,-172.74.

[0966] Example 7:

[0967] Compound 7-1: 6-((R)-1-fluoro-11-((2R,7aS)-2-fluorotetrahydro-1H-pyrrolazin-7a(5H)-yl)methoxy)-5a,6,8,9-tetrahydro-5H-7-oxa-4,4a,9a,10,12-pentaazabenzo[g]naphtho[2,1,8-cde]azulene-2-yl)-4-methyl-5-(trifluoromethyl)pyridin-2-amine

[0968] Step 1: Methyl (E)-2-amino-5-(3-(benzyloxy)-3-oxopropyl-1-en-1-yl)-4-(6-(bis(4-methoxybenzyl)amino)-4-methyl-3-(trifluoromethyl)pyridin-2-yl)-3,6-difluorobenzoic acid

[0969] Methyl 2-amino-4-(6-(bis(4-methoxybenzyl)amino)-4-methyl-3-(trifluoromethyl)pyridin-2-yl)-3,6-difluoro-5-iodobenzoate (19.76 g, 27.16 mmol) was dissolved in N,N-dimethylacetamide (200 mL). Benzyl acrylate (15.42 g, 95.06 mmol), palladium(II) acetate (1.22 g, 5.43 mmol), N,N-diisopropylethylamine (10.51 g, 81.48 mmol), and tri(o-methylphenyl)phosphine (3.31 g, 10.86 mmol) were added. The reaction mixture was purged with nitrogen and reacted at 135°C for 5 hours. Water (600 mL) was added to the reaction mixture, and the mixture was extracted with ethyl acetate (200 mL x 3). The mixture was washed with saturated sodium chloride solution (500 mL), dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (petroleum ether / tetrahydrofuran = 1:1, volume ratio) to give methyl (E)-2-amino-5-(3-(benzyloxy)-3-oxopropyl-1-en-1-yl)-4-(6-(bis(4-methoxybenzyl)amino)-4-methyl-3-(trifluoromethyl)pyridin-2-yl)-3,6-difluorobenzoate (9.0 g, yellow liquid) and methyl (E)-2-amino-5-(3-(benzyloxy)-3-oxopropyl-1-en-1-yl)-4-(6-(bis(4-methoxybenzyl)amino)-4-methyl-3-(trifluoromethyl)pyridin-2-yl)-3,6-difluorobenzoic acid (18.8 g, crude product, brown liquid).

[0970] Methyl (E)-2-amino-5-(3-(benzyloxy)-3-oxopropyl-1-en-1-yl)-4-(6-(bis(4-methoxybenzyl)amino)-4-methyl-3-(trifluoromethyl)pyridin-2-yl)-3,6-difluorobenzoate:

[0971] Characterization data are the same as in Example 1, step 2.

[0972] Methyl (E)-2-amino-5-(3-(benzyloxy)-3-oxopropyl-1-en-1-yl)-4-(6-(bis(4-methoxybenzyl)amino)-4-methyl-3-(trifluoromethyl)pyridin-2-yl)-3,6-difluorobenzoic acid:

[0973] ESI-MS m / z:748.4[M+1] + . 1H NMR (400MHz, DMSO-d6) δ7.40-7.35(m,1H),7.34-7.25(m,5H),7.12(d,J=8.0Hz,4H),7.09(s,1H),6.80(s,4H),6.78( s,2H),6.05(d,J=16.0Hz,1H),5.12(s,2H),4.86(s,2H),4.39(d,J=15.6Hz,2H),3.68(s,6H),2.36(d,J=2.4Hz,3H).

[0974] Step 2: Benzyl 3-(4-amino-2-(6-(bis(4-methoxybenzyl)amino)-4-methyl-3-(trifluoromethyl)pyridin-2-yl)-5-carbamoyl-3,6-difluorophenyl)acrylate

[0975] 2-Amino-5-(3-(benzyloxy)-3-oxoprop-1-en-1-yl)-4-(6-(bis(4-methoxybenzyl)amino)-4-methyl-3-(trifluoromethyl)pyridin-2-yl)-3,6-difluorobenzoic acid (700 mg, 0.936 mmol, crude) was dissolved in N,N-dimethylformamide (5 mL), and N,N-diisopropylethylamine (362 mg, 2.81 mmol), N,N,N′,N′-tetramethyl-O-(7-azabenzotriazol-1-yl)uronium hexafluorophosphate (533 mg, 1.40 mmol) and ammonium chloride (150 mg, 2.81 mmol) were added. The reaction was stirred at 35° C. for 16 hours. Water (50 mL) was added for dilution, and the mixture was extracted with ethyl acetate (50 mL x 2). The organic phase was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (petroleum ether / tetrahydrofuran = 2:1, volume ratio) to obtain the product as a yellow oil (380 mg, yield 54%). ESI-MS m / z: 747.3 [M+1] + .

[0976] Step 3: Benzyl-3-(7-(6-(bis(4-methoxybenzyl)amino)-4-methyl-3-(trifluoromethyl)pyridin-2-yl)-5,8-difluoro-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-yl)acrylate

[0977] Benzyl 3-(4-amino-2-(6-(bis(4-methoxybenzyl)amino)-4-methyl-3-(trifluoromethyl)pyridin-2-yl)-5-carbamoyl-3,6-difluorophenyl)acrylate (380 mg, 0.508 mmol) was dissolved in tetrahydrofuran (10 mL), and triphosgene (60 mg,...

Claims

1. A heterocyclic compound represented by Formula I, a pharmaceutically acceptable salt thereof, a solvate thereof, or a solvate of a pharmaceutically acceptable salt thereof, Among them, n is 1, 2 or 3; X is independently -C(R 7 )2-, -NR 7 -, -O-, -S-, -CR 7 =CR 7 -, -N=N- or -CR 7 =N-; R 7 Independently hydrogen, deuterium, halogen, cyano, hydroxy, amino, C1-C6 alkyl, C1-C6 alkyl-O-, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkyl substituted with one or more R 7a substituents, C1-C6 alkyl-O- substituted with one or more R 7b substituents, C2-C6 alkenyl substituted with one or more R 7c substituents or C2-C6 alkynyl substituted with one or more R 7d substituents; R 7a 、R 7b 、R 7c and R 7d are each independently deuterium, -CN, a halogen, or -OH; Y is -NR 4 -, -O-, -S-, -C(R 4 )2- or -(CH2) p NR 4 -; p is 1, 2 or 3; R 4 independently is hydrogen, C1-C6 alkyl, C3-C 10 cycloalkyl, 3-10 membered heterocycloalkyl, C3-C 10 cycloalkenyl, 3-10 membered heterocycloalkenyl, 5-10 membered heteroaryl, C6-C 10 aryl, -SO2R h , C1-C6 alkyl substituted by one or more R 4a , C3-C 4b cycloalkyl substituted by one or more R 10 , 3-10 membered heterocycloalkyl substituted by one or more R 4c , 3-10 membered heterocycloalkenyl substituted by one or more R 4d , 5-10 membered heteroaryl substituted by one or more R 4e , 5-10 membered heteroaryl fused to 3-10 membered heterocycloalkyl, C3-C 4f cycloalkenyl substituted by one or more R 10 , C6-C 4g aryl substituted by one or more R 10 or 5-10 membered heteroaryl fused to 3-10 membered heterocycloalkyl substituted by one or more R 4k ; the heteroatoms in the 3-10 membered heterocycloalkyl, 3-10 membered heterocycloalkenyl, 5-10 membered heteroaryl, 5-10 membered heteroaryl ring in the 5-10 membered heteroaryl fused to 3-10 membered heterocycloalkyl, 3-10 membered heterocycloalkyl in the 5-10 membered heteroaryl fused to 3-10 membered heterocycloalkyl, 5-10 membered heteroaryl ring in the 5-10 membered heteroaryl fused to 3-10 membered heterocycloalkyl substituted by one or more R 4k , 3-10 membered heterocycloalkyl in the 5-10 membered heteroaryl fused to 3-10 membered heterocycloalkyl substituted by one or more R 4k , 3-10 membered heterocycloalkyl in the 3-10 membered heterocycloalkyl substituted by one or more R 4c , 3-10 membered heterocycloalkyl in the 3-10 membered heterocycloalkenyl substituted by one or more R 4d and 3-10 membered heterocycloalkenyl in the 3-10 membered heterocycloalkenyl substituted by one or more R 4e and 5-10 membered heteroaryl in the 5-10 membered heteroaryl substituted by one or more R are each independently selected from one or more of N, O and S, and the number of heteroatoms is each independently 1, 2 or 3; R 4a , R 4b , R 4c , R 4d , R 4e , R 4f , R 4g , R 4k and R h are independently halogen, =O, cyano, -OR 10 、-N(R 8 )2. -SR 11 、-SO2R 11 、-C(O)N(R 10 )2. -C(O)R 10 、-C(O)OR 10 , C1-C6 alkyl, C3-C 10 cycloalkyl, 3- to 10-membered heteroalkenyl, 5- to 10-membered heteroaryl, 3- to 10-membered heterocycloalkyl, C3-C 10 cycloalkenyl, C6-C 10 aryl, carboxyl, C1-C6 alkyl substituted by one or more R 4-a substituted C1-C6 alkyl, C3-C 4-b substituted cycloalkyl, C3-C 10 substituted cycloalkyl, C3-C 4- c substituted 3- to 10-membered heterocycloalkyl, C3-C 4-d substituted 3- to 10-membered heteroalkenyl, C3-C 4-e substituted 5- to 10-membered heteroaryl, C3-C 4-f substituted cycloalkenyl, C3-C 10 substituted cycloalkenyl or C6-C 4-g substituted aryl; the 3- to 10-membered heterocycloalkyl, 3- to 10-membered heteroalkenyl, 5- to 10-membered heteroaryl, C3-C 10 substituted 3- to 10-membered heterocycloalkyl, the 3- to 10-membered heterocycloalkyl in the 3- to 10-membered heterocycloalkyl substituted by one or more R 4-c substituted 3- to 10-membered heteroalkenyl, the 3- to 10-membered heteroalkenyl in the 3- to 10-membered heteroalkenyl substituted by one or more R 4-d substituted 5- to 10-membered heteroaryl, and the 5- to 10-membered heteroaryl in the 5- to 10-membered heteroaryl substituted by one or more R 4-e The heteroatoms in the 5- to 10-membered heteroaryl are each independently selected from one or more of N, O, and S, and the number of heteroatoms is each independently 1, 2, or 3; R 4-a 、R 4-b 、R 4-c 、R 4-d 、R 4-e 、R 4-f and R 4-g each independently is halogen, =O, cyano, -OR 10 , -N(R 8 )2, -SR 11 , -SO2R 11 , -C(O)N(R 10 )2, -C(O)R 10 , C1-C6 alkyl, C3-C 10 cycloalkyl, 3- to 10-membered heteroalkenyl, 3- to 10-membered heteroalkyl, 5- to 10-membered heteroaryl, C3-C 10 cycloalkenyl, C6-C 10 aryl, C1-C6 alkyl substituted with one or more R 4-a-1 , C3-C 4- a-2 cycloalkyl substituted with one or more R 10 , 3- to 10-membered heteroalkyl substituted with one or more R 4-a-3 , 3- to 10-membered heteroalkenyl substituted with one or more R 4-a-4 , 5- to 10-membered heteroaryl substituted with one or more R 4-a-5 , C3-C 4-a-6 cycloalkenyl substituted with one or more R 10 or C6-C 4-a-7 aryl substituted with one or more R 10 ; the heteroatoms in the 3- to 10-membered heteroalkyl, 3- to 10-membered heteroalkenyl, 5- to 10-membered heteroaryl, and 3- to 10-membered heteroalkyl in the 3- to 10-membered heteroalkyl substituted with one or more R 4-a-3 , the 3- to 10-membered heteroalkenyl in the 3- to 10-membered heteroalkenyl substituted with one or more R 4-a-4 and the 5- to 10-membered heteroaryl in the 5- to 10-membered heteroaryl substituted with one or more R 4-a-5 are each independently selected from one or more of N, O, and S, and the number of heteroatoms is each independently 1, 2, or 3; R 4-i each independently is hydrogen or a C1-C6 alkyl group; R 4-a-1 、R 4-a-2 、R 4-a-3 、R 4-a-4 、R 4-a-5 、R 4-a-6 and R 4-a-7 each independently represents a halogen, =O, cyano, -C(O)CH3, -C(O)NH2, -OH, halo C1-C6 alkyl, -N(R 8 )2, -SCH3, -SO2CH3, C1-C6 alkyl, C3-C 10 cycloalkyl, 3- to 10-membered heterocycloalkyl or 3- to 10-membered heterocycloalkenyl; the heteroatoms in the 3- to 10-membered heterocycloalkyl and 3- to 10-membered heterocycloalkenyl each independently selected from one or more of N, O and S, and the number of heteroatoms is each independently 1, 2 or 3; R 8 independently is hydrogen, -C(O)N(R 10 )2, -C(O)R 10 , C1-C6 alkyl, C3-C 10 cycloalkyl, 3-10 membered heterocycloalkyl, 3-10 membered heterocycloalkenyl, 5-10 membered heteroaryl, C1-C6 alkyl substituted with one or more R 8a , C3-C 8b cycloalkyl substituted with one or more R 10 , 3-10 membered heterocycloalkyl substituted with one or more R 8c , 3-10 membered heterocycloalkenyl substituted with one or more R 8d or 5-10 membered heteroaryl substituted with one or more R 8e ; the 3-10 membered heterocycloalkyl in the 3-10 membered heterocycloalkyl, 3-10 membered heterocycloalkenyl, 5-10 membered heteroaryl, 3-10 membered heterocycloalkyl substituted with one or more R 8c , the 3-10 membered heterocycloalkenyl in the 3-10 membered heterocycloalkenyl substituted with one or more R 8d and the 5-10 membered heteroaryl in the 5-10 membered heteroaryl substituted with one or more R 8e each independently have a heteroatom selected from one or more of N, O and S, and the number of heteroatoms is independently 1, 2 or 3; R 8a 、R 8b 、R 8c 、R 8d and R 8e each independently represents a halogen, a cyano group, -C(O)R 10 , -C(O)N(R 10 )2, -OH, C1-C6 alkoxy, -N(R 10 )2, -SO2N(R 10 )2, -SO2R 10 , C1-C6 alkyl, C3-C 10 cycloalkyl, 3-10 membered heterocycloalkyl, 3-10 membered heterocycloalkenyl, 5-10 membered heteroaryl, C1-C6 alkyl substituted with one or more R 8-a , C3-C 8-b cycloalkyl substituted with one or more R 10 , 3-10 membered heterocycloalkyl substituted with one or more R 8-c , 3-10 membered heterocycloalkenyl substituted with one or more R 8-d or 5-10 membered heteroaryl substituted with one or more R 8-e ; the 3-10 membered heterocycloalkyl, 3-10 membered heterocycloalkenyl, 5-10 membered heteroaryl, substituted with one or more a R 8-c a 3- to 10-membered heterocycloalkyl in a substituted 3- to 10-membered heterocycloalkyl group, the 3- to 10-membered heterocycloalkyl group being substituted with one or more R 8-d a 3- to 10-membered heterocycloalkenyl in a substituted 3- to 10-membered heterocycloalkenyl group, and the 3- to 10-membered heterocycloalkenyl group being substituted with one or more R 8-e the heteroatoms in a 5- to 10-membered heteroaryl in a substituted 5- to 10-membered heteroaryl group are each independently selected from one or more of N, O, and S, and the number of heteroatoms is each independently 1, 2, or 3; R 8-a 、R 8-b 、R 8-c 、R 8-d and R 8-e are each independently a halogen, cyano, -C(O)R 10 , -C(O)N(R 10 )2, -OH, C1-C6 alkoxy-, -N(R 10 )2, -SO2N(R 10 )2, -SO2(R 10 ), C1-C6 alkyl, C3-C 10 cycloalkyl, 3-10 membered heterocycloalkyl, 3-10 membered heterocycloalkenyl, 5-10 membered heteroaryl, C1-C6 alkyl substituted with one or more R 8-a-1 s, C3-C 8-a-2 cycloalkyl substituted with one or more R 10 s, 3-10 membered heterocycloalkyl substituted with one or more R 8-a-3 s, 3-10 membered heterocycloalkenyl substituted with one or more R 8-a-4 s or 5-10 membered heteroaryl substituted with one or more R 8-a-5 s; the heteroatoms in the 3-10 membered heterocycloalkyl, 3-10 membered heterocycloalkenyl, 5-10 membered heteroaryl, 3-10 membered heterocycloalkyl in the 3-10 membered heterocycloalkyl substituted with one or more R 8-a-3 s, 3-10 membered heterocycloalkenyl in the 3-10 membered heterocycloalkenyl substituted with one or more R 8-a-4 s and 5-10 membered heteroaryl in the 5-10 membered heteroaryl substituted with one or more R 8-a-5 s are each independently selected from one or more of N, O and S, and the number of heteroatoms is each independently 1, 2 or 3; R 8-a-1 、R 8-a-2 、R 8-a-3 、R 8-a-4 and R 8-a-5 are each independently halogen, cyano, -C(O)R 10 , -C(O)N(R 10 )2, -OH, -OCH3, -N(R 10 )2, -SO2N(R 10 )2, -SO2R 10 , C1-C6 alkyl or halo-C1-C6 alkyl; R 10 independently hydrogen, C1-C6 alkyl, halo-C1-C6 alkyl, C3-C 10 cycloalkyl or 3-10 membered heterocycloalkyl; R 11 independently -NH2 or C1-C6 alkyl; R 5 and R 6 are each independently hydrogen, halogen, -N(R 8 )2, 3- to 10-membered heterocycloalkyl, C1-C6 alkyl, 3- to 10-membered heterocycloalkenyl, C3-C 10 cycloalkyl, C3-C 10 cycloalkenyl, 5- to 10-membered heteroaryl, C6-C 10 aryl, C1-C6 alkyl substituted with one or more R 5a , 3- to 10-membered heterocycloalkyl substituted with one or more R 5b , 3- to 10-membered heterocycloalkenyl substituted with one or more R 5c , C3-C 5d cycloalkyl substituted with one or more R 10 , C3-C 5e cycloalkenyl substituted with one or more R 10 , 5- to 10-membered heteroaryl substituted with one or more R 5f or C6-C 5g aryl substituted with one or more R 10 ; the heteroatoms in the 3- to 10-membered heterocycloalkyl, 3- to 10-membered heterocycloalkenyl, 5- to 10-membered heteroaryl, and 3- to 10-membered heterocycloalkyl in the 3- to 10-membered heterocycloalkyl substituted with one or more R 5b , 3- to 10-membered heterocycloalkenyl in the 3- to 10-membered heterocycloalkenyl substituted with one or more R 5c and 5- to 10-membered heteroaryl in the 5- to 10-membered heteroaryl substituted with one or more R 5f are each independently selected from one or more of N, O, and S, and the number of heteroatoms is each independently 1, 2, or 3; R 5a 、R 5b 、R 5c 、R 5d 、R 5e 、R 5f and R 5g each independently represents a halogen, =O, cyano, -OH, C1-C6 alkyl - O -, C1-C6 alkyl or halo C1-C6 alkyl; R 4 and R 5 may also together with an atom to which it is attached form a 3- to 10-membered saturated heterocycle, a 5- to 10-membered heteroaromatic ring, a 3- to 10-membered heterocyclene, a 3- to 10-membered saturated heterocycle substituted with one or more R 4h substituents, a 3- to 10-membered heterocyclene substituted with one or more R 4i substituents or a 5- to 10-membered heteroaromatic ring substituted with one or more R 4j substituents; the 3- to 10-membered saturated heterocycle, 3- to 10-membered heterocyclene, 5- to 10-membered heteroaromatic ring, 3- to 10-membered saturated heterocycle substituted with one or more R 4h substituents in the 3- to 10-membered saturated heterocycle, the 3- to 10-membered heterocyclene in the 3- to 10-membered heterocyclene substituted with one or more R 4i substituents and the 5- to 10-membered heteroaromatic ring in the 5- to 10-membered heteroaromatic ring substituted with one or more R 4j substituents, and the heteroatoms in the 3- to 10-membered saturated heterocycle, 3- to 10-membered heterocyclene and 5- to 10-membered heteroaromatic ring are each independently selected from one or more of N, O and S, and the number of heteroatoms is each independently 1, 2 or 3; R 4h , R 4i and R 4j are independently halogen, =O, cyano, -OH, -N(R 8 )2. -SR 11 、-SO2R 11 、-C(O)N(R 10 )2. -C(O)R 10 , C1-C6 alkyl or one or more R 4-h Substituted C1-C6 alkyl; or two adjacent Rs 4h together with the atoms to which they are attached form a 5- to 10-membered heteroaryl ring, said 5- to 10-membered heteroaryl ring being optionally substituted with substituted by one or more of the following groups: halogen, =O, cyano, -OH, -N(R 8 )2, -SR 11 , -SO2R 11 , -C(O)N(R 10 )2, -C(O)R 10 , C1-C6 alkyl or C1-C6 alkyl substituted by one or more R 4-h ; the heteroatoms in the 5-10 membered heteroaryl ring are each independently selected from one or more of N, O and S, and the number of heteroatoms is each independently 1, 2 or 3; R 4-h is independently halogen, =O, cyano or -N(R 8 )2; R 1 is C6-C 10 aryl, 5-10 membered heteroaryl, 3-10 membered heterocycloalkyl, C6-C 1a aryl substituted by one or more R 10 aryl, 5-10 membered heteroaryl substituted by one or more R 1b or 3-10 membered heterocycloalkyl substituted by one or more R 1c ; the 5-10 membered heteroaryl in the 5-10 membered heteroaryl, 3-10 membered heterocycloalkyl, 5-10 membered heteroaryl substituted by one or more R 1b and the 3-10 membered heterocycloalkyl in the 3-10 membered heterocycloalkyl substituted by one or more R 1c each independently have a heteroatom selected from one or more of N, O, and S, and the number of heteroatoms is independently 1, 2, or 3; R 1a 、R 1b and R 1c are each independently deuterium, a halogen, -OH, -CN, a C1-C6 alkyl group, a C2-C6 alkenyl group, a C2-C6 alkynyl group, a 5-10 membered heteroaryl group, a C1-C6 alkyl-O-, a C1-C6 alkyl-S-, -N(R 8 )2, -(CH2)-C(=O)N(R 8 )2, a C3-C 10 cycloalkyl group, a C1-C6 alkyl group substituted with one or more R 1-a s, a C1-C6 alkyl-O- substituted with one or more R 1-b s, a C1-C6 alkyl-S- substituted with one or more R 1-c s, a C2-C6 alkenyl group substituted with one or more R 1-d s, a C2-C6 alkynyl group substituted with one or more R 1-e s, a C3-C 1- f cycloalkyl group substituted with one or more R 10 s or a 5-10 membered heteroaryl group substituted with one or more R 1-g s; the heteroatoms in the 5-10 membered heteroaryl group in the 5-10 membered heteroaryl group and the 5-10 membered heteroaryl group substituted with one or more R 1-g s are each independently selected from one or more of N, O, and S, and the number of heteroatoms is each independently 1, 2, or 3; Or two adjacent R 1c The atoms to which they are attached together form a 5-10 membered heteroaromatic ring, wherein the 5-10 membered heteroaromatic ring is optionally substituted by one or more of the following groups: deuterium, halogen, -OH, -CN, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, 5-10 membered heteroaryl, C1-C6 alkyl-O-, C1-C6 alkyl-S-, -N(R 8 )2, -(CH2)-C(=O)N(R 8 2. C3-C 10 Cycloalkyl, with one or more R 1- a Substituted C1-C6 alkyl, one or more R 1-b Substituted C1-C6 alkyl-O-, substituted by one or more R 1-c Substituted C1-C6 alkyl-S-, substituted by one or more R 1-d Substituted C2-C6 alkenyl, substituted by one or more R 1-e Substituted C2-C6 alkynyl, substituted by one or more R 1-f Substituted C3-C 10 Cycloalkyl or one or more R 1-g substituted 5-10 membered heteroaryl; the 5-10 membered heteroaryl ring, the 5-10 membered heteroaryl and the 1-g The heteroatoms in the 5-10 membered heteroaryl in the substituted 5-10 membered heteroaryl are independently selected from one or more of N, O and S, and the number of heteroatoms is independently 1, 2 or 3; R 1-a 、R 1-b 、R 1-c 、R 1-d 、R 1-e 、R 1-f and R 1-g each independently is deuterium, a halogen, -CN, -OH, a C1-C4 alkyl group, a C1-C4 alkoxy group, or a C3-C 10 cycloalkyl group; L is absent, -O-(CR 9 R 9 ) n1 -, -S-(CR 9 R 9 ) n2 -, -N(R 8 )-(CR 9 R 9 ) n3 -, -SO-(CR 9 R 9 ) n4 - or -SO2-(CR 9 R 9 ) n5 -; R 9 independently hydrogen, halogen, -CN, C1-C6 alkyl, C1-C6 alkoxy, deuterated C1-C6 alkyl or 5-10 membered heteroaryl; n1, n2, n3, n4 and n5 are each independently 0, 1, 2 or 3; (when it is 0, it represents a connecting bond); R 2 is hydrogen, -COOH, C1-C6 alkyl, C1-C6 alkoxy, C3-C 10 cycloalkyl, C3-C 10 cycloalkenyl, 4-10 membered heterocycloalkyl, C6-C 10 aryl, 5-10 membered heteroaryl, -NHC(=NH)NH2, -C(O)N(R 8 )2, -(CH2OR 10 )(CH2) n6 OR 10 , -NR 8 C(=O)-C6-C 10 aryl, -C(=O)O-C1-C6 alkyl, C3-C 2a cycloalkyl substituted by one or more R 10 , C3-C 2b cycloalkenyl substituted by one or more R 10 , 4-10 membered heterocycloalkyl substituted by one or more R 2c , C6-C 2d aryl substituted by one or more R 10 or 5-10 membered heteroaryl substituted by one or more R 2e ; the 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, substituted by one or more R 2c substituted The 4- to 10-membered heterocycloalkyl in the 4- to 10-membered heterocycloalkyl and the 5- to 10-membered heteroaryl in the 5- to 10-membered heteroaryl substituted by one or more Rs 2e The heteroatoms in the 4- to 10-membered heterocycloalkyl and the 5- to 10-membered heteroaryl are each independently selected from one or more of N, O, and S, and the number of heteroatoms is each independently 1, 2, or 3; n6 is 0, 1, 2 or 3; R 2a 、R 2b 、R 2c 、R 2d and R 2e each independently is halogen, -OH, deuterium, -CN, -C(=O)H, =CR 2-c R 2-c , C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 alkyl-O-, -N(R 8 )2, (C l -C4 alkyl)-C(=O)-, oxo group (=O), -SO2F, (C l -C4 alkyl)-SO2-, (C l -C4 alkyl)-O-(C l -C4 alkyl)-, (C l -C4 alkyl)-O-(C l -C4 alkyl)-O-, -CH2OC(=O)N(R 8 )2, (C l -C4 alkyl)-O-C(=O)-NHCH2-, -CH2NHC(=O)N(R 8 )2, (C l -C4 alkyl)-C(=O)NHCH2-, (pyrazolyl)-CH2-, (C l -C4 alkyl)-SO2-NHCH2-, (4-10 membered heterocycloalkyl)-C(=O)-OCH2-, (R 8 )2N-C(=O)-O-, (C l -C4 alkyl)-O-(C l -C4 alkyl)-NH-C(=O)-O-, phenyl-C(=O)NH-, phenyl-(C l -C4 alkyl)-NH-C(=O)-O-, (4-10 membered heterocycloalkyl)-C(=O)-O-, (4-10 membered heterocycloalkyl)-CH2-, 4-10 membered heterocycloalkyl, C1-C4 alkyl substituted by one or more R 2-a , C1-C4 alkyl-O- substituted by one or more R 2-b or 4-10 membered heterocycloalkyl substituted by one or more R 2-d ; said phenyl-C(=O)NH- and phenyl-(C l The phenyl group in -C4 alkyl)-NH-C(=O)-O- is optionally substituted with -C(=O)H, halogen, -CN or -OH; the 4- to 10-membered heterocycloalkyl group in (4-10 membered heterocycloalkyl)-C(=O)-OCH2-, (4-10 membered heterocycloalkyl)-C(=O)-O- and (4-10 membered heterocycloalkyl)-CH2- is optionally substituted with =O, halogen, -CN, -OH or C l -C6 alkyl; the 4- to 10-membered heterocycloalkyl group in the 4- to 10-membered heterocycloalkyl group, the 4- to 10-membered heterocycloalkyl group substituted with one or more R 2-d The heteroatoms in the 4- to 10-membered heterocycloalkyl group in the 4- to 10-membered heterocycloalkyl group substituted with one or more R, the 4- to 10-membered heterocycloalkyl group in (4-10 membered heterocycloalkyl)-C(=O)-OCH2-, (4-10 membered heterocycloalkyl)-C(=O)-O- and (4-10 membered heterocycloalkyl)-CH2- are each independently selected from one or more of N, O and S, and the number of heteroatoms is each independently 1, 2 or 3; R 2-a 、R 2-b 、R 2-c and R 2-d are each independently deuterium, -CN, a halogen, or -OH; R 3 is H, deuterium, -N(R 8 )2, halogen, -OH, C1-C6 alkyl, -CN, halo C1-C6 alkyl, deuterated C1-C6 alkyl, C1-C6 alkoxy, deuterated C1-C6 alkoxy, C2-C6 alkenyl or C2-C6 alkynyl.

2. The heterocyclic compound represented by Formula I as described in Claim 1, its pharmaceutically acceptable salt, its solvate or the solvate of its pharmaceutically acceptable salt, Among them, n is 1, 2 or 3; X is independently -C(R 7 )2-, -NR 7 -, -O-, -S-, -CR 7 =CR 7 -, -N=N- or -CR 7 =N-; R 7 Independently hydrogen, deuterium, halogen, cyano, hydroxy, amino, C1-C6 alkyl, C1-C6 alkyl-O-, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkyl substituted with one or more R 7a substituents, C1-C6 alkyl-O- substituted with one or more R 7b substituents, C2-C6 alkenyl substituted with one or more R 7c substituents or C2-C6 alkynyl substituted with one or more R 7d substituents; R 7a 、R 7b 、R 7c and R 7d each independently is deuterium, -CN, a halogen or -OH; Y is -NR 4 -, -O-, -S-, -C(R 4 )2- or -(CH2) p NR 4 -; p is 1, 2 or 3; R 4 independently is hydrogen, C1-C6 alkyl, C3-C 10 cycloalkyl, 3- to 10-membered heterocycloalkyl, C3-C 10 cycloalkenyl, 3- to 10-membered heterocycloalkenyl, 5- to 10-membered heteroaryl, C6-C 10 aryl, -SO2R h , C1-C6 alkyl substituted by one or more R 4a , C3-C 4b cycloalkyl substituted by one or more R 10 , 3- to 10-membered heterocycloalkyl substituted by one or more R 4c , 3- to 10-membered heterocycloalkenyl substituted by one or more R 4d , 5- to 10-membered heteroaryl substituted by one or more R 4e , 5- to 10-membered heteroaryl fused to 3- to 10-membered heterocycloalkyl, C3-C 4f cycloalkenyl substituted by one or more R 10 , C6-C 4g aryl substituted by one or more R 10 or 5- to 10-membered heteroaryl fused to 3- to 10-membered heterocycloalkyl substituted by one or more R 4k ; the 3- to 10-membered heterocycloalkyl, 3- to 10-membered heterocycloalkenyl, 5- to 10-membered heteroaryl, 5- to 10-membered heteroaryl ring in 5- to 10-membered heteroaryl fused to 3- to 10-membered heterocycloalkyl, 3- to 10-membered heterocycloalkyl in 5- to 10-membered heteroaryl fused to 3- to 10-membered heterocycloalkyl, 5- to 10-membered heteroaryl ring in 5- to 10-membered heteroaryl fused to 3- to 10-membered heterocycloalkyl substituted by one or more R 4k , 3- to 10-membered heterocycloalkyl in 5- to 10-membered heteroaryl fused to 3- to 10-membered heterocycloalkyl substituted by one or more R 4k , 3- to 10-membered heterocycloalkyl in 3- to 10-membered heterocycloalkyl substituted by one or more R 4c , 3- to 10-membered heterocycloalkenyl in 3- to 10-membered heterocycloalkenyl substituted by one or more R 4d and 5- to 10-membered heteroaryl in 5- to 10-membered heteroaryl substituted by one or more R 4e The heteroatoms in the 5- to 10-membered heteroaryl are each independently selected from one or more of N, O, and S, and the number of heteroatoms is each independently 1, 2, or 3; R 4a 、R 4b 、R 4c 、R 4d 、R 4e 、R 4f 、R 4g 、R 4k and R h each independently is halogen, =O, cyano, -OR 10 、-N(R 8 )2、-SR 11 、-SO2R 11 、-C(O)N(R 10 )2、-C(O)R 10 、C1-C6 alkyl, C3-C 10 cycloalkyl, 3- to 10-membered heteroalkenyl, 5- to 10-membered heteroaryl, 3- to 10-membered heterocycloalkyl, C3-C 10 cycloalkenyl, C6-C 10 aryl, carboxyl, C1-C6 alkyl substituted with one or more R 4-a 、C3-C 4-b cycloalkyl substituted with one or more R 10 、3- to 10-membered heterocycloalkyl substituted with one or more R 4-c 、3- to 10-membered heteroalkenyl substituted with one or more R 4- d 、5- to 10-membered heteroaryl substituted with one or more R 4-e 、C3-C 4-f cycloalkenyl substituted with one or more R 10 or C6-C 4-g aryl substituted with one or more R 10 ; the heteroatoms in the 3- to 10-membered heterocycloalkyl, 3- to 10-membered heteroalkenyl, 5- to 10-membered heteroaryl, 3- to 10-membered heterocycloalkyl substituted with one or more R 4-c in the 3- to 10-membered heterocycloalkyl in the 3- to 10-membered heterocycloalkyl substituted with one or more R 4-d in the 3- to 10-membered heteroalkenyl in the 3- to 10-membered heteroalkenyl substituted with one or more R 4-e and the 5- to 10-membered heteroaryl in the 5- to 10-membered heteroaryl substituted with one or more R are each independently selected from one or more of N, O, and S, and the number of heteroatoms is each independently 1, 2, or 3; R 4-a 、R 4-b 、R 4-c 、R 4-d 、R 4-e 、R 4-f and R 4-g each independently is halogen, =O, cyano, -OR 10 , -N(R 8 )2, -SR 11 , -SO2R 11 , -C(O)N(R 10 )2, -C(O)R 10 , C1-C6 alkyl, C3-C 10 cycloalkyl, 3-10 membered heteroalkenyl, 3-10 membered heteroalkyl, 5-10 membered heteroaryl, C3-C 10 cycloalkenyl, C6-C 10 aryl, C1-C6 alkyl substituted with one or more R 4-a-1 , C3-C 4- a-2 cycloalkyl substituted with one or more R 10 , 3-10 membered heteroalkyl substituted with one or more R 4-a-3 , 3-10 membered heteroalkenyl substituted with one or more R 4-a-4 , 5-10 membered heteroaryl substituted with one or more R 4-a-5 , C3-C 4-a-6 cycloalkenyl substituted with one or more R 10 or C6-C 4-a-7 aryl substituted with one or more R 10 ; the heteroatoms in the 3-10 membered heteroalkyl, 3-10 membered heteroalkenyl, 5-10 membered heteroaryl, 3-10 membered heteroalkyl in the 3-10 membered heteroalkyl substituted with one or more R 4-a-3 , 3-10 membered heteroalkenyl in the 3-10 membered heteroalkenyl substituted with one or more R 4-a-4 and 5-10 membered heteroaryl in the 5-10 membered heteroaryl substituted with one or more R 4-a-5 are each independently selected from one or more of N, O, and S, and the number of heteroatoms is each independently 1, 2, or 3; R 4-a-1 、R 4-a-2 、R 4-a-3 、R 4-a-4 、R 4-a-5 、R 4-a-6 and R 4-a-7 each independently is halogen, =O, cyano, -C(O)CH3, -C(O)NH2, -OH, halo C1-C6 alkyl, -N(R 8 )2, -SCH3, -SO2CH3, C1-C6 alkyl, C3-C 10 cycloalkyl, 3-10 membered hetero cycloalkyl or 3-10 membered heteroalkenyl; the heteroatoms in the 3-10 membered heteroalkyl and 3-10 membered heteroalkenyl are each independently selected from one or more of N, O and S, and the number of heteroatoms is each independently 1, 2 or 3; R 8 independently is hydrogen, -C(O)N(R 10 )2, -C(O)R 10 , C1-C6 alkyl, C3-C 10 cycloalkyl, 3-10 membered heterocycloalkyl, 3-10 membered heterocycloalkenyl, 5-10 membered heteroaryl, C1-C6 alkyl substituted with one or more R 8a , C3-C 8b cycloalkyl substituted with one or more R 10 , 3-10 membered heterocycloalkyl substituted with one or more R 8c , 3-10 membered heterocycloalkenyl substituted with one or more R 8d or 5-10 membered heteroaryl substituted with one or more R 8e ; the 3-10 membered heterocycloalkyl, 3-10 membered heterocycloalkenyl, 5-10 membered heteroaryl, and the 3-10 membered heterocycloalkyl in the 3-10 membered heterocycloalkyl substituted with one or more R 8c , the 3-10 membered heterocycloalkenyl in the 3-10 membered heterocycloalkenyl substituted with one or more R 8d and the 5-10 membered heteroaryl in the 5-10 membered heteroaryl substituted with one or more R 8e each independently have heteroatoms selected from one or more of N, O, and S, and the number of heteroatoms is independently 1, 2, or 3; R 8a 、R 8b 、R 8c 、R 8d and R 8e each independently is halogen, cyano, -C(O)R 10 , -C(O)N(R 10 )2, -OH, C1-C6 alkyl-O-, -N(R 10 )2, -SO2N(R 10 )2, -SO2R 10 , C1-C6 alkyl, C3-C 10 cycloalkyl, 3- to 10-membered heterocycloalkyl, 3- to 10-membered heterocycloalkenyl, 5- to 10-membered heteroaryl, C1-C6 alkyl substituted with one or more R 8-a , C3-C 8-b cycloalkyl substituted with one or more R 10 , 3- to 10-membered heterocycloalkyl substituted with one or more R 8-c , 3- to 10-membered heterocycloalkenyl substituted with one or more R 8-d or 5- to 10-membered heteroaryl substituted with one or more R 8-e ; the heteroatoms in the 3- to 10-membered heterocycloalkyl, 3- to 10-membered heterocycloalkenyl, 5- to 10-membered heteroaryl, 3- to 10-membered heterocycloalkyl substituted with one or more R 8-c in the 3- to 10-membered heterocycloalkyl substituted with one or more R 8-d , the 3- to 10-membered heterocycloalkenyl in the 3- to 10-membered heterocycloalkenyl substituted with one or more R 8-e and the 5- to 10-membered heteroaryl in the 5- to 10-membered heteroaryl substituted with one or more R are each independently selected from one or more of N, O and S, and the number of heteroatoms is each independently 1, 2 or 3; R 8-a 、R 8-b 、R 8-c 、R 8-d and R 8-e are each independently a halogen, a cyano group, -C(O)R 10 , -C(O)N(R 10 )2, -OH, C1-C6 alkoxy-, -N(R 10 )2, -SO2N(R 10 )2, -SO2(R 10 ), C1-C6 alkyl, C3-C 10 cycloalkyl, 3-10 membered heteroalkyl, 3-10 membered heteroalkenyl, 5-10 membered heteroaryl, C1-C6 alkyl substituted with one or more R 8-a-1 s, C3-C 8-a-2 cycloalkyl substituted with one or more R 10 s, 3-10 membered heteroalkyl substituted with one or more R 8-a-3 s, 3-10 membered heteroalkenyl substituted with one or more R 8-a-4 s or 5-10 membered heteroaryl substituted with one or more R 8-a-5 s; the heteroatoms in the 3-10 membered heteroalkyl, 3-10 membered heteroalkenyl, 5-10 membered heteroaryl, 3-10 membered heteroalkyl substituted with one or more R 8-a-3 s in the 3-10 membered heteroalkyl substituted with one or more R 8-a-4 s, the 3-10 membered heteroalkenyl in the 3-10 membered heteroalkenyl substituted with one or more R 8-a-5 s and the 5-10 membered heteroaryl in the 5-10 membered heteroaryl substituted with one or more R s are each independently selected from one or more of N, O, and S, and the number of heteroatoms is each independently 1, 2, or 3; R 8-a-1 、R 8-a-2 、R 8-a-3 、R 8-a-4 and R 8-a-5 each independently represents a halogen, a cyano group, -C(O)R 10 , -C(O)N(R 10 )2, -OH, -OCH3, -N(R 10 )2, -SO2N(R 10 )2, -SO2R 10 , a C1-C6 alkyl group or a halogenated C1-C6 alkyl group; R 10 independently hydrogen, C1-C6 alkyl, halo-C1-C6 alkyl, C3-C 10 cycloalkyl or 3-10 membered heterocycloalkyl; R 11 independently -NH2 or C1-C6 alkyl; R 5 and R 6 each independently is hydrogen, halogen, -N(R 8 )2, 3- to 10-membered heterocycloalkyl, C1-C6 alkyl, 3- to 10-membered heterocycloalkenyl, C3-C 10 cycloalkyl, C3-C 10 cycloalkenyl, 5- to 10-membered heteroaryl, C6-C 10 aryl, C1-C6 alkyl substituted with one or more R 5a , 3- to 10-membered heterocycloalkyl substituted with one or more R 5b , 3- to 10-membered heterocycloalkenyl substituted with one or more R 5c , C3-C 5d cycloalkyl substituted with one or more R 10 , C3-C 5e cycloalkenyl substituted with one or more R 10 , 5- to 10-membered heteroaryl substituted with one or more R 5f or C6-C 5g aryl substituted with one or more R 10 ; the 3- to 10-membered heterocycloalkyl, 3- to 10-membered heterocycloalkenyl, 5- to 10-membered heteroaryl, substituted by one or more Rs 5b a 3- to 10-membered heterocycloalkyl in a 3- to 10-membered heterocycloalkyl substituted by one or more Rs, a 3- to 10-membered heteroalkenyl in a 3- to 10-membered heteroalkenyl substituted by one or more Rs 5c and a 5- to 10-membered heteroaryl in a 5- to 10-membered heteroaryl substituted by one or more Rs, wherein the heteroatoms are each independently selected from one or more of N, O, and S, and the number of heteroatoms is each independently 1, 2, or 3; 5f ​ R 5a 、R 5b 、R 5c 、R 5d 、R 5e 、R 5f and R 5g each independently represents a halogen, =O, cyano, -OH, C1-C6 alkoxy, C1-C6 alkyl or halo C1-C6 alkyl; R 4 and R 5 may also together with the atoms to which it is attached form a 3- to 10-membered saturated heterocycle, a 5- to 10-membered heteroaromatic ring, a 3- to 10-membered heterocyclene, a 3- to 10-membered saturated heterocycle substituted by one or more R 4h a 3- to 10-membered heterocyclene substituted by one or more R 4i or a 5- to 10-membered heteroaromatic ring substituted by one or more R 4j ; the heteroatoms in the 3- to 10-membered saturated heterocycle, the 3- to 10-membered heterocyclene, the 5- to 10-membered heteroaromatic ring, and the 3- to 10-membered saturated heterocycle substituted by one or more R 4h in the 3- to 10-membered saturated heterocycle, the 3- to 10-membered heterocyclene in the 3- to 10-membered heterocyclene substituted by one or more R 4i and the 5- to 10-membered heteroaromatic ring in the 5- to 10-membered heteroaromatic ring substituted by one or more R 4j are each independently selected from one or more of N, O, and S, and the number of heteroatoms is each independently 1, 2, or 3; R 4h , R 4i and R 4j are independently halogen, =O, cyano, -OH, -N(R 8 )2. -SR 11 、-SO2R 11 、-C(O)N(R 10 )2. -C(O)R 10 , C1-C6 alkyl or one or more R 4-h Substituted C1-C6 alkyl; or two adjacent Rs 4h together with the atoms to which they are attached form a 5- to 10-membered heteroaryl ring, said 5- to 10-membered heteroaryl ring being optionally substituted by one or more of the following groups: halogen, =O, cyano, -OH, -N(R 8 )2, -SR 11 , -SO2R 11 , -C(O)N(R 10 )2, -C(O)R 10 , C1-C6 alkyl or C1-C6 alkyl substituted by one or more Rs 4-h ; the heteroatoms in said 5- to 10-membered heteroaryl ring are each independently selected from one or more of N, O and S, and the number of heteroatoms is each independently 1, 2 or 3; R 4-h is independently halogen, =O, cyano or -N(R 8 )2; R 1 is C6-C 10 aryl, 5-10 membered heteroaryl, 3-10 membered heterocycloalkyl, C6-C 1a aryl substituted with one or more R 10 aryl, 5-10 membered heteroaryl substituted with one or more R 1b or 3-10 membered heterocycloalkyl substituted with one or more R 1c ; the heteroatoms in the 5-10 membered heteroaryl, 3-10 membered heterocycloalkyl, 5-10 membered heteroaryl substituted with one or more R 1b in the 5-10 membered heteroaryl and 3-10 membered heterocycloalkyl substituted with one or more R 1c in the 3-10 membered heterocycloalkyl are each independently selected from one or more of N, O, and S, and the number of heteroatoms is each independently 1, 2, or 3; R 1a 、 R 1b and R 1c are each independently deuterium, a halogen, -OH, -CN, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, 5-10 membered heteroaryl, C1-C6 alkyl-O-, C1-C6 alkyl-S-, -N(R 8 )2, -(CH2)-C(=O)N(R 8 )2, C3-C 10 cycloalkyl, C1-C6 alkyl substituted with one or more R 1-a , C1-C6 alkyl-O- substituted with one or more R 1-b , C1-C6 alkyl-S- substituted with one or more R 1-c , C2-C6 alkenyl substituted with one or more R 1-d , C2-C6 alkynyl substituted with one or more R 1-e , C3-C 1- f cycloalkyl substituted with one or more R 10 or 5-10 membered heteroaryl substituted with one or more R 1-g ; the heteroatoms in the 5-10 membered heteroaryl of the 5-10 membered heteroaryl and the 5-10 membered heteroaryl substituted with one or more R 1-g are each independently selected from one or more of N, O, and S, and the number of heteroatoms is each independently 1, 2, or 3; or two adjacent Rs 1c and the atoms connected to them together form a 5-10 membered heteroaryl ring, said 5-10 membered heteroaryl ring being optionally substituted by one or more of the following groups: deuterium, halogen, -OH, -CN, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, 5-10 membered heteroaryl, C1-C6 alkyl-O-, C1-C6 alkyl-S-, -N(R 8 )2, -(CH2)-C(=O)N(R 8 )2, C3-C 10 cycloalkyl, C1-C6 alkyl substituted by one or more Rs 1- a , C1-C6 alkyl-O- substituted by one or more Rs 1-b , C1-C6 alkyl- substituted by one or more Rs 1-c ​ S-, by one or more R 1-d Substituted C2-C6 alkenyl, substituted by one or more R 1-e Substituted C2-C6 alkynyl, substituted by one or more R 1-f Substituted C3-C 10 Cycloalkyl or one or more R 1-g substituted 5-10 membered heteroaryl; the 5-10 membered heteroaryl ring, the 5-10 membered heteroaryl and the 1-g The heteroatoms in the 5-10 membered heteroaryl in the substituted 5-10 membered heteroaryl are independently selected from one or more of N, O and S, and the number of heteroatoms is independently 1, 2 or 3; R 1-a 、R 1-b 、R 1-c 、R 1-d 、R 1-e 、R 1-f and R 1-g each independently is deuterium, a halogen, -CN, -OH, a C1-C4 alkyl group, a C1-C4 alkoxy group, or a C3-C 10 cycloalkyl group; L is absent, -O-(CR 9 R 9 ) n1 -, -S-(CR 9 R 9 ) n2 -, -N(R 8 )-(CR 9 R 9 ) n3 -, -SO-(CR 9 R 9 ) n4 - or -SO2-(CR 9 R 9 ) n5 -; R 9 independently hydrogen, halogen, -CN, C1-C6 alkyl, C1-C6 alkoxy, deuterated C1-C6 alkyl or 5-10 membered heteroaryl; n1, n2, n3, n4 and n5 are each independently 0, 1, 2 or 3; (when it is 0, it represents a connecting bond); R 2 is hydrogen, -COOH, C1-C6 alkyl, C1-C6 alkoxy, C3-C 10 cycloalkyl, C3-C 10 cycloalkenyl, 4-10 membered heterocycloalkyl, C6-C 10 aryl, 5-10 membered heteroaryl, -NHC(=NH)NH2, -C(O)N(R 8 )2, -(CH2OR 10 )(CH2) n6 OR 10 , -NR 8 C(=O)-C6-C 10 aryl, -C(=O)O-C1-C6 alkyl, C3-C 2a cycloalkyl substituted by one or more R 10 , C3-C 2b cycloalkenyl substituted by one or more R 10 , 4-10 membered heterocycloalkyl substituted by one or more R 2c , C6-C 2d aryl substituted by one or more R 10 or 5-10 membered heteroaryl substituted by one or more R 2e ; the 4-10 membered heterocycloalkyl in the 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl substituted by one or more R 2c and the 5-10 membered heteroaryl in the 5-10 membered heteroaryl substituted by one or more R 2e each independently have a heteroatom selected from one or more of N, O, and S, and the number of heteroatoms is independently 1, 2, or 3; n6 is 0, 1, 2 or 3; R 2a 、R 2b 、R 2c 、R 2d and R 2e are each independently halogen, -OH, deuterium, -CN, -C(=O)H, =CR 2-c R 2-c , C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 alkyl-O-, -N(R 8 )2, (C l -C4 alkyl)-C(=O)-, oxo group (=O), -SO2F, (C l -C4 alkyl)-SO2-, (C l -C4 alkyl)-O-(C l -C4 alkyl)-, (C l -C4 alkyl)-O-(C l -C4 alkyl)-O-, -CH2OC(=O)N(R 8 )2, (C l -C4 alkyl)-O-C(=O)-NHCH2-, -CH2NHC(=O)N(R 8 )2, (C l -C4 alkyl)-C(=O)NHCH2-, (pyrazolyl)-CH2-, (C l -C4 alkyl)-SO2-NHCH2-, (4-10 membered heterocycloalkyl)-C(=O)-OCH2-, (R 8 )2N-C(=O)-O-, (C l -C4 alkyl)-O-(C l -C4 alkyl)-NH-C(=O)-O-, phenyl-C(=O)NH-, phenyl-(C l -C4 alkyl)-NH-C(=O)-O-, (4-10 membered heterocycloalkyl)-C(=O)-O-, (4-10 membered heterocycloalkyl)-CH2-, 4-10 membered heterocycloalkyl, C1-C4 alkyl substituted with one or more R 2-a , C1-C4 alkyl-O- substituted with one or more R 2-b or 4-10 membered heterocycloalkyl substituted with one or more R 2-d ; said phenyl-C(=O)NH- and phenyl-(C l The phenyl in -C4 alkyl)-NH-C(=O)-O- is optionally substituted by -C(=O)H, halogen, -CN or -OH; the 4- to 10-membered heterocycloalkyl in (4-10 membered heterocycloalkyl)-C(=O)-OCH2-, (4-10 membered heterocycloalkyl)-C(=O)-O- and (4-10 membered heterocycloalkyl)-CH2- is optionally substituted by =O, halogen, -CN, -OH or C l -C6 alkyl; the 4- to 10-membered heterocycloalkyl in the 4- to 10-membered heterocycloalkyl, the 4- to 10-membered heterocycloalkyl substituted by one or more R 2-d substituted 4- to 10-membered heterocycloalkyl, the heteroatoms in the 4- to 10-membered heterocycloalkyl in (4-10 membered heterocycloalkyl)-C(=O)-OCH2-, (4-10 membered heterocycloalkyl)-C(=O)-O- and (4-10 membered heterocycloalkyl)-CH2- are each independently selected from one or more of N, O and S, and the number of heteroatoms is each independently 1, 2 or 3; R 2-a 、R 2-b 、R 2-c and R 2-d are each independently deuterium, -CN, a halogen or -OH; R 3 is H, deuterium, -N(R 8 )2, halogen, -OH, C1-C6 alkyl, -CN, halogenated C1-C6 alkyl, deuterated C1-C6 alkyl, C1-C6 alkoxy, deuterated C1-C6 alkoxy, C2-C6 alkenyl or C2-C6 alkynyl.

3. The heterocyclic compound represented by formula I according to claim 1 or 2, its pharmaceutically acceptable salt, its solvate or its pharmaceutically acceptable salt solvate, Among them, n is 1, 2 or 3; X is independently -C(R 7 )2-, -NR 7 -, -O-, -S-, -CR 7 =CR 7 -, -N=N- or -CR 7 =N-; R 7 independently hydrogen, deuterium, halogen, cyano, hydroxy, amino, C1-C6 alkyl, C1-C6 alkoxy, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkyl substituted with one or more R 7a groups, C1-C6 alkoxy substituted with one or more R 7b groups, C2-C6 alkenyl substituted with one or more R 7c groups or C2-C6 alkynyl substituted with one or more R 7d groups; R 7a 、R 7b 、R 7c and R 7d are each independently deuterium, -CN, a halogen or -OH; Y is -NR 4 -, -O-, -S-, -C(R 4 )2- or -(CH2) p NR 4 -; p is 1, 2 or 3; R 4 independently is hydrogen, C1-C6 alkyl, C3-C 10 cycloalkyl, 3-10 membered heteroalkyl, C3-C 10 cycloalkenyl, 3-10 membered heteroalkenyl, 5-10 membered heteroaryl, C6-C 10 aryl, -SO2R h , C1-C6 alkyl substituted by one or more R 4a , C3-C 4b cycloalkyl substituted by one or more R 10 , 3-10 membered heteroalkyl substituted by one or more R 4c , 3-10 membered heteroalkenyl substituted by one or more R 4d , 5-10 membered heteroaryl substituted by one or more R 4e , C3-C 4f cycloalkenyl substituted by one or more R 10 or C6-C 4g aryl substituted by one or more R 10 ; the heteroatoms in the 3-10 membered heteroalkyl, 3-10 membered heteroalkenyl, 5-10 membered heteroaryl, and 3-10 membered heteroalkyl in the 3-10 membered heteroalkyl substituted by one or more R 4c , 3-10 membered heteroalkenyl in the 3-10 membered heteroalkenyl substituted by one or more R 4d and 5-10 membered heteroaryl in the 5-10 membered heteroaryl substituted by one or more R 4e are each independently selected from one or more of N, O, and S, and the number of heteroatoms is each independently 1, 2, or 3; R 4a 、R 4b 、R 4c 、R 4d 、R 4e 、R 4f 、R 4g and R h each independently is halogen, =O, cyano, -OR 10 , -N(R 8 )2, -SR 11 , -SO2R 11 , -C(O)N(R 10 )2, -C(O)R 10 , C1-C6 alkyl, C3-C 10 cycloalkyl, 3-10 membered heteroalkenyl, 5-10 membered heteroaryl, 3-10 membered heteroalkyl, C3-C 10 cycloalkenyl, C6-C 10 aryl, C1-C6 alkyl substituted with one or more R 4-a , C3-C 4- b cycloalkyl substituted with one or more R 10 , 3-10 membered heteroalkyl substituted with one or more R 4-c , 3-10 membered heteroalkenyl substituted with one or more R 4-d , 5-10 membered heteroaryl substituted with one or more R 4-e , C3-C 4-f cycloalkenyl substituted with one or more R 10 or C6-C 4-g aryl substituted with one or more R 10 ; the heteroatoms in the 3-10 membered heteroalkyl, 3-10 membered heteroalkenyl, 5-10 membered heteroaryl, 3-10 membered heteroalkyl substituted with one or more R 4-c , the 3-10 membered heteroalkyl in the 3-10 membered heteroalkyl substituted with one or more R 4-d , the 3-10 membered heteroalkenyl in the 3-10 membered heteroalkenyl substituted with one or more R 4-e and the 5-10 membered heteroaryl in the 5-10 membered heteroaryl substituted with one or more R are each independently selected from one or more of N, O and S, and the number of heteroatoms is each independently 1, 2 or 3; R 4-a 、R 4-b 、R 4-c 、R 4-d 、R 4-e 、R 4-f and R 4-g each independently represents a halogen, =O, cyano, -OR 10 , -N(R 8 )2, -SR 11 , -SO2R 11 , -C(O)N(R 10 )2, -C(O)R 10 , C1-C6 alkyl, C3-C 10 cycloalkyl, 3-10 membered heteroalkenyl, 3-10 membered heteroalkyl, 5-10 membered heteroaryl, C3-C 10 cycloalkenyl, C6-C 10 aryl, C1-C6 alkyl substituted with one or more R 4-a-1 , C3-C 4- a-2 cycloalkyl substituted with one or more R 10 , 3-10 membered heteroalkyl substituted with one or more R 4-a-3 , 3-10 membered heteroalkenyl substituted with one or more R 4-a-4 , 5-10 membered heteroaryl substituted with one or more R 4-a-5 , C3-C 4-a-6 cycloalkenyl substituted with one or more R 10 or C6-C 4-a-7 aryl substituted with one or more R 10 ; the 3-10 membered heteroalkyl in the 3-10 membered heteroalkyl, 3-10 membered heteroalkenyl, 5-10 membered heteroaryl, 3-10 membered heteroalkyl substituted with one or more R 4-a-3 , the 3-10 membered heteroalkyl in the 3-10 membered heteroalkyl substituted with one or more R 4-a-4 substituted 3-10 membered 3- to 10-membered heterocyclenyl in heterocyclenyl and 5- to 10-membered heteroaryl in 5- to 10-membered heteroaryl substituted by one or more R 4-a-5 The heteroatoms in the 5- to 10-membered heteroaryl in 5- to 10-membered heteroaryl substituted by one or more R are each independently selected from one or more of N, O, and S, and the number of heteroatoms is each independently 1, 2, or 3; R 4-a-1 、R 4-a-2 、R 4-a-3 、R 4-a-4 、R 4-a-5 、R 4-a-6 and R 4-a-7 each independently represents a halogen, =O, cyano, -C(O)CH3, -C(O)NH2, -OH, halo C1-C6 alkyl, -N(R 8 )2, -SCH3, -SO2CH3, C1-C6 alkyl, C3-C 10 cycloalkyl, 3- to 10-membered heterocycloalkyl or 3- to 10-membered heterocycloalkenyl; the heteroatoms in the 3- to 10-membered heterocycloalkyl and 3- to 10-membered heterocycloalkenyl each independently selected from one or more of N, O and S, and the number of heteroatoms is independently 1, 2 or 3; R 8 independently is hydrogen, -C(O)N(R 10 )2, -C(O)R 10 , C1-C6 alkyl, C3-C 10 cycloalkyl, 3-10 membered heterocycloalkyl, 3-10 membered heterocycloalkenyl, 5-10 membered heteroaryl, C1-C6 alkyl substituted with one or more R 8a , C3-C 8b cycloalkyl substituted with one or more R 10 , 3-10 membered heterocycloalkyl substituted with one or more R 8c , 3-10 membered heterocycloalkenyl substituted with one or more R 8d or 5-10 membered heteroaryl substituted with one or more R 8e ; the 3-10 membered heterocycloalkyl in the 3-10 membered heterocycloalkyl, 3-10 membered heterocycloalkenyl, 5-10 membered heteroaryl, 3-10 membered heterocycloalkyl substituted with one or more R 8c , the 3-10 membered heterocycloalkenyl in the 3-10 membered heterocycloalkenyl substituted with one or more R 8d and the 5-10 membered heteroaryl in the 5-10 membered heteroaryl substituted with one or more R 8e each independently select one or more of N, O and S, and the number of heteroatoms is independently 1, 2 or 3; R 8a 、R 8b 、R 8c 、R 8d and R 8e are each independently halogen, cyano, -C(O)R 10 , -C(O)N(R 10 )2, -OH, C1-C6 alkyl-O-, -N(R 10 )2, -SO2N(R 10 )2, -SO2R 10 , C1-C6 alkyl, C3-C 10 cycloalkyl, 3- to 10-membered heterocycloalkyl, 3- to 10-membered heterocycloalkenyl, 5- to 10-membered heteroaryl, C1-C6 alkyl substituted with one or more R 8-a , C3-C 8-b cycloalkyl substituted with one or more R 10 , 3- to 10-membered heterocycloalkyl substituted with one or more R 8-c , 3- to 10-membered heterocycloalkenyl substituted with one or more R 8-d or 5- to 10-membered heteroaryl substituted with one or more R 8-e ; the heteroatoms in the 3- to 10-membered heterocycloalkyl, 3- to 10-membered heterocycloalkenyl, 5- to 10-membered heteroaryl, 3- to 10-membered heterocycloalkyl substituted with one or more R 8-c in the 3- to 10-membered heterocycloalkyl substituted with one or more R 8-d in the 3- to 10-membered heterocycloalkenyl substituted with one or more R 8-e and the 5- to 10-membered heteroaryl in the 5- to 10-membered heteroaryl substituted with one or more R are each independently selected from one or more of N, O, and S, and the number of heteroatoms is each independently 1, 2, or 3; R 8-a 、R 8-b 、R 8-c 、R 8-d and R 8-e are each independently halogen, cyano, -C(O)R 10 , -C(O)N(R 10 )2, -OH, C1-C6 alkyl-O-, -N(R 10 )2, -SO2N(R 10 )2, -SO2(R 10 ), C1-C6 alkyl, C3-C 10 cycloalkyl, 3-10 membered heterocycloalkyl, 3-10 membered heterocycloalkenyl, 5-10 membered heteroaryl, C1-C6 alkyl substituted with one or more R 8-a-1 s, C3-C 8-a-2 cycloalkyl substituted with one or more R 10 s, 3-10 membered heterocycloalkyl substituted with one or more R 8-a-3 s, 3-10 membered heterocycloalkenyl substituted with one or more R 8-a-4 s or 5-10 membered heteroaryl substituted with one or more R 8-a-5 s; the heteroatoms in the 3-10 membered heterocycloalkyl, 3-10 membered heterocycloalkenyl, 5-10 membered heteroaryl, 3-10 membered heterocycloalkyl substituted with one or more R 8-a-3 s in the 3-10 membered heterocycloalkyl substituted with one or more R 8-a-4 s, the 3-10 membered heterocycloalkenyl in the 3-10 membered heterocycloalkenyl substituted with one or more R 8-a-5 s and the 5-10 membered heteroaryl in the 5-10 membered heteroaryl substituted with one or more R s are each independently selected from one or more of N, O and S, and the number of heteroatoms is each independently 1, 2 or 3; R 8-a-1 、R 8-a-2 、R 8-a-3 、R 8-a-4 and R 8-a-5 each independently is halogen, cyano, -C(O)R 10 , -C(O)N(R 10 )2, -OH, -OCH3, -N(R 10 )2, -SO2N(R 10 )2, -SO2R 10 , C1-C6 alkyl or halo-C1-C6 alkyl; R 10 independently hydrogen, C1-C6 alkyl, halo-C1-C6 alkyl, C3-C 10 cycloalkyl or 3-10 membered heterocycloalkyl; R 11 independently -NH2 or C1-C6 alkyl; R 5 and R 6 each independently is hydrogen, halogen, -N(R 8 )2, 3- to 10-membered heterocycloalkyl, C1-C6 alkyl, 3- to 10-membered heterocycloalkenyl, C3- C 10 cycloalkyl, C3-C 10 cycloalkenyl, 5- to 10-membered heteroaryl, C6-C 10 aryl, C1-C6 alkyl substituted with one or more R 5a substituted, 3- to 10-membered heterocycloalkyl substituted with one or more R 5b substituted, 3- to 10-membered heterocycloalkenyl substituted with one or more R 5c substituted, C3-C cycloalkyl substituted with one or more R 5d substituted, C3-C 10 cycloalkyl, C3-C cycloalkenyl substituted with one or more R 5e substituted, C3-C 10 cycloalkenyl, 5- to 10-membered heteroaryl substituted with one or more R 5f substituted or C6-C aryl substituted with one or more R 5g substituted, C6-C 10 aryl; the 3- to 10-membered heterocycloalkyl, 3- to 10-membered heterocycloalkenyl, 5- to 10-membered heteroaryl, 3- to 10-membered heterocycloalkyl in the 3- to 10-membered heterocycloalkyl substituted with one or more R 5b substituted, 3- to 10-membered heterocycloalkenyl in the 3- to 10-membered heterocycloalkenyl substituted with one or more R 5c substituted, and 5- to 10-membered heteroaryl in the 5- to 10-membered heteroaryl substituted with one or more R 5f wherein the heteroatoms in the 5- to 10-membered heteroaryl are each independently selected from one or more of N, O, and S, and the number of heteroatoms is each independently 1, 2, or 3; R 5a 、R 5b 、R 5c 、R 5d 、R 5e 、R 5f and R 5g each independently is halogen, =O, cyano, -OH, C1-C6 alkyl -O-, C1-C6 alkyl or halo C1-C6 alkyl; R 4 and R 5 may also together with the atoms to which it is attached form a 3- to 10-membered saturated heterocycle, a 5- to 10-membered heteroaromatic ring, a 3- to 10-membered heterocyclene, a 3- to 10-membered saturated heterocycle substituted with one or more R 4h a 3- to 10-membered saturated heterocycle substituted with one or more R 4i a 3- to 10-membered heterocyclene substituted with one or more R 4j or a 5- to 10-membered heteroaromatic ring substituted with one or more R 4h the 3- to 10-membered saturated heterocycle in the 3- to 10-membered saturated heterocycle, the 3- to 10-membered heterocyclene in the 3- to 10-membered heterocyclene substituted with one or more R 4i and the 5- to 10-membered heteroaromatic ring in the 5- to 10-membered heteroaromatic ring substituted with one or more R 4j the heteroatoms in the 5- to 10-membered heteroaromatic ring are each independently selected from one or more of N, O and S, and the number of heteroatoms is each independently 1, 2 or 3; R 4h , R 4i and R 4j are independently halogen, =O, cyano, -OH, -N(R 8 )2. -SR 11 、-SO2R 11 、-C(O)N(R 10 )2. -C(O)R 10 , C1-C6 alkyl or one or more R 4-h Substituted C1-C6 alkyl; or two adjacent Rs 4h together with the atoms to which they are attached form a 5- to 10-membered heteroaromatic ring, which 5- to 10-membered heteroaromatic ring is optionally substituted by one or more of the following groups: halogen, ═O, cyano, -OH, -N(R 8 )2, -SR 11 , -SO2R 11 , -C(O)N(R 10 )2, -C(O)R 10 , C1-C6 alkyl or C1-C6 alkyl substituted by one or more Rs 4-h ; Rs 4-h are independently halogen, ═O, cyano or -N(R 8 )2, the heteroatoms in the 5- to 10-membered heteroaromatic ring are each independently selected from one or more of N, O and S, and the number of heteroatoms is each independently 1, 2 or 3; R 1 is C6-C 10 aryl, 5-10-membered heteroaryl, 3-10-membered heterocycloalkyl, C6-C 1a aryl substituted with one or more R 10 aryl, 5-10-membered heteroaryl substituted with one or more R 1b or 3-10-membered heterocycloalkyl substituted with one or more R 1c ; the 5-10-membered heteroaryl in the 5-10-membered heteroaryl, 3-10-membered heterocycloalkyl, 5-10-membered heteroaryl substituted with one or more R 1b and the 3-10-membered heterocycloalkyl in the 3-10-membered heterocycloalkyl substituted with one or more R 1c each independently have a heteroatom selected from one or more of N, O, and S, and the number of heteroatoms is independently 1, 2, or 3; R 1a 、 R 1b and R 1c are each independently deuterium, a halogen, -OH, -CN, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, 5-10 membered heteroaryl, C1-C6 alkyl-O-, C1-C6 alkyl-S-, -N(R 8 )2, -(CH2)-C(=O)N(R 8 )2, C3-C 10 cycloalkyl, C1-C6 alkyl substituted with one or more R 1-a , C1-C6 alkyl-O- substituted with one or more R 1-b , C1-C6 alkyl-S- substituted with one or more R 1-c , C2-C6 alkenyl substituted with one or more R 1-d , C2-C6 alkynyl substituted with one or more R 1-e , C3-C 1- f cycloalkyl substituted with one or more R 10 or 5-10 membered heteroaryl substituted with one or more R 1-g ; the heteroatoms in the 5-10 membered heteroaryl in the 5-10 membered heteroaryl and the 5-10 membered heteroaryl substituted with one or more R 1-g are each independently selected from one or more of N, O and S, and the number of heteroatoms is each independently 1, 2 or 3; Or two adjacent R 1c The atoms to which they are attached together form a 5-10 membered heteroaromatic ring, wherein the 5-10 membered heteroaromatic ring is optionally substituted by one or more of the following groups: deuterium, halogen, -OH, -CN, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, 5-10 membered heteroaryl, C1-C6 alkyl-O-, C1-C6 alkyl-S-, -N(R 8 )2, -(CH2)-C(=O)N(R 8 2. C3-C 10 Cycloalkyl, with one or more R 1- a Substituted C1-C6 alkyl, one or more R 1-b Substituted C1-C6 alkyl-O-, substituted by one or more R 1-c Substituted C1-C6 alkyl-S-, substituted by one or more R 1-d Substituted C2-C6 alkenyl, substituted by one or more R 1-e Substituted C2-C6 alkynyl, substituted by one or more R 1-f Substituted C3-C 10 Cycloalkyl or one or more R 1-g substituted 5-10 membered heteroaryl; the 5-10 membered heteroaryl ring, the 5-10 membered heteroaryl and the 1-g The heteroatoms in the 5-10 membered heteroaryl in the substituted 5-10 membered heteroaryl are independently selected from one or more of N, O and S, and the number of heteroatoms is independently 1, 2 or 3; R 1-a 、R 1-b 、R 1-c 、R 1-d 、R 1-e 、R 1-f and R 1-g each independently is deuterium, a halogen, -CN, -OH, a C1-C4 alkyl group, a C1-C4 alkoxy group or a C3-C 10 cycloalkyl group; L is -O-(CR 9 R 9 ) n1 -, -S-(CR 9 R 9 ) n2 -, -N(R 8 )-(CR 9 R 9 ) n3 -, -SO-(CR 9 R 9 ) n4 - or -SO2-(CR 9 R 9 ) n5 -; R 9 independently hydrogen, halogen, -CN, C1-C6 alkyl, C1-C6 alkoxy, deuterated C1-C6 alkyl or 5-10 membered heteroaryl; n1, n2, n3, n4 and n5 are each independently 0, 1, 2 or 3; (when it is 0, it represents a connecting bond); R 2 is hydrogen, -COOH, C1-C6 alkyl, C1-C6 alkyl-O-, C3-C 10 cycloalkyl, C3-C 10 cycloalkenyl, 4-10 membered heterocycloalkyl, C6-C 10 aryl, 5-10 membered heteroaryl, -NHC(=NH)NH2, -C(O)N(R 8 )2, -(CH2OR 10 )(CH2) n6 OR 10 、-NR 8 C(=O)-C6-C 10 aryl, -C(=O)O-C1-C6 alkyl, C3-C 2a substituted by one or more R 10 cycloalkyl, C3-C 2b substituted by one or more R 10 cycloalkenyl, C3-C 2c substituted by one or more R 2d 4-10 membered heterocycloalkyl, C6-C 10 aryl or 5-10 membered heteroaryl substituted by one or more R 2e ; the 4-10 membered heterocycloalkyl in the 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl substituted by one or more R 2c and the 5-10 membered heteroaryl in the 5-10 membered heteroaryl substituted by one or more R 2e The heteroatoms in the 5-10 membered heteroaryl are each independently selected from one or more of N, O, and S, and the number of heteroatoms is each independently 1, 2, or 3; n6 is 0, 1, 2 or 3; R 2a 、R 2b 、R 2c 、R 2d and R 2e are each independently halogen, -OH, deuterium, -CN, -C(=O)H, =CR 2-c R 2-c , C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 alkyl-O-, -N(R 8 )2, (C l -C4 alkyl)-C(=O)-, oxo group (=O), -SO2F, (C l -C4 alkyl)-SO2-, (C l -C4 alkyl)-O-(C l -C4 alkyl)-, (C l -C4 alkyl)-O-(C l -C4 alkyl)-O-, -CH2OC(=O)N(R 8 )2, (C l -C4 alkyl)-O-C(=O)-NHCH2-, -CH2NHC(=O)N(R 8 )2, (C l -C4 alkyl)-C(=O)NHCH2-, (pyrazolyl)-CH2-, (C l -C4 alkyl)-SO2-NHCH2-, (4-10 membered heterocycloalkyl)-C(=O)-OCH2-, (R 8 )2N-C(=O)-O-, (C l -C4 alkyl)-O-(C l -C4 alkyl)-NH-C(=O)-O-, phenyl-C(=O)NH-, phenyl-(C l -C4 alkyl)-NH-C(=O)-O-, (4-10 membered heterocycloalkyl)-C(=O)-O-, (4-10 membered heterocycloalkyl)-CH2-, C1-C4 alkyl substituted by one or more R 2-a or C1-C4 alkyl-O- substituted by one or more R 2-b ; the phenyl in the phenyl-C(=O)NH- and phenyl-(C l -C4 alkyl)-NH-C(=O)-O- is optionally substituted by -C(=O)H, halogen, -CN or -OH; the 4-10 membered heterocycloalkyl in the (4-10 membered heterocycloalkyl)-C(=O)-OCH2-, (4-10 membered heterocycloalkyl)-C(=O)-O- and (4-10 membered heterocycloalkyl)-CH2- is optionally substituted by =O, halogen, -CN, -OH or C l -C6 alkyl substitution; the heteroatoms in the 4-10-membered heterocycloalkyl group in (4-10-membered heterocycloalkyl)-C(=O)-OCH2-, (4-10-membered heterocycloalkyl)-C(=O)-O- and (4-10-membered heterocycloalkyl)-CH2- are each independently selected from one or more of N, O and S, and the number of heteroatoms is each independently 1, 2 or 3; R 2-a , R 2-b and R 2-c each independently is deuterium, -CN, halogen or -OH; R 3 is H, deuterium, -N(R 8 )2, halogen, -OH, C1-C6 alkyl, -CN, halo-C1-C6 alkyl, deuterated C1-C6 alkyl, C1-C6 alkoxy, deuterated C1-C6 alkoxy, C2-C6 alkenyl or C2-C6 alkynyl.

4. The heterocyclic compound represented by formula I according to any one of claims 1-3, its pharmaceutically acceptable salt, its solvate or its pharmaceutically acceptable salt solvate, characterized in that, n is 1, 2 or 3; X is independently -C(R 7 )2-, -NR 7 -, -O-, -S-, -CR 7 =CR 7 -, -N=N- or -CR 7 =N-; R 7 Independently hydrogen, deuterium, halogen, cyano, hydroxy, amino, C1-C6 alkyl, C1-C6 alkyl-O-, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkyl substituted with one or more R 7a substituents, C1-C6 alkyl-O- substituted with one or more R 7b substituents, C2-C6 alkenyl substituted with one or more R 7c substituents or C2-C6 alkynyl substituted with one or more R 7d substituents; R 7a 、R 7b 、R 7c and R 7d each independently is deuterium, -CN, a halogen or -OH; Y is -NR 4 -, -O-, -S- or -C(R 4 )2-; R 4 independently hydrogen, C1-C6 alkyl, C3-C 10 cycloalkyl, 3-10 membered heterocycloalkyl, C3-C 10 cycloalkenyl, 3-10 membered heterocycloalkenyl, 5-10 membered heteroaryl, C6-C 10 aryl, C1-C6 alkyl substituted with one or more R 4a substituents, C3-C 4b cycloalkyl substituted with one or more R 10 substituents, 3-10 membered heterocycloalkyl substituted with one or more R 4c substituents, 3-10 membered heterocycloalkenyl substituted with one or more R 4d substituents, 5-10 membered heteroaryl substituted with one or more R 4e substituents, C3-C 4f cycloalkenyl substituted with one or more R 10 substituents or C6-C 4g aryl substituted with one or more R 10 aryl; the 3-10 membered heterocycloalkyl, 3-10 membered heterocycloalkenyl, 5-10 membered heteroaryl, 3-10 membered heterocycloalkyl in the 3-10 membered heterocycloalkyl substituted with one or more R 4c substituents, 3-10 membered heterocycloalkenyl in the 3-10 membered heterocycloalkenyl substituted with one or more R 4d substituents and 5-10 membered heteroaryl in the 5-10 membered heteroaryl substituted with one or more R 4e substituents, the heteroatoms in the 5-10 membered heteroaryl are each independently selected from one or more of N, O, and S, and the number of heteroatoms is each independently 1, 2, or 3; R 4a 、R 4b 、R 4c 、R 4d 、R 4e 、R 4f and R 4g each independently is halogen, =O, cyano, -OR 10 、-N(R 8 )2、-SR 11 、-SO2R 11 、-C(O)N(R 10 )2、-C(O)R 10 、C1-C6 alkyl, C3-C 10 cycloalkyl, 3- to 10-membered heteroalkenyl, 5- to 10-membered heteroaryl, 3- to 10-membered heterocycloalkyl, C3-C 10 cycloalkenyl, C6-C 10 aryl, C1-C6 alkyl substituted with one or more R 4-a 、C3-C 4-b cycloalkyl substituted with one or more R 10 、3- to 10-membered heterocycloalkyl substituted with one or more R 4-c 、3- to 10-membered heteroalkenyl substituted with one or more R 4-d 、5- to 10-membered heteroaryl substituted with one or more R 4-e 、C3-C 4-f cycloalkenyl substituted with one or more R 10 or C6-C 4-g aryl substituted with one or more R 10 ; the heteroatoms in the 3- to 10-membered heterocycloalkyl, 3- to 10-membered heteroalkenyl, 5- to 10-membered heteroaryl, 3- to 10-membered heterocycloalkyl substituted with one or more R 4-c in the 3- to 10-membered heterocycloalkyl substituted with one or more R 4-d in the 3- to 10-membered heteroalkenyl substituted with one or more R 4-e and the 5- to 10-membered heteroaryl in the 5- to 10-membered heteroaryl substituted with one or more R each independently are selected from one or more of N, O, and S, and the number of heteroatoms is independently 1, 2, or 3; R 4-a 、R 4-b 、R 4-c 、R 4-d 、R 4-e 、R 4-f and R 4-g each independently is halogen, =O, cyano, -OR 10 、-N(R 8 )2, -SR 11 、-SO2R 11 、-C(O)N(R 10 )2, -C(O)R 10 、C1-C6 alkyl, C3-C 10 cycloalkyl, 3-10 membered heteroalkenyl, 3-10 membered heteroalkyl, 5-10 membered heteroaryl, C3-C 10 cycloalkenyl, C6-C 10 aryl, C1-C6 alkyl substituted with one or more R 4-a-1 、C3-C 4- a-2 cycloalkyl substituted with one or more R 10 、3-10 membered heteroalkyl substituted with one or more R 4-a-3 、3-10 membered heteroalkenyl substituted with one or more R 4-a-4 、5-10 membered heteroaryl substituted with one or more R 4-a-5 、C3-C 4-a-6 cycloalkenyl substituted with one or more R 10 or C6-C 4-a-7 aryl substituted with one or more R 10 ; the 3-10 membered heteroalkyl, 3-10 membered heteroalkenyl, 5-10 membered heteroaryl, substituted by one or more R 4-a-3 a 3- to 10-membered heterocycloalkyl in a 3- to 10-membered heterocycloalkyl substituted by one or more R 4-a-4 a 3- to 10-membered heterocycloalkenyl in a 3- to 10-membered heterocycloalkenyl substituted by one or more R 4-a-5 the heteroatoms in a 5- to 10-membered heteroaryl in a 5- to 10-membered heteroaryl substituted by one or more R are each independently selected from one or more of N, O, and S, and the number of heteroatoms is each independently 1, 2, or 3; R 4-a-1 、R 4-a-2 、R 4-a-3 、R 4-a-4 、R 4-a-5 、R 4-a-6 and R 4-a-7 each independently represents a halogen, =O, cyano, -C(O)CH3, -C(O)NH2, -OH, halogenated C1-C6 alkyl, -N(R 8 )2, -SCH3, -SO2CH3, C1-C6 alkyl, C3-C 10 cycloalkyl, 3- to 10-membered heterocycloalkyl or 3- to 10-membered heterocycloalkenyl; the heteroatoms in the 3- to 10-membered heterocycloalkyl and 3- to 10-membered heterocycloalkenyl each independently selected from one or more of N, O, and S, and the number of heteroatoms is each independently 1, 2, or 3; R 8 independently is hydrogen, -C(O)N(R 10 )2, -C(O)R 10 , C1-C6 alkyl, C3-C 10 cycloalkyl, 3-10 membered heterocycloalkyl, 3-10 membered heterocycloalkenyl, 5-10 membered heteroaryl, C1-C6 alkyl substituted with one or more R 8a , C3-C 8b cycloalkyl substituted with one or more R 10 , 3-10 membered heterocycloalkyl substituted with one or more R 8c , 3-10 membered heterocycloalkenyl substituted with one or more R 8d or 5-10 membered heteroaryl substituted with one or more R 8e ; the 3-10 membered heterocycloalkyl, 3-10 membered heterocycloalkenyl, 5-10 membered heteroaryl, 3-10 membered heterocycloalkyl in the 3-10 membered heterocycloalkyl substituted with one or more R 8c , 3-10 membered heterocycloalkenyl in the 3-10 membered heterocycloalkenyl substituted with one or more R 8d and 5-10 membered heteroaryl in the 5-10 membered heteroaryl substituted with one or more R 8e each independently have the heteroatoms selected from one or more of N, O, and S, and the number of heteroatoms is independently 1, 2, or 3; R 8a 、R 8b 、R 8c 、R 8d and R 8e are each independently a halogen, a cyano group, -C(O)R 10 , -C(O)N(R 10 )2, -OH, C1-C6 alkyl-O-, -N(R 10 )2, -SO2N(R 10 )2, -SO2R 10 , C1-C6 alkyl, C3-C 10 cycloalkyl, 3-10 membered heteroalkyl, 3-10 membered heteroalkenyl, 5-10 membered heteroaryl, C1-C6 alkyl substituted with one or more R 8-a , C3-C 8-b cycloalkyl substituted with one or more R 10 , 3-10 membered heteroalkyl substituted with one or more R 8-c , 3-10 membered heteroalkenyl substituted with one or more R 8-d or 5-10 membered heteroaryl substituted with one or more R 8-e ; the heteroatoms in the 3-10 membered heteroalkyl, 3-10 membered heteroalkenyl, 5-10 membered heteroaryl, 3-10 membered heteroalkyl substituted with one or more R 8-c in the 3-10 membered heteroalkyl substituted with one or more R 8-d in the 3-10 membered heteroalkenyl substituted with one or more R 8-e and the 5-10 membered heteroaryl in the 5-10 membered heteroaryl substituted with one or more R are each independently selected from one or more of N, O, and S, and the number of heteroatoms is each independently 1, 2, or 3; R 8-a 、R 8-b 、R 8-c 、R 8-d and R 8-e are each independently a halogen, a cyano group, -C(O)R 10 , -C(O)N(R 10 )2, -OH, C1-C6 alkoxy, -N(R 10 )2, -SO2N(R 10 )2, -SO2(R 10 ), C1-C6 alkyl, C3-C 10 cycloalkyl, 3-10 membered heteroalkyl, 3-10 membered heteroalkenyl, 5-10 membered heteroaryl, C1-C6 alkyl substituted with one or more R 8-a-1 s, C3-C 8-a-2 cycloalkyl substituted with one or more R 10 s, 3-10 membered heteroalkyl substituted with one or more R 8-a-3 s, 3-10 membered heteroalkenyl substituted with one or more R 8-a-4 s or 5-10 membered heteroaryl substituted with one or more R 8-a-5 s; the heteroatoms in the 3-10 membered heteroalkyl, 3-10 membered heteroalkenyl, 5-10 membered heteroaryl, 3-10 membered heteroalkyl substituted with one or more R 8-a-3 s in the 3-10 membered heteroalkyl substituted with one or more R 8-a-4 s, the 3-10 membered heteroalkenyl substituted with one or more R 8-a-5 s and the 5-10 membered heteroaryl substituted with one or more R s are each independently selected from one or more of N, O and S, and the number of heteroatoms is each independently 1, 2 or 3; R 8-a-1 、R 8-a-2 、R 8-a-3 、R 8-a-4 and R 8-a-5 each independently is halogen, cyano, -C(O)R 10 , -C(O)N(R 10 )2, -OH, -OCH3, -N(R 10 )2, -SO2N(R 10 )2, -SO2R 10 , C1-C6 alkyl or halo C1-C6 alkyl; R 10 independently hydrogen, C1-C6 alkyl, halo-C1-C6 alkyl, C3-C 10 cycloalkyl or 3-10 membered heterocycloalkyl; R 11 independently -NH2 or C1-C6 alkyl; R 5 and R 6 each independently is hydrogen, halogen, -N(R 8 )2, 3- to 10-membered heterocycloalkyl, C1-C6 alkyl, 3- to 10-membered heterocycloalkenyl, C3-C 10 cycloalkyl, C3-C 10 cycloalkenyl, 5- to 10-membered heteroaryl, C6-C 10 aryl, C1-C6 alkyl substituted with one or more R 5a , 3- to 10-membered heterocycloalkyl substituted with one or more R 5b , 3- to 10-membered heterocycloalkenyl substituted with one or more R 5c , C3-C 5d cycloalkyl substituted with one or more R 10 , C3-C 5e cycloalkenyl substituted with one or more R 10 , 5- to 10-membered heteroaryl substituted with one or more R 5f or C6-C 5g aryl substituted with one or more R 10 ; the heteroatoms in the 3- to 10-membered heterocycloalkyl, 3- to 10-membered heterocycloalkenyl, 5- to 10-membered heteroaryl, and 3- to 10-membered heterocycloalkyl in the 3- to 10-membered heterocycloalkyl substituted with one or more R 5b , 3- to 10-membered heterocycloalkenyl in the 3- to 10-membered heterocycloalkenyl substituted with one or more R 5c and 5- to 10-membered heteroaryl in the 5- to 10-membered heteroaryl substituted with one or more R 5f are each independently selected from one or more of N, O, and S, and the number of heteroatoms is each independently 1, 2, or 3; R 5a 、R 5b 、R 5c 、R 5d 、R 5e 、R 5f and R 5g each independently represents a halogen, =O, cyano, -OH, C1-C6 alkyl - O -, C1-C6 alkyl or halo C1-C6 alkyl; R 4 and R 5 may also together with the atoms to which it is attached form a 3- to 10-membered saturated heterocycle, a 5- to 10-membered heteroaryl ring, a 3- to 10-membered heterocyclene, a 3- to 10-membered saturated heterocycle substituted by one or more R 4h substituents, a 3- to 10-membered heterocyclene substituted by one or more R 4i substituents or a 5- to 10-membered heteroaryl ring substituted by one or more R 4j substituents; the heteroatoms in the 3- to 10-membered saturated heterocycle, 3- to 10-membered heterocyclene, 5- to 10-membered heteroaryl ring, 3- to 10-membered saturated heterocycle substituted by one or more R 4h substituents, the 3- to 10-membered saturated heterocycle in the 3- to 10-membered saturated heterocycle substituted by one or more R 4i substituents, the 3- to 10-membered heterocyclene in the 3- to 10-membered heterocyclene substituted by one or more R 4j substituents and the 5- to 10-membered heteroaryl ring in the 5- to 10-membered heteroaryl ring substituted by one or more R substituents are each independently selected from one or more of N, O and S, and the number of heteroatoms is each independently 1, 2 or 3; R 4h , R 4i and R 4j are independently halogen, =O, cyano, -OH, -N(R 8 )2. -SR 11 、-SO2R 11 、-C(O)N(R 10 )2. -C(O)R 10 , C1-C6 alkyl or one or more R 4-h Substituted C1-C6 alkyl; R 4-h independently is halogen, =O, cyano or -N(R 8 )2; R 1 is C6-C 10 aryl, 5- to 10-membered heteroaryl, C6-C 1a aryl substituted by one or more R 10 or 5- to 10-membered heteroaryl substituted by one or more R 1b ; the heteroatoms in the 5- to 10-membered heteroaryl and the 5- to 10-membered heteroaryl in the 5- to 10-membered heteroaryl substituted by one or more R 1b are each independently selected from one or more of N, O, and S, and the number of heteroatoms is each independently 1, 2, or 3; R 1a and R 1b each independently is deuterium, a halogen, -OH, -CN, a C1-C6 alkyl group, a C2-C6 alkenyl group, a C2-C6 alkynyl group, a 5-10 membered heteroaryl group, a C1-C6 alkyl-O-, a C1-C6 alkyl-S-, -N(R 8 )2, -(CH2)-C(=O)N(R 8 )2, a C3-C 10 cycloalkyl group, a C1-C6 alkyl group substituted with one or more R 1-a groups, a C1-C6 alkyl-O- substituted with one or more R 1-b groups, a C1-C6 alkyl-S- substituted with one or more R 1-c groups, a C2-C6 alkenyl group substituted with one or more R 1-d groups, a C2-C6 alkynyl group substituted with one or more R 1-e groups, a C3-C 1-f cycloalkyl group substituted with one or more R 10 groups or a 5-10 membered heteroaryl group substituted with one or more R 1-g groups; the heteroatoms in the 5-10 membered heteroaryl group in the 5-10 membered heteroaryl group and the 5-10 membered heteroaryl group substituted with one or more R 1-g groups are each independently selected from one or more of N, O, and S, and the number of heteroatoms is each independently 1, 2, or 3; R 1-a 、R 1-b 、R 1-c 、R 1-d 、R 1-e 、R 1-f and R 1-g each independently is deuterium, a halogen, -CN, -OH, C1-C4 alkyl, C1-C4 alkoxy or C3-C 10 cycloalkyl; L is -O-(CR 9 R 9 ) n1 -, -S-(CR 9 R 9 ) n2 -, -N(R 8 )-(CR 9 R 9 ) n3 -, -SO-(CR 9 R 9 ) n4 - or -SO2-(CR 9 R 9 ) n5 -; R 9 independently hydrogen, halogen, -CN, C1-C6 alkyl, C1-C6 alkoxy, deuterated C1-C6 alkyl or 5-10 membered heteroaryl; n1, n2, n3, n4 and n5 are each independently 0, 1, 2 or 3; (when it is 0, it represents a connecting bond); R 2 is hydrogen, -COOH, C1-C6 alkyl, C1-C6 alkoxy, C3-C 10 cycloalkyl, C3-C 10 cycloalkenyl, 4-10 membered heteroalkyl, C6-C 10 aryl, 5-10 membered heteroaryl, -NHC(=NH)NH2, -C(O)N(R 8 )2, -(CH2OR 10 )(CH2) n6 OR 10 , -NR 8 C(=O)-C6-C 10 aryl, -C(=O)O-C1-C6 alkyl, C3-C 2a substituted by one or more R 10 cycloalkyl, C3-C 2b substituted by one or more R 10 cycloalkenyl, 4-10 membered heteroalkyl substituted by one or more R 2c , 4-10 membered heteroalkyl substituted by one or more R 2d substituted C6-C 10 aryl or 5-10 membered heteroaryl substituted by one or more R 2e ; the heteroatoms in the 4-10 membered heteroalkyl in the 4-10 membered heteroalkyl, 5-10 membered heteroaryl, 4-10 membered heteroalkyl substituted by one or more R 2c and the 5-10 membered heteroaryl in the 5-10 membered heteroaryl substituted by one or more R 2e are each independently selected from one or more of N, O and S, and the number of heteroatoms is each independently 1, 2 or 3; n6 is 0, 1, 2 or 3; R 2a 、R 2b 、R 2c 、R 2d and R 2e are each independently halogen, -OH, deuterium, -CN, -C(=O)H, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 alkyl-O-, -N(R 8 )2, (C l -C4 alkyl)-C(=O)-, oxo group (=O), -SO2F, (C l -C4 alkyl)-SO2-, (C l -C4 alkyl)-O-(C l -C4 alkyl)-O-, -CH2OC(=O)N(R 8 )2, (C l -C4 alkyl)-O-C(=O)-NHCH2-, -CH2NHC(=O)N(R 8 )2, (C l -C4 alkyl)-C(=O)NHCH2-, (pyrazolyl)-CH2-, (C l -C4 alkyl)-SO2-NHCH2-, (4-10 membered heterocycloalkyl)-C(=O)-OCH2-, (R 8 )2N-C(=O)-O-, (C l -C4 alkyl)-O-(C l -C4 alkyl)-NH-C(=O)-O-, phenyl-C(=O)NH-, phenyl-(C l -C4 alkyl)-NH-C(=O)-O-, (4-10 membered heterocycloalkyl)-C(=O)-O-, (4-10 membered heterocycloalkyl)-CH2-, C1-C4 alkyl substituted with one or more R 2-a or C1-C4 alkyl-O- substituted with one or more R 2-b ; said phenyl-C(=O)NH- and phenyl-(C l The phenyl group in -C4 alkyl)-NH-C(=O)-O- is optionally substituted by -C(=O)H, halogen, -CN or -OH; the 4- to 10-membered heterocycloalkyl group in (4-10 membered heterocycloalkyl)-C(=O)-OCH2-, (4-10 membered heterocycloalkyl)-C(=O)-O- and (4-10 membered heterocycloalkyl)-CH2- is optionally substituted by =O, halogen, -CN or -OH; the heteroatoms in the 4- to 10-membered heterocycloalkyl group in (4-10 membered heterocycloalkyl)-C(=O)-OCH2-, (4-10 membered heterocycloalkyl)-C(=O)-O- and (4-10 membered heterocycloalkyl)-CH2- are each independently selected from one or more of N, O and S, and the number of heteroatoms is each independently 1, 2 or 3; R 2-a and R 2-b each independently is deuterium, -CN, a halogen or -OH; R 3 is H, deuterium, -N(R 8 )2, halogen, -OH, C1-C6 alkyl, -CN, halo-C1-C6 alkyl, deuterated C1-C6 alkyl, C1-C6 alkoxy, deuterated C1-C6 alkoxy, C2-C6 alkenyl or C2-C6 alkynyl.

5. The heterocyclic compound represented by Formula I, its pharmaceutically acceptable salt, its solvate or the solvate of its pharmaceutically acceptable salt according to any one of claims 1-4, characterized in that, It satisfies one or more of the following conditions: (1) Each "5-10 yuan heteroaryl" is independently a 5-6 membered monocyclic heteroaryl or an 8-10 membered bicyclic heteroaryl having one or more heteroatoms selected from N, O, and S, and the number of heteroatoms is 1, 2, or 3, such as a 5-6 membered monocyclic heteroaryl or a 9 membered bicyclic heteroaryl, further such as pyrrolyl, furyl, thienyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, imidazolyl, 1,2,3-triazolyl, 1,2,4-triazolyl, 1,2,3-triazinyl, 1,3,5-s-triazinyl, 1,3,4-triazinyl, quinolinyl, isoquinolinyl, 1H-pyrazolo[4,3-c]pyridinyl, 1H-pyrrolo[3,2-c]pyridinyl, 7H-pyrrolo[2,3-d]pyrimidinyl, indolyl, isoindolyl, indazolyl, benzothienyl or benzothiazolyl, preferably More preferably Even more preferably (2) Each "4-10 membered heteroalkyl" is independently a 4-6 membered monocyclic or 8-10 membered bicyclic heteroalkyl in which the heteroatom is selected from one or two of N and O, and the number of heteroatoms is 1 or 2, such as 4-6 membered monocyclic heteroalkyl, 8-10 membered fused heteroalkyl, 8-10 membered bridged heteroalkyl or 8-10 membered spiro heteroalkyl, for example any one of the following cases: Case 1: azetidinyl, oxetidinyl, pyrrolidinyl, imidazolidinyl, tetrahydrofuryl, piperidinyl, tetrahydropyranyl, morpholinyl, piperazinyl, hexahydro-1H-pyrrolizinyl, 1-azabicyclo[2.2.2]octyl or azaspiro[3.4]octyl, preferably hexahydro-1H-pyrrolizinyl, pyrrolidinyl, morpholinyl, tetrahydrofuryl, piperidinyl, piperazinyl, 1-azabicyclo[2.2.2]octyl, azaspiro[3.4]octyl or azetidinyl, such as Case 2: azetidinyl, oxetanyl, pyrrolidinyl, imidazolidinyl, tetrahydrofuryl, piperidinyl, tetrahydropyranyl, morpholinyl, piperazinyl, hexahydro-1H-pyrrolizinyl or 1-azabicyclo[2.2.2]octyl, preferably hexahydro-1H-pyrrolizinyl, pyrrolidinyl, morpholinyl, tetrahydrofuryl, piperidinyl, piperazinyl or 1-azabicyclo[2.2.2]octyl, such as 6. The heterocyclic compound represented by Formula I, a pharmaceutically acceptable salt thereof, a solvate thereof, or a solvate of a pharmaceutically acceptable salt thereof according to any one of claims 1-4, characterized in that, It satisfies one or more of the following conditions: (1) Each "C1-C6 alkyl group" is independently methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, n-pentyl, such as methyl, ethyl, isopropyl (2) Each "C2-C6 alkenyl" is independently a C2-C4 alkenyl, such as vinyl, allyl or propenyl; (3) Each "C2-C6 alkynyl" is independently a C2-C4 alkynyl, such as ethynyl, propargyl or propynyl; (4) Each "halogen" is independently F, Cl, Br or I, such as F, Cl or Br, further such as F or Cl, still further such as F; (5) Each "C3-C 10 cycloalkyl" is independently cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl, such as cyclopropyl, cyclobutyl or cyclopentyl; (6) Each "3- to 10-membered heterocycloalkyl" is independently a 4-, 5- or 6-membered heterocycloalkyl in which the heteroatom is selected from one or two of N and O, and the number of heteroatoms is 1 or 2, such as azetidinyl, oxetanyl, pyrrolidinyl, tetrahydrofuryl, piperidinyl, tetrahydropyranyl, tetrahydroimidazolyl, morpholinyl or piperazinyl, more preferably oxetanyl, tetrahydropyranyl or morpholinyl, preferably More preferably More preferably (7) Each "C3-C 10 cycloalkenyl" is independently cyclopropenyl, cyclobutenyl, cyclobutadienyl, cyclopentenyl, cyclopentadienyl, cyclohexenyl or cyclohexadienyl; (8) Each "3-10 membered heteroalkenyl" is independently a 5-10 membered heteroalkenyl in which the heteroatom is selected from one or two of N and O, and the number of heteroatoms is independently 1 or 2, for example any one of the following cases: Case 1: 5-membered heteroalkenyl or 6-membered heteroalkenyl, more specifically dihydropyrrolyl, dihydrofuranyl, dihydropyranyl, dihydropy pyridyl, tetrahydropyridyl, Preferably Case 2: 5-membered or 6-membered heteroalkenyl, more specifically pyrrolidinyl, dihydrofuryl, dihydropyranyl, dihydropyridyl or tetrahydropyridyl, preferably (9) Each "5-10 membered heteroaryl" is independently a 5-10 membered heteroaryl in which the heteroatom is selected from one or more of N, O, and S, and the number of heteroatoms is 1 or 2, such as pyrrolyl, furyl, thienyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, quinolinyl, or isoquinolinyl, preferably pyridyl, for example (10) Each "C6-C 10 aryl" is independently phenyl or naphthyl, such as phenyl; (11) Each "3-10 yuan saturated heterocycle" is independently a 3-6 yuan saturated heterocycle in which the heteroatom is selected from one or two of N and O, and the number of heteroatoms is 1, 2 or 3, such as azetidine, oxetane, pyrrolidine ring, tetrahydrofuran ring, piperidine ring, tetrahydropyran ring, morpholine ring, piperazine ring or 1,4-oxazepane ring, more specifically Preferably (12) Each "5- to 10-membered heteroaromatic ring" is independently a 5- to 10-membered heteroaromatic ring in which the heteroatom is selected from one or more of N, O, and S, and the number of heteroatoms is 1 or 2, such as a pyrrole ring, a furan ring, a thiophene ring, a pyrazole ring, an oxazole ring, an isoxazole ring, a thiazole ring, an isothiazole ring, a pyridine ring, a pyridazine ring, a pyrimidine ring, a pyrazine ring, a quinoline ring, or an isoquinoline ring, and further such as Preferably (13) Each "3-10 membered heteroalkenyl" is independently a 5-10 membered heteroalkenyl in which the heteroatom is selected from one or two of N and O, and the number of heteroatoms is independently 1 or 2, such as 5-membered heteroalkene or 6-membered heteroalkene, more specifically dihydropyrrole, dihydrofuran, dihydropyran, dihydropyridine or tetrahydropyridine; (14) Each "4- to 10-membered heterocycloalkyl" is independently a 4- to 6-membered monocyclic or 8- to 10-membered bicyclic heterocycloalkyl in which the heteroatom is selected from one or two of N and O, and the number of heteroatoms is 1 or 2, such as azetidinyl, oxetanyl, pyrrolidinyl, tetrahydrofuryl, piperidinyl, tetrahydropyranyl, morpholinyl, piperazinyl, hexahydro-1H-pyrrolizinyl, preferably hexahydro-1H-pyrrolizinyl, pyrrolidinyl or morpholinyl, for example (15) Each "C l -C4 alkyl" is independently methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl or tert-butyl, for example, methyl, ethyl or n-propyl; (16) Each "C2-C4 alkenyl" is independently vinyl, propenyl or allyl; (17) Each "C2-C4 alkynyl" is independently ethynyl, propynyl or propargyl; (18) Each "halo" is independently substituted by F, Cl, Br or I.

7. The compound of formula I, its pharmaceutically acceptable salt, its solvate or the solvate of its pharmaceutically acceptable salt according to claim 1 or 2, characterized in that, It satisfies one or more of the following conditions: (1) In each "5-10-membered heteroaryl fused to a 3-10-membered heterocycloalkyl", the 5-10-membered heteroaryl is independently a 5-10-membered heteroaryl having one or more heteroatoms selected from N, O and S, and the number of heteroatoms is 1 or 2, such as a pyrrole ring, a furan ring, a thiophene ring, a pyrazole ring, an oxazole ring, an isoxazole ring, a thiazole ring, an isothiazole ring, a pyridine ring, a pyridazine ring, a pyrimidine ring, a pyrazine ring, a quinoline ring or an isoquinoline ring, preferably a pyridine ring; (2) Each of the "5- to 10-membered heteroaryl-fused 3- to 10-membered heterocycloalkyl" groups, the 3- to 10-membered heterocycloalkyl is independently a 4-, 5- or 6-membered heterocycloalkyl in which the heteroatom is selected from one or two of N and O, and the number of heteroatoms is 1 or 2, such as azetidinyl, oxetanyl, pyrrolidinyl, tetrahydrofuryl, piperidinyl, tetrahydropyranyl, tetrahydroimidazolyl, morpholinyl, piperazinyl or More specifically, a piperazinyl group or Preferably Preferably, in the compound of formula I, each "5-10-membered heteroaryl fused to a 3-10-membered heterocycloalkyl" is For example (3)L is absent, -O-(CR 9 R 9 ) n1 -, -S-(CR 9 R 9 ) n2 - or -N(R 8 )-(CR 9 R 9 ) n3 -, R 8 independently is hydrogen, R 9 independently is hydrogen or C1-C6 alkyl, n1, n2 and n3 are each independently 0 or 1; preferably, L is absent or -O-(CR 9 R 9 ) n1 -, R 9 independently is hydrogen or C1-C6 alkyl, n1 is 0 or 1; (4)R 2 is hydrogen, C3-C 10 cycloalkyl, 4-10 membered heterocycloalkyl, C3-C 2a cycloalkyl substituted by one or more R 10 or 4-10 membered heterocycloalkyl substituted by one or more R 2c , R 2a independently is (4-10 membered heterocycloalkyl)-CH2-, and the 4-10 membered heterocycloalkyl in the (4-10 membered heterocycloalkyl)-CH2- is optionally substituted by C l -C6 alkyl, R 2c independently is halogen, C1-C4 alkyl, =CR 2-c R 2-c , C1-C4 alkyl-O-, -N(R 8 )2, (C l -C4 alkyl)-O-(C l -C4 alkyl)-, 4-10 membered heterocycloalkyl or 4-10 membered heterocycloalkyl substituted by one or more R 2-d , R 8 independently is H, R 2-c and R 2-d independently are halogen; Preferably, R 2 is hydrogen, a 4- to 10-membered heterocycloalkyl group, a C3-C 2a cycloalkyl group substituted by one or more R 10 or a 4- to 10-membered heterocycloalkyl group substituted by one or more R 2c , R 2a is independently (4- to 10-membered heterocycloalkyl)-CH2-, and the 4- to 10-membered heterocycloalkyl group in the (4- to 10-membered heterocycloalkyl)-CH2- is optionally substituted by C l -C6 alkyl, R 2c is independently halogen, C1-C4 alkyl, =CR 2-c R 2-c , C1-C4 alkyl-O-, -N(R 8 )2, (C l -C4 alkyl)-O-(C l -C4 alkyl)- or 4- to 10-membered heterocycloalkyl, R 8 is independently H, R 2-c is independently halogen; Preferably, R 2 is a 4- to 10-membered heterocycloalkyl group, a C3-C 2a cycloalkyl group substituted by one or more R 10 groups, or a 4- to 10-membered heterocycloalkyl group substituted by one or more R 2c groups, where R 2a is independently (4- to 10-membered heterocycloalkyl)-CH2-, and the 4- to 10-membered heterocycloalkyl group in the (4- to 10-membered heterocycloalkyl)-CH2- is optionally substituted by C l -C6 alkyl, R 2c is independently halogen, C1-C4 alkyl, C1-C4 alkoxy, -N(R 8 )2, (C l -C4 alkyl)-O-(C l -C4 alkyl)-, or 4- to 10-membered heterocycloalkyl, R 8 is independently H, and R 2-c is independently halogen.

8. The compound represented by formula I, its pharmaceutically acceptable salt, its solvate or the solvate of its pharmaceutically acceptable salt according to claim 1, characterized in that It satisfies one or more of the following conditions: (1)R 2 is a 4- to 10-membered heterocycloalkyl group, a C3-C 2a cycloalkyl group substituted by one or more R 10 or a 4- to 10-membered heterocycloalkyl group substituted by one or more R 2c ; R 2a is independently (4- to 10-membered heterocycloalkyl)-CH2-, wherein the 4- to 10-membered heterocycloalkyl in the (4- to 10-membered heterocycloalkyl)-CH2- is optionally substituted by C l -C6 alkyl; R 2c is independently halogen, =CR 2-c R 2-c , C1-C4 alkyl, C1-C4 alkyl-O-, -N(R 8 )2 or (C l -C4 alkyl)-O-(C l -C4 alkyl)-, R 8 is independently H, R 2-c is independently halogen; (2)R 4 independently hydrogen, C1-C6 alkyl, C3-C 10 cycloalkyl, 3-10 membered heterocycloalkyl, 5-10 membered heteroaryl, -SO2R h , 5-10 membered heteroaryl fused to 3-10 membered heterocycloalkyl, C1-C6 alkyl substituted with one or more R 4a , C3-C 4b cycloalkyl substituted with one or more R 10 , 3-10 membered heterocycloalkyl substituted with one or more R 4c , 5-10 membered heteroaryl substituted with one or more R 4e or 5-10 membered heteroaryl fused to 3-10 membered heterocycloalkyl substituted with one or more R, 4k ​ R h independently a 3- to 10-membered heteroalkenyl, 5- to 10-membered heteroaryl, a 3- to 10-membered heteroalkenyl substituted with one or more R 4-d or a 5- to 10-membered heteroaryl substituted with one or more R 4-e groups R 4a independently =O, -N(R 8 )2, -OR 10 , -C(O)N(R 10 )2, -C(O)OR 10 , C3-C 10 cycloalkyl, 3- to 10-membered heteroalkyl, 3- to 10-membered heteroalkenyl, 5- to 10-membered heteroaryl, C6-C 10 aryl, carboxyl, C3-C substituted with one or more R 4-b cycloalkyl, 3- to 10-membered heteroalkyl substituted with one or more R 10 3- to 10-membered heteroalkenyl substituted with one or more R 4-c 5- to 10-membered heteroaryl substituted with one or more R 4-e or 3- to 10-membered heteroalkenyl substituted with one or more R, 4-d ​ R 4-i each independently is hydrogen or a C1-C6 alkyl group, R 4-b and R 4-c each independently is -C(O)N(R 10 )2, R 4-e independently -N(R 8 )2, halogen, C1-C6 alkyl, -OR 10 , -C(O)R 10 , -C(O)N(R 10 )2 or C1-C6 alkyl substituted by one or more R 4-a-1 . R 4-d independently =O or -N(R 8 )2, R 4b and R 4c each independently is -C(O)N(R 10 )2, R 4e independently a 5- to 10-membered heteroaryl or a 5- to 10-membered heteroaryl substituted with one or more R 4-e substituents, R 4k independently =O or -N(R 8 )2, R 8 independently hydrogen, C1-C6 alkyl or -C(O)R 10 , R 10 independently hydrogen, C1-C6 alkyl or 3-10 membered heterocycloalkyl, R 4-a-1 independently -OH or -N(R 8 )2, Preferably, R 4 is independently hydrogen, C1-C6 alkyl, 3-10 membered heteroalkyl, -SO2R h , C1-C6 alkyl substituted by one or more R 4a , C3-C 4b cycloalkyl substituted by one or more R 10 , 5-10 membered heteroaryl substituted by one or more R 4e or 5-10 membered heteroaryl fused to 3-10 membered heteroalkyl substituted by one or more R 4k . R h independently a 5- to 10-membered heteroaryl, a 3- to 10-membered heteroalkenyl substituted with one or more R 4-d or a 5- to 10-membered heteroaryl substituted with one or more R 4-e ; R 4a Independently =O, -N(R 8 )2, -OR 10 , -C(O)N(R 10 )2, -C(O)OR 10 , C3-C 10 cycloalkyl, 3- to 10-membered heteroalkyl, 5- to 10-membered heteroaryl, C6-C 10 aryl, carboxyl, C3-C 4-b cycloalkyl substituted with one or more R 10 3- to 10-membered heteroalkyl substituted with one or more R 4-c 5- to 10-membered heteroaryl substituted with one or more R 4-e or 3- to 10-membered heteroalkenyl substituted with one or more R, 4-d ​ R 4-i each independently is hydrogen or a C1-C6 alkyl group, R 4-b and R 4-c each independently is -C(O)N(R 10 )2, R 4-e Independently -N(R 8 )2, halogen, C1-C6 alkyl, -OR 10 , -C(O)N(R 10 )2, -C(O)R 10 or C1-C6 alkyl substituted by one or more R 4-a-1 . R 4-d Independently =O or -N(R 8 )2, R 4b independently -C(O)N(R 10 )2, R 4e independently a 5- to 10-membered heteroaryl group substituted by one or more R 4-e groups, R 4k Independently =O or -N(R 8 )2, R 8 independently is hydrogen, C1-C6 alkyl or -C(O)R 10 , R 10 independently hydrogen, C1-C6 alkyl or 3-10 membered heterocycloalkyl, R 4-a-1 independently -OH or -N(R 8 )2, More preferably, R 4 is independently hydrogen, -SO2R h , C1-C6 alkyl substituted by one or more R 4a or 5-10-membered heteroaryl-fused 3-10-membered heterocycloalkyl substituted by one or more R 4k . R h independently a 3- to 10-membered heteroalkenyl group substituted with one or more R 4-d or a 5- to 10-membered heteroaryl group substituted with one or more R 4-e groups, R 4a independently =O, -OR 10 , -C(O)OR 10 , C3-C 10 cycloalkyl, 3- to 10-membered heteroalkyl, 5- to 10-membered heteroaryl, C6-C 10 aryl, carboxyl, C3-C substituted with one or more R 4-b cycloalkyl, 5- to 10-membered heteroaryl substituted with one or more R 10 or 3- to 10-membered heteroalkenyl substituted with one or more R 4-e 4-d ​​ R 4-i independently hydrogen or a C1-C6 alkyl group R 4-b independently -C(O)N(R 10 )2, R 4-e independently -N(R 8 )2, halogen, -OR 10 , -C(O)N(R 10 )2, -C(O)R 10 or C1-C6 alkyl substituted by one or more R 4-a-1 groups, R 4-d Independently =O or -N(R 8 )2, R 4k independently =O, R 8 independently hydrogen or -C(O)R 10 , R 10 independently hydrogen, C1-C6 alkyl or 3-10 membered heterocycloalkyl, R 4-a-1 independently -OH or -N(R 8 )2, For example, R 4 is independently hydrogen, -SO2R h , C1-C6 alkyl substituted by one or more R 4a , or 5-10 membered heteroaryl fused to 3-10 membered heterocycloalkyl substituted by one or more R 4k . R h independently a 3- to 10-membered heteroalkenyl group substituted by one or more R 4-d or a 5- to 10-membered heteroaryl group substituted by one or more R 4-e groups, R 4a independently =O, -OR 10 , -C(O)OR 10 , carboxyl, 5- to 10-membered heteroaryl, 3- to 10-membered heterocycloalkyl, C3-C substituted by one or more R 4-b cycloalkyl, C3-C 10 substituted by one or more R 4-e substituted 5- to 10-membered heteroaryl or 3- to 10-membered heterocycloalkenyl substituted by one or more R 4-d ​ R 4-i each independently is hydrogen or a C1-C6 alkyl group, R 4-b independently -C(O)N(R 10 )2, R 4-e independently -N(R 8 )2, halogen, -OR 10 , -C(O)N(R 10 )2 or C1-C6 alkyl substituted by one or more R 4-a-1 , R 4-d independently =O or -N(R 8 )2, R 4k independently =O, R 8 independently hydrogen, R 10 independently hydrogen or a C1-C6 alkyl group R 4-a-1 independently -OH or -N(R 8 )2.

9. The compound of formula I, its pharmaceutically acceptable salt, its solvate or the solvate of its pharmaceutically acceptable salt according to claim 1 or 2, characterized in that, It satisfies one or more of the following conditions: When L is absent, R 2 is a 4- to 10-membered heterocycloalkyl or a 4- to 10-membered heterocycloalkyl substituted by one or more R 2c ; R 2c is independently a C1-C4 alkyl, a 4- to 10-membered heterocycloalkyl or a 4- to 10-membered heterocycloalkyl substituted by one or more R 2-d ; R 2-d is independently a halogen; preferably, R 2 is a 4- to 10-membered heterocycloalkyl substituted by one or more R 2c ; R 2c is independently a C1-C4 alkyl, a 4- to 10-membered heterocycloalkyl or a 4- to 10-membered heterocycloalkyl substituted by one or more R 2-d ; R 2-d is independently a halogen; more preferably, R 2 is a 4- to 10-membered heterocycloalkyl substituted by one or more R 2c ; R 2c is independently a C1-C4 alkyl or a 4- to 10-membered heterocycloalkyl; (2) L is -O-(CR 9 R 9 ) n1 - When, R 2 is hydrogen, C3-C 10 cycloalkyl, 4- to 10-membered heterocycloalkyl, C3-C 2a cycloalkyl substituted by one or more R 10 or 4- to 10-membered heterocycloalkyl substituted by one or more R 2c , R 2a independently is (4- to 10-membered heterocycloalkyl)-CH2-, and the 4- to 10-membered heterocycloalkyl in the (4- to 10-membered heterocycloalkyl)-CH2- is optionally substituted by C l -C6 alkyl, R 2c independently is halogen, C1-C4 alkyl, =CR 2-c R 2-c , C1-C4 alkyl-O-, -N(R 8 )2 or (C l -C4 alkyl)-O-(C l -C4 alkyl)-, R 8 independently is H, R 2-c independently is halogen; Preferably, R 2 is hydrogen, a 4- to 10-membered heterocycloalkyl group, a C3-C 2a cycloalkyl group substituted by one or more R 10 groups, or a C3-C 2c Substituted 4- to 10-membered heterocycloalkyl, R 2a independently is (4- to 10-membered heterocycloalkyl)-CH2-, and the 4- to 10-membered heterocycloalkyl in the (4- to 10-membered heterocycloalkyl)-CH2- is optionally substituted by C l -C6 alkyl, R 2c independently is halogen, C1-C4 alkyl, =CR 2-c R 2-c , C1-C4 alkyl-O-, -N(R 8 )2 or (C l -C4 alkyl)-O-(C l -C4 alkyl)-, R 8 independently is H, R 2-c independently is halogen; More preferably, R 2 is a 4- to 10-membered heterocycloalkyl group, a C3-C 2a cycloalkyl group substituted with one or more R 10 groups, or a 4- to 10-membered heterocycloalkyl group substituted with one or more R 2c groups, where R 2a is independently (4- to 10-membered heterocycloalkyl)-CH2-, and the 4- to 10-membered heterocycloalkyl group in said (4- to 10-membered heterocycloalkyl)-CH2- is optionally substituted with C l -C6 alkyl, and R 2c is independently halogen, C1-C4 alkyl, C1-C4 alkoxy, -N(R 8 )2, or (C l -C4 alkyl)-O-(C l -C4 alkyl)-, and R 8 is independently H; Preferably, R 2 is a C3-C 2a cycloalkyl substituted by one or more R 10 or a 4- to 10-membered heterocycloalkyl substituted by one or more R 2c , where R 2a is independently (4- to 10-membered heterocycloalkyl)-CH2-, and R 2c is independently halogen or C1-C4 alkyl; (3)R 4 independently hydrogen, C1-C6 alkyl, C3-C 10 cycloalkyl, 3-10 membered heteroalkyl, 5-10 membered heteroaryl, -SO2R h , 5-10 membered heteroaryl fused to 3-10 membered heteroalkyl, C1-C6 alkyl substituted with one or more R 4a substituents, C3-C 4b cycloalkyl substituted with one or more R 10 substituents, 3-10 membered heteroalkyl substituted with one or more R 4c substituents, 5-10 membered heteroaryl substituted with one or more R 4e substituents or 5-10 membered heteroaryl fused to 3-10 membered heteroalkyl substituted with one or more R 4k substituents, R h independently a 3- to 10-membered heteroalkenyl, 5- to 10-membered heteroaryl, a 3- to 10-membered heteroalkenyl substituted with one or more R 4-d or a 5- to 10-membered heteroaryl substituted with one or more R 4-e ; R 4a independently =O, -N(R 8 )2, -OR 10 , -C(O)N(R 10 )2, C3-C 10 cycloalkyl, 3- to 10-membered heterocycloalkyl, 3- to 10-membered heterocycloalkenyl, 5- to 10-membered heteroaryl, carboxyl, C3-C 4-b cycloalkyl substituted with one or more R 10 , 3- to 10-membered heterocycloalkyl substituted with one or more R 4-c , 5- to 10-membered heteroaryl substituted with one or more R 4-e or 3- to 10-membered heterocycloalkenyl substituted with one or more R 4-d , R 4k independently =O or -N(R 8 )2, R 4-b and R 4-c each independently is -C(O)N(R 10 )2, R 4-e independently -N(R 8 )2, halogen, C1-C6 alkyl, -OR 10 , -C(O)N(R 10 )2 or C1-C6 alkyl substituted by one or more R 4-a-1 groups, R 4-d independently =O or -N(R 8 )2, R 4b and R 4c each independently is -C(O)N(R 10 )2, R 4e independently a 5- to 10-membered heteroaryl or a 5- to 10-membered heteroaryl substituted with one or more R 4-e substituents, R 8 and R 10 each independently represents hydrogen or a C1-C6 alkyl group, R 4-a-1 independently -OH or -N(R 8 )2, Preferably, R 4 is independently hydrogen, C1-C6 alkyl, 3-10 membered heteroalkyl, -SO2R h , C1-C6 alkyl substituted with one or more R 4a , C3-C 4b cycloalkyl substituted with one or more R 10 , 5-10 membered heteroaryl substituted with one or more R 4e or 5-10 membered heteroaryl fused to 3-10 membered heteroalkyl substituted with one or more R 4k . R h independently a 5- to 10-membered heteroaryl, a 3- to 10-membered heteroalkenyl substituted with one or more R 4-d or a 5- to 10-membered heteroaryl substituted with one or more R 4-e ​ R 4a independently =O, -N(R 8 )2, -OR 10 , -C(O)N(R 10 )2, C3-C 10 cycloalkyl, 3- to 10-membered heterocycloalkyl, 5- to 10-membered heteroaryl, carboxyl, C3-C 4-b substituted with one or more R 10 cycloalkyl, 3- to 10-membered heterocycloalkyl substituted with one or more R 4-c substituted, One or more R 4-e Substituted 5- to 10-membered heteroaryl or substituted 3- to 10-membered heteroalkenyl which is substituted by one or more R 4-d and R 4k independently =O or -N(R 8 )2, R 4-b and R 4-c each independently is -C(O)N(R 10 )2, R 4-e independently -N(R 8 )2, halogen, C1-C6 alkyl, -OR 10 , -C(O)N(R 10 )2 or C1-C6 alkyl substituted by one or more R 4-a-1 , R 4-d independently =O or -N(R 8 )2, R 4b independently -C(O)N(R 10 )2, R 4e independently a 5- to 10-membered heteroaryl group substituted by one or more R 4-e groups, R 8 independently hydrogen or a C1-C6 alkyl group, R 10 independently hydrogen or a C1-C6 alkyl group R 4-a-1 independently -OH or -N(R 8 )2, More preferably, R 4 is independently hydrogen, -SO2R h or a C1-C6 alkyl group substituted with one or more R 4a groups. R h independently a 3- to 10-membered heteroalkenyl group substituted by one or more R 4-d or a 5- to 10-membered heteroaryl group substituted by one or more R 4-e groups, R 4a Independently =O, -OR 10 , 5- to 10-membered heteroaryl, C3-C 4-b substituted by one or more R 10 cycloalkyl, 5- to 10-membered heteroaryl substituted by one or more R 4-e or 3- to 10-membered heterocycloalkenyl substituted by one or more R 4-d . R 4-b independently -C(O)N(R 10 )2, R 4-e independently -N(R 8 )2, halogen, -OR 10 , -C(O)N(R 10 )2 or C1-C6 alkyl substituted by one or more R 4-a-1 , R 4-d Independently =O or -N(R 8 )2, R 8 independently hydrogen, R 10 independently is hydrogen or a C1-C6 alkyl group R 4-a-1 independently -OH or -N(R 8 )2.

10. The compound represented by Formula I, its pharmaceutically acceptable salt, its solvate or the solvate of its pharmaceutically acceptable salt according to any one of claims 1-3, characterized in that, It satisfies one or more of the following conditions: (1) X is any of the following: Case 1: X is independently -C(R 7 )2-, -CR 7 =CR 7 -, -N=N- and -CR 7 =N-, R 7 is independently hydrogen or C1-C6 alkyl, and n is 1, 2 or 3; preferably, when n is 2 or 3, X is independently a -C(R 7 )2-, when n is 1, X is a -CR 7 =CR 7 -, a -N=N-, a -CR 7 =N- or a -N=CR 7 -, R 7 is independently hydrogen or C1-C6 alkyl, where the a side is connected to connected to the N atom in; Case 2: X is independently -C(R 7 )2-, -CR 7 =CR 7 - or -CR 7 =N-, R 7 is independently hydrogen or C1-C6 alkyl, and n is 1, 2 or 3; preferably, when n is 2 or 3, X is independently a -C(R 7 )2-, when n is 1, X is independently -CR 7 =CR 7 - or a -N=CR 7 -, R 7 alone is hydrogen or a C1-C6 alkyl group, wherein the a side is connected to connected to the N atom in; (2) L is -O-(CR 9 R 9 ) n1 -, -S-(CR 9 R 9 ) n2 - or -N(R 8 )-(CR 9 R 9 ) n3 , R 8 is independently hydrogen, R 9 is independently hydrogen or C1-C6 alkyl, n1, n2 and n3 are each independently 0 or 1; preferably, L is -O-(CR 9 R 9 ) n1 , R 9 is independently hydrogen or C1-C6 alkyl, n1 is 0 or 1; more preferably, L is -O-(CR 9 R 9 ) n1 - b , R 9 is independently hydrogen or C1-C6 alkyl, n1 is 0 or 1, wherein the b side is connected to R 2 ; (3)R 2 is hydrogen, C3-C 10 cycloalkyl, 4- to 10-membered heterocycloalkyl, C3-C 2a cycloalkyl substituted by one or more R 10 or 4- to 10-membered heterocycloalkyl substituted by one or more R 2c , where R 2a is independently (4- to 10-membered heterocycloalkyl)-CH2-, and the 4- to 10-membered heterocycloalkyl in the (4- to 10-membered heterocycloalkyl)-CH2- is optionally substituted by C l -C6 alkyl, R 2c is independently halogen, C1-C4 alkyl, =CR 2-c R 2-c , C1-C4 alkyl-O-, -N(R 8 )2 or (C l -C4 alkyl)-O-(C l -C4 alkyl)-, R 8 is independently H, R 2-c is independently halogen; preferably, R 2 is hydrogen, 4- to 10-membered heterocycloalkyl, C3-C 2a cycloalkyl substituted by one or more R 10 or 4- to 10-membered heterocycloalkyl substituted by one or more R 2c , where R 2a is independently (4- to 10-membered heterocycloalkyl)-CH2-, and the 4- to 10-membered heterocycloalkyl in the (4- to 10-membered heterocycloalkyl)-CH2- is optionally substituted by C l -C6 alkyl, R 2c is independently halogen, C1-C4 alkyl, =CR 2-c R 2-c , C1-C4 alkyl-O-, -N(R 8 )2 or (C l -C4 alkyl)-O-(C l -C4 alkyl)-, R 8 is independently H, R 2-c is independently halogen; More preferably, R 2 is a 4- to 10-membered heterocycloalkyl group, a C3-C 2a cycloalkyl group substituted with one or more R 10 groups, or a 4- to 10-membered heterocycloalkyl group substituted with one or more R 2c groups, where R 2a is independently (4- to 10-membered heterocycloalkyl)-CH2-, and the 4- to 10-membered heterocycloalkyl group in the (4- to 10-membered heterocycloalkyl)-CH2- is optionally substituted with C l -C6 alkyl groups, and R 2c is independently a halogen, a C1-C4 alkyl group, a C1-C4 alkoxy group, -N(R 8 )2, or (C l -C4 alkyl)-O-(C l -C4 alkyl)-, and R 8 is independently H; (4)R 1 is C6-C 10 aryl, 5- to 10-membered heteroaryl, 3- to 10-membered heterocycloalkyl, C6-C 1a aryl substituted by one or more R 10 groups, 5- to 10-membered heteroaryl substituted by one or more R 1b groups or 3- to 10-membered heterocycloalkyl substituted by one or more R 1c groups, where R 1a is independently halogen, -OH or -N(R 8 )2, R 1b is independently halogen, -CN, -OH, C1-C6 alkyl, -N(R 8 )2 or C1-C6 alkyl substituted by one or more R 1-a groups, R 1-a is independently halogen, R 8 is hydrogen, R 1c is independently C1-C6 alkyl, -CN or -N(R 8 )2, or two adjacent R 1c groups together with the atoms to which they are attached form a 5- to 10-membered heteroaryl ring, where the 5- to 10-membered heteroaryl ring is optionally substituted by one or more of the following groups: -CN, -N(R 8 )2 or C1-C6 alkyl; Preferably, R 1 is a C6-C 1a aryl substituted by one or more R 10 , a 5- to 10-membered heteroaryl substituted by one or more R 1b , or a 3- to 10-membered heterocycloalkyl substituted by one or more R 1c , where R 1a is independently halogen, -OH, or -N(R 8 )2, R 1b is independently halogen, -CN, -OH, C1-C6 alkyl, -N(R 8 )2, or C1-C6 alkyl substituted by one or more R 1-a , R 1-a is independently halogen, R 8 is hydrogen, R 1c is independently C1-C6 alkyl, or two adjacent R 1c together with the atoms to which they are attached form a 5- to 10-membered heteroaromatic ring, and the 5- to 10-membered heteroaromatic ring is optionally substituted by one or more of the following groups: -CN or -N(R 8 )2; Preferably, R 1 is a C6-C 1a aryl substituted by one or more R 10 or a 5- to 10-membered heteroaryl substituted by one or more R 1b ; R 1a is independently halogen, -OH or -N(R 8 )2, R 1b is independently halogen, -CN, C1-C6 alkyl, -N(R 8 )2 or C1-C6 alkyl substituted by one or more R 1- a ; R 1-a is independently halogen, R 8 is hydrogen; Preferably, R 1 is a 5- to 10-membered heteroaryl group substituted by one or more R 1b ; R 1b is independently halogen, -CN, C1-C6 alkyl, -N(R 8 )2 or C1-C6 alkyl substituted by one or more R 1-a ; R 1-a is independently halogen; R 8 is hydrogen; (5) Y is -NR 4 -, O, S or -(CH2) p NR 4 -, p is 1; preferably, Y is -NR 4 -, O or -(CH2) p NR 4 -, p is 1; more preferably, Y is -NR 4 -, O or c -(CH2) p NR 4 -, p is 1, the c side is connected to -CHR 5 -; most preferably, Y is -NR 4 - or c -(CH2) p NR 4 -, p is 1, the c side is connected to -CHR 5 -; (6)R 4 independently hydrogen, C1-C6 alkyl, C3-C 10 cycloalkyl, 3-10 membered heterocycloalkyl, 5-10 membered heteroaryl, -SO2R h ; C1-C6 alkyl substituted with one or more R 4a ; C3-C 4b cycloalkyl substituted with one or more R 10 ; 3-10 membered heterocycloalkyl substituted with one or more R 4c ; or 5-10 membered heteroaryl substituted with one or more R 4e , where R h is independently 5-10 membered heteroaryl or 5-10 membered heteroaryl substituted with one or more R 4-e , and R 4a is independently =O, -N(R 8 )2, -C(O)N(R 10 )2, C3-C 10 cycloalkyl, 3-10 membered heterocycloalkyl, 3-10 membered heterocycloalkenyl, 5-10 membered heteroaryl, C3-C 4-b cycloalkyl substituted with one or more R 10 ; 3-10 membered heterocycloalkyl substituted with one or more R 4- c ; 5-10 membered heteroaryl substituted with one or more R 4-e ; or 3-10 membered heterocycloalkenyl substituted with one or more R 4-d , where R 4-b and R 4-c are each independently -C(O)N(R 10 )2, R 4-e is independently -N(R 8 )2, R 4-d is independently =O, R 4b and R 4c are each independently -C(O)N(R 10 )2, R 4e is independently 5-10 membered heteroaryl or 5-10 membered heteroaryl substituted with one or more R 4-e , and R 8 and R 10 are each independently hydrogen or C1-C6 alkyl; Preferably, R 4 is independently hydrogen, C1-C6 alkyl, 3-10 membered heteroalkyl, -SO2R h , C1-C6 alkyl substituted with one or more R 4a , C3-C 4b cycloalkyl substituted with one or more R 10 or 5-10 membered heteroaryl substituted with one or more R 4e , R h is independently 5-10 membered heteroaryl or 5-10 membered heteroaryl substituted with one or more R 4-e , R 4a is independently =O, -N(R 8 )2, -C(O)N(R 10 )2, C3-C 10 cycloalkyl, 3-10 membered heteroalkyl, 5-10 membered heteroaryl, C3-C 4-b cycloalkyl substituted with one or more R 10 , 3-10 membered heteroalkyl substituted with one or more R 4-c , 5-10 membered heteroaryl substituted with one or more R 4-e or 3-10 membered heteroalkenyl substituted with one or more R 4-d , R 4-b and R 4-c are each independently -C(O)N(R 10 )2, R 4-e is independently -N(R 8 )2, R 4-d is independently =O, R 4b is independently -C(O)N(R 10 )2, R 4e is independently 5-10 membered heteroaryl substituted with one or more R 4-e , R 8 is independently hydrogen or C1-C6 alkyl, R 10 is independently hydrogen; (7)R 4 and R 5 may also together with the atoms to which they are attached form a 3- to 10-membered saturated heterocycle, a 5- to 10-membered heteroaryl ring, a 3- to 10-membered heterocyclene, a 3- to 10-membered saturated heterocycle substituted with one or more R 4h a 5- to 10-membered heteroaryl ring substituted with one or more R 4j or a 3- to 10-membered heterocyclene substituted with one or more R 4i , where R 4h is independently -OH, -N(R 8 )2, C1-C6 alkyl or C1-C6 alkyl substituted with one or more R 4-h , where R 4-h is independently -N(R 8 )2, or two adjacent R 4h together with the atoms to which they are attached form a 5- to 10-membered heteroaryl ring, where R 8 is independently hydrogen or C1-C6 alkyl, and R 4i and R 4j are each independently -C(O)N(R 10 )2, where R 10 is independently hydrogen; Preferably, R 4 and R 5 may also together with the atoms to which they are attached form a 3- to 10-membered saturated heterocycle, a 3- to 10-membered saturated heterocycle substituted with one or more R 4h or a 5- to 10-membered heteroaryl ring substituted with one or more R 4j , where R 4h is independently -OH, -N(R 8 )2, C1-C6 alkyl or C1-C6 alkyl substituted with one or more R 4-h , R 4-h is independently -N(R 8 )2, or two adjacent R 4h together with the atoms to which they are attached form a 5- to 10-membered heteroaryl ring, R 8 is independently hydrogen or C1-C6 alkyl, R 4j is independently -C(O)N(R 10 )2, R 10 is independently hydrogen; preferably, R 4 and R 5 may also together with the atoms to which they are attached form a 3- to 10-membered saturated heterocycle or a 3- to 10-membered saturated heterocycle substituted with one or more R 4h ; two adjacent R 4h together with the atoms to which they are attached form a 5- to 10-membered heteroaryl ring; preferably, R 4 and R 5 may also together with the atoms to which they are attached form a 3- to 10-membered saturated heterocycle.

11. The compound of formula I, its pharmaceutically acceptable salt, its solvate or the solvate of its pharmaceutically acceptable salt according to any one of claims 1-4, characterized in that, R 2 is hydrogen, C3-C 10 cycloalkyl, C3-C 2a cycloalkyl substituted with one or more R 10 4-10 membered heterocycloalkyl or 4-10 membered heterocycloalkyl substituted with one or more R 2c , where each R 2a is independently (4-10 membered heterocycloalkyl)-CH2-, and each R 2c is independently halogen or C1-C4 alkyl; preferably, each R 2 is hydrogen, C3-C 2a cycloalkyl substituted with one or more R 10 or 4-10 membered heterocycloalkyl substituted with one or more R 2c , where each R 2a is independently (4-10 membered heterocycloalkyl)-CH2-, and each R 2c is independently halogen or C1-C4 alkyl.

12. The heterocyclic compound represented by Formula I, its pharmaceutically acceptable salt, its solvate or solvate of its pharmaceutically acceptable salt according to any one of claims 1-4, characterized in that, It satisfies one or more of the following conditions: (1)X is independently -C(R 7 )2-, -CR 7 =CR 7 -, -N=N- and -CR 7 =N-, R 7 is independently hydrogen, n is 1, 2 or 3; preferably, when n is 2 or 3, X is independently a -C(R 7 )2-, when n is 1, X is a -CR 7 =CR 7 (20), a -N=N-, a -CR 7 =N- or a -N=CR 7 (30), R 7 is independently hydrogen, wherein the a side is connected to is connected to the N atom therein; more preferably, when n is 2 or 3, X is independently a -C(R 7 )2-, when n is 1, X is a -CR 7 =CR 7 -, a -N=N- and a -CR 7 =N-, wherein the a side is connected to is connected to the N atom therein, R 7 is independently hydrogen; (2) L is -O-(CR 9 R 9 ) n1 -, -S-(CR 9 R 9 ) n2 - or -N(R 8 )-(CR 9 R 9 ) n3 -, R 8 is independently hydrogen, R 9 is independently hydrogen, n1, n2 and n3 are each independently 0 or 1; preferably, L is -O-(CR 9 R 9 ) n1 -, R 9 is independently hydrogen, n1 is 0 or 1; (3)R 2 is hydrogen, C3-C 10 cycloalkyl, C3-C 2a substituted by one or more R 10 cycloalkyl, 4-10 membered heterocycloalkyl or 4-10 membered heterocycloalkyl substituted by one or more R 2c , R 2a independently is (4-10 membered heterocycloalkyl)-CH2-, R 2c independently is halogen; Preferably, R 2 is hydrogen, C3-C 2a cycloalkyl substituted by one or more R 10 or 4- to 10-membered heterocycloalkyl substituted by one or more R 2c , where R 2a is independently (4- to 10-membered heterocycloalkyl)-CH2-, and R 2c is independently halogen; (4)R 1 is a 5- to 10-membered heteroaryl or a 5- to 10-membered heteroaryl substituted by one or more R 1b , where R 1b is independently halogen, -OH, C1-C6 alkyl, -N(R 8 )2 or C1-C6 alkyl substituted by one or more R 1-a , where R 1-a is independently halogen, and R 8 is hydrogen; Preferably, R 1 is a 5- to 10-membered heteroaryl group substituted by one or more R 1b ; R 1b is independently C1-C6 alkyl, -N(R 8 )2 or C1-C6 alkyl substituted by one or more R 1-a ; R 1-a is independently halogen; R 8 is hydrogen; (5)R 4 independently is hydrogen, C1-C6 alkyl, C3-C 10 cycloalkyl, 3-10 membered heterocycloalkyl, C1-C6 alkyl substituted with one or more R 4a , C3-C 4b cycloalkyl substituted with one or more R 10 or 3-10 membered heterocycloalkyl substituted with one or more R 4c , where R 4a independently is -N(R 8 )2, -C(O)N(R 10 )2, C3-C 10 cycloalkyl, 3-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-C 4-b cycloalkyl substituted with one or more R 10 , 3-10 membered heterocycloalkyl substituted with one or more R 4-c or 5-10 membered heteroaryl substituted with one or more R 4-e , where R 4-b and R 4-c each independently is -C(O)N(R 10 )2, R 4-e independently is -N(R 8 )2, R 4b and R 4c each independently is -C(O)N(R 10 )2, R 8 and R 10 each independently represents hydrogen or a C1-C6 alkyl group; Preferably, R 4 is independently hydrogen, C1-C6 alkyl, 3-10 membered heterocycloalkyl, C1-C6 alkyl substituted with one or more R 4a or C3-C 4b cycloalkyl substituted with one or more R 10 , where R 4a is independently -N(R 8 )2, -C(O)N(R 10 )2, C3-C 10 cycloalkyl, C3-C 4-b cycloalkyl substituted with one or more R 10 , 3-10 membered heterocycloalkyl, 3-10 membered heterocycloalkyl substituted with one or more R 4-c or 5-10 membered heteroaryl substituted with one or more R 4-e , where R 4-b and R 4-c are each independently -C(O)N(R 10 )2, where R 4-e is independently -N(R 8 )2, where R 4b is independently -C(O)N(R 10 )2, where R 8 is independently hydrogen or C1-C6 alkyl, and where R 10 is independently hydrogen; (6)R 5 is hydrogen, 3- to 10-membered heteroalkyl, C1-C6 alkyl, C1-C6 alkyl substituted with one or more R 5a or 3- to 10-membered heteroalkyl substituted with one or more R 5b , where R 5a is -OH and R 5b is =O; Preferably, R 5 is hydrogen, C1-C6 alkyl substituted by one or more R 5a groups, or 3-10 membered heteroalkyl substituted by one or more R 5b groups, R 5a is -OH, R 5b is =O; preferably, R 5 is hydrogen or C1-C6 alkyl substituted by one or more R 5a groups, R 5a is -OH; preferably, R 5 is hydrogen; (7)R 4 and R 5 may also form, together with the atoms to which it is attached, a 3- to 10-membered saturated heterocycle or a 3- to 10-membered saturated heterocycle substituted with one or more R 4h groups, where R 4h is independently -OH, -N(R 8 )2, C1-C6 alkyl or C1-C6 alkyl substituted with one or more R 4-h groups, where R 4-h is independently -N(R 8 )2, and R 8 is independently hydrogen or C1-C6 alkyl; Preferably, R 4 and R 5 may also together with the atoms to which they are attached form a 3- to 10-membered saturated heterocycle substituted by one or more R 4h groups, where R 4h is independently -OH, -N(R 8 )2, C1-C6 alkyl or C1-C6 alkyl substituted by one or more R 4-h groups, and R 4-h is independently -N(R 8 )2, and R 8 is independently hydrogen or C1-C6 alkyl; (8)R 6 is hydrogen; (9)R 3 is hydrogen, -N(R 8 )2, halogen, -OH, and R 8 is hydrogen; preferably, R 3 is halogen; (10) Y is -NR 4 -, O or S; preferably, Y is -NR 4 - or O.

13. The heterocyclic compound represented by Formula I, its pharmaceutically acceptable salt, its solvate or the solvate of its pharmaceutically acceptable salt according to any one of claims 1-3, characterized in that, It satisfies one or more of the following conditions: (1) X is independently -C(R 7 )2-, -CR 7 =CR 7 -, or a -N=CR 7 (-), n is 1, 2 or 3, R 7 is independently hydrogen or C1-C6 alkyl, wherein the a side is connected to connected to the N atom in; Preferably, X is independently -C(R 7 )2-, n is 2 or 3, or X is independently -CR 7 =CR 7 - or a -N=CR 7 -, n is 1, R 7 is independently hydrogen or C1-C6 alkyl, wherein the a side is connected to connected to the N atom in; (2)R 1 is C6-C 1a aryl substituted by one or more R 10 or 5- to 10-membered heteroaryl substituted by one or more R 1b , where R 1a is independently halogen, -OH or -N(R 8 )2, R 8 is hydrogen, and R 1b is independently halogen, -CN, C1-C6 alkyl, -N(R 8 )2 or substituted by one or more R 1-a Substituted C1-C6 alkyl, R 1-a Independently is halogen; (3)R 2 is a 4- to 10-membered heterocycloalkyl group, a C3-C 2a cycloalkyl group substituted by one or more R 10 or a 4- to 10-membered heterocycloalkyl group substituted by one or more R 2c ; R 2a is independently (4- to 10-membered heterocycloalkyl)-CH2-, and the 4- to 10-membered heterocycloalkyl in the (4- to 10-membered heterocycloalkyl)-CH2- is optionally substituted by C l -C6 alkyl; R 2c is independently halogen, C1-C4 alkyl or (C l -C4 alkyl)-O-(C l -C4 alkyl)-; (4)R 4 and R 5 may also together with the atoms to which they are attached form a 3- to 10-membered saturated heterocycle or two R 4h substituted 3- to 10-membered saturated heterocycles, two R 4h being adjacent, and the two R 4h together with the atoms to which they are attached form a 5- to 10-membered heteroaromatic ring.

14. The heterocyclic compound represented by Formula I, a pharmaceutically acceptable salt thereof, a solvate thereof, or a solvate of a pharmaceutically acceptable salt thereof according to any one of claims 1-4, characterized in that, It satisfies one or more of the following conditions: (1) X is independently -C(R 7 )2-, -CR 7 =CR 7 -, or a -N=CR 7 (where) n is 1, 2 or 3, and R 7 is independently hydrogen, and the a side is connected to connected to the N atom in; Preferably, X is independently -C(R 7 )2-, n is 2 or 3, or X is independently -CR 7 =CR 7 - or a -N=CR 7 -, n is 1, R 7 is hydrogen, wherein the a side is connected to connected to the N atom in; (2)R 2 is a 4- to 10-membered heterocycloalkyl group substituted by one or more R 2c ; R 2c is independently halogen or C1-C4 alkyl; (3)R 4 independently is hydrogen or C1-C6 alkyl substituted by one or more R 4a groups; R 4a independently C3-C 10 cycloalkyl, 3- to 10-membered heteroalkyl, C3-C 4-b cycloalkyl substituted with one or more R 10 or 5- to 10-membered heteroaryl substituted with one or more R 4-e ; preferably, R 4a is independently C3-C 4-b cycloalkyl substituted with one or more R 10 or 5- to 10-membered heteroaryl substituted with one or more R 4-e ; R 4-b independently -C(O)N(R 10 )2; R 4-e independently -N(R 8 )2; R 8 independently hydrogen; R 10 independently hydrogen; (4)R 5 is hydrogen or a C1-C6 alkyl group substituted by one or more R 5a groups, where R 5a is independently -OH; (5)R 4 and R 5 may also together with the atoms to which it is attached form a 3- to 10-membered saturated heterocycle.

15. The heterocyclic compound represented by Formula I, its pharmaceutically acceptable salt, its solvate or the solvate of its pharmaceutically acceptable salt according to any one of claims 1-3, characterized in that The heterocyclic compound represented by Formula I satisfies any of the following schemes: Scheme 1: When n is 2 or 3, X is independently a -C(R 7 )2-, when n is 1, X is a -CR 7 =CR 7 -、 a -N=N-、 a -CR 7 =N- or a -N=CR 7 -, where side a is connected to connected to the N atom in; R 7 independently hydrogen or a C1-C6 alkyl group; L is -O-(CR 9 R 9 ) n1 - b , where the b side is connected to R 2 ; R 9 independently hydrogen or a C1-C6 alkyl group; n1 is 0 or 1; R 2 is hydrogen, a 4- to 10-membered heterocycloalkyl group, a C3-C 2a cycloalkyl group substituted by one or more R 10 groups, or a 4- to 10-membered heterocycloalkyl group substituted by one or more R 2c groups; R 2a independently being (4- to 10-membered heterocycloalkyl)-CH2-, wherein the 4- to 10-membered heterocycloalkyl in the (4- to 10-membered heterocycloalkyl)-CH2- is optionally substituted with C l -C6 alkyl; R 2c Independently a halogen, C1-C4 alkyl, =CR 2-c R 2-c , C1-C4 alkyl-O-, -N(R 8 )2 or (C l -C4 alkyl)-O-(C l -C4 alkyl)-; R 8 independently H or C1-C6 alkyl; R 2-c independently being halogen; R 1 C6-C aryl, 5-10-membered heteroaryl or 3-10-membered heterocycloalkyl substituted by one or more R 1a substituted by one or more R 10 substituted by one or more R 1b substituted by one or more R 1c ; R 1a independently a halogen, -OH or -N(R 8 )2; R 1b independently a halogen, -CN, -OH, C1-C6 alkyl, -N(R 8 )2 or C1-C6 alkyl substituted with one or more R 1-a ; R 1-a independently is halogen; R 1c independently a C1-C6 alkyl group; or two adjacent Rs 1c together with the atoms to which they are attached form a 5- to 10-membered heteroaryl ring, which 5- to 10-membered heteroaryl ring is optionally substituted by one or more of the following groups: -CN or -N(R 8 )2; R 3 is a halogen; Y is -NR 4 -, O or c -(CH2) p NR 4 -, p is 1, and the c side is connected to -CHR 5 -; R 4 is hydrogen, C1-C6 alkyl, 3-10 membered heteroalkyl, -SO2R h , C1-C6 alkyl substituted with one or more R 4a , C3-C 4b cycloalkyl substituted with one or more R 10 or 5-10 membered heteroaryl substituted with one or more R 4e ; R h independently a 5- to 10-membered heteroaryl or a 5- to 10-membered heteroaryl substituted with one or more R 4-e substituents; R 4a independently =O, -N(R 8 )2, -C(O)N(R 10 )2, C3-C 10 cycloalkyl, 3- to 10-membered heterocycloalkyl, C3-C 4-b cycloalkyl substituted with one or more R 10 , 3- to 10-membered heterocycloalkyl substituted with one or more R 4-c , 5- to 10-membered heteroaryl substituted with one or more R 4-e or 3- to 10-membered heterocycloalkenyl substituted with one or more R 4-d ; R 4-b and R 4-c each independently is -C(O)N(R 10 )2; R 4-e independently -N(R 8 )2; R 4-d independently =O; R 4b independently -C(O)N(R 10 )2; R 4e independently a 5- to 10-membered heteroaryl group substituted by one or more R 4-e substituents; R 10 independently hydrogen; R 5 is hydrogen, C1-C6 alkyl substituted by one or more R 5a or 3-10 membered heteroalkyl substituted by one or more R 5b ; R 5a is —OH; R 5b is = O; R 4 and R 5 may also form, together with the atoms to which it is attached, a 3- to 10-membered saturated heterocycle, a 3- to 10-membered saturated heterocycle substituted with one or more R 4h groups, or a 5- to 10-membered heteroaryl ring substituted with one or more R 4j groups; R 4h independently -OH, -N(R 8 )2, C1-C6 alkyl or C1-C6 alkyl substituted by one or more R 4-h substituents; or two adjacent Rs 4h together with the atoms to which they are attached form a 5- to 10-membered heteroaryl ring; R 4-h independently -N(R 8 )2; R 4j independently -C(O)N(R 10 )2; R 6 is hydrogen; Scheme 2: X is -C(R 7 )2-, n is 2 or 3, or, X is -CR 7 =CR 7 - or a -N=CR 7 -, n is 1, where the a side is connected to connected to the N atom in; R 7 independently hydrogen or a C1-C6 alkyl group; L is -O- b , -O-CH2- b or -O-CH(CH3)- b , where the b side is connected to R 2 ; R 2 is a 4- to 10-membered heterocycloalkyl group, a C3-C 2a cycloalkyl group substituted with one or more R 10 groups, or a 4- to 10-membered heterocycloalkyl group substituted with one or more R 2c groups; R 2a independently (4- to 10-membered heterocycloalkyl)-CH2-, wherein the 4- to 10-membered heterocycloalkyl in the (4- to 10-membered heterocycloalkyl)-CH2- is optionally substituted with C l -C6 alkyl; R 2c independently is halogen, C1-C4 alkyl or (C l -C4 alkyl)-O-(C l -C4 alkyl)-; R 1 is C6-C 1a aryl substituted by one or more R 10 or 5- to 10-membered heteroaryl substituted by one or more R 1b ; R 1a independently a halogen, -OH or -N(R 8 )2; R 1b independently being halogen, -CN, C1-C6 alkyl, -N(R 8 )2 or C1-C6 alkyl substituted with one or more R 1-a ; R 1-a independently being a halogen; R 3 is a halogen; Y is -NR 4 -, O or c -(CH2) p NR 4 -, p is 1, and the c side is connected to -CHR 5 -; R 4 independently hydrogen or C1-C6 alkyl substituted with one or more R 4a groups; R 4a independently C3-C 10 cycloalkyl, 3- to 10-membered heterocycloalkyl, C3-C 4-b substituted by one or more R 10 cycloalkyl or by one One or more R 4-e Substituted 5- to 10-membered heteroaryl; preferably, R 4a Independently is C3-C 4-b Cycloalkyl substituted by one or more R 10 Or 5- to 10-membered heteroaryl substituted by one or more R 4-e ; R 4-b independently -C(O)N(R 10 )2; R 4-e independently -N(R 8 )2; R 8 independently hydrogen; R 10 independently hydrogen; R 5 is hydrogen or a C1-C6 alkyl group substituted by one or more R 5a groups, where R 5a is independently -OH; Alternatively, R 4 and R 5 may also form, together with the atoms to which it is attached, a 3- to 10-membered saturated heterocycle or two R 4h substituted 3- to 10-membered saturated heterocycles, where the two R 4h are adjacent, and the two R 4h and the atoms to which they are attached together form a 5- to 10-membered heteroaromatic ring; R 6 is hydrogen; Scheme 3: When n is 2 or 3, X is independently a -C(R 7 )2-, when n is 1, X is a -CR 7 =CR 7 -, a -N=N-, a -CR 7 =N- or a -N=CR 7 -, where the a side is connected to connected to the N atom in; R 7 independently is hydrogen or a C1-C6 alkyl group; L and R 2 is defined to satisfy one of the following cases: Case (1): L is -O-(CR 9 R 9 ) n1 - b , where the b side is connected to R 2 ; R 9 independently hydrogen or a C1-C6 alkyl group; n1 is 0 or 1; R 2 is hydrogen, a 4- to 10-membered heterocycloalkyl group, a C3-C 2a cycloalkyl group substituted by one or more R 10 groups, or a 4- to 10-membered heterocycloalkyl group substituted by one or more R 2c groups; R 2a independently being (4- to 10-membered heterocycloalkyl)-CH2-, wherein the 4- to 10-membered heterocycloalkyl in the (4- to 10-membered heterocycloalkyl)-CH2- is optionally substituted with C l -C6 alkyl; R 2c Independently a halogen, C1-C4 alkyl, =CR 2-c R 2-c , C1-C4 alkyl-O-, -N(R 8 )2 or (C l -C4 alkyl)-O-(C l -C4 alkyl)-; R 2-c independently is a halogen; Case (2): L does not exist; R 2 is a 4- to 10-membered heterocycloalkyl group substituted by one or more R 2c ; R 2c is independently C1-C4 alkyl or 4- to 10-membered heterocycloalkyl; R 1 is C6-C 1a aryl substituted by one or more R 10 , 5-10 membered heteroaryl substituted by one or more R 1b or 3-10 membered heterocycloalkyl substituted by one or more R 1c ; R 1a independently is halogen, -OH or -N(R 8 )2; R 1b independently a halogen, -CN, -OH, C1-C6 alkyl, -N(R 8 )2 or C1-C6 alkyl substituted with one or more R 1-a ; R 1-a independently is a halogen; R 1c independently C1-C6 alkyl; or two adjacent Rs 1c together with the atoms to which they are attached form a 5- to 10-membered heteroaryl ring, said 5- to 10-membered heteroaryl ring being optionally substituted by one or more of the following groups: -CN or -N(R 8 )2; R 3 is a halogen; Y is -NR 4 -, O or c -(CH2) p NR 4 -, p is 1, the c side is connected to -CHR 5 -; R 4 is hydrogen, C1-C6 alkyl, 3-10 membered heteroalkyl, -SO2R h , C1-C6 alkyl substituted by one or more R 4a , C3-C 4b cycloalkyl substituted by one or more R 10 , 5-10 membered heteroaryl substituted by one or more R 4e or 5-10 membered heteroaryl fused to 3-10 membered heteroalkyl substituted by one or more R 4k ; R h independently a 5- to 10-membered heteroaryl, a 3- to 10-membered heterocycloalkenyl substituted with one or more R 4-d or a 5- to 10-membered heteroaryl substituted with one or more R 4-e ; R 4a independently =O, -N(R 8 )2, -OR 10 , 5-10 membered heteroaryl, -C(O)N(R 10 )2, C3-C 10 cycloalkyl, 3-10 membered heterocycloalkyl, carboxyl, C3-C 4-b cycloalkyl substituted with one or more R 10 , 3-10 membered heterocycloalkyl substituted with one or more R 4-c , 5-10 membered heteroaryl substituted with one or more R 4-e or 3-10 membered heterocycloalkenyl substituted with one or more R 4-d ; R 4k independently =O or -N(R 8 )2; R 4-b and R 4-c each independently is -C(O)N(R 10 )2; R 4-e independently -N(R 8 )2, halogen, C1-C6 alkyl, -OR 10 , -C(O)N(R 10 )2 or C1-C6 alkyl substituted with one or more R 4-a-1 ; R 4-d independently =O or -N(R 8 )2; R 4b independently -C(O)N(R 10 )2; R 4e independently a 5- to 10-membered heteroaryl group substituted by one or more R 4-e groups; R 8 independently H or a C1-C6 alkyl group; R 10 independently is hydrogen or a C1-C6 alkyl group; R 4-a-1 independently -OH or -N(R 8 )2; R 5 is hydrogen, a C1-C6 alkyl group substituted by one or more R 5a groups, or a 3-10 membered heterocycloalkyl group substituted by one or more R 5b groups; R 5a is -OH; R 5b is = O; R 4 and R 5 may also together with the atoms to which it is attached form a 3- to 10-membered saturated heterocycle, a 3- to 10-membered saturated heterocycle substituted with one or more R 4h or a 5- to 10-membered heteroaromatic ring substituted with one or more R 4j ; R 4h independently -OH, -N(R 8 )2, C1-C6 alkyl or C1-C6 alkyl substituted by one or more R 4-h ; or two adjacent R 4h together with the atoms to which they are attached form a 5- to 10-membered heteroaryl ring; R 4-h independently -N(R 8 )2; R 4j independently -C(O)N(R 10 )2; R 6 is hydrogen; Scheme 4: When n is 2 or 3, X is independently a -C(R 7 )2-, when n is 1, X is a -CR 7 =CR 7 - or a -N=CR 7 -, where the a side is connected to connected to the N atom in; R 7 independently hydrogen or C1-C6 alkyl; L and R 2 is defined to satisfy one of the following cases: Case (1): L is -O-(CR 9 R 9 ) n1 - b , where the b side is connected to R 2 ; R 9 independently hydrogen or a C1-C6 alkyl group; n1 is 0 or 1; R 2 is a 4- to 10-membered heterocycloalkyl group, a C3-C 2a cycloalkyl group substituted by one or more R 10 groups, or a 4- to 10-membered heterocycloalkyl group substituted by one or more R 2c groups; R 2a independently being (4-10-membered heterocycloalkyl)-CH2-, wherein the 4-10-membered heterocycloalkyl in the (4-10-membered heterocycloalkyl)-CH2- is optionally substituted by C l -C6 alkyl; R 2c independently a halogen, C1-C4 alkyl, C1-C4 alkoxy, -N(R 8 )2 or (C l -C4 alkyl)-O-(C l -C4 alkyl)-; Case (2): L does not exist; R 2 is a 4- to 10-membered heterocycloalkyl group substituted by one or more R 2c ; R 2c is independently a C1-C4 alkyl group or a 4- to 10-membered heterocycloalkyl group; R 1 substituted by one or more R 1a substituted C6-C 10 aryl or substituted by one or more R 1b substituted 5- to 10-membered heteroaryl; R 1a independently is halogen, -OH or -N(R 8 )2; R 1b independently is halogen, -CN, C1-C6 alkyl, -N(R 8 )2 or C1-C6 alkyl substituted by one or more R 1-a ; R 1-a each independently being a halogen; R 3 is a halogen; Y is -NR 4 -, O or c -(CH2) p NR 4 -, p is 1, and the c side is connected to -CHR 5 -; R 4 independently hydrogen, -SO2R h or C1-C6 alkyl substituted by one or more R 4a groups; R h independently a 3- to 10-membered heteroalkenyl group substituted by one or more R 4-d or a 5- to 10-membered heteroaryl group substituted by one or more R 4-e ; R 4a independently =O, -OR 10 , 5-10-membered heteroaryl, C3-C 4-b substituted by one or more R 10 cycloalkyl, 5-10-membered heteroaryl substituted by one or more R 4-e or 3-10-membered heterocycloalkenyl substituted by one or more R 4-d ; R 4-b independently -C(O)N(R 10 )2; R 4-e independently -N(R 8 )2, halogen, -OR 10 , -C(O)N(R 10 )2 or C1-C6 alkyl substituted with one or more R 4-a-1 ; R 4-d independently =O or -N(R 8 )2; R 8 independently hydrogen; R 10 independently hydrogen or a C1-C6 alkyl group; R 4-a-1 independently -OH or -N(R 8 )2; R 5 is hydrogen or a C1-C6 alkyl group substituted by one or more R 5a groups; R 5a is -OH; R 4 and R 5 may also together with the atoms to which they are attached form a 3- to 10-membered saturated heterocycle or a 3- to 10-membered saturated heterocycle substituted by one or more R 4h ; two adjacent R 4h together with the atoms to which they are attached form a 5- to 10-membered heteroaromatic ring; R 6 is hydrogen; Scheme 5: When n is 2 or 3, X is independently a -C(R 7 )2-, when n is 1, X is a -CR 7 =CR 7 -, a -N=N-, a -CR 7 =N- or a -N=CR 7 -, where the a side is connected to connected to the N atom in; R 7 independently hydrogen or a C1-C6 alkyl group; L and R 2 is defined to satisfy one of the following cases: Case (1): L is -O-(CR 9 R 9 ) n1 - b , where the b side is connected to R 2 ; R 9 independently hydrogen or a C1-C6 alkyl group; n1 is 0 or 1; R 2 is hydrogen, a 4- to 10-membered heterocycloalkyl group, a C3-C 2a cycloalkyl group substituted by one or more R 10 groups, or a 4- to 10-membered heterocycloalkyl group substituted by one or more R 2c groups; R 2a independently being (4- to 10-membered heterocycloalkyl)-CH2-, wherein the 4- to 10-membered heterocycloalkyl in the (4- to 10-membered heterocycloalkyl)-CH2- is optionally substituted with C l -C6 alkyl; R 2c Independently a halogen, C1-C4 alkyl, =CR 2-c R 2-c , C1-C4 alkyl-O-, -N(R 8 )2 or (C l -C4 alkyl)-O-(C l -C4 alkyl)-; R 2-c independently being halogen; Case (2): L does not exist; R 2 is a 4- to 10-membered heterocycloalkyl group substituted by one or more R 2c ; R 2c is independently a C1-C4 alkyl group or a 4- to 10-membered heterocycloalkyl group; R 1 is C6-C 1a aryl substituted by one or more R 10 , 5- to 10-membered heteroaryl substituted by one or more R 1b or 3- to 10-membered heterocycloalkyl substituted by one or more R 1c ; R 1a independently is halogen, -OH or -N(R 8 )2; R 1b independently being halogen, -CN, -OH, C1-C6 alkyl, -N(R 8 )2 or C1-C6 alkyl substituted by one or more R 1-a ; R 1-a independently being halogen; R 1c independently C1-C6 alkyl; or two adjacent Rs 1c together with the atoms to which they are attached form a 5- to 10-membered heteroaryl ring, said 5- to 10-membered heteroaryl ring being optionally substituted by one or more of the following groups: -CN or -N(R 8 )2; R 3 is a halogen; Y is -NR 4 -, O or c -(CH2) p NR 4 -, p is 1, and the c side is connected to -CHR 5 -; R 4 is hydrogen, C1-C6 alkyl, 3-10 membered heteroalkyl, -SO2R h , C1-C6 alkyl substituted by one or more R 4a , C3-C 4b cycloalkyl substituted by one or more R 10 , 5-10 membered heteroaryl substituted by one or more R 4e or 5-10 membered heteroaryl fused to 3-10 membered heteroalkyl substituted by one or more R 4k ; R h independently a 5- to 10-membered heteroaryl, a 3- to 10-membered heteroalkenyl substituted with one or more R 4-d or a 5- to 10-membered heteroaryl substituted with one or more R 4-e ; R 4a independently =O, -N(R 8 )2, -OR 10 , -C(O)OR 10 , 5-10 membered heteroaryl, -C(O)N(R 10 )2, C3-C 10 cycloalkyl, 3- to 10-membered heterocycloalkyl, carboxyl, C6-C 10 aryl, C3-C 4-b cycloalkyl substituted with one or more R 10 3- to 10-membered heterocycloalkyl substituted with one or more R 4-c 5- to 10-membered heteroaryl substituted with one or more R or 3- to 10-membered heterocycloalkenyl substituted with one or more R; 4-e 4-d ​​ R 4-i each independently is hydrogen or a C1-C6 alkyl group; R 4-b and R 4-c each independently is -C(O)N(R 10 )2; R 4-e independently -N(R 8 )2, halogen, C1-C6 alkyl, -OR 10 , -C(O)N(R 10 )2, -C(O)R 10 or C1-C6 alkyl substituted by one or more R 4-a-1 ; R 4-d Independently =O or -N(R 8 )2; R 4b independently -C(O)N(R 10 )2; R 4e independently a 5- to 10-membered heteroaryl group substituted by one or more R 4-e groups; R 4k independently =O or -N(R 8 )2; R 8 independently hydrogen, C1-C6 alkyl or -C(O)R 10 ; R 10 independently hydrogen, C1-C6 alkyl or 3-10 membered heterocycloalkyl; R 4-a-1 independently -OH or -N(R 8 )2; R 5 is hydrogen, C1-C6 alkyl substituted by one or more R 5a groups, or 3-10 membered heteroalkyl substituted by one or more R 5b groups; R 5a is -OH; R 5b is = O; R 4 and R 5 may also together with the atoms to which it is attached form a 3- to 10-membered saturated heterocycle, a 3- to 10-membered saturated heterocycle substituted with one or more R 4h or a 5- to 10-membered heteroaryl ring substituted with one or more R 4j ; R 4h independently -OH, -N(R 8 )2, C1-C6 alkyl or C1-C6 alkyl substituted by one or more R 4-h ; or two adjacent Rs 4h together with the atoms to which they are attached form a 5- to 10-membered heteroaryl ring; R 4-h independently -N(R 8 )2; R 4j independently -C(O)N(R 10 )2; R 6 is hydrogen; Scheme 6: When n is 2 or 3, X is independently a -C(R 7 )2-, when n is 1, X is a -CR 7 =CR 7 - or a -N=CR 7 -, where the a side is connected to connected to the N atom in; R 7 independently hydrogen or a C1-C6 alkyl group; L and R 2 is defined to satisfy one of the following cases: Case (1): L is -O-(CR 9 R 9 ) n1 - b , where the b side is connected to R 2 ; R 9 independently hydrogen or a C1-C6 alkyl group; n1 is 0 or 1; R 2 is a 4- to 10-membered heterocycloalkyl group, a C3-C 2a cycloalkyl group substituted by one or more R 10 groups, or a 4- to 10-membered heterocycloalkyl group substituted by one or more R 2c groups; R 2a independently being (4- to 10-membered heterocycloalkyl)-CH2-, wherein the 4- to 10-membered heterocycloalkyl in the (4- to 10-membered heterocycloalkyl)-CH2- is optionally substituted by C l -C6 alkyl; R 2c Independently halogen, =CR 2-c R 2-c , C1-C4 alkyl, C1-C4 alkyl-O-, -N(R 8 )2 or (C l -C4 alkyl)-O-(C l -C4 alkyl)-; R 2-c independently being halogen; Case (2): L does not exist; R 2 is a 4- to 10-membered heterocycloalkyl group substituted by one or more R 2c ; R 2c is independently a C1-C4 alkyl group or a 4- to 10-membered heterocycloalkyl group; R 1 C6-C aryl substituted by one or more R 1a or 5- to 10-membered heteroaryl substituted by one or more R 10 1b ;​ R 1a independently is halogen, -OH or -N(R 8 )2; R 1b independently is halogen, -CN, C1-C6 alkyl, -N(R 8 )2 or C1-C6 alkyl substituted by one or more R 1-a ; R 1-a independently is halogen; R 3 is a halogen; Y is -NR 4 -, O or c -(CH2) p NR 4 -, p is 1, and the c side is connected to -CHR 5 -; R 4 independently hydrogen, -SO2R h , C1-C6 alkyl substituted by one or more R 4a or 5-10-membered heteroaryl fused to a 3-10-membered heterocycloalkyl and substituted by one or more R 4k ; R h independently a 3- to 10-membered heteroalkenyl group substituted by one or more R 4-d or a 5- to 10-membered heteroaryl group substituted by one or more R 4-e ; R 4a independently =O, -OR 10 , -C(O)OR 10 , C3-C 10 cycloalkyl, 3- to 10-membered hetero Cycloalkyl, 5- to 10-membered heteroaryl, C6-C 10 aryl, carboxyl, C3-C substituted with one or more R 4-b 10 cycloalkyl, 5- to 10-membered heteroaryl substituted with one or more R 4-e or 3- to 10-membered heteroalkenyl substituted with one or more R; 4-d ​​ R 4-i each independently is hydrogen or a C1-C6 alkyl group; R 4-b independently -C(O)N(R 10 )2; R 4-e independently -N(R 8 )2, halogen, -OR 10 , -C(O)N(R 10 )2, -C(O)R 10 or C1-C6 alkyl substituted by one or more R 4-a-1 ; R 4-d independently =O or -N(R 8 )2; R 4k independently = O; R 8 independently hydrogen or -C(O)R 10 ; R 10 independently hydrogen, C1-C6 alkyl or 3-10 membered heterocycloalkyl; R 4-a-1 independently -OH or -N(R 8 )2; R 5 is hydrogen or a C1-C6 alkyl group substituted by one or more R 5a groups; R 5a is -OH; R 4 and R 5 may also form, together with the atoms to which they are attached, a 3- to 10-membered saturated heterocycle or a 3- to 10-membered saturated heterocycle substituted by one or more R 4h adjacent two Rs 4h together with the atoms to which they are attached form a 5- to 10-membered heteroaromatic ring; R 6 is hydrogen.

16. The heterocyclic compound represented by Formula I according to any one of claims 1-12, its pharmaceutically acceptable salt, its solvate or its solvate of a pharmaceutically acceptable salt, characterized in that: When n is 2 or 3, X is independently a -C(R 7 )2-, when n is 1, X is a -CR 7 =CR 7 -, a -N=N- and a -CR 7 =N-, where the a side is in contact with connected to the N atom in; R 7 independently hydrogen; L is -O-(CR 9 R 9 ) n1 - b , where the b side is connected to R 2 ; R 9 independently hydrogen; n1 is 0 or 1; R 2 is hydrogen, C3-C 2a cycloalkyl substituted by one or more R 10 or 4-10-membered heterocycloalkyl substituted by one or more R 2c ; R 2a independently (4-10-membered heterocycloalkyl)-CH2-; R 2c independently is a halogen; R 1 a 5- to 10-membered heteroaryl group substituted by one or more R 1b groups; R 1b independently a C1-C6 alkyl group, -N(R 8 )2 or a C1-C6 alkyl group substituted with one or more R 1-a substituents; R 8 independently hydrogen or a C1-C6 alkyl group; R 1-a independently being halogen; R 3 is a halogen; Y is -NR 4 - or O; R 4 is hydrogen, C1-C6 alkyl, 3-10 membered heterocycloalkyl, C1-C6 alkyl substituted with one or more R 4a or C3-C 4b cycloalkyl substituted with one or more R 10 ; R 4a independently -N(R 8 )2, -C(O)N(R 10 )2, C3-C 10 cycloalkyl, 3-10 membered heteroalkyl, C3-C 4-b substituted by one or more R 10 cycloalkyl, 3-10 membered heteroalkyl substituted by one or more R 4-c or 5-10 membered heteroaryl substituted by one or more R 4-e ; R 4b independently -C(O)N(R 10 )2; R 4-b independently -C(O)N(R 10 )2; R 4-c independently -C(O)N(R 10 )2; R 4-e independently -N(R 8 )2; R 10 independently hydrogen; R 5 is hydrogen, C1-C6 alkyl substituted by one or more R 5a or 3-10 membered heteroalkyl substituted by one or more R 5b ; R 5a is -OH; R 5b is = O; R 4 and R 5 may also together with the atoms to which it is attached form a 3- to 10-membered saturated heterocycle substituted by one or more R 4h groups; R 4h independently -OH, -N(R 8 )2, C1-C6 alkyl or C1-C6 alkyl substituted by one or more R 4-h substituents; R 4-h independently -N(R 8 )2; R 6 is hydrogen.

17. The heterocyclic compound represented by Formula I according to any one of claims 1-12, its pharmaceutically acceptable salt, its solvate or its solvate of a pharmaceutically acceptable salt, characterized in that: X is -C(R 7 )2- or -CR 7 =CR 7 -, n is 1, 2 or 3, R 7 is hydrogen; Preferably, X is -CR 7 =CR 7 -, n is 1, R 7 is hydrogen; L is -O-CH2-; R 2 is a 4- to 10-membered heterocycloalkyl group substituted by one or more R 2c substituents; R 2c independently being halogen; R 1 a 5- to 10-membered heteroaryl group substituted by one or more R 1b groups; R 1b independently C1-C6 alkyl, -N(R 8 )2 or C1-C6 alkyl substituted with one or more R 1-a substituents; R 8 independently hydrogen; R 1-a independently is a halogen; R 3 is a halogen; Y is -NR 4 ; R 4 is a C1-C6 alkyl group substituted by one or more R 4a groups; R 4a Independently C3-C 10 cycloalkyl, 3- to 10-membered heterocycloalkyl or 5- to 10-membered heteroaryl substituted with one or more R 4-e ; preferably, R 4a is independently 5- to 10-membered heteroaryl substituted with one or more R 4-e ; R 4-e independently -N(R 8 )2; R 5 is hydrogen; R 6 is hydrogen.

18. The heterocyclic compound represented by Formula I as described in claim 1, its pharmaceutically acceptable salt, its solvate or the solvate of its pharmaceutically acceptable salt, characterized in that, It satisfies one or more of the following conditions: (1)R 2 For Preferably, R 2 is (2)R 4 is hydrogen, -CH3, Preferably, R 4 is hydrogen, More preferably, R 4 is hydrogen, Optimally, R 4 is Alternatively, R 4 is 19. The heterocyclic compound represented by Formula I, its pharmaceutically acceptable salt, its solvate or the solvate of its pharmaceutically acceptable salt according to claim 1 or 2, characterized in that, It satisfies one or more of the following conditions: (1)-(X) n - is -CH2-CH2-, -CH2-CH2-CH2-, -CH=CH-, -N=N-, -C(CH3)=N-, or -CH=N-; preferably Good place, -(X) n - is a -CH2-CH2-、 a -CH2-CH2-CH2-、 a -CH=CH-、 a -N=N-、-C(CH3)=N- a 、 a -N=CH- or a -CH=N-, the a side is connected to is connected to the N atom therein; more preferably, (X) n - is a -CH2-CH2-CH2-, a -CH=CH-, -C(CH3)=N- a or a -N=CH-, the a side is connected to is connected to the N atom therein; optimally, -(X) n - is a -CH=CH- or a -N=CH-, wherein the a side is connected to connected to the N atom in; (2)L is absent, -O-, For example, L is absent, -O- b , where side b is connected to R 2 connected; for another example, L is non-existent or where side b is connected to R 2 and is connected; (3)R 2 is hydrogen, Preferably, R 2 is More preferably, R 2 is Optimally, R 2 is (4)R 1 For Preferably, R 1 is More preferably, R 1 is Optimally, R 1 is (5)R 4 is hydrogen, -CH3, Preferably, R 4 is hydrogen, More preferably, R 4 is hydrogen, Optimally, R 4 is Alternatively, R 4 is 20. The heterocyclic compound represented by Formula I, its pharmaceutically acceptable salt, its solvate or the solvate of its pharmaceutically acceptable salt according to any one of claims 1-3, characterized in that, It satisfies one or more of the following conditions: (1)L is -O-、 For example, -O- b , where side b is connected to R 2 connected; (2)R 2 is hydrogen, Preferably, R 2 is (3)R 1 For Preferably, R 1 is (4)R 4 is hydrogen, -CH3, Preferably, R 4 is Hydrogen (5)R 4 and R 5 may also form together with the atoms to which it is attached Preferably, R 4 and R 5 together with the atoms to which it may also be attached form 21. The heterocyclic compound represented by Formula I, its pharmaceutically acceptable salt, its solvate or the solvate of its pharmaceutically acceptable salt according to any one of claims 1-12, characterized in that, It satisfies one or more of the following conditions: (1)-(X) n - is a -CH2-CH2-, a -CH2-CH2-CH2-, a -CH=CH-, a -N=N-, a -CH=N- or a -N=CH-, the a side is connected to is connected to the N atom therein; more preferably, -(X) n - is a -CH2-CH2-, a -CH2-CH2-CH2-, a -CH=CH- or a -N=CH-, wherein the a side is connected to connected to the N atom in; (2)R 2 is hydrogen, Preferably, R 2 is (3)R 4 and R 5 may also together with the atoms to which it is attached form Preferably, R 4 and R 5 may also together with the atoms to which they are attached form 22. The heterocyclic compound represented by Formula I, a pharmaceutically acceptable salt thereof, a solvate thereof, or a solvate of a pharmaceutically acceptable salt thereof according to any one of claims 1-12, characterized in that, It satisfies one or more of the following conditions: (1)-(X) n - is -CH2-CH2-, -CH2-CH2-CH2-, -CH=CH-, -N=N- or -CH=N-; preferably, -(X) n - is a -CH2-CH2- a -CH2-CH2-CH2- a -CH=CH- a -N=N- or a -CH=N-, the a side is connected to is connected to the N atom therein; more preferably, -(X) n - is a -CH=CH-, wherein the a side is connected to connected to the N atom in; (2) L is -O-, For example, -O- b or where the b side is connected to R 2 connected; preferably, L is where side b is connected to R 2 and is connected; (3)R 2 is hydrogen, Preferably, R 2 is (4)R 1 For Preferably, R 1 is (5)R 3 is a halogen, such as F; (6) Y is -NR 4 or O; preferably Y is -NR 4 ; (7)R 4 is hydrogen, -CH3, Preferably, R 4 is hydrogen, More preferably, R 4 is (8)R 5 is hydrogen, Preferably, R 5 is hydrogen or More preferably, R 5 is hydrogen; (9)R 4 and R 5 may also together with the atoms to which it is attached form 23. The heterocyclic compound represented by Formula I, its pharmaceutically acceptable salt, its solvate or the solvate of its pharmaceutically acceptable salt according to any one of claims 1-22, characterized in that It is any of the following schemes: Scheme 1: The heterocyclic compound represented by Formula I is a compound represented by Formula I-1-1, I-1-2, I-1-3, I-1-4, I-1-5, I-1-6, I-1-7, I-1-8 or I-1-9: m is 1, 2 or 3; Preferably, in the compounds represented by Formula I-1-1, I-1-2, I-1-3, I-1-4, I-1-5, I-1-6, I-1-7, I-1-8 or I-1-9, Y is -NR 4 -; More preferably, in the compounds represented by Formula I-1-1, I-1-2, I-1-3, I-1-4, I-1-5, I-1-6, I-1-7, I-1-8 or I-1-9, Y is -NR 4 -, R 4 is a mixture of; Scheme 2: The heterocyclic compound represented by Formula I is a compound represented by Formula I-4-1, I-4-2 or I-4-3: Among them, represents a single bond or a double bond; m is 1, 2 or 3; R 4 be substituted by one or more R 4b substituted C3-C 10 cycloalkyl " of the mixture"; preferably a C3-C substituted by one or more R 4b cycloalkyl, 10 substituted by a mixture of; R 4a independently a 5- to 10-membered heteroaryl group substituted by one or more R 4-e substituted cyclopropyl group; 4-b substituted by one or more R Among them, when R 4 is a C3-C 4b cycloalkyl group substituted by one or more R 10 groups, in the C3-C 10 cycloalkyl group, the one connected to The configuration of the N-linked carbon atom is the R configuration, and the said R 4b At the C3-C 10 The configuration of the carbon atom at the attachment site on the cycloalkyl group is also the R configuration; Scheme 3: The heterocyclic compound represented by Formula I is the compound represented by Formula I-5: wherein, m is 1, 2 or 3; The carbon atom with "*" is a chiral carbon, and its configuration is the R configuration; R 4 For or a 3- to 10-membered heterocycloalkyl group, wherein the 3- to 10-membered heterocycloalkyl group is bonded to The configuration of the carbon atom connected to the N in is the R configuration; R 4a is C3-C 10 cycloalkyl or 4-membered heterocycloalkyl; R 5 C1-C6 alkyl substituted by one or more R 5a or 3- to 10-membered heterocycloalkyl substituted by one or more R 5b wherein in said 3- to 10-membered heterocycloalkyl, the one bonded to The configuration of the carbon atom connected to is the R configuration.

24. The heterocyclic compound represented by Formula I, a pharmaceutically acceptable salt thereof, a solvate thereof, or a solvate of a pharmaceutically acceptable salt thereof according to any one of claims 1-22, characterized in that, The heterocyclic compound represented by Formula I is the compound represented by Formula I-6, satisfying Scheme 1 or Scheme 2: Solution 1: L, Y, R 1 , R 2 , R 3 and R 7 are defined as described in any one of claims 1 - 22; Preferably, L and R 3 are defined as described in any one of claims 1-22, and R 7 is hydrogen, Y is -NR 4 - or c -(CH2) p NR 4 -, p is 1, the c side is connected to -CHR 5 -, R 5 is hydrogen, and R 1 , R 2 and R 4 are defined as any of the following cases: Case 1: R 1 is substituted by one or more R 1b substituted R 1b independently is halogen, -CN or -N(R 8 )2, where R 8 is hydrogen; R 2 is C3-C 2a cycloalkyl substituted by one or more R 10 or 4- to 10-membered heterocycloalkyl substituted by one or more R 2c wherein each R is independently (4- to 10-membered heterocycloalkyl)-CH2- and each R 2a is independently halogen or C1-C4 alkyl; 2c ​ R 4 is a C1-C6 alkyl group substituted by one or more R 4a ; R 4a is independently a 5-10 membered heteroaryl group substituted by one or more R 4-e ; R 4-e is independently -N(R 8 )2; Case 2: R 1 is substituted by one or more R 1b substituted R 1b independently a C1-C6 alkyl group, -N(R 8 )2 or a C1-C6 alkyl group substituted by one or more R 1-a ; R 8 is hydrogen; R 1-a is independently halogen; R 2 C3-C cycloalkyl substituted by one or more R 2a or 8-10 membered fused heterocycloalkyl substituted by one or more R 10 wherein R is independently (4-10 membered heterocycloalkyl)-CH2- 2c and R is independently halogen; 2a 2c ​​ R 4 is a C1-C6 alkyl group substituted by one or more R 4a ; R 4a is independently a 5-10 membered heteroaryl group substituted by one or more R 4-e ; R 4-e is independently -N(R 8 )2; Solution 2: L, Y, R 1 , R 2 , R 3 and R 7 are defined as described in any one of claims 1 - 22; Preferably, L and R 3 are defined as described in any one of claims 1-22, R 7 is hydrogen, Y is -NR 4 - or c -(CH2) p NR 4 -, p is 1, the c side is connected to -CHR 5 -, R 5 is hydrogen, R 1 , R 2 and R 4 are defined as any of the following cases: Case 1: R 1 is substituted by one or more R 1b substituted R 1b independently is halogen, -CN or -N(R 8 )2, where R 8 is hydrogen; R 2 is C3-C 2a cycloalkyl substituted by one or more R 10 or 4- to 10-membered heterocycloalkyl substituted by one or more R 2c wherein each R 2a is independently (4- to 10-membered heterocycloalkyl)-CH2- 2c and each R is independently halogen, C1-C4 alkyl or 4- to 10-membered heterocycloalkyl; R 4 is -SO2R h or a C1-C6 alkyl group substituted by one or more R 4a ; R 4a is independently -OR 10 or a 5-10 membered heteroaryl group substituted by one or more R 4-e ; R 4-e is independently -N(R 8 )2 or a halogen; R h is independently a 5-10 membered heteroaryl group substituted by one or more R 4-e ; R 10 is hydrogen; Case 2: R 1 is substituted by one or more R 1b substituted R 1b independently a C1-C6 alkyl group, -N(R 8 )2 or a C1-C6 alkyl group substituted by one or more R 1-a ; R 8 is hydrogen; R 1-a is independently halogen; R 2 is C3-C 2a cycloalkyl substituted by one or more R 10 or 8-10 membered fused heterocycloalkyl substituted by one or more R 2c , where R 2a is independently (4-10 membered heterocycloalkyl)-CH2-, and R 2c is independently halogen; R 4 is a C1-C6 alkyl group substituted by one or more R 4a ; R 4a is independently a 5-10 membered heteroaryl group substituted by one or more R 4-e ; R 4-e is independently -N(R 8 )2; Case 3: R 1 is substituted by one or more R 1b substituted R 1b independently is halogen, -CN or -N(R 8 )2, where R 8 is hydrogen; R 2 is a 4- to 10-membered heterocycloalkyl group substituted by one or more R 2c wherein R 2c is independently halogen; R 4 is a C1-C6 alkyl group substituted by one or more R 4a ; R 4a is independently a 5-10 membered heteroaryl group substituted by one or more R 4-e ; R 4-e is independently halogen, -N(R 8 )2 or -OR 10 ; R 10 is a C1-C6 alkyl group; Case 4: R 1 is substituted by one or more R 1b substituted R 1b independently is halogen, -CN or -N(R 8 )2, where R 8 is hydrogen; R 2 C3-C cycloalkyl substituted by one or more R 2a or 4-10 membered heterocycloalkyl substituted by one or more R 10 wherein R is independently (4-10 membered heterocycloalkyl)-CH2- 2c and R is independently halogen, =CR 2a R 2c C1-C4 alkyl or 4-10 membered heterocycloalkyl, and R is independently halogen; 2-c R 2-c 2-c ​​ R 4 is -SO2R h or a C1-C6 alkyl group substituted by one or more R 4a ; R 4a is independently -OR 10 , a 3-10 membered heteroalkyl group or a 5-10 membered heteroaryl group substituted by one or more R 4-e ; R 4-e is independently -N(R 8 )2 or a halogen; R h is independently a 5-10 membered heteroaryl group substituted by one or more R 4-e ; R 10 is hydrogen or a C1-C6 alkyl group; Case 5: R 1 is substituted by one or more R 1b substituted R 1b independently is halogen, -CN or -N(R 8 )2, where R 8 is hydrogen; R 2 is a 4- to 10-membered heterocycloalkyl group substituted by one or more R 2c , where R 2c is independently halogen or C1-C4 alkyl; R 4 is a C1-C6 alkyl group substituted by one or more R 4a ; R 4a is independently -OR 10 , a 3- to 10-membered heterocycloalkyl or a 5- to 10-membered heteroaryl substituted with one or more R 4-e , where R 4-e is independently halogen, -N(R 8 )2 or -OR 10 ; R 10 is independently hydrogen or C1-C6 alkyl; R 4-i Each independently is a C1-C6 alkyl group.

25. The heterocyclic compound represented by Formula I, its pharmaceutically acceptable salt, its solvate or its solvate of the pharmaceutically acceptable salt according to claim 1, characterized in that, The heterocyclic compound represented by Formula I is any one of the following compounds: And / or, the pharmaceutically acceptable salts of the heterocyclic compound represented by Formula I are:

26. The heterocyclic compound represented by Formula I as described in claim 1, its pharmaceutically acceptable salt, its solvate or its solvate of the pharmaceutically acceptable salt, characterized in that, The heterocyclic compound represented by Formula I is any of the following compounds: Compounds that elute first under the following conditions: The stationary phase is C18, the mobile phase is a mixture of A and B, where A is 0.1% (v / v) ammonia water, B is acetonitrile, the volume percentage of B in the mobile phase is 19%, isocratic elution, flow rate 25 mL / min; the said conditions are preferably: Column model: Prep C18 OBD TM 19 * 250 mm * 5 μM, the mobile phase is a mixture of A and B, where A is 0.1% (v / v) ammonia water, B is acetonitrile, the volume percentage of B in the mobile phase is 19%, isocratic elution, flow rate 25 mL / min; preferably, under the said conditions, the retention time of the compound eluting first is 6.42 min; Compounds eluting after the following conditions: the stationary phase is C18, the mobile phase is a mixture of A and B, where A is 0.1% (v / v) ammonia water, B is acetonitrile, the volume percentage of B in the mobile phase is 19%, isocratic elution, flow rate 25 mL / min; the said conditions are preferably: column model: Prep C18 OBD TM 19*250mm*5μM, the mobile phase is a mixture of A and B, where A is 0.1% (v / v) ammonia water, B is acetonitrile, the volume percentage of B in the mobile phase is 19%, isocratic elution, flow rate 25 mL / min; preferably, under the above conditions, the retention time of the later-eluting compound is 8.08 min; The compound that elutes first under the following conditions: the stationary phase is C18, the mobile phase is a mixture of A and B, where A is 0.1% (v / v) ammonia water, B is acetonitrile, the volume percentage of B in the mobile phase is 19%, isocratic elution, flow rate 25 mL / min; the said conditions are preferably: column model: Prep C18 OBD TM 19 * 250 mm * 5 μM, the mobile phase is a mixture of A and B, where A is 0.1% (v / v) ammonia water, B is acetonitrile, the volume percentage of B in the mobile phase is 19%, isocratic elution, flow rate 25 mL / min; preferably, under the said conditions, the retention time of the compound eluting first is 6.45 min; Compounds eluting later under the following conditions: the stationary phase is C18, the mobile phase is a mixture of A and B, where A is 0.1% (v / v) ammonia water, B is acetonitrile, the volume percentage of B in the mobile phase is 19%, isocratic elution, flow rate 25 mL / min; the said conditions are preferably: column model: Prep C18 OBD TM 19 * 250 mm * 5 μM, the mobile phase is a mixture of A and B, where A is 0.1% (v / v) ammonia water, B is acetonitrile, the volume percentage of B in the mobile phase is 19%, isocratic elution, flow rate 25 mL / min; preferably, under the said conditions, the retention time of the later eluting compound is 7.63 min; The compound that elutes first under the following conditions: the stationary phase is C18, the mobile phase is a mixture of A and B, where A is 0.1% (v / v) ammonia water, B is acetonitrile, the volume percentage of B in the mobile phase is 19%, isocratic elution, flow rate 25 mL / min; the said conditions are preferably: column model: Prep C18 OBD TM 19 * 250 mm * 5 μM, the mobile phase is a mixture of A and B, where A is 0.1% (v / v) ammonia water, B is acetonitrile, the volume percentage of B in the mobile phase is 19%, isocratic elution, flow rate 25 mL / min; preferably, under the said conditions, the retention time of the compound eluting first is 6.15 min; Compounds eluting later under the following conditions: the stationary phase is C18, the mobile phase is a mixture of A and B, where A is 0.1% (v / v) ammonia water, B is acetonitrile, the volume percentage of B in the mobile phase is 19%, isocratic elution, flow rate 25 mL / min; the said conditions are preferably: column model: Prep C18 OBD TM 19 * 250 mm * 5 μM, the mobile phase is a mixture of A and B, where A is 0.1% (v / v) ammonia water, B is acetonitrile, the volume percentage of B in the mobile phase is 19%, isocratic elution, flow rate 25 mL / min; preferably, under the said conditions, the retention time of the later-eluting compound is 6.95 min; Retention time is 2.53 min under the following conditions Stereoisomers: Column model: AcquityUPLC@BEH C18 OBD TM 2.1 * 50 mm * 1.7 μM, mobile phase is a mixture of A and B, where A is 0.1% (v / v) formic acid aqueous solution, B is acetonitrile, the volume percentage of B in the mobile phase is 5 - 95%, flow rate 0.5 mL / min, analysis time 8 min; Retention time is 3.81 min under the following conditions Stereoisomers: Column model: AcquityUPLC@BEH C18 OBD TM 2.1 * 50 mm * 1.7 μM, mobile phase is a mixture of A and B, where A is 0.1% (v / v) formic acid aqueous solution, B is acetonitrile, the volume percentage of B in the mobile phase is 5 - 95%, flow rate 0.5 mL / min, analysis time 8 min; The compound that elutes first under the following conditions: the stationary phase is C18, the mobile phase is a mixture of A and B, where A is 0.1% (v / v) ammonia water, B is acetonitrile, the volume percentage of B in the mobile phase is 35 - 50%, and the flow rate is 25 mL / min; the said conditions are preferably: column model: Prep C18 OBD TM 19 * 250 mm * 5 μM, the mobile phase is a mixture of A and B, where A is 0.1% (v / v) ammonia water, B is acetonitrile, the volume percentage of B in the mobile phase is 35 - 50%, the flow rate is 25 mL / min, and the analysis time is 13 min; preferably, under the above conditions, the retention time of the compound eluting first is 8.2 min; Compounds eluting later under the following conditions: the stationary phase is C18, the mobile phase is a mixture of A and B, where A is 0.1% (v / v) ammonia water, B is acetonitrile, the volume percentage of B in the mobile phase is 35 - 50%, and the flow rate is 25 mL / min; the said conditions are preferably: column model: Prep C18 OBD TM 19*250mm*5μM, the mobile phase is a mixture of A and B, where A is 0.1% (v / v) ammonia water and B is acetonitrile. The volume percentage of B in the mobile phase is 35 - 50%, the flow rate is 25 mL / min, and the analysis time is 13 min; preferably, under the above conditions, the retention time of the later-eluting compound is 8.5 min; The compound that elutes first under the following conditions: the stationary phase is C18, the mobile phase is a mixture of A and B, where A is an aqueous solution of 0.1% (v / v) formic acid and B is acetonitrile, the volume percentage of B in the mobile phase is 5 - 95%, and the flow rate is 0.5 mL / min; preferably, the conditions are: column model: AcquityUPLC@BEH C18 OBD TM 2.1 * 50 mm * 1.7 μM, the mobile phase is a mixture of A and B, where A is an aqueous solution of 0.1% (v / v) formic acid and B is acetonitrile, the volume percentage of B in the mobile phase is 5 - 95%, the flow rate is 0.5 mL / min, and the analysis time is 8 min; preferably, under the said conditions, the retention time of the compound that elutes first is 3.80 - 4.10 min; Compounds eluting later under the following conditions: The stationary phase is C18, the mobile phase is a mixture of A and B, where A is an aqueous solution of 0.1% (v / v) formic acid, B is acetonitrile, and the volume percentage of B in the mobile phase is 5 - 95%, and the flow rate is 0.5 mL / min; The above conditions are preferably: column type Part No.: Acquity UPLC@BEH C18 OBD TM 2.1 * 50 mm * 1.7 μM. The mobile phase is a mixture of A and B, where A is an aqueous solution of 0.1% (v / v) formic acid, B is acetonitrile, the volume percentage of B in the mobile phase is 5 - 95%, the flow rate is 0.5 mL / min, and the analysis time is 8 min; preferably, under the above conditions, the retention time of the later-eluting compound is 4.30 - 4.55 min; The compound that elutes first under the following conditions: the stationary phase is C18, the mobile phase is a mixture of A and B, where A is an aqueous solution of 0.1% (v / v) formic acid and B is acetonitrile, the volume percentage of B in the mobile phase is 5 - 95%, and the flow rate is 0.5 mL / min; the said conditions are preferably: column model: AcquityUPLC@BEH C18 OBD TM 2.1 * 50 mm * 1.7 μM, the mobile phase is a mixture of A and B, where A is an aqueous solution of 0.1% (v / v) formic acid and B is acetonitrile, the volume percentage of B in the mobile phase is 5 - 95%, the flow rate is 0.5 mL / min, and the analysis time is 8 min; preferably, under the said conditions, the retention time of the compound that elutes first is 3.67 - 3.87 min; Compounds that elute later under the following conditions: the stationary phase is C18, the mobile phase is a mixture of A and B, where A is an aqueous solution of 0.1% (v / v) formic acid and B is acetonitrile, and the volume percentage of B in the mobile phase is 5 - 95%, and the flow rate is 0.5 mL / min; the preferred conditions are: column model: AcquityUPLC@BEH C18 OBD TM 2.1 * 50 mm * 1.7 μM, the mobile phase is a mixture of A and B, where A is an aqueous solution of 0.1% (v / v) formic acid and B is acetonitrile, the volume percentage of B in the mobile phase is 5 - 95%, the flow rate is 0.5 mL / min, and the analysis time is 8 min; preferably, under the above conditions, the retention time of the later-eluting compound is 3.89 - 3.98 min; among those under the following conditions Compounds eluting first: The stationary phase is C18, and the mobile phase is a mixture of A and B, where A is 0.1% (v / v) ammonia water and B is acetonitrile. The volume percentage of B in the mobile phase is 45 - 55%, and the flow rate is 25 mL / min. Preferably, the conditions are as follows: Column model: Prep C18 OBD TM 19 * 250 mm * 5 μM, the mobile phase is a mixture of A and B, where A is 0.1% (v / v) ammonia water, B is acetonitrile, the volume percentage of B in the mobile phase is 45 - 55%, the flow rate is 25 mL / min, and the analysis time is 13.2 min; preferably, under the above conditions, the retention time of the compound eluting first is 7.25 min; Compounds that elute later under the following conditions: the stationary phase is C18, the mobile phase is a mixture of A and B, where A is 0.1% (v / v) ammonia water, B is acetonitrile, and the volume percentage of B in the mobile phase is 45 - 55%, and the flow rate is 25 mL / min; the said conditions are preferably: column model: Prep C18 OBD TM 19 * 250 mm * 5 μM, the mobile phase is a mixture of A and B, where A is 0.1% (v / v) ammonia water, B is acetonitrile, the volume percentage of B in the mobile phase is 45 - 55%, the flow rate is 25 mL / min, and the analysis time is 13.2 min; preferably, under the above conditions, the retention time of the later eluting compound is 8.3 min; The compound that elutes first under the following conditions: the stationary phase is C18, the mobile phase is a mixture of A and B, where A is an aqueous solution of 0.1% (v / v) formic acid and B is acetonitrile, and the volume percentage of B in the mobile phase is 5 - 95%, with a flow rate of 0.5 mL / min; preferably, the conditions are: column model: AcquityUPLC@BEH C18 OBD TM 2.1 * 50 mm * 1.7 μM, the mobile phase is a mixture of A and B, where A is an aqueous solution of 0.1% (v / v) formic acid and B is acetonitrile; the volume percentage of B in the mobile phase is 5 - 95%; the flow rate is 0.5 mL / min; the analysis time is 8 min; preferably, under the said conditions, the retention time of the compound that elutes first is 3.65 - 3.85 min; Compounds eluting later under the following conditions: The stationary phase is C18, the mobile phase is a mixture of A and B, where A is an aqueous solution of 0.1% (v / v) formic acid, B is Nitrile, the volume percentage of B in the mobile phase is 5 - 95%, and the flow rate is 0.5 mL / min; preferably, the conditions are: column model: AcquityUPLC@BEH C18 OBD TM 2.1 * 50 mm * 1.7 μM, the mobile phase is a mixture of A and B, where A is an aqueous solution of 0.1% (v / v) formic acid, and B is acetonitrile; the volume percentage of B in the mobile phase is 5 - 95%; the flow rate is 0.5 mL / min; the analysis time is 8 min; preferably, under the said conditions, the retention time of the later-eluting compound is 3.87 - 3.95 min; The compound that elutes first under the following conditions: the stationary phase is C18, the mobile phase is a mixture of A and B, where A is an aqueous solution of 0.1% (v / v) formic acid, B is acetonitrile, and the volume percentage of B in the mobile phase is 5 - 95%, and the flow rate is 0.5 mL / min; preferably, the conditions are: column model: AcquityUPLC@BEH C18 OBD TM 2.1 * 50 mm * 1.7 μM, the mobile phase is a mixture of A and B, where A is an aqueous solution of 0.1% (v / v) formic acid, B is acetonitrile; the volume percentage of B in the mobile phase is 5 - 95%; the flow rate is 0.5 mL / min; the analysis time is 8 min; preferably, under the said conditions, the retention time of the compound that elutes first is 3.64 - 3.84 min; Compounds eluting later under the following conditions: the stationary phase is C18, the mobile phase is a mixture of A and B, where A is an aqueous solution of 0.1% (v / v) formic acid and B is acetonitrile, and the volume percentage of B in the mobile phase is 5 - 95%, and the flow rate is 0.5 mL / min; preferably, the conditions are as follows: column model: AcquityUPLC@BEH C18 OBD TM 2.1 * 50 mm * 1.7 μM, the mobile phase is a mixture of A and B, where A is an aqueous solution of 0.1% (v / v) formic acid and B is acetonitrile; the volume percentage of B in the mobile phase is 5 - 95%; the flow rate is 0.5 mL / min; the analysis time is 8 min; preferably, under the said conditions, the retention time of the compounds eluting later is 3.84 - 3.93 min; Retention time is 3.60 - 3.69 min under the following conditions stereoisomers of, column Column: Acquity UPLC@BEH C18 OBD TM 2.1 * 50 mm * 1.7 μM, the mobile phase is a mixture of A and B, where A is an aqueous solution of 0.1% (v / v) formic acid and B is acetonitrile; the volume percentage of B in the mobile phase is 5 - 95%; the flow rate is 0.5 mL / min; the analysis time is 8 min; Retention time is 3.69 - 3.77 min under the following conditions Stereoisomers, column: Acquity UPLC@BEH C18 OBD TM 2.1 * 50 mm * 1.7 μM, the mobile phase is a mixture of A and B, where A is an aqueous solution of 0.1% (v / v) formic acid and B is acetonitrile; the volume percentage of B in the mobile phase is 5 - 95%; the flow rate is 0.5 mL / min; the analysis time is 8 min; Retention time is 3.88 - 3.97 min under the following conditions Stereoisomers, column: Acquity UPLC@BEH C18 OBD TM 2.1 * 50 mm * 1.7 μM, mobile phase is a mixture of A and B, where A is 0.1% (v / v) aqueous formic acid solution and B is acetonitrile; the volume percentage of B in the mobile phase is 5 - 95%; flow rate 0.5 mL / min; analysis time 8 min; The compound that elutes first under the following conditions: the stationary phase is C18, the mobile phase is a mixture of A and B, where A is an aqueous solution of 0.1% (v / v) formic acid and B is acetonitrile, and the volume percentage of B in the mobile phase is 5 - 95%, and the flow rate is 0.5 mL / min; preferably, the conditions are: column model: AcquityUPLC@BEH C18 OBD TM 2.1 * 50 mm * 1.7 μM, the mobile phase is a mixture of A and B, where A is an aqueous solution of 0.1% (v / v) formic acid and B is acetonitrile; the volume percentage of B in the mobile phase is 5 - 95%; the flow rate is 0.5 mL / min; the analysis time is 8 min; preferably, under the said conditions, the retention time of the compound that elutes first is 3.67 - 3.87 min; Compounds eluting later under the following conditions: the stationary phase is C18, the mobile phase is a mixture of A and B, where A is an aqueous solution of 0.1% (v / v) formic acid and B is acetonitrile, and the volume percentage of B in the mobile phase is 5 - 95%, and the flow rate is 0.5 mL / min; preferably, the conditions are as follows: column model: AcquityUPLC@BEH C18 OBD TM 2.1 * 50 mm * 1.7 μM, the mobile phase is a mixture of A and B, where A is an aqueous solution of 0.1% (v / v) formic acid and B is acetonitrile; the volume percentage of B in the mobile phase is 5 - 95%; the flow rate is 0.5 mL / min; the analysis time is 8 min; preferably, under the said conditions, the retention time of the compounds eluting later is 3.89 - 3.98 min; The compound that elutes first under the following conditions: the stationary phase is C18, the mobile phase is a mixture of A and B, where A is an aqueous solution of 0.1% (v / v) formic acid, B is acetonitrile, and the volume percentage of B in the mobile phase is 5 - 95%, and the flow rate is 0.5 mL / min; the said conditions are preferably: column model: AcquityUPLC@BEH C18 OBD TM 2.1 * 50 mm * 1.7 μM, the mobile phase is a mixture of A and B, where A is an aqueous solution of 0.1% (v / v) formic acid, B is acetonitrile; the volume percentage of B in the mobile phase is 5 - 95%; the flow rate is 0.5 mL / min; the analysis time is 8 min; preferably, under the said conditions, the retention time of the compound that elutes first is 3.65 - 3.74 min; Compounds that elute later under the following conditions: the stationary phase is C18, the mobile phase is a mixture of A and B, where A is an aqueous solution of 0.1% (v / v) formic acid and B is acetonitrile, and the volume percentage of B in the mobile phase is 5 - 95%, and the flow rate is 0.5 mL / min; preferably, the conditions are: column model: AcquityUPLC@BEH C18 OBD TM 2.1 * 50 mm * 1.7 μM, the mobile phase is a mixture of A and B, where A is an aqueous solution of 0.1% (v / v) formic acid and B is acetonitrile; the volume percentage of B in the mobile phase is 5 - 95%; the flow rate is 0.5 mL / min; the analysis time is 8 min; preferably, under the said conditions under which the retention time of the compounds eluting later is 3.86 - 3.95 min; Compounds that elute first under the following conditions: the stationary phase is C18, the mobile phase is a mixture of A and B, where A is an aqueous solution of 0.1% (v / v) formic acid and B is acetonitrile, and the volume percentage of B in the mobile phase is 5 - 95%, and the flow rate is 0.5 mL / min; the said conditions are preferably: column model: AcquityUPLC@BEH C18 OBD TM 2.1 * 50 mm * 1.7 μM, the mobile phase is a mixture of A and B, where A is an aqueous solution of 0.1% (v / v) formic acid and B is acetonitrile; the volume percentage of B in the mobile phase is 5 - 95%; the flow rate is 0.5 mL / min; the analysis time is 8 min; preferably, under the said conditions, the retention time of the compounds that elute first is 3.66 - 3.75 min; Compounds that elute later under the following conditions: The stationary phase is C18, the mobile phase is a mixture of A and B, where A is an aqueous solution of 0.1% (v / v) formic acid and B is acetonitrile, and the volume percentage of B in the mobile phase is 5 - 95%, and the flow rate is 0.5 mL / min; The preferred conditions are: Column model: AcquityUPLC@BEH C18 OBD TM 2.1 * 50 mm * 1.7 μM, the mobile phase is a mixture of A and B, where A is an aqueous solution of 0.1% (v / v) formic acid and B is acetonitrile; the volume percentage of B in the mobile phase is 5 - 95%; the flow rate is 0.5 mL / min; the analysis time is 8 min; Preferably, under the above conditions, the retention time of the compounds that elute later is 3.86 - 3.95 min; The compound that elutes first under the following conditions: the stationary phase is C18, the mobile phase is a mixture of A and B, where A is an aqueous solution of 0.1% (v / v) formic acid, B is acetonitrile, and the volume percentage of B in the mobile phase is 5 - 95%, and the flow rate is 0.5 mL / min; preferably, the conditions are: column model: AcquityUPLC@BEH C18 OBD TM 2.1 * 50 mm * 1.7 μM, the mobile phase is a mixture of A and B, where A is an aqueous solution of 0.1% (v / v) formic acid, B is acetonitrile; the volume percentage of B in the mobile phase is 5 - 95%; the flow rate is 0.5 mL / min; the analysis time is 8 min; preferably, under the said conditions, the retention time of the compound that elutes first is 3.67 - 3.76 min; Compounds eluting later under the following conditions: the stationary phase is C18, the mobile phase is a mixture of A and B, where A is an aqueous solution of 0.1% (v / v) formic acid and B is acetonitrile, and the volume percentage of B in the mobile phase is 5 - 95%, and the flow rate is 0.5 mL / min; the said conditions are preferably: column model: AcquityUPLC@BEH C18 OBD TM 2.1 * 50 mm * 1.7 μM, the mobile phase is a mixture of A and B, where A is an aqueous solution of 0.1% (v / v) formic acid and B is acetonitrile; the volume percentage of B in the mobile phase is 5 - 95%; the flow rate is 0.5 mL / min; the analysis time is 8 min; preferably, under the said conditions, the retention time of the compounds eluting later is 3.85 - 3.94 min.

27. A pharmaceutical composition comprising substance X and a pharmaceutically acceptable excipient, wherein substance X is a heterocyclic compound represented by formula I as described in any one of claims 1 - 26, its pharmaceutically acceptable salt, its solvate, or a solvate of its pharmaceutically acceptable salt.

28. Use of a heterocyclic compound represented by formula I as described in any one of claims 1 - 26, its pharmaceutically acceptable salt, its solvate, or a solvate of its pharmaceutically acceptable salt in the preparation of a KRAS mutant inhibitor; preferably, the KRAS mutant is KRAS G12C, KRAS G12D, KRAS G12V, KRAS G12A, KRAS G12R, KRAS G12S, KRAS G13C, KRAS G13D, KRAS Q61H, KRAS Q61K, or KRAS Q61R, such as KRAS G12C, KRAS G12V, or KRAS G12D.

29. Use of a heterocyclic compound represented by formula I as described in any one of claims 1 - 26, its pharmaceutically acceptable salt, its solvate, or a solvate of its pharmaceutically acceptable salt in the preparation of a drug for treating and / or preventing diseases associated with KRAS mutations; preferably, the KRAS mutation is KRAS G12C, KRAS G12D, KRAS G12V, KRAS G12A, KRAS G12R, KRAS G12S, KRAS G13C, KRAS G13D, KRAS Q61H, KRAS Q61K, or KRAS Q61R, such as KRAS G12C, KRAS G12V, or KRAS G12D; preferably, the diseases associated with KRAS mutations are selected from one or more of breast cancer, prostate cancer, lung cancer, brain cancer, ovarian cancer, cervical cancer, kidney cancer, head and neck cancer, bone cancer, skin cancer, liver cancer, colorectal cancer, esophageal cancer, gastric cancer, thyroid cancer, bladder cancer, lymphoma, leukemia, melanoma, and pancreatic cancer, preferably lung cancer, pancreatic cancer, or colorectal cancer; preferably, the lung cancer is non - small cell lung cancer or small cell lung cancer; preferably, the colorectal cancer is colon cancer and rectal cancer.

30. Use of a heterocyclic compound represented by Formula I as described in any one of claims 1-26, its pharmaceutically acceptable salt, its solvate or its solvate of the pharmaceutically acceptable salt in the preparation of a drug for treating and / or preventing cancer; preferably, the cancer is selected from one or more of breast cancer, prostate cancer, lung cancer, brain cancer, ovarian cancer, cervical cancer, kidney cancer, head and neck cancer, bone cancer, skin cancer, liver cancer, colorectal cancer, esophageal cancer, gastric cancer, thyroid cancer, bladder cancer, lymphoma, leukemia, melanoma and pancreatic cancer, and preferably is lung cancer, pancreatic cancer or colorectal cancer; preferably, the lung cancer is non-small cell lung cancer or small cell lung cancer; preferably, the colorectal cancer is colon cancer and rectal cancer.

31. A compound represented by formula (II-1), (II-2), (II-3), (II-4), (II-5), (II-6), (II-7), (II-8) or (II-9): In the above formulas, PG is independently an amino protecting group or a hydroxyl protecting group, R d and R b are each independently hydrogen or a C1-C6 alkyl group, R c is independently hydrogen or an amino protecting group, X1 and X2 are each independently a halogen, p1 is 0 or 1, and the definitions of X, n, R 5 , R 6 , R 3 and R 4 are as defined in any one of claims 1-26; The carbon atom with "*" is a chiral carbon, and its configuration is R configuration, S configuration or a mixture thereof; Preferably, p1 is 0; Preferably, the amino protecting group or the hydroxyl protecting group is p-methoxybenzyl. Any one of the compounds shown below:

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