Fused ring nitrogen-containing compounds, intermediates thereof, preparation method and uses

Abstract

The present invention discloses fused-ring nitrogen-containing compounds, their intermediates, preparation methods, and uses. The present invention provides a compound represented by Formula I, its pharmaceutically acceptable salts, or isotope compounds. The ATPase activity and protein inhibitory effects of the compounds of the present invention are significantly improved compared to those of the prior art. TIFF2025533951000445.tif2157

Description

[Technical Field]

[0001] This application claims priority from Chinese Patent Application No. 2022113390715 filed on October 28, 2022, Chinese Patent Application No. 2023100413978 filed on January 12, 2023, Chinese Patent Application No. 2023100486339 filed on January 31, 2023, Chinese Patent Application No. 2023101385833 filed on February 20, 2023, Chinese Patent Application No. 2023106346553 filed on May 31, 2023, Chinese Patent Application No. 2023108473638 filed on July 11, 2023, and Chinese Patent Application No. 2023113518111 filed on October 18, 2023. This application cites the entire text of the aforementioned Chinese patent applications.

[0002] [Technical field] The present invention relates to fused ring nitrogen-containing compounds, their intermediates, preparation methods and uses. [Background technology]

[0003] DNA damage is an important mechanism by which many chemotherapeutic drugs exert their antitumor effects. DNA double-strand breaks (DSBs) are one of the most common lesions in cells. They can be directly induced by ionizing radiation, UV light, reactive oxygen species (ROS), or other mutagens. Common chemotherapeutic drugs include cisplatin, 5-FU, and etoposide. Unrepaired DNA damage blocks cellular functions such as transcription and replication, induces apoptosis or necrosis, and is removed by immune cells. Tumor cells possess efficient damage repair or alternative repair pathways, and targeting key proteins in the DNA damage repair pathways allows the accumulation of unrepaired DNA damage, ultimately leading to cell death. This is an important strategy for cancer treatment.

[0004] DNA double-strand breaks are generally repaired by three mechanisms: non-homologous end joining (NHEJ), homologous recombination (HR), and alternative non-homologous end joining (Alt-NHEJ, also known as microhomology-mediated end joining (MMEJ) or TMEJ). The HR repair pathway occurs only during G2 and S phases and repairs double-strand breaks error-free in the presence of sister chromatids. In mammals, over 90% of DSBs are repaired by the NHEJ pathway, which is error-prone and results in deletions of less than 30 bp, insertions of less than 5 bp, or microhomology sequences of less than 2 bp. Recent studies have shown that defective HR and / or NHEJ result in cells becoming highly dependent on the third mechanism, i.e., MMEJ, for repairing DNA breaks. Inhibition of MMEJ leads to apoptosis. MMEJ is also an error-prone repair pathway that repairs DNA double-strand breaks by DNA polymerase theta-mediated end joining (TMEJ).

[0005] DNA polymerase theta (Pol theta, or Pol θ) is a key protein in the MMEJ repair pathway. It is a unique multifunctional polymerase consisting of an N-terminal helicase domain, a central domain, and a single C-terminal polymerase domain. While the polymerase structural domain is required for DNA elongation at DSB repair sites, basic research has revealed that the helicase and central domains play important roles in substrate recognition and binding by Pol θ. Pol θ disrupts the interaction between DNA and damage repair complexes (e.g., single-stranded DNA, which competitively binds to RAD51), thereby inhibiting the HR repair pathway. The helicase domain of Pol θ is also involved in blocking DNA replication, and its loss of function increases replication pressure in tumor cells, leading to apoptosis.

[0006] Pol θ is either absent or expressed at low levels in normal tissue cells, but is highly expressed in various tumors, including lung cancer, breast cancer, HR-deficient ovarian cancer, gastric cancer, and colon cancer, and is associated with poor prognosis. Among these, Pol θ is overexpressed in approximately 70% or more of breast cancers. These phenomena suggest that Pol θ plays an important role in these cancers and may be a tumor-specific target.

[0007] Studies of Pol θ knockdown or knockout in tumor cells have revealed that Pol θ deficiency sensitizes these cells to radiation, induces DSB production, increases replication fork instability, and may sensitize tumor cells to mutagens (genotoxic substances), potentially enhancing the efficacy of radiation therapy and chemotherapy, making it a potential drug target. Furthermore, studies have shown that Pol θ and HR deficiency have a combined lethal effect, and that small molecule inhibitors can kill HR-deficient tumor cells in vitro and in vivo. In particular, in PARP inhibitor-resistant tumors with HR deficiency reversion mutations, Pol θ inhibitors can resensitize cells to PARPi, providing a valuable therapeutic opportunity. Furthermore, given that Pol θ is a key protein in the MMEJ pathway, its functional loss increases genomic instability in cancer cells, increases somatic mutations, and promotes the generation of tumor neoantigens. Furthermore, because Pol θ has been reported to be involved in cGAS-STING-mediated immune activation, targeting Pol θ may enhance immunotherapy.

[0008] As described above, Pol θ is a promising target for cancer therapy. Designing ATPase inhibitors that target the Pol θ protein, which inhibits intracellular MMEJ, and administering them alone or in combination with other chemotherapy, radiation therapy, antibody therapy, immunotherapy, etc., can achieve the goal of killing tumor cells. This holds great promise for the treatment of tumors such as lung cancer, breast cancer, HR-deficient ovarian cancer, gastric cancer, colon cancer, prostate cancer, and pancreatic adenocarcinoma. Summary of the Invention

[0009] The technical problem to be solved by the present invention is to overcome the relatively simple structure of polymerase theta inhibitor compounds in the prior art. To this end, the present invention provides fused-ring nitrogen-containing compounds, their intermediates, preparation methods and uses. The ATPase activity and protein inhibitory effects of these compounds are significantly improved compared to those of the prior art.

[0010] The present invention solves the above technical problems by the following technical solutions.

[0011] The present invention provides a compound represented by formula I, a pharmaceutically acceptable salt thereof, or an isotopic compound thereof: TIFF2025533951000002.tif2360 where, m is 0, 1, 2 or 3, and n is 1, 2 or 3; TIFF2025533951000003.tif18125 Ring A is a 6- to 12-membered aryl ring or a 5- to 12-membered heteroaryl ring, and the heteroatom in the 5- to 12-membered heteroaryl ring is one or more of N, O, and S, and the number of heteroatoms is 1, 2, or 3; R 1 is unsubstituted or contains one or more R 1-1 a 6-12 membered aryl group substituted by, or unsubstituted or one or more R 1-2wherein the heteroatoms in the 5-12 membered heteroaryl group are one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3; Each R 1-1 and R 1-2 are independently deuterium, halogen, cyano, amino, hydroxy, unsubstituted or one or more R 1-1-1 C1-C6 alkyl group, unsubstituted or substituted by one or more R 1-1-2 C1-C6 alkoxy group, unsubstituted or substituted by one or more R 1-1-3 C2-C6 alkenyl group, unsubstituted or substituted by one or more R 1-1-4 C2-C6 alkynyl group, unsubstituted or substituted by one or more R 1-1-5 a 3-6 membered cycloalkyl group, unsubstituted or substituted by one or more R 1-1-6 a 4-6 membered heterocyclyl group substituted by -COOR 1-1-7 , -C(O)R 1-1-8 , -C(O)NR 1-1-9 R 1-1-9 , TIFF2025533951000004.tif1449, wherein the heteroatom in the 4- to 6-membered heterocyclyl group is selected from one or more of N, O, and S, and the number of heteroatoms is 1, 2, or 3; Each R 1-1-1 , R 1-1-2 , R 1-1-3 , R 1-1-4 , R 1-1-5 and R 1-1-6 are independently deuterium, a hydroxy group, a cyano group, or a halogen; Each R 1-1-7 , R 1-1-8 and R 1-1-9 are independently hydrogen or a C1-C6 alkyl group; Each R 1-1-10 and R 1-1-11 are independently a hydroxy group or a C1-C6 alkyl group, Each R 2 is independently TIFF2025533951000005.tif1218Deuterium, halogen, cyano group, amino group, hydroxy group, unsubstituted or one or more R 2-1 C1-C6 alkyl group, unsubstituted or substituted by one or more R 2-2 C1-C6 alkoxy group, unsubstituted or substituted by one or more R 2-3 C2-C6 alkenyl group, unsubstituted or substituted by one or more R 2-4 C2-C6 alkynyl group, unsubstituted or substituted by one or more R 2-5 a 3-6 membered cycloalkyl group substituted by, or unsubstituted or substituted by one or more R 2-6 wherein the heteroatoms in the 4-6 membered heterocyclyl group are selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3; Each R 2-1 , R 2-2 , R 2-3 , R 2-4 , R 2-5 and R 2-6 are independently deuterium, a hydroxy group, a cyano group, or a halogen; Ring B may be unsubstituted or may contain one or more R b-1 wherein the heteroatoms in the 5-20 membered fused ring heteroaryl ring are selected from one or more of N, O and S, and the number of heteroatoms is 1, 2, 3, 4, 5, 6, 7 or 8; the single heteroaryl ring in the 5-20 membered fused ring heteroaryl ring is a 5-7 membered heteroaryl ring, and the number of rings in the 5-20 membered fused ring heteroaryl ring is 2, 3 or 4; Each R b-1 are independently deuterium, oxo (=O), halogen, cyano, hydroxy, unsubstituted or one or more R b-1-1 C1-C6 alkyl group, unsubstituted or substituted by one or more R b-1-2 C1-C6 alkoxy group substituted by -NR b-1-3 R b-1-3, -C(O)NR b-1-4 R b-1-4 , -COOR b-1-5 , TIFF2025533951000006.tif1569 each R b-1-1 and R b-1-2 are independently a hydroxy group, a halogen, or -NR b-1-1-1 R b-1-1-1 and Each R b-1-3 , R b-1-4 , R b-1-5 and R b-1-7 are independently hydrogen or a C1-C6 alkyl group; Each R b-1-6 are independently a hydroxy group or a C1-C6 alkyl group, Each R b-1-1-1 are independently hydrogen, a C1-C6 alkyl group, or -C(O)R b-1-1-1-1 and R b-1-1-1-1 is a C1-C6 alkyl group, R 3 is hydrogen, TIFF2025533951000007.tif1520 No substitution or one or more R 3-1 a 3- to 12-membered cycloalkyl group, unsubstituted or substituted by one or more R 3-2 a 4-12 membered heterocyclyl group, unsubstituted or substituted by one or more R 3-3 a 4-12 membered cycloalkenyl group, unsubstituted or substituted by one or more R 3-4 a 4-12 membered heterocycloalkenyl group, unsubstituted or substituted by one or more R 3-5 a 6-10 membered aryl group, unsubstituted or substituted by one or more R 3-6 a 5-10 membered heteroaryl group substituted by -C(O)R 4 , -NH(CH2) p R 5 , -O(CH2) q R 6 , unsubstituted or one or more R 3-7 C1-C6 alkyl group substituted with, or unsubstituted or one or more R3-8 -OR is replaced by 7 wherein the heteroatoms in the 4- to 12-membered heterocyclyl group, the 4- to 12-membered heterocycloalkenyl group, and the 5- to 10-membered heteroaryl group are selected from one or more of N, O, and S, and the number of heteroatoms is 1, 2, 3, or 4; p is 0, 1, 2 or 3; q is 1, 2 or 3; Each R 3-1 , R 3-2 , R 3-3 , R 3-4 , R 3-7 and R 3-8 are independently deuterium, hydroxyl group, halogen, cyano group, amino group, -NHC(O)R 3-2-1 , unsubstituted or one or more R 3-2-2 C1-C6 alkyl group, C1-C6 alkoxy group, C2-C6 alkenyl group, C2-C6 alkynyl group, oxo group (=O), -C(O)NH2, unsubstituted or substituted with one or more R 3-2-3 a 3- to 6-membered cycloalkyl group, a 4- to 6-membered heterocyclyl group, -S(O)R 3-4-1 , -NR 3-4-2 R 3-4-2 , TIFF2025533951000008.tif1447, wherein the heteroatom in the 4- to 6-membered heterocyclyl group is selected from one or more of N, O, and S, and the number of heteroatoms is 1 or 2; Each R 3-5 and R 3-6 are independently deuterium, TIFF2025533951000009.tif1218Hydroxy group, halogen, cyano group, amino group, -NHC(O)R 3-2-1 , unsubstituted or one or more R 3-2-2 C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, —C(O)NH2, unsubstituted or substituted with one or more R 3-2-3 a 3-6 membered cycloalkyl group, unsubstituted or substituted by one or more R 3-6-1a 4-6 membered heterocyclyl group substituted by -S(O)R 3-4-1 , -NR 3-4-2 R 3-4-2 , TIFF2025533951000010.tif1547, wherein the heteroatom in the 4- to 6-membered heterocyclyl group is selected from one or more of N, O, and S, and the number of heteroatoms is 1 or 2; Each R 3-2-1 and R 3-4-2 are independently hydrogen, -S(O)R 3-4-1 , unsubstituted or one or more R 3-2-1-1 is a 3-6 membered cycloalkyl group or a C1-C6 alkyl group substituted by Each R 3-2-1-1 are independently a C1-C6 alkyl group, Each R 3-2-3 and R 3-5-1 are independently a hydroxy group or a C1-C6 alkyl group, Each R 3-5-2 are independently a hydroxy group, a C1-C6 alkyl group, or a 1-10 membered heteroalkyl group, or two R 3-5-2 form a 4-10 membered heterocyclyl group, wherein the heteroatoms in the 1-10 membered heteroalkyl group include, in addition to phosphorus, any one or more selected from N, O and S, and the number of heteroatoms is 1, 2, 3 or 4; the heteroatoms in the 4-10 membered heterocyclyl group include, in addition to phosphorus, any one or more selected from N, O and S, and the number of heteroatoms is 1, 2, 3 or 4; Each R 3-6-1 are independently a C1-C6 alkyl group, Each R 3-2-2 are independently deuterium, a hydroxy group, or a halogen (e.g., each R 3-2-2 are independently a hydroxy group or a halogen; R 3-4-1 is a hydroxy group, an amino group, or a C1-C6 alkyl group, R 3-9 is a C1-C6 alkyl group, R 4is unsubstituted or contains one or more R 4-1 wherein the heteroatoms in the 4-6 membered heterocyclyl group are selected from one or more of N, O and S, and the number of heteroatoms is 1 or 2; Each R 4-1 are independently a hydroxy group, R 5 is unsubstituted or contains one or more R 5-1 a 3-6 membered cycloalkyl group substituted by -S(O)R 5-2 , unsubstituted or one or more R 5-3 wherein the heteroatoms in the 4-6 membered heterocyclyl group are selected from one or more of N, O and S, and the number of heteroatoms is 1 or 2; R 5-2 is a C1-C6 alkyl group, Each R 5-3 are independently -S(O)R 5-3-1 and each R 5-3-1 are independently a C1-C6 alkyl group, R 6 is unsubstituted or contains one or more R 6-1 a 3- to 6-membered cycloalkyl group or a 4- to 6-membered heterocyclyl group substituted with, wherein the heteroatoms in the 4- to 6-membered heterocyclyl group are selected from one or more of N, O and S, and the number of heteroatoms is 1 or 2; Each R 5-1 and R 6-1 are independently a hydroxy group, R 7 is a 3-6 membered cycloalkyl group.

[0012] In a preferred embodiment, in the compound of formula I, a pharmaceutically acceptable salt thereof, or an isotopic compound thereof, certain groups may be defined as described below, and other groups may be defined as described in any of the preceding embodiments (hereinafter referred to as "preferred embodiments"): TIFF2025533951000011.tif2657 where, m is 0, 1, 2 or 3, and n is 1, 2 or 3; TIFF2025533951000012.tif15125 Ring A is a 6- to 12-membered aryl ring or a 5- to 12-membered heteroaryl ring, and the heteroatom in the 5- to 12-membered heteroaryl ring is selected from one or more of N, O, and S, and the number of heteroatoms is 1, 2, or 3; R 1 is unsubstituted or contains one or more R 1-1 a 6-12 membered aryl group substituted by, or unsubstituted or one or more R 1-2 wherein the heteroatoms in the 5-12 membered heteroaryl group are selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3; Each R 1-1 and R 1-2 are independently deuterium, halogen, cyano, amino, hydroxy, unsubstituted or one or more R 1-1-1 C1-C6 alkyl group, unsubstituted or substituted by one or more R 1-1-2 C1-C6 alkoxy group, unsubstituted or substituted by one or more R 1-1-3 C2-C6 alkenyl group, unsubstituted or substituted by one or more R 1-1-4 C2-C6 alkynyl group, unsubstituted or substituted by one or more R 1-1-5 a 3-6 membered cycloalkyl group, unsubstituted or substituted by one or more R 1-1-6 a 4-6 membered heterocyclyl group substituted by -COOR 1-1-7 , -C(O)R 1-1-8 , -C(O)NR 1-1-9 R 1-1-9 , TIFF2025533951000013.tif1550, wherein the heteroatom in the 4- to 6-membered heterocyclyl group is selected from one or more of N, O, and S, and the number of heteroatoms is 1, 2, or 3; Each R 1-1-1 , R 1-1-2 , R1-1-3 , R 1-1-4 , R 1-1-5 and R 1-1-6 are independently deuterium, a hydroxy group, a cyano group, or a halogen; Each R 1-1-7 , R 1-1-8 and R 1-1-9 are independently hydrogen or a C1-C6 alkyl group; Each R 1-1-10 and R 1-1-11 are independently a hydroxy group or a C1-C6 alkyl group, Each R 2 are independently deuterium, halogen, cyano, amino, hydroxy, unsubstituted or one or more R 2-1 C1-C6 alkyl group, unsubstituted or substituted by one or more R 2-2 C1-C6 alkoxy group, unsubstituted or substituted by one or more R 2-3 C2-C6 alkenyl group, unsubstituted or substituted by one or more R 2-4 C2-C6 alkynyl group, unsubstituted or substituted by one or more R 2-5 a 3-6 membered cycloalkyl group substituted by, or unsubstituted or substituted by one or more R 2-6 wherein the heteroatoms in the 4-6 membered heterocyclyl group are selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3; Each R 2-1 , R 2-2 , R 2-3 , R 2-4 , R 2-5 and R 2-6 are independently deuterium, a hydroxy group, a cyano group, or a halogen; Ring B may be unsubstituted or may contain one or more R b-1a 5- to 20-membered fused-ring heteroaryl ring substituted by: wherein the heteroatoms in said 5- to 20-membered fused-ring heteroaryl ring are selected from one or more of N, O and S, and the number of heteroatoms is 1, 2, 3, 4, 5 or 6; wherein the single heteroaryl ring in said 5- to 20-membered fused-ring heteroaryl ring is a 5- to 7-membered heteroaryl ring; and wherein the number of rings in said 5- to 20-membered fused-ring heteroaryl ring is 2, 3 or 4; Each R b-1 are independently deuterium, oxo (=O), halogen, cyano, hydroxy, unsubstituted or one or more R b-1-1 C1-C6 alkyl group, unsubstituted or substituted by one or more R b-1-2 C1-C6 alkoxy group substituted by -NR b-1-3 R b-1-3 , -C(O)NR b-1-4 R b-1-4 , -COOR b-1-5 , TIFF2025533951000014.tif1774 each R b-1-1 and R b-1-2 are independently a hydroxy group, a halogen, or -NR b-1-1-1 R b-1-1-1 and Each R b-1-3 , R b-1-4 , R b-1-5 and R b-1-7 are independently hydrogen or a C1-C6 alkyl group; Each R b-1-6 are independently a hydroxy group or a C1-C6 alkyl group, Each R b-1-1-1 are independently hydrogen, a C1-C6 alkyl group, or -C(O)R b-1-1-1-1 and R b-1-1-1-1 is a C1-C6 alkyl group, R 3 is hydrogen, unsubstituted or one or more R 3-1 a 3- to 12-membered cycloalkyl group, unsubstituted or substituted by one or more R 3-2 a 4-12 membered heterocyclyl group, unsubstituted or substituted by one or more R 3-3a 4-12 membered cycloalkenyl group, unsubstituted or substituted by one or more R 3-4 a 4-12 membered heterocycloalkenyl group, unsubstituted or substituted by one or more R 3-5 a 6-10 membered aryl group, unsubstituted or substituted by one or more R 3-6 a 5-10 membered heteroaryl group substituted by -C(O)R 4 , -NH(CH2) p R 5 , -O(CH2) q R 6 , unsubstituted or one or more R 3-7 C1-C6 alkyl group substituted with, or unsubstituted or one or more R 3-8 -OR is replaced by 7 wherein the heteroatoms in the 4- to 12-membered heterocyclyl group, the 4- to 12-membered heterocycloalkenyl group, and the 5- to 10-membered heteroaryl group are selected from one or more of N, O, and S, and the number of heteroatoms is 1, 2, 3, or 4; p is 0, 1, 2 or 3; q is 1, 2 or 3; Each R 3-1 , R 3-2 , R 3-3 , R 3-4 , R 3-7 and R 3-8 are independently deuterium, hydroxyl group, halogen, cyano group, -NHC(O)R 3-2-1 , unsubstituted or one or more R 3-2-2 C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, oxo group (=O), -C(O)NH2, unsubstituted or substituted with one or more R 3-2-3 a 3- to 6-membered cycloalkyl group, a 4- to 6-membered heterocyclyl group, -S(O)R 3-4-1 , -NR 3-4-2 R 3-4-2 , TIFF2025533951000015.tif1850, wherein the heteroatom in the 4- to 6-membered heterocyclyl group is selected from one or more of N, O, and S, and the number of heteroatoms is 1 or 2; Each R 3-5 and R 3-6 are independently deuterium, hydroxyl group, halogen, cyano group, amino group, -NHC(O)R 3-2-1 , unsubstituted or one or more R 3-2-2 C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, —C(O)NH2, unsubstituted or substituted with one or more R 3-2-3 a 3- to 6-membered cycloalkyl group, a 4- to 6-membered heterocyclyl group, -S(O)R 3-4-1 , -NR 3-4-2 R 3-4-2 , TIFF2025533951000016.tif1749, wherein the heteroatom in the 4- to 6-membered heterocyclyl group is selected from one or more of N, O, and S, and the number of heteroatoms is 1 or 2; Each R 3-2-1 and R 3-4-2 are independently hydrogen or a C1-C6 alkyl group; Each R 3-2-3 , R 3-5-1 and R 3-5-2 are independently a hydroxy group or a C1-C6 alkyl group, Each R 3-2-2 are independently a hydroxy group or a halogen; R 3-4-1 is a hydroxy group, an amino group, or a C1-C6 alkyl group, R 4 is a 4- to 6-membered heterocyclyl group, wherein the heteroatoms in the 4- to 6-membered heterocyclyl group are selected from one or more of N, O and S, and the number of heteroatoms is 1 or 2; R 5 is unsubstituted or contains one or more R 5-1 is a 3- to 6-membered cycloalkyl group substituted by R 6is unsubstituted or contains one or more R 6-1 is a 3- to 6-membered cycloalkyl group substituted by Each R 5-1 and R 6-1 are independently a hydroxy group, R 7 is a 3-6 membered cycloalkyl group.

[0013] In a preferred embodiment, the compound of formula I is a compound of formula I'.

[0014] TIFF2025533951000017.tif2355

[0015] In a preferred embodiment, in ring A, the 5- to 12-membered heteroaryl ring may be a 5- to 10-membered heteroaryl ring, and the heteroatom in the 5- to 10-membered heteroaryl ring may be selected from any one or two of N, O and S. Preferably, the 5- to 10-membered heteroaryl ring is a 5- to 6-membered heteroaryl ring, a 5,6-heteroaryl ring or a 6,6-heteroaryl ring, and preferably TIFF2025533951000018.tif60150

[0016] In a preferred embodiment, R 1 In the formula (I), the 6-12 membered aryl group may be a 6-10 membered aryl group, and may also be a phenyl group or a naphthalene group, for example, a phenyl group.

[0017] In a preferred embodiment, R 1 In the above, the 5-12 membered heteroaryl group may be a 5-10 membered heteroaryl group, the heteroatom in the 5-10 membered heteroaryl group may be N and / or O, and the number of heteroatoms may be 1 or 2, preferably the 5-12 membered heteroaryl group is a 5-6 membered heteroaryl group or a 5,6-heteroaryl group, particularly preferably TIFF2025533951000019.tif26157

[0018] In a preferred embodiment, each R 1-1 wherein the halogen can be fluorine, chlorine, bromine or iodine, for example fluorine.

[0019] In a preferred embodiment, each R 1-1 wherein the C1-C6 alkyl group can be a C1-C4 alkyl group, such as a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group, or a tert-butyl group.

[0020] In a preferred embodiment, each R 1-1 wherein the C1-C6 alkoxy group may be a C1-C4 alkoxy group, and may also be a methoxy group, an ethoxy group, an n-propoxy group, an isopropoxy group, an n-butoxy group, an isobutoxy group, a primary butoxy group, a sec-butoxy group, or a tert-butoxy group, for example, a methoxy group.

[0021] In a preferred embodiment, each R 1-2 wherein the halogen may be fluorine, chlorine, bromine or iodine, for example fluorine or chlorine.

[0022] In a preferred embodiment, each R 1-2 wherein the C1-C6 alkyl group may be a C1-C4 alkyl group, and may also be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group, or a tert-butyl group, and is preferably a methyl group.

[0023] In a preferred embodiment, each R 1-2 wherein the C1-C6 alkoxy group may be a C1-C4 alkoxy group, and may also be a methoxy group, an ethoxy group, an n-propoxy group, an isopropoxy group, an n-butoxy group, an isobutoxy group, a primary butoxy group, a sec-butoxy group, or a tert-butoxy group, for example, a methoxy group.

[0024] In a preferred embodiment, each R 1-1-1wherein the halogen can be fluorine, chlorine, bromine or iodine, and is preferably fluorine.

[0025] In a preferred embodiment, each R 1-1-2 wherein the halogen can be fluorine, chlorine, bromine or iodine, for example fluorine.

[0026] In a preferred embodiment, each R 2 wherein the C1-C6 alkyl group may be a C1-C4 alkyl group, and may also be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, for example, a methyl group.

[0027] In a preferred embodiment, each R 2 wherein the halogen can be fluorine, chlorine, bromine or iodine, for example fluorine.

[0028] In a preferred embodiment, in ring B, the number of heteroatoms in the 5- to 20-membered fused heteroaryl ring is 1, 2, 3, or 4, and preferably, the 5- to 20-membered fused heteroaryl ring is a 5,5-heteroaryl ring, a 5,6-heteroaryl ring, a 6,6-heteroaryl ring, a 5,6,6,6-heteroaryl ring, or a 5,6,7,6-heteroaryl ring, and particularly preferably, TIFF2025533951000020.tif144164 TIFF2025533951000021.tif241164 TIFF2025533951000022.tif58164

[0029] In a preferred embodiment, each R b-1 wherein the halogen can be fluorine, chlorine, bromine or iodine, for example fluorine.

[0030] In a preferred embodiment, each R b-1wherein the C1-C6 alkyl group may be a C1-C4 alkyl group, and may also be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, for example, a methyl group.

[0031] In a preferred embodiment, each R b-1 wherein the C1-C6 alkoxy group may be a C1-C4 alkoxy group, and may also be a methoxy group, an ethoxy group, an n-propoxy group, an isopropoxy group, an n-butoxy group, an isobutoxy group, a primary butoxy group, a sec-butoxy group, or a tert-butoxy group, such as a methoxy group or an ethoxy group.

[0032] In a preferred embodiment, each R b-1-1 wherein the halogen can be fluorine, chlorine, bromine or iodine.

[0033] In a preferred embodiment, each R b-1-2 wherein the halogen can be fluorine, chlorine, bromine or iodine.

[0034] In a preferred embodiment, each R b-1-2-1 wherein the C1-C6 alkyl group may be a C1-C4 alkyl group, and may also be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group, or a tert-butyl group, and is preferably a methyl group.

[0035] In a preferred embodiment, each R b-1-4 and R b-1-5 wherein the C1-C6 alkyl group may be a C1-C4 alkyl group, and may also be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group, or a tert-butyl group, and is preferably a methyl group.

[0036] In a preferred embodiment, R 3In the above, the 3- to 12-membered cycloalkyl group may be a 3- to 6-membered cycloalkyl group, and may also be a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, or a cyclohexyl group, and is preferably a cyclobutyl group or a cyclohexyl group, for example, a cyclohexyl group.

[0037] In a preferred embodiment, R 3 wherein the 3- to 12-membered cycloalkyl group is a 7- to 10-membered cycloalkyl group, the ring in the 7- to 10-membered cycloalkyl group is a single ring, a spiro ring, a fused ring or a bridged ring, the number of rings in the spiro ring, the fused ring or the bridged ring may be 2, the spiro ring may be a 4-membered spiro 4-membered cycloalkyl group, a 4-membered spiro 5-membered cycloalkyl group or a 4-membered spiro 6-membered cycloalkyl group, the fused ring may be a 5,5-cycloalkyl group or a 5,6-cycloalkyl group, and the bridged ring may be a 5-membered bridged 7-membered cycloalkyl group, preferably TIFF2025533951000023.tif25157

[0038] In a preferred embodiment, R 3 In the above, the ring in the 4-12 membered heterocyclyl group may be a monocycle, a spiro ring, a fused ring or a bridged ring, the number of rings in the spiro ring, the fused ring or the bridged ring may be two, and the spiro ring may be a 3-membered spiro 5-membered heterocyclyl group, a 3-membered spiro 6-membered heterocyclyl group, a 4-membered spiro 5-membered heterocyclyl group, a 4-membered spiro 6-membered heterocyclyl group, a 4-membered spiro 4-membered heterocyclyl group, a 4-membered spiro 7-membered heterocyclyl group, a 5-membered spiro The fused ring may be a 3,5-heterocyclyl group, a 4,5-heterocyclyl group, or a 5,5-heterocyclyl group. The bridged ring may be a 5-membered bridged 6-membered heterocyclyl group. The number of heteroatoms in the 4- to 12-membered heterocyclyl group may be 1 or 2, preferably TIFF2025533951000024.tif98157

[0039] In a preferred embodiment, R 3 In the 4-12 membered heterocyclyl group, preferably, the monocycle is a 4-7 membered heterocyclyl group, and the number of heteroatoms may be 1 or 2, and preferably, the heteroatoms are N and / or O.

[0040] In a preferred embodiment, R 3 In the above, the ring in the 4-10-membered cycloalkenyl group may be a single ring, a spiro ring, a fused ring or a bridged ring, the number of rings in the spiro ring, the fused ring or the bridged ring may be two, the spiro ring may be a 4-membered spiro 4-membered cycloalkenyl group, a 4-membered spiro 5-membered cycloalkenyl group or a 4-membered spiro 6-membered cycloalkenyl group, the fused ring may be a 5,5-cycloalkenyl group or a 5,6-cycloalkenyl group, and the bridged ring may be a 5-membered bridged 7-membered cycloalkenyl group, preferably TIFF2025533951000025.tif30157

[0041] In a preferred embodiment, R 3 In the above, the ring in the 4- to 10-membered heterocycloalkenyl group may be a monocycle or a spiro ring, the number of rings in the spiro ring may be 2, the spiro ring may be a 4-membered spiro 4-membered heterocycloalkenyl group, a 4-membered spiro 5-membered heterocycloalkenyl group or a 4-membered spiro 6-membered heterocycloalkenyl group, the number of heteroatoms in the 4- to 10-membered heterocycloalkenyl group may be 1, and preferably TIFF2025533951000026.tif61157

[0042] In a preferred embodiment, R 3 In the formula (I), the 6-10 membered aryl group can be an aryl group or a naphthalene group, and is preferably an aryl group.

[0043] In a preferred embodiment, R 3 In the above formula, the heteroatom in the 5-10 membered heteroaryl group may be N, and the number of heteroatoms may be 1, 2 or 3.

[0044] In a preferred embodiment, R 3 In the above, the 5-10 membered heteroaryl group may be a single ring or a fused ring heteroaryl group, the number of rings in the fused ring may be 2, the fused ring may be a 5,5-heteroaryl group or a 5,6-heteroaryl group (preferably, both rings in the fused ring have aromatic rings), the heteroatom in the 5-10 membered heteroaryl group may be N and / or O, the number of heteroatoms may be 1, and preferably TIFF2025533951000027.tif17157 TIFF2025533951000028.tif87157

[0045] In a preferred embodiment, R 3 wherein the C1-C6 alkyl group may be a C1-C4 alkyl group, and may also be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group, or a tert-butyl group, and is preferably a methyl group or an isopropyl group, for example, a methyl group.

[0046] In a preferred embodiment, each R 3-1 wherein the halogen can be fluorine, chlorine, bromine or iodine, and is preferably fluorine.

[0047] In a preferred embodiment, each R 3-1 wherein the C1-C6 alkyl group may be a C1-C4 alkyl group, and may also be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group, or a tert-butyl group, and is preferably a methyl group.

[0048] In a preferred embodiment, each R 3-2 wherein the halogen can be fluorine, chlorine, bromine or iodine, for example fluorine.

[0049] In a preferred embodiment, each R3-2 wherein the C1-C6 alkyl group may be a C1-C4 alkyl group, and may also be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group, or a tert-butyl group, and is preferably a methyl group or an isopropyl group, for example, a methyl group.

[0050] In a preferred embodiment, each R 3-2 wherein the C2-C6 alkenyl group may be a C2-C4 alkenyl group; TIFF2025533951000029.tif26157

[0051] In a preferred embodiment, each R 3-2 wherein the C2-C6 alkynyl group may be a C2-C4 alkynyl group; TIFF2025533951000030.tif26157

[0052] In a preferred embodiment, each R 3-2 In the formula (I), the 3- to 6-membered cycloalkyl group can be a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, or a cyclohexyl group, and is preferably a cyclobutyl group.

[0053] In a preferred embodiment, each R 3-2 In the above, the number of heteroatoms in the 4- to 6-membered heterocyclyl group may be 1 or 2, and preferably, TIFF2025533951000031.tif26134

[0054] In a preferred embodiment, R 3-2-1 wherein the C1-C6 alkyl group may be a C1-C4 alkyl group, and may also be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group, or a tert-butyl group, and is preferably a methyl group.

[0055] In a preferred embodiment, each R 3-2-2wherein the halogen can be fluorine, chlorine, bromine or iodine, and is preferably fluorine.

[0056] In a preferred embodiment, each R 3-2-1-1 wherein the C1-C6 alkyl group may be a C1-C4 alkyl group, and may also be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group, or a tert-butyl group, and is preferably a methyl group.

[0057] In a preferred embodiment, each R 3-2-3 wherein the C1-C6 alkyl group may be a C1-C4 alkyl group, and may also be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group, or a tert-butyl group, and is preferably a methyl group.

[0058] In a preferred embodiment, each R 3-3 wherein the halogen can be fluorine, chlorine, bromine or iodine, and is preferably fluorine.

[0059] In a preferred embodiment, each R 3-4 wherein the C1-C6 alkyl group may be a C1-C4 alkyl group, and may also be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group, or a tert-butyl group, and is preferably a methyl group.

[0060] In a preferred embodiment, each R 3-4 wherein the halogen can be fluorine, chlorine, bromine or iodine.

[0061] In a preferred embodiment, each R 3-4 wherein the number of heteroatoms in the 4- to 6-membered heterocyclyl group may be 1 or 2; TIFF2025533951000032.tif27139

[0062] In a preferred embodiment, R 3-4-1 wherein the C1-C6 alkyl group may be a C1-C4 alkyl group, and may also be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group, or a tert-butyl group, and is preferably a methyl group.

[0063] In a preferred embodiment, each R 3-4-2 wherein the C1-C6 alkyl group may be a C1-C4 alkyl group, and may also be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group, or a tert-butyl group, and is preferably a methyl group.

[0064] In a preferred embodiment, R 3-5-1 wherein the C1-C6 alkyl group may be a C1-C4 alkyl group, and may also be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group, or a tert-butyl group, and is preferably a methyl group.

[0065] In a preferred embodiment, R 3-5-2 wherein the C1-C6 alkyl group may be a C1-C4 alkyl group, and may also be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group, or a tert-butyl group, and is preferably a methyl group or an ethyl group.

[0066] In a preferred embodiment, R 3-5-2 In the above, the 1-10 membered heteroalkyl group may be a 1-4 membered heteroalkyl group.

[0067] In a preferred embodiment, R 3-5-2 In the above, the heteroatoms in the 1-10 membered heteroalkyl group include those selected from N and / or O in addition to phosphorus.

[0068] In a preferred embodiment, R 3-5-2 In the formula, the 1-10 membered heteroalkyl group has 3 heteroatoms.

[0069] In a preferred embodiment, R 3-5-2 wherein the 4-10 membered heterocyclyl group can be a 4-8 membered heteroalkyl group, for example: TIFF2025533951000033.tif1731

[0070] In a preferred embodiment, R 3-5-2 In the 4-10 membered heterocyclyl group, heteroatoms include those selected from N and / or O in addition to phosphorus.

[0071] In a preferred embodiment, R 3-5-2 wherein the 4- to 10-membered heterocyclyl group has 1 or 3 heteroatoms.

[0072] In a preferred embodiment, each R 3-6 wherein the halogen can be fluorine, chlorine, bromine or iodine, and is preferably chlorine.

[0073] In a preferred embodiment, each R 3-6 wherein the C1-C6 alkyl group may be a C1-C4 alkyl group, and may also be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group, or a tert-butyl group, and is preferably a methyl group.

[0074] In a preferred embodiment, each R 3-6 In the above, the heteroatom in the 4- to 6-membered heterocyclyl group may be selected from N, and the number of heteroatoms may be 1 or 2, for example, TIFF2025533951000034.tif1237

[0075] In a preferred embodiment, each R 3-6In the formula (I), the 3- to 6-membered cycloalkyl group can be a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, or a cyclohexyl group, and is preferably a cyclopropyl group.

[0076] In a preferred embodiment, each R 3-6-1 wherein the C1-C6 alkyl group may be a C1-C4 alkyl group, and may also be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group, or a tert-butyl group, and is preferably a methyl group.

[0077] In a preferred embodiment, each R 3-7 wherein the halogen can be fluorine, chlorine, bromine or iodine.

[0078] In a preferred embodiment, each R 3-7 wherein the heteroatoms in the 4- to 6-membered heterocyclyl group may be selected from one or more of N, O and S, and the number of heteroatoms may be 1 or 2; TIFF2025533951000035.tif29157

[0079] In a preferred embodiment, each R 3-9 wherein the C1-C6 alkyl group may be a C1-C4 alkyl group, and may also be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group, or a tert-butyl group, and is preferably a methyl group.

[0080] In a preferred embodiment, R 4 wherein the number of heteroatoms in the 4- to 6-membered heterocyclyl group may be 1 or 2; TIFF2025533951000036.tif29157

[0081] In a preferred embodiment, R 5In the formula (I), the 3- to 6-membered cycloalkyl group can be a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, or a cyclohexyl group, and is preferably a cyclobutyl group.

[0082] In a preferred embodiment, R 5 In the above, the heteroatom in the 4- to 6-membered heterocyclyl group can be selected from one or more of N, O and S, and the number of heteroatoms can be 1 or 2, for example, TIFF2025533951000037.tif1236

[0083] In a preferred embodiment, each R 5-2 wherein the C1-C6 alkyl group may be a C1-C4 alkyl group, and may also be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group, or a tert-butyl group, and is preferably a methyl group.

[0084] In a preferred embodiment, each R 5-3-1 wherein the C1-C6 alkyl group may be a C1-C4 alkyl group, and may also be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group, or a tert-butyl group, and is preferably a methyl group.

[0085] In a preferred embodiment, R 6 In the above, the number of heteroatoms in the 4- to 6-membered heterocyclyl group can be 1 or 2.

[0086] In a preferred embodiment, R 6 In the formula (I), the 3- to 6-membered cycloalkyl group can be a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, or a cyclohexyl group, and is preferably a cyclohexyl group.

[0087] In a preferred embodiment, R 7In the formula (I), the 3- to 6-membered cycloalkyl group can be a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, or a cyclohexyl group, and is preferably a cyclohexyl group.

[0088] In a preferred embodiment, the pharmaceutically acceptable salt may be a trifluorohydrochloride salt.

[0089] In a preferred embodiment, the pharmaceutically acceptable salt may be a trifluoroacetate or formate salt.

[0090] In a preferred embodiment, the compound of formula I, a pharmaceutically acceptable salt thereof, or an isotopic compound thereof is a compound of formula Ia, Ib, Ic, Id, or Ie: TIFF2025533951000038.tif61145 In a preferred embodiment, ring A is a 5-12 membered heteroaryl ring, and heteroatoms in the 5-12 membered heteroaryl ring are selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3.

[0091] In a preferred embodiment, each R 1-1 are independently deuterium, halogen, cyano group, amino group, unsubstituted or one or more R 1-1-1 C1-C6 alkyl group substituted with, or unsubstituted or one or more R 1-1-2 is a C1-C6 alkoxy group substituted by

[0092] In a preferred embodiment, each R 1-2 are independently deuterium, halogen, cyano group, amino group, unsubstituted or one or more R 1-1-1 C1-C6 alkyl group substituted with, or unsubstituted or one or more R 1-1-2 is a C1-C6 alkoxy group substituted by

[0093] In a preferred embodiment, each R 1-2 are independently deuterium, halogen, unsubstituted or one or more R 1-1-1C1-C6 alkyl group substituted with, or unsubstituted or one or more R 1-1-2 is a C1-C6 alkoxy group substituted by

[0094] In a preferred embodiment, each R 1-1-1 are independently deuterium or halogen.

[0095] In a preferred embodiment, each R 1-1-2 are independently deuterium or halogen.

[0096] In a preferred embodiment, each R 2 are independently deuterium, or unsubstituted or one or more R 2-1 is a C1-C6 alkyl group substituted by

[0097] In a preferred embodiment, each R 2 are independently deuterium or a C1-C6 alkyl group.

[0098] In a preferred embodiment, each R 2 are independently unsubstituted or one or more R 2-1 is a C1-C6 alkyl group substituted by

[0099] In a preferred embodiment, each R 2-1 are independently deuterium.

[0100] In preferred embodiments, m is 0, 1, 2 or 3.

[0101] In a preferred embodiment, each R b-1 are independently deuterium, oxo (=O), halogen, cyano, hydroxy, unsubstituted or one or more R b-1-1 C1-C6 alkyl group substituted with, or unsubstituted or one or more R b-1-2 is a C1-C6 alkoxy group substituted by

[0102] In a preferred embodiment, each Rb-1-1 are independently a hydroxy group, a halogen, or an unsubstituted or one or two R b-1-2-1 is an amino group substituted by

[0103] In a preferred embodiment, each R b-1-2 are independently a hydroxy group, a halogen, or an unsubstituted or one or two R b-1-2-1 is an amino group substituted by

[0104] In a preferred embodiment, each R b-1-2-1 are independently hydrogen or a C1-C6 alkyl group.

[0105] In a preferred embodiment, R 3 is hydrogen, unsubstituted or one or more R 3-1 a 3-6 membered cycloalkyl group, unsubstituted or substituted by one or more R 3-2 a 4-12 membered heterocyclyl group, unsubstituted or substituted by one or more R 3-3 a 4-10 membered cycloalkenyl group, unsubstituted or substituted by one or more R 3-4 a 4-10 membered heterocycloalkenyl group, unsubstituted or substituted by one or more R 3-5 a 6-10 membered aryl group, unsubstituted or substituted by one or more R 3-6 a 5-10 membered heteroaryl group substituted by -C(O)R 4 , -NH(CH2) p R 5 , -O(CH2) q R 6 , unsubstituted or one or more R 3-7 C1-C6 alkyl group substituted with, or unsubstituted or one or more R 3-8 -OR is replaced by 7 wherein the heteroatoms in the 4- to 12-membered heterocyclyl group, 4- to 10-membered heterocycloalkenyl group, or 5- to 10-membered heteroaryl group are selected from one or more of N, O, and S, and the number of heteroatoms is 1, 2, 3, or 4.

[0106] In a preferred embodiment, each R 3-1 are independently deuterium, a hydroxy group, a halogen, or a C1-C6 alkyl group.

[0107] In a preferred embodiment, each R 3-1 are independently a hydroxy group or deuterium.

[0108] In a preferred embodiment, each R 3-2 are independently deuterium, hydroxyl group, halogen, cyano group, amino group, -NHC(O)R 3-2-1 , unsubstituted or one or more R 3-2-2 C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, oxo group (=O), -C(O)NH2, unsubstituted or substituted with one or more R 3-2-3 and the heteroatoms in the 4-6 membered heterocyclyl group are selected from one or more of N, O and S, and the number of heteroatoms is 1 or 2.

[0109] In a preferred embodiment, each R 3-2 are independently a hydroxy group, deuterium, or a C1-C6 alkyl group.

[0110] In a preferred embodiment, R 3-2-1 is a C1-C6 alkyl group.

[0111] In a preferred embodiment, each R 3-2-2 are independently a hydroxy group or a halogen.

[0112] In a preferred embodiment, each R 3-2-2 are independently deuterium, a hydroxy group, or a halogen.

[0113] In a preferred embodiment, each R 3-2-2 are independently deuterium.

[0114] In a preferred embodiment, each R 3-2-3 are independently a C1-C6 alkyl group or a hydroxy group.

[0115] In a preferred embodiment, each R 3-3 are independently deuterium, hydroxyl group, halogen, cyano group, amino group, -S(O)2R 3-4-1 or -NR 3-4-2 R 3-4-2 is.

[0116] In a preferred embodiment, each R 3-3 are independently a hydroxy group or deuterium.

[0117] In a preferred embodiment, each R 3-4 are independently deuterium, hydroxyl group, C1-C6 alkyl group, oxo group (=O), cyano group, halogen, 4- to 6-membered heterocyclyl group, -S(O)2R 3-4-1 or -NR 3-4-2 R 3-4-2 is.

[0118] In a preferred embodiment, R 3-4-1 is a C1-C6 alkyl group.

[0119] In a preferred embodiment, each R 3-4-2 are independently hydrogen or a C1-C6 alkyl group.

[0120] In a preferred embodiment, each R 3-5 are independently deuterium or TIFF2025533951000039.tif1430

[0121] In a preferred embodiment, each R 3-5 are independently deuterium, TIFF2025533951000040.tif1858

[0122] In a preferred embodiment, each R 3-5 is independently TIFF2025533951000041.tif1757

[0123] In a preferred embodiment, R 3-5-1 is a C1-C6 alkyl group.

[0124] In a preferred embodiment, R 3-5-1 and R 3-5-2 are independently a C1-C6 alkyl group.

[0125] In a preferred embodiment, each R 3-6 are independently deuterium, halogen, or a C1-C6 alkyl group.

[0126] In a preferred embodiment, each R 3-6 are independently deuterium, halogen, or unsubstituted or one or more R 3-2-2 is a C1-C6 alkyl group substituted by

[0127] In a preferred embodiment, each R 3-7 are independently deuterium, a hydroxy group, a halogen atom, or a 4- to 6-membered heterocyclyl group, the heteroatom in the 4- to 6-membered heterocyclyl group is O, and the number of heteroatoms is 1.

[0128] In a preferred embodiment, R 3-8 is a hydroxy group.

[0129] In a preferred embodiment, R 5 is one or more R 5-1 is a 3-6 membered cycloalkyl group substituted by

[0130] In a preferred embodiment, R 6 is one or more R 6-1 is a 3-6 membered cycloalkyl group substituted by

[0131] In a preferred embodiment, ring A is a 5- to 10-membered heteroaryl ring, and the heteroatom in the 5- to 10-membered heteroaryl ring is selected from any one or two of N, O, and S, and the number of heteroatoms is 1 or 2.

[0132] In a preferred embodiment, R 1 is unsubstituted or contains one or more R 1-1 or a phenyl group substituted with one or more R 1-2 The heteroatoms in the 5-10 membered heteroaryl group are N and / or O, and the number of heteroatoms is 1 or 2.

[0133] In a preferred embodiment, each R 1-1 are independently halogen, or unsubstituted or one or more R 1-1-2 is a C1-C6 alkoxy group substituted by

[0134] In a preferred embodiment, each R 1-2 are independently halogen, or unsubstituted or one or more R 1-1-2 is a C1-C6 alkoxy group substituted by

[0135] In a preferred embodiment, each R 1-1-2 are independently halogen.

[0136] In a preferred embodiment, each R 2 are independently a C1-C6 alkyl group.

[0137] In a preferred embodiment, m is 0 or 1.

[0138] In a preferred embodiment, ring B is unsubstituted or contains one or more R b-1 wherein the heteroatoms in the 5-12 membered fused ring heteroaryl ring are N and / or S, and the number of heteroatoms is 1, 2, 3 or 4; the single heteroaryl group ring in the 5-12 membered fused ring heteroaryl ring is a 5-7 membered heteroaryl ring; the number of rings in the 5-12 membered fused ring heteroaryl ring is 2; and preferably TIFF2025533951000042.tif2097, and preferably, ring B is TIFF2025533951000043.tif46151

[0139] In a preferred embodiment, each R b-1 are independently halogen or a C1-C6 alkyl group.

[0140] In a preferred embodiment, R 3 is hydrogen, unsubstituted or one or more R 3-1 a 3-6 membered cycloalkyl group, unsubstituted or substituted by one or more R 3-2 a 4-6 membered heterocyclyl group, unsubstituted or substituted by one or more R 3-3 a 4-6 membered cycloalkenyl group, unsubstituted or substituted by one or more R 3-4 a 4-6 membered heterocycloalkenyl group, unsubstituted or substituted by one or more R 3-5 a phenyl group, unsubstituted or substituted by one or more R 3-6 a 5-6 membered heteroaryl group substituted by -C(O)R 4 , or unsubstituted or one or more R 3-7 and the heteroatoms in the 4- to 6-membered heterocyclyl group, 4- to 6-membered heterocycloalkenyl group, or 5- to 6-membered heteroaryl group are N and / or O, and the number of heteroatoms is 1 or 2.

[0141] In a preferred embodiment, R 3 is hydrogen, unsubstituted or one or more R 3-1 a 3-6 membered cycloalkyl group, unsubstituted or substituted by one or more R 3-2 a 4-6 membered heterocyclyl group, unsubstituted or substituted by one or more R 3-3 a 4-6 membered cycloalkenyl group, unsubstituted or substituted by one or more R 3-4 a 4-6 membered heterocycloalkenyl group, unsubstituted or substituted by one or more R3-5 a phenyl group, unsubstituted or substituted by one or more R 3-6 a 5-6 membered heteroaryl group substituted by -C(O)R 4 , or unsubstituted or one or more R 3-7 wherein the heteroatoms in the 4- to 6-membered heterocyclyl group, 4- to 6-membered heterocycloalkenyl group, or 5- to 6-membered heteroaryl group are N and / or O, and the number of heteroatoms is 1, 2, or 3.

[0142] In a preferred embodiment, R 3 is hydrogen, unsubstituted or one or more R 3-1 a 3-6 membered cycloalkyl group, unsubstituted or substituted by one or more R 3-2 a 4-6 membered heterocyclyl group, unsubstituted or substituted by one or more R 3-3 a 4-6 membered cycloalkenyl group, unsubstituted or substituted by one or more R 3-4 a 4-6 membered heterocycloalkenyl group, unsubstituted or substituted by one or more R 3-5 a phenyl group, unsubstituted or substituted by one or more R 3-6 a 5-6 membered heteroaryl group substituted by -C(O)R 4 , or unsubstituted or one or more R 3-7 wherein the heteroatoms in the 4- to 6-membered heterocyclyl group or the 4- to 6-membered heterocycloalkenyl group are N and / or O and the number of heteroatoms is 1 or 2, or the heteroatoms in the 5- to 6-membered heteroaryl group are N and / or O and the number of heteroatoms is 1, 2, or 3.

[0143] In a preferred embodiment, each R 3-1 are independently a hydroxy group.

[0144] In a preferred embodiment, each R 3-2 are independently a hydroxy group or a C1-C6 alkyl group.

[0145] In a preferred embodiment, each R 3-3 are independently a hydroxy group.

[0146] In a preferred embodiment, each R 3-4 are independently a C1-C6 alkyl group.

[0147] In a preferred embodiment, each R 3-5 is independently TIFF2025533951000044.tif1431

[0148] In a preferred embodiment, each R 3-6 are independently halogen or a C1-C6 alkyl group.

[0149] In a preferred embodiment, each R 3-7 are independently a 4- to 6-membered heterocyclyl group, the heteroatom in the 4- to 6-membered heterocyclyl group is O, and the number of heteroatoms is 1.

[0150] In a preferred embodiment, R 4 is a 4- to 6-membered heterocyclyl group, the heteroatom in the 4- to 6-membered heterocyclyl group is O, and the number of heteroatoms is 1.

[0151] In a preferred embodiment, ring A is a 6- to 12-membered aryl ring or a 5- to 6-membered heteroaryl ring, and the heteroatoms in the 5- to 6-membered heteroaryl ring are selected from any one or two of N, O, and S, and the number of heteroatoms is 1, 2, or 3.

[0152] In a preferred embodiment, R 1 is unsubstituted or contains one or more R 1-1 a 6-12 membered aryl group substituted by, or unsubstituted or one or more R 1-2wherein the heteroatoms in the 5- or 6-membered heteroaryl ring are selected from any one or two of N, O and S, and the number of heteroatoms is 1, 2 or 3.

[0153] In a preferred embodiment, each R 1-1 and R 1-2 are independently halogen or a C1-C6 alkoxy group.

[0154] In a preferred embodiment, ring B is unsubstituted or contains one or more R b-1 wherein the heteroatoms in the 5-20 membered fused ring heteroaryl ring are selected from one or more of N, O and S, and the number of heteroatoms is 1, 2, 3, 4, 5, 6, 7 or 8; the single heteroaryl ring in the 5-20 membered fused ring heteroaryl ring is a 5-7 membered heteroaryl ring; and the number of rings in the 5-20 membered fused ring heteroaryl ring is 3 or 4.

[0155] In a preferred embodiment, each R b-1 are independently deuterium, cyano, halogen, or unsubstituted or one or more R b-1-1 is a C1-C6 alkyl group substituted by

[0156] In a preferred embodiment, R 3 is hydrogen, TIFF2025533951000045.tif1520 No substitution or one or more R 3-1 a 3-6 membered cycloalkyl group, unsubstituted or substituted by one or more R 3-2 a 4-9 membered heterocyclyl group, unsubstituted or substituted by one or more R 3-3 a 4-6 membered cycloalkenyl group, unsubstituted or substituted by one or more R 3-4 a 4-6 membered heterocycloalkenyl group, unsubstituted or substituted by one or more R 3-5 a phenyl group, unsubstituted or substituted by one or more R3-6 a 5-10 membered heteroaryl group substituted by -C(O)R 4 , or unsubstituted or one or more R 3-7 The heteroatoms in the 4- to 6-membered heterocycloalkenyl group and the 5- to 10-membered heteroaryl group are N and / or O, and the number of heteroatoms is 1 or 2; the heteroatoms in the 4- to 9-membered heterocyclyl group are selected from one or two of N, O, and S, and the number of heteroatoms is 1 or 2.

[0157] In a preferred embodiment, each R 3-2 are independently deuterium, oxo, halogen, C1-C6 alkoxy group, -NR 3-4-2 R 3-4-2 , -S(O)2R 3-4-1 , a hydroxy group, or unsubstituted or one or more R 3-2-2 is a C1-C6 alkyl group substituted by

[0158] In a preferred embodiment, each R 3-3 are independently deuterium, oxo, amino, or hydroxy.

[0159] In a preferred embodiment, each R 3-4 are independently deuterium, oxo, or a C1-C6 alkyl group.

[0160] In a preferred embodiment, R 3-4-1 is a C1-C6 alkyl group.

[0161] In a preferred embodiment, each R 3-4-2 are independently -S(O)R 3-4-1 , hydrogen or a C1-C6 alkyl group.

[0162] In a preferred embodiment, each R 3-5 are independently deuterium, TIFF2025533951000046.tif1774

[0163] In a preferred embodiment, each R 3-5-2 are independently a hydroxy group, a C1-C6 alkyl group, or a 1-10 membered heteroalkyl group, or two R 3-5-2 form a 4- to 10-membered heterocyclyl group, wherein the heteroatoms in the 1- to 10-membered heteroalkyl group include, in addition to phosphorus, any one or more selected from N, O, and S, and the number of heteroatoms is 1, 2, 3, or 4; and the heteroatoms in the 4- to 10-membered heterocyclyl group include, in addition to phosphorus, any one or more selected from N, O, and S, and the number of heteroatoms is 1, 2, 3, or 4.

[0164] In a preferred embodiment, each R 3-6 are independently deuterium, halogen, unsubstituted or one or more R 3-2-2 C1-C6 alkyl group substituted with, or unsubstituted or one or more R 3-6-1 The heteroatoms in the 4- to 6-membered heterocyclyl group are selected from any one or two of N, O and S, and the number of heteroatoms is 1 or 2.

[0165] In a preferred embodiment, each R 3-6-1 are independently a C1-C6 alkyl group.

[0166] In a preferred embodiment, each R 3-2-2 are independently deuterium or a hydroxy group.

[0167] In a preferred embodiment, each R 3-7 are independently deuterium, hydroxyl group, -S(O)R 3-4-1 , a 4- to 6-membered heterocyclyl group, the heteroatom in the 4- to 6-membered heterocyclyl group is O, and the number of heteroatoms is 1.

[0168] In a preferred embodiment, R 3 is hydrogen, TIFF2025533951000047.tif1520 No substitution or one or more R 3-1a 3-6 membered cycloalkyl group, unsubstituted or substituted by one or more R 3-2 a 4-9 membered heterocyclyl group, unsubstituted or substituted by one or more R 3-3 a 4-6 membered cycloalkenyl group, unsubstituted or substituted by one or more R 3-4 a 4-6 membered heterocycloalkenyl group, unsubstituted or substituted by one or more R 3-5 a phenyl group, unsubstituted or substituted by one or more R 3-6 a 5-10 membered heteroaryl group substituted by -C(O)R 4 , or unsubstituted or one or more R 3-7 The heteroatoms in the 4- to 6-membered heterocycloalkenyl group and the 5- to 10-membered heteroaryl group are N and / or O, and the number of heteroatoms is 1, 2, or 3; the heteroatoms in the 4- to 9-membered heterocyclyl group are selected from one or two of N, O, and S, and the number of heteroatoms is 1 or 2.

[0169] In a preferred embodiment, R 3 is hydrogen, TIFF2025533951000048.tif1520 No substitution or one or more R 3-1 a 3-6 membered cycloalkyl group, unsubstituted or substituted by one or more R 3-2 a 4-9 membered heterocyclyl group, unsubstituted or substituted by one or more R 3-3 a 4-6 membered cycloalkenyl group, unsubstituted or substituted by one or more R 3-4 a 4-6 membered heterocycloalkenyl group, unsubstituted or substituted by one or more R 3-5 a phenyl group, unsubstituted or substituted by one or more R 3-6 a 5-10 membered heteroaryl group substituted by -C(O)R 4 , or unsubstituted or one or more R 3-7the heteroatoms in the 4- to 6-membered heterocycloalkenyl group are N and / or O and the number of heteroatoms is 1 or 2; the heteroatoms in the 5- to 10-membered heteroaryl group are N and / or O and the number of heteroatoms is 1, 2 or 3; and the heteroatoms in the 4- to 9-membered heterocyclyl group are selected from one or two of N, O and S and the number of heteroatoms is 1 or 2.

[0170] In a preferred embodiment, R 3 is hydrogen, unsubstituted or one or more R 3-1 a 3-6 membered cycloalkyl group, unsubstituted or substituted by one or more R 3-2 a 4-12 membered heterocyclyl group, unsubstituted or substituted by one or more R 3-3 a 4-10 membered cycloalkenyl group, unsubstituted or substituted by one or more R 3-4 a 4-10 membered heterocycloalkenyl group, unsubstituted or substituted by one or more R 3-5 a 6-10 membered aryl group, unsubstituted or substituted by one or more R 3-6 a 5-10 membered heteroaryl group substituted by -C(O)R 4 , unsubstituted or one or more R 3-7 C1-C6 alkyl group substituted with, or unsubstituted or one or more R 3-8 -OR is replaced by 7 The heteroatoms in the 4- to 12-membered heterocyclyl group or the 4- to 10-membered heterocycloalkenyl group are one or more of N, O, and S, and the number of heteroatoms is 1 or 2; the heteroatoms in the 5- to 10-membered heteroaryl group are N and / or O, and the number of heteroatoms is 1, 2, 3, or 4.

[0171] In a preferred embodiment, ring B contains one or more R b-1wherein the heteroatoms in the 5-20 membered fused ring heteroaryl ring are selected from one or more of N, O and S, and the number of heteroatoms is 1, 2, 3, 4, 5, 6, 7 or 8; the single heteroaryl ring in the 5-20 membered fused ring heteroaryl ring is a 5-7 membered heteroaryl ring; and the number of rings in the 5-20 membered fused ring heteroaryl ring is 2, 3 or 4.

[0172] In a preferred embodiment, ring B is unsubstituted or contains one or more R b-1 wherein the heteroatoms in the 5-20 membered fused ring heteroaryl ring are selected from one or more of N, O and S, and the number of heteroatoms is 1, 2, 3, 4, 5, 6, 7 or 8; the single heteroaryl ring in the 5-20 membered fused ring heteroaryl ring is a 5-7 membered heteroaryl ring; the number of rings in the 5-20 membered fused ring heteroaryl ring is 2, 3 or 4; and the unsubstituted 5-20 membered fused ring heteroaryl ring is TIFF2025533951000049.tif1942

[0173] In a preferred embodiment, ring A is a 5- to 12-membered heteroaryl ring, and the heteroatoms in the 5- to 12-membered heteroaryl ring are one or more of N, O, and S, and the number of heteroatoms is 1, 2, or 3; R 1 is unsubstituted or contains one or more R 1-2 wherein the heteroatoms in the 5-12 membered heteroaryl ring are selected from any one or two of N, O and S, and the number of heteroatoms is 1, 2 or 3; R 3 is hydrogen, TIFF2025533951000050.tif1419 Unsubstituted or one or more R 3-1 a 3- to 12-membered cycloalkyl group substituted by one or more R 3-2a 4-12 membered heterocyclyl group, unsubstituted or substituted by one or more R 3-3 a 4-12 membered cycloalkenyl group, unsubstituted or substituted by one or more R 3-4 a 4-12 membered heterocycloalkenyl group, unsubstituted or substituted by one or more R 3-5 a 6-10 membered aryl group, unsubstituted or substituted by one or more R 3-6 a 5-10 membered heteroaryl group substituted by -C(O)R 4 , -NH(CH2) p R 5 , -O(CH2) q R 6 , a C1-C6 alkyl group, or an unsubstituted or one or more R 3-8 -OR is replaced by 7 wherein the heteroatoms in the 4- to 12-membered heterocyclyl group, the 4- to 12-membered heterocycloalkenyl group, and the 5- to 10-membered heteroaryl group are selected from one or more of N, O, and S, and the number of heteroatoms is 1, 2, 3, or 4; Each R 3-5 and R 3-6 are independently deuterium, TIFF2025533951000051.tif1018Hydroxy group, amino group, -NHC(O)R 3-2-1 , a C1-C6 alkyl group, a C2-C6 alkenyl group, a C2-C6 alkynyl group, —C(O)NH2, one or more R 3-2-3 a 3-6 membered cycloalkyl group, unsubstituted or substituted by one or more R 3-6-1 a 4-6 membered heterocyclyl group substituted by -S(O)R 3-4-1 , -NR 3-4-2 R 3-4-2 , TIFF2025533951000052.tif1445, and the heteroatom in the 4- to 6-membered heterocyclyl group is one or more selected from N, O and S, and the number of heteroatoms is one or two.

[0174] In one embodiment, TIFF2025533951000053.tif1741 Ring A is a 5- to 12-membered heteroaryl ring, and the heteroatom in the 5- to 12-membered heteroaryl ring is one or more of N, O, and S, and the number of heteroatoms is 1, 2, or 3; R 1 is unsubstituted or contains one or more R 1-1 a 6-12 membered aryl group substituted by, or unsubstituted or substituted by one or more R 1-2 wherein the heteroatoms in the 5-12 membered heteroaryl group are one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3; Each R 1-1 and R 1-2 are independently deuterium, halogen, cyano group, amino group, unsubstituted or one or more R 1-1-1 C1-C6 alkyl group substituted with, or unsubstituted or one or more R 1-1-2 is a C1-C6 alkoxy group substituted by Each R 1-1-1 and R 1-1-2 are independently deuterium or a halogen; Each R 2 are independently deuterium or a C1-C6 alkyl group; m is 0, 1, 2 or 3; Ring B may be unsubstituted or may contain one or more R b-1 wherein the heteroatoms in the 5-20 membered fused ring heteroaryl ring are one or more of N, O and S, and the number of heteroatoms is 1, 2, 3, 4, 5 or 6; the single heteroaryl ring in the 5-20 membered fused ring heteroaryl ring is a 5-7 membered heteroaryl ring, and the number of rings in the 5-20 membered fused ring heteroaryl ring is 2, 3 or 4; Each R b-1 are independently deuterium, oxo (=O), halogen, cyano, hydroxy, unsubstituted or one or more R b-1-1C1-C6 alkyl group substituted with, or unsubstituted or one or more R b-1-2 is a C1-C6 alkoxy group substituted by Each R b-1-1 and R b-1-2 are independently a hydroxy group, a halogen, or an unsubstituted or one or two R b-1-2-1 is an amino group substituted by Each R b-1-2-1 are independently hydrogen or a C1-C6 alkyl group; R 3 is hydrogen, unsubstituted or one or more R 3-1 a 3-6 membered cycloalkyl group, unsubstituted or substituted by one or more R 3-2 a 4-12 membered heterocyclyl group, unsubstituted or substituted by one or more R 3-3 a 4-10 membered cycloalkenyl group, unsubstituted or substituted by one or more R 3-4 a 4-10 membered heterocycloalkenyl group, unsubstituted or substituted by one or more R 3-5 a 6-10 membered aryl group, unsubstituted or substituted by one or more R 3-6 a 5-10 membered heteroaryl group substituted by -C(O)R 4 , -NH(CH2) p R 5 , -O(CH2) q R 6 , unsubstituted or one or more R 3-7 C1-C6 alkyl group substituted with, or unsubstituted or one or more R 3-8 -OR is replaced by 7 wherein the heteroatoms in the 4- to 12-membered heterocyclyl group, the 4- to 10-membered heterocycloalkenyl group, or the 5- to 10-membered heteroaryl group are selected from one or more of N, O, and S, and the number of heteroatoms is 1, 2, or 3; p is 0, 1, 2 or 3; q is 1, 2 or 3; Each R 3-1are independently deuterium, a hydroxy group, a halogen, or a C1-C6 alkyl group; Each R 3-2 are independently deuterium, hydroxyl group, halogen, cyano group, amino group, -NHC(O)R 3-2-1 , unsubstituted or one or more R 3-2-2 C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, oxo group (=O), -C(O)NH2, unsubstituted or substituted with one or more R 3-2-3 a 3- to 6-membered cycloalkyl group or a 4- to 6-membered heterocyclyl group substituted with, wherein the heteroatoms in the 4- to 6-membered heterocyclyl group are selected from one or more of N, O and S, and the number of heteroatoms is 1 or 2; R 3-2-1 is a C1-C6 alkyl group, Each R 3-2-2 are independently a hydroxy group or a halogen; Each R 3-2-3 are independently a C1-C6 alkyl group or a hydroxy group, Each R 3-3 are independently deuterium, hydroxyl group, halogen, cyano group, amino group, -S(O)2R 3-4-1 or -NR 3-4-2 R 3-4-2 and Each R 3-4 are independently deuterium, hydroxyl group, C1-C6 alkyl group, oxo group (=O), cyano group, halogen, 4- to 6-membered heterocyclyl group, -S(O)2R 3-4-1 or -NR 3-4-2 R 3-4-2 and R 3-4-1 is a C1-C6 alkyl group, Each R 3-4-2 are independently hydrogen or a C1-C6 alkyl group; Each R 3-5 are independently deuterium or TIFF2025533951000054.tif1529R 3-5-1 is a C1-C6 alkyl group, Each R 3-6are independently deuterium, halogen, or a C1-C6 alkyl group; Each R 3-7 are independently deuterium, a hydroxy group, a halogen atom, or a 4- to 6-membered heterocyclyl group, the heteroatom in the 4- to 6-membered heterocyclyl group is O, and the number of heteroatoms is 1; R 3-8 is a hydroxy group, R 4 is a 4- to 6-membered heterocyclyl group, wherein the heteroatoms in the 4- to 6-membered heterocyclyl group are selected from one or more of N, O and S, and the number of heteroatoms is 1 or 2; R 5 is unsubstituted or contains one or more R 5-1 is a 3- to 6-membered cycloalkyl group substituted by Each R 5-1 are independently a hydroxy group, R 6 is unsubstituted or contains one or more R 6-1 is a 3- to 6-membered cycloalkyl group substituted by Each R 6-1 are independently a hydroxy group, R 7 is a 3-6 membered cycloalkyl group.

[0175] In one embodiment, TIFF2025533951000055.tif1539 Ring A is a 5- to 10-membered heteroaryl ring, the heteroatom in the 5- to 10-membered heteroaryl ring is N, and the number of heteroatoms is 1 or 2; R 1 is unsubstituted or contains one or more R 1-1 a 6-10 membered aryl group substituted by, or unsubstituted or one or more R 1-2 wherein the heteroatom in the 5-6 membered heteroaryl group is N and the number of heteroatoms is 1 or 2; Each R 1-1 and R 1-2are independently deuterium, halogen, unsubstituted or one or more R 1-1-1 C1-C6 alkyl group, unsubstituted or substituted by one or more R 1-1-2 or a C1-C6 alkoxy group substituted by TIFF2025533951000056.tif1534 each R 1-1-1 and R 1-1-2 are independently halogen; Each R 1-1-11 are independently a hydroxy group or a C1-C6 alkyl group, R 2 are independently deuterium, or unsubstituted or one or more R 2-1 is a C1-C6 alkyl group substituted by Each R 2-1 are independently halogen or deuterium, m is 0 or 1, Ring B may be unsubstituted or may contain one or more R b-1 wherein the heteroatoms in the 5-12 membered fused ring heteroaryl ring are N and / or S, the number of heteroatoms is 1, 2, 3 or 4, and the number of rings in the 5-12 membered fused ring heteroaryl ring is 2; Each R b-1 are independently deuterium, cyano, halogen, or unsubstituted or one or more R b-1-1 is a C1-C6 alkyl group substituted by Each R b-1-1 are independently halogen; R 3 is hydrogen, TIFF2025533951000057.tif1521 Unsubstituted or one or more R 3-1 a 3-6 membered cycloalkyl group, unsubstituted or substituted by one or more R 3-2 a 4-9 membered heterocyclyl group, unsubstituted or substituted by one or more R 3-3 a 4-6 membered cycloalkenyl group, unsubstituted or substituted by one or more R 3-4a 4- to 6-membered heterocycloalkenyl group, unsubstituted or substituted by one or more R 3-5 a phenyl group, unsubstituted or substituted by one or more R 3-6 a 5-10 membered heteroaryl group substituted by -C(O)R 4 , or unsubstituted or one or more R 3-7 wherein the heteroatoms in the 4- to 6-membered heterocycloalkenyl group and the 5- to 10-membered heteroaryl group are N and / or O, and the number of heteroatoms is 1 or 2; the heteroatoms in the 4- to 9-membered heterocyclyl group are selected from one or two of N, O, and S, and the number of heteroatoms is 1 or 2; Each R 3-1 are independently deuterium or a hydroxy group, Each R 3-2 are independently deuterium, oxo, halogen, C1-C6 alkoxy group, -NR 3-4-2 R 3-4-2 , -S(O)2R 3-4-1 , a hydroxy group, or unsubstituted or one or more R 3-2-2 is a C1-C6 alkyl group substituted by Each R 3-3 are independently deuterium, oxo, amino, or hydroxy; Each R 3-4 are independently deuterium, oxo, or a C1-C6 alkyl group; R 3-4-1 is a C1-C6 alkyl group, Each R 3-4-2 are independently -S(O)R 3-4-1 , hydrogen or a C1-C6 alkyl group; Each R 3-5 are independently deuterium, TIFF2025533951000058.tif1774R 3-5-1 are independently a C1-C6 alkyl group, Each R 3-5-2 are independently a hydroxy group, a C1-C6 alkyl group, or a 1-10 membered heteroalkyl group, or two R 3-5-2form a 4-10 membered heterocyclyl group, wherein the heteroatoms in the 1-10 membered heteroalkyl group include, in addition to phosphorus, any one or more selected from N, O and S, and the number of heteroatoms is 1, 2, 3 or 4; the heteroatoms in the 4-10 membered heterocyclyl group include, in addition to phosphorus, any one or more selected from N, O and S, and the number of heteroatoms is 1, 2, 3 or 4; Each R 3-6 are independently deuterium, halogen, unsubstituted or one or more R 3-2-2 C1-C6 alkyl group substituted with, or unsubstituted or one or more R 3-6-1 wherein the heteroatoms in the 4-6 membered heterocyclyl group are selected from any one or two of N, O and S, and the number of heteroatoms is 1 or 2; Each R 3-6-1 are independently a C1-C6 alkyl group, Each R 3-2-2 are independently deuterium or a hydroxy group, Each R 3-7 are independently deuterium, hydroxyl group, -S(O)R 3-4-1 a 4- to 6-membered heterocyclyl group, wherein the heteroatom in the 4- to 6-membered heterocyclyl group is O and the number of heteroatoms is 1; R 4 is a 4- to 6-membered heterocyclyl group, the heteroatom in the 4- to 6-membered heterocyclyl group is O, the number of heteroatoms is 1, and R 4 is a 4- to 6-membered heterocyclyl group, wherein the heteroatoms in the 4- to 6-membered heterocyclyl group are selected from one or more of N, O and S, and the number of heteroatoms is 1 or 2; R 5 is unsubstituted or contains one or more R 5-1 is a 3- to 6-membered cycloalkyl group substituted by Each R 5-1 are independently a hydroxy group, R 6 is unsubstituted or contains one or more R 6-1is a 3- to 6-membered cycloalkyl group substituted by Each R 6-1 are independently a hydroxy group, R 7 is a 3-6 membered cycloalkyl group.

[0176] In one embodiment, TIFF2025533951000059.tif1440 Ring A is a 5- to 10-membered heteroaryl ring, the heteroatom in the 5- to 10-membered heteroaryl ring is N, and the number of heteroatoms is 1 or 2; R 1 is unsubstituted or contains one or more R 1-1 a 6-10 membered aryl group substituted by, or unsubstituted or substituted by one or more R 1-2 wherein the heteroatom in the 5-6 membered heteroaryl group is N and the number of heteroatoms is 1 or 2; Each R 1-1 and R 1-2 are independently deuterium, halogen, unsubstituted or one or more R 1-1-1 C1-C6 alkyl group, unsubstituted or substituted by one or more R 1-1-2 or a C1-C6 alkoxy group substituted by TIFF2025533951000060.tif1433 each R 1-1-1 and R 1-1-2 are independently halogen; Each R 1-1-11 are independently a hydroxy group or a C1-C6 alkyl group, R 2 are independently deuterium, or unsubstituted or one or more R 2-1 is a C1-C6 alkyl group substituted by Each R 2-1 are independently halogen; m is 0 or 1, Ring B may be unsubstituted or may contain one or more R b-1wherein the heteroatoms in the 5-12 membered fused ring heteroaryl ring are N and / or S, the number of heteroatoms is 1, 2, 3 or 4, and the number of rings in the 5-12 membered fused ring heteroaryl ring is 2; Each R b-1 are independently deuterium, halogen, or unsubstituted or one or more R b-1-1 is a C1-C6 alkyl group substituted by Each R b-1-1 are independently halogen; R 3 is hydrogen, unsubstituted or one or more R 3-1 a 3-6 membered cycloalkyl group, unsubstituted or substituted by one or more R 3-2 a 4-6 membered heterocyclyl group, unsubstituted or substituted by one or more R 3-3 a 4-6 membered cycloalkenyl group, unsubstituted or substituted by one or more R 3-4 a 4- to 6-membered heterocycloalkenyl group, unsubstituted or substituted by one or more R 3-5 a phenyl group, unsubstituted or substituted by one or more R 3-6 a 5-6 membered heteroaryl group substituted by -C(O)R 4 , or unsubstituted or one or more R 3-7 wherein the heteroatoms in the 4- to 6-membered heterocyclyl group, 4- to 6-membered heterocycloalkenyl group, or 5- to 6-membered heteroaryl group are N and / or O, and the number of heteroatoms is 1 or 2; Each R 3-1 are independently deuterium or a hydroxy group, Each R 3-2 are independently deuterium, a hydroxy group, or a C1-C6 alkyl group; Each R 3-3 are independently deuterium or a hydroxy group, Each R 3-4 are independently deuterium or a C1-C6 alkyl group; Each R3-5 are independently deuterium or TIFF2025533951000061.tif1528R 3-5-1 is a C1-C6 alkyl group, Each R 3-6 are independently deuterium, halogen, or a C1-C6 alkyl group; Each R 3-7 are independently deuterium or a 4- to 6-membered heterocyclyl group, the heteroatom in the 4- to 6-membered heterocyclyl group is O, and the number of heteroatoms is 1; R 4 is a 4- to 6-membered heterocyclyl group, the heteroatom in the 4- to 6-membered heterocyclyl group is O, and the number of heteroatoms is 1.

[0177] In one embodiment, TIFF2025533951000062.tif1437 Ring A is a 5- to 10-membered heteroaryl ring, the heteroatom in the 5- to 10-membered heteroaryl ring is N, and the number of heteroatoms is 1 or 2; R 1 is unsubstituted or contains one or more R 1-1 a 6-10 membered aryl group substituted by, or unsubstituted or substituted by one or more R 1-2 wherein the heteroatom in the 5-6 membered heteroaryl group is N and the number of heteroatoms is 1 or 2; Each R 1-1 and R 1-2 are independently deuterium, halogen, unsubstituted or one or more R 1-1-1 C1-C6 alkyl group, unsubstituted or substituted by one or more R 1-1-2 or a C1-C6 alkoxy group substituted by TIFF2025533951000063.tif1433 each R 1-1-1 and R 1-1-2 are independently halogen or deuterium, Each R 1-1-11 are independently a hydroxy group or a C1-C6 alkyl group, R 2 are independently deuterium, or unsubstituted or one or more R 2-1 is a C1-C6 alkyl group substituted by Each R 2-1 are independently halogen or deuterium, m is 0 or 1, Ring B may be unsubstituted or may contain one or more R b-1 wherein the heteroatoms in the 5-12 membered fused ring heteroaryl ring are N and / or S, the number of heteroatoms is 1, 2, 3 or 4, and the number of rings in the 5-12 membered fused ring heteroaryl ring is 2; Each R b-1 are independently deuterium, cyano, halogen, or unsubstituted or one or more R b-1-1 is a C1-C6 alkyl group substituted by Each R b-1-1 are independently halogen; R 3 is hydrogen, TIFF2025533951000064.tif1520 No substitution or one or more R 3-1 a 3-6 membered cycloalkyl group, unsubstituted or substituted by one or more R 3-2 a 4-9 membered heterocyclyl group, unsubstituted or substituted by one or more R 3-3 a 4-6 membered cycloalkenyl group, unsubstituted or substituted by one or more R 3-4 a 4- to 6-membered heterocycloalkenyl group, unsubstituted or substituted by one or more R 3-5 a phenyl group, unsubstituted or substituted by one or more R 3-6 a 5-10 membered heteroaryl group substituted by -C(O)R 4 , or unsubstituted or one or more R 3-7wherein the heteroatoms in the 4- to 6-membered heterocycloalkenyl group or the 5- to 10-membered heteroaryl group are N and / or O, and the number of heteroatoms is 1 or 2; the heteroatoms in the 4- to 9-membered heterocyclyl group are selected from one or two of N, O, and S, and the number of heteroatoms is 1 or 2; Each R 3-1 are independently deuterium or a hydroxy group, Each R 3-2 are independently deuterium, oxo, halogen, C1-C6 alkoxy group, -NR 3-4-2 R 3-4-2 , -S(O)2R 3-4-1 , a hydroxy group, or unsubstituted or one or more R 3-2-2 is a C1-C6 alkyl group substituted by Each R 3-3 are independently deuterium, oxo, amino, or hydroxy; Each R 3-4 are independently deuterium, oxo, or a C1-C6 alkyl group; R 3-4-1 is a C1-C6 alkyl group, Each R 3-4-2 are independently -S(O)R 3-4-1 , hydrogen or a C1-C6 alkyl group; Each R 3-5 are independently deuterium, TIFF2025533951000065.tif1774R 3-5-1 is a C1-C6 alkyl group, Each R 3-6 are independently deuterium, halogen, unsubstituted or one or more R 3-2-2 C1-C6 alkyl group substituted with, or unsubstituted or one or more R 3-6-1 wherein the heteroatoms in the 4-6 membered heterocyclyl group are selected from any one or two of N, O and S, and the number of heteroatoms is 1 or 2; Each R 3-5-2are independently a hydroxy group, a C1-C6 alkyl group, or a 1-10 membered heteroalkyl group, or two R 3-5-2 form a 4-10 membered heterocyclyl group, wherein the heteroatoms in the 1-10 membered heteroalkyl group include, in addition to phosphorus, any one or more selected from N, O and S, and the number of heteroatoms is 1, 2, 3 or 4; the heteroatoms in the 4-10 membered heterocyclyl group include, in addition to phosphorus, any one or more selected from N, O and S, and the number of heteroatoms is 1, 2, 3 or 4; Each R 3-6-1 are independently a C1-C6 alkyl group, Each R 3-2-2 are independently deuterium or a hydroxy group; Each R 3-7 are independently deuterium, hydroxyl group, -S(O)R 3-4-1 a 4- to 6-membered heterocyclyl group, wherein the heteroatom in the 4- to 6-membered heterocyclyl group is O and the number of heteroatoms is 1; R 4 is a 4- to 6-membered heterocyclyl group, the heteroatom in the 4- to 6-membered heterocyclyl group is O, and the number of heteroatoms is 1.

[0178] In one embodiment, TIFF2025533951000066.tif1438 Ring A is a 5- to 10-membered heteroaryl ring, the heteroatom in the 5- to 10-membered heteroaryl ring is N, and the number of heteroatoms is 1 or 2; R 1 is unsubstituted or contains one or more R 1-1 a 6-10 membered aryl group substituted by, or unsubstituted or substituted by one or more R 1-2 wherein the heteroatom in the 5-6 membered heteroaryl group is N and the number of heteroatoms is 1; Each R 1-1 and R 1-2 are independently halogen, or unsubstituted or one or more R 1-1-2is a C1-C6 alkoxy group substituted by Each R 1-1-2 are independently halogen; R 2 are independently a C1-C6 alkyl group, m is 0 or 1, Ring B may be unsubstituted or may contain one or more R b-1 wherein the heteroatoms in the 5-12 membered fused ring heteroaryl ring are N and / or S and the number of heteroatoms is 1, 2, 3 or 4, the single heteroaryl ring in the 5-12 membered fused ring heteroaryl ring is a 5-7 membered heteroaryl ring and the number of rings in the 5-12 membered fused ring heteroaryl ring is 2, Each R b-1 are independently halogen; R 3 is hydrogen, unsubstituted or one or more R 3-1 a 3-6 membered cycloalkyl group, unsubstituted or substituted by one or more R 3-2 a 4-6 membered heterocyclyl group, unsubstituted or substituted by one or more R 3-3 a 4-6 membered cycloalkenyl group, unsubstituted or substituted by one or more R 3-4 a 4-6 membered heterocycloalkenyl group, unsubstituted or substituted by one or more R 3-5 a phenyl group, unsubstituted or substituted by one or more R 3-6 or a 5-6 membered heteroaryl group substituted by -C(O)R 4 wherein the heteroatoms in the 4- to 6-membered heterocyclyl group, the 4- to 6-membered heterocycloalkenyl group, or the 5- to 6-membered heteroaryl group are N and / or O, and the number of heteroatoms is 1 or 2; Each R 3-1 are independently a hydroxy group, Each R 3-2 are independently a hydroxy group or a C1-C6 alkyl group, Each R 3-3 are independently a hydroxy group, Each R 3-4 are independently a C1-C6 alkyl group, Each R 3-5 is independently TIFF2025533951000067.tif1528R 3-5-1 is a C1-C6 alkyl group, Each R 3-6 are independently halogen or a C1-C6 alkyl group; R 4 is a 4- to 6-membered heterocyclyl group, the heteroatom in the 4- to 6-membered heterocyclyl group is O, and the number of heteroatoms is 1.

[0179] In one embodiment, TIFF2025533951000068.tif1538 Ring A is a 5- to 10-membered heteroaryl ring, the heteroatom in the 5- to 10-membered heteroaryl ring is N, and the number of heteroatoms is 1 or 2; R 1 is unsubstituted or contains one or more R 1-1 a 6-10 membered aryl group substituted by, or unsubstituted or one or more R 1-2 wherein the heteroatom in the 5-6 membered heteroaryl group is N and the number of heteroatoms is 1; Each R 1-1 and R 1-2 are independently halogen, or unsubstituted or one or more R 1-1-2 is a C1-C6 alkoxy group substituted by Each R 1-1-2 are independently deuterium or a halogen; Each R 2 are independently unsubstituted or one or more R 2-1 is a C1-C6 alkyl group substituted by Each R 2-1 are independently deuterium, m is 0 or 1, Ring B may be unsubstituted or may contain one or more R b-1wherein the heteroatoms in the 5-12 membered fused ring heteroaryl ring are N and / or S and the number of heteroatoms is 1, 2, 3 or 4, the single heteroaryl ring in the 5-12 membered fused ring heteroaryl ring is a 5-7 membered heteroaryl ring and the number of rings in the 5-12 membered fused ring heteroaryl ring is 2, Each R b-1 are independently halogen; R 3 is hydrogen, unsubstituted or one or more R 3-1 a 3-6 membered cycloalkyl group, unsubstituted or substituted by one or more R 3-2 a 4-6 membered heterocyclyl group, unsubstituted or substituted by one or more R 3-3 a 4-6 membered cycloalkenyl group, unsubstituted or substituted by one or more R 3-4 a 4-6 membered heterocycloalkenyl group, unsubstituted or substituted by one or more R 3-5 a phenyl group, unsubstituted or substituted by one or more R 3-6 or a 5-6 membered heteroaryl group substituted by -C(O)R 4 wherein the heteroatoms in the 4- to 6-membered heterocyclyl group, the 4- to 6-membered heterocycloalkenyl group, or the 5- to 6-membered heteroaryl group are N and / or O, and the number of heteroatoms is 1 or 2; Each R 3-1 are independently a hydroxy group or deuterium; Each R 3-2 are independently a hydroxy group, deuterium, or a C1-C6 alkyl group; Each R 3-3 are independently a hydroxy group or deuterium; Each R 3-4 are independently a C1-C6 alkyl group, Each R 3-5 is independently TIFF2025533951000069.tif1874R 3-5-1 is a C1-C6 alkyl group, Each R3-5-2 are independently a hydroxy group, a C1-C6 alkyl group, or a 1-10 membered heteroalkyl group, or two R 3-5-2 form a 4-10 membered heterocyclyl group, wherein the heteroatoms in the 1-10 membered heteroalkyl group include, in addition to phosphorus, any one or more selected from N, O and S, and the number of heteroatoms is 1, 2, 3 or 4; the heteroatoms in the 4-10 membered heterocyclyl group include, in addition to phosphorus, any one or more selected from N, O and S, and the number of heteroatoms is 1, 2, 3 or 4; Each R 3-6 are independently halogen, unsubstituted or substituted with one or more R 3-2-2 is replaced by Each R 3-2-2 are independently deuterium, R 4 is a 4- to 6-membered heterocyclyl group, the heteroatom in the 4- to 6-membered heterocyclyl group is O, and the number of heteroatoms is 1.

[0180] In one embodiment, TIFF2025533951000070.tif1438 Ring A is a 5- or 6-membered heteroaryl ring, the heteroatom in the 5- or 6-membered heteroaryl ring is N, and the number of heteroatoms is 1 or 2; R 1 is unsubstituted or contains one or more R 1-1 or a phenyl group substituted with one or more R 1-2 wherein the heteroatom in the 5-6 membered heteroaryl group is N and the number of heteroatoms is 1; Each R 1-1 and R 1-2 are independently halogen, or unsubstituted or one or more R 1-1-2 is a C1-C6 alkoxy group substituted by Each R 1-1-2 are independently halogen; R 2 are independently a C1-C6 alkyl group, m is 0 or 1, Ring B is a 5,6-heteroaryl ring (both 5- and 6-membered rings are aromatic rings), the heteroatoms in the 5,6-heteroaryl ring are N and / or S, and the number of heteroatoms is 1, 2, or 3; R 3 is hydrogen, unsubstituted or one or more R 3-1 a 3-6 membered cycloalkyl group, unsubstituted or substituted by one or more R 3-2 a 4-6 membered heterocyclyl group substituted by, or unsubstituted or substituted by one or more R 3-3 wherein the heteroatoms in the 4-6 membered heterocyclyl group are N and / or O, and the number of heteroatoms is 1 or 2; Each R 3-1 are independently a hydroxy group, Each R 3-2 are independently a hydroxy group or a C1-C6 alkyl group, Each R 3-3 are independently a hydroxy group.

[0181] In one embodiment, TIFF2025533951000071.tif1438 Ring A is a 5- or 6-membered heteroaryl ring, the heteroatom in the 5- or 6-membered heteroaryl ring is N, and the number of heteroatoms is 1; R 1 is unsubstituted or contains one or more R 1-1 or a phenyl group substituted with one or more R 1-2 wherein the heteroatom in the 5-6 membered heteroaryl group is N and the number of heteroatoms is 1; Each R 1-1 and R 1-2 are independently halogen, or unsubstituted or one or more R 1-1-2 is a C1-C6 alkoxy group substituted by Each R 1-1-2are independently halogen or deuterium, R 2 are independently unsubstituted or one or more R 2-1 is a C1-C6 alkyl group substituted by Each R 2-1 are independently deuterium, m is 0 or 1, Ring B is a 5,6-ring heteroaryl ring, the heteroatoms in the 5,6-ring heteroaryl ring are N and / or S, and the number of heteroatoms is 1, 2, 3, or 4; R 3 is unsubstituted or contains one or more R 3-1 a 3-6 membered cycloalkyl group, unsubstituted or substituted by one or more R 3-3 a 4-6 membered cycloalkenyl group, unsubstituted or substituted by one or more R 3-5 or a phenyl group substituted with one or more R 3-6 wherein the heteroatoms in the 4-6 membered heterocyclyl group are N and / or O and the number of heteroatoms is 1 or 2, and the heteroatom in the 5-6 membered heteroaryl ring is N and the number of heteroatoms is 2; Each R 3-1 are independently a hydroxy group, Each R 3-3 are independently a hydroxy group, Each R 3-5 is independently TIFF2025533951000072.tif1757R 3-5-1 and R 3-5-2 are independently a C1-C6 alkyl group, Each R 3-6 are independently halogen, unsubstituted or substituted with one or more R 3-2-2 is replaced by Each R 3-2-2 are independently deuterium.

[0182] In one embodiment, TIFF2025533951000073.tif1439 Ring A is a 5- or 6-membered heteroaryl ring, the heteroatom in the 5- or 6-membered heteroaryl ring is N, and the number of heteroatoms is 1; R 1 is unsubstituted or contains one or more R 1-1 or a phenyl group substituted with one or more R 1-2 wherein the heteroatom in the 5-6 membered heteroaryl group is N and the number of heteroatoms is 1; Each R 1-1 and R 1-2 are independently halogen, or unsubstituted or one or more R 1-1-2 is a C1-C6 alkoxy group substituted by Each R 1-1-2 are independently halogen; R 2 are independently a C1-C6 alkyl group, m is 0 or 1, Ring B is a 5,6-ring heteroaryl ring, the heteroatoms in the 5,6-ring heteroaryl ring are N and / or S, and the number of heteroatoms is 1, 2 or 3; R 3 is unsubstituted or contains one or more R 3-1 a 3-6 membered cycloalkyl group substituted by, or unsubstituted or substituted by one or more R 3-3 is a 4-6 membered cycloalkenyl group substituted by Each R 3-1 are independently a hydroxy group, Each R 3-3 are independently a hydroxy group.

[0183] In one embodiment, TIFF2025533951000074.tif1438 Ring A is a 5- or 6-membered heteroaryl ring, the heteroatom in the 5- or 6-membered heteroaryl ring is N, and the number of heteroatoms is 1; R 1is unsubstituted or contains one or more R 1-1 or a phenyl group substituted with one or more R 1-2 wherein the heteroatom in the 5-6 membered heteroaryl group is N and the number of heteroatoms is 1; Each R 1-1 and R 1-2 are independently halogen, or unsubstituted or one or more R 1-1-2 is a C1-C6 alkoxy group substituted by Each R 1-1-2 are independently halogen or deuterium, R 2 are independently unsubstituted or one or more R 2-1 is a C1-C6 alkyl group substituted by Each R 2-1 are independently deuterium, m is 0 or 1, Ring B may be unsubstituted or may contain one or more R b-1 is a 5-12 membered fused heteroaryl ring substituted by The 5- to 12-membered fused heteroaryl ring is TIFF2025533951000075.tif38151 each R b-1 are independently halogen; R 3 is unsubstituted or contains one or more R 3-1 a 3-6 membered cycloalkyl group, unsubstituted or substituted by one or more R 3-3 a 4-6 membered cycloalkenyl group, unsubstituted or substituted by one or more R 3-5 or a phenyl group substituted with one or more R 3-6 wherein the heteroatoms in the 4-6 membered heterocyclyl group are N and / or O and the number of heteroatoms is 1 or 2, and the heteroatom in the 5-6 membered heteroaryl ring is N and the number of heteroatoms is 2; Each R 3-1are independently a hydroxy group, Each R 3-3 are independently a hydroxy group, Each R 3-5 is independently TIFF2025533951000076.tif1857R 3-5-1 and R 3-5-2 are independently a C1-C6 alkyl group, Each R 3-6 are independently halogen, unsubstituted or substituted with one or more R 3-2-2 is replaced by Each R 3-2-2 are independently deuterium.

[0184] In one embodiment, TIFF2025533951000077.tif1438 Ring A is a 6- to 12-membered aryl ring or a 5- to 6-membered heteroaryl ring, in which the heteroatom in the 5- to 6-membered heteroaryl ring is selected from any one or two of N, O, and S, and the number of heteroatoms is 1, 2, or 3; R 1 is unsubstituted or contains one or more R 1-1 a 6-12 membered aryl group substituted by, or unsubstituted or one or more R 1-2 wherein the heteroatoms in the 5- or 6-membered heteroaryl ring are selected from any one or two of N, O and S, and the number of heteroatoms is 1, 2 or 3; Each R 1-1 and R 1-2 are independently a halogen or a C1-C6 alkoxy group; Ring B may be unsubstituted or may contain one or more R b-1wherein the heteroatoms in the 5-20 membered fused ring heteroaryl ring are selected from one or more of N, O and S, and the number of heteroatoms is 1, 2, 3, 4, 5, 6, 7 or 8; the single heteroaryl ring in the 5-20 membered fused ring heteroaryl ring is a 5-7 membered heteroaryl ring; and the number of rings in the 5-20 membered fused ring heteroaryl ring is 3 or 4; R 3 is hydrogen.

[0185] In one embodiment, TIFF2025533951000078.tif1338 Ring A is a 5- to 10-membered heteroaryl ring, the heteroatom in the 5- to 10-membered heteroaryl ring is N, and the number of heteroatoms is 1 or 2; R 1 is unsubstituted or contains one or more R 1-1 a 6-10 membered aryl group substituted by, or unsubstituted or one or more R 1-2 wherein the heteroatom in the 5-6 membered heteroaryl group is N and the number of heteroatoms is 1 or 2; Each R 1-1 and R 1-2 are independently deuterium, halogen, unsubstituted or one or more R 1-1-1 C1-C6 alkyl group, unsubstituted or substituted by one or more R 1-1-2 or a C1-C6 alkoxy group substituted by TIFF2025533951000079.tif1534 each R 1-1-1 and R 1-1-2 are independently halogen or deuterium, Each R 1-1-11 are independently a hydroxy group or a C1-C6 alkyl group, R 2 are independently deuterium, or unsubstituted or one or more R 2-1 is a C1-C6 alkyl group substituted by Each R2-1 are independently halogen or deuterium, m is 0 or 1, Ring B is one or more R b-1 wherein the heteroatoms in the 5-12 membered fused ring heteroaryl ring are N and / or S, the number of heteroatoms is 1, 2, 3 or 4, and the number of rings in the 5-12 membered fused ring heteroaryl ring is 2; Each R b-1 are independently halogen, or unsubstituted or one or more R b-1-1 is a C1-C6 alkyl group substituted by Each R b-1-1 are independently halogen; R 3 is hydrogen, unsubstituted or one or more R 3-1 a 3-6 membered cycloalkyl group, unsubstituted or substituted by one or more R 3-2 a 4-12 membered heterocyclyl group, unsubstituted or substituted by one or more R 3-3 a 4-10 membered cycloalkenyl group, unsubstituted or substituted by one or more R 3-4 a 4-10 membered heterocycloalkenyl group, unsubstituted or substituted by one or more R 3-5 a 6-10 membered aryl group, unsubstituted or substituted by one or more R 3-6 a 5-10 membered heteroaryl group substituted by -C(O)R 4 , unsubstituted or one or more R 3-7 C1-C6 alkyl group substituted with, or unsubstituted or one or more R 3-8 -OR is replaced by 7 wherein the heteroatoms in the 4- to 12-membered heterocyclyl group or the 4- to 10-membered heterocycloalkenyl group are one or more of N, O, and S, and the number of heteroatoms is 1 or 2; the heteroatoms in the 5- to 10-membered heteroaryl group are N and / or O, and the number of heteroatoms is 1, 2, 3, or 4; Each R 3-1are independently deuterium or a hydroxy group; Each R 3-2 are independently deuterium, oxo, halogen, C1-C6 alkoxy group, -NR 3-4-2 R 3-4-2 , -S(O)2R 3-4-1 , a hydroxy group, or unsubstituted or one or more R 3-2-2 is a C1-C6 alkyl group substituted by Each R 3-3 are independently deuterium, oxo, amino, or hydroxy; Each R 3-4 are independently deuterium, oxo, or a C1-C6 alkyl group; R 3-4-1 is a C1-C6 alkyl group, Each R 3-4-2 are independently -S(O)R 3-4-1 , hydrogen or a C1-C6 alkyl group; Each R 3-5 are independently deuterium, TIFF2025533951000080.tif1774R 3-5-1 is a C1-C6 alkyl group, Each R 3-6 are independently deuterium, halogen, unsubstituted or one or more R 3-2-2 C1-C6 alkyl group substituted with, or unsubstituted or one or more R 3-6-1 wherein the heteroatoms in the 4-6 membered heterocyclyl group are selected from any one or two of N, O and S, and the number of heteroatoms is 1 or 2; Each R 3-5-2 are independently a hydroxy group, a C1-C6 alkyl group, or a 1-10 membered heteroalkyl group, or two R 3-5-2form a 4-10 membered heterocyclyl group, wherein the heteroatoms in the 1-10 membered heteroalkyl group include, in addition to phosphorus, any one or more selected from N, O and S, and the number of heteroatoms is 1, 2, 3 or 4; the heteroatoms in the 4-10 membered heterocyclyl group include, in addition to phosphorus, any one or more selected from N, O and S, and the number of heteroatoms is 1, 2, 3 or 4; Each R 3-6-1 are independently a C1-C6 alkyl group, Each R 3-2-2 are independently deuterium or a hydroxy group, Each R 3-7 are independently deuterium, hydroxyl group, -S(O)R 3-4-1 a 4- to 6-membered heterocyclyl group, wherein the heteroatom in the 4- to 6-membered heterocyclyl group is O and the number of heteroatoms is 1; Each R 3-8 are independently deuterium or a hydroxy group, R 4 is a 4- to 6-membered heterocyclyl group, the heteroatom in the 4- to 6-membered heterocyclyl group is O, and the number of heteroatoms is 1; R 7 is a 3-6 membered cycloalkyl group.

[0186] In one embodiment, TIFF2025533951000081.tif1438 Ring A is a 5- to 10-membered heteroaryl ring, the heteroatom in the 5- to 10-membered heteroaryl ring is N, and the number of heteroatoms is 1 or 2; R 1 is unsubstituted or contains one or more R 1-1 a 6-10 membered aryl group substituted by, or unsubstituted or one or more R 1-2 wherein the heteroatom in the 5-6 membered heteroaryl group is N and the number of heteroatoms is 1 or 2; Each R 1-1 and R 1-2are independently deuterium, halogen, unsubstituted or one or more R 1-1-1 C1-C6 alkyl group substituted with, or unsubstituted or one or more R 1-1-2 is a C1-C6 alkoxy group substituted by Each R 1-1-1 and R 1-1-2 are independently halogen or deuterium, Each R 1-1-11 are independently a hydroxy group or a C1-C6 alkyl group, R 2 are independently deuterium, or unsubstituted or one or more R 2-1 is a C1-C6 alkyl group substituted by Each R 2-1 are independently halogen or deuterium, m is 0 or 1, Ring B is one or more R b-1 wherein the heteroatoms in the 5-12 membered fused ring heteroaryl ring are N and / or S, the number of heteroatoms is 1, 2, 3 or 4, and the number of rings in the 5-12 membered fused ring heteroaryl ring is 2; Each R b-1 are independently halogen, or unsubstituted or one or more R b-1-1 is a C1-C6 alkyl group substituted by Each R b-1-1 are independently halogen; R 3 is hydrogen, unsubstituted or one or more R 3-1 a 3-6 membered cycloalkyl group, unsubstituted or substituted by one or more R 3-2 a 4-12 membered heterocyclyl group, unsubstituted or substituted by one or more R 3-3 a 4-10 membered cycloalkenyl group, unsubstituted or substituted by one or more R 3-4 a 4-10 membered heterocycloalkenyl group, unsubstituted or substituted by one or more R 3-5a 6-10 membered aryl group, unsubstituted or substituted by one or more R 3-6 a 5-10 membered heteroaryl group substituted by -C(O)R 4 , unsubstituted or one or more R 3-7 C1-C6 alkyl group substituted with, or unsubstituted or one or more R 3-8 -OR is replaced by 7 wherein the heteroatoms in the 4- to 12-membered heterocyclyl group or the 4- to 10-membered heterocycloalkenyl group are one or more of N, O, and S, and the number of heteroatoms is 1 or 2; the heteroatoms in the 5- to 10-membered heteroaryl group are N and / or O, and the number of heteroatoms is 1, 2, 3, or 4; Each R 3-1 are independently deuterium or a hydroxy group; Each R 3-2 are independently deuterium, oxo, halogen, C1-C6 alkoxy group, -NR 3-4-2 R 3-4-2 , -S(O)2R 3-4-1 , a hydroxy group, or unsubstituted or one or more R 3-2-2 is a C1-C6 alkyl group substituted by Each R 3-3 are independently deuterium, oxo, amino, or hydroxy; Each R 3-4 are independently deuterium, oxo, or a C1-C6 alkyl group; R 3-4-1 is a C1-C6 alkyl group, Each R 3-4-2 are independently -S(O)R 3-4-1 , hydrogen or a C1-C6 alkyl group; Each R 3-5 are independently deuterium, TIFF2025533951000082.tif1874R 3-5-1 is a C1-C6 alkyl group, Each R 3-6 are independently deuterium, halogen, unsubstituted or one or more R 3-2-2C1-C6 alkyl group substituted with, or unsubstituted or one or more R 3-6-1 wherein the heteroatoms in the 4-6 membered heterocyclyl group are selected from any one or two of N, O and S, and the number of heteroatoms is 1 or 2; Each R 3-5-2 are independently a hydroxy group, a C1-C6 alkyl group, or a 1-10 membered heteroalkyl group, or two R 3-5-2 form a 4-10 membered heterocyclyl group, wherein the heteroatoms in the 1-10 membered heteroalkyl group include, in addition to phosphorus, any one or more selected from N, O and S, and the number of heteroatoms is 1, 2, 3 or 4; the heteroatoms in the 4-10 membered heterocyclyl group include, in addition to phosphorus, any one or more selected from N, O and S, and the number of heteroatoms is 1, 2, 3 or 4; Each R 3-6-1 are independently a C1-C6 alkyl group, Each R 3-2-2 are independently deuterium or a hydroxy group, Each R 3-7 are independently deuterium, hydroxyl group, -S(O)R 3-4-1 a 4- to 6-membered heterocyclyl group, wherein the heteroatom in the 4- to 6-membered heterocyclyl group is O and the number of heteroatoms is 1; Each R 3-8 are independently deuterium or a hydroxy group, R 4 is a 4- to 6-membered heterocyclyl group, the heteroatom in the 4- to 6-membered heterocyclyl group is O, and the number of heteroatoms is 1; R 7 is a 3-6 membered cycloalkyl group.

[0187] In one embodiment, TIFF2025533951000083.tif1438 Ring A is a 5- or 6-membered heteroaryl ring, the heteroatom in the 5- or 6-membered heteroaryl ring is N, and the number of heteroatoms is 1; R1 is unsubstituted or contains one or more R 1-2 wherein the heteroatom in the 5-6 membered heteroaryl group is N and the number of heteroatoms is 1 or 2; Each R 1-2 are independently deuterium, halogen, unsubstituted or one or more R 1-1-1 C1-C6 alkyl group, unsubstituted or substituted by one or more R 1-1-2 or a C1-C6 alkoxy group substituted by TIFF2025533951000084.tif1534 each R 1-1-1 and R 1-1-2 are independently halogen or deuterium, Each R 1-1-11 are independently a hydroxy group or a C1-C6 alkyl group, R 2 are independently deuterium, or unsubstituted or one or more R 2-1 is a C1-C6 alkyl group substituted by Each R 2-1 are independently halogen or deuterium, m is 0 or 1, Ring B is one or more R b-1 wherein the heteroatoms in the 5-12 membered fused ring heteroaryl ring are N and / or S, the number of heteroatoms is 1, 2, 3 or 4, and the number of rings in the 5-12 membered fused ring heteroaryl ring is 2; Each R b-1 are independently halogen, or unsubstituted or one or more R b-1-1 is a C1-C6 alkyl group substituted by Each R b-1-1 are independently halogen; R 3 is unsubstituted or contains one or more R 3-1 a 3-6 membered cycloalkyl group, unsubstituted or substituted by one or more R 3-2a 4-9 membered heterocyclyl group, unsubstituted or substituted by one or more R 3-3 a 4-6 membered cycloalkenyl group, unsubstituted or substituted by one or more R 3-4 a 4-6 membered heterocycloalkenyl group, unsubstituted or substituted by one or more R 3-5 or a phenyl group substituted with one or more R 3-6 wherein the heteroatoms in the 4-9 membered heterocyclyl group or the 4-6 membered heterocycloalkenyl group are N and / or O and the number of heteroatoms is 1 or 2, and the heteroatoms in the 5-10 membered heteroaryl group are selected from N and the number of heteroatoms is 1, 2, 3 or 4; Each R 3-1 are independently deuterium or a hydroxy group; Each R 3-2 are independently deuterium, oxo, halogen, C1-C6 alkoxy group, -NR 3-4-2 R 3-4-2 , -S(O)2R 3-4-1 , a hydroxy group, or unsubstituted or one or more R 3-2-2 is a C1-C6 alkyl group substituted by Each R 3-3 are independently deuterium, oxo, amino, or hydroxy; Each R 3-4 are independently deuterium, oxo, or a C1-C6 alkyl group; R 3-4-1 is a C1-C6 alkyl group, Each R 3-4-2 are independently -S(O)R 3-4-1 , hydrogen or a C1-C6 alkyl group; Each R 3-5 are independently deuterium, TIFF2025533951000085.tif1775R 3-5-1 is a C1-C6 alkyl group, Each R 3-6 are independently deuterium, halogen, unsubstituted or one or more R 3-2-2C1-C6 alkyl group substituted with, or unsubstituted or one or more R 3-6-1 wherein the heteroatoms in the 4-6 membered heterocyclyl group are selected from any one or two of N, O and S, and the number of heteroatoms is 1 or 2; Each R 3-5-2 are independently a hydroxy group, a C1-C6 alkyl group, or a 1-10 membered heteroalkyl group, or two R 3-5-2 form a 4-10 membered heterocyclyl group, wherein the heteroatoms in the 1-10 membered heteroalkyl group include, in addition to phosphorus, any one or more selected from N, O and S, and the number of heteroatoms is 1, 2, 3 or 4; the heteroatoms in the 4-10 membered heterocyclyl group include, in addition to phosphorus, any one or more selected from N, O and S, and the number of heteroatoms is 1, 2, 3 or 4; Each R 3-6-1 are independently a C1-C6 alkyl group, Each R 3-2-2 are independently deuterium or a hydroxy group.

[0188] In one embodiment, TIFF2025533951000086.tif1438 Ring A is a 5- or 6-membered heteroaryl ring, the heteroatom in the 5- or 6-membered heteroaryl ring is N, and the number of heteroatoms is 1; R 1 is unsubstituted or contains one or more R 1-2 wherein the heteroatom in the 5-6 membered heteroaryl group is N and the number of heteroatoms is 1 or 2; Each R 1-2 are independently deuterium, halogen, unsubstituted or one or more R 1-1-1 C1-C6 alkyl group substituted with, or unsubstituted or one or more R 1-1-2 is a C1-C6 alkoxy group substituted by Each R 1-1-1 and R 1-1-2are independently halogen or deuterium, Each R 1-1-11 are independently a hydroxy group or a C1-C6 alkyl group, R 2 are independently deuterium, or unsubstituted or one or more R 2-1 is a C1-C6 alkyl group substituted by Each R 2-1 are independently halogen or deuterium, m is 0 or 1, Ring B is one or more R b-1 wherein the heteroatoms in the 5-12 membered fused ring heteroaryl ring are N and / or S, the number of heteroatoms is 1, 2, 3 or 4, and the number of rings in the 5-12 membered fused ring heteroaryl ring is 2; Each R b-1 are independently halogen, or unsubstituted or one or more R b-1-1 is a C1-C6 alkyl group substituted by Each R b-1-1 are independently halogen; R 3 is unsubstituted or contains one or more R 3-1 a 3-6 membered cycloalkyl group, unsubstituted or substituted by one or more R 3-2 a 4-9 membered heterocyclyl group, unsubstituted or substituted by one or more R 3-3 a 4-6 membered cycloalkenyl group, unsubstituted or substituted by one or more R 3-4 a 4-6 membered heterocycloalkenyl group, unsubstituted or substituted by one or more R 3-5 or a phenyl group substituted with one or more R 3-6wherein the heteroatoms in the 4-9 membered heterocyclyl group or the 4-6 membered heterocycloalkenyl group are N and / or O and the number of heteroatoms is 1 or 2, and the heteroatoms in the 5-10 membered heteroaryl group are selected from N and the number of heteroatoms is 1, 2, 3 or 4; Each R 3-1 are independently deuterium or a hydroxy group, Each R 3-2 are independently deuterium, oxo, halogen, C1-C6 alkoxy group, -NR 3-4-2 R 3-4-2 , -S(O)2R 3-4-1 , a hydroxy group, or unsubstituted or one or more R 3-2-2 is a C1-C6 alkyl group substituted by Each R 3-3 are independently deuterium, oxo, amino, or hydroxy; Each R 3-4 are independently deuterium, oxo, or a C1-C6 alkyl group; R 3-4-1 is a C1-C6 alkyl group, Each R 3-4-2 are independently -S(O)R 3-4-1 , hydrogen or a C1-C6 alkyl group; Each R 3-5 are independently deuterium, TIFF2025533951000087.tif1875R 3-5-1 is a C1-C6 alkyl group, Each R 3-6 are independently deuterium, halogen, unsubstituted or one or more R 3-2-2 C1-C6 alkyl group substituted with, or unsubstituted or one or more R 3-6-1 wherein the heteroatoms in the 4-6 membered heterocyclyl group are selected from any one or two of N, O and S, and the number of heteroatoms is 1 or 2; Each R 3-5-2are independently a hydroxy group, a C1-C6 alkyl group, or a 1-10 membered heteroalkyl group, or two R 3-5-2 form a 4-10 membered heterocyclyl group, wherein the heteroatoms in the 1-10 membered heteroalkyl group include, in addition to phosphorus, any one or more selected from N, O and S, and the number of heteroatoms is 1, 2, 3 or 4; the heteroatoms in the 4-10 membered heterocyclyl group include, in addition to phosphorus, any one or more selected from N, O and S, and the number of heteroatoms is 1, 2, 3 or 4; Each R 3-6-1 are independently a C1-C6 alkyl group, Each R 3-2-2 are independently deuterium or a hydroxy group.

[0189] In one embodiment, m is 0 or 1, n is 1, TIFF2025533951000088.tif1544 Ring A is a 5- or 6-membered heteroaryl ring, the heteroatom in the 5- or 6-membered heteroaryl ring is N, and the number of heteroatoms is 1; R 1 is unsubstituted or contains one or more R 1-2 wherein the heteroatom in the 5-6 membered heteroaryl group is N and the number of heteroatoms is 1, 2 or 3; Each R 1-2 are independently deuterium, halogen, cyano, amino, hydroxy, unsubstituted or one or more R 1-1-1 C1-C6 alkyl group, unsubstituted or substituted by one or more R 1-1-2 C1-C6 alkoxy group, unsubstituted or substituted by one or more R 1-1-3 or a C2-C6 alkenyl group unsubstituted or substituted by one or more R 1-1-4 is a C2-C6 alkynyl group substituted by Each R 1-1-1 , R 1-1-2 , R 1-1-3 and R 1-1-4are independently deuterium, a hydroxy group, a cyano group, or a halogen; Each R 2 are independently deuterium, halogen, cyano, amino, hydroxy, unsubstituted or one or more R 2-1 C1-C6 alkyl group, unsubstituted or substituted by one or more R 2-2 C1-C6 alkoxy group, unsubstituted or substituted by one or more R 2-3 C2-C6 alkenyl group, unsubstituted or substituted by one or more R 2-4 C2-C6 alkynyl group, unsubstituted or substituted by one or more R 2-5 a 3-6 membered cycloalkyl group substituted by, or unsubstituted or substituted by one or more R 2-6 wherein the heteroatoms in said 4-12 membered heterocyclyl group are selected from N and the number of heteroatoms is 1, 2 or 3; Each R 2-1 , R 2-2 , R 2-3 , R 2-4 , R 2-5 and R 2-6 are independently deuterium, a hydroxy group, a cyano group, or a halogen; Ring B may be unsubstituted or may contain one or more R b-1 wherein the heteroatoms in the 5-20 membered fused ring heteroaryl ring are selected from one or more of N, O and S, and the number of heteroatoms is 1, 2, 3, 4, 5, 6, 7 or 8; the single heteroaryl ring in the 5-20 membered fused ring heteroaryl ring is a 5-7 membered heteroaryl ring; the number of rings in the 5-20 membered fused ring heteroaryl ring is 2 or 3; and when the number of rings in the 5-20 membered fused ring heteroaryl ring is 2, the ring B may be substituted with one or more of R b-1 is a 5-20 membered fused heteroaryl ring substituted by Each R b-1 are independently halogen, or unsubstituted or one or more R b-1-1is a C1-C6 alkyl group substituted by Each R b-1-1 are independently a hydroxy group or a halogen; R 3 is hydrogen, unsubstituted or one or more R 3-1 a 3- to 12-membered cycloalkyl group, unsubstituted or substituted by one or more R 3-2 a 4-12 membered heterocyclyl group, unsubstituted or substituted by one or more R 3-3 a 4-12 membered cycloalkenyl group, unsubstituted or substituted by one or more R 3-4 a 4-12 membered heterocycloalkenyl group, unsubstituted or substituted by one or more R 3-5 a 6-10 membered aryl group, unsubstituted or substituted by one or more R 3-6 a 5-10 membered heteroaryl group substituted by -C(O)R 4 , unsubstituted or one or more R 3-7 C1-C6 alkyl group substituted with, or unsubstituted or one or more R 3-8 -OR is replaced by 7 wherein the heteroatoms in the 4- to 12-membered heterocyclyl group, the 4- to 12-membered heterocycloalkenyl group, and the 5- to 10-membered heteroaryl group are selected from one or more of N, O, and S, and the number of heteroatoms is 1, 2, 3, or 4; Each R 3-1 , R 3-2 , R 3-3 and R 3-4 are independently deuterium, hydroxyl group, halogen, cyano group, amino group, -NHC(O)R 3-2-1 , unsubstituted or one or more R 3-2-2 C1-C6 alkyl group, C1-C6 alkoxy group, C2-C6 alkenyl group, C2-C6 alkynyl group, oxo group (=O), -C(O)NH2, unsubstituted or substituted with one or more R 3-2-3 a 3- to 6-membered cycloalkyl group, a 4- to 6-membered heterocyclyl group, -S(O)R 3-4-1 , -NR 3-4-2 R 3-4-2 , TIFF2025533951000089.tif1545, wherein the heteroatom in the 4- to 6-membered heterocyclyl group is selected from one or more of N, O, and S, and the number of heteroatoms is 1 or 2, and the heteroatom in the 5- to 6-membered heteroaryl group is N, and the number of heteroatoms is 1 or 2, Each R 3-7 are independently deuterium, a hydroxy group, a halogen, a cyano group, or an amino group; Each R 3-8 are independently a hydroxy group or a 4- to 6-membered heterocyclyl group; Each R 3-5 and R 3-6 are independently deuterium, TIFF2025533951000090.tif1017Hydroxy group, halogen, cyano group, amino group, -NHC(O)R 3-2-1 , unsubstituted or one or more R 3-2-2 C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, —C(O)NH2, unsubstituted or substituted with one or more R 3-2-3 a 3-6 membered cycloalkyl group, unsubstituted or substituted by one or more R 3-6-1 a 4-6 membered heterocyclyl group substituted by TIFF2025533951000091.tif1446, wherein the heteroatom in the 4- to 6-membered heterocyclyl group is selected from one or more of N, O, and S, and the number of heteroatoms is 1 or 2; Each R 3-2-1 and R 3-4-2 are independently hydrogen or a C1-C6 alkyl group; Each R 3-2-3 and R 3-5-1 are independently a hydroxy group or a C1-C6 alkyl group, Each R 3-5-2 are independently a hydroxy group, a C1-C6 alkyl group, or a 1-10 membered heteroalkyl group, or two R 3-5-2form a 4-10 membered heterocyclyl group, wherein the heteroatoms in the 1-10 membered heteroalkyl group include, in addition to phosphorus, any one or more selected from N, O and S, and the number of heteroatoms is 1, 2, 3 or 4; the heteroatoms in the 4-10 membered heterocyclyl group include, in addition to phosphorus, any one or more selected from N, O and S, and the number of heteroatoms is 1, 2, 3 or 4; Each R 3-6-1 are independently a C1-C6 alkyl group, Each R 3-2-2 are independently deuterium, a hydroxyl group, or a halogen; R 3-4-1 is a hydroxy group, an amino group, or a C1-C6 alkyl group, R 4 is unsubstituted or contains one or more R 4-1 wherein the heteroatoms in the 4-6 membered heterocyclyl group are selected from N and the number of heteroatoms is 1 or 2; Each R 4-1 are independently a hydroxy group, R 7 is a 3-6 membered cycloalkyl group.

[0190] In one embodiment, m is 0 or 1, n is 1, TIFF2025533951000092.tif1444 Ring A is a 5- or 6-membered heteroaryl ring, the heteroatom in the 5- or 6-membered heteroaryl ring is N, and the number of heteroatoms is 1; R 1 is unsubstituted or contains one or more R 1-2 wherein the heteroatom in the 5-6 membered heteroaryl group is N and the number of heteroatoms is 1; Each R 1-2 are independently deuterium, halogen, or unsubstituted or one or more R 1-1-2 is a C1-C6 alkoxy group substituted by Each R1-1-2 are independently deuterium, a hydroxy group, a cyano group, or a halogen; Each R 2 are independently deuterium, or unsubstituted or one or more R 2-1 is a C1-C6 alkyl group substituted by Each R 2-1 are independently deuterium, a hydroxy group, a cyano group, or a halogen; Ring B may be unsubstituted or may contain one or more R b-1 wherein the heteroatoms in the 5-20 membered fused ring heteroaryl ring are selected from one or more of N, O and S, and the number of heteroatoms is 1, 2, 3, 4, 5, 6, 7 or 8; the single heteroaryl ring in the 5-20 membered fused ring heteroaryl ring is a 5-7 membered heteroaryl ring; the number of rings in the 5-20 membered fused ring heteroaryl ring is 2 or 3; and when the number of rings in the 5-20 membered fused ring heteroaryl ring is 2, the ring B may be substituted with one or more of R b-1 is a 5-20 membered fused heteroaryl ring substituted by Each R b-1 are independently halogen or a C1-C6 alkyl group; R 3 is unsubstituted or contains one or more R 3-1 a 3- to 12-membered cycloalkyl group, unsubstituted or substituted by one or more R 3-2 a 4-12 membered heterocyclyl group, unsubstituted or substituted by one or more R 3-3 a 4-12 membered cycloalkenyl group, unsubstituted or substituted by one or more R 3-4 a 4-12 membered heterocycloalkenyl group, unsubstituted or substituted by one or more R 3-5 a 6-10 membered aryl group, unsubstituted or substituted by one or more R 3-6 a 5-10 membered heteroaryl group substituted by, or unsubstituted or substituted by one or more R 3-8 -OR is replaced by 7wherein the heteroatoms in the 4- to 12-membered heterocyclyl group, the 4- to 12-membered heterocycloalkenyl group, and the 5- to 10-membered heteroaryl group are selected from one or more of N, O, and S, and the number of heteroatoms is 1, 2, 3, or 4; Each R 3-1 , R 3-2 , R 3-3 and R 3-4 are independently deuterium, hydroxyl group, halogen, cyano group, amino group, -NHC(O)R 3-2-1 , unsubstituted or one or more R 3-2-2 a C1-C6 alkyl group, a C1-C6 alkoxy group, a C2-C6 alkenyl group, a C2-C6 alkynyl group, an oxo group (=O), TIFF2025533951000093.tif1559 each R 3-8 are independently a hydroxy group or a 4- to 6-membered heterocyclyl group; Each R 3-5 and R 3-6 are independently deuterium, TIFF2025533951000094.tif1018Hydroxy group, halogen, cyano group, amino group, unsubstituted or one or more R 3-2-2 C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, —C(O)NH2, unsubstituted or substituted with one or more R 3-2-3 a 3-6 membered cycloalkyl group, unsubstituted or substituted by one or more R 3-6-1 a 4-6 membered heterocyclyl group substituted by TIFF2025533951000095.tif1446, wherein the heteroatom in the 4- to 6-membered heterocyclyl group is selected from one or more of N, O, and S, and the number of heteroatoms is 1 or 2; Each R 3-2-1 are independently hydrogen or a C1-C6 alkyl group; Each R 3-2-3 and R 3-5-1 are independently a hydroxy group or a C1-C6 alkyl group, Each R 3-5-2are independently a hydroxy group, a C1-C6 alkyl group, or a 1-10 membered heteroalkyl group, or two R 3-5-2 form a 4-10 membered heterocyclyl group, wherein the heteroatoms in the 1-10 membered heteroalkyl group include, in addition to phosphorus, any one or more selected from N, O and S, and the number of heteroatoms is 1, 2, 3 or 4; the heteroatoms in the 4-10 membered heterocyclyl group include, in addition to phosphorus, any one or more selected from N, O and S, and the number of heteroatoms is 1, 2, 3 or 4; Each R 3-6-1 are independently a C1-C6 alkyl group, Each R 3-2-2 are independently deuterium, a hydroxyl group, or a halogen; R 7 is a 3-6 membered cycloalkyl group.

[0191] In one embodiment, m is 0 or 1, n is 1, TIFF2025533951000096.tif1438 Ring A is a 5- or 6-membered heteroaryl ring, the heteroatom in the 5- or 6-membered heteroaryl ring is N, and the number of heteroatoms is 1; R 1 is unsubstituted or contains one or more R 1-2 wherein the heteroatom in the 5-6 membered heteroaryl group is N and the number of heteroatoms is 1; Each R 1-2 are independently deuterium, halogen, or unsubstituted or one or more R 1-1-2 is a C1-C6 alkoxy group substituted by Each R 1-1-2 are independently deuterium, a hydroxy group, a cyano group, or a halogen; Each R 2 are independently deuterium, or unsubstituted or one or more R 2-1 is a C1-C6 alkyl group substituted by Each R 2-1are independently deuterium, a hydroxy group, a cyano group, or a halogen; Ring B is one or more R b-1 wherein the heteroatoms in the 5-12 membered fused heteroaryl ring are selected from N and S, and the number of heteroatoms is 1, 2, 3 or 4 (e.g., TIFF2025533951000097.tif41150 each R b-1 are independently a halogen or a C1-C6 alkyl group (e.g., fluorine or methyl); R 3 is unsubstituted or contains one or more R 3-1 a 3-6 membered cycloalkyl group, unsubstituted or substituted by one or more R 3-2 a 4-6 membered heterocyclyl group, unsubstituted or substituted by one or more R 3-3 a 4-6 membered cycloalkenyl group, unsubstituted or substituted by one or more R 3-4 a 4-6 membered heterocycloalkenyl group, unsubstituted or substituted by one or more R 3-5 or a phenyl group substituted with one or more R 3-6 wherein the heteroatoms in the 4- to 6-membered heterocyclyl group or the 4- to 6-membered heterocycloalkenyl group are N and / or O and the number of heteroatoms is 1 or 2, and the heteroatom in the 5- to 6-membered heteroaryl group is N and the number of heteroatoms is 1, 2 or 3; Each R 3-1 , R 3-2 , R 3-3 and R 3-4 are independently deuterium, a hydroxy group, or a C1-C6 alkyl group; Each R 3-5 is independently TIFF2025533951000098.tif1774R 3-5-1 is a C1-C6 alkyl group, Each R 3-5-2 are independently a hydroxy group or a C1-C6 alkyl group, Each R 3-6 are independently halogen, or unsubstituted or one or more R 3-2-2 is a C1-C6 alkyl group substituted by Each R 3-2-2 are independently deuterium.

[0192] In one embodiment, R 3 is hydrogen, unsubstituted or one or more R 3-1 a 3-6 membered cycloalkyl group, unsubstituted or substituted by one or more R 3-2 a 4-12 membered heterocyclyl group, unsubstituted or substituted by one or more R 3-3 a 4-10 membered cycloalkenyl group, unsubstituted or substituted by one or more R 3-4 a 4-10 membered heterocycloalkenyl group, unsubstituted or substituted by one or more R 3-5 a 6-10 membered aryl group, unsubstituted or substituted by one or more R 3-6 or a 5-10 membered heteroaryl group substituted by -C(O)R 4 The heteroatoms in the 4- to 12-membered heterocyclyl group, 4- to 10-membered heterocycloalkenyl group, or 5- to 10-membered heteroaryl group are one or more of N, O, and S, and the number of heteroatoms is 1, 2, 3, or 4.

[0193] In one embodiment, R 3 is hydrogen, unsubstituted or one or more R 3-1 a 3-6 membered cycloalkyl group, unsubstituted or substituted by one or more R 3-2 a 4-12 membered heterocyclyl group, unsubstituted or substituted by one or more R 3-3 a 4-10 membered cycloalkenyl group, unsubstituted or substituted by one or more R 3-4 a 4-10 membered heterocycloalkenyl group, unsubstituted or substituted by one or more R 3-5 a 6-10 membered aryl group, unsubstituted or substituted by one or more R 3-6a 5-10 membered heteroaryl group substituted by -C(O)R 4 , -NH(CH2) p R 5 , -O(CH2) q R 6 , unsubstituted or one or more R 3-7 C1-C6 alkyl group substituted with, or unsubstituted or one or more R 3-8 -OR is replaced by 7 The heteroatoms in the 4- to 12-membered heterocyclyl group, 4- to 10-membered heterocycloalkenyl group, or 5- to 10-membered heteroaryl group are one or more of N, O, and S, and the number of heteroatoms is 1, 2, 3, or 4.

[0194] In one embodiment, R 1 teeth, TIFF2025533951000099.tif79157

[0195] In one embodiment, TIFF2025533951000100.tif224157 TIFF2025533951000101.tif3447

[0196] In one embodiment, TIFF2025533951000102.tif1749

[0197] In one embodiment, TIFF2025533951000103.tif209164 TIFF2025533951000104.tif228164

[0198] In one embodiment, R 3 is a hydrogen, a methyl group, TIFF2025533951000105.tif178159 TIFF2025533951000106.tif241162 TIFF2025533951000107.tif235162 TIFF2025533951000108.tif146156

[0199] In one embodiment, the compound of Formula I is any of the following compounds: TIFF2025533951000109.tif79162 TIFF2025533951000110.tif238162 TIFF2025533951000111.tif239162 TIFF2025533951000112.tif237162 TIFF2025533951000113.tif239162 TIFF2025533951000114.tif224162 TIFF2025533951000115.tif234162 TIFF2025533951000116.tif239162 TIFF2025533951000117.tif239162 TIFF2025533951000118.tif237162 TIFF2025533951000119.tif238162 TIFF2025533951000120.tif236162 TIFF2025533951000121.tif236162 TIFF2025533951000122.tif235162 TIFF2025533951000123.tif238162 TIFF2025533951000124.tif227162 TIFF2025533951000125.tif220162 TIFF2025533951000126.tif239162 TIFF2025533951000127.tif220162 TIFF2025533951000128.tif218162 TIFF2025533951000129.tif237162 TIFF2025533951000130.tif226162 TIFF2025533951000131.tif233162 TIFF2025533951000132.tif81162

[0200] The present invention provides a method for preparing a compound of formula I', comprising embodiment a, embodiment b or embodiment c, The above embodiment a includes the steps of: subjecting a compound represented by formula II to a condensation reaction with a compound represented by formula III in a solvent as follows to obtain the compound represented by formula I'; TIFF2025533951000133.tif25131 The embodiment b includes the following steps: (a) subjecting a compound represented by formula II to a condensation reaction with a compound represented by formula III' in a solvent as follows to obtain a compound represented by formula I''; TIFF2025533951000134.tif26135wherein X is dimethyl tert-butylsilyl ether (OTBS) or tert-butoxycarbonyl (Boc); (b) subjecting the compound of formula I″ obtained in step (a) to a deprotection reaction as described below in a solvent in the presence of an acid to obtain the compound of formula I′; TIFF2025533951000135.tif21111 The above embodiment c includes the following steps: in a solvent, in the presence of a condensing agent, a compound represented by formula IV is subjected to a condensation reaction with a compound represented by formula V as follows to obtain a compound represented by formula I': TIFF2025533951000136.tif26111Y is hydrogen or a carbonyl group, where R 1 , R 2 , m, ring A, L, ring B and R 3 is as described above.

[0201] In embodiment a or b, in the condensation reaction, the molar ratio of the compound represented by formula II to the compound represented by formula III may be 1:(0.5-1.5), for example, 1:1, 1:1.35, or 1:0.83.

[0202] In embodiment a or b, in the condensation reaction, the molar ratio of the compound represented by formula II to the compound represented by formula III may be 1:(0.5-1.5), for example, 1:1 or 0.67.

[0203] In embodiment a or b, in the condensation reaction, the solvent is an organic solvent conventional in the art, preferably an amide solvent and / or a cyanide solvent, the amide solvent is preferably N,N-dimethylformamide, and the cyanide solvent is preferably acetonitrile.

[0204] In embodiment a or b, in the condensation reaction, the condensing agent is a condensing agent conventional in the art, for example, N,N,N',N'-tetramethylformamidinium hexafluorophosphate and 1-methylimidazole.

[0205] In embodiment a or b, in the condensation reaction, the molar ratio of the compound represented by formula II to the condensing agent can be 1:(2-5), for example, 1:4 or 1:4.3, 1:3.7 or 1:4.1.

[0206] In embodiment a or b, in the condensation reaction, the reaction temperature of the condensation reaction is a temperature conventional for such reactions in the art, for example, room temperature.

[0207] In embodiment a or b, the condensation reaction further comprises post-treatment, and the post-treatment step is a post-treatment step for organic reactions commonly used in the art, and may include one or more of concentration, washing with water, extraction, drying, column chromatography, and preparative chromatography.

[0208] In embodiment c, in the condensation reaction, when Y is a carbonyl group, the molar ratio of the compound represented by formula IV to the compound represented by formula V can be 1:(0.3-0.6), for example, 1:0.46.

[0209] In embodiment c, in the condensation reaction, when Y is a carbonyl group, the solvent is an organic solvent conventional in the art, preferably an alcohol solvent, for example, methanol.

[0210] In embodiment c, in the above condensation reaction, when Y is a carbonyl group, the condensing agent is a condensing agent conventional in the art, such as sodium cyanoborohydride and tetraethyl titanate.

[0211] In embodiment c, when Y is a carbonyl group in the condensation reaction, the molar ratio of the compound represented by formula IV to the condensing agent can be 1:(2-5), for example, 1:3.2.

[0212] In embodiment c, when Y is a carbonyl group in the condensation reaction, the reaction temperature of the condensation reaction is a temperature conventional in the art, for example, room temperature.

[0213] In embodiment c, when Y is a carbonyl group in the condensation reaction, the condensation reaction may further include post-treatment, and the post-treatment step may be a post-treatment step for an organic reaction conventionally used in the art, and may include one or more steps of filtration, concentration, and preparative chromatography.

[0214] In embodiment c, in the condensation reaction, when Y is hydrogen, the molar ratio of the compound represented by formula IV to the compound represented by formula V can be 1:(1-1.5), for example, 1:1.49.

[0215] In embodiment c, in the condensation reaction, when Y is hydrogen, the solvent is an organic solvent conventional in the art, preferably an amide solvent and / or a cyanide solvent, the amide solvent is preferably N,N-dimethylformamide, and the cyanide solvent is preferably acetonitrile.

[0216] In embodiment c, in the above condensation reaction, when Y is hydrogen, the condensing agent is a condensing agent conventional in the art, such as N,N,N',N'-tetramethylformamidinium hexafluorophosphate and 1-methylimidazole.

[0217] In embodiment c, in the condensation reaction, when Y is hydrogen, the molar ratio of the compound represented by formula IV to the condensing agent can be 1:(2-5), for example, 1:4.2.

[0218] In embodiment c, when Y is hydrogen in the condensation reaction, the reaction temperature of the condensation reaction is a temperature conventional in the art, for example, room temperature.

[0219] In embodiment c, when Y is hydrogen in the condensation reaction, the condensation reaction may further include post-treatment, and the post-treatment step may be a post-treatment step for an organic reaction conventionally used in the art, and may include one or more steps of extraction, drying, concentration, and preparative chromatography.

[0220] Additionally, the present invention provides a compound of formula VI TIFF2025533951000137.tif2543 Ring B is unsubstituted or contains one or more R b-1wherein the heteroatoms in the 5-20 membered fused ring heteroaryl ring are selected from one or more of N, O and S, and the number of heteroatoms is 1, 2, 3, 4, 5 or 6; the single heteroaryl ring in the 5-20 membered fused ring heteroaryl ring is a 5-7 membered heteroaryl ring; the number of rings in the 5-20 membered fused ring heteroaryl ring is 3 or 4; and R 3 and n is as defined above.

[0221] Furthermore, the present invention provides a compound represented by the following formula: TIFF2025533951000138.tif19162 TIFF2025533951000139.tif219162 TIFF2025533951000140.tif201162 TIFF2025533951000141.tif222162 TIFF2025533951000142.tif114162

[0222] The present invention provides (1) a therapeutically effective amount of substance A, which is a compound represented by formula I, a pharmaceutically acceptable salt thereof, or an isotopic compound thereof; (2) a pharmaceutically acceptable additive; The present invention provides a pharmaceutical composition comprising:

[0223] The present invention provides the use of Substance A, which is a compound represented by Formula I above, a pharmaceutically acceptable salt or an isotopic compound thereof, in the preparation of a polymerase theta inhibitor.

[0224] The present invention provides use of Substance A, which is a compound represented by Formula I above, a pharmaceutically acceptable salt or an isotopic compound thereof, in the preparation of a medicament for treating lung cancer, breast cancer, HR-deficient ovarian cancer, gastric cancer, prostate cancer, pancreatic adenocarcinoma, or colon cancer.

[0225] Terminology The term "group B unsubstituted or substituted by multiple groups A" means that one or more hydrogen atoms in group B are independently substituted by groups A or B. At the same time, when multiple A groups appear, their definitions are independent of each other and do not influence each other unless otherwise specified. For example, "C6-C substituted by 3 halogens" 10 "Aryl group" means a C6-C 10 The aryl group is substituted with three halogens, and the definitions of the three halogens are independent of each other and do not influence each other; This includes, but is not limited to, TIFF2025533951000143.tif2551.

[0226] The term "plurality" refers to two and more than two, for example, 2, 3, 4, 5.

[0227] The term "pharmaceutically acceptable" refers to being relatively non-toxic, safe, and suitable for use by patients.

[0228] The term "pharmaceutically acceptable salt" refers to a salt obtained by reacting a compound with a pharmaceutically acceptable acid or base. When a compound contains a relatively acidic functional group, a base addition salt can be obtained by contacting the compound with a sufficient amount of a pharmaceutically acceptable base in a suitable inert solvent. Pharmaceutically acceptable base addition salts include, but are not limited to, sodium, potassium, calcium, aluminum, magnesium, bismuth, ammonium salts, etc. When a compound contains a relatively basic functional group, an acid addition salt can be obtained by contacting the compound with a sufficient amount of a pharmaceutically acceptable acid in a suitable inert solvent. Pharmaceutically acceptable acid addition salts include, but are not limited to, hydrochloride, sulfate, trifluoroacetate, formate, methanesulfonate, etc. See, specifically, Handbook of Pharmaceutical Salts: Properties, Selection, and Use (P. Heinrich Stahl, Camille G. Wermuth, 2011, 2nd Revised Edition).

[0229] The "-" in a group indicates that the group is attached to the rest of the molecule through that site. For example, CH3-C(=O)- refers to an acetyl group.

[0230] The term "halogen" refers to fluorine, chlorine, bromine, or iodine. In the present invention, halogen substitution includes, but is not limited to, substitution by one halogen, substitution by two halogens, or substitution by three halogens, and typically multiple substitutions occur on the same carbon atom.

[0231] The term "oxa" refers to =0, where two hydrogens on the same carbon atom are replaced by an oxygen atom, ie, replacing a carbonyl group with a methylene group.

[0232] The term "alkyl group" refers to a straight- or branched-chain saturated monovalent hydrocarbon group having the specified number of carbon atoms (e.g., C1-C6). Alkyl groups include, but are not limited to, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, n-hexyl, and the like.

[0233] The term "alkoxy group" refers to R X -O-Il refers to R X has the same definition as the term “alkyl group.” Alkoxy groups include, but are not limited to, methoxy, ethoxy, n-propoxy, isopropoxy, and the like.

[0234] The term "alkenyl group" refers to one or more (e.g., 1, 2, or 3) carbon-carbon sp 2 An alkenyl group refers to a linear or branched unsaturated monovalent hydrocarbon group having a specified number of carbon atoms (e.g., C2 to C6) and a double bond. Alkenyl groups include vinyl groups, This includes, but is not limited to, TIFF2025533951000144.tif937.

[0235] The term "alkynyl group" refers to one or more (e.g., 1, 2, or 3) carbon-carbon sp 3 An alkynyl group refers to a linear or branched unsaturated monovalent hydrocarbon group having a specified number of carbon atoms (e.g., C2 to C6) and a triple bond. Alkynyl groups include ethynyl, This includes, but is not limited to, TIFF2025533951000145.tif1537.

[0236] For purposes of this invention, unless otherwise specified, the term "cycloalkyl group" refers to a cyclic saturated monovalent hydrocarbon group having a specified number of carbon atoms (e.g., 3 to 10 members), which is monocyclic. Monocyclic rings include: This includes, but is not limited to, TIFF2025533951000146.tif1673.

[0237] In the present invention, unless otherwise specified, the term "aryl group" refers to a cyclic saturated monovalent hydrocarbon group having a specified number of carbon atoms (e.g., 6-10 members), which may be monocyclic or multicyclic (e.g., 2 or 3) in which the monocyclic rings share two carbon atoms and one bond, and which (at least one ring / each ring) are aromatic. An aryl group is bonded to the rest of the molecule via an aromatic or non-aromatic ring. Aryl groups include phenyl, naphthalene, This includes, but is not limited to, TIFF2025533951000147.tif1556.

[0238] As used herein, unless otherwise specified, the term "cycloalkenyl group" refers to a cyclic, unsaturated, monovalent hydrocarbon group having a specified number of carbon atoms (e.g., 4 to 10 members), which may be monocyclic or multicyclic (e.g., 2 or 3, bridged, spirocyclic, fused) rings. Monocyclic cycloalkenyl groups include: TIFF2025533951000148.tif1258 and the like. Examples of bridged-ring cycloalkenyl groups include, but are not limited to, TIFF2025533951000149.tif1218 and the like. Spirocyclic cycloalkenyl groups include, but are not limited to, TIFF2025533951000150.tif1794 and the like. Fused-ring cycloalkenyl groups include, but are not limited to, This includes, but is not limited to, TIFF2025533951000151.tif1126.

[0239] For purposes of this invention, unless otherwise specified, the term "heterocycloalkyl group" refers to a monocyclic, bridged, spiro, or fused ring system having a specified number of ring atoms (e.g., 3-10 members), a specified number of heteroatoms (e.g., 1, 2, or 3), and a specified type of heteroatom (one or more of N, O, and S). A monocyclic heterocyclyl group is attached to the rest of the molecule through a carbon atom or a heteroatom. A monocyclic heterocyclyl group includes: TIFF2025533951000152.tif28145 and the like. Spirocyclic heterocyclyl groups include, but are not limited to, TIFF2025533951000153.tif45157 and the like. Bridged ring heterocyclyl groups include, but are not limited to, Fused ring heterocyclyl groups include, but are not limited to, This includes, but is not limited to, TIFF2025533951000155.tif1284.

[0240] As used herein, unless otherwise specified, the term "heterocycloalkenyl group" refers to a cyclic, unsaturated, monovalent group having a specified number of ring atoms (e.g., 5-10 members), a specified number of heteroatoms (e.g., 1, 2, or 3), and a specified type of heteroatom (one or more of N, O, and S), which may be monocyclic or multicyclic (e.g., 2 or 3, spirocyclic). Monocyclic heterocycloalkenyl groups include: TIFF2025533951000156.tif14145 and the like. Spirocyclic heterocycloalkenyl groups include, but are not limited to, This includes, but is not limited to, TIFF2025533951000157.tif19134.

[0241] In the present invention, unless otherwise specified, the term "heteroaryl group" refers to a cyclic, unsaturated, monovalent group having a specified number of ring atoms (e.g., 5-10 members), a specified number of heteroatoms (e.g., 1, 2, or 3), and a specified type of heteroatom (one or more of O and S), which may be monocyclic or polycyclic, in which the monocyclic rings share two carbon atoms and one bond, and in which at least one ring is aromatic. Heteroaryl groups are bonded to the rest of the molecule through a carbon atom or heteroatom, heteroaryl groups are bonded to the rest of the molecule through a ring with or without a heteroatom, and heteroaryl groups are bonded to the rest of the molecule through an aromatic or non-aromatic ring. Heteroaryl groups include: This includes, but is not limited to, TIFF2025533951000158.tif68150.

[0242] In the present invention, unless otherwise specified, the term "fused-ring heteroaryl ring" refers to a "heteroaryl ring" formed with another ring, and a "fused-ring heteroaryl ring" includes at least two rings, at least one of which is a heteroaryl ring. Here, the other definitions of "heteroaryl ring" are the same as those of "heteroaryl group."

[0243] The term "isotopic compound" refers to a compound in which the isotopic abundance of one or more atoms differs from its natural abundance. For example, a hydrogen atom in the compound is replaced by deuterium, or C is replaced by 13 One or more atoms in the compound are replaced with naturally occurring atoms with low mass numbers, such as C.

[0244] In the present invention, "room temperature" refers to "20 to 40°C."

[0245] The above preferred conditions can be combined in any way consistent with the common sense of a person skilled in the art to obtain preferred embodiments of the present invention.

[0246] The reagents and materials used in the present invention are commercially available.

[0247] Positive and progressive effects of the present invention: The ATPase activity and protein inhibitory effects of the compounds of the present invention are significantly improved compared with those of the prior art.

[0248] Specific Embodiments The present invention will be further described below with reference to examples, but the present invention is not limited to these examples. In the following examples, test methods for which no specific conditions are given should be selected according to conventional methods and conditions or product instructions.

[0249] All compounds of the present invention can be synthesized by a variety of methods by those skilled in the art of organic chemistry. General synthetic embodiments for preparing compounds of the present invention are described below. These methods are general in nature and do not limit the techniques that one skilled in the art can use to prepare the compounds disclosed herein. Different methods for preparing compounds of the present invention will be apparent to those skilled in the art. Furthermore, individual steps in the synthesis can be alternated to obtain one or more desired compounds. The Preparations and Examples section below provides examples of preparations of compounds of the present invention using the methods described in the general embodiments. Preparation of embodiment compounds containing chiral centers can be carried out using techniques known to those skilled in the art. For example, chiral compounds can be prepared by separating racemic products by chiral resolution using HPLC, or exemplary compounds can be prepared by known methods to obtain chiral compounds.

[0250] The chemical reactions and synthetic techniques described herein are carried out in the reagents and corresponding solvents described herein, and the corresponding reaction yields are also affected by the reagents and solvents used. Furthermore, it should be understood by those skilled in the art that all mentioned reaction conditions in the synthetic methods described below, including solvent selection, reaction atmosphere, reaction temperature, test duration, and reaction order, should be considered as operating conditions for the reaction. At the same time, it should be understood by those skilled in the art of organic synthesis. Functional groups present in each part of the molecule must be compatible with the reagents used and the reaction itself. Those skilled in the art will readily understand that alternative methods are required for the limitations of incompatibility of some functional groups present in each part of the molecule with the reaction conditions. It is clear that judgment is required to adjust the order of synthetic steps or select specific synthetic step embodiments to obtain the desired compounds of the present invention. This is understandable and readily recognized by those skilled in the art of organic synthesis. It should also be recognized that the rational selection of protecting groups to protect the resistance of reactive functional groups present in the compounds described herein is another major consideration in any synthetic route devised in the art. Specifically, see Protective Groups in Organic Synthesis, Third Edition, Wiley and Sons (1999) by Greene et al., an authority in the field of chemistry.

[0251] Example The preparation of compounds and intermediates used in preparing compounds can be prepared using the processes shown in the examples and related steps below. The methods and conditions used in these examples, and the actual compounds prepared in these examples, are not intended to be limiting, but rather to illustrate how to prepare related compounds. The starting materials and reagents used in these examples, when not prepared by the processes described herein, are generally commercially available, reported in the relevant chemical literature, or can be prepared by processes described in the chemical literature.

[0252] In the examples described herein, the term "drying and concentrating" typically refers to adding a dry solution of anhydrous sodium sulfate or magnesium sulfate to an organic solvent, followed by filtration and removal of the solvent from the filtrate (usually under reduced pressure and at a temperature appropriate for the stability of the prepared compound). Column methods typically involve column separation and purification by conventional or flash column chromatography, or by using a medium-pressure chromatograph (Biotage Isola One) pre-packed with a silica gel column and eluting with a specified solvent or solvent mixture. In some cases, the final product is rapidly purified by preparative thin-layer chromatography using 20 cm x 20 cm x 0.5 mm or 20 cm x 20 cm x 1 mm silica gel plates in an appropriate solvent system. Preparative high-performance liquid chromatography (HPLC) is performed on a reverse-phase column (Waters Sunfire C18, Waters Xbridge C18, or equivalent) of a size appropriate for the amount of compound to be separated. Elution is typically performed with a gradient of methanol or acetonitrile in the aqueous phase, with eluents containing 0.05% or 0.1% formic acid, trifluoroacetic acid, or 10 mM ammonium acetate. The elution rate depends on the size of the reverse-phase column used and the resolution of the preparation.

[0253] TIFF2025533951000159.tif241164 TIFF2025533951000160.tif125164

[0254] Intermediate 1: 2'-chloro-3'-fluoro-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-carboxylic acid TIFF2025533951000161.tif55135

[0255] Step 1: 2-chloro-3-fluoro-5-methoxypyridine 6-Chloro-5-fluoropyridin-3-ol (10 g, 67.8 mmol) was dissolved in acetonitrile (100 mL), potassium carbonate (32.7 g, 237 mmol) was added, and then iodomethane (33.7 g, 237 mmol) was added. The mixture was reacted at room temperature for 18 hours. After the reaction was completed, water was added, and the mixture was extracted with ethyl acetate, washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by column chromatography (eluent: petroleum ether / ethyl acetate, gradient: 10%-40% ethyl acetate) to give the title compound (colorless liquid, 7.1 g, 64.8% yield). LC / MS (ESI) m / z: 161.8 [M+H] + .

[0256] Step 2: 2-chloro-3-fluoro-4-iodo-5-methoxypyridine Under nitrogen gas protection, 2-chloro-3-fluoro-5-methoxypyridine (11 g, 68.1 mmol) was dissolved in tetrahydrofuran (100 mL) and cooled to -60 °C. While maintaining the temperature at -60 °C, a solution of n-butyllithium in n-hexane (2.5 mol / L, 40.8 mL, 102.1 mmol) was slowly added and the mixture was reacted at -60 °C for 30 minutes. After that, a solution of iodine monomer (19.0 g, 74.9 mmol) in tetrahydrofuran (20 mL) was added, and the mixture was reacted at -60 °C for 1 hour. After completion of the reaction, the mixture was quenched by slowly adding saturated ammonium chloride, water, and extracted with ethyl acetate. The organic phase was washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by column chromatography (eluent: petroleum ether / ethyl acetate, gradient: 10%-40% ethyl acetate) to give the title compound (white solid, 12.5 g, yield 6.4%). LC / MS (ESI) m / z: 288.1 [M+H] + .

[0257] Step 3: 2'-chloro-3'-fluoro-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-carboxylic acid methyl ester Under nitrogen gas protection, 2-chloro-3-fluoro-4-iodo-5-methoxypyridine (288 mg, 1.0 mmol), methyl 6-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)nicotinate (277 mg, 1.0 mmol), [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium dichloromethane complex (164 mg, 0.20 mmol), and potassium carbonate (415 mg, 3.0 mmol) were dissolved in a mixture of 1,4-dioxane (10 mL) and water (2 mL). The mixture was stirred under nitrogen gas protection at 65 °C for 2 hours. Water was added, followed by extraction with ethyl acetate. The organic phase was washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by column chromatography (eluent: petroleum ether / ethyl acetate, gradient: 20%-50% ethyl acetate) to give the title compound (white solid, 50 mg, yield 16.1%). LC / MS (ESI) m / z: 311.0 [M+H] + .

[0258] Step 4: 2'-chloro-3'-fluoro-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-carboxylic acid 2'-Chloro-3'-fluoro-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-carboxylic acid methyl ester (500 mg, 1.60 mmol) was dissolved in a mixture of tetrahydrofuran (5 mL), methanol (5 mL), and water (5 mL), and lithium hydroxide monohydrate (67 mg, 1.60 mmol) was added. The mixture was reacted at room temperature for 5 hours and then concentrated under reduced pressure to give the title compound (white solid, 445 mg, 93.1% yield). LC / MS (ESI) m / z: 296.9 [M+H] + .

[0259] Intermediate 2: 2'-chloro-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-carboxylic acid TIFF2025533951000162.tif46121

[0260] Step 1: (2-chloro-5-methoxypyridin-4-yl)boronic acid 2-Chloro-5-methoxypyridine (10.0 g, 69.5 mmol) was dissolved in tetrahydrofuran (250 mL) and cooled to 65°C under nitrogen gas protection. 2 mol / L lithium diisopropylamide (70 mL) was slowly added dropwise at temperatures below -60°C. After the addition was complete, the mixture was allowed to react at the same low temperature for 2 hours. Next, triisopropyl borate (26.2 g, 139 mmol) was slowly added dropwise at -65°C. The mixture was stirred at -65°C for 1 hour, then warmed to room temperature and left overnight. The reaction mixture was quenched by slowly adding water (100 mL) in an ice-water bath. The resulting aqueous solution was extracted twice with ethyl acetate. The organic phase was discarded, and the aqueous phase was adjusted to pH 5-6 with 2M aqueous hydrochloric acid. A large amount of solid precipitated. The solid phase was filtered and dried under reduced pressure to obtain the title compound (11.4 g, white solid, yield: 88.1%). LC / MS (ESI) m / z: 188.0 [M+H] + .

[0261] Step 2: 2'-chloro-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-carboxylic acid methyl ester Methyl 4-bromo-6-methylnicotinate (5 g, 21.7 mmol), (2-chloro-5-methoxypyridin-4-yl)boronic acid (4.07 g, 21.7 mmol), and potassium carbonate (9 g, 65.2 mmol) were dissolved in a mixture of 1,4-dioxane (180 mL) and water (36 mL). Under nitrogen gas protection, bis(triphenylphosphine)palladium dichloride (1.59 g, 2.17 mmol) was added and the mixture was heated to 80 °C for 2 hours. The reaction mixture was allowed to cool, filtered, and then partitioned and extracted with water and ethyl acetate. The organic phase was concentrated and purified by silica gel column chromatography (petroleum ether-ethyl acetate system: 0-50% ethyl acetate) to give the title compound (5.20 g, white solid, 81.7% yield). LC / MS (ESI) m / z: 293.0 [M+1] + .

[0262] Step 3: 2'-chloro-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-carboxylic acid 2'-Chloro-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-carboxylic acid methyl ester (5.2 g, 17.7 mmol) was dissolved in tetrahydrofuran (50 mL) and water (50 mL), lithium hydroxide (0.64 g, 26.6 mmol) was added, and the mixture was stirred overnight at room temperature. The mixture was concentrated under reduced pressure to remove the tetrahydrofuran, and the pH was adjusted to 5-6 with hydrogen chloride. A large amount of white solid precipitated. This was filtered under reduced pressure, and the resulting filter cake was dried to give the title compound (4.82 g, white solid, 96.7% yield). LC / MS (ESI) m / z: 279.1 [M+H] + .

[0263] Intermediate 3: 6-Bromothiazol[4,5-b]pyridin-2-amine TIFF2025533951000163.tif52122

[0264] Step 1: N-((3,5-dibromopyridin-2-yl)aminomethylthio)benzamide To a solution of 3,5-dibromopyridin-2-amine (100 g, 397 mmol) in acetone (1.2 L) was added benzoyl isothiocyanate (130 g, 794 mmol). The mixture was stirred at room temperature for 16 hours. After the reaction was completed, the mixture was filtered, and the filter cake was washed with acetone and dried to give the title compound (pale yellow solid, 149 g, yield: 90.4%).

[0265] Step 2: 1-(3,5-dibromopyridin-2-yl)thiourea N-((3,5-Dibromopyridin-2-yl)aminomethylthio)benzamide (149 g, 359 mmol) was dissolved in an aqueous solution of sodium hydroxide (598 mL, 3 M) and reacted at 100°C for 2 hours. After completion of the reaction, the mixture was filtered, and the filter cake was washed with water and ethanol and dried to obtain the title compound (yellow solid, 101 g, yield 90.5%).

[0266] Step 3: 6-Bromothiazol[4,5-b]pyridin-2-amine To a solution of 1-(3,5-dibromopyridin-2-yl)thiourea (101 g, 325 mmol) in N,N-dimethylformamide (600 mL) was added 60% sodium hydride (26 g, 650 mmol). The reaction mixture was stirred under nitrogen gas protection at 80°C for 3 hours. After completion of the reaction, the mixture was quenched by slowly adding saturated aqueous ammonium chloride solution, filtered, and the filter cake was washed with water and ethanol. The mixture was dried to obtain the title compound (brown solid, 56 g, yield 74.9%). 1 H NMR (400 MHz, DMSO-d6) δ 8.32 (s, 1H), 8.27 (s, 1H), 8.12 (s, 2H). LC / MS (ESI) m / z: 229.9 [M+H] + .

[0267] Step 4: N-(6-bromothiazolo[4,5-b]pyridin-2-yl)-2'-chloro-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-formamide 6-Bromothiazolo[4,5-b]pyridin-2-amine (10 g, 43.4 mmol) and 2-chloro-5-methoxy-6-methyl-4,4-bipyridine-3-carboxylic acid (13.3 g, 47.8 mmol) were dissolved in acetonitrile (300 mL) and DMF (180 mL), 1-methylimidazole (10.4 mL, 130.4 mmol) was added, and the mixture was heated to 75°C and stirred for 30 minutes. N,N,N',N'-tetramethylformamidinium hexafluorophosphate (12.2 g, 43.4 mmol) was then added, and the mixture was allowed to react at 75°C for 3 hours. Ethyl acetate and water were added to the reaction mixture, followed by layer separation. The organic phase was washed with saturated sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The resulting residue was purified by column chromatography (eluent: dichloromethane / methanol, gradient: 3% - 5% methanol) to give the title compound (pale yellow solid, 8 g, yield 37.5%). LC / MS (ESI) m / z: 491 [M+H] + .

[0268] Example 1: 2'-chloro-N-(5-((1r,4r)-4-hydroxycyclohexyl)thiazole[5,4-b]pyridin-2-yl)-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-formamide and 2'-chloro-N-(5-((1s,4s)-4-hydroxycyclohexyl)thiazole[5,4-b]pyridin-2-yl)-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-formamide TIFF2025533951000164.tif102131

[0269] Step 1: 4-(tert-butyldimethylsiloxy)cyclohexan-1-one 4-Hydroxycyclohexanone (25.0 g, 219 mmol) was dissolved in 450 mL of dichloromethane, and imidazole (14.9 g, 219 mmol) and tert-butyldimethylchlorosilane (33.0 g, 219 mmol) were added. The mixture was allowed to react at room temperature for 18 hours. The reaction mixture was washed with water and saturated brine, and the dichloromethane was removed using a rotary evaporator. The residue was purified by silica gel column chromatography (eluent: petroleum ether / ethyl acetate = 20 / 1, V / V) to give 4-(tert-butyldimethylsiloxy)cyclohexan-1-one (42.0 g, colorless oil, 84% yield).

[0270] Step 2: 4-(tert-butyldimethylsiloxy)cyclohex-1-en-1-yl-trifluoromethanesulfonate 4-(tert-Butyldimethylsiloxy)cyclohexan-1-one (20.0 g, 87.6 mmol) was dissolved in anhydrous tetrahydrofuran (400 mL) and operated under nitrogen gas protection. The mixture was cooled to -65°C and a 1 mol / L solution of lithium bis(trimethylsilyl)amide in tetrahydrofuran (175 mL, 175 mmol) was added dropwise. The reaction mixture was then allowed to react at -65°C for 1 hour. Next, a solution of N-phenylbis(trifluoromethanesulfonyl)imide (200 mL) in tetrahydrofuran (62.6 g, 175 mmol) was added dropwise at -65°C, and the reaction mixture was slowly heated to -20°C over 1 hour. The reaction mixture was then quenched with saturated brine, extracted with ethyl acetate, and the solvent was removed using a rotary evaporator. The residue was purified by silica gel column chromatography (eluent: petroleum ether / ethyl acetate = 30 / 1, V / V) to give 4-(tert-butyldimethylsiloxy)cyclohex-1-en-1-yl trifluoromethanesulfonate (24.0 g, yellow solid, 76.1% yield).

[0271] Step 3: tert-butyldimethyl(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)cyclohexyl-3-en-1-yl)oxysilane 4-(tert-Butyldimethylsiloxy)cyclohex-1-en-1-yl trifluoromethanesulfonate (22.0 g, 61.0 mmol) and bis(pinacolato)diboron (18.6 g, 73.2 mmol) were dissolved in anhydrous 1,4-dioxane (286 mL), and potassium acetate (44.9 g, 458 mmol) and [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium dichloromethane complex (1.50 g, 1.83 mmol) were added. The mixture was heated to 80°C under nitrogen gas protection and operated under anhydrous conditions, and the reaction was carried out for 18 hours. The reaction mixture was cooled to room temperature, the 1,4-dioxane was removed using a rotary evaporator, water was added, and the mixture was extracted with ethyl acetate. The organic phase was washed with water and saturated brine, and the residue was purified by silica gel column chromatography (eluent: dichloromethane / methanol = 50 / 1, V / V) to give tert-butyldimethyl (4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)cyclohexyl-3-en-1-yl)oxysilane (7.60 g, yellow oily liquid, 79.0% yield). 1 H NMR (400 MHz, CDCl3) δ 6.45 - 6.41 (m, 1H), 3.93 - 3.76 (m, 1H), 2.41 - 2.24 (m, 2H), 2.19 - 1.99 (m, 2H), 1.86 - 1.73 (m, 1H), 1.58 - 1.45 (m, 1H), 1.25 (s, 12H), 0.88 (s, 9H), 0.05 (s, 6H).

[0272] Step 4: 5-Bromothiazolo[5,4-b]pyridin-2-yl-acetamide A 100 mL reaction flask was charged with 5-bromothiazolo[5,4-b]pyridin-2-amine (1.40 g, 6.09 mmol), 4-dimethylaminopyridine (850 mg, 7.00 mmol), acetic anhydride (710 mg, 7.00 mmol), and dichloromethane (20 mL). The mixture was reacted at room temperature for 18 hours, concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (eluent: dichloromethane / methanol = 30 / 1, v / v) to give 5-bromothiazolo[5,4-b]pyridin-2-ylacetamide (800 mg, yellow solid, 48.3% yield). LC / MS (ESI) m / z: 272.2 [M+H] + .

[0273] Step 5: N-(5-(4-(tert-butyldimethylsiloxy)cyclohexyl-1-en-1-yl)thiazolo[5,4-b]pyridin-2-yl)acetamide 5-Bromothiazolo[5,4-b]pyridin-2-yl-acetamide (300 mg, 1.10 mmol) and tert-butyldimethyl (4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)cyclohexyl-3-en-1-yl)oxysilane (410 mg, 1.21 mmol) were dissolved in 1,4-dioxane (27 mL) and water (9 mL). Potassium carbonate (305 mg, 2.21 mmol) and 1,1-bis(diphenylphosphino)ferrocenedichloropalladium (80.7 mg, 0.110 mmol) were added, and the mixture was heated to 90°C under nitrogen gas protection and operated under anhydrous conditions for 2 hours. The reaction mixture was cooled to room temperature, the 1,4-dioxane was removed using a rotary evaporator, water was added, and the mixture was extracted with ethyl acetate. The organic phase was washed with water and saturated brine, and the residue was purified by silica gel column chromatography (eluent: dichloromethane / methanol = 30 / 1, V / V) to give N-(5-(4-(tert-butyldimethylsiloxy)cyclohexyl-1-en-1-yl)thiazolo[5,4-b]pyridin-2-yl)acetamide (380 mg, yellow solid, 85.4% yield). LC / MS (ESI) m / z: 404.2 [M+H] + .

[0274] Step 6: 5-(4-((tert-butyldimethylsilyl)oxy)cyclohex-1-en-1-yl)thiazo[5,4-b]pyridin-2-amine N-(5-(4-(tert-butyldimethylsiloxy)cyclohexyl-1-en-1-yl)thiazolo[5,4-b]pyridin-2-yl)acetamide (380 mg, 0.941 mmol) and sodium hydroxide (377 mg, 9.42 mmol) were dissolved in methanol (15 mL) and water (5 mL) and reacted at 85°C for 3 hours. The reaction mixture was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (eluent: dichloromethane / methanol = 20 / 1, V / V) to give 5-(4-((tert-butyldimethylsilyl)oxy)cyclohex-1-en-1-yl)thiazolo[5,4-b]pyridin-2-amine (220 mg, yellow solid, 65% yield). LC / MS (ESI) m / z: 362.2 [M+H] + .

[0275] Step 7: N-(5-(4-((tert-butyldimethylsilyl)oxy)cyclohex-1-en-1-yl)thiazole[5,4-b]pyridin-2-yl)-2'-chloro-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-formamide 5-(4-((tert-Butyldimethylsilyl)oxy)cyclohex-1-en-1-yl)thiazole[5,4-b]pyridin-2-amine (120 mg, 0.332 mmol), 2'-chloro-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-carboxylic acid (92.5 mg, 0.332 mmol), and methylimidazole (81.8 mg, 0.996 mmol) were dissolved in acetonitrile (5 mL) and N,N-dimethylformamide (2 mL), and a solution of N,N,N',N'-tetramethylformamidinium hexafluorophosphate (1 mL) in acetonitrile (93.1 mg, 0.332 mmol) was added dropwise, and the mixture was allowed to react at room temperature for 18 hours. The reaction mixture was concentrated under reduced pressure, water was added, and the mixture was extracted with ethyl acetate. The residue was purified by silica gel column chromatography (eluent: petroleum ether / ethyl acetate = 3 / 1, V / V) to give N-(5-(4-((tert-butyldimethylsilyl)oxy)cyclohex-1-en-1-yl)thiazole[5,4-b]pyridin-2-yl)-2'-chloro-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-formamide (80.2 mg, yellow solid, 38.7% yield). LC / MS (ESI) m / z: 622.2 [M+H] + .

[0276] Step 8: 2'-chloro-N-(5-(4-hydroxycyclohex-1-en-1-yl)thiazole[5,4-b]pyridin-2-yl)-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-formamide N-(5-(4-((tert-butyldimethylsilyl)oxy)cyclohex-1-en-1-yl)thiazole[5,4-b]pyridin-2-yl)-2'-chloro-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-formamide (80.1 mg, 0.129 mmol) was dissolved in dichloromethane (3 mL) and trifluoroacetic acid (3 mL) and the mixture was allowed to react at room temperature for 18 hours. The reaction mixture was concentrated under reduced pressure, extracted with saturated aqueous sodium bicarbonate and ethyl acetate, separated, and concentrated under reduced pressure to give a residue. The residue was purified by prep-HPLC (eluent: acetonitrile / 0.1% aqueous formic acid solution = 25% to 90%, V / V) to give 2'-chloro-N-(5-(4-hydroxycyclohex-1-en-1-yl)thiazole[5,4-b]pyridin-2-yl)-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-formamide (40.1 mg, yellow solid, yield 61.3%). 1 H NMR (400 MHz, DMSO-d6)δ13.02 (s, 1H), 8.85 (s, 1H), 8.17 (s, 1H), 8.04 (d,J= 8.6 Hz, 1H), 7.65 (d,J= 8.6 Hz, 1H), 7.58 (s, 1H), 7.47 (s, 1H), 6.66 - 6.60 (m, 1H), 4.71 (d,J= 3.9 Hz, 1H), 3.85 - 3.80 (m, 1H), 3.62 (s, 3H), 2.75 - 2.64 (m, 1H), 2.61 (s, 3H), 2.54 - 2.50 (m, 1H), 2.47 (s, 1H), 2.17 - 2.05 (m, 1H), 1.95 - 1.85 (m, 1H), 1.65 - 1.58 (m, 1H). LC / MS (ESI) m / z:508.2 [M+H] + . The compounds of the examples in Table 1 were synthesized using commercially available raw materials with reference to the synthesis process of Example 1.

[0277] [Table 1] TIFF2025533951000166.tif243155 TIFF2025533951000167.tif238155 TIFF2025533951000168.tif244155 TIFF2025533951000169.tif223155 TIFF2025533951000170.tif244155 TIFF2025533951000171.tif166155

[0278] Example 26 and Example 27: 2'-chloro-N-(6-((1s,4s)-4-hydroxycyclohexyl)thiazole[4,5-b]pyridin-2-yl)-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-formamide and 2'-chloro-N-(6-((1r,4r)-4-hydroxycyclohexyl)thiazole[4,5-b]pyridin-2-yl)-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-formamide TIFF2025533951000172.tif22147

[0279] Step 1: 2'-chloro-N-(6-((1s,4s)-4-hydroxycyclohexyl)thiazole[4,5-b]pyridin-2-yl)-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-formamide and 2'-chloro-N-(6-((1r,4r)-4-hydroxycyclohexyl)thiazole[4,5-b]pyridin-2-yl)-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-formamide 2'-chloro-N-(6-(4-hydroxycyclohex-1-en-1-yl)thiazole[4,5-b]pyridin-2-yl)-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-formamide (40 mg, 78.7 μmol) was dissolved in methanol (10 mL), platinum oxide (40 mg, 176 μmol) was added, and the mixture was reacted under a hydrogen balloon for 6 hours. The mixture was filtered, and the filtrate was concentrated under reduced pressure and purified by preparative HPLC to obtain two isomers. Each is lyophilized to give 2'-chloro-N-(6-((1s,4s)-4-hydroxycyclohexyl)thiazole[4,5-b]pyridin-2-yl)-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-formamide (white powder, 2.8 mg, yield 7.0%). 1 H NMR (400 MHz, CD3OD) δ 8.86 (s, 1H), 8.47 (s, 1H), 8.39 (s, 1H), 8.04 (s, 1H), 7.51 (s, 1H), 7.45 (s, 1H), 3.70 (s, 3H), 3.68 - 3.64 (m, 1H), 2.80 - 2.74 (m, 1H), 2.71 (s, 3H), 2.14 - 2.08 (m, 2H), 2.04 - 1.97 (m, 2H), 1.73 - 1.61 (m, 2H), 1.43 - 1.45 (m, 2H). LC / MS (ESI) m / z: 510.2 [M+H] + , and 2'-chloro-N-(6-((1r,4r)-4-hydroxycyclohexyl)thiazole[4,5-b]pyridin-2-yl)-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-formamide (white powder, 5.6 mg, yield 13.9%). 1H NMR (400 MHz, CD3OD) δ 8.85 (s, 1H), 8.46 (s, 1H), 8.32 (s, 1H), 8.04 (s, 1H), 7.50 (s, 1H), 7.43 (s, 1H), 4.11 - 4.07 (m, 1H), 3.70 (s, 3H), 2.78 - 2.74 (m, 1H), 2.69 (s, 3H), 2.05 - 1.90 (m, 4H), 1.78 - 1.68 (m, 4H). LC / MS (ESI) m / z: 510.1[M+H] + The compounds of the examples in Table 2 were synthesized with reference to the synthesis steps of Examples 26 and 27.

[0280] [Table 2] TIFF2025533951000174.tif237155 TIFF2025533951000175.tif157155

[0281] Example 38: 2'-chloro-3'-fluoro-5'-methoxy-6-methyl-N-(thiazol[5,4-b]pyridin-2-yl)-[4,4'-bipyridine]-3-formamide TIFF2025533951000176.tif30101

[0282] Step 1: 2'-chloro-3'-fluoro-5'-methoxy-6-methyl-N-(thiazol[5,4-b]pyridin-2-yl)-[4,4'-bipyridine]-3-formamide 4-(2-Chloro-3-fluoro-5-methoxypyridin-4-yl)-6-methylpyridine-3-carboxylic acid (40.0 mg, 0.135 mmol) and benzo[d][1,3]thiazol-2-amine (20.4 mg, 0.135 mmol) were dissolved in acetonitrile (2 mL). 1-Methylimidazole (33.21 mg, 0.404 mmol) was added, and N,N,N',N'-tetramethylformamidinium hexafluorophosphate (37.83 mg, 0.135 mmol) was dissolved in acetonitrile (1 mL) with stirring. The mixture was allowed to react at room temperature for 1 hour. The reaction mixture was concentrated under reduced pressure, and the resulting residue was purified by reverse-phase C18 column chromatography to give 2'-chloro-3'-fluoro-5'-methoxy-6-methyl-N-(thiazol[5,4-b]pyridin-2-yl)-[4,4'-bipyridine]-3-formyl. 1 H NMR (400 MHz, DMSO-d6) δ 13.22 (s, 1H), 9.03 (s, 1H), 8.48 (d, J = 3.9 Hz, 1H), 8.19 (s, 1H), 8.13 (d, J = 6.0 Hz, 1H), 7.53 - 7.48 (m, 2H), 3.73 (s, 3H), 2.61 (s, 3H). LC / MS (ESI) m / z: 430.1 [M+H] + . The compounds of the examples in Table 3 were synthesized using commercially available raw materials with reference to the synthesis process of Example 38.

[0283] [Table 3]

[0284] Example 40: 2'-chloro-3'-fluoro-5'-methoxy-6-methyl-N-(5-((tetrahydrofuran-3-yl)methyl)-4,5,6,7-tetrahydrothiazol[5,4-c]pyridin-2-yl)-[4,4'-bipyridine]-3-formamide TIFF2025533951000178.tif53135

[0285] Step 1: 2-Amino-6,7-dihydrothiazolo[5,4-c]pyridine-5(4H)-carboxylic acid tert-butyl ester N-tert-Butoxycarbonyl-4-piperidone (2 g, 10.1 mmol), cyanamide (844 mg, 20.2 mmol), and sulfur powder (684 mg, 20.2 mmol) were dissolved in pyridine (10 mL), heated to 130 °C, and reacted for 2 hours. The reaction mixture was allowed to cool, filtered, extracted with water and ethyl acetate, and the organic phase was centrifuged to give the title compound (2.11 g, dark brown solid, 82.3% yield). LC / MS (ESI) m / z: 256.1 [M+H] + .

[0286] Step 2: 4,5,6,7-Tetrahydrothiazol[5,4-c]pyridin-2-amine hydrochloride 2-Amino-6,7-dihydrothiazolo[5,4-c]pyridine-5(4H)-carboxylic acid tert-butyl ester (2 g, 7.83 mmol) and a 4 mol / L solution of hydrogen chloride in 1,4-dioxane (20 mL) were dissolved in 1,4-dioxane (10 mL) and reacted at room temperature for 2 hours. The reaction mixture was filtered under reduced pressure, and the solid phase was washed with ethyl acetate. After drying under reduced pressure, the title compound (1.5 g, white solid, 100% yield) was obtained. LC / MS (ESI) m / z: 156.1 [M+H] + .

[0287] Step 3: 5-((tetrahydrofuran-3-yl)methyl)-4,5,6,7-tetrahydrothiazol[5,4-c]pyridin-2-amine 4,5,6,7-Tetrahydrothiazole[5,4-c]pyridin-2-amine hydrochloride (500 mg, 2.61 mmol) was dissolved in methanol (10 mL), ammonia was released by dropwise addition, centrifuged under reduced pressure, and the solution was dissolved in N,N-dimethylformamide (10 mL). (Tetrahydrofuran-3-yl)methyl-4-methylbenzenesulfonate (668 mg, 2.61 mmol), potassium carbonate (1.08 g, 7.82 mmol), N,N-diisopropylethylamine (674 mg, 5.22 mmol), and sodium iodide (78.2 mg, 0.522 mmol) were added sequentially. The mixture was heated to 60 °C and reacted for 24 h. The reaction mixture was filtered and concentrated under reduced pressure. The filtrate was concentrated, and the residue was purified by silica gel column chromatography (dichloromethane-methanol system, gradient: 0-5% methanol) to give the title compound (133 mg, white solid, yield: 26.7%). LC / MS (ESI) m / z: 240.1 [M+H] + .

[0288] Step 4: 2'-chloro-3'-fluoro-5'-methoxy-6-methyl-N-(5-((tetrahydrofuran-3-yl)methyl)-4,5,6,7-tetrahydrothiazol[5,4-c]pyridin-2-yl)-[4,4'-bipyridine]-3-formamide 5-((tetrahydrofuran-3-yl)methyl)-4,5,6,7-tetrahydrothiazole[5,4-c]pyridin-2-amine (80 mg, 0.270 mmol), 2'-chloro-3'-fluoro-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-carboxylic acid (70.1 mg, 0.2 mmol), 1-methylimidazole (44.1 mg, 0.539 mmol), and N,N,N',N'-tetramethylformamidinium hexafluorophosphate (90.1 mg, 0.324 mmol) were dissolved in a mixed solvent of acetonitrile (1 mL) and N,N-dimethylformamide (1 mL) and reacted for 24 hours with stirring at room temperature. The reaction mixture was washed with a small amount of water and extracted with ethyl acetate. The organic phase was then dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated and centrifuged, and the residue was purified by preparative HPLC to obtain the title compound (30 mg, pale yellow solid, yield: 20%). 1 H NMR (400 MHz, CDCl3) δ 9.38 (s, 1H), 7.97 (s, 1H), 7.47 (s, 1H), 4.52 - 4.40(m, 2H), 3.99 - 3.89 (m, 2H), 3.81 - 3.76 (m, 2 H), 3.75 (s, 3H), 3.59 - 3.51 (m, 2H), 3.27 - 3.24 (m, 2H), 3.06 - 3.01 (m, 2H), 2.84 (s, 3H), 2.81 - 2.72 (m, 1H), 2.26 - 2.23 (m, 1H), 1.75 - 1.71 (m, 1H).LC / MS (ESI) m / z: 518.2 [M+H] + .

[0289] Example 41: 2'-chloro-5'-methoxy-6-methyl-N-(4,5,6,7-tetrahydrothiazol[5,4-c]pyridin-2-yl)-[4,4'-bipyridine]-3-formamide TIFF2025533951000179.tif29147

[0290] Step 1: 2-(2'-chloro-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-formamido)-6,7-dihydrothiazole[5,4-c]pyridine-5(4H)-carboxylic acid tert-butyl ester 2-Amino-6,7-dihydrothiazole[5,4-c]pyridine-5(4H)-carboxylic acid tert-butyl ester (200 mg, 0.783 mmol) and 2'-chloro-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-carboxylic acid (190 mg, 0.783 mmol) were dissolved in acetonitrile (5 mL). Under nitrogen gas protection, N,N,N',N'-tetramethylformamidinium hexafluorophosphate (219 mg, 0.783 mmol) and 1-methylimidazole (193 mg, 2.35 mmol) were added, and the mixture was allowed to react at room temperature for 16 hours. The reaction mixture was concentrated under reduced pressure, and the resulting residue was purified by silica gel column chromatography (petroleum ether / ethyl acetate system) to give 2-(2'-chloro-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-formamide)-6,7-dihydrothiazole[5,4-c]pyridine-5(4H)-carboxylic acid tert-butyl ester (100 mg, yellow oil, yield: 28.4%). LC / MS m / z (ESI): 244.0 [M+H] + .

[0291] Step 2: 2'-chloro-5'-methoxy-6-methyl-N-(4,5,6,7-tetrahydrothiazol[5,4-c]pyridin-2-yl)-[4,4'-bipyridine]-3-formamide 2-(2'-Chloro-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-formamide)-6,7-dihydrothiazole[5,4-c]pyridine-5(4H)-carboxylic acid tert-butyl ester (100 mg, 0.194 mmol) was dissolved in acetonitrile (1 mL), and 2 mol / L hydrochloric acid-ethyl acetate solution (1 mL) was added. The mixture was stirred at room temperature for 2 hours. The reaction mixture was concentrated under reduced pressure, and the resulting residue was purified by reverse-phase C18 column chromatography to give 2'-chloro-5'-methoxy-6-methyl-N-(4,5,6,7-tetrahydrothiazole[5,4-c]pyridin-2-yl)-[4,4'-bipyridine]-3-formamide (16.9 mg, white solid, 21.0% yield). 1 H NMR (400 MHz, CD3OD) δ 8.75 (s, 1H), 8.05 (s, 1H), 7.49 (s, 1H), 7.43 (s, 1H), 4.29 (s, 2H), 3.68 (s, 3H), 3.48 (t, J = 6.0 Hz, 2H), 2.95 (t, J = 6.0 Hz, 2H), 2.67 (s, 3H). LC / MS m / z (ESI): 290.2 [M+H] + .

[0292] Example 42: 2'-chloro-N-(5-(4-hydroxycyclohexyl)-4,5,6,7-tetrahydrothiazol[5,4-c]pyridin-2-yl)-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-formamide TIFF2025533951000180.tif25128

[0293] Step 1: 2'-chloro-N-(5-(4-hydroxycyclohexyl)-4,5,6,7-tetrahydrothiazol[5,4-c]pyridin-2-yl)-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-formamide 2'-Chloro-5'-methoxy-6-methyl-N-(4,5,6,7-tetrahydrothiazol[5,4-c]pyridin-2-yl)-[4,4'-bipyridine]-3-formamide (170 mg, 0.447 mmol) and tetraethyl titanate (0.043 mL, 0.205 mmol) were dissolved in methanol (5 mL), 4-hydroxycyclohexan-1-one (0.043 mL, 0.205 mmol) was added, and the mixture was stirred at room temperature for 30 minutes. Sodium cyanoborohydride (77.2 mg, 1.23 mmol) was then added, and the mixture was allowed to react at room temperature for 16 hours. The reaction mixture was filtered, and the mother liquor was concentrated under reduced pressure. The resulting residue was separated using a reversed-phase C18 column (acetonitrile-water system) to give 2'-chloro-N-(5-(4-hydroxycyclohexyl)-4,5,6,7-tetrahydrothiazole[5,4-c]pyridin-2-yl)-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-formamide (3.5 mg, white solid, yield: 1.6%). 1 H NMR (400 MHz, CD3OD) δ 8.75 (s, 1H), 8.05 (s, 1H), 7.49 (s, 1H), 7.43 (s, 1H), 4.34 (s, 2H), 4.02 - 3.97 (m, 1H), 3.67 (s, 3H), 3.55 - 3.48, (m, 2H), 3.20 - 3.16(m, 1H), 3.04 - 2.98 (m, 2H), 2.67 (s, 3H), 2.01 - 1.92, (m, 4H), 1.91 - 1.85, (m, 2H), 1.69 - 1.59 (m, 2H). LC / MS m / z (ESI): 559.8 [M+H] + .

[0294] Example 43: 2'-chloro-5'-methoxy-6-methyl-N-(5-(4-methylpiperazin-1-yl)thiazole[5,4-b]pyridin-2-yl)-[4,4'-bipyridine]-3-formamide TIFF2025533951000181.tif54152

[0295] Step 1: N-(5-(4-methylpiperazin-1-yl)thiazole[5,4-b]pyridin-2-yl)acetamide N-(5-Bromothiazole[5,4-b]pyridin-2-yl)acetamide (100 mg, 0.367 mmol), 1-methylpiperazine (55 mg, 0.551 mmol), and sodium tert-butoxide (106 mg, 1.101 mmol) were dissolved in dioxane (8 mL). Tris(dibenzylideneacetone)dipalladium (34 mg, 0.037 mmol) and 44,5-bis(diphenylphosphino)-9,9-dimethylxanthene (42 mg, 0.073 mmol) were added under nitrogen gas protection. The mixture was heated to 100°C under nitrogen gas protection and reacted for 10 hours. After completion of the reaction, the reaction mixture was filtered and the filtrate was concentrated. The residue was purified by column chromatography (eluent: dichloromethane / methanol, gradient: 0-10% methanol) to give the title compound (yellow oil, 70 mg, yield: 65.5%). LC / MS (ESI) m / z: 292 [M+H] + .

[0296] Step 2: 5-(4-methylpiperazin-1-yl)thiazole[5,4-b]pyridin-2-amine N-(5-(4-methylpiperazin-1-yl)thiazole[5,4-b]pyridin-2-yl)acetamide (65 mg, 0.223 mmol) was dissolved in ethanol (3 mL) and water (3 mL). Sodium hydroxide (18 mg, 0.446 mmol) was added to the mixture, which was then stirred at 60°C for 10 hours. The reaction mixture was cooled to room temperature and acidified to pH 7 with 1N hydrochloric acid. The resulting residue was purified by reverse-phase C18 column chromatography to give the title compound (yellow solid, 40 mg, 70.9% yield). LC / MS (ESI) m / z: 250 [M+H] + .

[0297] Step 3: 2'-chloro-5'-methoxy-6-methyl-N-(5-(4-methylpiperazin-1-yl)thiazole[5,4-b]pyridin-2-yl)-[4,4'-bipyridine]-3-formamide 5-(4-Methylpiperazin-1-yl)thiazole[5,4-b]pyridin-2-amine (40 mg, 0.161 mmol) and 2'-chloro-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-carboxylic acid (54 mg, 0.193 mmol) were dissolved in acetonitrile (2 mL) and N,N-dimethylformamide (2 mL). Under nitrogen gas protection, N,N,N',N'-tetramethylformamidinium hexafluorophosphate (68 mg, 0.241 mmol) and 1-methylimidazole (40 mg, 0.481 mmol) were added and the mixture was allowed to react at room temperature for 10 hours. The reaction mixture was concentrated under reduced pressure, and the residue was purified by preparative HPLC to give the title compound (yellow solid, 11 mg, 13.5% yield). 1 H NMR (400 MHz, CD3OD) δ 8.85 (s, 1H), 8.08 (s, 1H), 7.92 (d, J = 9.0 Hz, 1H), 7.55 (s, 1H), 7.53 (s, 1H), 7.07 (d, J = 9.1 Hz, 1H), 4.56 - 4.53 (m, 2H), 3.71 (s, 3H), 3.62 - 3.60 (m, 2H), 3.26 - 3.20 (m, 4H), 2.96 (s, 3H), 2.71 (s, 3H). LC / MS (ESI) m / z: 510.1 [M+H] + .

[0298] Example 44: 2'-chloro-N-(5-(5-chloropyridin-2-yl)thiazole[5,4-b]pyridin-2-yl)-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-formamide TIFF2025533951000182.tif62147

[0299] Step 1: N-(5-(5-chloropyridin-2-yl)thiazole[5,4-b]pyridine-2-alkyl)acetamide N-(5-bromothiazole[5,4-b]pyridin-2-yl)acetamide (100 mg, 0.367 mmol) and 5-chloro-2-(tributyltinyl)pyridine (148 mg, 0.367 mmol) were dissolved in dioxane (8 mL). Tetrakis(triphenylphosphine)palladium (42 mg, 0.037 mmol) was added under nitrogen gas protection, and the reaction was carried out at 120°C for 10 hours. After completion of the reaction, the reaction mixture was filtered, and the filtrate was concentrated. The residue was purified by reverse-phase C18 column chromatography to give the title compound (yellow solid, 80 mg, yield: 71.4%). LC / MS (ESI) m / z: 305 [M+H] + .

[0300] Step 2: 5-(5-chloropyridin-2-yl)thiazole[5,4-b]pyridin-2-amine N-(5-(5-chloropyridin-2-yl)thiazole[5,4-b]pyridine-2-alkyl)acetamide (80 mg, 0.263 mmol) was dissolved in a mixture of ethanol (3 mL) and water (3 mL), and sodium hydroxide (21 mg, 0.526 mmol) was added. The mixture was stirred at 60°C for 10 hours. The mixture was acidified with 1N hydrochloric acid to pH 7, and the resulting residue was purified by reverse-phase C18 column chromatography to give the title compound (yellow solid, 50 mg, 72.5% yield). LC / MS (ESI) m / z: 263 [M+H] + .

[0301] Step 3: 2'-chloro-N-(5-(5-chloropyridin-2-yl)thiazole[5,4-b]pyridin-2-yl)-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-formamide 5-(5-Chloropyridin-2-yl)thiazole[5,4-b]pyridin-2-amine (50 mg, 0.191 mmol) and 2'-chloro-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-carboxylic acid (64 mg, 0.228 mmol) were dissolved in acetonitrile (2 mL) and N,N-dimethylformamide (2 mL). Under nitrogen gas protection, N,N,N',N'-tetramethylformamidinium hexafluorophosphate (80 mg, 0.285 mmol) and 1-methylimidazole (47 mg, 0.571 mmol) were added and the mixture was allowed to react at room temperature for 10 hours. The reaction mixture was concentrated under reduced pressure, and the residue was purified by preparative HPLC to give the title compound (yellow solid, 10 mg, 10.0% yield). 1 H NMR (400 MHz, DMSO-d6) δ 13.23 (s, 1H), 8.88 (s, 1H), 8.75 (s, 1H), 8.49(d, J = 8.0 Hz, 1H), 8.44 (d, J = 8.0 Hz, 1H), 8.27 (d, J = 8.4 LC / MS (ESI) m / z: 523 [M+H] + .

[0302] Example 45: 2-chloro-5-methoxy-6-methyl-N-(6-morpholinylbenzothiazol-2-yl)-4,4'-bipyridine-3-formamide TIFF2025533951000183.tif55143

[0303] Step 1: N-(6-morpholinylbenzothiazol-2-yl)acetamide 6-Bromo-2-acetamidobenzothiazole (500 mg, 1.84 mmol), morpholine (0.18 mL, 2.03 mmol), sodium tert-butoxide (354 mg, 3.69 mmol), 2-dicyclohexylphosphonium-2',6'-diisopropoxy-1,1'-biphenyl (86.1 mg, 0.18 mmol), and tris(dibenzylideneacetone)dipalladium (84.4 mg, 0.09 mmol) were dissolved in anhydrous 1,4-dioxane (10 mL). The mixture was purged with nitrogen gas three times and heated to 100°C under nitrogen gas protection for 3 hours. The reaction mixture was cooled to room temperature and concentrated under reduced pressure. The residue was purified by column chromatography (eluent: dichloromethane / methanol, gradient: 3% - 5% methanol) to give the title compound (white solid, 360 mg, yield 70.4%). LC / MS (ESI) m / z: 278.0 [M+H] + .

[0304] Step 2: 6-morpholinobenzo[d]thiazol-2-amine The resulting N-(6-morpholinylbenzothiazol-2-yl)acetamide (360 mg, 1.3 mmol) was dissolved in water (3 mL) and methanol (9 mL), sodium hydroxide (519 mg, 13.0 mmol) was added, and the mixture was heated to 90°C and reacted for 3 hours. The reaction mixture was then concentrated under reduced pressure. The residue was purified by column chromatography (eluent: dichloromethane / methanol, gradient: 3% - 5% methanol) to give the title compound (white solid, 240 mg, yield: 78.5%). LC / MS (ESI) m / z: 236.0 [M+H] + .

[0305] Step 3: 5-(2,7-diazaspiro[3.5]nonadien-2-yl)-1,3,4-thiadiazol-2-yl-2-chloro-5-methoxy-6-methyl-4,4′-bipyridine-3-formamide 6-Morpholinobenzo[d]thiazol-2-amine (240 mg, 1.02 mmol) and 2-chloro-5-methoxy-6-methyl-4,4-bipyridine-3-carboxylic acid (284 mg, 1.02 mmol) were dissolved in acetonitrile (10 mL) and DMF (3 mL), 1-methylimidazole (0.24 mL, 3.06 mmol) was added, and the mixture was stirred for 10 minutes. N,N,N',N'-tetramethylformamidinium hexafluorophosphate (286 mg, 1.02 mmol) was then added, and the mixture was allowed to react at room temperature for 18 hours. Ethyl acetate and water were added to the reaction mixture, followed by layer separation. The organic phase was washed with saturated sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by preparative HPLC (eluent: acetonitrile / 0.1% aqueous formic acid solution, gradient: 25% to 90%) to obtain the title compound (yellow solid, 175 mg, yield: 34.6%). 1 HNMR (400MHz, DMSO-d6) δ 12.74 (s, 1H), 8.82 (s, 1H), 8.16 (s, 1H), 7.62 (d, J = 9.0 Hz, 1H), 7.56 (s, 1H), 7.47 (d, J = 2.2 Hz, 1H), 7.44 (s, 1H), 7.15 (dd, J = 9.0, 2.4 Hz, 1H), 3.78 - 3.75 (m, 4H), 3.60 (s, 3H), 3.15 - 3.12 (m, 4H), 2.60 (s, 3H). LC / MS (ESI) m / z: 496.1 [M+H] + .

[0306] The compounds of the examples in Table 4 were synthesized using commercially available raw materials with reference to the synthesis process of Example 45.

[0307] [Table 4] TIFF2025533951000185.tif238155 TIFF2025533951000186.tif84155

[0308] Example 54: 2'-chloro-3'-fluoro-5'-methoxy-6-methyl-N-(5-(tetrahydrofuran-3-carbonyl)-4,5,6,7-tetrahydrothiazol[5,4-c]pyridin-2-yl)-[4,4'-bipyridine]-3-formamide TIFF2025533951000187.tif65139

[0309] Step 1: 2-(2'-chloro-3'-fluoro-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-formamido)-6,7-dihydrothiazole[5,4-c]pyridine-5(4H)-carboxylic acid tert-butyl ester To a solution of 2-amino-6,7-dihydrothiazole[5,4-c]pyridine-5(4H)-carboxylic acid tert-butyl ester (50 mg, 0.196 mmol) in N,N-dimethylformamide (1 mL) and acetonitrile (1 mL) was added 2'-chloro-3'-fluoro-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-carboxylic acid (58 mg, 0.195 mmol), 1-methylimidazole (48 mg, 0.585 mmol), and N,N,N',N'-tetramethylformamidinium hexafluorophosphate (66 mg, 0.235 mmol). The mixture was stirred at room temperature for 16 hours. After completion of the reaction, water was added, followed by extraction with ethyl acetate. The organic phase was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by column chromatography (eluent: petroleum ether / ethyl acetate, gradient: 0-100% ethyl acetate) to give the title compound (pale yellow oil, 20 mg, yield 19.1%). LC / MS (ESI) m / z: 534.2 [M+H] + .

[0310] Step 2: 2'-chloro-3'-fluoro-5'-methoxy-6-methyl-N-(4,5,6,7-tetrahydrothiazol[5,4-c]pyridin-2-yl)-[4,4'-bipyridine]-3-formamide To a solution of 2-(2'-chloro-3'-fluoro-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-formamide)-6,7-dihydrothiazole[5,4-c]pyridine-5(4H)-carboxylic acid tert-butyl ester (20 mg, 0.037 mmol) in ethyl acetate (1 mL) was added 4M hydrochloric acid-ethyl acetate solution (1 mL). The reaction mixture was stirred at room temperature for 1 hour. After completion of the reaction, the mixture was concentrated under reduced pressure to give the title compound (pale yellow oil, 16 mg, 100.0% yield). The product was used in the next reaction without purification. LC / MS (ESI) m / z: 434.1 [M+H] + .

[0311] Step 3: 2'-chloro-3'-fluoro-5'-methoxy-6-methyl-N-(5-(tetrahydrofuran-3-carbonyl)-4,5,6,7-tetrahydrothiazol[5,4-c]pyridin-2-yl)-[4,4'-bipyridine]-3-formamide To a solution of 2'-chloro-3'-fluoro-5'-methoxy-6-methyl-N-(4,5,6,7-tetrahydrothiazol[5,4-c]pyridin-2-yl)-[4,4'-bipyridine]-3-formamide (16 mg, 0.037 mmol) in N,N-dimethylformamide (1 mL) and acetonitrile (1 mL) was added 3-tetrahydrofurancarboxylic acid (6 mg, 0.055 mmol), 1-methylimidazole (9 mg, 0.111 mmol), and N,N,N',N'-tetramethylformamidinium hexafluorophosphate (12 mg, 0.044 mmol), sequentially. The mixture was stirred at room temperature for 16 hours. After completion of the reaction, water was added, followed by extraction with ethyl acetate. The organic phase was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by preparative HPLC to give the title compound (white solid, 4.4 mg, yield 23.9%). 1H NMR (400 MHz, DMSO-d6) δ 12.74 (s, 1H), 8.95 (s, 1H), 8.17 (s, 1H), 7.45 (s, 1H), 4.76 - 4.52 (m, 2H), 3.94 - 3.78 (m, 3H), 3.74 - 3.64 (m, 6H), 3.52 - 3.42 (m, 1H), 2.76 - 2.72 (m, 1H), 2.69 - 2.61 (m, 1H), 2.59 (s, 3H), 2.11 - 1.92 (m, 2H). LC / MS (ESI) m / z: 532.2[M+H] + .

[0312] Example 55: 7-(2-chloro-5-methoxypyridin-4-yl)-N-(5-(4-hydroxycyclohex-1-en-1-yl)thiazole[5,4-b]pyridin-2-yl)-3-methylimidazole[1,5-a]pyridine-6-formamide TIFF2025533951000188.tif103151

[0313] Step 1: 4-bromo-5-(methoxycarbonyl)-2-methylpyridine-1-oxide To a solution of 4-bromo-6-methylpyridine-3-carboxylic acid methyl ester (2.00 g, 8.69 mmol) stored in dichloromethane (30 mL) was added 3-chlorobenzeneperoxybenzoic acid (2.65 g, 13.0 mmol) at 0 °C. The reaction mixture was then stirred at 50 °C for 2 hours. After completion of the reaction, the mixture was cooled to room temperature. The mixture was filtered through diatomaceous earth and washed with saturated aqueous sodium bicarbonate (100 mL × 2) and brine (100 mL). The combined organic phase was dried over anhydrous sodium sulfate and concentrated on a rotary evaporator. The residue was purified by column chromatography (eluent: petroleum ether / ethyl acetate, gradient: 0 to 80% ethyl acetate) to give the title compound (white solid, 1.60 g, yield: 74.8%). 1H NMR (400 MHz, CDCl3) δ 8.70 (s, 1H), 7.57 (s, 1H), 3.96 (s, 3H), 2.53 (s, 3H).

[0314] Step 2: methyl 4-bromo-6-(hydroxymethyl)nicotinate Trifluoroacetic anhydride (3.41 g, 16.3 mmol) was added to a solution of 4-bromo-5-(methoxycarbonyl)-2-methylpyridine 1-oxide (1.6 g, 6.50 mmol) stored in dichloromethane (30 mL) at 0 °C. The solution was stirred under reflux. After completion of the reaction as monitored by TLC (PE:EA = 1:1), the solution was concentrated on a rotary evaporator. The residue was dissolved in methanol (30 mL), and triethylamine was added dropwise until the solution became neutral. The solution was stirred at room temperature for 4 h. Methanol, methyl trifluoroacetate, trifluoroacetic acid, and triethylamine were all removed on a rotary evaporator. Purification by high-performance chromatography (eluent: petroleum ether / ethyl acetate, gradient: 0 - 50% ethyl acetate) gave the title compound (yellow solid, 1.35 g, 84.4%). 1 H NMR (400 MHz, CDCl3) δ 8.95 (s, 1H), 7.66 (s, 1H), 4.80 (s, 2H), 3.98 (s, 3H), 3.18 (s, 1H).

[0315] Step 3: 2'-chloro-6-(hydroxymethyl)-5'-methoxy-[4,4'-bipyridine]-3-carboxylic acid methyl ester To a solution of methyl 4-bromo-6-(hydroxymethyl)pyridine-3-carboxylate (1.35 g, 5.49 mmol) and (2-chloro-5-methoxypyridin-4-yl)boraziol (1.08 g, 5.76 mmol) in dioxane / water (24 mL) (V:V = 5:1), potassium carbonate (2.27 g, 16.5 mmol) and Pd(dppf)Cl2 (0.20 g, 0.274 mmol) were added, and the reaction mixture was stirred at 80 °C under nitrogen gas protection for 1 h. After completion of the reaction, the reaction mixture was cooled to room temperature and concentrated in vacuo to remove most of the solvent. The residue was poured into water (10 mL) and extracted with ethyl acetate (20 mL). The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated. Purification by high performance chromatography (eluent: petroleum ether / ethyl acetate, gradient: 0-40% ethyl acetate) gave the title compound (yellow solid, 1.50 g, 88.6%). 1 H NMR (400 MHz, CDCl3) δ 9.11 (s, 1H), 8.05 (s, 1H), 7.22 (s, 1H), 7.19 (s, 1H), 4.87 (s, 2H), 3.81 (s, 3H), 3.77 (s, 3H), 3.42 (s, 1H).

[0316] Step 4: 2'-chloro-6-formyl-5'-methoxy-[4,4'-bipyridine]-3-carboxylic acid methyl ester Activated manganese dioxide (0.841 mL, 48.6 mmol) was added to a solution of 4-(2-chloro-5-methoxypyridin-4-yl)-6-(hydroxymethyl)pyridine-3-carboxylic acid methyl ester (1.5 g, 4.859 mmol) stored in dichloromethane (30 mL) at room temperature, and the mixture was stirred at 50 °C for 1 hour. After completion of the reaction, the reaction mixture was filtered, and the filtrate was concentrated. Purification by high-performance chromatography (eluent: petroleum ether / ethyl acetate, gradient: 0 - 30% ethyl acetate) gave the title compound (white solid, 1.20 g, 3.91 mmol, 80.5%). 1H NMR (400 MHz, CDCl3) δ 10.16 (s, 1H), 9.27 (s, 1H), 8.08 (s, 1H), 7.87 (s, 1H), 7.23 (s, 1H), 3.83 (s, 3H), 3.81 (s, 3H).

[0317] Step 5: Methyl (E)-2'-chloro-6-((hydroxyimino)methyl)-5'-methoxy-[4,4'-bipyridine]-3-carboxylate Sodium acetate (0.960 g, 11.7 mmol) was dissolved in methanol (20 mL) at room temperature, and hydroxylamine hydrochloride (0.820 g, 11.7 mmol) was added. The mixture was stirred for 0.5 h. The precipitate formed was removed by filtration, and the filtrate was added dropwise to a solution of 4-bromo-6-formylpyridine-3-carboxylic acid methyl ester (135 mg, 0.553 mmol) in methanol (20 mL). The reaction mixture was stirred at room temperature for 1 h. The reaction mixture was concentrated and dissolved in ethyl acetate (60 mL). The mixture was washed with saturated sodium bicarbonate solution, dried over anhydrous sodium sulfate, filtered, and concentrated to give the title compound (white solid, 1.10 g, 87.4%). 1 H NMR (400 MHz, CDCl3) δ 9.14 (s, 2H), 8.35 (s, 1H), 8.05 (s, 1H), 7.75 (s, 1H), 7.23 (s, 1H), 3.81 (s, 3H), 3.77 (s, 3H).

[0318] Step 6: 6-(aminomethyl)-2-chloro-5'-methoxy-[4,4'-bipyridine]-3-carboxylic acid methyl ester Platinum dioxide (0.021 mL, 0.932 mmol) was added to a solution of 4-(2-chloro-5-methoxypyridin-4-yl)-6-[(E)-(hydroxyimino)methyl]pyridine-3-carboxylic acid methyl ester (1 g, 3.108 mmol) in methanol (30 mL) at room temperature. The mixture was then purged with a hydrogen balloon three times at room temperature and stirred under hydrogen gas for 4 hours. After completion of the reaction, the reaction mixture was filtered, and the filtrate was concentrated to give the title compound (yellow solid, 950 mg, 99.32%). LC / MS (ESI) m / z: 308 [M+H] + .

[0319] Step 7: 7-(2-chloro-5-methoxypyridin-4-yl)-3-methylimidazo[1,5-a]pyridine-6-carboxylic acid methyl ester To a solution of 6-(aminomethyl)-4-(2-chloro-5-methoxypyridin-4-yl)pyridine-3-carboxylic acid methyl ester (0.95 g, 3.09 mmol) stored in acetic anhydride (20 mL) was added 4-methylbenzenesulfonic acid (0.497 mL, 3.087 mmol) at room temperature. The reaction mixture was then stirred at 110°C for 12 hours. After completion of the reaction, the reaction mixture was concentrated. Purification by high-performance chromatography (eluent: petroleum ether / ethyl acetate, gradient: 0-60% ethyl acetate) afforded the title compound (yellow solid, 680 mg, 66.4%). 1 H NMR (400 MHz, CDCl3) δ 8.42 (s, 1H), 7.98 (s, 1H), 7.46 (s, 1H), 7.34 (s, 1H), 7.28 (s, 1H), 3.81 (s, 3H), 3.74 (s, 3H), 2.76 (s, 3H).

[0320] Step 8: 7-(2-chloro-5-methoxypyridin-4-yl)-3-methylimidazo[1,5-a]pyridine-6-carboxylic acid To a solution of 7-(2-chloro-5-methoxypyridin-4-yl)-3-methylimidazo[1,5-a]pyridine-6-carboxylic acid methyl ester (280 mg, 0.844 mmol) stored in acetonitrile (9 mL) and water (3 mL) at room temperature, 1,3,4,6,7,8-hexahydro-2H-pyrimido[1,2-a]pyrimidine (235 mg, 1.69 mmol) was added. The mixture was stirred at 50°C for 1 hour. After completion of the reaction, the reaction mixture was concentrated. Purification by high-performance chromatography (eluent: dichloromethane / ethyl acetate (ethyl acetate with 0.3% acetic acid added), gradient: 0-80% ethyl acetate) afforded the title compound (yellow solid, 160 mg, 59.7%). 1 H NMR (400 MHz, DMSO-d6) δ 12.49 (m, 1H), 8.61 (s, 1H), 8.18 (s, 1H), 7.63 (s, 1H), 7.52 (s, 1H), 7.45 (s, 1H), 3.83 (s, 3H), 2.74 (s, 3H).

[0321] Step 9: N-(5-(4-((tert-butyldimethylsilyl)oxy)cyclohex-1-en-1-yl)thiazole[5,4-b]pyridin-2-yl)-7-(2-chloro-5-methoxypyridin-4-yl)-3-methylimidazole[1,5-a]pyridine-6-formamide 7-(2-Chloro-5-methoxypyridin-4-yl)-3-methylimidazo[1,5-a]pyridine-6-carboxylic acid (80 mg, 0.252 mmol), 5-(4-((tert-butyldimethylsilyl)oxy)cyclohex-1-en-1-yl)thiazole[5,4-b]pyridin-2-amine (91 mg, 0.252 mmol), and 1-methylimidazole (62.1 mg, 0.756 mmol) were dissolved in acetonitrile (5 mL) and stirred at 40 °C for 5 min. N,N,N',N'-tetramethylformamidinium hexafluorophosphate (77.7 mg, 0.277 mmol) was added and dissolved in acetonitrile (2 mL). The mixture was stirred under nitrogen gas protection at 40 °C for 1 h. After the reaction was completed, water was added, extracted with ethyl acetate, washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by column chromatography (eluent: dichloromethane / methanol, gradient: 0%-8% methanol) to obtain the title compound (white powder, 56 mg, yield 33.6%). LC / MS (ESI) m / z: 661.3 [M+H] + .

[0322] Step 10: 7-(2-chloro-5-methoxypyridin-4-yl)-N-(5-(4-hydroxycyclohex-1-en-1-yl)thiazole[5,4-b]pyridin-2-yl)-3-methylimidazole[1,5-a]pyridine-6-formamide N-(5-(4-((tert-butyldimethylsilyl)oxy)cyclohex-1-en-1-yl)thiazole[5,4-b]pyridin-2-yl)-7-(2-chloro-5-methoxypyridin-4-yl)-3-methylimidazole[1,5-a]pyridine-6-formamide (40 mg, 0.061 mmol) was dissolved in 1,4-dioxane (2 mL), and 4 M hydrochloric acid-1,4-dioxane solution (2 mL) was slowly added. After reacting at room temperature for 1 hour, the mixture was concentrated under reduced pressure. Saturated sodium bicarbonate solution was added to the residue, and the mixture was extracted with ethyl acetate, washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by preparative HPLC and lyophilized to obtain the target compound (white powder, 12 mg, yield 36.3%). 1 H NMR (400 MHz, DMSO-d6) δ 8.74 (s, 1H), 8.07 (s, 1H), 7.99 (d, J = 8.3 Hz, 1H), 7.68 (s, 1H), 7.62 (d, J = 8.5 Hz, 1H), 7.55 (s, 1H), 7.44 (s, 1H), 6.62 - 6.57 (m, 1H), 4.74 - 4.66 (m, 1H), 3.85 - 3.78 (m, 1H), 3.60 (s, 3H), 2.71 (s, 3H), 2.71 - 2.63 (m, 1H), 2.55 - 2.51 (m, 1H), 2.48 - 2.42 (m, 1H), 2.17 - 2.05 (m,1H), 1.94 - 1.86 (m, 1H), 1.65 - 1.55 (m, 1H). LC / MS (ESI) m / z: 547.2 [M+H] + .

[0323] Example 56: 2'-chloro-N-(5-(4-hydroxycyclohex-1-en-1-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-formamide TIFF2025533951000189.tif101147

[0324] Step 1: 6-Bromo-N-(4-methoxybenzyl)-3-nitropyridin-2-amine 2,6-Dibromo-3-nitropyridine (1.0 g, 3.55 mmol) was dissolved in ethanol (15 mL), triethylamine (0.718 g, 7.09 mmol) was added, followed by p-methoxybenzylamine (0.487 g, 3.55 mmol), and the mixture was allowed to react at room temperature for 18 hours. After completion of the reaction, the mixture was concentrated under reduced pressure, and the solid was washed with ethyl acetate to give the title compound (yellow solid, 0.58 g, 48.3% yield). LC / MS (ESI) m / z: 338 [M+H] + .

[0325] Step 2: 6-Bromo-N 2 -(4-Methoxybenzyl)pyridine-2,3-diamine 6-Bromo-N-(4-methoxybenzyl)-3-nitropyridin-2-amine (4.8 g, 14.19 mmol) was dissolved in ethanol (50 mL), and tin chloride dihydrate (16.0 g, 70.95 mmol) was added. The mixture was reacted at 50°C for 3 hours. After the reaction was complete, the mixture was cooled to room temperature and 10% sodium bicarbonate solution was added. A large amount of white solid appeared. When the solid stopped increasing, the mixture was filtered, washed with ethanol, and the filtrate was concentrated under reduced pressure. Diatomaceous earth was added, and the mixture was filtered. The filtrate was washed with ethanol and concentrated under reduced pressure again to give the title compound (dark yellow solid, 1.2 g, 27.5% yield). LC / MS (ESI) m / z: 308 [M+H] + .

[0326] Step 3: 5-Bromo-3-(4-methoxybenzyl)-3H-imidazo[4,5-b]pyridin-2-amine 6-Bromo-N 24-(4-Methoxybenzyl)pyridine-2,3-diamine (1.2 g, 3.89 mmol) was dissolved in ethanol (20 mL), and a solution of bromonitrile in dichloromethane (0.493 g, 4.65 mmol) was added. The mixture was allowed to react overnight at room temperature. After completion of the reaction, the reaction mixture was made alkaline with a solution of ammonia in methanol, concentrated under reduced pressure, stirred, and purified by column chromatography (eluent: dichloromethane / methanol = 5 / 1, V / V) to give the title compound (pale yellow solid, 720 mg, 55.4% yield). LC / MS (ESI) m / z: 333 [M+H] + .

[0327] Step 4: N-(5-bromo-3-(4-methoxybenzyl)-3H-imidazo[4,5-b]pyridin-2-yl)acetamide A 100 mL reaction flask was charged with 5-bromo-3-(4-methoxybenzyl)-3H-imidazo[4,5-b]pyridin-2-amine (0.72 g, 2.16 mmol), 4-dimethylaminopyridine (290 mg, 2.38 mmol), acetic anhydride (243 mg, 2.38 mmol), and 20 mL of dichloromethane. The mixture was reacted at room temperature for 18 hours, concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (eluent: dichloromethane / methanol = 30 / 1, v / v) to give N-(5-bromo-3-(4-methoxybenzyl)-3H-imidazo[4,5-b]pyridin-2-yl)acetamide (600 mg, yellow solid, 74.0% yield). LC / MS (ESI) m / z: 375 [M+H] + .

[0328] Step 5: N-(5-(4-(tert-butyldimethylsilyl)oxy)cyclohex-1-en-1-yl)-3-(4-methoxybenzyl)-3H-imidazo[4,5-b]pyridin-2-yl)acetamide N-(5-Bromo-3-(4-methoxybenzyl)-3H-imidazo[4,5-b]pyridin-2-yl)acetamide (600 mg, 1.60 mmol) and tert-butyldimethyl((4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)cyclohex-3-en-1-yl)oxy)silane (812.1 mg, 2.40 mmol) were dissolved in 1,4-dioxane (27 mL) and water (9 mL). Potassium carbonate (663.4 mg, 4.80 mmol) and 1,1'-bis(di-tert-butylphosphine)ferrocenepalladium dichloride (51.7 mg, 0.08 mmol) were added, and the mixture was heated to 90°C under nitrogen gas protection and reacted for 3 hours. The reaction mixture was cooled to room temperature, the 1,4-dioxane was removed using a rotary evaporator, water was added, and the mixture was extracted with ethyl acetate. The organic phase was washed with water and saturated brine, and the organic phase was concentrated under reduced pressure to give the crude product N-(5-(4-(tert-butyldimethylsilyl)oxy)cyclohex-1-en-1-yl)-3-(4-methoxybenzyl)-3H-imidazo[4,5-b]pyridin-2-yl)acetamide (1.0 g, yellow solid), which was directly used in the next step. LC / MS (ESI) m / z: 507 [M+H] + .

[0329] Step 6: 5-(4-((tert-butyldimethylsilyl)oxy)cyclohex-1-en-1-yl)-3-(4-methoxybenzyl)-3H-imidazo[4,5-b]pyridin-2-amine The crude product, N-(5-(4-(tert-butyldimethylsilyl)oxy)cyclohex-1-en-1-yl)-3-(4-methoxybenzyl)-3H-imidazo[4,5-b]pyridin-2-yl)acetamide (1.0 g), sodium hydroxide (400 mg, 10 mmol) were dissolved in methanol (15 mL) and water (5 mL) and reacted at 50°C for 3 hours. The reaction mixture was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (eluent: dichloromethane / methanol = 20 / 1, V / V) to give the crude product, 5-(4-((tert-butyldimethylsilyl)oxy)cyclohex-1-en-1-yl)-3-(4-methoxybenzyl)-3H-imidazo[4,5-b]pyridin-2-amine (600 mg, yellow solid). LC / MS (ESI) m / z: 465 [M+H] + .

[0330] Step 7: N-(5-(4-(tert-butyldimethylsilyl)oxy)cyclohex-1-en-1-yl)-3-(4-methoxybenzyl)-3H-imidazo[4,5-b]pyridin-2-yl)-2'-chloro-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-formamide 5-(4-((tert-Butyldimethylsilyl)oxy)cyclohex-1-en-1-yl)-3-(4-methoxybenzyl)-3H-imidazo[4,5-b]pyridin-2-amine (200 mg, 0.430 mmol), 2'-chloro-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-carboxylic acid (179.8 mg, 0.645 mmol), and methylimidazole (105.8 mg, 1.29 mmol) were dissolved in acetonitrile (10 mL) and stirred at 70°C for 10 minutes. N,N,N',N'-tetramethylformamidinium hexafluorophosphate (361.9 mg, 1.29 mmol) was added, and the mixture was reacted at 70°C for 18 hours. The reaction mixture was concentrated under reduced pressure, water was added, and the mixture was extracted with ethyl acetate. The residue was purified by silica gel column chromatography (eluent: petroleum ether / ethyl acetate = 3 / 1, V / V) to give N-(5-(4-(tert-butyldimethylsilyl)oxy)cyclohex-1-en-1-yl)-3-(4-methoxybenzyl)-3H-imidazo[4,5-b]pyridin-2-yl)-2'-chloro-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-formamide (200 mg, yellow solid, 64.1% yield). LC / MS (ESI) m / z: 725[M+H] + .

[0331] Step 8: 4-(2-(2'-chloro-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-formamido)-3H-imidazo[4,5-b]pyridin-5-yl)cyclohex-3-en-1-yl-2,2,2-trifluoroacetic acid N-(5-(4-(tert-butyldimethylsilyl)oxy)cyclohex-1-en-1-yl)-3-(4-methoxybenzyl)-3H-imidazo[4,5-b]pyridin-2-yl)-2'-chloro-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-formamide (150 mg, 0.207 mmol) was dissolved in trifluoroacetic acid (5 mL) and reacted at 75°C for 2 hours. The reaction mixture was concentrated under reduced pressure, and dichloromethane was added and concentrated. This was repeated three times to obtain the crude product, 4-(2-(2'-chloro-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-formamido)-3H-imidazo[4,5-b]pyridin-5-yl)cyclohex-3-en-1-yl 2,2,2-trifluoroacetic acid (121.5 mg, yellow solid, 100% yield). LC / MS (ESI) m / z: 587 [M+H] + .

[0332] Step 9: 2'-chloro-N-(5-(4-hydroxycyclohex-1-en-1-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-formamide The crude product, 4-(2-(2'-chloro-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-formamido)-3H-imidazo[4,5-b]pyridin-5-yl)cyclohex-3-en-1-yl 2,2,2-trifluoroacetic acid (121.5 mg, 0.207 mmol), was dissolved in an aqueous solution of methanol (3 mL) and lithium hydroxide (1 mL) (49.6 mg, 2.07 mmol), and the mixture was allowed to react at room temperature for 10 minutes. 5 mL of water was added to the reaction mixture, which was then extracted with ethyl acetate, separated, and concentrated under reduced pressure to obtain a residue. This residue was purified by prep-HPLC (eluent: acetonitrile / 0.1% aqueous formic acid solution = 0% to 70%, V / V) to obtain 2'-chloro-N-(5-(4-hydroxycyclohex-1-en-1-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-formamide (63.9 mg, off-white solid, yield 62.9%). 1H NMR (400 MHz, DMSO-d6) δ 12.50 - 12.05 (m, 2H), 8.90 (s, 1H), 8.17 (s, 1H), 7.66 (d, J = 8.3 Hz, 1H), 7.53 (s, 1H), 7.39 (s, 1H), 7.29 (d, J = 8.3 Hz, 1H), 6.50 - 6.44 (m, 1H), 4.70 - 4.63 (m, 1H), 3.85 - 3.75 (m, 1H), 3.65 (s, 3H), 2.76 - 2.65 (m, 1H), 2.59 (s, 3H), 2.49 - 2.41 (m, 2H), 2.15 - 2.05 (m, 1H), 1.95 - 1.85 (m, 1H), 1.68 - 1.51 (m, 1H). LC / MS (ESI) m / z: 491.2 [M+H] + .

[0333] Example 57: N-(6-(4-acetamidopiperidin-1-yl)thiazolo[4,5-b]pyridin-2-yl)-2'-chloro-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-formamide TIFF2025533951000190.tif26121

[0334] Step 1: N-(6-(4-acetamidopiperidin-1-yl)thiazolo[4,5-b]pyridin-2-yl)-2'-chloro-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-formamide Under nitrogen gas protection, N-(6-bromothiazolo[4,5-b]pyridin-2-yl)-2'-chloro-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-formamide (120 mg, 0.245 mmol), N-(piperidin-4-yl)acetamide (34.8 mg, 0.245 mmol), sodium tert-butoxide (66 mg, 0.735 mmol), 2-bicyclohexylphosphine-2',6'-diisopropoxybiphenyl (69 mg, 0.15 mmol), and tris(dibenzylideneacetone)dipalladium (137 mg, 0.15 mmol) were dissolved in 1,4-dioxane (8 mL). The mixture was reacted at 100 °C for 2 h under nitrogen gas protection. After the reaction was completed, water was added, and the mixture was extracted with ethyl acetate. The organic phase was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The resulting residue was purified by column chromatography (eluent: dichloromethane, methanol, gradient: 0%-8% methanol) to give the title compound as a crude product. The crude product was purified by preparative HPLC and lyophilized to give the target compound (yellow solid, 15 mg, yield 24%). 1 H NMR (400 MHz, DMSO-d6) δ 12.97 (s, 1H), 8.85 (s, 1H), 8.35 (s, 1H), 8.16 (s, 1H), 7.96 (s, 1H), 7.84 (d, J = 7.3 Hz, 1H), 7.57 (s, 1H), 7.45 (s, 1H), 3.77 - 3.73 (m, 1H), 3.73 - 3.65(m, 2H),3.61 (s, 3H), 2.87 (t, J = 11.3 Hz, 2H), 2.60 (s, 3H), 1.88 - 1.84 (m, 2H), 1.80 (s, 3H), 1.55 - 1.45 (m, 2H). LC / MS (ESI) m / z: 552.2 [M+H] + . The compounds of the examples in Table 5 were synthesized using commercially available raw materials with reference to the synthesis process of Example 57.

[0335] [Table 5] TIFF2025533951000192.tif233155 TIFF2025533951000193.tif233155 TIFF2025533951000194.tif234155 TIFF2025533951000195.tif127155

[0336] Example 75: 2'-chloro-N-(6-(4-(dimethylphosphoryl)phenyl)thiazole[4,5-b]pyridin-2-yl)-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-formamide TIFF2025533951000196.tif27122

[0337] Step 1: 2'-chloro-N-(6-(4-(dimethylphosphoryl)phenyl)thiazole[4,5-b]pyridin-2-yl)-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-formamide N-(6-bromothiazolo[4,5-b]pyridin-2-yl)-2'-chloro-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-formamide (150 mg, 0.306 mmol), dimethyl(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)phosphine oxide (85.6 mg, 0.306 mmol), dichloro[1,1'-bis(di-tert-butylphosphine)ferrocenepalladium(II)] (19.9 mg, 0.031 mmol), and potassium phosphate (194 mg, 0.917 mmol) were dissolved in 1,4-dioxane (10 mL) and water (2 mL), and the mixture was reacted at 90°C under nitrogen gas protection for 2 hours. After completion of the reaction, water was added to the reaction mixture, which was then extracted with ethyl acetate. The organic phase was washed with saturated sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The resulting residue was purified by silica gel chromatography (eluent: petroleum ether / ethyl acetate, gradient: 50-70% ethyl acetate) to give 2'-chloro-N-(6-(4-(dimethylphosphoryl)phenyl)thiazole[4,5-b]pyridin-2-yl)-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-formamide (white solid, 50 mg, yield: 29.0%). 1 H NMR (400 MHz, DMSO- d6) δ 13.31 (s, 1H), 8.91 (d, J = 18.9 Hz, 2H), 8.83 (s, 1H), 8.18 (s, 1H), 7.95 - 7.85 (m, 4H), 7.61 (s, 1H), 7.49 (s, 1H), 3.61 (s, 3H), 2.62 (s, 3H), 1.71 (s, 3H), 1.68 (s, 3H). LC / MS (ESI) m / z: 564.2 [M+H] + . The compounds of the examples in Table 6 were synthesized using commercially available raw materials with reference to the synthesis process of Example 75.

[0338] [Table 6] TIFF2025533951000198.tif221155 TIFF2025533951000199.tif227155 TIFF2025533951000200.tif46155

[0339] Example 88: 2'-chloro-N-(6-(7-hydroxy-2-oxaspiro[3.5]amino-7-yl)thiazol[4,5-b]pyridin-2-yl)-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-formamide TIFF2025533951000201.tif26121

[0340] Step 1: 2'-chloro-N-(6-(7-hydroxy-2-oxaspiro[3.5]amino-7-yl)thiazol[4,5-b]pyridin-2-yl)-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-formamide To a solution of N-(6-(2-oxaspiro[3.5]-6-en-7-yl)thiazole[4,5-b]pyridin-2-yl)-2'-chloro-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-formamide (100 mg, 0.19 mmol) in isopropanol (18 mL) and dichloromethane (2 mL) was added manganese tris(2,2,6,6-tetramethyl-3,5-heptenoate) (34 mg, 0.06 mmol) under oxygen and 0°C. The mixture was reacted for 10 minutes at 0°C. Phenylsilane (0.1 mL, 0.94 mmol) was added dropwise to the reaction mixture and the mixture was reacted for 3 hours at 0°C. The completion of the reaction was confirmed by LCMS. Water and dichloromethane were added, and the organic phase was concentrated to give the crude product. The crude product was separated to give the title compound (white solid, 11.7 mg, 11.3%). 1H NMR (400 MHz, DMSO-d6) δ 13.14 (s, 1H), 8.86 (s, 1H), 8.68 (s, 1H), 8.47 (s, 1H), 8.16 (s, 1H), 7.59 (s, 1H), 7.47 (s, 1H), 5.08 (s, 1H), 4.41 (s, 2H), 4.26 (s, 2H), 3.59 (s, 3H), 2.61 (s, 3H), 1.98 - 1.88 (m, 4H), 1.82 - 1.76 (m, 2H), 1.67 - 1.64 (m, 2H). LC / MS (ESI) m / z: 552.2 [M+H] + . The compounds of the examples in Table 7 were synthesized using commercially available raw materials with reference to the synthesis process of Example 88.

[0341] [Table 7]

[0342] Example 90: 2'-chloro-5'-methoxy-6-methyl-N-(4H-pyrrolo[3,2-d]thiazol-2-yl)-[4,4'-bipyridine]-3-formamide TIFF2025533951000203.tif26152

[0343] Step 1: 2-Amino-4H-pyrrolo[3,2-d]thiazole-4-carboxylic acid tert-butyl ester 1-tert-Butoxycarbonyl-3-pyrrolidinone (5.00 g, 27.0 mmol), cyanamide (2.27 g, 54.0 mmol), and sulfur (1.84 g, 54.0 mmol) were dissolved in pyridine (50 mL) and reacted at 100°C for 2 hours under nitrogen gas protection. After completion of the reaction, saturated aqueous sodium bicarbonate (200 mL) was added to the reaction mixture, which was then extracted with ethyl acetate. The organic phase was washed with saturated sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel chromatography (eluent: petroleum ether / ethyl acetate, gradient: 40-60% ethyl acetate) to give 2-amino-4H-pyrrolo[3,2-d]thiazole-4-carboxylic acid tert-butyl ester (yellow solid, 1.80 g, yield: 27.9%). LC / MS (ESI) m / z: 240.1 [M+H] + .

[0344] Step 2: 2-(2'-chloro-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-formamido)-4H-pyrrolo[3,2-d]thiazole-4-carboxylic acid tert-butyl ester 2-Amino-4H-pyrrolo[3,2-d]thiazole-4-carboxylic acid tert-butyl ester (100 mg, 0.418 mmol), 2'-chloro-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-carboxylic acid (116 mg, 0.418 mmol), N,N,N',N'-tetramethylformamidinium hexafluorophosphate (117 mg, 0.418 mmol), and 1-methylimidazole (103 mg, 1.25 mmol) were dissolved in DMF (10 mL) and reacted at room temperature for 12 hours. After the reaction was completed, water was added to the reaction mixture, which was then extracted with ethyl acetate. The organic phase was washed with saturated sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The resulting residue was purified by silica gel chromatography (eluent: petroleum ether / ethyl acetate, gradient: 50-70% ethyl acetate) to give 2-(2'-chloro-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-formamide)-4H-pyrrolo[3,2-d]thiazole-4-carboxylic acid tert-butyl ester (white solid, 70 mg, yield: 33.5%). LC / MS (ESI) m / z: 500.1 [M+H] + .

[0345] Step 3: 2'-chloro-5'-methoxy-6-methyl-N-(4H-pyrrolo[3,2-d]thiazol-2-yl)-[4,4'-bipyridine]-3-formamide 2-(2'-chloro-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-formamide)-4H-pyrrolo[3,2-d]thiazole-4-carboxylic acid tert-butyl ester (70 mg, 0.140 mmol) was added to a solution of hydrochloric acid in dioxane (4.0 M, 10 mL) and reacted at room temperature for 3 hours. The reaction mixture was concentrated under reduced pressure, and the resulting residue was purified by prep-HPLC (SilaSep TMPurification using a C18 silica flash cartridge (25%-85% MeCN in HO with 0.01% FA) gave 2'-chloro-5'-methoxy-6-methyl-N-(4H-pyrrolo[3,2-d]thiazol-2-yl)-[4,4'-bipyridine]-3-formamide (white solid, 20 mg, yield: 35.7%). 1 H NMR (400 MHz, DMSO-d6) δ 12.44 (s, 1H), 11.13 (s, 1H), 8.78 (s, 1H), 8.16 (s, 1H), 7.53 (s, 1H), 7.42 (s, 1H), 7.00 (t, J = 2.7 Hz, 1H), 6.31 (dd, J = 2.9, 1.8 Hz, 1H), 3.60 (s, 3H), 2.58 (s, 3H).LC / MS (ESI) m / z: 400.0 [M+H] + .

[0346] Example 91: 2'-chloro-N-(5-(4-hydroxycyclohex-1-en-1-yl)thiazolo[5,4-d]pyrimidin-2-yl)-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-formamide TIFF2025533951000204.tif41159

[0347] Step 1: 5-chlorothiazol[5,4-d]pyrimidin-2-amine To a solution of 2,4-dichloropyrimidin-5-amine (5 g, 30.5 mmol) in acetic acid (30 mL) was added potassium thiocyano (3.11 g, 32.0 mmol). The mixture was then stirred at 110°C for 3 hours. After the reaction was complete, water was added and the mixture was filtered. The filter cake was washed with water and cold ether and dried to give the title compound (orange solid, 5 g, 87.9% yield). LC / MS (ESI) m / z: 187.0 [M+H] + .

[0348] Step 2: N -(5-chlorothiazolo[5,4-d]pyrimidin-2-yl)acetamide To a solution of 5-chlorothiazole[5,4-d]pyrimidin-2-amine (4.6 g, 24.6 mmol) in 1,2-dichloroethane (50 mL) were added acetic anhydride (3.5 mL, 37.3 mmol) and 4-dimethylaminopyridine (0.60 g, 4.93 mmol). The mixture was then reacted at 80°C for 5 hours. After the reaction was complete, methanol was added, the mixture was filtered, slurried in 10% methanol, and dried to give the title compound (white solid, 5.2 g, 92.3% yield). LC / MS (ESI) m / z: 229.0 [M+H] + .

[0349] Step 3: N-(5-(4-((tert-butyldimethylsilyl)oxy)cyclohex-1-en-1-yl)thiazolo[5,4-d]pyrimidin-2-yl)acetamide To a solution of N-(5-chlorothiazolo[5,4-d]pyrimidin-2-yl)acetamide (1 g, 4.37 mmol) in 1,4-dioxane (100 mL) and water (25 mL) was added tert-butyldimethyl((4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)cyclohex-3-en-1-yl)oxy)silane (4.44 g, 13.1 mmol), cesium carbonate (1.71 g, 5.25 mmol), and Pd(dppf)Cl.CHCl (0.71 g, 0.875 mmol). The reaction mixture was stirred under nitrogen gas protection at 90 °C for 16 hours. After completion of the reaction, the mixture was concentrated under reduced pressure. The residue was purified by column chromatography (eluent: petroleum ether / ethyl acetate, gradient: 0-50% ethyl acetate) to give the title compound (white solid, 900 mg, yield 50.9%). LC / MS (ESI) m / z: 405.1 [M+H] + .

[0350] Step 4: 5-(4-((tert-butyldimethylsilyl)oxy)cyclohex-1-en-1-yl)thiazolo[5,4-d]pyrimidin-2-amine To a solution of N-(5-(4-((tert-butyldimethylsilyl)oxy)cyclohex-1-en-1-yl)thiazolo[5,4-d]pyrimidin-2-yl)acetamide (900 mg, 2.22 mmol) in a mixture of methanol (12 mL) and water (4 mL) was added sodium hydroxide (890 mg, 22.3 mmol). The reaction mixture was stirred at 80°C for 3 hours. After completion of the reaction, the mixture was concentrated under reduced pressure. The residue was purified by column chromatography (eluent: petroleum ether / ethyl acetate, gradient: 0 - 70% ethyl acetate) to give the title compound (white solid, 220 mg, yield: 27.3%). LC / MS (ESI) m / z: 363.2 [M+H] + .

[0351] Step 5: N-(5-(4-((tert-butyldimethylsilyl)oxy)cyclohex-1-en-1-yl) thiazolo[5,4-d]pyrimidin-2-yl)-2'-chloro-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-formamide To a solution of 5-(4-((tert-butyldimethylsilyl)oxy)cyclohex-1-en-1-yl)thiazolo[5,4-d]pyrimidin-2-amine (220 mg, 0.607 mmol) in N,N-dimethylformamide (3 mL) and acetonitrile (5 mL), 2'-chloro-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-carboxylic acid (254 mg, 0.911 mmol) and 1-methylimidazole (149 mg, 1.82 mmol) were added sequentially. Next, N,N,N',N'-tetramethylformamidinium hexafluorophosphate (187 mg, 0.666 mmol) was added to the mixture at 70 °C. The mixture was stirred at 70 °C for 2 hours. After completion of the reaction, water was added, followed by extraction with ethyl acetate. The organic phase was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by column chromatography (eluent: petroleum ether / ethyl acetate, gradient: 0-70% ethyl acetate) to give the title compound (white solid, 200 mg, yield 52.9%). LC / MS (ESI) m / z: 623.2 [M+H] + .

[0352] Step 6: 2'-chloro-N-(5-(4-hydroxycyclohex-1-en-1-yl)thiazolo[5,4-d]pyrimidin-2-yl)-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-formamide To a solution of N-(5-(4-((tert-butyldimethylsilyl)oxy)cyclohex-1-en-1-yl)thiazolo[5,4-d]pyrimidin-2-yl)-2'-chloro-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-formamide (100 mg, 0.160 mmol) in dichloromethane (1 mL) was added 4 M hydrochloric acid in dioxane (2 mL). The reaction mixture was stirred at room temperature for 1 hour. After completion of the reaction, the mixture was concentrated under reduced pressure, and the residue was purified by preparative HPLC to obtain the title compound (white solid, 35.1 mg, yield 43.0%). 1H NMR (400 MHz, DMSO-d6) δ 13.27 (s, 1H), 9.12 (s, 1H), 8.86 (s, 1H), 8.17 (s, 1H), 7.60 (s, 1H), 7.48 (s, 1H), 7.17 - 7.13 (m, 1H), 4.72 (d, J = 4.0 Hz, 1H), 3.87 - 3.78 (m, 1H), 3.62 (s, 3H), 2.83 - 2.73 (m, 1H), 2.61 (s, 3H), 2.57 - 2.53 (m, 2H), 2.20 - 2.10 (m, 1H), 1.95 - 1.85 (m, 1H), 1.66 - 1.56 (m, 1H). LC / MS (ESI) m / z: 509.2 [M+H] + .

[0353] Example 92: 2'-chloro-N-(5-(5-chloropyridin-2-yl)-4,5,6,7-tetrahydrothiazole[5,4-c]pyridine-2-)-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-formamide TIFF2025533951000205.tif24110

[0354] Step 1: 2'-chloro-N-(5-(5-chloropyridin-2-yl)-4,5,6,7-tetrahydrothiazole[5,4-c]pyridine-2-)-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-formamide To a solution of 2'-chloro-5'-methoxy-6-methyl-N-(4,5,6,7-tetrahydrothiazol[5,4-c]pyridin-2-yl)-[4,4'-bipyridine]-3-formamide (480 mg, 1.154 mmol) and 5-chloro-2-fluoropyridine (455.41 mg, 3.462 mmol) in dimethyl sulfoxide (5 mL), N,N-diisopropylethylamine (0.572 mL, 3.462 mmol) was added, and the reaction mixture was stirred at 120 °C for 16 hours. After completion of the reaction, the mixture was filtered, and the mother liquor was purified by preparative HPLC to obtain the title compound (yellow solid, 75 mg, 12.3% yield).1 H NMR (400 MHz, DMSO-d6) δ 12.60 (s, 1H), 8.76 (s, 1H), 8.20 - 8.00 (m, 2H), 7.63 (d, J = 9.4 Hz, 1H), 7.52 (s, 1H), 7.42 (s, 1H), 7.00 (d, J = 8.8 Hz, 1H), 4.69 (s, 2H), 3.98 - 3.86 (m, 2H), 3.60 (s, 3H), 2.78 - 2.70 (m, 2H), 2.58 (s, 3H). LC / MS (ESI) m / z: 527 [M+H] + .

[0355] Example 93: 2'-chloro-N-(6-(2-hydroxy-2-methylpropyl)thiazolo[4,5-b]pyridin-2-yl)-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-formamide TIFF2025533951000206.tif41143

[0356] Step 1: 2-(2-(2,5-dimethyl-1H-pyrrol-1-yl)thiazol[4,5-b]pyridin-6-yl)ethyl acetate 6-Bromo-2-(2,5-dimethyl-1H-pyrrol-1-yl)thiazole[4,5-b]pyridine (500 mg, 1.62 mmol) was dissolved in anhydrous tetrahydrofuran (5 mL), and palladium acetate (27.0 mg, 0.16 mmol) and 2-dicyclohexylphosphino-2',4',6'-triisopropylbiphenyl (77.3 mg, 0.16 mmol) were added. Then, (2-ethoxy-2-oxoethyl)zinc(II) bromide (15 mL, 16.22 mmol) was added. The mixture was refluxed under nitrogen gas protection and reacted for 18 hours. After the reaction was completed, the reaction mixture was quenched by slowly adding saturated ammonium chloride, extracted with ethyl acetate, concentrated under reduced pressure, and purified by column chromatography (eluent: ethyl acetate / petroleum ether = 1 / 8, V / V) to obtain the title compound (white solid, 500 mg, yield 97.7%). LC / MS (ESI) m / z: 316.2 [M+H]+ .

[0357] Step 2: 1-(2-(2,5-dimethyl-1H-pyrrol-1-yl)thiazol[4,5-b]pyridin-6-yl)-2-methylpropyl-2-ol Ethyl 2-(2-(2,5-dimethyl-1H-pyrrol-1-yl)thiazole[4,5-b]pyridin-6-yl)acetate (500 mg, 1.59 mmol) was dissolved in anhydrous tetrahydrofuran (10 mL). 1M methylmagnesium bromide (16 mL, 16 mmol) was added dropwise under nitrogen gas protection in an ice bath, and the mixture was allowed to react at room temperature for 18 hours. The reaction mixture was quenched by slowly adding saturated ammonium chloride, extracted with ethyl acetate, concentrated under reduced pressure, and purified by column chromatography (eluent: methanol / dichloromethane = 1 / 20, V / V) to give the crude title compound (yellow solid, 250 mg, 52.3% yield). LC / MS (ESI) m / z: 302.2 [M+H] + .

[0358] Step 3: 1-(2-aminothiazol[4,5-b]pyridin-6-yl)-2-methylpropyl-2-ol The crude product, 1-(2-(2,5-dimethyl-1H-pyrrol-1-yl)thiazole[4,5-b]pyridin-6-yl)-2-methylpropyl-2-ol (250 mg, 0.83 mmol), was dissolved in trifluoroacetic acid (10 mL), two drops of water were added, and the mixture was refluxed and reacted for 2 hours. After the reaction was completed, the mixture was directly centrifuged to dryness, dichloromethane was added, and centrifuged to dryness three times to directly obtain the crude product, the title compound (yellow oil, 250 mg). LC / MS (ESI) m / z: 224.2 [M+H] + .

[0359] Step 4: 2'-chloro-N-(6-(2-hydroxy-2-methylpropyl)thiazolo[4,5-b]pyridin-2-yl)-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-formamide The crude product, 1-(2-aminothiazole[4,5-b]pyridin-6-yl)-2-methylpropyl-2-ol (125 mg, 0.56 mmol), 2'-chloro-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-carboxylic acid (171.7 mg, 8.4 mmol), and methylimidazole (229.9 mg, 2.8 mmol) were dissolved in acetonitrile (10 mL) and stirred at room temperature for 10 minutes. N,N,N',N'-tetramethylformamidinium hexafluorophosphate (0.785 g, 2.8 mmol) was added, and the mixture was allowed to react at room temperature for 5 hours. The reaction mixture was concentrated under reduced pressure and purified by prep-HPLC (eluent: acetonitrile / 0.1% aqueous formic acid solution = 0% to 70%, V / V) to give 2'-chloro-N-(6-(2-hydroxy-2-methylpropyl)thiazolo[4,5-b]pyridin-2-yl)-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-formamide (3.7 mg, white solid, yield 1.4%). 1 H NMR (400 MHz, DMSO-d6) δ 13.14 (s, 1H), 8.86 (s, 1H), 8.39 (s, 1H), 8.24 (s, 1H), 8.15 (s, 1H), 7.59 (s, 1H), 7.46 (s, 1H), 4.45 (s, 1H), 3.60 (s, 3H), 2.76 (s, 2H), 2.60 (s, 3H), 1.09 (s, 6H). LC / MS (ESI) m / z:484.2 [M+H] + .

[0360] Example 94: 2'-chloro-5'-methoxy-6-methyl-N-(6-(methylsulfonyl)thiazole[4,5-b]pyridin-2-yl)-[4,4'-bipyridine]-3-formamide TIFF2025533951000207.tif2290

[0361] Step 1: 2'-chloro-5'-methoxy-6-methyl-N-(6-(methylsulfonyl)thiazole[4,5-b]pyridin-2-yl)-[4,4'-bipyridine]-3-formamide To a solution of N-(6-bromothiazole[4,5-b]pyridin-2-yl)-2'-chloro-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-formamide (200 mg, 0.408 mmol) in dimethyl sulfoxide (10 mL) was added sodium methanesulfonate (166 mg, 0.816 mmol), L-proline (94 mg, 0.816 mmol), cuprous iodide (116 mg, 0.609 mmol), and cesium carbonate (266 mg, 0.816 mmol). The mixture was stirred at 100 °C for 16 h. After completion of the reaction, water was added, followed by extraction with 10% methanol / dichloromethane. The organic phase was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by preparative HPLC to obtain the title compound (pale yellow solid, 74.2 mg, yield 37.2%). 1 H NMR (400 MHz, DMSO-d6) δ 13.58 (s, 1H), 9.04 (s, 2H), 8.90 (s, 1H), 8.17 (s, 1H), 7.62 (s, 1H), 7.49 (s, 1H), 3.59 (s, 3H), 3.34 (s, 3H), 2.62 (s, 3H). LC / MS (ESI) m / z: 490.1 [M+H] + .

[0362] Example 95: 2'-chloro-N-(6-(2-hydroxypropan-2-yl)thiazole[4,5-b]pyridin-2-yl)-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-formamide TIFF2025533951000208.tif47124

[0363] Step 1: 6-Bromo-2-(2,5-dimethyl-1H-pyrrol-1-yl)thiazole[4,5-b]pyridine 6-Bromothiazole[4,5-b]pyridin-2-amine (2.0 g, 8.69 mmol) was dissolved in anhydrous toluene (15 mL), and hexane-2,5-dione (2.04 mL) and p-toluenesulfonic acid (165 mg, 0.958 mmol) were added. The mixture was reacted at 120 °C for 24 hours under nitrogen gas protection. After cooling to room temperature, saturated sodium bicarbonate was added and the mixture was filtered. The filtrate was extracted with ethyl acetate, washed with saturated brine, concentrated under reduced pressure, and purified by column chromatography (eluent: ethyl acetate / petroleum ether = 1 / 5, V / V) to give the title compound (white solid, 1.3 g, 48.5% yield). LC / MS (ESI) m / z: 308.2 [M+H] + .

[0364] Step 2: 2-(2,5-dimethyl-1H-pyrrol-1-yl)thiazolo[4,5-b]pyridine-6-carboxylic acid ethyl ester 6-Bromo-2-(2,5-dimethyl-1H-pyrrol-1-yl)thiazole[4,5-b]pyridine (500 mg, 1.62 mmol) was dissolved in anhydrous dimethylformamide (15 mL) and absolute ethanol (5 mL). [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (116.1 mg, 0.16 mmol) and triethylamine (491.8 mg, 4.86 mmol) were added, and the mixture was reacted under carbon monoxide protection at 100 °C for 24 hours. After cooling to room temperature, saturated ammonium chloride was slowly added to the reaction mixture. The mixture was extracted with ethyl acetate, washed with saturated brine, concentrated under reduced pressure, and purified by column chromatography (eluent: ethyl acetate / petroleum ether = 1 / 5, v / v) to give the title compound (white solid, 300 mg, 61.4% yield). LC / MS (ESI) m / z: 302.1 [M+H] + .

[0365] Step 3: 2-(2-(2,5-dimethyl-1H-pyrrol-1-yl)thiazol[4,5-b]pyridin-6-yl)propyl-2-ol 2-(2,5-Dimethyl-1H-pyrrol-1-yl)thiazolo[4,5-b]pyridine-6-carboxylic acid ethyl ester (300 mg, 0.995 mmol) was dissolved in anhydrous tetrahydrofuran (10 mL). Methylmagnesium bromide (10 mL, 9.95 mmol) was added dropwise under nitrogen gas protection in an ice bath, and the mixture was reacted at room temperature for 18 hours. The reaction mixture was quenched by slowly adding saturated ammonium chloride, extracted with ethyl acetate, concentrated under reduced pressure, and purified by column chromatography (eluent: methanol / dichloromethane = 1 / 20, V / V) to give the crude title compound (yellow solid, 100 mg, 35.0% yield). LC / MS (ESI) m / z: 288.2 [M+H] + .

[0366] Step 4: 2-(2-aminothiazol[4,5-b]pyridin-6-yl)propyl-2-ol 2-(2-(2,5-Dimethyl-1H-pyrrol-1-yl)thiazole[4,5-b]pyridin-6-yl)propyl-2-ol (100 mg, 0.478 mmol) was dissolved in trifluoroacetic acid (10 mL), two drops of water were added, and the mixture was refluxed and reacted for 2 hours. After the reaction was completed, the mixture was directly centrifuged to dryness, dichloromethane was added, and centrifuged to dryness three times to directly obtain the crude product, the title compound (yellow oil, 263.2 mg). LC / MS (ESI) m / z: 210.2 [M+H] + .

[0367] Step 5: 2'-chloro-N-(6-(2-hydroxypropan-2-yl)thiazole[4,5-b]pyridin-2-yl)-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-formamide The crude product, 2-(2-aminothiazole[4,5-b]pyridin-6-yl)propyl-2-ol (263.2 mg, 0.56 mmol), 2'-chloro-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-carboxylic acid (171.7 mg, 8.4 mmol), and methylimidazole (229.9 mg, 2.8 mmol) were dissolved in acetonitrile (10 mL) and stirred at room temperature for 10 minutes. N,N,N',N'-tetramethylformamidinium hexafluorophosphate (0.785 g, 2.8 mmol) was added, and the mixture was allowed to react at room temperature for 5 hours. The reaction mixture was concentrated under reduced pressure and purified by prep-HPLC (eluent: acetonitrile / 0.1% aqueous trifluoroacetic acid solution = 0% to 70%, V / V) to give 2'-chloro-N-(6-(2-hydroxypropan-2-yl)thiazole[4,5-b]pyridin-2-yl)-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-formamide (13.9 mg, yellow solid, yield 2.4%). 1 H NMR (400 MHz, DMSO-d6) δ 13.25 (s, 1H), 8.90 (s, 1H), 8.71 (s, 1H), 8.63 (s, 1H), 8.16 (s, 1H), 7.60 (s, 1H), 7.52 (s, 1H), 3.59 (s, 3H), 3.04 (s, 1H), 2.62 (s, 3H), 1.52 (s, 6H). LC / MS (ESI) m / z: 470.2 [M+H] + .

[0368] Example 96: 2'-chloro-N-(6-(4-hydroxypiperidine-1-carbonyl)thiazole[4,5-b]pyridin-2-yl)-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-formamide TIFF2025533951000209.tif51143

[0369] Step 1: 2-(2,5-dimethyl-1H-pyrrol-1-yl)thiazolo[4,5-b]pyridine-6-carboxylic acid 2-(2,5-Dimethyl-1H-pyrrol-1-yl)thiazolo[4,5-b]pyridine-6-carboxylic acid ethyl ester (160 mg, 0.531 mmol) was dissolved in methanol (3 mL), tetrahydrofuran (3 mL), and water (3 mL). Lithium hydroxide monohydrate (111.4 mg, 2.65 mmol) was added and the mixture was allowed to react at 30°C for 3 hours. After the reaction was complete, saturated ammonium chloride was added to the reaction mixture, which was then quenched until neutral. The mixture was then directly centrifuged and dried to give the crude title compound (yellow solid, 300 mg). LC / MS (ESI) m / z: 274.2 [M+H] + .

[0370] Step 2: (4-((tert-butyldimethylsilyl)oxy)piperidin-1-yl)(2-(2,5-dimethyl-1H-pyrrol-1-yl)thiazolo[4,5-b]pyridin-6-yl)methanone The crude product, 2-(2,5-dimethyl-1H-pyrrol-1-yl)thiazolo[4,5-b]pyridine-6-carboxylic acid (300 mg, 0.531 mmol base), 4-((tert-butyldimethylsilyl)oxy)piperidine (228.8 mg, 1.06 mmol), and methylimidazole (229.9 mg, 2.8 mmol) were dissolved in acetonitrile (10 mL) and stirred at room temperature for 10 minutes. N,N,N',N'-Tetramethylformamidinium hexafluorophosphate (0.785 g, 2.8 mmol) was added and the mixture was allowed to react at room temperature for 5 hours. The reaction mixture was concentrated under reduced pressure, stirred, and purified by column chromatography (eluent: methanol / dichloromethane = 1 / 10, V / V) to give the title compound (yellow solid, 150 mg, 60.0% yield). LC / MS (ESI) m / z: 471.2 [M+H] + .

[0371] Step 3: 1-(2-aminothiazole[4,5-b]pyridine-6-carbonyl)piperidin-4-yl 2,2,2-trifluoroacetate (4-((tert-butyldimethylsilyl)oxy)piperidin-1-yl)(2-(2,5-dimethyl-1H-pyrrol-1-yl)thiazolo[4,5-b]pyridin-6-yl)methanone (150 mg, 0.319 mmol) was dissolved in trifluoroacetic acid (10 mL), two drops of water were added, and the mixture was refluxed and reacted for 2 hours. After the reaction was completed, the mixture was directly centrifuged to dryness, dichloromethane was added, and centrifuged to dryness three times to directly obtain the crude product, the title compound (yellow oil, 150 mg). LC / MS (ESI) m / z: 375.2 [M+H] + .

[0372] Step 4: 2'-chloro-N-(6-(4-hydroxypiperidine-1-carbonyl)thiazole[4,5-b]pyridin-2-yl)-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-formamide The crude product, 1-(2-aminothiazole[4,5-b]pyridine-6-carbonyl)piperidin-4-yl 2,2,2-trifluoroacetate (150 mg, 0.401 mmol), 2'-chloro-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-carboxylic acid (55.7 mg, 2.00 mmol), and methylimidazole (164.2 mg, 2.00 mmol) were dissolved in acetonitrile (10 mL) and stirred at room temperature for 10 minutes. N,N,N',N'-tetramethylformamidinium hexafluorophosphate (560.7 mg, 2.0 mmol) was added, and the mixture was allowed to react at room temperature for 5 hours. The reaction mixture was concentrated under reduced pressure, stirred, and purified by column chromatography (eluent: methanol / dichloromethane = 1 / 10, V / V) to obtain the title compound as a crude product. This was purified by prep-HPLC (eluent: acetonitrile / 0.1% aqueous formic acid solution = 0% to 70%, V / V) to obtain 2'-chloro-N-(6-(4-hydroxypiperidine-1-carbonyl)thiazole[4,5-b]pyridin-2-yl)-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-formamide (34.3 mg, white solid, yield 15.9%). 1H NMR (400 MHz, DMSO-d6)δ 13.30 (s, 1H), 8.88 (s, 1H), 8.57 (s, 1H), 8.51 (s, 1H), 8.15 (s, 1H), 7.59 (s, 1H), 7.47 (s, 1H), 4.85 - 4.77 (m, 1H), 4.00 (m, 1H), 3.76 (m, 1H), 3.60 (s, 3H), 2.87 (m, 3H), 2.61 (s, 3H), 1.76 (m, 2H), 1.40 (m, 2H). LC / MS (ESI) m / z: 539.2 [M+H] + .

[0373] Example 97: 2'-chloro-5'-methoxy-6-methyl-N-(6-(pyridin-2-yl)imidazole[2,1-b][1,3,4]thiadiazol-2-yl)-[4,4'-bipyridine]-3-formamide TIFF2025533951000210.tif27131

[0374] Step 1: 6-(pyridin-2-yl)imidazo[2,1-b][1,3,4]thiadiazol-2-amine 2-Bromo-1-(2-pyridinyl)-1-ethanone hydrobromide (200 mg, 0.712 mmol) and 2,5-diamino-1,3,4-thiadiazole (82.5 mg, 0.712 mmol) were dissolved in absolute ethanol (10 mL), and the mixture was refluxed overnight with stirring under nitrogen gas protection. After the reaction was completed, the reaction mixture was concentrated, and the residue was dissolved in water. A saturated aqueous solution of sodium bicarbonate was added to adjust the pH to alkaline. Extraction was performed with ethyl acetate, and the organic phase was dried, filtered, and then centrifuged. The residue was separated by column chromatography (dichloromethane / methanol system) to obtain the crude product, the title compound (yellow solid, 100 mg). LC / MS (ESI) m / z: 218.0 [M+H] + .

[0375] Step 2: 2'-chloro-5'-methoxy-6-methyl-N-(6-(pyridin-2-yl)imidazole[2,1-b][1,3,4]thiadiazol-2-yl)-[4,4'-bipyridine]-3-formamide 2-(2,5-Dimethyl-1H-pyrrol-1-yl)thiazolo[4,5-b]pyridine-6-carboxylic acid (141 mg, 0.507 mmol), 6-(pyridin-2-yl)imidazo[2,1-b][1,3,4]thiadiazol-2-amine (100 mg, 0.46 mmol), and methylimidazole (188 mg, 2.3 mmol) were dissolved in acetonitrile (10 mL) and stirred at 70 °C for 5 min. N,N,N',N'-tetramethylformamidinium hexafluorophosphate (142 mg, 0.507 mmol) was added. The mixture was reacted at 70 °C for 2 h. The reaction mixture was poured into water and extracted with ethyl acetate. The resulting organic phase was dried over anhydrous sodium sulfate, filtered, and centrifuge-dried. The residue was directly purified by reverse-phase preparative HPLC (acetonitrile-water system) to give the title compound (white solid, 3.4 mg, yield 1.5%). 1 H NMR (400 MHz, DMSO-d6) δ 13.31 (s, 1H), 8.87 (s, 1H), 8.54 (d, J = 4.1 Hz, 1H), 8.47 (s, 1H), 8.20 (s, 1H), 7.94 (d, J = 7.9 Hz, 1H), 7.83 (t, J = 7.5 Hz, 1H), 7.59 (s, 1H), 7.47 (s, 1H), 7.31 - 7.21 (m, 1H), 3.68 (s, 3H), 2.61 (s, 3H). LC / MS (ESI) m / z: 478.1 [M+H] + .

[0376] Example 98: 2'-chloro-N-(6-(4-(hydroxymethyl)piperidin-1-yl)thiazole[4,5-b]pyridin-2-yl)-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-formamide TIFF2025533951000211.tif52143

[0377] Step 1: 4-(((tert-butyldimethylsilyl)oxy)methyl)piperidine To a solution of piperidin-4-ylmethanol (1 g, 8.68 mmol) in dichloromethane (10 mL) was added imidazole (1.77 g, 26.0 mmol) and tert-butyldimethylchlorosilane (1.31 g, 8.68 mmol). The mixture was stirred at room temperature for 16 hours. After the reaction was complete, water was added, and the mixture was extracted with dichloromethane. The organic phase was washed repeatedly with water until imidazole was completely removed, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to give the title compound (pale yellow oil, 1.35 g, 67.8% yield). LC / MS (ESI) m / z: 230.3 [M+H] + .

[0378] Step 2: N-(6-(4-(((tert-butyldimethylsilyl)oxy)methyl)piperidin-1-yl)thiazole[4,5-b]pyridin-2-yl)-2'-chloro-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-formamide To a solution of N-(6-bromothiazole[4,5-b]pyridin-2-yl)-2'-chloro-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-formamide (300 mg, 0.611 mmol) in 1,4-dioxane (30 mL), 4-(((tert-butyldimethylsilyl)oxy)methyl)piperidine (285 mg, 1.22 mmol), sodium tert-butoxide (117 mg, 1.22 mmol), 2-bicyclohexylphosphine-2',6'-diisopropoxybiphenyl (57 mg, 0.122 mmol), and tris(dibenzylideneacetone)dipalladium (112 mg, 0.122 mmol) were added sequentially. The reaction mixture was stirred under nitrogen gas protection at 90 °C for 2 hours. After completion of the reaction, the mixture was concentrated under reduced pressure. The residue was purified by column chromatography (eluent: dichloromethane / methanol, gradient: 0-5% methanol) to give the title compound (yellow solid, 190 mg, yield 28.0%). LC / MS (ESI) m / z: 639.3 [M+H] + .

[0379] Step 3: 2'-chloro-N-(6-(4-(hydroxymethyl)piperidin-1-yl)thiazole[4,5-b]pyridin-2-yl)-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-formamide N-(6-(4-(((tert-butyldimethylsilyl)oxy)methyl)piperidin-1-yl)thiazole[4,5-b]pyridin-2-yl)-2'-chloro-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-formamide (190 mg, 0.297 mmol) was added to a 4 mol / L hydrochloric acid-dioxane solution (2 mL). The reaction mixture was stirred at room temperature for 2 hours. After completion of the reaction, the mixture was concentrated under reduced pressure, and the residue was purified by preparative HPLC to obtain the title compound (yellow solid, 30.2 mg, yield 19.4%). 1H NMR (400 MHz, DMSO-d6)δ12.95 (s, 1H), 8.85 (s, 1H), 8.35 (d,J= 2.8 Hz, 1H), 8.16 (s, 1H), 7.94 (d,J= 2.8 Hz, 1H), 7.57 (s, 1H), 7.45 (s, 1H), 4.49 (t,J= 5.0 Hz, 1H), 3.75 - 3.72 (m, 2H), 3.61 (s, 3H),3.31 - 3.23 (m, 2H), 2.78 - 2.67 (m, 2H), 2.60 (s, 3H), 1.82 - 1.72 (m, 2H), 1.60 - 1.47 (m, 1H), 1.36 - 1.22 (m, 2H).LC / MS (ESI) m / z: 525.3 [M+H] + . The compounds of the examples in Table 8 were synthesized using commercially available raw materials with reference to the synthesis process of Example 98.

[0380] [Table 8] TIFF2025533951000213.tif191155

[0381] Example 105: (R)-2'-chloro-5'-methoxy-6-methyl-N-(6-(2-(3-methylpiperazin-1-yl)pyridin-4-yl)thiazole[4,5-b]pyridin-2-yl)-[4,4'-bipyridine]-3-formamide TIFF2025533951000214.tif63143

[0382] Step 1: (R)-4-(4-bromopyridin-2-yl)-2-methylpiperazine-1-carboxylic acid tert-butyl ester 4-Bromo-2-fluoropyridine (1.00 g, 5.68 mmol), (R)-2-methylpiperazine-1-carboxylic acid tert-butyl ester (1.71 g, 8.52 mmol), and potassium carbonate (2.36 g, 17.0 mmol) were dissolved in dimethyl sulfoxide (8 mL) and allowed to react for 3 hours with stirring at room temperature. After completion of the reaction, the reaction mixture was extracted with water (50 mL) and ethyl acetate (50 mL). The organic phase was washed with saturated brine. The residue was purified by column chromatography (eluent: dichloromethane / methanol, gradient: 0%-10% methanol) to give the title compound (1.6 g, white solid, yield: 79.0%). LC / MS (ESI) m / z: 356.2 [M+H] + .

[0383] Step 2: (R)-(2-(4-(tert-butoxycarbonyl)-3-methylpiperazin-1-yl)pyridin-4-yl)boronic acid (R)-4-(4-Bromopyridin-2-yl)-2-methylpiperazine-1-carboxylic acid tert-butyl ester (1.00 g, 2.807 mmol), potassium acetate (1.10 g, 11.2 mmol), bis(pinacolato)diboron (2.14 g, 8.42 mmol), and DPPF palladium dichloride complex (0.410 g, 0.561 mmol) were dissolved in 1,4-dioxane (25 mL) and reacted at 85°C for 2 hours. After completion of the reaction, the reaction mixture was concentrated under reduced pressure, and the residue was purified by column chromatography (eluent: dichloromethane / methanol, gradient: 0%-10% methanol) to give the title compound (300 mg, brown solid, yield: 33.3%). LC / MS (ESI) m / z: 322.1 [M+H] + .

[0384] Step 3: (R)-4-(4-(2-(2'-chloro-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-formamido)thiazole[4,5-b]pyridin-6-yl)pyridin-2-yl)-2-methylpiperazine-1-carboxylic acid tert-butyl ester (R)-(2-(4-(tert-butoxycarbonyl)-3-methylpiperazin-1-yl)pyridin-4-yl)boronic acid (235.60 mg, 0.734 mmol), N-(6-bromothiazole[4,5-b]pyridin-2-yl)-2'-chloro-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-formamide (360 mg, 0.734 mmol), potassium carbonate (304.13 mg, 2.201 mmol), and DPPF palladium dichloride complex (107.35 mg, 0.147 mmol) were dissolved in 1,4-dioxane (6 mL) and water (2 mL). The mixture was heated to 85°C under nitrogen gas protection and reacted for 3 hours. After completion of the reaction, the reaction mixture was concentrated under reduced pressure, and the residue was purified by column chromatography (eluent: dichloromethane / methanol, gradient: 0%-10% methanol) to give the title compound (110 mg, brown solid, yield: 3.3%). LC / MS (ESI) m / z: 687.4 [M+H] + .

[0385] Step 4: (R)-2'-chloro-5'-methoxy-6-methyl-N-(6-(2-(3-methylpiperazin-1-yl)pyridin-4-yl)thiazole[4,5-b]pyridin-2-yl)-[4,4'-bipyridine]-3-formamide (R)-4-(4-(2-(2'-chloro-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-formamide)thiazole[4,5-b]pyridin-6-yl)pyridin-2-yl)-2-methylpiperazine-1-carboxylic acid tert-butyl ester (110 mg, 0.205 mmol) was dissolved in 1,4-dioxane (5 mL), and a hydrochloric acid-dioxane solution (3 mL) was added. The mixture was allowed to react at room temperature for 3 hours. After completion of the reaction, the reaction mixture was concentrated under reduced pressure, and the residue was purified by reverse-phase preparative separation to obtain the title compound (25 mg, pale yellow solid, yield: 29.3%). 1H NMR (400 MHz, DMSO-d6)δ8.99 (s, 1H), 8.85 (s, 1H), 8.64 (s, 1H), 8.21 - 8.18 (m, 2H), 8.15 (s, 1H), 7.49 (s, 1H), 7.33 (s, 1H), 7.22 (s, 1H), 7.08 (d, J = 5.1 Hz, 1H), 4.43 - 4.35 (m, 2H), 3.62 (s, 3H), 3.22 - 3.17 (m, 1H), 3.08 - 3.02 (m, 1H), 2.98 - 2.90 m, 2H), 2.75 - 2.62 (m, 1H), 2.58 (s, 3H), 1.18 (d, J = 6.4 Hz, 3H). LC / MS (ESI) m / z: 587.3 [M+H] + .

[0386] Example 106: 2'-chloro-N-(6-(4-hydroxy-4-(hydroxymethyl)piperidin-1-yl)thiazole[4,5-b]pyridin-2-yl)-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-formamide TIFF2025533951000215.tif20157

[0387] Step 1: 2'-chloro-5'-methoxy-6-methyl-N-(6-(4-methoxy-piperidin-1-yl)thiazole[4,5-b]pyridin-2-yl)-[4,4'-bipyridine]-3-formamide N-(6-Bromothiazolo[4,5-b]pyridin-2-yl)-2'-chloro-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-formamide (500 mg, 1.02 mmol), 4-methylenepiperidine hydrochloride (136 mg, 1.02 mmol), tris(dibenzylideneacetone)dipalladium (93.3 mg, 0.102 mmol), 2-dicyclohexylphosphonium-2',6'-diisopropoxy-1,1'-biphenyl (95.1 mg, 0.204 mmol), and sodium tert-butoxide (391 mg, 4.08 mmol) were dissolved in 1,4-dioxane (20 mL) and reacted at 100°C for 4 hours under nitrogen gas protection. After completion of the reaction, water was added to the reaction mixture, which was then extracted with ethyl acetate. The organic phase was washed with saturated sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The resulting residue was purified by silica gel chromatography (eluent: petroleum ether / ethyl acetate, gradient: 50-70% ethyl acetate) to give 2'-chloro-5'-methoxy-6-methyl-N-(6-(4-methoxy-piperidin-1-yl)thiazole[4,5-b]pyridin-2-yl)-[4,4'-bipyridine]-3-formamide (yellow solid, 110 mg, yield: 21.3%). LC / MS (ESI) m / z: 507.0 [M+H] + .

[0388] Step 2: 2'-chloro-N-(6-(4-hydroxy-4-(hydroxymethyl)piperidin-1-yl)thiazole[4,5-b]pyridin-2-yl)-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-formamide 2'-Chloro-5'-methoxy-6-methyl-N-(6-(4-methoxy-piperidin-1-yl)thiazole[4,5-b]pyridin-2-yl)-[4,4'-bipyridine]-3-formamide (100 mg, 0.197 mmol), osmium tetroxide (0.50 mg, 0.002 mmol) (0.25 mL of a 4% aqueous solution, 0.04 mmol), and N-methylmorpholine oxide (69.3 mg, 0.592 mmol) were dissolved in acetone (4 mL) and water (1 mL) and reacted at room temperature for 12 hours. The reaction mixture was concentrated under reduced pressure, and the resulting residue was purified by prep-HPLC (SilaSep TM Purification using a C18 silica flash cartridge (25%-85% MeCN in HO with 0.01% FA) gave 2'-chloro-N-(6-(4-hydroxy-4-(hydroxymethyl)piperidin-1-yl)thiazole[4,5-b]pyridin-2-yl)-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-formamide (yellow solid, 28.0 mg, yield: 26.4%). 1 H NMR (400 MHz, DMSO-d6) δ 8.85 (s, 1H), 8.34 (s, 1H), 8.16 (s, 1H), 7.93 (s, 1H), 7.56 (s, 1H), 7.43 (s, 1H), 4.58 (s, 1H), 4.20 (s, 1H), 3.61 (s, 3H), 3.51 - 3.45 (m, 2H), 3.22 (s, 2H), 3.10 (t, J = 11.3 Hz, 2H), 2.60 (s, 3H), 1.80 - 1.63 (m, 2H), 1.45 (d, J = 13.1 Hz, 2H).LC / MS (ESI) m / z: 541.2 [M+H] + .

[0389] Example 107: 2'-chloro-N-(5-(4-hydroxypiperidin-1-yl)thiazole[5,4-b]pyridin-2-yl)-5'-deuteromethoxy-6-methyl-[4,4'-bipyridine]-3-formamide TIFF2025533951000216.tif58147

[0390] Step 1: 2-Chloro-5-deuterated methoxypyridine 6-Chloropyridin-3-ol (1 g, 7.72 mmol) and potassium carbonate (2.13 g, 15.4 mmol) were dissolved in N,N-dimethylformamide (40 mL), and (2H3)methyl iodide (1.34 g, 9.26 mmol) was added dropwise. The mixture was allowed to react at room temperature for 18 hours. The reaction mixture was extracted with ethyl acetate and water, and the organic phase was purified by silica gel column chromatography (petroleum ether-ethyl acetate system: 0-25% ethyl acetate) to give the title compound (670 mg, white solid, 59.3% yield). LC / MS (ESI) m / z: 147.2 [M+H] + .

[0391] Step 2: (2-chloro-5-deuterated methoxypyridin-4-yl)boronic acid 2-Chloro-5-deuterated methoxypyridine (670 mg, 4.57 mmol) was dissolved in tetrahydrofuran (15 mL) and cooled to -65 °C under nitrogen gas protection. Lithium diisopropylamide (4.57 mL, 2 mol / L) was added dropwise and the mixture was allowed to react at the same low temperature for 2 hours. Triisopropyl borate (1.72 g, 9.14 mmol) was then added dropwise and the mixture was stirred for 1 hour while maintaining the low temperature. The mixture was then slowly heated to room temperature and left overnight. The reaction mixture was quenched by adding water (15 mL) in an ice-water bath, washed with ethyl acetate, and the aqueous phase was adjusted to pH 5-6 with 1M dilute aqueous hydrochloric acid. The solid phase was filtered and dried under reduced pressure to give the title compound (740 mg, white solid, 85.1% yield). LC / MS (ESI) m / z: 191.1 [M+H] + .

[0392] Step 3: 2'-chloro-5'-deuteromethoxy-6-methyl-[4,4'-bipyridine]-3-carboxylic acid methyl ester Methyl 4-bromo-6-methylnicotinate (700 mg, 3.04 mmol), (2-chloro-5-deuterated methoxypyridin-4-yl)boronic acid (579 mg, 3.04 mmol), and potassium carbonate (1.26 g, 9.12 mmol) were dissolved in a mixture of 1,4-dioxane (30 mL) and water (6 mL). Under nitrogen gas protection, the catalyst bis(triphenylphosphine)palladium dichloride (111.3 mg, 0.152 mmol) was added and the mixture was heated to 80 °C for 2 hours. The reaction mixture was allowed to cool, filtered, and extracted with water and ethyl acetate. The organic phase was purified by silica gel column chromatography (petroleum ether-ethyl acetate system: 0-50% ethyl acetate) to give the title compound (720 mg, white solid, 80% yield). LC / MS (ESI) m / z: 296.1 [M+H] + .

[0393] Step 4: 2'-chloro-5'-deuteromethoxy-6-methyl-[4,4'-bipyridine]-3-carboxylic acid 2'-Chloro-5'-deuteromethoxy-6-methyl-[4,4'-bipyridine]-3-carboxylic acid methyl ester (720 mg, 2.44 mmol) was dissolved in tetrahydrofuran (10 mL) and water (10 mL), lithium hydroxide (87.5 mg, 3.65 mmol) was added, and the mixture was stirred overnight at room temperature. Most of the tetrahydrofuran was removed from the reaction mixture using a rotary evaporator, followed by extraction with ethyl acetate. The aqueous phase was adjusted to pH 5-6 with 1M hydrochloric acid solution, and a white solid precipitated. This was filtered under reduced pressure, and the filter cake was dried to give the title compound (420 mg, white solid, 60.9% yield). LC / MS (ESI) m / z: 282.1 [M+H] + .

[0394] Step 5: 2'-chloro-N-(5-(4-hydroxypiperidin-1-yl)thiazole[5,4-b]pyridin-2-yl)-5'-deuteromethoxy-6-methyl-[4,4'-bipyridine]-3-formamide 2'-Chloro-5'-deuteromethoxy-6-methyl-[4,4'-bipyridine]-3-carboxylic acid (100 mg, 0.355 mmol), 1-(2-aminothiazole[5,4-b]pyridin-5-yl)piperidin-4-ol (88.8 mg, 0.355 mmol) and 1-methylimidazole (87.4 mg, 1.07 mmol) were dissolved in acetonitrile (5 mL) and N,N-dimethylformamide (1 mL) and stirred at 70 ° C for 15 minutes. N,N,N,N-tetramethylchlorourea hexafluorophosphate (99.6 mg, 0.355 mmol) was added and the mixture was refluxed for 2 hours with stirring at the same temperature. The reaction mixture was extracted with water and ethyl acetate, and the organic phase was concentrated and then purified by preparative HPLC to obtain the title compound (71 mg, yellow solid, yield: 31.4%). 1 H NMR (400 MHz, DMSO-d6) δ12.68 (s, 1H), 8.81 (s, 1H), 8.16 (s, 1H), 7.85 (d, J = 9.1 Hz, 1H), 7.56 (s, 1H), 7.45 (s, 1H), 6.99 (d, J = 9.1 Hz, 1H), 4.70 (d, J = 4.4 Hz, 1H), 4.08 - 3.98 (m, 2H), 3.78 - 3.67 (m, 1H), 3.16 - 3.06 (m, 2H), 2.58 (s, 3H), 1.86 - 1.74 (m, 2H), 1.43 - 1.33 (m, 2H). LC / MS (ESI) m / z: 514.2 [M+H] + .

[0395] Example 108: 2'-chloro-N-(6-(4-hydroxycyclohex-1-en-1-yl)thiazole[4,5-c]pyridin-2-yl)-5'-deuteromethoxy-6-methyl-[4,4'-bipyridine]-3-formamide TIFF2025533951000217.tif25156

[0396] Step 1: 4-(2-(2'-chloro-5'-deuteromethoxy-6-methyl-[4,4'-bipyridine]-3-formamido)thiazole[4,5-c]pyridin-6-yl)cyclohex-3-en-1-yl 2,2,2-trifluoroacetic acid 2'-Chloro-5'-deuteromethoxy-6-methyl-[4,4'-bipyridine]-3-carboxylic acid (200 mg, 0.71 mmol), 4-(2-aminothiazole[4,5-c]pyridin-6-yl)cyclohex-3-en-1-yl 2,2,2-trifluoroacetic acid (243 mg, 0.355 mmol), and 1-methylimidazole (174 mg, 2.13 mmol) were dissolved in acetonitrile (7 mL) and N,N-dimethylformamide (2 mL), and the mixture was stirred at 70°C for 15 minutes. N,N,N,N-tetramethylchlorourea hexafluorophosphate (199 mg, 0.71 mmol) was added, and the mixture was refluxed for 2 hours with stirring at the same temperature. The reaction mixture was extracted with water and ethyl acetate, and the organic phase was dried by centrifugation to obtain the crude product, the title compound (200 mg, yellow solid, yield: 27.8%). LC / MS (ESI) m / z: 607.2 [M+H] + .

[0397] Step 2: 2'-chloro-N-(6-(4-hydroxycyclohex-1-en-1-yl)thiazole[4,5-c]pyridin-2-yl)-5'-deuteromethoxy-6-methyl-[4,4'-bipyridine]-3-formamide 4-(2-(2'-chloro-5'-deuteromethoxy-6-methyl-[4,4'-bipyridine]-3-formamide)thiazole[4,5-c]pyridin-6-yl)cyclohex-3-en-1-yl 2,2,2-trifluoroacetic acid (200 mg, 0.329 mmol) and lithium hydroxide (138 mg, 3.29 mmol) were dissolved in methanol (7 mL) and stirred at room temperature for 30 minutes. The reaction mixture was then purified by preparative HPLC to obtain the title compound (34.2 mg, yellow solid, yield: 21.3%). 1H NMR (400 MHz, DMSO-d6) δ13.19 (s, 1H), 9.01 (s, 1H), 8.92 (s, 1H), 8.22 (s, 1H), 8.19 (s, 1H), 7.65 (s, 1H), 7.53 (s, 1H), 6.72 (s, 1H), 4.76 (d, J = 3.6 Hz, 1H), 3.91 - 3.82(m, 1H), 2.80 - 2.70 (m, 1H), 2.67 (s, 3H), 2.60 - 2.57 (m, 1H), 2.54 - 2.49(m, 1H), 2.23 - 2.06 (m, 1H), 2.05 - 1.93 (m, 1H), 1.72 - 1.63 (m, 1H). LC / MS (ESI) m / z: 511.2 [M+H] + .

[0398] Example 109: 2-chloro-N-(5-(4-hydroxypiperidin-1-yl)thiazolo[5,4-b]pyridin-2-yl)-5'-methoxy-6-dodeuteromethyl-[4,4'-bipyridine]-3-formamide TIFF2025533951000218.tif61131

[0399] Step 1: 4-chloro-6-dodeuteromethyl nicotinic acid ethyl ester Ethyl 4,6-dichloronicotinate (2 g, 9.1 mmol) and iron acetylacetonate (320 mg, 0.91 mmol) were dissolved in anhydrous tetrahydrofuran (30 mL). Under nitrogen gas protection, 1 mol / L deuterated methylmagnesium iodide (10.5 mL, 10.5 mmol) was slowly added dropwise while maintaining the temperature at room temperature. The reaction was allowed to proceed at room temperature for 1 hour. The reaction mixture was quenched with saturated aqueous ammonium chloride, extracted with ethyl acetate, washed with water, backwashed with saturated brine, and dried over anhydrous sodium sulfate. The residue was purified by column chromatography (eluent: petroleum ether / ethyl acetate, gradient: 0-17% ethyl acetate) to give the title compound (pale yellow solid, 410 mg, yield: 22.3%). LC / MS (ESI) m / z: 203.0 [M+H] + .

[0400] Step 2: 2-chloro-5-methoxy-6-dodeuteromethyl-[4,4'-bipyridine]-3-carboxylate ethyl Ethyl 4-chloro-6-dodeuteratemethylnicotinate (410 mg, 2.02 mmol), 2-chloro-5-methoxypyridine-4-boronic acid (380 mg, 2.02 mmol), and potassium carbonate (838 mg, 6.06 mmol) were dissolved in 1,4-dioxane (10 mL) and water (2 mL). 1,1-bis(diphenylphosphino)ferrocenedichloropalladium (148 mg, 0.2 mmol) was added and the mixture was heated to 80 °C under nitrogen gas protection for 1 hour. The reaction mixture was filtered through diatomaceous earth, the filter cake was washed with methanol, and the filtrate was concentrated under reduced pressure. The residue was purified by column chromatography (eluent: petroleum ether / ethyl acetate, gradient: 10% to 40% ethyl acetate) to give the title compound (yellow solid, 175 mg, yield: 27.7%). LC / MS (ESI) m / z: 631.0 [M+H] + .

[0401] Step 3: 2-chloro-5-methoxy-6-dodeuteromethyl-[4,4'-bipyridine]-3-carboxylic acid Ethyl 2-chloro-5-methoxy-6-dodeuteratemethyl-[4,4'-bipyridine]-3-carboxylate (175 mg, 0.56 mmol) was dissolved in water (2 mL) and tetrahydrofuran (2 mL), and lithium hydroxide (34 mg, 0.84 mmol) was added. The mixture was allowed to react at room temperature for 16 hours. The reaction mixture was concentrated under reduced pressure, and the residue was adjusted to pH 4-5 with 2N hydrochloric acid. A solid precipitated. After filtration, the solid was dried under reduced pressure and the water was removed to give the title compound (white solid, 140 mg, yield: 87.5%). LC / MS (ESI) m / z: 282.0 [M+H] + .

[0402] Step 4: 2-chloro-N-(5-(4-hydroxypiperidin-1-yl)thiazolo[5,4-b]pyridin-2-yl)-5'-methoxy-6-dodeuteromethyl-[4,4'-bipyridine]-3-formamide 2-Chloro-5-methoxy-6-dodeuteratemethyl-[4,4'-bipyridine]-3-carboxylic acid (20 mg, 0.07 mmol) and 1-(2-aminothiazolo[5,4-b]pyridin-5-yl)piperidin-4-ol (19 mg, 0.07 mmol) were dissolved in acetonitrile (5 mL) and N,N-dimethylformamide (3 mL), 1-methylimidazole (17 mg, 0.21 mmol) was added, and the mixture was stirred for 20 minutes. After that, N,N,N',N'-tetramethylformamidinium hexafluorophosphate (20 mg, 0.07 mmol) was added, and the mixture was allowed to react at room temperature for 2 hours. Ethyl acetate and water were added to the reaction mixture, which was then layered. The organic phase was washed with saturated sodium chloride solution, dried over anhydrous sodium sulfate, and filtered. The filtrate was concentrated under reduced pressure. The resulting residue was purified by column chromatography. The reaction mixture was concentrated under reduced pressure, and the residue was purified by preparative HPLC (eluent: acetonitrile / 0.1% aqueous formic acid solution, gradient: 25% to 90%) to obtain the title compound (white solid, 12.7 mg, yield: 34.8%). 1 HNMR (400MHz, DMSO-d6) δ 12.66 (s, 1H), 8.82 (s, 1H), 8.16 (s, 1H), 7.83 (d, J = 9.0 Hz, 1H), 7.55 (s, 1H), 7.43 (s, 1H), 6.98 (d, J = 9.1 Hz, 1H), 4.70 (d, J = 4.0 Hz, 1H), 4.07 - 3.98 (m, 2H), 3.76 - 3.65 (m, 1H), 3.62 (s, 3H), 3.17 - 3.09 (m, 2H), 1.85 - 1.76 (m, 2H), 1.44 - 1.34 (m, 2H). LC / MS (ESI) m / z: 514.2 [M+H] + .

[0403] Example 110: 2'-chloro-N-(6-(4-hydroxycyclohex-1-en-1-yl)thiazole[4,5-c]pyridin-2-yl)-5'-methoxy-6-(methyl-d3)-[4,4'-bipyridine]-3-formamide TIFF2025533951000219.tif47131

[0404] Step 1: 4-(2-aminothiazol[4,5-c]pyridin-6-yl)cyclohex-3-en-1-ol 4-(2-aminothiazole[4,5-c]pyridin-6-yl)cyclohex-3-en-1-yl 2,2,2-trifluoroacetate (500 mg, 1.46 mmol) was dissolved in anhydrous methanol (10 mL), and lithium hydroxide (35 mg, 1.46 mmol) was added. The mixture was allowed to react at room temperature for 18 hours. After completion of the reaction, the mixture was concentrated under reduced pressure and purified to give the title compound (white powder, 350 mg, 97% yield). LC / MS (ESI) m / z: 247.9 [M+H] + .

[0405] Step 2: 6-(4-((tert-butyldimethylsilyl)oxy)cyclohex-1-en-1-yl)thiazolo[4,5-c]pyridin-2-amine 4-(2-aminothiazole[4,5-c]pyridin-6-yl)cyclohex-3-en-1-ol (350 mg, 1.42 mmol) was dissolved in dichloromethane (10 mL), followed by the addition of imidazole (483 mg, 7.1 mmol) and tert-butyldimethylchlorosilane (642 mg, 4.26 mmol). The mixture was allowed to react overnight at room temperature. Saturated ammonium chloride solution was added to the reaction mixture, which was then extracted with dichloromethane, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated. The residue was purified by column chromatography (eluent: dichloromethane / methanol, gradient: 0%-10% methanol) to obtain the target compound (white powder, 350 mg, 68.4% yield). LC / MS (ESI) m / z: 362.1 [M+H] + .

[0406] Step 3: N-(6-(4-((tert-butyldimethylsilyl)oxy)cyclohex-1-en-1-yl)thiazole[4,5-c]pyridin-2-yl)-2'-chloro-5'-methoxy-6-(methyl-d3)-[4,4'-bipyridine]-3-formamide 6-(4-(tert-butyldimethylsiloxy)cyclohexyl-1-en-1-ylthiazolo[5,4-b]pyridin-2-amine (50 mg, 0.14 mmol) and 2'-chloro-5'-methoxy-6-(methyl-d3)-[4,4'-bipyridine]-3-carboxylic acid (39 mg, 0.14 mmol) were dissolved in acetonitrile (3 mL) and N,N-dimethylformamide (1 mL), 1-methylimidazole (43 mg, 0.52 mmol) was added, and the mixture was stirred for 10 minutes. After stirring, N,N,N',N'-tetramethylformamidinium hexafluorophosphate (39 mg, 0.14 mmol) was added. The reaction mixture was added with ethyl acetate and water, and the mixture was separated into layers. The organic phase was washed with saturated sodium chloride solution and dried over anhydrous sodium sulfate. The mixture was then filtered and the filtrate was concentrated under reduced pressure. The residue was purified by column chromatography (eluent: petroleum ether / ethyl acetate, gradient: 30% to 50% ethyl acetate) to give the title compound (white solid, 35 mg, yield: 40.5%). LC / MS (ESI) m / z: 625.3 [M+H] + .

[0407] Step 4: 2-chloro-6-(4-hydroxycyclohexyl-1-en-1-yl)thiazolopyridine-5,4-b-pyridin-2-yl-5'-methoxy-6-methyl-4,4'-bipyridine-3-formamide N-(6-(4-((tert-butyldimethylsilyl)oxy)cyclohex-1-en-1-yl)thiazole[4,5-c]pyridin-2-yl)-2'-chloro-5'-methoxy-6-(methyl-d3)-[4,4'-bipyridine]-3-formamide (40 mg, 0.064 mmol) was dissolved in dioxane (2 mL), and 4M hydrochloric acid in dioxane (2 mL) was added. The mixture was allowed to react at room temperature for 3 hours. The reaction mixture was concentrated under reduced pressure, and the residue was purified by preparative HPLC (eluent: acetonitrile / 0.1% formic acid in water, gradient: 25% to 90%) to give the title compound (white solid, 25 mg, yield: 76.4%). 1 H NMR (400 MHz, DMSO-d6) δ 13.08 (s, 1H), 8.93 (s, 1H), 8.87 (s, 1H), 8.16 (s, 1H), 8.10 (s, 1H), 7.57 (s, 1H), 7.45 (s, 1H), 6.67 - 6.63 (m, 1H), 4.69 (d, J = 3.6 Hz, 1H), 3.85 - 3.78 (m, 1H), 3.60 (s, 3H), 2.73 - 2.65 (m, 1H), 2.48 - 2.40 (m, 2H), 2.14 - 2.06 (m, 1H), 1.95 - 1.87 (m, 1H), 1.67 - 1.57 (m, 1H). LC / MS (ESI) m / z: 511.2 [M+H] + .

[0408] Example 111: 2'-chloro-N-(6-(4-hydroxycyclohex-1-en-1-yl-4-d)thiazole[4,5-c]pyridin-2-yl)-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-formamide TIFF2025533951000220.tif45121

[0409] Step 1: 2-(2,5-dimethyl-1H-pyrrol-1-yl)-6-(1,4-dioxacetyl[4.5]dec-7-en-8-yl)thiazole[4,5-c]pyridine 6-Chloro-2-(2,5-dimethyl-1H-pyrrol-1-yl)thiazolo[4,5-c]pyridine (1.7 g, 6.45 mmol) was dissolved in 1,4-dioxane (20 mL) / water (4 mL), and 4,4,5,5-tetramethyl-2-(1,4-dioxopyrimidin[4.5]dec-7-en-8-yl)-1,3,2-dioxaborane (2.57 g, 9.68 mmol), [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (94.4 mg, 0.129 mmol), and sodium tert-butoxide (1.86 g, 19.35 mmol) were added. The mixture was reacted at 95°C for 3 hours under nitrogen gas protection. After cooling to room temperature, saturated ammonium chloride was slowly added to the reaction mixture, which was then extracted with ethyl acetate, washed with saturated brine, concentrated under reduced pressure, and purified by column chromatography (eluent: ethyl acetate / petroleum ether = 1 / 1, V / V) to give the title compound (yellow solid, 1.2 g, yield 50.6%). LC / MS (ESI) m / z: 368.2 [M+H] + .

[0410] Step 2: 4-(2-aminothiazol[4,5-c]pyridin-6-yl)cyclohex-3-en-1-one 2-(2,5-Dimethyl-1H-pyrrol-1-yl)-6-(1,4-dioxacetyl[4.5]dec-7-en-8-yl)thiazole[4,5-c]pyridine (1.2 g, 3.27 mmol) was dissolved in trifluoroacetic acid (15 mL), two drops of water were added, and the mixture was refluxed and reacted for 30 minutes. After the reaction was complete, the mixture was directly dried by centrifugation and purified by reverse phase chromatography (eluent: acetonitrile / water = 1 / 1, V / V) to obtain the title compound (yellow solid, 500 mg, 62.5% yield). LC / MS (ESI) m / z: 246.1 [M+H] + .

[0411] Step 3: 4-(2-aminothiazol[4,5-c]pyridin-6-yl)cyclohex-3-en-1-deutero-1-ol 4-(2-Aminothiazole[4,5-c]pyridin-6-yl)cyclohex-3-en-1-one (250 mg, 1.02 mmol) was dissolved in deuterated methanol (1 mL), tetrahydrofuran (5 mL) was added, and the mixture was stirred in an ice bath for 5 minutes. Sodium borodeuteride (51.4 mg, 1.22 mmol) was then added, and the mixture was allowed to react at room temperature for 30 minutes. After completion of the reaction, the mixture was quenched with saturated ammonium chloride, extracted with ethyl acetate, and the organic phase was washed with saturated sodium chloride, dried, and directly centrifuged to give the crude title compound (yellow solid, 50 mg). LC / MS (ESI) m / z: 249.1 [M+H] + .

[0412] Step 4: 2'-chloro-N-(6-(4-hydroxycyclohex-1-en-1-yl-4-d)thiazole[4,5-c]pyridin-2-yl)-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-formamide The crude product, 4-(2-aminothiazole[4,5-c]pyridin-6-yl)cyclohex-3-en-1-deutero-1-ol (50 mg, 0.20 mmol), 2'-chloro-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-carboxylic acid (84.2 mg, 0.30 mmol), and methylimidazole (0.5 mL) were dissolved in acetonitrile (10 mL) and stirred at room temperature for 10 minutes. N,N,N',N'-tetramethylformamidinium hexafluorophosphate (280.6 mg, 1.0 mmol) was added, and the mixture was allowed to react at room temperature for 1 hour. The reaction mixture was quenched by the addition of saturated ammonium chloride, extracted with ethyl acetate, and the organic phase was concentrated under reduced pressure and purified by prep-HPLC (eluent: acetonitrile / 0.1% aqueous trifluoroacetic acid solution = 0% to 70%, V / V) to obtain the title compound (1.7 mg, white solid, yield 1.7%). 1H NMR (400 MHz, DMSO-d6) δ 13.18 (s, 1H), 8.98 (s, 1H), 8.86 (s, 1H), 8.18 (s, 1H), 8.17(s, 1H), 7.59 (s, 1H), 7.48 (s, 1H), 6.67 - 6.63 (m, 1H), 3.60 (s, 3H), 2.71 - 2.66 (m, 1H), 2.61 (s, 3H), 2.47 - 2.42 (m, 2H), 2.18 - 2.05 (m, 1H), 1.95 - 1.85 (m, 1H), 1.69 - 1.57 (m, 1H).LC / MS (ESI) m / z: 509.3 [M+H] + .

[0413] Example 112: 2'-chloro-N-(5-(4-hydroxypiperidin-1-yl-4-deutero)thiazole[5,4-b]pyridin-2-yl)-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-formamide TIFF2025533951000221.tif50147

[0414] Step 1: 4-Hydroxypiperidine-1-carboxylic acid tert-butyl ester-4-deuterated N-tert-Butoxycarbonyl-4-piperidone (5 g, 25.1 mmol) was dissolved in methanol (50 mL) and cooled to 0-10 °C under nitrogen gas protection. Sodium borodeuteride (1.58 g, 37.6 mmol) was added in portions, then the ice bath was removed and the mixture was stirred at room temperature for 2 hours. The reaction was quenched with water, concentrated under reduced pressure, dried, and stratified with water and dichloromethane. The aqueous phase was extracted with dichloromethane. The combined organic phases were washed with saturated brine, dried over anhydrous sodium sulfate, filtered, concentrated under reduced pressure, and dried to give 4-hydroxypiperidine-1-carboxylic acid tert-butyl ester-4-deuterated (4.5 g, yellow liquid, 88.6% yield). LC / MS (ESI) m / z: 203.1 [M+H] + .

[0415] Step 2: Piperidin-4-deutero-4-ol hydrochloride 4-Hydroxypiperidine-1-carboxylic acid tert-butyl ester-4-deuterium (4.5 g, 22.2 mmol) was dissolved in ethyl acetate (20 mL), and hydrochloric acid-ethyl acetate (30 mL, 60.0 mmol) was added. The mixture was stirred at room temperature for 18 hours. The reaction mixture was filtered, rinsed with ethyl acetate, and dried under vacuum at 50°C for 1 hour to give piperidin-4-deuterium-4-ol hydrochloride (3 g, white solid, 38.9% yield). LC / MS (ESI) m / z: 103.1 [M+H] + .

[0416] Step 3: N-(5-(4-hydroxypiperidin-1-yl-4-deutero)thiazole[5,4-b]pyridin-2-yl)acetamide N-(5-fluorothiazole[5,4-b]pyridin-2-yl)acetamide (250 mg, 1.18 mmol) and piperidin-4-deutero-4-ol hydrochloride (328 mg, 2.37 mmol) were dissolved in N-methylpyrrolidone (7 mL), and N,N-diisopropylethylamine (765 mg, 5.92 mmol) was added. The mixture was stirred at 120°C for 48 hours. The reaction mixture was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (eluent: dichloromethane / methanol = 20 / 1, V / V) to give N-(5-(4-hydroxypiperidin-1-yl-4-deutero)thiazole[5,4-b]pyridin-2-yl)acetamide (135 mg, yellow solid, 38.9% yield). LC / MS (ESI) m / z: 294.2 [M+H] + .

[0417] Step 4: 1-(2-aminothiazol[5,4-b]pyridin-5-yl)piperidin-4-deutero-4-ol 1-(2-aminothiazole[5,4-b]pyridin-5-yl)piperidin-4-deutero-4-ol (135 mg, 0.460 mmol) and sodium hydroxide (184 mg, 4.60 mmol) were dissolved in methanol (6 mL) and water (2 mL) and stirred at 80°C for 3 hours. The reaction mixture was cooled to 0°C, adjusted to pH 8-9 with 1N hydrochloric acid, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: dichloromethane / methanol = 15 / 1, V / V) to give 1-(2-aminothiazole[5,4-b]pyridin-5-yl)piperidin-4-deutero-4-ol (100 mg, yellow solid, 86.5% yield). LC / MS (ESI) m / z: 252.2 [M+H] + .

[0418] Step 5: 2'-chloro-N-(5-(4-hydroxypiperidin-1-yl-4-deutero)thiazole[5,4-b]pyridin-2-yl)-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-formamide 1-(2-Aminothiazole[5,4-b]pyridin-5-yl)piperidin-4-deutero-4-ol (100 mg, 0.398 mmol), 2'-chloro-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-carboxylic acid (111 mg, 0.398 mmol), and methylimidazole (98.1 mg, 1.20 mmol) were dissolved in acetonitrile (16 mL) and N,N-dimethylformamide (4 mL). The mixture was stirred at 70°C for 20 minutes, and then a 4 mL solution of N,N,N',N'-tetramethylformamidinium hexafluorophosphate in acetonitrile (112 mg, 0.398 mmol) was added dropwise. The mixture was stirred at 70°C for 2 hours. The reaction mixture was concentrated under reduced pressure, water was added, and the mixture was extracted with ethyl acetate. The organic phase was washed with water and brine and concentrated under reduced pressure. The residue was purified by prep-HPLC (eluent: acetonitrile / 0.1% aqueous formic acid solution = 25% to 90%, V / V) to give 2'-chloro-N-(5-(4-hydroxypiperidin-1-yl-4-deuterated)thiazole[5,4-b]pyridin-2-yl)-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-formamide (100 mg, yellow solid, yield 49.0%). 1 H NMR (400 MHz, DMSO-d6) δ 12.68 (s, 1H), 8.81 (s, 1H), 8.17 (s, 1H), 7.85 (d, J = 9.1 Hz, 1H), 7.56 (s, 1H), 7.45 (s, 1H), 6.99 (d, J = 9.1 Hz, 1H), 4.68 (s, 1H), 4.04 - 4.00 (m, 2H), 3.33 (s, 3H), 3.22 - 3.06 (m, 2H), 2.60 (s, 3H), 1.82 - 1.76 (m, 2H), 1.45 - 1.32 (m, 2H). LC / MS (ESI) m / z: 512.1 [M+H] + .

[0419] Example 113: 2'-chloro-N-(7-fluoro-6-(4-hydroxypiperidin-1-yl-4-deutero)benzo[d]thiazol-2-yl)-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-formamide TIFF2025533951000222.tif85143

[0420] Step 1: 4-((tert-butyldimethylsilyl)oxy)piperidine-4-deuterated Piperidin-4-deutero-4-ol (300 mg, 2.94 mmol) was dissolved in dichloromethane (20 mL), and imidazole (600.0 mg, 8.81 mmol) and tert-butyldimethylchlorosilane (443.1 mg, 2.94 mmol) were added at room temperature. The mixture was stirred at room temperature for 18 hours. Dichloromethane (200 mL) was added, and the mixture was washed with water eight times. The organic phase was dried and concentrated under reduced pressure to give the title compound (350 mg, colorless oil, 55.1% yield). LC / MS (ESI) m / z: 217.1 [M+H] + .

[0421] Step 2: N-(6-(4-((tert-butyldimethylsilyl)oxy)piperidin-1-yl-4-deutero)-7-fluorobenzo[d]thiazol-2-yl)acetamide 4-((tert-butyldimethylsilyl)oxy)piperidine-4-deuterium (250 mg, 1.16 mmol), N-(6-bromo-7-fluorobenzo[d]thiazol-2-yl)acetamide (400.8 mg, 1.39 mmol), bis(dibenzylideneacetone)palladium(II) (106.2 mg, 0.116 mmol), 2-dicyclohexylphosphonium-2',6'-diisopropoxy-1,1'-biphenyl (108.3 mg, 0.232 mmol), and sodium tert-butoxide (334.4 mg, 3.48 mmol) were dissolved in anhydrous 1,4-dioxane (20 mL) at room temperature. The atmosphere was purged with nitrogen gas three times and the mixture was stirred at 100°C for 1 hour. After the reaction was completed, the mixture was concentrated under reduced pressure and purified by column chromatography (eluent: petroleum ether / ethyl acetate = 1 / 1, V / V) to obtain the title compound (pale yellow solid, 380 mg, yield 77.5%). LC / MS (ESI) m / z: 425.1 [M+H] + .

[0422] Step 3: 6-(4-((tert-butyldimethylsilyl)oxy)piperidin-1-yl-4-deutero)-7-fluorobenzo[d]thiazol-2-amine N-(6-(4-((tert-butyldimethylsilyl)oxy)piperidin-1-yl-4-deutero)-7-fluorobenzo[d]thiazol-2-yl)acetamide (380 mg, 0.895 mmol) and sodium hydroxide (179 mg, 4.47 mmol) were dissolved in methanol (20 mL) and water (8 mL) and stirred at 80°C for 3 hours. Ethyl acetate (100 mL) was added, and the mixture was washed twice with water. The organic phase was dried and concentrated under reduced pressure to give the title compound (300 mg, yellow solid, 88.7% yield). LC / MS (ESI) m / z: 383.2 [M+H] + .

[0423] Step 4: N-(6-(4-((tert-butyldimethylsilyl)oxy)piperidin-1-yl-4-deutero)-7-fluorobenzo[d]thiazol-2-yl)-2'-chloro-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-formamide 6-(4-((tert-Butyldimethylsilyl)oxy)piperidin-1-yl-4-deutero)-7-fluorobenzo[d]thiazol-2-amine (300 mg, 0.784 mmol), 2'-chloro-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-carboxylic acid (327.8 mg, 1.18 mmol), and methylimidazole (321.8 mg, 3.92 mmol) were dissolved in acetonitrile (16 mL) and N,N-dimethylformamide (2 mL) and stirred at 75°C for 5 minutes. N,N,N',N'-tetramethylformamidinium hexafluorophosphate (1.1 g, 3.92 mmol) was added, and the mixture was stirred at 75°C for 30 minutes. Saturated ammonium chloride was added, and the mixture was extracted with ethyl acetate. The organic phase was washed with water, washed with brine, concentrated under reduced pressure, and purified by column chromatography (eluent: dichloromethane / methanol = 10 / 1, V / V) to give the title compound (pale yellow solid, 300 mg, yield 59.5%). LC / MS (ESI) m / z: 643.2 [M+H] + .

[0424] Step 5: 2'-chloro-N-(7-fluoro-6-(4-hydroxypiperidin-1-yl-4-deutero)benzo[d]thiazol-2-yl)-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-formamide N-(6-(4-((tert-butyldimethylsilyl)oxy)piperidin-1-yl-4-deuterated)-7-fluorobenzo[d]thiazol-2-yl)-2'-chloro-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-formamide (300 mg, 0.466 mmol) was dissolved in methanol (2 mL), and 4 M hydrochloric acid-1,4-dioxane solution (10 mL) was added in an ice bath. The mixture was stirred at room temperature for 30 minutes. After the reaction was completed, the mixture was concentrated, and the residue was analyzed by prep-HPLC (eluent: acetonitrile / 0.1% formic acid aqueous solution = 20% to 90%, V / V). This was purified by HPLC to give 2'-chloro-N-(7-fluoro-6-(4-hydroxypiperidin-1-yl-4-deutero)benzo[d]thiazol-2-yl)-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-formamide (100 mg, pale yellow solid, 40.5% yield). 1 H NMR (400 MHz, DMSO-d6) δ 13.02 (s, 1H), 8.84 (s, 1H), 8.17 (s, 1H), 7.58 (s, 1H), 7.53 (d, J = 8.6 Hz, 1H), 7.46 (s, 1H), 7.22 (t, J = 8.7 Hz, 1H), 4.67 (s, 1H), 3.60 (s, 3H), 3.30 - 3.22 (m, 2H), 2.83 (t, J = 9.5 Hz, 2H), 2.59 (s, 3H), 1.90 -1.80 (m, 2H), 1.61 - 1.50 (m, 2H). LC / MS (ESI) m / z: 529.2 [M+H] + .

[0425] Example 114 and Example 115: (R)-2'-chloro-N-(6-(4-hydroxycyclohex-1-en-1-yl)thiazole[4,5-c]pyridin-2-yl)-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-formamide (Example 114) and (S)-2'-chloro-N-(6-(4-hydroxycyclohex-1-en-1-yl)thiazole[4,5-c]pyridin-2-yl)-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-formamide (Example 115) TIFF2025533951000223.tif50151

[0426] Step 1: (R)-N-(6-(4-((tert-butyldimethylsilyl)oxy)cyclohex-1-en-1-yl)thiazole[4,5-c]pyridin-2-yl)-2'-chloro-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-formamide and (S)-N-(6-(4-((tert-butyldimethylsilyl)oxy)cyclohex-1-en-1-yl)thiazole[4,5-c]pyridin-2-yl)-2'-chloro-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-formamide N-(6-(4-((tert-butyldimethylsilyl)oxy)cyclohex-1-en-1-yl)thiazole[5,4-b]pyridin-2-yl)-2'-chloro-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-formamide (160 mg, 0.257 mmol) was separated by chiral separation (OX column, 30% methanol (containing 0.05% diethylamine): 70% supercritical carbon dioxide, 8 min), and each fraction was concentrated to give (R)-N-(6-(4-((tert-butyldimethylsilyl)oxy)cyclohex-1-en-1-yl)thiazole[4,5-c]pyridin-2-yl)-2'-chloro-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-formamide (60 mg, 0.193 mmol, Rt=4.046 min, yield 37.5%) LC / MS (ESI) m / z: 623.2 [M+H] + and (S)-N-(6-(4-((tert-butyldimethylsilyl)oxy)cyclohex-1-en-1-yl)thiazole[4,5-c]pyridin-2-yl)-2'-chloro-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-formamide (60 mg, 0.193 mmol, Rt=4.789 min, yield 37.5%) LC / MS (ESI) m / z: 623.2 [M+H] + obtained.

[0427] Step 2: (R)-2'-chloro-N-(6-(4-hydroxycyclohex-1-en-1-yl)thiazole[4,5-c]pyridin-2-yl)-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-formamide and (S)-2'-chloro-N-(6-(4-hydroxycyclohex-1-en-1-yl)thiazole[4,5-c]pyridin-2-yl)-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-formamide (R)-N-(6-(4-((tert-butyldimethylsilyl)oxy)cyclohex-1-en-1-yl)thiazole[4,5-c]pyridin-2-yl)-2'-chloro-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-formamide (50 mg, 0.18 mmol) was dissolved in acetonitrile (2 mL), ethyl acetate-hydrochloric acid solution (2 mL) was added, and the mixture was stirred at room temperature for 3 hours. The reaction mixture was concentrated under reduced pressure, and the residue was purified by preparative HPLC (eluent: acetonitrile / 0.1% aqueous formic acid, gradient: 25% to 90%) to give the title compound (white solid, 25 mg, yield: 61.2%). 1 H NMR (400 MHz, DMSO-d6)δ 13.08 (s, 1H), 8.94 (s, 1H), 8.86 (s, 1H), 8.18 (s, 1H), 8.12 (s, 1H), 7.59 (s, 1H), 7.47 (s, 1H), 6.66 - 6.62 (m, 1H), 4.74 - 4.62 (m, 1H), 3.85 - 3.78 (m, 1H), 3.61 (s, 3H), 2.72 - 2.65 (m, 1H), 2.61 (s, 3H), 2.52 - 2.43 (m, 2H), 2.15 - 2.05 (m, 1H), 1.96 - 1.88 (m, 1H), 1.69 - 1.57 (m, 1H). LC / MS (ESI) m / z: 508.2 [M+H] + .

[0428] (S)-N-(6-(4-((tert-butyldimethylsilyl)oxy)cyclohex-1-en-1-yl)thiazole[4,5-c]pyridin-2-yl)-2'-chloro-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-formamide (50 mg, 0.18 mmol) was dissolved in acetonitrile (2 mL), ethyl acetate-hydrochloric acid solution (2 mL) was added, and the mixture was stirred at room temperature for 3 hours. The reaction mixture was concentrated under reduced pressure, and the residue was purified by preparative HPLC (eluent: acetonitrile / 0.1% aqueous formic acid, gradient: 25% to 90%) to give the title compound (white solid, 25 mg, yield: 61.2%). 1 H NMR (400 MHz, DMSO-d6)δ 13.07 (s, 1H), 8.93 (s, 1H), 8.85 (s, 1H), 8.17 (s, 1H), 8.12 (s, 1H), 7.58 (s, 1H), 7.47 (s, 1H), 6.67 - 6.63 (m, 1H), 4.73 - 4.62 (m, 1H), 3.84 - 3.78 (m, 1H), 3.60 (s, 3H), 2.72 - 2.65 (m, 1H), 2.61 (s, 3H), 2.52 - 2.43 (m, 2H), 2.16 - 2.06 (m, 1H), 1.96 - 1.88 (m, 1H), 1.67 - 1.57 (m, 1H).LC / MS (ESI) m / z: 508.2 [M+H] + .

[0429] Example 116: 2'-chloro-N-(5-(4-hydroxy-3,3-dimethylpiperidin-1-yl)thiazole[5,4-b]pyridin-2-yl)-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-formamide TIFF2025533951000224.tif46143

[0430] Step 1: N-(5-(4-hydroxy-3,3-dimethylpiperidin-1-yl)thiazole[5,4-b]pyridin-2-yl)acetamide N-(5-fluorothiazole[5,4-b]pyridin-2-yl)acetamide (500 mg, 2.37 mmol) and 3,3-dimethylpiperidin-4-ol (459 mg, 3.55 mmol) were dissolved in 1-methyl-2-pyrrolidinone (10 mL), N,N-diisopropylethylamine (2.14 g, 16.6 mmol) was added, and the mixture was reacted at 120 °C for 48 hours. After completion of the reaction, the reaction mixture was extracted with water and ethyl acetate. The organic phase was washed with saturated brine. The residue was purified by column chromatography (eluent: dichloromethane / methanol, gradient: 0%-10% methanol) to give the title compound (400 mg, white solid, yield: 52.6%). LC / MS (ESI) m / z: 321.0 [M+H] + .

[0431] Step 2: N-(5-(4-((tert-butyldimethylsilyl)oxy)-3,3-dimethylpiperidin-1-yl)thiazolo[5,4-b]pyridin-2-yl)acetamide N-(5-(4-hydroxy-3,3-dimethylpiperidin-1-yl)thiazole[5,4-b]pyridin-2-yl)acetamide (300 mg, 0.936 mmol) was dissolved in dichloromethane (5 mL), and imidazole (637 mg, 9.36 mmol) and tert-butyldimethylchlorosilane (1.13 g, 7.49 mmol) were added. The mixture was stirred at room temperature for 12 hours. After completion of the reaction, the reaction mixture was extracted with water and ethyl acetate. The organic phase was washed with saturated brine. The residue was purified by column chromatography (eluent: petroleum ether / ethyl acetate, gradient: 10%-50% ethyl acetate) to give the title compound (200 mg, white solid, yield: 49.1%). LC / MS (ESI) m / z: 435.3 [M+H] + .

[0432] Step 3: 5-(4-((tert-butyldimethylsilyl)oxy)-3,3-dimethylpiperidin-1-yl)thiazolo[5,4-b]pyridin-2-amine N-(5-(4-((tert-butyldimethylsilyl)oxy)-3,3-dimethylpiperidin-1-yl)thiazolo[5,4-b]pyridin-2-yl)acetamide (200 mg, 0.460 mmol) and sodium hydroxide (184 mg, 4.60 mmol) were dissolved in methanol / water (6 / 2 mL), heated to 80°C, and reacted for 2 hours. After completion of the reaction, the reaction mixture was concentrated under reduced pressure, and the residue was purified by column chromatography (eluent: dichloromethane / methanol, gradient: 0%-10% methanol) to give the title compound (150 mg, white solid, yield: 83.0%). LC / MS (ESI) m / z: 393.3 [M+H] + .

[0433] Step 4: N-(5-(4-((tert-butyldimethylsilyl)oxy)-3,3-dimethylpiperidin-1-yl)thiazolo[5,4-b]pyridin-2-yl)-2'-chloro-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-formamide 2'-Chloro-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-carboxylic acid (17.2 mg, 0.062 mmol), 5-(4-((tert-butyldimethylsilyl)oxy)-3,3-dimethylpiperidin-1-yl)thiazolo[5,4-b]pyridin-2-amine (29.0 mg, 0.074 mmol), and 1-methylimidazole (22.2 mg, 0.277 mmol) were dissolved in acetonitrile / N,N-dimethylformamide (3 / 0.5 mL) and stirred at 75°C for 15 min. Next, N,N,N',N'-tetramethylformamidinium hexafluorophosphate (25.9 mg, 0.092 mmol) dissolved in acetonitrile (0.5 mL) was added, and the mixture was stirred at 75°C for 1 h. After the reaction was completed, water and ethyl acetate were added for extraction. The organic phase was washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by column chromatography (eluent: dichloromethane / methanol, gradient: 0%-10% methanol) to give the title compound (30 mg, yellow solid, yield: 74.6%). LC / MS (ESI) m / z: 653.3 [M+H] + .

[0434] Step 4: 2'-chloro-3'-fluoro-N-(6-(4-hydroxypiperidin-1-yl)thiazolo[4,5-b]pyridin-2-yl)-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-formamide N-(5-(4-((tert-butyldimethylsilyl)oxy)-3,3-dimethylpiperidin-1-yl)thiazolo[5,4-b]pyridin-2-yl)-2'-chloro-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-formamide (30 mg, 0.046 mmol) was dissolved in a solution of hydrochloric acid in dioxane (3 mL), and the mixture was reacted at room temperature for 2 hours. After completion of the reaction, the reaction solution was concentrated under reduced pressure, and the residue was purified by reverse-phase preparative fractionation to obtain the title compound (18 mg, yellow solid, yield: 72.7%). 1H NMR (400 MHz, DMSO-d6) δ 12.64 (s, 1H), 8.81 (s, 1H), 8.16 (s, 1H), 7.82 - 7.78 (m, 1H), 7.55 (s, 1H), 7.44 (s, 1H), 7.00 - 6.96 (m, 1H), 4.66 - 4.62 (m, 1H), 4.12 - 4.04 (m, 1H), 3.77 - 3.71 (m, 1H), 3.62 (s, 3H), 3.30 - 3.27(m, 1H), 3.11 - 3.05 (m, 1H), 2.86 - 2.79 (m, 1H), 2.59 (s, 3H), 1.77 - 1.65 (m, 1H), 1.58 - 1.45 (m, 1H), 0.93 (s, 3H), 0.82 (s, 3H). LC / MS (ESI) m / z: 539.2 [M+H] + .

[0435] The compounds of the examples in Table 9 were synthesized using commercially available raw materials with reference to the synthesis process of Example 116.

[0436] [Table 9] TIFF2025533951000226.tif233155 TIFF2025533951000227.tif227155 TIFF2025533951000228.tif228155 TIFF2025533951000229.tif226155 TIFF2025533951000230.tif221155 TIFF2025533951000231.tif146155

[0437] Example 147: 2'-chloro-N-(5-(1,4-dimethyl-1H-1,2,3-triazol-5-yl)thiazolo[5,4-b]pyridin-2-yl)-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-formamide TIFF2025533951000232.tif29135

[0438] Step 1: 1,4-dimethyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-1,2,3-triazole A 2.5M n-butyllithium solution in n-hexane (0.5 mL) was added to a solution of 1,4-dimethyl-1,2,3-triazole (100 mg, 1.030 mmol) in THF (10 mL) at -78°C and the mixture was stirred for 1 hour. 4,4,5,5-tetramethyl-2-(propyl-2-yloxy)-1,3,2-dioxaborane (210 mg, 1.13 mmol) was added to the reaction solution at -78°C, and the mixture was stirred overnight at 25°C. The reaction was quenched by slowly adding saturated aqueous ammonium chloride solution. The resulting mixture was extracted three times with ethyl acetate. The organic phases were combined, dried over anhydrous sodium sulfate, filtered, and concentrated. The crude product (crude brown oil, 100 mg, 43.54% yield) was directly used in the next step.

[0439] Step 2: 2'-chloro-N-(5-(1,4-dimethyl-1H-1,2,3-triazol-5-yl)thiazolo[5,4-b]pyridin-2-yl)-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-formamide To a mixture of 1,4-dimethyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3-triazole (100 mg, 0.448 mmol) and N-(5-bromo[1,3]thiazolo[5,4-b]pyridin-2-yl)-4-(2-chloro-5-methoxypyridin-4-yl)-6-methylpyridine-3-formamide (220.0 mg, 0.448 mmol) in 1,4-dioxane (30 mL) and HO (6 mL) was added KCO (186 mg, 1.35 mmol) and Pd(dppf)Cl (33 mg, 0.045 mmol). The mixture was heated to 90 °C under nitrogen gas protection and stirred for 3 h. After completion of the reaction, the reaction mixture was quenched with water and extracted three times with ethyl acetate. The organic phase was concentrated to give a crude product, which was separated and purified by reverse fractionation (acetonitrile / water system) to give the title compound (white solid, 3 mg, yield 1.32%). 1 H NMR (400 MHz, DMSO-d6) δ 13.21 (s, 1H), 8.82 (s, 1H), 8.29 (d, J = 8.4 Hz, 1H), 8.17 (s, 1H), 7.78 (d, J = 8.4 Hz, 1H), 7.60 (s, 1H), 7.48 (s, 1H), 4.15 (s, 3H), 3.63 (s, 3H), 2.62 (s, 3H), 2.39 (s, 3H). LC / MS (ESI) m / z: 507.2 [M+H] + . The compounds of the examples in Table 10 were synthesized using commercially available raw materials with reference to the synthesis process of Example 147.

[0440] [Table 10] TIFF2025533951000234.tif234155 TIFF2025533951000235.tif234155 TIFF2025533951000236.tif241155 TIFF2025533951000237.tif233155 TIFF2025533951000238.tif144155

[0441] Example 175: 2'-chloro-N-(6-(1,4-dimethyl-1H-1,2,3-triazol-5-yl)thiazolo[4,5-c]pyridin-2-yl)-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-formamide TIFF2025533951000239.tif54118

[0442] Step 1: 1,4-dimethyl-5-(tributyltinyl)-1H-1,2,3-triazole To a solution of 1,4-dimethyl-1H-1,2,3-triazole (300 mg, 3.09 mmol) in tetrahydrofuran (30 mL) was slowly added dropwise n-butyllithium (2.3 mL, 3.71 mmol, 1.6 mol / L) at -78°C. The reaction mixture was stirred at -78°C for 1 hour under nitrogen gas protection, and then tributyltin chloride (0.922 mL, 3.40 mmol) was added. The reaction mixture was stirred at -78°C for 30 minutes under nitrogen gas protection. After completion of the reaction, the reaction mixture was returned to room temperature, saturated ammonium chloride solution was added, extracted with ethyl acetate, washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel chromatography (eluent: petroleum ether / ethyl acetate, gradient: 0-10% ethyl acetate) to give 1,4-dimethyl-5-(tributylthinyl)-1H-1,2,3-triazole (yellow oil, 1100 mg, yield: 92.2%). LC / MS (ESI) m / z: 388.2 [M+H] + .

[0443] Step 2: 6-(1,4-dimethyl-1H-1,2,3-triazol-5-yl)-2-(2,5-dimethyl-1H-pyrrol-1-yl)thiazole[4,5-c]pyridine To a solution of 1,4-dimethyl-5-(tributylthienyl)-1H-1,2,3-triazole (1000 mg, 2.59 mmol) and 6-chloro-2-(2,5-dimethyl-1H-pyrrol-1-yl)thiazolo[4,5-c]pyridine (683 mg, 2.59 mmol) in 1,4-dioxane (30 mL) was added tris(dibenzylideneacetone)dipalladium (355.7 mg, 0.39 mmol), tricyclohexylphosphine (217.9 mg, 0.78 mmol), and cesium carbonate (1687 mg, 5.18 mmol). The reaction mixture was stirred under nitrogen gas protection at 110 °C for 5 hours. After completion of the reaction, the mixture was cooled to room temperature, water was added, and the mixture was extracted with ethyl acetate, washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel chromatography (eluent: petroleum ether / ethyl acetate, gradient: 0-30% ethyl acetate) to give 6-(1,4-dimethyl-1H-1,2,3-triazol-5-yl)-2-(2,5-dimethyl-1H-pyrrol-1-yl)thiazole[4,5-c]pyridine (yellow solid, 140 mg, yield: 16.7%). LC / MS (ESI) m / z: 325.1 [M+H] + .

[0444] Step 3: 6-(1,4-dimethyl-1H-1,2,3-triazol-5-yl)thiazole[4,5-c]pyridin-2-amine 6-(1,4-dimethyl-1H-1,2,3-triazol-5-yl)-2-(2,5-dimethyl-1H-pyrrol-1-yl)thiazole[4,5-c]pyridine (140 mg, 0.432 mmol) was added to trifluoroacetic acid (5.0 mL) and water (one drop) and reacted at 70 °C with stirring for 1 hour. After completion of the reaction, the reaction mixture was concentrated under reduced pressure, and the resulting crude product, 6-(1,4-dimethyl-1H-1,2,3-triazol-5-yl)thiazole[4,5-c]pyridin-2-amine (yellow solid, 43.0 mg, yield: 40.5%), was directly used in the next step. LC / MS (ESI) m / z: 247.1 [M+H] + .

[0445] Step 4: 2'-chloro-N-(6-(1,4-dimethyl-1H-1,2,3-triazol-5-yl)thiazolo[4,5-c]pyridin-2-yl)-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-formamide 6-(1,4-Dimethyl-1H-1,2,3-triazol-5-yl)thiazole[4,5-c]pyridin-2-amine (30.0 mg, 0.12 mmol), 2'-chloro-5'-methoxy-[3,4'-bipyridine]-4-carboxylic acid (34.0 mg, 0.12 mmol), N,N,N',N'-tetramethylformamidinium hexafluorophosphate (34.2 mg, 0.12 mmol), and 1-methylimidazole (30.0 mg, 0.36 mmol) were dissolved in acetonitrile (10 mL), and the reaction mixture was stirred at 70°C for 4 hours. After completion of the reaction, the reaction mixture was concentrated under reduced pressure, and the resulting residue was purified by preparative HPLC to obtain 2'-chloro-N-(6-(1,4-dimethyl-1H-1,2,3-triazol-5-yl)thiazolo[4,5-c]pyridin-2-yl)-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-formamide (white solid, 12.2 mg, yield: 19.8%). 1 H NMR (400 MHz, DMSO-d6) δ 13.30 (s, 1H), 9.20 (s, 1H), 8.88 (s, 1H), 8.40 (s, 1H), 8.17 (s, 1H), 7.61 (s, 1H), 7.49 (s, 1H), 4.14 (s, 3H), 3.60 (s, 3H), 2.62 (s, 3H), 2.39 (s, 3H). LC / MS (ESI) m / z: 507.2 [M+H] + .

[0446] Example 176: 2'-chloro-5'-methoxy-6-methyl-N-(6-(1-methyl-4-(methyl-d3)-1H-pyrazol-5-yl)thiazolo[4,5-c]pyridin-2-yl)-[4,4'-bipyridine]-3-formamide TIFF2025533951000240.tif44128

[0447] Step 1: 2-(2,5-dimethyl-1H-pyrrol-1-yl)-6-(4-iodo-1-methyl-1H-pyrazol-5-yl)thiazole[4,5-c]pyridine 6-(4-Iodo-1-methyl-1H-pyrazol-5-yl)thiazolo[4,5-c]pyridin-2-amine (602 mg, 1.69 mmol), acetonylacetone (482 mg, 4.2 mmol), and p-toluenesulfonic acid (58.1 mg, 3.4 mmol) were dissolved in anhydrous toluene (10 mL) and reacted at 120°C for 18 hours. The reaction mixture was concentrated under reduced pressure, and the resulting residue was purified by column chromatography (eluent: petroleum ether / ethyl acetate, gradient: 5%-25% ethyl acetate) to give the title compound (brown solid, 440 mg, yield: 60%). LC / MS (ESI) m / z: 436.1 [M+H] + .

[0448] Step 2: 2-(2,5-dimethyl-1H-pyrrol-1-yl)-6-(1-methyl-4-(methyl-d3)-1H-pyrazol-5-yl)thiazolo[4,5-c]pyridine 2-(2,5-Dimethyl-1H-pyrrol-1-yl)-6-(4-iodo-1-methyl-1H-pyrazol-5-yl)thiazole[4,5-c]pyridine (350 mg, 0.80 mmol) was dissolved in tetrahydrofuran (10 mL) and 1 mL N-methylpyrrolidone. Under nitrogen gas protection, iron acetylacetonate (56.5 mg, 0.16 mmol) was added, followed by the slow dropwise addition of 1 M / L deuterated methylmagnesium iodide (2.4 mL). The reaction mixture was allowed to react at room temperature for 2 hours. The reaction mixture was quenched with saturated ammonium chloride solution, extracted with ethyl acetate, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and the filtrate was centrifuged to dryness. The residue was purified by column chromatography (eluent: petroleum ether / ethyl acetate, gradient: 5% to 30% ethyl acetate) to give the crude title compound (brown solid, 50 mg, yield: 15.2%). LC / MS (ESI) m / z: 327.1 [M+H] + .

[0449] Step 3: 6-(1-methyl-4-(methyl-d3)-1H-pyrazol-5-yl)thiazole[4,5-c]pyridin-2-amine 2-(2,5-Dimethyl-1H-pyrrol-1-yl)-6-(1-methyl-4-(methyl-d3)-1H-pyrazol-5-yl)thiazolo[4,5-c]pyridine (40 mg, 0.12 mmol) was dissolved in 2M hydrochloric acid solution and reacted at 80°C for 1 hour. After completion of the reaction, the reaction solution was concentrated under reduced pressure to give the title compound (white solid, 30 mg, yield: 99%). LC / MS (ESI) m / z: 248.8 [M+H] + .

[0450] Step 4: 2'-chloro-5'-methoxy-6-methyl-N-(6-(1-methyl-4-(methyl-d3)-1H-pyrazol-5-yl)thiazolo[4,5-c]pyridin-2-yl)-[4,4'-bipyridine]-3-formamide 6-(1-Methyl-4-(methyl-d3)-1H-pyrazol-5-yl)thiazole[4,5-c]pyridin-2-amine (30 mg, 0.12 mmol) and 2'-chloro-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-carboxylic acid (34 mg, 0.12 mmol) were dissolved in acetonitrile (5 mL) and N,N-dimethylformamide (1 mL), 1-methylimidazole (39 mg, 0.48 mmol) was added, and the mixture was stirred at 70°C for 10 minutes. After that, N,N,N',N'-tetramethylformamidinium hexafluorophosphate (50 mg, 0.18 mmol) was added, and the mixture was reacted at 70°C for 1 hour. Ethyl acetate and water were added to the reaction mixture, followed by layer separation. The organic phase was washed with saturated sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The resulting residue was purified by preparative HPLC (eluent: acetonitrile / 0.1% aqueous formic acid solution, gradient: 25% to 90%) to give the title compound (white solid, 5.1 mg, yield: 8.3%). 1 H NMR (400 MHz, CDCl3) δ 8.93 (s, 1H), 8.86 (s, 1H), 8.07 (s, 1H), 7.85 (d, J = 0.8 Hz, 1H), 7.39 (s, 1H), 7.26 (s, 1H), 7.22 (s, 1H), 3.98 (s, 3H), 3.77 (s, 3H), 2.69 (s, 3H). LC / MS (ESI) m / z: 509.2 [M+H] +

[0451] Example 177: 2'-chloro-N-(6-(1,4-dimethyl-1H-pyrazol-5-yl)-5-methoxythiazolo[4,5-b]pyridin-2-yl)-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-formamide TIFF2025533951000241.tif71143

[0452] Step 1: 5-Bromo-6-methoxypyridin-2-amine To a solution of 2-amino-6-methoxypyridine (10.0 g, 80.55 mmol) in acetonitrile (80 mL) was added N-bromosuccinimide (7.17 g, 40.28 mmol), and the reaction mixture was stirred at room temperature for 1.5 hours. To the reaction mixture was added a solution of N-bromosuccinimide (7.17 g, 40.278 mmol) in acetonitrile (80 mL), and the reaction mixture was stirred at room temperature for 1.5 hours. After the reaction was complete, water was added, and the mixture was extracted with ethyl acetate, washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel chromatography (eluent: petroleum ether / ethyl acetate, gradient: 0-10% ethyl acetate) to give 5-bromo-6-methoxypyridin-2-amine (yellow solid, 7.5 g, yield: 45.8%). LC / MS (ESI) m / z: 203.0 [M+H] + .

[0453] Step 2: N-((5-bromo-6-methoxypyridin-2-yl)aminomethylthio)benzamide To a solution of 5-bromo-6-methoxypyridin-2-amine (7.50 g, 36.94 mmol) in acetone (80 mL) was added benzoyl isothiocyanate (9.04 g, 55.41 mmol). The mixture was stirred at room temperature under nitrogen gas protection for 2 hours. After completion of the reaction, the reaction mixture was filtered, and the filter cake was washed with acetone to give N-((5-bromo-6-methoxypyridin-2-yl)aminomethylthio)benzamide (yellow solid, 12.6 g, yield: 93.1%). LC / MS (ESI) m / z: 366.0 [M+H] + .

[0454] Step 3: 1-(5-bromo-6-methoxypyridin-2-yl)thiourea To a solution of sodium hydroxide (6.88 g, 172.0 mmol) in water (86 mL) was added N-((5-bromo-6-methoxypyridin-2-yl)aminomethylthio)benzamide (12.6 g, 34.40 mmol). The mixture was stirred at 100°C for 2 hours. After completion of the reaction, the reaction mixture was filtered, and the filter cake was washed with water to obtain 1-(5-bromo-6-methoxypyridin-2-yl)thiourea (yellow solid, 9.0 g, yield: 99.8%). LC / MS (ESI) m / z: 262.0 [M+H] + .

[0455] Step 4: 6-Bromo-5-methoxythiazolo[4,5-b]pyridin-2-amine To a solution of 1-(5-bromo-6-methoxypyridin-2-yl)thiourea (9.00 g, 34.33 mmol) in chloroform (90 mL) was added liquid bromide (3.5 mL, 68.66 mmol). The mixture was stirred at 60 °C for 12 hours. After the reaction was completed, the mixture was concentrated under reduced pressure. The residue was slurried in dichloromethane to give 6-bromo-5-methoxythiazolo[4,5-b]pyridin-2-amine (yellow solid, 6.0 g, yield: 67.2%). LC / MS (ESI) m / z: 260.0 [M+H] + .

[0456] Step 5: 6-Bromo-2-(2,5-dimethyl-1H-pyrrol-1-yl)-5-methoxythiazolo[4,5-b]pyridine To a solution of 6-bromo-5-methoxythiazolo[4,5-b]pyridin-2-amine (3.00 g, 11.53 mmol) in toluene (80 mL), 2,5-hexanedione (2.63 g, 23.07 mmol) and p-toluenesulfonic acid (0.20 g, 1.15 mmol) were added, and the reaction mixture was stirred at 120 °C for 12 hours. After completion of the reaction, water was added, and the mixture was extracted with ethyl acetate, washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel chromatography (eluent: petroleum ether / ethyl acetate, gradient: 0-30% ethyl acetate) to give 6-bromo-2-(2,5-dimethyl-1H-pyrrol-1-yl)-5-methoxythiazolo[4,5-b]pyridine (white solid, 0.5 g, yield: 12.8%). LC / MS (ESI) m / z: 338.1 [M+H] + .

[0457] Step 6: 6-(1,4-dimethyl-1H-pyrazol-5-yl)-2-(2,5-dimethyl-1H-pyrrol-1-yl)-5-methoxythiazolo[4,5-b]pyridine To a solution of 6-bromo-2-(2,5-dimethyl-1H-pyrrol-1-yl)-5-methoxythiazolo[4,5-b]pyridine (500.0 mg, 1.48 mmol) and 1,4-dimethylpyrazole-5-boronic acid pinacol ester (393.9 mg, 1.77 mmol) in 1,4-dioxane / water (50 mL / 10 mL) was added [1,1'-bis(di-tert-butylphosphino)ferrocene]palladium dichloride (95.5 mg, 0.15 mmol) and potassium phosphate (941.4 mg, 4.44 mmol). The reaction mixture was stirred at 90 °C under nitrogen gas protection for 4 hours. After completion of the reaction, the mixture was cooled to room temperature, water was added, and the mixture was extracted with ethyl acetate, washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel chromatography (eluent: petroleum ether / ethyl acetate, gradient: 20-60% ethyl acetate) to give 6-(1,4-dimethyl-1H-pyrazol-5-yl)-2-(2,5-dimethyl-1H-pyrrol-1-yl)-5-methoxythiazolo[4,5-b]pyridine (yellow solid, 330.0 mg, yield: 63.2%). LC / MS (ESI) m / z: 354.2 [M+H] + .

[0458] Step 7: 6-(1,4-dimethyl-1H-pyrazol-5-yl)-5-methoxythiazole[4,5-b]pyridin-2-amine 6-(1,4-dimethyl-1H-pyrazol-5-yl)-2-(2,5-dimethyl-1H-pyrrol-1-yl)-5-methoxythiazolo[4,5-b]pyridine (200 mg, 0.566 mmol) was added to a hydrochloric acid solution (2.0 M, 10 mL) and stirred at 90°C for 1 hour. After completion of the reaction, the reaction mixture was concentrated under reduced pressure, and the resulting crude product, 6-(1,4-dimethyl-1H-pyrazol-5-yl)-5-methoxythiazolo[4,5-b]pyridin-2-amine (yellow solid, 150.0 mg, yield: 96.3%), was directly used in the next step. LC / MS (ESI) m / z: 276.1 [M+H] + .

[0459] Step 8: 2'-chloro-N-(6-(1,4-dimethyl-1H-pyrazol-5-yl)-5-methoxythiazolo[4,5-b]pyridin-2-yl)-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-formamide 6-(1,4-Dimethyl-1H-pyrazol-5-yl)-5-methoxythiazole[4,5-b]pyridin-2-amine (150 mg, 0.545 mmol), 2'-chloro-5'-methoxy-[3,4'-bipyridine]-4-carboxylic acid (151.83 mg, 0.545 mmol), N,N,N',N'-tetramethylformamidinium hexafluorophosphate (152.86 mg, 0.545 mmol), and 1-methylimidazole (134.20 mg, 1.634 mmol) were dissolved in acetonitrile (20 mL), and the reaction mixture was stirred at 70 °C for 4 hours. After completion of the reaction, the reaction mixture was concentrated under reduced pressure, and the resulting residue was purified by preparative HPLC to obtain 2'-chloro-N-(6-(1,4-dimethyl-1H-pyrazol-5-yl)-5-methoxythiazolo[4,5-b]pyridin-2-yl)-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-formamide (white solid, 193.6 mg, yield: 66.3%). 1 H NMR (400 MHz, DMSO-d6) δ 13.16 (s, 1H), 8.86 (s, 1H), 8.32 (s, 1H), 8.17 (s, 1H), 7.60 (s, 1H), 7.49 (s, 1H), 7.32 (s, 1H), 3.95 (s, 3H), 3.61 (s, 3H), 3.59 (s, 3H), 2.62 (s, 3H), 1.88 (s, 3H).LC / MS (ESI) m / z: 536.1 [M+H] + .

[0460] Example 178: 2'-chloro-N-(6-(1,4-dimethyl-1H-pyrazol-5-yl)-5-oxo-4,5-dihydrothiazol[4,5-b]pyridin-2-yl)-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-formamide TIFF2025533951000242.tif291102'-Chloro-N-(6-(1,4-dimethyl-1H-pyrazol-5-yl)-5-methoxythiazolo[4,5-b]pyridin-2-yl)-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-formamide (100 mg, 0.187 mmol) was added to a hydrogen bromide solution (10 mL, 33% wt. in acetic acid) and stirred at 50°C for 2 hours. After completion of the reaction, the reaction mixture was concentrated under reduced pressure, and the resulting residue was purified by preparative HPLC to obtain 2'-chloro-N-(6-(1,4-dimethyl-1H-pyrazol-5-yl)-5-oxo-4,5-dihydrothiazole[4,5-b]pyridin-2-yl)-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-formamide (white solid, 60.0 mg, yield: 61.6%). 1 H NMR (400 MHz, DMSO-d6) δ 13.35 (s, 1H), 8.90 (s, 1H), 8.19 (s, 1H), 8.10 (s, 1H), 7.60 (s, 1H), 7.57 (s, 1H), 7.31 (s, 1H), 3.64 (s, 3H), 3.62 (s, 3H), 2.64 (s, 3H), 1.91 (s, 3H).LC / MS (ESI) m / z: 522.1 [M+H] + .

[0461] Example 179: 2'-chloro-N-(6-(1,4-dimethyl-1H-pyrazol-5-yl)-4-oxo-4,5-dihydrothiazol[4,5-c]pyridin-2-yl)-5'-methoxy-6-methyl-[4,4'-bipyridine]-3-formamide TIFF2025533951000243.tif67143

[0462] Step 1: 6-Bromo-4-chloro-2-...

Claims

1. Wherein: m is 0, 1, 2 or 3, and n is 1, 2 or 3; L is Ring A is a 6- to 12-membered aryl ring or a 5- to 12-membered heteroaryl ring, and the heteroatom in the 5- to 12-membered heteroaryl ring is one or more of N, O, and S, and the number of heteroatoms is 1, 2, or 3; R 1 is unsubstituted or one or more R 1-1 a 6-12 membered aryl group substituted by, or unsubstituted or one or more R 1-2 wherein the heteroatoms in the 5-12 membered heteroaryl group are one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3; Each R 1-1 and R 1-2 are independently deuterium, halogen, cyano, amino, hydroxy, unsubstituted or one or more R 1-1-1 C is replaced by 1 -C 6 Alkyl group, unsubstituted or one or more R 1-1-2 C is replaced by 1 -C 6 Alkoxy group, unsubstituted or one or more R 1-1-3 C is replaced by 2 -C 6 Alkenyl group, unsubstituted or with one or more R 1-1-4 C is replaced by 2 -C 6 Alkynyl group, unsubstituted or with one or more R 1-1-5 a 3-6 membered cycloalkyl group, unsubstituted or substituted by one or more R 1-1-6 a 4-6 membered heterocyclyl group substituted by -COOR 1-1-7 , -C(O)R 1-1-8 , -C(O)NR 1-1-9 R 1-1-9 , wherein the heteroatoms in the 4- to 6-membered heterocyclyl group are selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3; Each R 1-1-1 , R 1-1-2 , R 1-1-3 , R 1-1-4 , R 1-1-5 and R 1-1-6 are independently deuterium, a hydroxy group, a cyano group, or a halogen; Each R 1-1-7 , R 1-1-8 and R 1-1-9 are independently hydrogen or C 1 -C 6 is an alkyl group, Each R 1-1-10 and R 1-1-11 are independently a hydroxy group or C 1 -C 6 is an alkyl group, Each R 2 independently Deuterium, halogen, cyano group, amino group, hydroxy group, unsubstituted or one or more R 2-1 C is replaced by 1 -C 6 Alkyl group, unsubstituted or one or more R 2-2 C is replaced by 1 -C 6 Alkoxy group, unsubstituted or one or more R 2-3 C is replaced by 2 -C 6 Alkenyl group, unsubstituted or with one or more R 2-4 C is replaced by 2 -C 6 Alkynyl group, unsubstituted or with one or more R 2-5 a 3- to 6-membered cycloalkyl group substituted by, or unsubstituted or substituted by one or more R 2-6 wherein the heteroatoms in the 4-6 membered heterocyclyl group are selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3; Each R 2-1 , R 2-2 , R 2-3 , R 2-4 , R 2-5 and R 2-6 are independently deuterium, a hydroxy group, a cyano group, or a halogen; Ring B may be unsubstituted or may contain one or more R b-1 wherein the heteroatoms in the 5-20 membered fused ring heteroaryl ring are selected from one or more of N, O and S, and the number of heteroatoms is 1, 2, 3, 4, 5, 6, 7 or 8; the single heteroaryl ring in the 5-20 membered fused ring heteroaryl ring is a 5-7 membered heteroaryl ring, and the number of rings in the 5-20 membered fused ring heteroaryl ring is 2, 3 or 4; Each R b-1 are independently deuterium, oxo (=O), halogen, cyano, hydroxy, unsubstituted or one or more R b-1-1 C is replaced by 1 -C 6 Alkyl group, unsubstituted or one or more R b-1-2 C is replaced by 1 -C 6 Alkoxy group, -NR b-1-3 R b-1-3 , -C(O)NR b-1-4 R b-1-4 , -COOR b-1-5 , Each R b-1-1 and R b-1-2 are independently a hydroxy group, a halogen, or -NR b-1-1-1 R b-1-1-1 and Each R b-1-3 , R b-1-4 , R b-1-5 and R b-1-7 are independently hydrogen or C 1 -C 6 is an alkyl group, Each R b-1-6 are independently a hydroxy group or C 1 -C 6 is an alkyl group, Each R b-1-1-1 are independently hydrogen, C 1 -C 6 Alkyl group or -C(O)R b-1-1-1-1 and R b-1-1-1-1 is C 1 -C 6 is an alkyl group, R 3 is hydrogen, Unsubstituted or one or more R 3-1 a 3- to 12-membered cycloalkyl group, unsubstituted or substituted by one or more R 3-2 a 4-12 membered heterocyclyl group, unsubstituted or substituted by one or more R 3-3 a 4-12 membered cycloalkenyl group, unsubstituted or substituted by one or more R 3-4 a 4-12 membered heterocycloalkenyl group, unsubstituted or substituted by one or more R 3-5 a 6-10 membered aryl group, unsubstituted or substituted by one or more R 3-6 a 5-10 membered heteroaryl group substituted by -C(O)R 4 , -NH(CH 2 ) p R 5 , -O(CH 2 ) q R 6 , unsubstituted or one or more R 3-7 C is replaced by 1 -C 6 alkyl group, or unsubstituted or one or more R 3-8 -OR is replaced by 7 wherein the heteroatoms in the 4- to 12-membered heterocyclyl group, the 4- to 12-membered heterocycloalkenyl group, and the 5- to 10-membered heteroaryl group are selected from one or more of N, O, and S, and the number of heteroatoms is 1, 2, 3, or 4; p is 0, 1, 2 or 3; q is 1, 2 or 3; Each R 3-1 , R 3-2 , R 3-3 , R 3-4 , R 3-7 and R 3-8 are independently deuterium, hydroxyl group, halogen, cyano group, amino group, -NHC(O)R 3-2-1 , unsubstituted or one or more R 3-2-2 C is replaced by 1 -C 6 Alkyl group, C 1 -C 6 Alkoxy group, C 2 -C 6 Alkenyl group, C 2 -C 6 Alkynyl group, oxo group (=O), -C(O)NH 2 , unsubstituted or one or more R 3-2-3 a 3- to 6-membered cycloalkyl group, a 4- to 6-membered heterocyclyl group, -S(O) 2 R 3-4-1 , -NR 3-4-2 R 3-4-2 , wherein the heteroatoms in the 4- to 6-membered heterocyclyl group are selected from one or more of N, O and S, and the number of heteroatoms is 1 or 2; Each R 3-5 and R 3-6 are independently deuterium, Hydroxy group, halogen, cyano group, amino group, -NHC(O)R 3-2-1 , unsubstituted or one or more R 3-2-2 C is replaced by 1 -C 6 Alkyl group, C 2 -C 6 Alkenyl group, C 2 -C 6 Alkynyl group, -C(O)NH 2 , unsubstituted or one or more R 3-2-3 a 3-6 membered cycloalkyl group, unsubstituted or substituted by one or more R 3-6-1 4-6 membered heterocyclyl groups substituted by -S(O) 2 R 3-4-1 , -NR 3-4-2 R 3-4-2 , wherein the heteroatoms in the 4- to 6-membered heterocyclyl group are selected from one or more of N, O and S, and the number of heteroatoms is 1 or 2; Each R 3-2-1 and R 3-4-2 are independently hydrogen, -S(O) 2 R 3-4-1 , unsubstituted or one or more R 3-2-1-1 3-6 membered cycloalkyl group substituted by or C 1 -C 6 is an alkyl group, Each R 3-2-1-1 independently C 1 -C 6 is an alkyl group, Each R 3-2-3 and R 3-5-1 are independently a hydroxy group or C 1 -C 6 is an alkyl group, Each R 3-5-2 are independently a hydroxy group, C 1 -C 6 alkyl group or 1-10 membered heteroalkyl group, or two R 3-5-2 form a 5-10 membered heterocyclyl group, wherein the heteroatoms in the 1-10 membered heteroalkyl group include, in addition to phosphorus, any one or more selected from N, O and S, and the number of heteroatoms is 1, 2, 3 or 4; the heteroatoms in the 5-10 membered heterocyclyl group include, in addition to phosphorus, any one or more selected from N, O and S, and the number of heteroatoms is 1, 2, 3 or 4; Each R 3-6-1 independently C 1 -C 6 is an alkyl group, Each R 3-2-2 are independently deuterium, hydroxyl, or halogen (e.g., each R 3-2-2 are independently a hydroxy group or a halogen; R 3-4-1 is a hydroxy group, an amino group or C 1 -C 6 is an alkyl group, R 3-9 is C 1 -C 6 is an alkyl group, R 4 is unsubstituted or one or more R 4-1 wherein the heteroatoms in the 4-6 membered heterocyclyl group are selected from one or more of N, O and S, and the number of heteroatoms is 1 or 2; Each R 4-1 are independently a hydroxy group, R 5 is unsubstituted or one or more R 5-1 3-6 membered cycloalkyl groups substituted by -S(O) 2 R 5-2 , unsubstituted or one or more R 5-3 wherein the heteroatoms in the 4-6 membered heterocyclyl group are selected from one or more of N, O and S, and the number of heteroatoms is 1 or 2; R 5-2 is C 1 -C 6 is an alkyl group, Each R 5-3 are independently -S(O) 2 R 5-3-1 and each R 5-3-1 independently C 1 -C 6 is an alkyl group, R 6 is unsubstituted or one or more R 6-1 is a 3- to 6-membered cycloalkyl group substituted by Each R 5-1 and R 6-1 are independently a hydroxy group, R 7 is a 3- to 6-membered cycloalkyl group, a pharmaceutically acceptable salt thereof, or an isotopic compound thereof.

2. m is 0, 1, 2 or 3, and n is 1, 2 or 3; L is Ring A is a 6- to 12-membered aryl ring or a 5- to 12-membered heteroaryl ring, wherein the heteroatom in the 5- to 12-membered heteroaryl ring is selected from one or more of N, O, and S, and the number of heteroatoms is 1, 2, or 3; R 1 is unsubstituted or one or more R 1-1 a 6-12 membered aryl group substituted by, or unsubstituted or one or more R 1-2 wherein the heteroatoms in the 5-12 membered heteroaryl group are selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3; Each R 1-1 and R 1-2 are independently deuterium, halogen, cyano, amino, hydroxy, unsubstituted or one or more R 1-1-1 C is replaced by 1 -C 6 Alkyl group, unsubstituted or one or more R 1-1-2 C is replaced by 1 -C 6 Alkoxy group, unsubstituted or one or more R 1-1-3 C is replaced by 2 -C 6 Alkenyl group, unsubstituted or with one or more R 1-1-4 C is replaced by 2 -C 6 Alkynyl group, unsubstituted or with one or more R 1-1-5 a 3-6 membered cycloalkyl group, unsubstituted or substituted by one or more R 1-1-6 a 4-6 membered heterocyclyl group substituted by -COOR 1-1-7 , -C(O)R 1-1-8 , -C(O)NR 1-1-9 R 1-1-9 , wherein the heteroatoms in the 4- to 6-membered heterocyclyl group are selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3; Each R 1-1-1 , R 1-1-2 , R 1-1-3 , R 1-1-4 , R 1-1-5 and R 1-1-6 are independently deuterium, a hydroxy group, a cyano group, or a halogen; Each R 1-1-7 , R 1-1-8 and R 1-1-9 are independently hydrogen or C 1 -C 6 is an alkyl group, Each R 1-1-10 and R 1-1-11 are independently a hydroxy group or C 1 -C 6 is an alkyl group, Each R 2 are independently deuterium, halogen, cyano, amino, hydroxy, unsubstituted or one or more R 2-1 C is replaced by 1 -C 6 Alkyl group, unsubstituted or one or more R 2-2 C is replaced by 1 -C 6 Alkoxy group, unsubstituted or one or more R 2-3 C is replaced by 2 -C 6 Alkenyl group, unsubstituted or with one or more R 2-4 C is replaced by 2 -C 6 Alkynyl group, unsubstituted or with one or more R 2-5 a 3- to 6-membered cycloalkyl group substituted by, or unsubstituted or substituted by one or more R 2-6 wherein the heteroatoms in the 4-6 membered heterocyclyl group are selected from one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3; Each R 2-1 , R 2-2 , R 2-3 , R 2-4 , R 2-5 and R 2-6 are independently deuterium, a hydroxy group, a cyano group, or a halogen; Ring B may be unsubstituted or may contain one or more R b-1 a 5- to 20-membered fused-ring heteroaryl ring substituted by: wherein the heteroatoms in said 5- to 20-membered fused-ring heteroaryl ring are selected from one or more of N, O and S, and the number of heteroatoms is 1, 2, 3, 4, 5 or 6; wherein the single heteroaryl ring in said 5- to 20-membered fused-ring heteroaryl ring is a 5- to 7-membered heteroaryl ring; and wherein the number of rings in said 5- to 20-membered fused-ring heteroaryl ring is 2, 3 or 4; Each R b-1 are independently deuterium, oxo (=O), halogen, cyano, hydroxy, unsubstituted or one or more R b-1-1 C is replaced by 1 -C 6 Alkyl group, unsubstituted or one or more R b-1-2 C is replaced by 1 -C 6 Alkoxy group, -NR b-1-3 R b-1-3 , -C(O)NR b-1-4 R b-1-4 , -COOR b-1-5 , Each R b-1-1 and R b-1-2 are independently a hydroxy group, a halogen, or -NR b-1-1-1 R b-1-1-1 and Each R b-1-3 , R b-1-4 , R b-1-5 and R b-1-7 are independently hydrogen or C 1 -C 6 is an alkyl group, Each R b-1-6 are independently a hydroxy group or C 1 -C 6 is an alkyl group, Each R b-1-1-1 are independently hydrogen, C 1 -C 6 Alkyl group or -C(O)R b-1-1-1-1 and R b-1-1-1-1 is C 1 -C 6 is an alkyl group, R 3 is hydrogen, unsubstituted or one or more R 3-1 a 3- to 12-membered cycloalkyl group, unsubstituted or substituted by one or more R 3-2 a 4-12 membered heterocyclyl group, unsubstituted or substituted by one or more R 3-3 a 4-12 membered cycloalkenyl group, unsubstituted or substituted by one or more R 3-4 a 4-12 membered heterocycloalkenyl group, unsubstituted or substituted by one or more R 3-5 a 6-10 membered aryl group, unsubstituted or substituted by one or more R 3-6 a 5-10 membered heteroaryl group substituted by -C(O)R 4 , -NH(CH 2 ) p R 5 , -O(CH 2 ) q R 6 , unsubstituted or one or more R 3-7 C is replaced by 1 -C 6 alkyl group, or unsubstituted or one or more R 3-8 -OR is replaced by 7 wherein the heteroatoms in the 4- to 12-membered heterocyclyl group, the 4- to 12-membered heterocycloalkenyl group, and the 5- to 10-membered heteroaryl group are selected from one or more of N, O, and S, and the number of heteroatoms is 1, 2, 3, or 4; p is 0, 1, 2 or 3; q is 1, 2 or 3; Each R 3-1 , R 3-2 , R 3-3 , R 3-4 , R 3-7 and R 3-8 are independently deuterium, hydroxyl group, halogen, cyano group, -NHC(O)R 3-2-1 , unsubstituted or one or more R 3-2-2 C is replaced by 1 -C 6 Alkyl group, C 2 -C 6 Alkenyl group, C 2 -C 6 Alkynyl group, oxo group (=O), -C(O)NH 2 , unsubstituted or one or more R 3-2-3 a 3- to 6-membered cycloalkyl group, a 4- to 6-membered heterocyclyl group, -S(O) 2 R 3-4-1 , -NR 3-4-2 R 3-4-2 , wherein the heteroatoms in the 4- to 6-membered heterocyclyl group are selected from one or more of N, O and S, and the number of heteroatoms is 1 or 2; Each R 3-5 and R 3-6 are independently deuterium, hydroxyl group, halogen, cyano group, amino group, -NHC(O)R 3-2-1 , unsubstituted or one or more R 3-2-2 C is replaced by 1 -C 6 Alkyl group, C 2 -C 6 Alkenyl group, C 2 -C 6 Alkynyl group, -C(O)NH 2 , unsubstituted or one or more R 3-2-3 a 3- to 6-membered cycloalkyl group, a 4- to 6-membered heterocyclyl group, -S(O) 2 R 3-4-1 , -NR 3-4-2 R 3-4-2 , wherein the heteroatoms in the 4- to 6-membered heterocyclyl group are selected from one or more of N, O and S, and the number of heteroatoms is 1 or 2; Each R 3-2-1 and R 3-4-2 are independently hydrogen or C 1 -C 6 is an alkyl group, Each R 3-2-3 , R 3-5-1 and R 3-5-2 are independently a hydroxy group or C 1 -C 6 is an alkyl group, Each R 3-2-2 are independently a hydroxy group or a halogen; R 3-4-1 is a hydroxy group, an amino group or C 1 -C 6 is an alkyl group, R 4 is a 4- to 6-membered heterocyclyl group, wherein the heteroatoms in the 4- to 6-membered heterocyclyl group are selected from one or more of N, O and S, and the number of heteroatoms is 1 or 2; R 5 is unsubstituted or one or more R 5-1 is a 3- to 6-membered cycloalkyl group substituted by R 6 is unsubstituted or one or more R 6-1 is a 3- to 6-membered cycloalkyl group substituted by Each R 5-1 and R 6-1 are independently a hydroxy group, R 7 The compound of formula I according to claim 1, a pharmaceutically acceptable salt thereof or an isotope thereof, wherein is a 3- to 6-membered cycloalkyl group.

3. The compound represented by formula I according to claim 1, characterized in that the compound represented by formula I' is a compound represented by formula I', a pharmaceutically acceptable salt thereof, or an isotope thereof:

4. The compound represented by formula I according to claim 1, a pharmaceutically acceptable salt thereof, or an isotope thereof, is characterized in that the compound represented by formula I satisfies one or more of the following conditions: (1) In ring A, the 5- to 12-membered heteroaryl ring may be a 5- to 10-membered heteroaryl ring, and the heteroatom in the 5- to 10-membered heteroaryl ring may be selected from any one or two of N, O, and S. Preferably, the 5- to 10-membered heteroaryl ring is a 5- to 6-membered heteroaryl ring, a 5,6-heteroaryl ring, or a 6,6-heteroaryl ring, and preferably, (2) R 1 wherein the 6-12 membered aryl group may be a 6-10 membered aryl group, and may also be a phenyl group or a naphthalene group, for example, a phenyl group; (3) R 1 In the above, the 5-12 membered heteroaryl group may be a 5-10 membered heteroaryl group, the heteroatom in the 5-10 membered heteroaryl group may be N and / or O, and the number of heteroatoms may be 1 or 2, preferably, the 5-12 membered heteroaryl group is a 5-6 membered heteroaryl group or a 5,6-heteroaryl group, preferably, particularly preferably, (4) Each R 1-1 wherein the halogen is fluorine, chlorine, bromine or iodine, for example, fluorine; (5) Each R 1-1 In the above, C 1 -C 6 Alkyl groups are C 1 -C 4 is an alkyl group, which may be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group, or a tert-butyl group; (6) Each R 1-1 In the above, C 1 -C 6 The alkoxy group is C 1 -C 4 an alkoxy group, which may be a methoxy group, an ethoxy group, an n-propoxy group, an isopropoxy group, an n-butoxy group, an isobutoxy group, a primary butoxy group, a sec-butoxy group, or a tert-butoxy group, for example a methoxy group; (7) Each R 1-2 wherein the halogen is fluorine, chlorine, bromine or iodine, for example, fluorine or chlorine; (8) Each R 1-2 In the above, C 1 -C 6 The alkyl group is C 1 -C 4 an alkyl group, which may be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, preferably a methyl group; (9) Each R 1-2 In the above, C 1 -C 6 The alkoxy group is C 1 -C 4 an alkoxy group, which may be a methoxy group, an ethoxy group, an n-propoxy group, an isopropoxy group, an n-butoxy group, an isobutoxy group, a primary butoxy group, a sec-butoxy group, or a tert-butoxy group, for example a methoxy group; (10) Each R 1-1-1 wherein the halogen is fluorine, chlorine, bromine or iodine, preferably fluorine; (11) Each R 1-1-2 wherein the halogen is fluorine, chlorine, bromine or iodine, for example, fluorine; (12) Each R 2 In the above, C 1 -C 6 The alkyl group is C 1 -C 4 is an alkyl group, which may be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group, or a tert-butyl group, for example, a methyl group; (13) In ring B, the number of heteroatoms in the 5- to 20-membered fused heteroaryl ring is 1, 2, 3, or 4, and the 5- to 20-membered fused heteroaryl ring is preferably a 5,5-heteroaryl ring, a 5,6-heteroaryl ring, a 6,6-heteroaryl ring, a 5,6,6,6-heteroaryl ring, or a 5,6,7,6-heteroaryl ring, and particularly preferably (14) Each R b-1 wherein the halogen is fluorine, chlorine, bromine or iodine, for example, fluorine; (15) Each R b-1 In the above, C 1 -C 6 The alkyl group is C 1 -C 4 is an alkyl group, which may be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group, or a tert-butyl group, for example, a methyl group; (16) Each R b-1 In the above, C 1 -C 6 The alkoxy group is C 1 -C 4 an alkoxy group, which may be a methoxy group, an ethoxy group, an n-propoxy group, an isopropoxy group, an n-butoxy group, an isobutoxy group, a primary butoxy group, a sec-butoxy group, or a tert-butoxy group, for example a methoxy group or an ethoxy group; (17) Each R b-1-1 wherein the halogen is fluorine, chlorine, bromine or iodine; (18) Each R b-1-2 wherein the halogen is fluorine, chlorine, bromine or iodine; (19) Each R b-1-2-1 In the above, C 1 -C 6 The alkyl group is C 1 -C 4 an alkyl group, which may be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, preferably a methyl group; (20) R 3 wherein the 3- to 12-membered cycloalkyl group is a 3- to 6-membered cycloalkyl group, which may be a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, or a cyclohexyl group, and is preferably a cyclobutyl group or a cyclohexyl group, for example, a cyclohexyl group; (21) R 3 In the above, the ring in the 4-12-membered heterocyclyl group is a monocycle, a spiro ring, a fused ring or a bridged ring, and the number of rings in the spiro ring, the fused ring or the bridged ring may be two, and the spiro ring may be a 3-membered spiro 5-membered heterocyclyl group, a 3-membered spiro 6-membered heterocyclyl group, a 4-membered spiro 5-membered heterocyclyl group, a 4-membered spiro 6-membered heterocyclyl group, a 4-membered spiro 4-membered heterocyclyl group, a 4-membered spiro 7-membered heterocyclyl group, a 5-membered spiro 4-membered heterocyclyl group, a 5-membered spiro 7-membered heterocyclyl group, a 5-membered spiro 5-membered heterocyclyl group, a The fused ring may be a 3,5-heterocyclyl group, a 4,5-heterocyclyl group, or a 5,5-heterocyclyl group, the bridged ring may be a 5-membered bridged 6-membered heterocyclyl group, the number of heteroatoms in the 4-12 membered heterocyclyl group may be 1 or 2, preferably the single ring is a 4-7 membered heterocyclyl group, the number of heteroatoms may be 1 or 2, preferably the heteroatom is N and / or O, preferably (22) R 3 wherein the ring in the 4-10-membered cycloalkenyl group is a monocycle, a spiro ring, a fused ring or a bridged ring, the number of rings in the spiro ring, the fused ring or the bridged ring may be two, the spiro ring may be a 4-membered spiro 4-membered cycloalkenyl group, a 4-membered spiro 5-membered cycloalkenyl group or a 4-membered spiro 6-membered cycloalkenyl group, the fused ring may be a 5,5-cycloalkenyl group or a 5,6-cycloalkenyl group, and the bridged ring may be a 5-membered bridged 7-membered cycloalkenyl group, preferably (23) R 3 In the above, the ring in the 4- to 10-membered heterocycloalkenyl group is a monocycle or a spiro ring, the number of rings in the spiro ring may be 2, the spiro ring may be a 4-membered spiro 4-membered heterocycloalkenyl group, a 4-membered spiro 5-membered heterocycloalkenyl group or a 4-membered spiro 6-membered heterocycloalkenyl group, the number of heteroatoms in the 4- to 10-membered heterocycloalkenyl group may be 1, and preferably (24) R 3 wherein the 6- to 10-membered aryl group is an aryl group or a naphthalene group, preferably an aryl group; (25) R 3 wherein the 5-10 membered heteroaryl group is a single ring or fused ring heteroaryl group, the number of rings in the fused ring may be 2, the fused ring may be a 5,5-heteroaryl group or a 5,6-heteroaryl group, the heteroatom in the 5-10 membered heteroaryl group may be N and / or O, the number of heteroatoms may be 1, and preferably (26) R 3 In the above, C 1 -C 6 The alkyl group is C 1 -C 4 an alkyl group, which may be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, preferably a methyl group or an isopropyl group, for example a methyl group; (27) Each R 3-1 wherein the halogen is fluorine, chlorine, bromine or iodine, preferably fluorine; (28) Each R 3-1 In the above, C 1 -C 6 The alkyl group is C 1 -C 4 an alkyl group, which may be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, preferably a methyl group; (29) Each R 3-2 wherein the halogen is fluorine, chlorine, bromine or iodine, for example, fluorine; (30) Each R 3-2 In the above, C 1 -C 6 The alkyl group is C 1 -C 4 an alkyl group, which may be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, preferably a methyl group or an isopropyl group, for example a methyl group; (31) Each R 3-2 In the above, C 2 -C 6 The alkenyl group is C 2 -C 4 is an alkenyl group, (32) Each R 3-2 In the above, C 2 -C 6 The alkynyl group is C 2 -C 4 is an alkynyl group, (33) Each R 3-2 wherein the 3- to 6-membered cycloalkyl group is a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, or a cyclohexyl group, and preferably a cyclobutyl group; (34) Each R 3-2 In the above, the number of heteroatoms in the 4- to 6-membered heterocyclyl group may be 1 or 2, and preferably, (35) R 3-2-1 In the above, C 1 -C 6 The alkyl group is C 1 -C 4 an alkyl group, which may be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, preferably a methyl group; (36) Each R 3-2-2 wherein the halogen is fluorine, chlorine, bromine or iodine, preferably fluorine; (37) Each R 3-2-3 In the above, C 1 -C 6 The alkyl group is C 1 -C 4 an alkyl group, which may be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, preferably a methyl group; (38) Each R 3-3 wherein the halogen is fluorine, chlorine, bromine or iodine, preferably fluorine; (39) Each R 3-4 In the above, C 1 -C 6 The alkyl group is C 1 -C 4 an alkyl group, which may be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, preferably a methyl group; (40) Each R 3-4 wherein the halogen is fluorine, chlorine, bromine or iodine; (41) Each R 3-4 wherein the number of heteroatoms in the 4- to 6-membered heterocyclyl group may be 1 or 2; (42) R 3-4-1 In the above, C 1 -C 6 The alkyl group is C 1 -C 4 an alkyl group, which may be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, preferably a methyl group; (43) Each R 3-4-2 In the above, C 1 -C 6 The alkyl group is C 1 -C 4 an alkyl group, which may be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, preferably a methyl group; (44) R 3-5-1 In the above, C 1 -C 6 The alkyl group is C 1 -C 4 an alkyl group, which may be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, preferably a methyl group; (45) Each R 3-6 wherein the halogen is fluorine, chlorine, bromine or iodine, preferably chlorine; (46) Each R 3-6 In the above, C 1 -C 6 The alkyl group is C 1 -C 4 an alkyl group, which may be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, preferably a methyl group; (47) Each R 3-7 wherein the halogen is fluorine, chlorine, bromine or iodine; (48) Each R 3-7 wherein the number of heteroatoms in the 4- to 6-membered heterocyclyl group may be 1 or 2; (49) R 4 wherein the number of heteroatoms in the 4- to 6-membered heterocyclyl group may be 1 or 2; (50) R 5 wherein the 3- to 6-membered cycloalkyl group is a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, or a cyclohexyl group, and preferably a cyclobutyl group; (51) R 6 wherein the 3- to 6-membered cycloalkyl group is a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, or a cyclohexyl group, and preferably a cyclohexyl group; (52) R 7 wherein the 3- to 6-membered cycloalkyl group is a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, or a cyclohexyl group, and preferably a cyclohexyl group; (53) Each R 3-2-1-1 In the above, C 1 -C 6 The alkyl group is C 1 -C 4 an alkyl group, which may be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, preferably a methyl group; (54) Each R 3-6-1 In the above, C 1 -C 6 The alkyl group is C 1 -C 4 an alkyl group, which may be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, preferably a methyl group; (55) Each R 3-9 In the above, C 1 -C 6 The alkyl group is C 1 -C 4 an alkyl group, which may be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, preferably a methyl group; (56) R 5 In the above, the heteroatom in the 4- to 6-membered heterocyclyl group is selected from one or more of N, O and S, and the number of heteroatoms can be 1 or 2, for example, (57) Each R 5-2 In the above, C 1 -C 6 The alkyl group is C 1 -C 4 an alkyl group, which may be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, preferably a methyl group; (58) Each R 5-3-1 In the above, C 1 -C 6 The alkyl group is C 1 -C 4 an alkyl group, which may be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, preferably a methyl group; (59) R 3-5-2 In the above, C 1 -C 6 The alkyl group is C 1 -C 4 may be an alkyl group, and may be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, and is preferably a methyl group or an ethyl group; (60) R 3-5-2 wherein the 1-10 membered heteroalkyl group may be a 1-4 membered heteroalkyl group; (61) R 3-5-2 wherein the heteroatoms in the 1-10 membered heteroalkyl group include, in addition to phosphorus, those selected from N and / or O; (62) R 3-5-2 wherein the 1-10 membered heteroalkyl group has 3 heteroatoms; (63) R 3-5-2 wherein the 4-10 membered heterocyclyl group can be a 4-8 membered heteroalkyl group, for example: (64) R 3-5-2 wherein the heteroatoms in the 4- to 10-membered heterocyclyl group include, in addition to phosphorus, those selected from N and / or O; (65) R 3-5-2 wherein the 4- to 10-membered heterocyclyl group has 1 or 3 heteroatoms; (66) R 3 wherein the 3- to 12-membered cycloalkyl group is a 7- to 10-membered cycloalkyl group, a ring in the 7- to 10-membered cycloalkyl group may be a spiro ring, a fused ring or a bridged ring, the number of rings in the spiro ring, the fused ring or the bridged ring may be 2, the spiro ring may be a 4-membered spiro 4-membered cycloalkyl group, a 4-membered spiro 5-membered cycloalkyl group or a 4-membered spiro 6-membered cycloalkyl group, the fused ring may be a 5,5-cycloalkyl group or a 5,6-cycloalkyl group, and the bridged ring may be a 5-membered bridged 7-membered cycloalkyl group, preferably (67) The pharmaceutically acceptable salt is a trifluorohydrochloride or formate; (68) Each R 2 wherein the halogen may be fluorine, chlorine, bromine or iodine, for example fluorine; (69) Each R b-1-4 and R b-1-5 In the above, C 1 -C 6 The alkyl group is C 1 -C 4 may be an alkyl group, and may also be a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a primary butyl group, a sec-butyl group or a tert-butyl group, and is preferably a methyl group; (70) R 3 wherein the heteroatom in the 5-10 membered heteroaryl group may be N, and the number of heteroatoms may be 1, 2 or 3; (71) Each R 3-6 In the above, the heteroatom in the 4- to 6-membered heterocyclyl group may be selected from N, and the number of heteroatoms may be 1 or 2, for example, and (72) each R 3-6 In the formula (I), the 3- to 6-membered cycloalkyl group can be a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, or a cyclohexyl group, and is preferably a cyclopropyl group.

5. The compound of formula I according to any one of claims 1 to 4, its pharmaceutically acceptable salt or isotope thereof, is characterized in that the compound of formula I satisfies one or more of the following conditions: (1) Ring A is a 5- to 12-membered heteroaryl ring, preferably a 5- to 10-membered heteroaryl ring, in which the heteroatom in the 5- to 10-membered heteroaryl ring is N, and the number of heteroatoms is 1 or 2; (2) R 1 is unsubstituted or one or more R 1-1 or a phenyl group substituted with one or more R 1-2 wherein the heteroatoms in the 5-10 membered heteroaryl group are N and / or O, and the number of heteroatoms is 1 or 2; (3) Each R 1-1 are independently deuterium, halogen, cyano, amino, unsubstituted or one or more R 1-1-1 C is replaced by 1 -C 6 alkyl group, or unsubstituted or one or more R 1-1-2 C is replaced by 1 -C 6 is an alkoxy group, and preferably, each R 1-1 are independently halogen, or unsubstituted or one or more R 1-1-2 C is replaced by 1 -C 6 is an alkoxy group, (4) Each R 1-2 are independently deuterium, halogen, cyano, amino, unsubstituted or one or more R 1-1-1 C is replaced by 1 -C 6 alkyl group, or unsubstituted or one or more R 1-1-2 C is replaced by 1 -C 6 is an alkoxy group, and preferably, each R 1-2 are independently deuterium, halogen, unsubstituted or one or more R 1-1-1 C is replaced by 1 -C 6 alkyl group, or unsubstituted or one or more R 1-1-2 C is replaced by 1 -C 6 An alkoxy group is particularly preferred, and each R 1-2 are independently halogen, or unsubstituted or one or more R 1-1-2 C is replaced by 1 -C 6 is an alkoxy group, (5) Each R 1-1-1 are independently deuterium or a halogen; (6) Each R 1-1-2 are independently deuterium or halogen, and preferably, each R 1-1-2 are independently halogen; (7) Each R 2 are independently deuterium, or unsubstituted or one or more R 2-1 C is replaced by 1 -C 6 is an alkyl group, and preferably, each R 2 are independently deuterium or C 1 -C 6 alkyl group, or unsubstituted or one or more R 2-1 C is replaced by 1 -C 6 is an alkyl group, and preferably, each R 2 independently C 1 -C 6 is an alkyl group, (8) m is 0 or 1, (9) Ring B is unsubstituted or contains one or more R b-1 The heteroatoms in the 5-12 membered fused ring heteroaryl ring are N and / or S, and the number of heteroatoms is 1, 2, 3 or 4. The single heteroaryl ring in the 5-12 membered fused ring heteroaryl ring is a 5-7 membered heteroaryl ring, and the number of rings in the 5-12 membered fused ring heteroaryl ring is 2, and preferably and preferably, ring B is (10) Each R b-1 are independently deuterium, oxo (=O), halogen, cyano, hydroxy, unsubstituted or one or more R b-1-1 C is replaced by 1 -C 6 alkyl group, or unsubstituted or one or more R b-1-2 C is replaced by 1 -C 6 is an alkoxy group, and preferably, each R b-1 are independently halogen or C 1 -C 6 is an alkyl group, (11) Each R b-1-1 are independently a hydroxy group, a halogen, or an unsubstituted or one or two R b-1-2-1 is an amino group substituted by (12) Each R b-1-2 are independently a hydroxy group, a halogen, or an unsubstituted or one or two R b-1-2-1 is an amino group substituted by (13) Each R b-1-2-1 are independently hydrogen or C 1 -C 6 is an alkyl group, (14) R 3 is hydrogen, unsubstituted or one or more R 3-1 a 3-6 membered cycloalkyl group, unsubstituted or substituted by one or more R 3-2 a 4-12 membered heterocyclyl group, unsubstituted or substituted by one or more R 3-3 a 4-10 membered cycloalkenyl group, unsubstituted or substituted by one or more R 3-4 a 4-10 membered heterocycloalkenyl group, unsubstituted or substituted by one or more R 3-5 a 6-10 membered aryl group, unsubstituted or substituted by one or more R 3-6 a 5-10 membered heteroaryl group substituted by -C(O)R 4 , -NH(CH 2 ) p R 5 , -O(CH 2 ) q R 6 , unsubstituted or one or more R 3-7 C is replaced by 1 -C 6 alkyl group, or unsubstituted or one or more R 3-8 -OR is replaced by 7 The heteroatoms in the 4- to 12-membered heterocyclyl group, 4- to 10-membered heterocycloalkenyl group, or 5- to 10-membered heteroaryl group are one or more of N, O, and S, and the number of heteroatoms is 1, 2, 3, or 4, and preferably R 3 is hydrogen, unsubstituted or one or more R 3-1 a 3-6 membered cycloalkyl group, unsubstituted or substituted by one or more R 3-2 a 4-6 membered heterocyclyl group, unsubstituted or substituted by one or more R 3-3 a 4-6 membered cycloalkenyl group, unsubstituted or substituted by one or more R 3-4 a 4-6 membered heterocycloalkenyl group, unsubstituted or substituted by one or more R 3-5 a phenyl group, unsubstituted or substituted by one or more R 3-6 a 5-6 membered heteroaryl group substituted by -C(O)R 4 , or unsubstituted or one or more R 3-7 C is replaced by 1 -C 6 an alkyl group, wherein the heteroatoms in the 4- to 6-membered heterocyclyl group, 4- to 6-membered heterocycloalkenyl group, or 5- to 6-membered heteroaryl group are N and / or O, and the number of heteroatoms is 1 or 2; (15) p is 0, 1, 2 or 3, and q is 1, 2 or 3; (16) Each R 3-1 are independently deuterium, a hydroxyl group, a halogen, or C 1 -C 6 is an alkyl group, and preferably, each R 3-1 are independently a hydroxy group or deuterium, e.g., each R 3-1 are independently a hydroxy group, (17) Each R 3-2 are independently deuterium, hydroxyl group, halogen, cyano group, amino group, -NHC(O)R 3-2-1 , unsubstituted or one or more R 3-2-2 C is replaced by 1 -C 6 Alkyl group, C 2 -C 6 Alkenyl group, C 2 -C 6 Alkynyl group, oxo group (=O), -C(O)NH 2 , unsubstituted or one or more R 3-2-3 and a 3- to 6-membered cycloalkyl group or a 4- to 6-membered heterocyclyl group substituted with, in which the heteroatoms in the 4- to 6-membered heterocyclyl group are selected from one or more of N, O and S, and the number of heteroatoms is 1 or 2, and preferably each R 3-2 are independently a hydroxy group, deuterium, or C 1 -C 6 is an alkyl group, for example, each R 3-2 are independently a hydroxy group or C 1 -C 6 is an alkyl group, (18) R 3-2-1 is C 1 -C 6 is an alkyl group, (19) Each R 3-2-2 are independently deuterium, a hydroxy group, or a halogen, and preferably, each R 3-2-2 are independently a hydroxy group or a halogen, e.g., each R 3-2-2 are independently deuterium, (20) Each R 3-2-3 independently C 1 -C 6 is an alkyl group or a hydroxy group, (21) Each R 3-3 are independently deuterium, hydroxyl group, halogen, cyano group, amino group, -S(O) 2 R 3-4-1 or -NR 3-4-2 R 3-4-2 and preferably, each R 3-3 are independently a hydroxy group or deuterium, e.g., each R 3-3 are independently a hydroxy group, (22) Each R 3-4 are independently deuterium, hydroxyl group, C 1 -C 6 Alkyl group, oxo group (=O), cyano group, halogen, 4-6 membered heterocyclyl group, -S(O) 2 R 3-4-1 or -NR 3-4-2 R 3-4-2 and preferably, each R 3-4 independently C 1 -C 6 is an alkyl group, (23) R 3-4-1 is C 1 -C 6 is an alkyl group, (24) Each R 3-4-2 are independently hydrogen or C 1 -C 6 is an alkyl group, (25) Each R 3-5 are independently deuterium, and preferably, each R 3-5 independently or each R 3-5 are independently deuterium or and preferably, each R 3-5 independently (26) R 3-5-1 and R 3-5-2 independently C 1 -C 6 is an alkyl group, preferably R 3-5-1 is C 1 -C 6 is an alkyl group, (27) Each R 3-6 are independently deuterium, halogen, or unsubstituted or one or more R 3-2-2 C is replaced by 1 -C 6 is an alkyl group, and preferably, each R 3-6 are independently deuterium, halogen or C 1 -C 6 is an alkyl group, for example, each R 3-6 are independently halogen or C 1 -C 6 is an alkyl group, (28) Each R 3-7 are independently deuterium, a hydroxy group, a halogen atom, or a 4- to 6-membered heterocyclyl group, and the heteroatom in the 4- to 6-membered heterocyclyl group is O, and the number of heteroatoms is 1. Preferably, each R 3-7 are independently a 4- to 6-membered heterocyclyl group, the heteroatom in the 4- to 6-membered heterocyclyl group is O, and the number of heteroatoms is 1; (29) R 3-8 is a hydroxy group, (30) R 4 is a 4- to 6-membered heterocyclyl group, the heteroatom in the 4- to 6-membered heterocyclyl group is O, and the number of heteroatoms is 1; (31) R 5 is one or more R 5-1 is a 3- to 6-membered cycloalkyl group substituted by (32) R 6 is one or more R 6-1 is a 3- to 6-membered cycloalkyl group substituted by and (33) each R 2-1 are independently deuterium.

6. The compound of formula I according to any one of claims 1 to 4, its pharmaceutically acceptable salt or isotope thereof, is characterized in that the compound of formula I satisfies one or more of the following conditions: (1) Ring A is a 6- to 12-membered aryl ring or a 5- to 6-membered heteroaryl ring, and the heteroatom in the 5- to 6-membered heteroaryl ring is selected from any one or two of N, O, and S, and the number of heteroatoms is 1, 2, or 3; (2)R 1 is unsubstituted or one or more R 1-1 a 6-12 membered aryl group substituted by, or unsubstituted or one or more R 1-2 wherein the heteroatoms in the 5- or 6-membered heteroaryl ring are selected from any one or two of N, O and S, and the number of heteroatoms is 1, 2 or 3; (3)Each R 1-1 and R 1-2 are independently halogen or C 1 -C 6 is an alkoxy group, (4) Ring B is unsubstituted or has one or more R b-1 wherein the heteroatoms in the 5-20 membered fused ring heteroaryl ring are selected from one or more of N, O and S, and the number of heteroatoms is 1, 2, 3, 4, 5, 6, 7 or 8; the single heteroaryl ring in the 5-20 membered fused ring heteroaryl ring is a 5-7 membered heteroaryl ring; and the number of rings in the 5-20 membered fused ring heteroaryl ring is 3 or 4; (5)Each R b-1 are independently deuterium, cyano, halogen, or unsubstituted or one or more R b-1-1 C is replaced by 1 -C 6 is an alkyl group, (6)R 3 is hydrogen, Unsubstituted or one or more R 3-1 a 3-6 membered cycloalkyl group, unsubstituted or substituted by one or more R 3-2 a 4-9 membered heterocyclyl group, unsubstituted or substituted by one or more R 3-3 a 4-6 membered cycloalkenyl group, unsubstituted or substituted by one or more R 3-4 a 4- to 6-membered heterocycloalkenyl group, unsubstituted or substituted by one or more R 3-5 a phenyl group, unsubstituted or substituted by one or more R 3-6 a 5-10 membered heteroaryl group substituted by -C(O)R 4 , or unsubstituted or one or more R 3-7 C is replaced by 1 -C 6 an alkyl group, wherein the heteroatoms in the 4- to 6-membered heterocycloalkenyl group and the 5- to 10-membered heteroaryl group are N and / or O, and the number of heteroatoms is 1 or 2; the heteroatoms in the 4- to 9-membered heterocyclyl group are selected from any one or two of N, O, and S, and the number of heteroatoms is 1 or 2; (7)Each R 3-2 are independently deuterium, oxo, halogen, C 1 -C 6 Alkoxy group, -NR 3-4-2 R 3-4-2 , -S(O) 2 R 3-4-1 , a hydroxy group, or unsubstituted or one or more R 3-2-2 C is replaced by 1 -C 6 is an alkyl group, (8)Each R 3-3 are independently deuterium, oxo, amino, or hydroxy; (9)Each R 3-4 are independently deuterium, oxo or C 1 -C 6 is an alkyl group, (10)R 3-4-1 is C 1 -C 6 is an alkyl group, (11)Each R 3-4-2 are independently -S(O) 2 R 3-4-1 , hydrogen or C 1 -C 6 is an alkyl group, (12)Each R 3-6 are independently deuterium, halogen, unsubstituted or one or more R 3-2-2 C is replaced by 1 -C 6 alkyl group, or unsubstituted or one or more R 3-6-1 wherein the heteroatoms in the 4-6 membered heterocyclyl group are selected from any one or two of N, O and S, and the number of heteroatoms is 1 or 2; (13)Each R 3-6-1 independently C 1 -C 6 is an alkyl group, (14)Each R 3-2-2 are independently deuterium or a hydroxy group, (15)Each R 3-7 are independently deuterium, hydroxyl group, -S(O) 2 R 3-4-1 a 4- to 6-membered heterocyclyl group, wherein the heteroatom in the 4- to 6-membered heterocyclyl group is O and the number of heteroatoms is 1; (16) Each R 3-5 are independently deuterium, and (17) each R 3-5-2 are independently a hydroxy group, C 1 -C 6 alkyl group or 1-10 membered heteroalkyl group, or two R 3-5-2 form a 4- to 10-membered heterocyclyl group, and includes those in which the heteroatoms in the 1- to 10-membered heteroalkyl group are selected from one or more of N, O, and S, in addition to phosphorus, and the number of heteroatoms is 1, 2, 3, or 4; and also includes those in which the heteroatoms in the 4- to 10-membered heterocyclyl group are selected from one or more of N, O, and S, in addition to phosphorus, and the number of heteroatoms is 1, 2, 3, or 4.

7. In the compound of formula I, R 3 The compound of formula I according to any one of claims 1 to 4, its pharmaceutically acceptable salt or isotope thereof, characterized in that it satisfies any of the following conditions: (1) R 3 is hydrogen, unsubstituted or one or more R 3-1 a 3-6 membered cycloalkyl group, unsubstituted or substituted by one or more R 3-2 a 4-6 membered heterocyclyl group, unsubstituted or substituted by one or more R 3-3 a 4-6 membered cycloalkenyl group, unsubstituted or substituted by one or more R 3-4 a 4-6 membered heterocycloalkenyl group, unsubstituted or substituted by one or more R 3-5 a phenyl group, unsubstituted or substituted by one or more R 3-6 a 5-6 membered heteroaryl group substituted by -C(O)R 4 , or unsubstituted or one or more R 3-7 C is replaced by 1 -C 6 an alkyl group, wherein the heteroatoms in the 4- to 6-membered heterocyclyl group, 4- to 6-membered heterocycloalkenyl group, or 5- to 6-membered heteroaryl group are N and / or O, and the number of heteroatoms is 1, 2, or 3; (2) R 3 is hydrogen, unsubstituted or one or more R 3-1 a 3-6 membered cycloalkyl group, unsubstituted or substituted by one or more R 3-2 a 4-6 membered heterocyclyl group, unsubstituted or substituted by one or more R 3-3 a 4-6 membered cycloalkenyl group, unsubstituted or substituted by one or more R 3-4 a 4-6 membered heterocycloalkenyl group, unsubstituted or substituted by one or more R 3-5 a phenyl group, unsubstituted or substituted by one or more R 3-6 a 5-6 membered heteroaryl group substituted by -C(O)R 4 , or unsubstituted or one or more R 3-7 C is replaced by 1 -C 6 an alkyl group, wherein the heteroatoms in the 4- to 6-membered heterocyclyl group or the 4- to 6-membered heterocycloalkenyl group are N and / or O and the number of heteroatoms is 1 or 2, or the heteroatoms in the 5- to 6-membered heteroaryl group are N and / or O and the number of heteroatoms is 1, 2 or 3; (3) R 3 is hydrogen, Unsubstituted or one or more R 3-1 a 3-6 membered cycloalkyl group, unsubstituted or substituted by one or more R 3-2 a 4-9 membered heterocyclyl group, unsubstituted or substituted by one or more R 3-3 a 4-6 membered cycloalkenyl group, unsubstituted or substituted by one or more R 3-4 a 4- to 6-membered heterocycloalkenyl group, unsubstituted or substituted by one or more R 3-5 a phenyl group, unsubstituted or substituted by one or more R 3-6 a 5-10 membered heteroaryl group substituted by -C(O)R 4 , or unsubstituted or one or more R 3-7 C is replaced by 1 -C 6 an alkyl group, wherein the heteroatoms in the 4- to 6-membered heterocycloalkenyl group and the 5- to 10-membered heteroaryl group are N and / or O, and the number of heteroatoms is 1, 2, or 3; the heteroatoms in the 4- to 9-membered heterocyclyl group are selected from any one or two of N, O, and S, and the number of heteroatoms is 1 or 2; (4) R 3 is hydrogen, Unsubstituted or one or more R 3-1 a 3-6 membered cycloalkyl group, unsubstituted or substituted by one or more R 3-2 a 4-9 membered heterocyclyl group, unsubstituted or substituted by one or more R 3-3 a 4-6 membered cycloalkenyl group, unsubstituted or substituted by one or more R 3-4 a 4- to 6-membered heterocycloalkenyl group, unsubstituted or substituted by one or more R 3-5 a phenyl group, unsubstituted or substituted by one or more R 3-6 a 5-10 membered heteroaryl group substituted by -C(O)R 4 , or unsubstituted or one or more R 3-7 C is replaced by 1 -C 6 the heteroatom in the 4- to 6-membered heterocycloalkenyl group is N and / or O, and the number of heteroatoms is 1 or 2; the heteroatom in the 5- to 10-membered heteroaryl group is N and / or O, and the number of heteroatoms is 1, 2, or 3; the heteroatom in the 4- to 9-membered heterocyclyl group is selected from any one or two of N, O, and S, and the number of heteroatoms is 1 or 2; and (5) R 3 is hydrogen, unsubstituted or one or more R 3-1 a 3-6 membered cycloalkyl group, unsubstituted or substituted by one or more R 3-2 a 4-12 membered heterocyclyl group, unsubstituted or substituted by one or more R 3-3 a 4-10 membered cycloalkenyl group, unsubstituted or substituted by one or more R 3-4 a 4-10 membered heterocycloalkenyl group, unsubstituted or substituted by one or more R 3-5 a 6-10 membered aryl group, unsubstituted or substituted by one or more R 3-6 a 5-10 membered heteroaryl group substituted by -C(O)R 4 , unsubstituted or one or more R 3-7 C is replaced by 1 -C 6 alkyl group, or unsubstituted or one or more R 3-8 -OR is replaced by 7 The heteroatoms in the 4- to 12-membered heterocyclyl group or the 4- to 10-membered heterocycloalkenyl group are one or more of N, O, and S, and the number of heteroatoms is 1 or 2; the heteroatoms in the 5- to 10-membered heteroaryl group are N and / or O, and the number of heteroatoms is 1, 2, 3, or 4.

8. The compound of formula I according to claim 1, its pharmaceutically acceptable salt or isotope thereof, is characterized in that the compound of formula I satisfies one or two of the following conditions: (1) Ring B is unsubstituted or contains one or more R b-1 wherein the heteroatoms in the 5-20 membered fused ring heteroaryl ring are selected from one or more of N, O and S, and the number of heteroatoms is 1, 2, 3, 4, 5, 6, 7 or 8; the single heteroaryl ring in the 5-20 membered fused ring heteroaryl ring is a 5-7 membered heteroaryl ring; the number of rings in the 5-20 membered fused ring heteroaryl ring is 2, 3 or 4; and the unsubstituted 5-20 membered fused ring heteroaryl ring is and preferably, ring B is one or more R b-1 wherein the heteroatoms in the 5-20 membered fused ring heteroaryl ring are selected from one or more of N, O and S, and the number of heteroatoms is 1, 2, 3, 4, 5, 6, 7 or 8; the single heteroaryl ring in the 5-20 membered fused ring heteroaryl ring is a 5-7 membered heteroaryl ring, and the number of rings in the 5-20 membered fused ring heteroaryl ring is 2, 3 or 4; (2) Ring A is a 5- to 12-membered heteroaryl ring, and the heteroatom in the 5- to 12-membered heteroaryl ring is one or more of N, O, and S, and the number of heteroatoms is 1, 2, or 3; R 1 is unsubstituted or one or more R 1-2 wherein the heteroatoms in the 5-12 membered heteroaryl ring are selected from any one or two of N, O and S, and the number of heteroatoms is 1, 2 or 3; R 3 is hydrogen, Unsubstituted or one or more R 3-1 a 3- to 12-membered cycloalkyl group substituted by one or more R 3-2 a 4-12 membered heterocyclyl group, unsubstituted or substituted by one or more R 3-3 a 4-12 membered cycloalkenyl group, unsubstituted or substituted by one or more R 3-4 a 4-12 membered heterocycloalkenyl group, unsubstituted or substituted by one or more R 3-5 a 6-10 membered aryl group, unsubstituted or substituted by one or more R 3-6 a 5-10 membered heteroaryl group substituted by -C(O)R 4 , -NH(CH 2 ) p R 5 , -O(CH 2 ) q R 6 , C 1 -C 6 alkyl group, or unsubstituted or one or more R 3-8 -OR is replaced by 7 wherein the heteroatoms in the 4- to 12-membered heterocyclyl group, the 4- to 12-membered heterocycloalkenyl group, and the 5- to 10-membered heteroaryl group are selected from one or more of N, O, and S, and the number of heteroatoms is 1, 2, 3, or 4; Each R 3-5 and R 3-6 are independently deuterium, Hydroxy group, amino group, -NHC(O)R 3-2-1 , C 1 -C 6 Alkyl group, C 2 -C 6 Alkenyl group, C 2 -C 6 Alkynyl group, -C(O)NH 2 , one or more R 3-2-3 a 3-6 membered cycloalkyl group, unsubstituted or substituted by one or more R 3-6-1 4-6 membered heterocyclyl groups substituted by -S(O) 2 R 3-4-1 , -NR 3-4-2 R 3-4-2 , The heteroatoms in the 4- to 6-membered heterocyclyl group are selected from one or more of N, O and S, and the number of heteroatoms is 1 or 2.

9. The compound of formula I according to claim 1, characterized in that the compound of formula I is a compound of formula Ia, Ib, Ic, Id or Ie, a pharmaceutically acceptable salt or isotope thereof:

10. The compound of formula I according to claim 1, its pharmaceutically acceptable salts or isotopic compounds thereof, characterized in that the compound of formula I is embodiment 1, embodiment 1', embodiment 2, embodiment 2', embodiment 3, embodiment 3', embodiment 4, embodiment 4', embodiment 5, embodiment 6, embodiment 7, embodiment 8, embodiment 8', embodiment 9, embodiment 9', embodiment 10, embodiment 11 or embodiment 12: Embodiment 1: Ring A is a 5- to 12-membered heteroaryl ring, and the heteroatom in the 5- to 12-membered heteroaryl ring is one or more of N, O, and S, and the number of heteroatoms is 1, 2, or 3; R 1 is unsubstituted or one or more R 1-1 a 6-12 membered aryl group substituted by, or unsubstituted or one or more R 1-2 wherein the heteroatoms in the 5-12 membered heteroaryl group are one or more of N, O and S, and the number of heteroatoms is 1, 2 or 3; Each R 1-1 and R 1-2 are independently deuterium, halogen, cyano, amino, unsubstituted or one or more R 1-1-1 C is replaced by 1 -C 6 alkyl group, or unsubstituted or one or more R 1-1-2 C is replaced by 1 -C 6 is an alkoxy group, Each R 1-1-1 and R 1-1-2 are independently deuterium or a halogen; Each R 2 are independently deuterium or C 1 -C 6 is an alkyl group, m is 0, 1, 2 or 3; Ring B may be unsubstituted or may contain one or more R b-1 wherein the heteroatoms in the 5-20 membered fused ring heteroaryl ring are one or more of N, O and S, and the number of heteroatoms is 1, 2, 3, 4, 5 or 6; the single heteroaryl ring in the 5-20 membered fused ring heteroaryl ring is a 5-7 membered heteroaryl ring, and the number of rings in the 5-20 membered fused ring heteroaryl ring is 2, 3 or 4; Each R b-1 are independently deuterium, oxo (=O), halogen, cyano, hydroxy, unsubstituted or one or more R b-1-1 C is replaced by 1 -C 6 alkyl group, or unsubstituted or one or more R b-1-2 C is replaced by 1 -C 6 is an alkoxy group, Each R b-1-1 and R b-1-2 are independently a hydroxy group, a halogen, or an unsubstituted or one or two R b-1-2-1 is an amino group substituted by Each R b-1-2-1 are independently hydrogen or C 1 -C 6 is an alkyl group, R 3 is hydrogen, unsubstituted or one or more R 3-1 a 3-6 membered cycloalkyl group, unsubstituted or substituted by one or more R 3-2 a 4-12 membered heterocyclyl group, unsubstituted or substituted by one or more R 3-3 a 4-10 membered cycloalkenyl group, unsubstituted or substituted by one or more R 3-4 a 4-10 membered heterocycloalkenyl group, unsubstituted or substituted by one or more R 3-5 a 6-10 membered aryl group, unsubstituted or substituted by one or more R 3-6 a 5-10 membered heteroaryl group substituted by -C(O)R 4 , -NH(CH 2 ) p R 5 , -O(CH 2 ) q R 6 , unsubstituted or one or more R 3-7 C is replaced by 1 -C 6 alkyl group, or unsubstituted or one or more R 3-8 -OR is replaced by 7 wherein the heteroatoms in the 4- to 12-membered heterocyclyl group, the 4- to 10-membered heterocycloalkenyl group, or the 5- to 10-membered heteroaryl group are selected from one or more of N, O, and S, and the number of heteroatoms is 1, 2, or 3; p is 0, 1, 2 or 3; q is 1, 2 or 3; Each R 3-1 are independently deuterium, a hydroxyl group, a halogen, or C 1 -C 6 is an alkyl group, Each R 3-2 are independently deuterium, hydroxyl group, halogen, cyano group, amino group, -NHC(O)R 3-2-1 , unsubstituted or one or more R 3-2-2 C is replaced by 1 -C 6 Alkyl group, C 2 -C 6 Alkenyl group, C 2 -C 6 Alkynyl group, oxo group (=O), -C(O)NH 2 , unsubstituted or one or more R 3-2-3 a 3- to 6-membered cycloalkyl group or a 4- to 6-membered heterocyclyl group substituted with, wherein the heteroatoms in the 4- to 6-membered heterocyclyl group are selected from one or more of N, O and S, and the number of heteroatoms is 1 or 2; R 3-2-1 is C 1 -C 6 is an alkyl group, Each R 3-2-2 are independently a hydroxy group or a halogen; Each R 3-2-3 independently C 1 -C 6 is an alkyl group or a hydroxy group, Each R 3-3 are independently deuterium, hydroxyl group, halogen, cyano group, amino group, -S(O) 2 R 3-4-1 or -NR 3-4-2 R 3-4-2 and Each R 3-4 are independently deuterium, hydroxyl group, C 1 -C 6 Alkyl group, oxo group (=O), cyano group, halogen, 4-6 membered heterocyclyl group, -S(O) 2 R 3-4-1 or -NR 3-4-2 R 3-4-2 and R 3-4-1 is C 1 -C 6 is an alkyl group, Each R 3-4-2 are independently hydrogen or C 1 -C 6 is an alkyl group, Each R 3-5 are independently deuterium or R 3-5-1 is C 1 -C 6 is an alkyl group, Each R 3-6 are independently deuterium, halogen or C 1 -C 6 is an alkyl group, Each R 3-7 are independently deuterium, a hydroxy group, a halogen atom, or a 4- to 6-membered heterocyclyl group, the heteroatom in the 4- to 6-membered heterocyclyl group is O, and the number of heteroatoms is 1; R 3-8 is a hydroxy group, R 4 is a 4- to 6-membered heterocyclyl group, wherein the heteroatoms in the 4- to 6-membered heterocyclyl group are selected from one or more of N, O and S, and the number of heteroatoms is 1 or 2; R 5 is unsubstituted or one or more R 5-1 is a 3- to 6-membered cycloalkyl group substituted by Each R 5-1 are independently a hydroxy group, R 6 is unsubstituted or one or more R 6-1 is a 3- to 6-membered cycloalkyl group substituted by Each R 6-1 are independently a hydroxy group, R 7 is a 3- to 6-membered cycloalkyl group, Embodiment 1': Ring A is a 5- to 10-membered heteroaryl ring, the heteroatom in the 5- to 10-membered heteroaryl ring is N, and the number of heteroatoms is 1 or 2; R 1 is unsubstituted or one or more R 1-1 a 6-10 membered aryl group substituted by, or unsubstituted or one or more R 1-2 wherein the heteroatom in the 5-6 membered heteroaryl group is N and the number of heteroatoms is 1 or 2; Each R 1-1 and R 1-2 are independently deuterium, halogen, unsubstituted or one or more R 1-1-1 C is replaced by 1 -C 6 Alkyl group, unsubstituted or one or more R 1-1-2 C is replaced by 1 -C 6 an alkoxy group or Each R 1-1-1 and R 1-1-2 are independently halogen; Each R 1-1-11 are independently a hydroxy group or C 1 -C 6 is an alkyl group, R 2 are independently deuterium, or unsubstituted or one or more R 2-1 C is replaced by 1 -C 6 is an alkyl group, Each R 2-1 are independently halogen or deuterium, m is 0 or 1, Ring B may be unsubstituted or may contain one or more R b-1 wherein the heteroatoms in the 5-12 membered fused ring heteroaryl ring are N and / or S, the number of heteroatoms is 1, 2, 3 or 4, and the number of rings in the 5-12 membered fused ring heteroaryl ring is 2; Each R b-1 are independently deuterium, cyano, halogen, or unsubstituted or one or more R b-1-1 C is replaced by 1 -C 6 is an alkyl group, Each R b-1-1 are independently halogen; R 3 is hydrogen, Unsubstituted or one or more R 3-1 a 3-6 membered cycloalkyl group, unsubstituted or substituted by one or more R 3-2 a 4-9 membered heterocyclyl group, unsubstituted or substituted by one or more R 3-3 a 4-6 membered cycloalkenyl group, unsubstituted or substituted by one or more R 3-4 a 4- to 6-membered heterocycloalkenyl group, unsubstituted or substituted by one or more R 3-5 a phenyl group, unsubstituted or substituted by one or more R 3-6 a 5-10 membered heteroaryl group substituted by -C(O)R 4 , or unsubstituted or one or more R 3-7 C is replaced by 1 -C 6 an alkyl group, wherein the heteroatoms in the 4- to 6-membered heterocycloalkenyl group and the 5- to 10-membered heteroaryl group are N and / or O, and the number of heteroatoms is 1 or 2; the heteroatoms in the 4- to 9-membered heterocyclyl group are selected from any one or two of N, O, and S, and the number of heteroatoms is 1 or 2; Each R 3-1 are independently deuterium or a hydroxy group, Each R 3-2 are independently deuterium, oxo, halogen, C 1 -C 6 Alkoxy group, -NR 3-4-2 R 3-4-2 , -S(O) 2 R 3-4-1 , a hydroxy group, or unsubstituted or one or more R 3-2-2 C is replaced by 1 -C 6 is an alkyl group, Each R 3-3 are independently deuterium, oxo, amino, or hydroxy; Each R 3-4 are independently deuterium, oxo or C 1 -C 6 is an alkyl group, R 3-4-1 is C 1 -C 6 is an alkyl group, Each R 3-4-2 are independently -S(O) 2 R 3-4-1 , hydrogen or C 1 -C 6 is an alkyl group, Each R 3-5 are independently deuterium, R 3-5-1 independently, C 1 -C 6 is an alkyl group, Each R 3-5-2 are independently a hydroxy group, C 1 -C 6 alkyl group or 1-10 membered heteroalkyl group, or two R 3-5-2 form a 4-10 membered heterocyclyl group, wherein the heteroatoms in the 1-10 membered heteroalkyl group include, in addition to phosphorus, any one or more selected from N, O and S, and the number of heteroatoms is 1, 2, 3 or 4; the heteroatoms in the 4-10 membered heterocyclyl group include, in addition to phosphorus, any one or more selected from N, O and S, and the number of heteroatoms is 1, 2, 3 or 4; Each R 3-6 are independently deuterium, halogen, unsubstituted or one or more R 3-2-2 C is replaced by 1 -C 6 alkyl group, or unsubstituted or one or more R 3-6-1 wherein the heteroatoms in the 4-6 membered heterocyclyl group are selected from any one or two of N, O and S, and the number of heteroatoms is 1 or 2; Each R 3-6-1 independently C 1 -C 6 is an alkyl group, Each R 3-2-2 are independently deuterium or a hydroxy group, Each R 3-7 are independently deuterium, hydroxyl group, -S(O) 2 R 3-4-1 a 4- to 6-membered heterocyclyl group, wherein the heteroatom in the 4- to 6-membered heterocyclyl group is O and the number of heteroatoms is 1; R 4 is a 4- to 6-membered heterocyclyl group, the heteroatom in the 4- to 6-membered heterocyclyl group is O, the number of heteroatoms is 1, and R 4 is a 4- to 6-membered heterocyclyl group, wherein the heteroatoms in the 4- to 6-membered heterocyclyl group are selected from one or more of N, O and S, and the number of heteroatoms is 1 or 2; R 5 is unsubstituted or one or more R 5-1 is a 3- to 6-membered cycloalkyl group substituted by Each R 5-1 are independently a hydroxy group, R 6 is unsubstituted or one or more R 6-1 is a 3- to 6-membered cycloalkyl group substituted by Each R 6-1 are independently a hydroxy group, R 7 is a 3- to 6-membered cycloalkyl group, Embodiment 2: Ring A is a 5- to 10-membered heteroaryl ring, the heteroatom in the 5- to 10-membered heteroaryl ring is N, and the number of heteroatoms is 1 or 2; R 1 is unsubstituted or one or more R 1-1 a 6-10 membered aryl group substituted by, or unsubstituted or one or more R 1-2 wherein the heteroatom in the 5-6 membered heteroaryl group is N and the number of heteroatoms is 1 or 2; Each R 1-1 and R 1-2 are independently deuterium, halogen, unsubstituted or one or more R 1-1-1 C is replaced by 1 -C 6 Alkyl group, unsubstituted or one or more R 1-1-2 C is replaced by 1 -C 6 an alkoxy group or Each R 1-1-1 and R 1-1-2 are independently halogen; Each R 1-1-11 are independently a hydroxy group or C 1 -C 6 is an alkyl group, R 2 are independently deuterium, or unsubstituted or one or more R 2-1 C is replaced by 1 -C 6 is an alkyl group, Each R 2-1 are independently halogen; m is 0 or 1, Ring B may be unsubstituted or may contain one or more R b-1 wherein the heteroatoms in the 5-12 membered fused ring heteroaryl ring are N and / or S, the number of heteroatoms is 1, 2, 3 or 4, and the number of rings in the 5-12 membered fused ring heteroaryl ring is 2; Each R b-1 are independently deuterium, halogen, or unsubstituted or one or more R b-1-1 C is replaced by 1 -C 6 is an alkyl group, Each R b-1-1 are independently halogen; R 3 is hydrogen, unsubstituted or one or more R 3-1 a 3-6 membered cycloalkyl group, unsubstituted or substituted by one or more R 3-2 a 4-6 membered heterocyclyl group, unsubstituted or substituted by one or more R 3-3 a 4-6 membered cycloalkenyl group, unsubstituted or substituted by one or more R 3-4 a 4- to 6-membered heterocycloalkenyl group, unsubstituted or substituted by one or more R 3-5 a phenyl group, unsubstituted or substituted by one or more R 3-6 a 5-6 membered heteroaryl group substituted by -C(O)R 4 , or unsubstituted or one or more R 3-7 C is replaced by 1 -C 6 an alkyl group, wherein the heteroatoms in the 4- to 6-membered heterocyclyl group, 4- to 6-membered heterocycloalkenyl group, or 5- to 6-membered heteroaryl group are N and / or O, and the number of heteroatoms is 1 or 2; Each R 3-1 are independently deuterium or a hydroxy group, Each R 3-2 are independently deuterium, a hydroxyl group, or C 1 -C 6 is an alkyl group, Each R 3-3 are independently deuterium or a hydroxy group, Each R 3-4 are independently deuterium or C 1 -C 6 is an alkyl group, Each R 3-5 are independently deuterium or R 3-5-1 is C 1 -C 6 is an alkyl group, Each R 3-6 are independently deuterium, halogen or C 1 -C 6 is an alkyl group, Each R 3-7 are independently deuterium or a 4- to 6-membered heterocyclyl group, the heteroatom in the 4- to 6-membered heterocyclyl group is O, and the number of heteroatoms is 1; R 4 is a 4- to 6-membered heterocyclyl group, the heteroatom in the 4- to 6-membered heterocyclyl group is O, and the number of heteroatoms is 1; Embodiment 2': Ring A is a 5- to 10-membered heteroaryl ring, the heteroatom in the 5- to 10-membered heteroaryl ring is N, and the number of heteroatoms is 1 or 2; R 1 is unsubstituted or one or more R 1-1 a 6-10 membered aryl group substituted by, or unsubstituted or one or more R 1-2 wherein the heteroatom in the 5-6 membered heteroaryl group is N and the number of heteroatoms is 1 or 2; Each R 1-1 and R 1-2 are independently deuterium, halogen, unsubstituted or one or more R 1-1-1 C is replaced by 1 -C 6 Alkyl group, unsubstituted or one or more R 1-1-2 C is replaced by 1 -C 6 an alkoxy group or Each R 1-1-1 and R 1-1-2 are independently halogen or deuterium, Each R 1-1-11 are independently a hydroxy group or C 1 -C 6 is an alkyl group, R 2 are independently deuterium, or unsubstituted or one or more R 2-1 C is replaced by 1 -C 6 is an alkyl group, Each R 2-1 are independently halogen or deuterium, m is 0 or 1, Ring B may be unsubstituted or may contain one or more R b-1 wherein the heteroatoms in the 5-12 membered fused ring heteroaryl ring are N and / or S, the number of heteroatoms is 1, 2, 3 or 4, and the number of rings in the 5-12 membered fused ring heteroaryl ring is 2; Each R b-1 are independently deuterium, cyano, halogen, or unsubstituted or one or more R b-1-1 C is replaced by 1 -C 6 is an alkyl group, Each R b-1-1 are independently halogen; R 3 is hydrogen, Unsubstituted or one or more R 3-1 a 3-6 membered cycloalkyl group, unsubstituted or substituted by one or more R 3-2 a 4-9 membered heterocyclyl group, unsubstituted or substituted by one or more R 3-3 a 4-6 membered cycloalkenyl group, unsubstituted or substituted by one or more R 3-4 a 4- to 6-membered heterocycloalkenyl group, unsubstituted or substituted by one or more R 3-5 a phenyl group, unsubstituted or substituted by one or more R 3-6 a 5-10 membered heteroaryl group substituted by -C(O)R 4 , or unsubstituted or one or more R 3-7 C is replaced by 1 -C 6 an alkyl group, wherein the heteroatoms in the 4- to 6-membered heterocycloalkenyl group or the 5- to 10-membered heteroaryl group are N and / or O, and the number of heteroatoms is 1 or 2; the heteroatoms in the 4- to 9-membered heterocyclyl group are selected from any one or two of N, O, and S, and the number of heteroatoms is 1 or 2; Each R 3-1 are independently deuterium or a hydroxy group, Each R 3-2 are independently deuterium, oxo, halogen, C 1 -C 6 Alkoxy group, -NR 3-4-2 R 3-4-2 , -S(O) 2 R 3-4-1 , a hydroxy group, or unsubstituted or one or more R 3-2-2 C is replaced by 1 -C 6 is an alkyl group, Each R 3-3 are independently deuterium, oxo, amino, or hydroxy; Each R 3-4 are independently deuterium, oxo or C 1 -C 6 is an alkyl group, R 3-4-1 is C 1 -C 6 is an alkyl group, Each R 3-4-2 are independently -S(O) 2 R 3-4-1 , hydrogen or C 1 -C 6 is an alkyl group, Each R 3-5 are independently deuterium, R 3-5-1 is C 1 -C 6 is an alkyl group, Each R 3-5-2 are independently a hydroxy group, C 1 -C 6 alkyl group or 1-10 membered heteroalkyl group, or two R 3-5-2 form a 4-10 membered heterocyclyl group, wherein the heteroatoms in the 1-10 membered heteroalkyl group include, in addition to phosphorus, any one or more selected from N, O and S, and the number of heteroatoms is 1, 2, 3 or 4; the heteroatoms in the 4-10 membered heterocyclyl group include, in addition to phosphorus, any one or more selected from N, O and S, and the number of heteroatoms is 1, 2, 3 or 4; Each R 3-6 are independently deuterium, halogen, unsubstituted or one or more R 3-2-2 C is replaced by 1 -C 6 alkyl group, or unsubstituted or one or more R 3-6-1 wherein the heteroatoms in the 4-6 membered heterocyclyl group are selected from any one or two of N, O and S, and the number of heteroatoms is 1 or 2; Each R 3-6-1 independently C 1 -C 6 is an alkyl group, Each R 3-2-2 are independently deuterium or a hydroxy group, Each R 3-7 are independently deuterium, hydroxyl group, -S(O) 2 R 3-4-1 a 4- to 6-membered heterocyclyl group, wherein the heteroatom in the 4- to 6-membered heterocyclyl group is O and the number of heteroatoms is 1; R 4 is a 4- to 6-membered heterocyclyl group, the heteroatom in the 4- to 6-membered heterocyclyl group is O, and the number of heteroatoms is 1; Embodiment 3: Ring A is a 5- to 10-membered heteroaryl ring, the heteroatom in the 5- to 10-membered heteroaryl ring is N, and the number of heteroatoms is 1 or 2; R 1 is unsubstituted or one or more R 1-1 a 6-10 membered aryl group substituted by, or unsubstituted or one or more R 1-2 wherein the heteroatom in the 5-6 membered heteroaryl group is N and the number of heteroatoms is 1; Each R 1-1 and R 1-2 are independently halogen, or unsubstituted or one or more R 1-1-2 C is replaced by 1 -C 6 is an alkoxy group, Each R 1-1-2 are independently halogen; R 2 independently C 1 -C 6 is an alkyl group, m is 0 or 1, Ring B may be unsubstituted or may contain one or more R b-1 wherein the heteroatoms in the 5-12 membered fused ring heteroaryl ring are N and / or S and the number of heteroatoms is 1, 2, 3 or 4; the single heteroaryl ring in the 5-12 membered fused ring heteroaryl ring is a 5-7 membered heteroaryl ring and the number of rings in the 5-12 membered fused ring heteroaryl ring is 2; Each R b-1 are independently halogen; R 3 is hydrogen, unsubstituted or one or more R 3-1 a 3-6 membered cycloalkyl group, unsubstituted or substituted by one or more R 3-2 a 4-6 membered heterocyclyl group, unsubstituted or substituted by one or more R 3-3 a 4-6 membered cycloalkenyl group, unsubstituted or substituted by one or more R 3-4 a 4-6 membered heterocycloalkenyl group, unsubstituted or substituted by one or more R 3-5 a phenyl group, unsubstituted or substituted by one or more R 3-6 or a 5-6 membered heteroaryl group substituted by -C(O)R 4 wherein the heteroatoms in the 4- to 6-membered heterocyclyl group, the 4- to 6-membered heterocycloalkenyl group, or the 5- to 6-membered heteroaryl group are N and / or O, and the number of heteroatoms is 1 or 2; Each R 3-1 are independently a hydroxy group, Each R 3-2 are independently a hydroxy group or C 1 -C 6 is an alkyl group, Each R 3-3 are independently a hydroxy group, Each R 3-4 independently C 1 -C 6 is an alkyl group, Each R 3-5 independently R 3-5-1 is C 1 -C 6 is an alkyl group, Each R 3-6 are independently halogen or C 1 -C 6 is an alkyl group, R 4 is a 4- to 6-membered heterocyclyl group, the heteroatom in the 4- to 6-membered heterocyclyl group is O, and the number of heteroatoms is 1; Embodiment 3': Ring A is a 5- to 10-membered heteroaryl ring, the heteroatom in the 5- to 10-membered heteroaryl ring is N, and the number of heteroatoms is 1 or 2; R 1 is unsubstituted or one or more R 1-1 a 6-10 membered aryl group substituted by, or unsubstituted or one or more R 1-2 wherein the heteroatom in the 5-6 membered heteroaryl group is N and the number of heteroatoms is 1; Each R 1-1 and R 1-2 are independently halogen, or unsubstituted or one or more R 1-1-2 C is replaced by 1 -C 6 is an alkoxy group, Each R 1-1-2 are independently deuterium or a halogen; Each R 2 are independently unsubstituted or one or more R 2-1 C is replaced by 1 -C 6 is an alkyl group, Each R 2-1 are independently deuterium, m is 0 or 1, Ring B may be unsubstituted or may contain one or more R b-1 wherein the heteroatoms in the 5-12 membered fused ring heteroaryl ring are N and / or S and the number of heteroatoms is 1, 2, 3 or 4; the single heteroaryl ring in the 5-12 membered fused ring heteroaryl ring is a 5-7 membered heteroaryl ring and the number of rings in the 5-12 membered fused ring heteroaryl ring is 2; Each R b-1 are independently halogen; R 3 is hydrogen, unsubstituted or one or more R 3-1 a 3-6 membered cycloalkyl group, unsubstituted or substituted by one or more R 3-2 a 4-6 membered heterocyclyl group, unsubstituted or substituted by one or more R 3-3 a 4-6 membered cycloalkenyl group, unsubstituted or substituted by one or more R 3-4 a 4-6 membered heterocycloalkenyl group, unsubstituted or substituted by one or more R 3-5 a phenyl group, unsubstituted or substituted by one or more R 3-6 or a 5-6 membered heteroaryl group substituted by -C(O)R 4 wherein the heteroatoms in the 4- to 6-membered heterocyclyl group, the 4- to 6-membered heterocycloalkenyl group, or the 5- to 6-membered heteroaryl group are N and / or O, and the number of heteroatoms is 1 or 2; Each R 3-1 are independently a hydroxy group or deuterium; Each R 3-2 are independently a hydroxy group, deuterium, or C 1 -C 6 is an alkyl group, Each R 3-3 are independently a hydroxy group or deuterium; Each R 3-4 independently C 1 -C 6 is an alkyl group, Each R 3-5 independently R 3-5-1 is C 1 -C 6 is an alkyl group, Each R 3-5-2 are independently a hydroxy group, C 1 -C 6 alkyl group or 1-10 membered heteroalkyl group, or two R 3-5-2 form a 4-10 membered heterocyclyl group, wherein the heteroatoms in the 1-10 membered heteroalkyl group include, in addition to phosphorus, any one or more selected from N, O and S, and the number of heteroatoms is 1, 2, 3 or 4; the heteroatoms in the 4-10 membered heterocyclyl group include, in addition to phosphorus, any one or more selected from N, O and S, and the number of heteroatoms is 1, 2, 3 or 4; Each R 3-6 are independently halogen, unsubstituted or one or more R 3-2-2 is replaced by Each R 3-2-2 are independently deuterium, R 4 is a 4- to 6-membered heterocyclyl group, the heteroatom in the 4- to 6-membered heterocyclyl group is O, and the number of heteroatoms is 1; Embodiment 4: Ring A is a 5- or 6-membered heteroaryl ring, the heteroatom in the 5- or 6-membered heteroaryl ring is N, and the number of heteroatoms is 1 or 2; R 1 is unsubstituted or one or more R 1-1 or a phenyl group substituted with one or more R 1-2 wherein the heteroatom in the 5-6 membered heteroaryl group is N and the number of heteroatoms is 1; Each R 1-1 and R 1-2 are independently halogen, or unsubstituted or one or more R 1-1-2 C is replaced by 1 -C 6 is an alkoxy group, Each R 1-1-2 are independently halogen; R 2 independently C 1 -C 6 is an alkyl group, m is 0 or 1, Ring B is a 5,6-heteroaryl ring, the heteroatoms in the 5,6-heteroaryl ring are N and / or S, and the number of heteroatoms is 1 or 3; R 3 is hydrogen, unsubstituted or one or more R 3-1 a 3-6 membered cycloalkyl group, unsubstituted or substituted by one or more R 3-2 a 4-6 membered heterocyclyl group substituted by, or unsubstituted or one or more R 3-3 wherein the heteroatoms in the 4-6 membered heterocyclyl group are N and / or O, and the number of heteroatoms is 1 or 2; Each R 3-1 are independently a hydroxy group, Each R 3-2 are independently a hydroxy group or C 1 -C 6 is an alkyl group, Each R 3-3 are independently a hydroxy group, Embodiment 4': Ring A is a 5- or 6-membered heteroaryl ring, the heteroatom in the 5- or 6-membered heteroaryl ring is N, and the number of heteroatoms is 1; R 1 is unsubstituted or one or more R 1-1 or a phenyl group substituted with one or more R 1-2 wherein the heteroatom in the 5-6 membered heteroaryl group is N and the number of heteroatoms is 1; Each R 1-1 and R 1-2 are independently halogen, or unsubstituted or one or more R 1-1-2 C is replaced by 1 -C 6 is an alkoxy group, Each R 1-1-2 are independently halogen or deuterium, R 2 are independently unsubstituted or one or more R 2-1 C is replaced by 1 -C 6 is an alkyl group, Each R 2-1 are independently deuterium, m is 0 or 1, Ring B is a 5,6-ring heteroaryl ring, the heteroatoms in the 5,6-heteroaryl ring are N and / or S, and the number of heteroatoms is 1, 2, 3, or 4; R 3 is unsubstituted or one or more R 3-1 a 3-6 membered cycloalkyl group, unsubstituted or substituted by one or more R 3-3 a 4-6 membered cycloalkenyl group, unsubstituted or substituted by one or more R 3-5 or a phenyl group substituted with one or more R 3-6 wherein the heteroatom in the 4-6 membered heterocyclyl group is N and / or O and the number of heteroatoms is 1 or 2, and the heteroatom in the 5-6 membered heteroaryl ring is N and the number of heteroatoms is 2; Each R 3-1 are independently a hydroxy group, Each R 3-3 are independently a hydroxy group, Each R 3-5 independently R 3-5-1 and R 3-5-2 independently C 1 -C 6 is an alkyl group, Each R 3-6 are independently halogen, unsubstituted or one or more R 3-2-2 is replaced by Each R 3-2-2 are independently deuterium, Embodiment 5: Ring A is a 5- or 6-membered heteroaryl ring, the heteroatom in the 5- or 6-membered heteroaryl ring is N, and the number of heteroatoms is 1; R 1 is unsubstituted or one or more R 1-1 or a phenyl group substituted with one or more R 1-2 wherein the heteroatom in the 5-6 membered heteroaryl group is N and the number of heteroatoms is 1; Each R 1-1 and R 1-2 are independently halogen, or unsubstituted or one or more R 1-1-2 C is replaced by 1 -C 6 is an alkoxy group, Each R 1-1-2 are independently halogen; R 2 independently C 1 -C 6 is an alkyl group, m is 0 or 1, Ring B is a 5,6-heteroaryl ring, the heteroatoms in the 5,6-heteroaryl ring are N and / or S, and the number of heteroatoms is 1 or 3; R 3 is unsubstituted or one or more R 3-1 a 3- to 6-membered cycloalkyl group substituted by, or unsubstituted or substituted by one or more R 3-3 is a 4-6 membered cycloalkenyl group substituted by Each R 3-1 are independently a hydroxy group, Each R 3-3 are independently a hydroxy group, Embodiment 6: Ring A is a 5- or 6-membered heteroaryl ring, the heteroatom in the 5- or 6-membered heteroaryl ring is N, and the number of heteroatoms is 1; R 1 is unsubstituted or one or more R 1-1 or a phenyl group substituted with one or more R 1-2 wherein the heteroatom in the 5-6 membered heteroaryl group is N and the number of heteroatoms is 1; Each R 1-1 and R 1-2 are independently halogen, or unsubstituted or one or more R 1-1-2 C is replaced by 1 -C 6 is an alkoxy group, Each R 1-1-2 are independently halogen or deuterium, R 2 are independently unsubstituted or one or more R 2-1 C is replaced by 1 -C 6 is an alkyl group, Each R 2-1 are independently deuterium, m is 0 or 1, Ring B may be unsubstituted or may contain one or more R b-1 is a 5-12 membered fused heteroaryl ring substituted by The 5- to 12-membered fused heteroaryl ring is Each R b-1 are independently halogen; R 3 is unsubstituted or one or more R 3-1 a 3-6 membered cycloalkyl group, unsubstituted or substituted by one or more R 3-3 a 4-6 membered cycloalkenyl group, unsubstituted or substituted by one or more R 3-5 or a phenyl group substituted with one or more R 3-6 wherein the heteroatom in the 4-6 membered heterocyclyl group is N and / or O and the number of heteroatoms is 1 or 2, and the heteroatom in the 5-6 membered heteroaryl ring is N and the number of heteroatoms is 2; Each R 3-1 are independently a hydroxy group, Each R 3-3 are independently a hydroxy group, Each R 3-5 independently R 3-5-1 and R 3-5-2 independently C 1 -C 6 is an alkyl group, Each R 3-6 are independently halogen, unsubstituted or one or more R 3-2-2 is replaced by Each R 3-2-2 are independently deuterium, Embodiment 7: Ring A is a 6- to 12-membered aryl ring or a 5- to 6-membered heteroaryl ring, in which heteroatoms in the 5- to 6-membered heteroaryl ring are selected from any one or two of N, O, and S, and the number of heteroatoms is 1, 2, or 3; R 1 is unsubstituted or one or more R 1-1 a 6-12 membered aryl group substituted by, or unsubstituted or one or more R 1-2 wherein the heteroatoms in the 5- or 6-membered heteroaryl ring are selected from any one or two of N, O and S, and the number of heteroatoms is 1, 2 or 3; Each R 1-1 and R 1-2 are independently halogen or C 1 -C 6 is an alkoxy group, Ring B may be unsubstituted or may contain one or more R b-1 wherein the heteroatoms in the 5-20 membered fused ring heteroaryl ring are selected from one or more of N, O and S, and the number of heteroatoms is 1, 2, 3, 4, 5, 6, 7 or 8; the single heteroaryl ring in the 5-20 membered fused ring heteroaryl ring is a 5-7 membered heteroaryl ring; and the number of rings in the 5-20 membered fused ring heteroaryl ring is 3 or 4; R 3 is hydrogen, Embodiment 8: Ring A is a 5- to 10-membered heteroaryl ring, the heteroatom in the 5- to 10-membered heteroaryl ring is N, and the number of heteroatoms is 1 or 2; R 1 is unsubstituted or one or more R 1-1 a 6-10 membered aryl group substituted by, or unsubstituted or one or more R 1-2 wherein the heteroatom in the 5-6 membered heteroaryl group is N and the number of heteroatoms is 1 or 2; Each R 1-1 and R 1-2 are independently deuterium, halogen, unsubstituted or one or more R 1-1-1 C is replaced by 1 -C 6 Alkyl group, unsubstituted or one or more R 1-1-2 C is replaced by 1 -C 6 an alkoxy group or Each R 1-1-1 and R 1-1-2 are independently halogen or deuterium, Each R 1-1-11 are independently a hydroxy group or C 1 -C 6 is an alkyl group, R 2 are independently deuterium, or unsubstituted or one or more R 2-1 C is replaced by 1 -C 6 is an alkyl group, Each R 2-1 are independently halogen or deuterium, m is 0 or 1, Ring B is one or more R b-1 wherein the heteroatoms in the 5-12 membered fused ring heteroaryl ring are N and / or S, the number of heteroatoms is 1, 2, 3 or 4, and the number of rings in the 5-12 membered fused ring heteroaryl ring is 2; Each R b-1 are independently halogen, or unsubstituted or one or more R b-1-1 C is replaced by 1 -C 6 is an alkyl group, Each R b-1-1 are independently halogen; R 3 is hydrogen, unsubstituted or one or more R 3-1 a 3-6 membered cycloalkyl group, unsubstituted or substituted by one or more R 3-2 a 4-12 membered heterocyclyl group, unsubstituted or substituted by one or more R 3-3 a 4-10 membered cycloalkenyl group, unsubstituted or substituted by one or more R 3-4 a 4-10 membered heterocycloalkenyl group, unsubstituted or substituted by one or more R 3-5 a 6-10 membered aryl group, unsubstituted or substituted by one or more R 3-6 a 5-10 membered heteroaryl group substituted by -C(O)R 4 , unsubstituted or one or more R 3-7 C is replaced by 1 -C 6 alkyl group, or unsubstituted or one or more R 3-8 -OR is replaced by 7 wherein the heteroatoms in the 4- to 12-membered heterocyclyl group or the 4- to 10-membered heterocycloalkenyl group are one or more of N, O, and S, and the number of heteroatoms is 1 or 2; the heteroatoms in the 5- to 10-membered heteroaryl group are N and / or O, and the number of heteroatoms is 1, 2, 3, or 4; Each R 3-1 are independently deuterium or a hydroxy group, Each R 3-2 are independently deuterium, oxo, halogen, C 1 -C 6 Alkoxy group, -NR 3-4-2 R 3-4-2 , -S(O) 2 R 3-4-1 , a hydroxy group, or unsubstituted or one or more R 3-2-2 C is replaced by 1 -C 6 is an alkyl group, Each R 3-3 are independently deuterium, oxo, amino, or hydroxy; Each R 3-4 are independently deuterium, oxo or C 1 -C 6 is an alkyl group, R 3-4-1 is C 1 -C 6 is an alkyl group, Each R 3-4-2 are independently -S(O) 2 R 3-4-1 , hydrogen or C 1 -C 6 is an alkyl group, Each R 3-5 are independently deuterium, R 3-5-1 is C 1 -C 6 is an alkyl group, Each R 3-6 are independently deuterium, halogen, unsubstituted or one or more R 3-2-2 C is replaced by 1 -C 6 alkyl group, or unsubstituted or one or more R 3-6-1 wherein the heteroatoms in the 4-6 membered heterocyclyl group are selected from any one or two of N, O and S, and the number of heteroatoms is 1 or 2; Each R 3-5-2 are independently a hydroxy group, C 1 -C 6 alkyl group or 1-10 membered heteroalkyl group, or two R 3-5-2 form a 4-10 membered heterocyclyl group, wherein the heteroatoms in the 1-10 membered heteroalkyl group include, in addition to phosphorus, any one or more selected from N, O and S, and the number of heteroatoms is 1, 2, 3 or 4; the heteroatoms in the 4-10 membered heterocyclyl group include, in addition to phosphorus, any one or more selected from N, O and S, and the number of heteroatoms is 1, 2, 3 or 4; Each R 3-6-1 independently C 1 -C 6 is an alkyl group, Each R 3-2-2 are independently deuterium or a hydroxy group, Each R 3-7 are independently deuterium, hydroxyl group, -S(O) 2 R 3-4-1 a 4- to 6-membered heterocyclyl group, wherein the heteroatom in the 4- to 6-membered heterocyclyl group is O and the number of heteroatoms is 1; Each R 3-8 are independently deuterium or a hydroxy group, R 4 is a 4- to 6-membered heterocyclyl group, the heteroatom in the 4- to 6-membered heterocyclyl group is O, and the number of heteroatoms is 1; R 7 is a 3- to 6-membered cycloalkyl group, Embodiment 8': Ring A is a 5- to 10-membered heteroaryl ring, the heteroatom in the 5- to 10-membered heteroaryl ring is N, and the number of heteroatoms is 1 or 2; R 1 is unsubstituted or one or more R 1-1 a 6-10 membered aryl group substituted by, or unsubstituted or one or more R 1-2 wherein the heteroatom in the 5-6 membered heteroaryl group is N and the number of heteroatoms is 1 or 2; Each R 1-1 and R 1-2 are independently deuterium, halogen, unsubstituted or one or more R 1-1-1 C is replaced by 1 -C 6 alkyl group, or unsubstituted or one or more R 1-1-2 C is replaced by 1 -C 6 is an alkoxy group, Each R 1-1-1 and R 1-1-2 are independently halogen or deuterium, Each R 1-1-11 are independently a hydroxy group or C 1 -C 6 is an alkyl group, R 2 are independently deuterium, or unsubstituted or one or more R 2-1 C is replaced by 1 -C 6 is an alkyl group, Each R 2-1 are independently halogen or deuterium, m is 0 or 1, Ring B is one or more R b-1 wherein the heteroatoms in the 5-12 membered fused ring heteroaryl ring are N and / or S, the number of heteroatoms is 1, 2, 3 or 4, and the number of rings in the 5-12 membered fused ring heteroaryl ring is 2; Each R b-1 are independently halogen, or unsubstituted or one or more R b-1-1 C is replaced by 1 -C 6 is an alkyl group, Each R b-1-1 are independently halogen; R 3 is hydrogen, unsubstituted or one or more R 3-1 a 3-6 membered cycloalkyl group, unsubstituted or substituted by one or more R 3-2 a 4-12 membered heterocyclyl group, unsubstituted or substituted by one or more R 3-3 a 4-10 membered cycloalkenyl group, unsubstituted or substituted by one or more R 3-4 a 4-10 membered heterocycloalkenyl group, unsubstituted or substituted by one or more R 3-5 a 6-10 membered aryl group, unsubstituted or substituted by one or more R 3-6 a 5-10 membered heteroaryl group substituted by -C(O)R 4 , unsubstituted or one or more R 3-7 C is replaced by 1 -C 6 alkyl group, or unsubstituted or one or more R 3-8 -OR is replaced by 7 wherein the heteroatoms in the 4- to 12-membered heterocyclyl group or the 4- to 10-membered heterocycloalkenyl group are one or more of N, O, and S, and the number of heteroatoms is 1 or 2; the heteroatoms in the 5- to 10-membered heteroaryl group are N and / or O, and the number of heteroatoms is 1, 2, 3, or 4; Each R 3-1 are independently deuterium or a hydroxy group, Each R 3-2 are independently deuterium, oxo, halogen, C 1 -C 6 Alkoxy group, -NR 3-4-2 R 3-4-2 , -S(O) 2 R 3-4-1 , a hydroxy group, or unsubstituted or one or more R 3-2-2 C is replaced by 1 -C 6 is an alkyl group, Each R 3-3 are independently deuterium, oxo, amino, or hydroxy; Each R 3-4 are independently deuterium, oxo or C 1 -C 6 is an alkyl group, R 3-4-1 is C 1 -C 6 is an alkyl group, Each R 3-4-2 are independently -S(O) 2 R 3-4-1 , hydrogen or C 1 -C 6 is an alkyl group, Each R 3-5 are independently deuterium, R 3-5-1 is C 1 -C 6 is an alkyl group, Each R 3-6 are independently deuterium, halogen, unsubstituted or one or more R 3-2-2 C is replaced by 1 -C 6 alkyl group, or unsubstituted or one or more R 3-6-1 wherein the heteroatoms in the 4-6 membered heterocyclyl group are selected from any one or two of N, O and S, and the number of heteroatoms is 1 or 2; Each R 3-5-2 are independently a hydroxy group, C 1 -C 6 alkyl group or 1-10 membered heteroalkyl group, or two R 3-5-2 form a 4-10 membered heterocyclyl group, wherein the heteroatoms in the 1-10 membered heteroalkyl group include, in addition to phosphorus, any one or more selected from N, O and S, and the number of heteroatoms is 1, 2, 3 or 4; the heteroatoms in the 4-10 membered heterocyclyl group include, in addition to phosphorus, any one or more selected from N, O and S, and the number of heteroatoms is 1, 2, 3 or 4; Each R 3-6-1 independently C 1 -C 6 is an alkyl group, Each R 3-2-2 are independently deuterium or a hydroxy group, Each R 3-7 are independently deuterium, hydroxyl group, -S(O) 2 R 3-4-1 a 4- to 6-membered heterocyclyl group, wherein the heteroatom in the 4- to 6-membered heterocyclyl group is O and the number of heteroatoms is 1; Each R 3-8 are independently deuterium or a hydroxy group, R 4 is a 4- to 6-membered heterocyclyl group, the heteroatom in the 4- to 6-membered heterocyclyl group is O, and the number of heteroatoms is 1; R 7 is a 3- to 6-membered cycloalkyl group, Embodiment 9: Ring A is a 5- or 6-membered heteroaryl ring, the heteroatom in the 5- or 6-membered heteroaryl ring is N, and the number of heteroatoms is 1; R 1 is unsubstituted or one or more R 1-2 wherein the heteroatom in the 5-6 membered heteroaryl group is N and the number of heteroatoms is 1 or 2; Each R 1-2 are independently deuterium, halogen, unsubstituted or one or more R 1-1-1 C is replaced by 1 -C 6 Alkyl group, unsubstituted or one or more R 1-1-2 C is replaced by 1 -C 6 an alkoxy group or Each R 1-1-1 and R 1-1-2 are independently halogen or deuterium, Each R 1-1-11 are independently a hydroxy group or C 1 -C 6 is an alkyl group, R 2 are independently deuterium, or unsubstituted or one or more R 2-1 C is replaced by 1 -C 6 is an alkyl group, Each R 2-1 are independently halogen or deuterium, m is 0 or 1, Ring B is one or more R b-1 wherein the heteroatoms in the 5-12 membered fused ring heteroaryl ring are N and / or S, the number of heteroatoms is 1, 2, 3 or 4, and the number of rings in the 5-12 membered fused ring heteroaryl ring is 2; Each R b-1 are independently halogen, or unsubstituted or one or more R b-1-1 C is replaced by 1 -C 6 is an alkyl group, Each R b-1-1 are independently halogen; R 3 is unsubstituted or one or more R 3-1 a 3-6 membered cycloalkyl group, unsubstituted or substituted by one or more R 3-2 a 4-9 membered heterocyclyl group, unsubstituted or substituted by one or more R 3-3 a 4-6 membered cycloalkenyl group, unsubstituted or substituted by one or more R 3-4 a 4-6 membered heterocycloalkenyl group, unsubstituted or substituted by one or more R 3-5 or a phenyl group substituted with one or more R 3-6 wherein the heteroatoms in the 4-9 membered heterocyclyl group or the 4-6 membered heterocycloalkenyl group are N and / or O and the number of heteroatoms is 1 or 2, and the heteroatoms in the 5-10 membered heteroaryl group are selected from N and the number of heteroatoms is 1, 2, 3 or 4; Each R 3-1 are independently deuterium or a hydroxy group, Each R 3-2 are independently deuterium, oxo, halogen, C 1 -C 6 Alkoxy group, -NR 3-4-2 R 3-4-2 , -S(O) 2 R 3-4-1 , a hydroxy group, or unsubstituted or one or more R 3-2-2 C is replaced by 1 -C 6 is an alkyl group, Each R 3-3 are independently deuterium, oxo, amino, or hydroxy; Each R 3-4 are independently deuterium, oxo or C 1 -C 6 is an alkyl group, R 3-4-1 is C 1 -C 6 is an alkyl group, Each R 3-4-2 are independently -S(O) 2 R 3-4-1 , hydrogen or C 1 -C 6 is an alkyl group, Each R 3-5 are independently deuterium, R 3-5-1 is C 1 -C 6 is an alkyl group, Each R 3-6 are independently deuterium, halogen, unsubstituted or one or more R 3-2-2 C is replaced by 1 -C 6 alkyl group, or unsubstituted or one or more R 3-6-1 wherein the heteroatoms in the 4-6 membered heterocyclyl group are selected from any one or two of N, O and S, and the number of heteroatoms is 1 or 2; Each R 3-5-2 are independently a hydroxy group, C 1 -C 6 alkyl group or 1-10 membered heteroalkyl group, or two R 3-5-2 form a 4-10 membered heterocyclyl group, wherein the heteroatoms in the 1-10 membered heteroalkyl group include, in addition to phosphorus, any one or more selected from N, O and S, and the number of heteroatoms is 1, 2, 3 or 4; the heteroatoms in the 4-10 membered heterocyclyl group include, in addition to phosphorus, any one or more selected from N, O and S, and the number of heteroatoms is 1, 2, 3 or 4; Each R 3-6-1 independently C 1 -C 6 is an alkyl group, Each R 3-2-2 are independently deuterium or a hydroxy group, Embodiment 9': Ring A is a 5- or 6-membered heteroaryl ring, the heteroatom in the 5- or 6-membered heteroaryl ring is N, and the number of heteroatoms is 1; R 1 is unsubstituted or one or more R 1-2 wherein the heteroatom in the 5-6 membered heteroaryl group is N and the number of heteroatoms is 1 or 2; Each R 1-2 are independently deuterium, halogen, unsubstituted or one or more R 1-1-1 C is replaced by 1 -C 6 alkyl group, or unsubstituted or one or more R 1-1-2 C is replaced by 1 -C 6 is an alkoxy group, Each R 1-1-1 and R 1-1-2 are independently halogen or deuterium, Each R 1-1-11 are independently a hydroxy group or C 1 -C 6 is an alkyl group, R 2 are independently deuterium, or unsubstituted or one or more R 2-1 C is replaced by 1 -C 6 is an alkyl group, Each R 2-1 are independently halogen or deuterium, m is 0 or 1, Ring B is one or more R b-1 wherein the heteroatoms in the 5-12 membered fused ring heteroaryl ring are N and / or S, the number of heteroatoms is 1, 2, 3 or 4, and the number of rings in the 5-12 membered fused ring heteroaryl ring is 2; Each R b-1 are independently halogen, or unsubstituted or one or more R b-1-1 C is replaced by 1 -C 6 is an alkyl group, Each R b-1-1 are independently halogen; R 3 is unsubstituted or one or more R 3-1 a 3-6 membered cycloalkyl group, unsubstituted or substituted by one or more R 3-2 a 4-9 membered heterocyclyl group, unsubstituted or substituted by one or more R 3-3 a 4-6 membered cycloalkenyl group, unsubstituted or substituted by one or more R 3-4 a 4-6 membered heterocycloalkenyl group, unsubstituted or substituted by one or more R 3-5 or a phenyl group substituted with one or more R 3-6 wherein the heteroatoms in the 4-9 membered heterocyclyl group or the 4-6 membered heterocycloalkenyl group are N and / or O and the number of heteroatoms is 1 or 2, and the heteroatoms in the 5-10 membered heteroaryl group are selected from N and the number of heteroatoms is 1, 2, 3 or 4; Each R 3-1 are independently deuterium or a hydroxy group, Each R 3-2 are independently deuterium, oxo, halogen, C 1 -C 6 Alkoxy group, -NR 3-4-2 R 3-4-2 , -S(O) 2 R 3-4-1 , a hydroxy group, or unsubstituted or one or more R 3-2-2 C is replaced by 1 -C 6 is an alkyl group, Each R 3-3 are independently deuterium, oxo, amino, or hydroxy; Each R 3-4 are independently deuterium, oxo or C 1 -C 6 is an alkyl group, R 3-4-1 is C 1 -C 6 is an alkyl group, Each R 3-4-2 are independently -S(O) 2 R 3-4-1 , hydrogen or C 1 -C 6 is an alkyl group, Each R 3-5 are independently deuterium, R 3-5-1 is C 1 -C 6 is an alkyl group, Each R 3-6 are independently deuterium, halogen, unsubstituted or one or more R 3-2-2 C is replaced by 1 -C 6 alkyl group, or unsubstituted or one or more R 3-6-1 wherein the heteroatoms in the 4-6 membered heterocyclyl group are selected from any one or two of N, O and S, and the number of heteroatoms is 1 or 2; Each R 3-5-2 are independently a hydroxy group, C 1 -C 6 alkyl group or 1-10 membered heteroalkyl group, or two R 3-5-2 form a 4-10 membered heterocyclyl group, wherein the heteroatoms in the 1-10 membered heteroalkyl group include, in addition to phosphorus, any one or more selected from N, O and S, and the number of heteroatoms is 1, 2, 3 or 4; the heteroatoms in the 4-10 membered heterocyclyl group include, in addition to phosphorus, any one or more selected from N, O and S, and the number of heteroatoms is 1, 2, 3 or 4; Each R 3-6-1 independently C 1 -C 6 is an alkyl group, Each R 3-2-2 are independently deuterium or a hydroxy group, Embodiment 10: m is 0 or 1, n is 1, Ring A is a 5- or 6-membered heteroaryl ring, the heteroatom in the 5- or 6-membered heteroaryl ring is N, and the number of heteroatoms is 1; R 1 is unsubstituted or one or more R 1-2 wherein the heteroatom in the 5-6 membered heteroaryl group is N and the number of heteroatoms is 1, 2 or 3; Each R 1-2 are independently deuterium, halogen, cyano, amino, hydroxy, unsubstituted or one or more R 1-1-1 C is replaced by 1 -C 6 Alkyl group, unsubstituted or one or more R 1-1-2 C is replaced by 1 -C 6 Alkoxy group, unsubstituted or one or more R 1-1-3 C is replaced by 2 -C 6 Alkenyl group, or unsubstituted or one or more R 1-1-4 C is replaced by 2 -C 6 is an alkynyl group, Each R 1-1-1 , R 1-1-2 , R 1-1-3 and R 1-1-4 are independently deuterium, a hydroxy group, a cyano group, or a halogen; Each R 2 are independently deuterium, halogen, cyano, amino, hydroxy, unsubstituted or one or more R 2-1 C is replaced by 1 -C 6 Alkyl group, unsubstituted or one or more R 2-2 C is replaced by 1 -C 6 Alkoxy group, unsubstituted or one or more R 2-3 C is replaced by 2 -C 6 Alkenyl group, unsubstituted or with one or more R 2-4 C is replaced by 2 -C 6 Alkynyl group, unsubstituted or with one or more R 2-5 a 3- to 6-membered cycloalkyl group substituted by, or unsubstituted or substituted by one or more R 2-6 wherein the heteroatoms in said 4-12 membered heterocyclyl group are selected from N and the number of heteroatoms is 1, 2 or 3; Each R 2-1 , R 2-2 , R 2-3 , R 2-4 , R 2-5 and R 2-6 are independently deuterium, a hydroxy group, a cyano group, or a halogen; Ring B may be unsubstituted or may contain one or more R b-1 wherein the heteroatoms in the 5-20 membered fused ring heteroaryl ring are selected from one or more of N, O and S, and the number of heteroatoms is 1, 2, 3, 4, 5, 6, 7 or 8; the single heteroaryl ring in the 5-20 membered fused ring heteroaryl ring is a 5-7 membered heteroaryl ring; the number of rings in the 5-20 membered fused ring heteroaryl ring is 2 or 3; and when the number of rings in the 5-20 membered fused ring heteroaryl ring is 2, the ring B may be substituted with one or more of R b-1 is a 5-20 membered fused heteroaryl ring substituted by Each R b-1 are independently halogen, or unsubstituted or one or more R b-1-1 C is replaced by 1 -C 6 is an alkyl group, Each R b-1-1 are independently a hydroxy group or a halogen; R 3 is hydrogen, unsubstituted or one or more R 3-1 a 3- to 12-membered cycloalkyl group, unsubstituted or substituted by one or more R 3-2 a 4-12 membered heterocyclyl group, unsubstituted or substituted by one or more R 3-3 a 4-12 membered cycloalkenyl group, unsubstituted or substituted by one or more R 3-4 a 4-12 membered heterocycloalkenyl group, unsubstituted or substituted by one or more R 3-5 a 6-10 membered aryl group, unsubstituted or substituted by one or more R 3-6 a 5-10 membered heteroaryl group substituted by -C(O)R 4 , unsubstituted or one or more R 3-7 C is replaced by 1 -C 6 alkyl group, or unsubstituted or one or more R 3-8 -OR is replaced by 7 wherein the heteroatoms in the 4- to 12-membered heterocyclyl group, the 4- to 12-membered heterocycloalkenyl group, and the 5- to 10-membered heteroaryl group are selected from one or more of N, O, and S, and the number of heteroatoms is 1, 2, 3, or 4; Each R 3-1 , R 3-2 , R 3-3 and R 3-4 are independently deuterium, hydroxyl group, halogen, cyano group, amino group, -NHC(O)R 3-2-1 , unsubstituted or one or more R 3-2-2 C is replaced by 1 -C 6 Alkyl group, C 1 -C 6 Alkoxy group, C 2 -C 6 Alkenyl group, C 2 -C 6 Alkynyl group, oxo group (=O), -C(O)NH 2 , unsubstituted or one or more R 3-2-3 a 3- to 6-membered cycloalkyl group, a 4- to 6-membered heterocyclyl group, -S(O) 2 R 3-4-1 , -NR 3-4-2 R 3-4-2 , wherein the heteroatom in the 4- to 6-membered heterocyclyl group is selected from one or more of N, O and S, and the number of heteroatoms is 1 or 2; the heteroatom in the 5- to 6-membered heteroaryl group is N, and the number of heteroatoms is 1 or 2; Each R 3-7 are independently deuterium, a hydroxy group, a halogen, a cyano group, or an amino group; Each R 3-8 are independently a hydroxy group or a 4- to 6-membered heterocyclyl group; Each R 3-5 and R 3-6 are independently deuterium, Hydroxy group, halogen, cyano group, amino group, -NHC(O)R 3-2-1 , unsubstituted or one or more R 3-2-2 C is replaced by 1 -C 6 Alkyl group, C 2 -C 6 Alkenyl group, C 2 -C 6 Alkynyl group, -C(O)NH 2 , unsubstituted or one or more R 3-2-3 a 3-6 membered cycloalkyl group, unsubstituted or substituted by one or more R 3-6-1 a 4-6 membered heterocyclyl group substituted by wherein the heteroatoms in the 4- to 6-membered heterocyclyl group are selected from one or more of N, O and S, and the number of heteroatoms is 1 or 2; Each R 3-2-1 and R 3-4-2 are independently hydrogen or C 1 -C 6 is an alkyl group, Each R 3-2-3 and R 3-5-1 are independently a hydroxy group or C 1 -C 6 is an alkyl group, Each R 3-5-2 are independently a hydroxy group, C 1 -C 6 alkyl group or 1-10 membered heteroalkyl group, or two R 3-5-2 form a 4-10 membered heterocyclyl group, wherein the heteroatoms in the 1-10 membered heteroalkyl group include, in addition to phosphorus, any one or more selected from N, O and S, and the number of heteroatoms is 1, 2, 3 or 4; the heteroatoms in the 4-10 membered heterocyclyl group include, in addition to phosphorus, any one or more selected from N, O and S, and the number of heteroatoms is 1, 2, 3 or 4; Each R 3-6-1 independently C 1 -C 6 is an alkyl group, Each R 3-2-2 are independently deuterium, a hydroxyl group, or a halogen; R 3-4-1 is a hydroxy group, an amino group or C 1 -C 6 is an alkyl group, R 4 is unsubstituted or one or more R 4-1 wherein the heteroatoms in the 4-6 membered heterocyclyl group are selected from N and the number of heteroatoms is 1 or 2; Each R 4-1 are independently a hydroxy group, R 7 is a 3- to 6-membered cycloalkyl group, Embodiment 11: m is 0 or 1, n is 1, Ring A is a 5- or 6-membered heteroaryl ring, the heteroatom in the 5- or 6-membered heteroaryl ring is N, and the number of heteroatoms is 1; R 1 is unsubstituted or one or more R 1-2 wherein the heteroatom in the 5-6 membered heteroaryl group is N and the number of heteroatoms is 1; Each R 1-2 are independently deuterium, halogen, or unsubstituted or one or more R 1-1-2 C is replaced by 1 -C 6 is an alkoxy group, Each R 1-1-2 are independently deuterium, a hydroxy group, a cyano group, or a halogen; Each R 2 are independently deuterium, or unsubstituted or one or more R 2-1 C is replaced by 1 -C 6 is an alkyl group, Each R 2-1 are independently deuterium, a hydroxy group, a cyano group, or a halogen; Ring B may be unsubstituted or may contain one or more R b-1 wherein the heteroatoms in the 5-20 membered fused ring heteroaryl ring are selected from one or more of N, O and S, and the number of heteroatoms is 1, 2, 3, 4, 5, 6, 7 or 8; the single heteroaryl ring in the 5-20 membered fused ring heteroaryl ring is a 5-7 membered heteroaryl ring; the number of rings in the 5-20 membered fused ring heteroaryl ring is 2 or 3; and when the number of rings in the 5-20 membered fused ring heteroaryl ring is 2, the ring B may be substituted with one or more of R b-1 is a 5-20 membered fused heteroaryl ring substituted by Each R b-1 are independently halogen or C 1 -C 6 is an alkyl group, R 3 is unsubstituted or one or more R 3-1 a 3- to 12-membered cycloalkyl group, unsubstituted or substituted by one or more R 3-2 a 4-12 membered heterocyclyl group, unsubstituted or substituted by one or more R 3-3 a 4-12 membered cycloalkenyl group, unsubstituted or substituted by one or more R 3-4 a 4-12 membered heterocycloalkenyl group, unsubstituted or substituted by one or more R 3-5 a 6-10 membered aryl group, unsubstituted or substituted by one or more R 3-6 a 5-10 membered heteroaryl group substituted by, or unsubstituted or one or more R 3-8 -OR is replaced by 7 wherein the heteroatoms in the 4- to 12-membered heterocyclyl group, the 4- to 12-membered heterocycloalkenyl group, and the 5- to 10-membered heteroaryl group are selected from one or more of N, O, and S, and the number of heteroatoms is 1, 2, 3, or 4; Each R 3-1 , R 3-2 , R 3-3 and R 3-4 are independently deuterium, hydroxyl group, halogen, cyano group, amino group, -NHC(O)R 3-2-1 , unsubstituted or one or more R 3-2-2 C is replaced by 1 -C 6 Alkyl group, C 1 -C 6 Alkoxy group, C 2 -C 6 Alkenyl group, C 2 -C 6 Alkynyl group, oxo group (=O), Each R 3-8 are independently a hydroxy group or a 4- to 6-membered heterocyclyl group; Each R 3-5 and R 3-6 are independently deuterium, Hydroxy group, halogen, cyano group, amino group, unsubstituted or one or more R 3-2-2 C is replaced by 1 -C 6 Alkyl group, C 2 -C 6 Alkenyl group, C 2 -C 6 Alkynyl group, -C(O)NH 2 , unsubstituted or one or more R 3-2-3 a 3-6 membered cycloalkyl group, unsubstituted or substituted by one or more R 3-6-1 a 4-6 membered heterocyclyl group substituted by wherein the heteroatoms in the 4- to 6-membered heterocyclyl group are selected from one or more of N, O and S, and the number of heteroatoms is 1 or 2; Each R 3-2-1 are independently hydrogen or C 1 -C 6 is an alkyl group, Each R 3-2-3 and R 3-5-1 are independently a hydroxy group or C 1 -C 6 is an alkyl group, Each R 3-5-2 are independently a hydroxy group, C 1 -C 6 alkyl group or 1-10 membered heteroalkyl group, or two R 3-5-2 form a 4-10 membered heterocyclyl group, wherein the heteroatoms in the 1-10 membered heteroalkyl group include, in addition to phosphorus, any one or more selected from N, O and S, and the number of heteroatoms is 1, 2, 3 or 4; the heteroatoms in the 4-10 membered heterocyclyl group include, in addition to phosphorus, any one or more selected from N, O and S, and the number of heteroatoms is 1, 2, 3 or 4; Each R 3-6-1 independently C 1 -C 6 is an alkyl group, Each R 3-2-2 are independently deuterium, a hydroxyl group, or a halogen; R 7 is a 3- to 6-membered cycloalkyl group, Embodiment 12: m is 0 or 1, n is 1, Ring A is a 5- or 6-membered heteroaryl ring, the heteroatom in the 5- or 6-membered heteroaryl ring is N, and the number of heteroatoms is 1; R 1 is unsubstituted or one or more R 1-2 wherein the heteroatom in the 5-6 membered heteroaryl group is N and the number of heteroatoms is 1; Each R 1-2 are independently deuterium, halogen, or unsubstituted or one or more R 1-1-2 C is replaced by 1 -C 6 is an alkoxy group, Each R 1-1-2 are independently deuterium, a hydroxy group, a cyano group, or a halogen; Each R 2 are independently deuterium, or unsubstituted or one or more R 2-1 C is replaced by 1 -C 6 is an alkyl group, Each R 2-1 are independently deuterium, a hydroxy group, a cyano group, or a halogen; Ring B is one or more R b-1 wherein the heteroatoms in the 5-12 membered fused heteroaryl ring are selected from N and S, and the number of heteroatoms is 1, 2, 3 or 4 (e.g., Each R b-1 are independently halogen or C 1 -C 6 an alkyl group (e.g., a fluorine or methyl group); R 3 is unsubstituted or one or more R 3-1 a 3-6 membered cycloalkyl group, unsubstituted or substituted by one or more R 3-2 a 4-6 membered heterocyclyl group, unsubstituted or substituted by one or more R 3-3 a 4-6 membered cycloalkenyl group, unsubstituted or substituted by one or more R 3-4 a 4-6 membered heterocycloalkenyl group, unsubstituted or substituted by one or more R 3-5 or a phenyl group substituted with one or more R 3-6 wherein the heteroatoms in the 4- to 6-membered heterocyclyl group or the 4- to 6-membered heterocycloalkenyl group are N and / or O and the number of heteroatoms is 1 or 2, and the heteroatom in the 5- to 6-membered heteroaryl group is N and the number of heteroatoms is 1, 2 or 3; Each R 3-1 , R 3-2 , R 3-3 and R 3-4 are independently deuterium, a hydroxyl group, or C 1 -C 6 is an alkyl group, Each R 3-5 independently R 3-5-1 is C 1 -C 6 is an alkyl group, Each R 3-5-2 are independently a hydroxy group or C 1 -C 6 is an alkyl group, Each R 3-6 are independently halogen, or unsubstituted or one or more R 3-2-2 C is replaced by 1 -C 6 is an alkyl group, Each R 3-2-2 are independently deuterium.

11. The compound represented by formula I according to claim 1, a pharmaceutically acceptable salt thereof, or an isotope thereof, is characterized in that the compound represented by formula I satisfies one or more of the following conditions:

12. The compound represented by formula I according to claim 1, characterized in that the compound represented by formula I is any of the following compounds, a pharmaceutically acceptable salt thereof, or an isotope thereof:

13. A method for preparing a compound of formula I', comprising embodiment a, embodiment b or embodiment c: The above embodiment a includes the steps of: subjecting a compound represented by formula II to a condensation reaction with a compound represented by formula III in a solvent as follows to obtain the compound represented by formula I'; The embodiment b includes the steps of: (a) subjecting a compound represented by formula II to a condensation reaction with a compound represented by formula III' in a solvent as follows to obtain the compound represented by formula I"; where X is dimethyl tert-butylsilyl ether or tert-butoxycarbonyl; (b) subjecting the compound of formula I″ obtained in step (a) to a deprotection reaction as described below in a solvent in the presence of an acid to obtain the compound of formula I′; The embodiment c includes the following steps: subjecting a compound represented by formula IV to a condensation reaction with a compound represented by formula V in a solvent in the presence of a condensing agent, as follows, to obtain the compound represented by formula I': Y is hydrogen or a carbonyl group; where R 1 , R 2 , m, ring A, L, ring B and R 3 is as defined in any one of claims 1 to 10, Preferably, the process for preparing the compound of formula I satisfies one or more of the following conditions: (1) In embodiment a, in the condensation reaction, the molar ratio of the compound represented by formula II to the compound represented by formula III is 1:(0.5-1.5), for example, 1:1, 1:1.35, or 1:0.83; (2) In embodiment b, in the condensation reaction, the molar ratio of the compound represented by formula II to the compound represented by formula III is 1:(0.5-1.5), for example, 1:1 or 0.67; (3) In embodiment a or b, in the condensation reaction, the solvent is an amide solvent and / or a cyanide solvent, preferably the amide solvent is N,N-dimethylformamide, and preferably the cyanide solvent is acetonitrile; (4) In embodiment a or b, in the condensation reaction, the condensing agent is N,N,N',N'-tetramethylformamidinium hexafluorophosphate and 1-methylimidazole; (5) In embodiment a or b, in the condensation reaction, the molar ratio of the compound represented by formula II to the condensing agent is 1:(2-5), for example, 1:4 or 1:4.3, 1:3.7 or 1:4.1; (6) In embodiment a or b, in the condensation reaction, the reaction temperature of the condensation reaction is room temperature; (7) In embodiment a or b, the condensation reaction further includes post-treatment, and the post-treatment step includes any one or more steps of concentration, washing with water, extraction, drying, column chromatography, and preparative chromatography; (8) In embodiment c, in the condensation reaction, when Y is a carbonyl group, the molar ratio of the compound represented by formula IV to the compound represented by formula V is 1:(0.3-0.6), for example, 1:0.46; (9) In embodiment c, in the condensation reaction, when Y is a carbonyl group, the solvent is an alcohol solvent, for example, methanol; (10) In embodiment c, in the condensation reaction, when Y is a carbonyl group, the condensing agents are sodium cyanoborohydride and tetraethyl titanate; (11) In embodiment c, in the condensation reaction, when Y is a carbonyl group, the molar ratio of the compound represented by formula IV to the condensing agent is 1:(2-5), for example, 1:3.2; (12) In embodiment c, when Y is a carbonyl group in the condensation reaction, the reaction temperature of the condensation reaction is room temperature; (13) In embodiment c, when Y is a carbonyl group in the condensation reaction, the condensation reaction further comprises post-treatment, and the post-treatment step comprises one or more steps of filtration, concentration, and preparative chromatography; (14) In embodiment c, in the condensation reaction, when Y is hydrogen, the molar ratio of the compound represented by formula IV to the compound represented by formula V is 1:(1 to 1.5), for example, 1:1.49; (15) In embodiment c, in the condensation reaction, when Y is hydrogen, the solvent is an amide solvent and / or a cyanide solvent, preferably the amide solvent is N,N-dimethylformamide, and preferably the cyanide solvent is acetonitrile; (16) In embodiment c, in the condensation reaction, when Y is hydrogen, the condensing agent is N,N,N',N'-tetramethylformamidinium hexafluorophosphate and 1-methylimidazole; (17) In embodiment c, in the condensation reaction, when Y is hydrogen, the molar ratio of the compound represented by formula IV to the condensing agent is 1:(2-5), for example, 1:4.2; (18) In embodiment c, when Y is hydrogen in the condensation reaction, the reaction temperature of the condensation reaction is room temperature; And (19) In embodiment c, when Y is hydrogen in the condensation reaction, the condensation reaction further comprises post-treatment, and the post-treatment step comprises one or more steps of extraction, drying, concentration, and preparative chromatography.

14. (1) A (therapeutically effective amount) of a substance A which is a compound according to any one of claims 1 to 12, a pharmaceutically acceptable salt thereof, or an isotopic compound thereof; (2) pharmaceutically acceptable additives; The present invention provides a pharmaceutical composition comprising:

15. 13. Use of substance A, which is a compound according to any one of claims 1 to 12, a pharmaceutically acceptable salt or an isotopic compound thereof, in the preparation of a polymerase theta inhibitor.

16. 13. Use of substance A, which is a compound according to any one of claims 1 to 12, a pharmaceutically acceptable salt or an isotopic compound thereof, in the preparation of a medicament for treating lung cancer, breast cancer, HR-deficient ovarian cancer, gastric cancer, prostate cancer, pancreatic adenocarcinoma or colon cancer.

17. A compound represented by any of the following:

18. A compound represented by formula VI: Ring B may be unsubstituted or may contain one or more R b-1 wherein the heteroatoms in the 5-20 membered fused ring heteroaryl ring are selected from one or more of N, O and S, and the number of heteroatoms is 1, 2, 3, 4, 5, 6, 7 or 8; the single heteroaryl ring in the 5-20 membered fused ring heteroaryl ring is a 5-7 membered heteroaryl ring; the number of rings in the 5-20 membered fused ring heteroaryl ring is 3 or 4; and R 3 and n is as defined in any one of claims 1 to 11.

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