PI3Kα inhibitors and their use

Abstract

A PI3Kα inhibitor and its use, wherein the inhibitor has the structure shown in formula (I), has excellent selective inhibitory activity against mutant PI3Kα, and can be used in the preparation of antitumor drugs.

Description

[Technical Field]

[0001] The present invention relates to the field of pharmaceutical technology, and more specifically to a group of compounds used as PI3Kα inhibitors, and their stereoisomers, deuterides, pharmaceutically acceptable salts, solvates, or prodrugs, to pharmaceutical compositions containing such compounds and salts, and to their use and their application in the regulation of PI3Kα activity or the treatment of PI3Kα-related diseases. [Background technology]

[0002] Phosphatidylinositol 3-kinases (PI3Ks) belong to a unique and conserved family of intracellular lipid kinases and can phosphorylate phosphatidylinositol or the 3'-OH group on phosphatidylinositol. They play important roles in many fundamental biological processes (proliferation, survival, differentiation, and metabolism). PI3Ks are currently classified into classes IA, IB, II, and III. Class IPI3Ks (p110α, p110β, p110δ, and p110γ) are typically activated by tyrosine kinases or G protein-coupled receptors to produce PIP3, which binds to downstream effectors such as Akt / PDK1, mTOR, Tec family kinases, and effectors in the Rho family GTPases pathway. Class II and Class III PI3Ks play important roles in intracellular transport by synthesizing PI(3)P and PI(3,4)P2. Here, the class IA family consists of three isoforms: α, β, and δ. The Class IB family contains only the γ isoform. In different PI3K subfamily proteins, PI3Kα is a heterodimer containing the p110α catalytic subunit and the p85α regulatory subunit. The gene encoding the p110α subunit PIK3CA mutates at a rate of nearly 30% in human cancers, including colorectal cancer, glioblastoma, and gastric cancer. Importantly, hyperactivation of PI3Kα is directly associated with drug resistance to existing therapeutic agents and poor prognosis.

[0003] Mutations in the PI3Kα coding gene primarily occur as point mutations in several hotspots of the helical and kinase domains, such as E542K, E545K, and H1047R. These mutations have been proven to be gain-of-function mutations that cause cancer. Due to the high incidence of PI3Kα mutations, targeting this pathway may offer valuable therapeutic opportunities. While other PI3K isomers such as PI3Kδ and PI3Kγ are mainly expressed in hematopoietic cells, PI3Kα and PI3Kβ are constitutively expressed. Because PI3Kα plays a central role in regulating glucose stability in the body, PI3K inhibition can typically cause hyperglycemia and / or hyperinsulinemia in patients. High levels of circulating insulin may weaken the antiproliferative effects of PI3K inhibitors by promoting mitosis and / or anti-apoptosis in cancer cells.

[0004] In the cancerous environment of PI3Kα mutations, one way to overcome the problem of compensatory insulin and / or glucose production after systemic PI3Kα inhibition is to develop inhibitors that show higher selectivity for mutant PI3Kα than for wild-type PI3Kα. This would broaden the range of drug dose adjustments for selectively inhibiting the pathological signaling of mutant PI3Kα in cancer cells without affecting wild-type PI3Kα, which regulates systemic metabolism in host tissues. This would reduce toxicity and allow for higher doses and more complete inhibition of the drug target point.

[0005] Currently, PI3Kα inhibitors are nearly equivalent for wild-type and mutant PI3Kα. Because the mutation sites of PI3Kα are far from the active site, developing selective inhibitors for mutations is much more difficult. Therefore, inhibitors targeting the allosteric binding pocket near known mutations (e.g., H1047R, E542K, E545K) may offer a novel pathway for selectively inhibiting PI3Kα. Conversely, targeting the allosteric binding pocket of PI3Kα mutations may offer valuable therapeutic target points in drug development. [Overview of the project] [Problems that the invention aims to solve]

[0006] The object of the present invention is to provide a compound represented by formula (I), a method for preparing the same, and its drug applications as a selective PI3Kα inhibitor. [Means for solving the problem]

[0007] A first aspect of the present invention provides a compound, which is a compound of formula (I), or a pharmaceutically acceptable salt, stereoisomer, deuteride, solvate, or prodrug thereof. [ka] Here, X1 is N, O, S, NR 11 , C(R 11 ) q Selected from the group consisting of, X2 and X3 are each independently selected from the group consisting of N and C. X4 is N or CR, X5 does not exist, O, NR 51 , C 1-6 Alkylene group, C 3-6 Selected from the group consisting of a cycloalkylene group and a 3-6 membered heterocyclic alkylene group containing 1-4 heteroatoms selected from N, O, or S, where the C 1-6 Alkylene group, C 3-6A cycloalkylene group or a 3- to 6-membered heterocyclic alkylene group is optionally substituted by 1, 2, 3, 4, 5 or 6 R 52 , X6 is selected from the group consisting of absent, NR 61 , C 1-6 alkylene, wherein said C 1-6 alkylene group is optionally substituted by 1, 2, 3, 4, 5 or 6 R 62 ,

[0008] X7 is selected from the group consisting of C=O, C=S, CR 71 , Ring B is a 5- to 7-membered heterocyclic alkyl group containing one N atom and 0 to 3 heteroatoms selected from N, O or S, optionally substituted by one or more R5, Ring A is selected from the group consisting of C 6-10 aryl, a 5- to 10-membered heteroaryl containing 1 to 4 heteroatoms selected from N, O or S, and a 5- to 10-membered heterocyclic alkyl containing 1 to 4 heteroatoms selected from N, O or S, wherein said C 6-10 aryl and 5- to 10-membered heteroaryl are optionally substituted by m R6,

[0009] R, R2, R3, R 11 , R 52 , R 62 are each independently selected from the group consisting of H, deuterium, halogen, oxo (=O), -CN, -NO2, C 1-6 alkyl, halogenated C 1-6 alkyl, deuterated C 1-6 alkyl, C 1-6 alkoxy, halogenated C 1-6 alkoxy, deuterated C 1-6 alkoxy, C 3-6 cycloalkyl, halogenated C 3-6 cycloalkyl, and deuterated C 3-6 cycloalkyl, alternatively, R and R2, together with the atoms to which they are bonded, form C 4-6A cycloalkyl group or a 4-6 membered heterocyclic alkyl group containing 1-4 heteroatoms selected from N, O, or S is formed, where the C 4-6 Cycloalkyl groups and 4-6 membered heterocyclic alkyl groups are optionally substituted with 1, 2, 3, 4, 5, or 6 R6 atoms. Alternatively, R2 and R3, together with the atoms they are bonded to, become C 4-6 A cycloalkyl group or a 4-6 membered heterocyclic alkyl group containing 1-4 heteroatoms selected from N, O, or S is formed, where the C 4-6 Cycloalkyl groups and 4-6 membered heterocyclic alkyl groups are optionally substituted with 1, 2, 3, 4, 5, or 6 R6 atoms.

[0010] R 51 , R 61 These are H, -CN, -NO2, and C, respectively, independently. 1-6 Alkyl alkyl groups, C halogenated compounds 1-6 Alkyl groups, deuterated C 1-6 Alkyl alkyl group, C 1-6 Alkoxy group, halogenated C 1-6 Alkoxy group, deuterated C 1-6 Alkoxy group, C 3-6 Cycloalkyl groups, halogenated C 3-6 Selected from the group consisting of cycloalkyl groups, R 71 H, halogen, -CN, -NO2, C 1-6 Alkyl alkyl groups, C halogenated compounds 1-6 Alkyl alkyl group, C 1-6 Alkoxy group, halogenated C 1-6 Alkoxy group, C 3-6 Cycloalkyl groups, halogenated C 3-6 Selected from the group consisting of cycloalkyl groups and -C(O)R8,

[0011] R4 is -L-(C 1-6 Alkyl), -LC 6-10 Aryl group, -L- (5-10 membered heteroaryl containing 1-4 heteroatoms selected from N, O, or S), -L- (saturated or partially unsaturated C) 3-8Selected from the group consisting of cycloalkyl, -L-(saturated or partially unsaturated 4-8 member heterocyclic alkyl containing 1-4 heteroatoms selected from N, O, or S), where the C 1-6 Alkyl alkyl group, C 6-10 Aryl group, 5-10 membered heteroaryl group, C 3-8 Cycloalkyl groups and 4- to 8-membered heterocyclic alkyl groups are optionally substituted with n R7 atoms.

[0012] Each R5 represents H, deuterium, halogen, -CN, oxo (=O), or C. 1-6 Alkyl alkyl groups, C halogenated compounds 1-6 Alkyl groups, deuterated C 1-6 Alkyl alkyl group, C 1-6 Alkoxy group, halogenated C 1-6 Alkoxy group, deuterated C 1-6 Alkoxy group, C 3-6 Cycloalkyl groups, halogenated C 3-6 Independently selected from the group consisting of cycloalkyl groups, 3-8 membered heterocyclic alkyl groups containing 1-3 heteroatoms selected from N, O, or S, Each R6 represents H, deuterium, halogen, -CN, -NO2, C 1-6 Alkyl alkyl groups, C halogenated compounds 1-6 Alkyl groups, deuterated C 1-6 Alkyl alkyl group, C 1-6 Alkoxy group, halogenated C 1-6 Independently selected from the group consisting of alkoxy groups, -C(O)R8, -C(O)OR8, -C(O)NR8R9, -SO2R8, -S(O)(NR8)R9, -SO2NR8R9, and -P(O)R8R9,

[0013] Each R7 represents hydrogen, deuterium, halogen, oxo (=O), -CN, -OH, -NO2, and C. 1-6 Alkyl alkyl group, C 1-6 Alkoxy group, halogenated C 1-6 Alkyl alkyl groups, C halogenated compounds 1-6 Alkoxy group, deuterated C 1-6 C containing 1 to 4 heteroatoms selected from alkyl groups, N, O, or S 1-6heteroalkyl group, halogenated C containing 1 to 4 heteroatoms selected from N, O or S 1-6 heteroalkyl group, -NR8R9, =NR8, -C(O)R8, -C(O)OR8, -C(O)NR8R9, -NR8C(O)R9, -SR8, -SO2R8, -NR8SO2R9, -SO2NR8R9, -NR8SO2NR9R 10 , -P(O)R8R9, -L1-(C 1-6 alkyl), -L1-(saturated or partially unsaturated C 3-10 cycloalkyl), -L1-(C 6-10 aryl), -L1-(saturated or partially unsaturated 3- to 12-membered heterocyclic alkyl containing 1 to 4 heteroatoms selected from N, O or S), -L1-(5- to 10-membered heteroaryl containing 1 to 4 heteroatoms selected from N, O or S), wherein said C 1-6 alkyl group, C 1-6 heteroalkyl group, C 3-10 cycloalkyl group, C 6-10 aryl group, 3- to 12-membered heterocyclic alkyl group, and 5- to 10-membered heteroaryl group are each deuterium, halogen, =O, -CN, -OH, -NH2, C 1-6 alkyl group, halogenated C 1-6 alkyl group, C 1-6 alkoxy group, halogenated C 1-6 alkoxy group, C 3-6 cycloalkyl group, halogenated C 3-6 cycloalkyl group, 3- to 6-membered heterocyclic alkyl group containing 1 to 4 heteroatoms selected from N, O or S, -SO2R8, -C(O)R8, -C(O)OR8, -C(O)NR8R9, -NR8R9, optionally substituted with 0 to 6 substituents selected from the group consisting of,

[0014] Alternatively, two R7, together with the atoms to which they are bonded, form C 3-6 cycloalkyl group, C 6-10 aryl group, 3- to 6-membered heterocyclic alkyl group containing 1 to 4 heteroatoms selected from N, O or S, or 5- to 6-membered heteroaryl group containing 1 to 4 heteroatoms selected from N, O or S, wherein said C3-6 Cycloalkyl group, C 6-10 aryl group, 3- to 6-membered heterocyclic alkyl group, and 5- to 6-membered heteroaryl group are each optionally substituted with deuterium, halogen, =O, -CN, -OH, -NR8R9, =NR8, -C(O)R8, -C(O)OR8, -C(O)NR8R9, -NR8C(O)R9, -SR8, -SO2R8, -NR8SO2R9, -SO2NR8R9, -NR8SO2NR9R 10 , -P(O)R8R9, C 1-6 alkyl group, C 1-6 alkoxy group, C containing 1 to 4 heteroatoms selected from N, O or S 1-6 heteroalkyl group, halogenated C 1-6 alkyl group, halogenated C 1-6 alkoxy group, halogenated C containing 1 to 4 heteroatoms selected from N, O or S 1-6 heteroalkyl group, C 3-6 cycloalkyl group, and 3- to 6-membered heterocyclic alkyl group containing 1 to 4 heteroatoms selected from N, O or S, wherein the number of optional substituents is 0 to 6 selected from said group,

[0015] L and L1 are each independently a bond, or C 1-6 alkylene group, C 2-6 alkenylene group, C 2-6 alkynylene group, 1- to 6-membered heteroalkylene group containing 1 to 4 heteroatoms selected from N, O or S, -NR8-, -O-, -C(O)-, -C(O)NR8-, -C(O)O-, -NR8C(O)-, -(SO2)-, -SO2NR8-, -NR8SO2-, -NR8SO2NR9-, and -S(O)(NR8)-, wherein said C 1-6 alkylene group, C 2-6 alkenylene group, C 2-6 alkynylene group and 1- to 6-membered heteroalkylene group are each optionally substituted with 0 to 6 substituents selected from the group consisting of deuterium, halogen, =O, -CN, -OH, -NR8R9 and =NR8,

[0016] Each R8, R9, R 10 are each independently H, C1-6 Alkyl alkyl groups, C halogenated compounds 1-6 Alkyl alkyl group, C 3-6 Cycloalkyl groups, C 6-10 Selected from the group consisting of an aryl group, a 3-6 membered heterocyclic alkyl group containing 1-4 heteroatoms selected from N, O, or S, and a 5-6 membered heteroaryl group containing 1-4 heteroatoms selected from N, O, or S, where the C 3-6 Cycloalkyl groups, C 6-10 Aryl groups, 3-6 membered heterocyclic alkyl groups, and 5-6 membered heteroaryl groups are composed of deuterium, halogens, =O, -CN, -OH, -NH2, and C. 1-6 Alkyl alkyl groups, C halogenated compounds 1-6 Alkyl alkyl group, C 1-6 Alkoxy group, halogenated C 1-6 Alkoxy group, C 1-6 Alkylamino group, halogenated C 1-6 Alkylamino group, C 1-6 Alkylthio group, halogenated C 1-6 C containing 1 to 4 heteroatoms selected from alkylthio groups, N, O, or S 1-6 C halogens containing 1 to 4 heteroatoms selected from heteroalkyl groups, N, O, or S. 1-6 Heteroalkyl groups, C 3-6 Cycloalkyl groups, 3-6 membered heterocyclic alkyl groups containing 1-4 heteroatoms selected from N, O, or S, and halogenated carbon atoms. 3-6 It is optionally substituted by 0 to 6 substitutions selected from the group consisting of cycloalkyl groups, 3 to 6-membered heterocyclic alkyl groups containing 1 to 4 heteroatoms selected from N, O, or S,

[0017] Alternatively, R8 and R9, together with the heteroatoms to which they are bonded, form a 3-6 member heterocyclic alkyl group containing 1-4 heteroatoms selected from N, O, or S, where the 3-6 member heterocyclic alkyl group is composed of deuterium, halogen, =O, -CN, -OH, -NH2, or C 1-6 Alkyl alkyl groups, C halogenated compounds 1-6 Alkyl alkyl group, C 1-6 Alkoxy group, halogenated C 1-6 Alkoxy group, C1-6 Alkylamino group, halogenated C 1-6 Alkylamino group, C 1-6 Alkylthio group, halogenated C 1-6 C containing 1 to 4 heteroatoms selected from alkylthio groups, N, O, or S 1-6 C halogens containing 1 to 4 heteroatoms selected from heteroalkyl groups, N, O, or S. 1-6 Heteroalkyl groups, C 3-6 Cycloalkyl groups, 3-6 membered heterocyclic alkyl groups containing 1-4 heteroatoms selected from N, O, or S, and halogenated carbon atoms. 3-6 It is optionally substituted by 0 to 6 substitutions selected from the group consisting of cycloalkyl groups, 3 to 6-membered heterocyclic alkyl groups containing 1 to 4 heteroatoms selected from N, O, or S,

[0018] Alternatively, R9, R 10 These, together with the heteroatoms to which they are bonded, form a 3-6 member heterocyclic alkyl group containing 1-4 heteroatoms selected from N, O, or S, where the 3-6 member heterocyclic alkyl group is composed of deuterium, halogen, =O, -CN, -OH, -NH2, C 1-6 Alkyl alkyl groups, C halogenated compounds 1-6 Alkyl alkyl group, C 1-6 Alkoxy group, halogenated C 1-6 Alkoxy group, C 1-6 Alkylamino group, halogenated C 1-6 Alkylamino group, C 1-6 Alkylthio group, halogenated C 1-6 C containing 1 to 4 heteroatoms selected from alkylthio groups, N, O, or S 1-6 C halogens containing 1 to 4 heteroatoms selected from heteroalkyl groups, N, O, or S. 1-6 Heteroalkyl groups, C 3-6 Cycloalkyl groups, 3-6 membered heterocyclic alkyl groups containing 1-4 heteroatoms selected from N, O, or S, and halogenated carbon atoms. 3-6It is optionally substituted by 0 to 6 substitutions selected from the group consisting of cycloalkyl groups, 3 to 6-membered heterocyclic alkyl groups containing 1 to 4 heteroatoms selected from N, O, or S,

[0019] each [ka] Each of these is independently either a single bond or a double bond. Each of m, n, and q is independently selected from the group consisting of 0, 1, 2, 3, 4, and 5. In another preferred example, the compound has a structure selected from the group consisting of the following: [ka] Here, X4, X5, X6, R2, R3, R4, ring A, and ring B are as defined above.

[0020] X1 is N, CR 11 Selected from the group consisting of, R 11 H, halogen, -CN, -NO2, C 1-6 Alkyl alkyl groups, C halogenated compounds 1-6 Alkyl groups, deuterated C 1-6 Alkyl alkyl group, C 1-6 Alkoxy group, halogenated C 1-6 Alkoxy group, deuterated C 1-6 Alkoxy group, C 3-6 Cycloalkyl groups, halogenated C 3-6 Selected from the group consisting of cycloalkyl groups, R 71 H, halogen, -CN, -NO2, C 1-6 Alkyl alkyl groups, C halogenated compounds 1-6 Alkyl alkyl group, C 1-6 Alkoxy group, halogenated C 1-6 Alkoxy group, C 3-6 Cycloalkyl groups, halogenated C 3-6 Selected from the group consisting of cycloalkyl groups and -C(O)R8,

[0021] R8 is H, C 1-6 alkyl, halogenated C 1-6 alkyl, C 3-6 cycloalkyl, and 3- to 6-membered heterocyclic alkyl containing 1 to 4 heteroatoms selected from N, O or S, wherein said C 3-6 cycloalkyl and 3- to 6-membered heterocyclic alkyl are optionally substituted with 0 to 6 substituents selected from the group consisting of deuterium, halogen, =O, -CN, -OH, -NH2, C 1-6 alkyl, halogenated C 1-6 alkyl, C 1-6 alkoxy, halogenated C 1-6 alkoxy, C containing 1 to 4 heteroatoms selected from N, O or S 1-6 heteroalkyl, and halogenated C containing 1 to 4 heteroatoms selected from N, O or S 1-6 heteroalkyl.

[0022] In another preferred embodiment, said compound has a structure selected from the group consisting of:

Chemical Formula

Chemical Formula

Chemical Formula

[0023] R 52 , R 62 are each independently selected from H, halogen, oxo (=O), -CN, -NO2, C 1-6 alkyl, halogenated C 1-6 alkyl, deuterated C 1-6 alkyl, C 1-6 alkoxy, halogenated C 1-6Alkoxy group, deuterated C 1-6 Alkoxy group, C 3-6 Cycloalkyl groups, halogenated C 3-6 Selected from the group consisting of cycloalkyl groups, R 51 , R 61 These are H, -CN, -NO2, and C, respectively, independently. 1-6 Alkyl alkyl groups, C halogenated compounds 1-6 Alkyl groups, deuterated C 1-6 Alkyl alkyl group, C 1-6 Alkoxy group, halogenated C 1-6 Alkoxy group, deuterated C 1-6 Alkoxy group, C 3-6 Cycloalkyl groups, halogenated C 3-6 Selected from the group consisting of cycloalkyl groups.

[0024] In another preferred example, the compound has a structure selected from the group consisting of the following: [ka] Here, X1, X2, X3, X4, X6, R2, R3, R4, ring A, and ring B are as defined above.

[0025] In another preferred example, the compound has a structure selected from the group consisting of the following: [ka] structure [ka] The following arrangements are selected: [ka] Here, X4, X6, R2, R3, R4, R5, ring A, and p are as defined above.

[0026] R 62 H, halogen, oxo (=O), -CN, -NO2, C 1-6Alkyl alkyl groups, C halogenated compounds 1-6 Alkyl groups, deuterated C 1-6 Alkyl alkyl group, C 1-6 Alkoxy group, halogenated C 1-6 Alkoxy group, deuterated C 1-6 Alkoxy group, C 3-6 Cycloalkyl groups, halogenated C 3-6 Selected from the group consisting of cycloalkyl groups, R 61 H, -CN, -NO2, C 1-6 Alkyl alkyl groups, C halogenated compounds 1-6 Alkyl groups, deuterated C 1-6 Alkyl alkyl group, C 1-6 Alkoxy group, halogenated C 1-6 Alkoxy group, deuterated C 1-6 Alkoxy group, C 3-6 Cycloalkyl groups, halogenated C 3-6 Selected from the group consisting of cycloalkyl groups.

[0027] In another preferred example, the compound has a structure selected from the group consisting of the following: [ka] Here, X1, X2, X3, X4, X6, R2, R3, R4, R 51 Ring A and ring B are as defined above. In another preferred example, the compound has a structure selected from the group consisting of the following: [ka] structure [ka] The following arrangements are selected: [ka] Here, X4, X6, R2, R3, R4, R5, ring A, and p are as defined above.

[0028] R51 , R 61 are each independently selected from the group consisting of H, -CN, -NO2, C 1-6 alkyl group, halogenated C 1-6 alkyl group, deuterated C 1-6 alkyl group, C 1-6 alkoxy group, halogenated C 1-6 alkoxy group, deuterated C 1-6 alkoxy group, C 3-6 cycloalkyl group, halogenated C 3-6 cycloalkyl group R 62 is selected from the group consisting of H, halogen, oxo (=O), -CN, -NO2, C 1-6 alkyl group, halogenated C 1-6 alkyl group, deuterated C 1-6 alkyl group, C 1-6 alkoxy group, halogenated C 1-6 alkoxy group, deuterated C 1-6 alkoxy group, C 3-6 cycloalkyl group, halogenated C 3-6 cycloalkyl group.

[0029] In another preferred embodiment, said compound is a compound of formula (I-a), or a pharmaceutically acceptable salt, stereoisomer, deuteride, solvate or prodrug thereof,

Chemical Structure

[0030] Ring A is C 6-10 ​Selected from the group consisting of an aryl group, a 5-8 membered heteroaryl group containing 1-4 heteroatoms selected from N, O, or S, where the C 6-10 The aryl group and the 5- to 8-membered heteroaryl group are optionally substituted with m R6 groups. R1 is H, deuterium, halogen, -CN, C 1-6 Alkyl alkyl groups, C halogenated compounds 1-6 Alkyl groups, deuterated C 1-6 Alkyl alkyl group, C 1-6 Alkoxy group, halogenated C 1-6 Selected from the group consisting of alkoxy groups, R, R2, R3, R 11 These are H, halogen, -CN, and C, respectively, independently. 1-6 Alkyl alkyl groups, C halogenated compounds 1-6 Alkyl groups, deuterated C 1-6 Alkyl alkyl group, C 1-6 Alkoxy group, halogenated C 1-6 Alkoxy group, deuterated C 1-6 Alkoxy group, C 3-6 Cycloalkyl groups, halogenated C 3-6 Selected from the group consisting of cycloalkyl groups,

[0031] R4 is -L-(C 1-6 Alkyl), -LC 6-10 Aryl group, -L- (5-8 membered heteroaryl containing 1-4 heteroatoms selected from N, O, or S), -L- (saturated or partially unsaturated C) 3-8 Selected from the group consisting of cycloalkyl, -L-(saturated or partially unsaturated 4-8 member heterocyclic alkyl containing 1-4 heteroatoms selected from N, O, or S), where the C 1-6 Alkyl alkyl group, C 6-10 Aryl group, 5-8 membered heteroaryl group, C 3-8 Cycloalkyl groups and 4- to 8-membered heterocyclic alkyl groups are optionally substituted with n R7 atoms. Each R5 represents H, deuterium, halogen, -CN, oxo (=O), or C. 1-6 Alkyl alkyl groups, C halogenated compounds 1-6 Alkyl groups, deuterated C 1-6 Alkyl alkyl group, C1-6 Alkoxy group, halogenated C 1-6 Alkoxy group, deuterated C 1-6 Alkoxy group, C 3-6 Cycloalkyl groups, halogenated C 3-6 Independently selected from the group consisting of cycloalkyl groups, 3-8 membered heterocyclic alkyl groups containing 1-3 heteroatoms selected from N, O, or S,

[0032] Each R6 represents H, deuterium, halogen, -CN, -NO2, C 1-6 Alkyl alkyl groups, C halogenated compounds 1-6 Alkyl groups, deuterated C 1-6 Alkyl alkyl group, C 1-6 Alkoxy group, halogenated C 1-6 Independently selected from the group consisting of alkoxy groups, -C(O)R8, -C(O)OR8, -C(O)NR8R9, -SO2R8, -S(O)(NR8)R9, -SO2NR8R9, and -P(O)R8R9, Each R7 represents hydrogen, deuterium, halogen, oxo (=O), -CN, -OH, -NO2, and C. 1-6 Alkyl alkyl group, C 1-6 Alkoxy group, halogenated C 1-6 Alkyl alkyl groups, C halogenated compounds 1-6 Alkoxy group, deuterated C 1-6 C containing 1 to 4 heteroatoms selected from alkyl groups, N, O, or S 1-6 C halogens containing 1 to 4 heteroatoms selected from heteroalkyl groups, N, O, or S. 1-6 Heteroalkyl groups, -NR8R9, =NR8, -C(O)R8, -C(O)OR8, -C(O)NR8R9, -NR8C(O)R9, -SR8, -SO2R8, -NR8SO2R9, -SO2NR8R9, -NR8SO2NR9R 10 -P(O)R8R9, -L1-(C 1-6 Alkyl), -L1- (saturated or partially unsaturated C 3-10 Cycloalkyl), -L1-(C 6-10A C is independently selected from the group consisting of aryl, -L1- (saturated or partially unsaturated 3-12 member heterocyclic alkyl containing 1-4 heteroatoms selected from N, O, or S), and -L1- (5-10 member heteroaryl containing 1-4 heteroatoms selected from N, O, or S), where the C 1-6 Alkyl alkyl group, C 1-6 Heteroalkyl groups, C 3-10 Cycloalkyl groups, C 6-10 Aryl groups, 3-10 membered heterocyclic alkyl groups, and 5-10 membered heteroaryl groups are composed of deuterium, halogens, =O, -CN, -OH, -NH2, and C. 1-6 Alkyl alkyl groups, C halogenated compounds 1-6 Alkyl alkyl group, C 1-6 Alkoxy group, halogenated C 1-6 Alkoxy group, C 3-6 Cycloalkyl groups, halogenated C 3-6 It is optionally substituted by 0 to 6 substitutions selected from the group consisting of cycloalkyl groups, 3 to 6 membered heterocyclic alkyl groups containing 1 to 4 heteroatoms selected from N, O, or S, -SO2R8, -C(O)R8, -C(O)OR8, -C(O)NR8R9, and -NR8R9.

[0033] Alternatively, the two R7 atoms, together with the atom they are bonded to, become C 3-6 Cycloalkyl groups, C 6-10 A 3-6 member heterocyclic alkyl group containing an aryl group, 1-4 heteroatoms selected from N, O, or S, or a 5-6 member heteroaryl group containing 1-4 heteroatoms selected from N, O, or S is formed, where the C 3-6 Cycloalkyl groups, C 6-10 Aryl groups, 3-6 member heterocyclic alkyl groups, and 5-6 member heteroaryl groups are composed of deuterium, halogens, =O, -CN, -OH, -NR8R9, =NR8, -C(O)R8, -C(O)OR8, -C(O)NR8R9, -NR8C(O)R9, -SR8, -SO2R8, -NR8SO2R9, -SO2NR8R9, and -NR8SO2NR9R. 10 ,-P(O)R8R9,C 1-6 Alkyl alkyl group, C 1-6C containing 1 to 4 heteroatoms selected from an alkoxy group, N, O, or S 1-6 Heteroalkyl groups, halogenated C 1-6 Alkyl alkyl groups, C halogenated compounds 1-6 C halogenated carbon containing 1 to 4 heteroatoms selected from an alkoxy group, N, O, or S. 1-6 Heteroalkyl groups, C 3-6 It is optionally substituted by 0 to 6 substitutions selected from the group consisting of cycloalkyl groups, 3 to 6-membered heterocyclic alkyl groups containing 1 to 4 heteroatoms selected from N, O, or S,

[0034] L and L1 are either independently combined or C 1-6 An alkylene group, a 1-6 membered heteroalkylene group containing 1-4 heteroatoms selected from N, O, or S, selected from the group consisting of -NR8-, -O-, -C(O)-, -C(O)NR8-, -C(O)O-, -NR8C(O)-, -(SO2)-, -SO2NR8-, -NR8SO2-, -NR8SO2NR9-, -S(O)(NR8)-, Each R8, R9, R 10 These are H and C, respectively, independently. 1-6 Alkyl alkyl groups, C halogenated compounds 1-6 Alkyl alkyl group, C 3-6 Cycloalkyl groups, C 6-10 Selected from the group consisting of an aryl group, a 3-6 membered heterocyclic alkyl group containing 1-4 heteroatoms selected from N, O, or S, and a 5-6 membered heteroaryl group containing 1-4 heteroatoms selected from N, O, or S, where the C 3-6 Cycloalkyl groups, C 6-10 Aryl groups, 3-6 membered heterocyclic alkyl groups, and 5-6 membered heteroaryl groups are composed of deuterium, halogens, =O, -CN, -OH, -NH2, and C. 1-6 Alkyl alkyl groups, C halogenated compounds 1-6 Alkyl alkyl group, C 1-6 Alkoxy group, halogenated C 1-6 C containing 1 to 4 heteroatoms selected from an alkoxy group, N, O, or S 1-6 C halogens containing 1 to 4 heteroatoms selected from heteroalkyl groups, N, O, or S. 1-6It is optionally substituted by 0 to 6 substitutions selected from the group consisting of heteroalkyl groups.

[0035] Alternatively, R8 and R9, together with the heteroatoms to which they are bonded, form a 3-6 membered heterocyclic alkyl group containing 1-4 heteroatoms selected from N, O, or S, or R9, R 10 These, together with the heteroatoms to which they are bonded, form a 3-6 membered heterocyclic alkyl group containing 1-4 heteroatoms selected from N, O, or S. [ka] These are single or double bonds, Each of m, n, and q is independently selected from the group consisting of 0, 1, 2, 3, 4, and 5.

[0036] In another preferred example, ring A is C 6-10 Selected from the group consisting of an aryl group, a 5-10 membered heteroaryl group containing 1-4 heteroatoms selected from N, O, or S, where the C 6-10 The aryl group and the 5- to 10-membered heteroaryl group can be optionally substituted with m R6 groups. In another preferred example, each R6 is H, deuterium, halogen, C 1-6 Alkyl alkyl groups, C halogenated compounds 1-6 Alkyl groups, deuterated C 1-6 It is independently selected from the group consisting of alkyl groups, -C(O)R8, -C(O)OR8, and -SO2R8.

[0037] In another preferred example, each R8, R9, R 10 These are H and C, respectively, independently. 1-6 Alkyl alkyl groups, C halogenated compounds 1-6 Selected from the group consisting of alkyl groups. In another preferred example, X6 is NR 61 , C 1-6 Selected from the group consisting of alkylene groups. In another preferred example, R 51 , R 61These are H and C, respectively, independently. 1-6 Alkyl alkyl groups, C halogenated compounds 1-6 Alkyl groups, deuterated C 1-6 Selected from the group consisting of alkyl groups. In another preferred example, X5 is C 1-6 It is an alkylene group, where the C 1-6 The alkylene group consists of 1, 2, 3, 4, 5, or 6 R groups. 52 It can be arbitrarily replaced by. In another preferred example, each R, R2, R3, R 11 , R 52 , R 62 These are H, deuterium, halogen, and C, respectively, independently. 1-6 Alkyl alkyl groups, C halogenated compounds 1-6 Alkyl groups, deuterated C 1-6 Selected from the group consisting of alkyl groups.

[0038] In another preferred example, X4 is CR. In another preferred example, R is H, C 1-3 Alkyl alkyl groups, C halogenated compounds 1-3 Alkyl groups, deuterated C 1-3 Alkyl alkyl group, C 1-3 Alkoxy group, halogenated C 1-3 Alkoxy group, deuterated C 1-3 Alkoxy group, C 3-5 Cycloalkyl groups, halogenated C 3-5 Selected from the group consisting of cycloalkyl groups. In another preferred example, R is H, C 1-3 Alkyl alkyl groups, C halogenated compounds 1-3 Alkyl groups, deuterated C 1-3 Selected from the group consisting of alkyl groups.

[0039] In another preferred example, R is H. In another preferred example, X4 is CH. In another preferred example, X1 is N, O, C(R 11 ) q It is selected from the group consisting of the following. In another preferred example, X1 is selected from the group consisting of N and O. In another preferred example, X2 and X3 are each independently selected from the group consisting of N and C. In another preferred example, X7 is selected from the group consisting of C=O and C=S.

[0040] In another preferred example, the B ring is a 5- to 7-membered heterocyclic alkyl group optionally substituted with one or more R5 atoms, comprising one N atom and 0-3 heteroatoms selected from N, O, or S. In another preferred example, each R5 is H, deuterium, halogen, oxo (=O), C 1-6 Alkyl alkyl groups, C halogenated compounds 1-6 Alkyl groups, deuterated C 1-6 It is independently selected from the group consisting of alkyl groups. In another preferred example, R4 is -L-(C 1-6 Alkyl), -LC 6-10 Aryl group, -L- (5-10 membered heteroaryl containing 1-4 heteroatoms selected from N, O, or S), -L- (saturated or partially unsaturated C) 3-8 Selected from the group consisting of cycloalkyl, -L-(saturated or partially unsaturated 4-8 member heterocyclic alkyl containing 1-4 heteroatoms selected from N, O, or S), where the C 1-6 Alkyl alkyl group, C 6-10 Aryl group, 5-10 membered heteroaryl group, C 3-8 Cycloalkyl groups and 4- to 8-membered heterocyclic alkyl groups can be optionally substituted with n R7 atoms.

[0041] In another preferred example, L and L1 are independently a combination or C 1-6 The group is selected from the group consisting of alkylene groups, -NR8-, -O-, -C(O)-, -C(O)NR8-, -C(O)O-, -NR8C(O)-, -(SO2)-, -SO2NR8-, -NR8SO2-, -NR8SO2NR9-, and -S(O)(NR8)-. In another preferred example, L and L1 are independently a combination or C1-6 The group is selected from the group consisting of an alkylene group, -C(O)-, -C(O)NR8-, -C(O)O-, -NR8C(O)-, -(SO2)-, -SO2NR8-, -NR8SO2-, -NR8SO2NR9-, and -S(O)(NR8)-.

[0042] In another preferred example, each R7 is hydrogen, deuterium, halogen, oxo (=O), -CN, -OH, C 1-6 Alkyl alkyl group, C 1-6 Alkoxy group, halogenated C 1-6 Alkyl alkyl groups, C halogenated compounds 1-6 Alkoxy group, deuterated C 1-6 A molecule is independently selected from the group consisting of alkyl groups, -C(O)NR8R9, -NR8C(O)R9, -SO2R8, -NR8SO2R9, and -SO2NR8R9, where the C 1-6 Alkyl groups are -OH, C 1-6 Alkyl alkyl groups, C halogenated compounds 1-6 It is optionally substituted by 0 to 6 substitutions selected from the group consisting of alkyl groups.

[0043] Alternatively, the two R7 atoms, together with the atom they are bonded to, become C 3-6 It forms a cycloalkyl group or a 3-6 membered heterocyclic alkyl group containing 1-4 heteroatoms selected from N, O, or S. In another preferred example, the compound has a structure selected from the group consisting of the following: [ka]

[0044] Here, X1 is N, O, C(R 11 ) q Selected from the group consisting of, X2 and X3 are each independently selected from the group consisting of N and C. Y1, Y2, Y3, and Y4 are each independently selected from the group consisting of O, C(R5)2, CHR5, C(=O), S(=O), S(=O)2, and NR5. Ring A is selected from the group consisting of a phenyl group and a 5-6 membered heteroaryl group containing 1-4 heteroatoms selected from N, O, or S, where the phenyl group and the 5-6 membered heteroaryl group are optionally substituted by m R6 groups.

[0045] R1 is H, deuterium, halogen, -CN, C 1-3 Alkyl alkyl groups, C halogenated compounds 1-3 Alkyl groups, deuterated C 1-3 Alkyl alkyl group, C 1-3 Alkoxy group, halogenated C 1-3 Selected from the group consisting of alkoxy groups, R2, R3, R 11 These are H, halogen, -CN, and C, respectively, independently. 1-3 Alkyl alkyl groups, C halogenated compounds 1-3 Alkyl groups, deuterated C 1-3 Alkyl alkyl group, C 1-3 Alkoxy group, halogenated C 1-3 Alkoxy group, deuterated C 1-3 Alkoxy group, C 3-5 Cycloalkyl groups, halogenated C 3-5 Selected from the group consisting of cycloalkyl groups,

[0046] R4 is -L-(C 1-6 Alkyl), -L-phenyl group, -L-(5-6 member heteroaryl containing 1-4 heteroatoms selected from N, O, or S), -L-(saturated or partially unsaturated C) 3-6 Selected from the group consisting of cycloalkyl, -L-(saturated or partially unsaturated 4-6 member heterocyclic alkyl containing 1-4 heteroatoms selected from N, O, or S), where the C 1-6 Alkyl group, phenyl group, 5-6 membered heteroaryl group, C 3-6 Cycloalkyl groups and 4-6 membered heterocyclic alkyl groups are optionally substituted with n R7 atoms. Each R5 represents H, deuterium, halogen, -CN, oxo (=O), or C. 1-3 Alkyl alkyl groups, C halogenated compounds 1-3 Alkyl groups, deuterated C 1-3 Alkyl alkyl group, C 1-3Alkoxy group, halogenated C 1-3 Alkoxy group, deuterated C 1-3 Alkoxy group, C 3-5 Cycloalkyl groups, halogenated C 3-5 Independently selected from the group consisting of cycloalkyl groups, 3-5 heterocyclic alkyl groups containing 1 to 3 heteroatoms selected from N, O, or S,

[0047] Each R6 represents H, deuterium, halogen, -CN, -NO2, C 1-6 Alkyl alkyl groups, C halogenated compounds 1-6 Alkyl groups, deuterated C 1-3 Alkyl alkyl group, C 1-6 Alkoxy group, halogenated C 1-6 Independently selected from the group consisting of alkoxy groups, -C(O)R8, -C(O)OR8, -C(O)NR8R9, -SO2R8, -S(O)(NR8)R9, -SO2NR8R9, and -P(O)R8R9,

[0048] Each R7 represents hydrogen, deuterium, halogen, oxo (=O), -CN, -OH, -NO2, and C. 1-6 Alkyl alkyl group, C 1-6 Alkoxy group, halogenated C 1-6 Alkyl alkyl groups, C halogenated compounds 1-6 Alkoxy group, deuterated C 1-6 C containing 1 to 4 heteroatoms selected from alkyl groups, N, O, or S 1-6 C halogens containing 1 to 4 heteroatoms selected from heteroalkyl groups, N, O, or S. 1-6 Heteroalkyl groups, -NR8R9, =NR8, -C(O)R8, -C(O)OR8, -C(O)NR8R9, -NR8C(O)R9, -SR8, -SO2R8, -NR8SO2R9, -SO2NR8R9, -NR8SO2NR9R 10 -P(O)R8R9, -L1-(C 1-6 Alkyl), -L1- (saturated or partially unsaturated C 3-10 Cycloalkyl), -L1-(C 6-10A C is independently selected from the group consisting of aryl, -L1- (saturated or partially unsaturated 3-12 member heterocyclic alkyl containing 1-4 heteroatoms selected from N, O, or S), and -L1- (5-10 member heteroaryl containing 1-4 heteroatoms selected from N, O, or S), where the C 1-6 Alkyl alkyl group, C 1-6 Heteroalkyl groups, C 3-10 Cycloalkyl groups, C 6-10 Aryl groups, 3-10 membered heterocyclic alkyl groups, and 5-10 membered heteroaryl groups are composed of deuterium, halogens, =O, -CN, -OH, -NH2, and C. 1-6 Alkyl alkyl groups, C halogenated compounds 1-6 Alkyl alkyl group, C 1-6 Alkoxy group, halogenated C 1-6 Alkoxy group, C 3-6 Cycloalkyl groups, halogenated C 3-6 It is optionally substituted by 0 to 6 substitutions selected from the group consisting of cycloalkyl groups, 3 to 6 membered heterocyclic alkyl groups containing 1 to 4 heteroatoms selected from N, O, or S, -SO2R8, -C(O)R8, -C(O)OR8, -C(O)NR8R9, and -NR8R9.

[0049] Alternatively, the two R7 atoms, together with the atom they are bonded to, become C 3-6 Cycloalkyl groups, C 6-10 A 3-6 member heterocyclic alkyl group containing an aryl group, 1-4 heteroatoms selected from N, O, or S, or a 5-6 member heteroaryl group containing 1-4 heteroatoms selected from N, O, or S is formed, where the C 3-6 Cycloalkyl groups, C 6-10 Aryl groups, 3-6 member heterocyclic alkyl groups, and 5-6 member heteroaryl groups are composed of deuterium, halogens, =O, -CN, -OH, -NR8R9, =NR8, -C(O)R8, -C(O)OR8, -C(O)NR8R9, -NR8C(O)R9, -SR8, -SO2R8, -NR8SO2R9, -SO2NR8R9, and -NR8SO2NR9R. 10 ,-P(O)R8R9,C 1-6 Alkyl alkyl group, C 1-6C containing 1 to 4 heteroatoms selected from an alkoxy group, N, O, or S 1-6 Heteroalkyl groups, halogenated C 1-6 Alkyl alkyl groups, C halogenated compounds 1-6 C halogenated carbon containing 1 to 4 heteroatoms selected from an alkoxy group, N, O, or S. 1-6 Heteroalkyl groups, C 3-6 It is optionally substituted by 0 to 6 substitutions selected from the group consisting of cycloalkyl groups, 3 to 6-membered heterocyclic alkyl groups containing 1 to 4 heteroatoms selected from N, O, or S,

[0050] L and L1 are either independently combined or C 1-6 An alkylene group, a 1-6 membered heteroalkylene group containing 1-4 heteroatoms selected from N, O, or S, selected from the group consisting of -NR8-, -O-, -C(O)-, -C(O)NR8, -C(O)O-, -NR8C(O)-, -(SO2)-, -SO2NR8-, -NR8SO2-, -NR8SO2NR9-,

[0051] Each R8, R9, R 10 These are H and C, respectively, independently. 1-6 Alkyl alkyl groups, C halogenated compounds 1-6 Alkyl alkyl group, C 3-6 Cycloalkyl groups, C 6-10 Selected from the group consisting of an aryl group, a 3-6 membered heterocyclic alkyl group containing 1-4 heteroatoms selected from N, O, or S, and a 5-6 membered heteroaryl group containing 1-4 heteroatoms selected from N, O, or S, where the C 3-6 Cycloalkyl groups, C 6-10 Aryl groups, 3-6 membered heterocyclic alkyl groups, and 5-6 membered heteroaryl groups are composed of deuterium, halogens, =O, -CN, -OH, -NH2, and C. 1-6 Alkyl alkyl groups, C halogenated compounds 1-6 Alkyl alkyl group, C 1-6 Alkoxy group, halogenated C 1-6 C containing 1 to 4 heteroatoms selected from an alkoxy group, N, O, or S 1-6 C halogens containing 1 to 4 heteroatoms selected from heteroalkyl groups, N, O, or S.1-6 It is optionally substituted by 0 to 6 substitutions selected from the group consisting of heteroalkyl groups.

[0052] Alternatively, R8 and R9, together with the heteroatoms to which they are bonded, form a 3-6 membered heterocyclic alkyl group containing 1-4 heteroatoms selected from N, O, or S, or R9, R 10 These, together with the heteroatoms to which they are bonded, form a 3-6 membered heterocyclic alkyl group containing 1-4 heteroatoms selected from N, O, or S. [ka] These are single or double bonds, Each of m, n, and q is independently selected from 0, 1, 2, 3, 4, and 5.

[0053] In another preferred example, X2 and X3 are all C, or one of X2 and X3 is N and the other is C. In another preferred example, X2 is C and X3 is N. In another preferred example, Y1, Y2, Y3, and Y4 are each independently selected from the group consisting of O, C(R5)2, CHR5, and C(=O). In another preferred example, Y1, Y2, Y3, and Y4 are each independently selected from the group consisting of O, CH2, CHR5, and C(=O). In another preferred example, Y1, Y2, Y3, and Y4 are each independently selected from the group consisting of CH2 and CHR5. In another preferred example, one of Y1, Y2, Y3, and Y4 is O, CHR5, or C (=O), and all the others are CH2.

[0054] In another preferred example, each R5 independently consists of H, deuterium, halogen, -CN, oxo (=O), and C. 1-3 Alkyl alkyl groups, C halogenated compounds 1-3 Alkyl groups, deuterated C 1-3 Alkyl alkyl group, C 1-3 Alkoxy group, halogenated C 1-3Alkoxy group, deuterated C 1-3 Alkoxy group, C 3-5 Cycloalkyl groups, halogenated C 3-5 The group consists of cycloalkyl groups and 3-5 heterocyclic alkyl groups containing 1 to 3 heteroatoms selected from N, O, or S. In another preferred example, each R5 is H, deuterium, halogen, oxo (=O), C 1-3 Alkyl alkyl groups, C halogenated compounds 1-3 Alkyl groups, deuterated C 1-3 Alkyl alkyl group, C 1-3 Alkoxy group, halogenated C 1-3 Alkoxy group, deuterated C 1-3 It is independently selected from the group consisting of alkoxy groups. In another preferred example, each R5 is H, deuterium, halogen, oxo (=O), C 1-3 Alkyl alkyl groups, C halogenated compounds 1-3 Alkyl groups, deuterated C 1-3 It is independently selected from the group consisting of alkyl groups.

[0055] In another preferred example, the compound has a structure selected from the group consisting of the following: [ka]

[0056] Here, R1, R2, R3, R4, R 11 Y1, Y2, Y3, Y4, and the A ring are as defined herein. structure [ka] teeth, [ka] Includes the arrangement of. In another preferred example, structure [ka] teeth, [ka] Includes the arrangement of.

[0057] In another preferred example, the compound has a structure selected from the group consisting of the following: [ka] [ka] [ka]

[0058] Here, R1, R2, R3, R4, R5, R 11 Ring A is as defined herein, and p is 0, 1, 2, 3 or 4. structure [ka] teeth, [ka] Includes the arrangement of. In another preferred example, ring A is C 6-10 The group is selected from the group consisting of an aryl group and a 5-6 membered heteroaryl group containing one N atom and 0-3 heteroatoms selected from N, O, or S, where the phenyl group and the 5-6 membered heteroaryl group are optionally substituted with m R6 atoms. In another preferred example, the A ring is selected from the group consisting of a phenyl group and a 5-6 membered heteroaryl group containing 1-4 N heteroatoms, where the phenyl group and the 5-6 membered heteroaryl group are optionally substituted with m R6 atoms.

[0059] In another preferred example, the A ring is selected from the group consisting of phenyl, pyridinyl, thiophenyl, furanyl, pyrazolyl, pyridadinyl, pyrimidinyl, pyrazolyl, and thiazolyl groups, of which any of these groups is optionally substituted by m R6 groups. In another preferred example, the A ring is selected from the group consisting of phenyl groups and pyridinyl groups, where the phenyl groups and pyridinyl groups are optionally substituted by m R6 groups. In another preferred example, each R6 is H, deuterium, halogen, C 1-6 Alkyl alkyl groups, C halogenated compounds 1-6 Alkyl groups, deuterated C 1-6 Alkyl alkyl group, C 1-6 Alkoxy group, halogenated C 1-6 It is independently selected from the group consisting of an alkoxy group, -C(O)R8, -C(O)OR8, and -C(O)NR8R9.

[0060] In another preferred example, each R6 is independently selected from the group consisting of H, deuterium, halogen, -C(O)R8, -C(O)OR8, -C(O)NR8R9, and -SO2R8. In another preferred example, each R6 is independently selected from the group consisting of H, deuterium, halogen, -C(O)OR8, and -SO2R8. In another preferred example, each R6 is independently selected from the group consisting of H, deuterium, halogens, and -C(O)OH. In another preferred example, R1 is H, deuterium, halogen, -CN, C 1-3 Alkyl alkyl groups, C halogenated compounds 1-3 Alkyl groups, deuterated C 1-3 Alkyl alkyl group, C 1-3 Alkoxy group, halogenated C 1-3 Selected from the group consisting of alkoxy groups.

[0061] In another preferred example, R1 is H, deuterium, C 1-6 Alkyl alkyl groups, C halogenated compounds 1-6 Alkyl groups, deuterated C 1-6 Alkyl alkyl group, C 1-6 Alkoxy group, halogenated C1-6 Selected from the group consisting of alkoxy groups. In another preferred example, R1 is C 1-6 Alkyl alkyl groups, C halogenated compounds 1-6 Alkyl groups, deuterated C 1-6 Selected from the group consisting of alkyl groups. In another preferred example, R1 is a C such as a methyl group, ethyl group, n-propyl group, or isopropyl group. 1-3 It is an alkyl group. In another preferred example, R1 is either an R configuration or an S configuration. In another preferred example, R1 is a methyl group in the R configuration.

[0062] In another preferred example, R, R2, and R3 are independently H, halogen, -CN, and C, respectively. 1-3 Alkyl alkyl groups, C halogenated compounds 1-3 Alkyl groups, deuterated C 1-3 Alkyl alkyl group, C 1-3 Alkoxy group, halogenated C 1-3 Alkoxy group, deuterated C 1-3 Alkoxy group, C 3-5 Cycloalkyl groups, halogenated C 3-5 Selected from the group consisting of cycloalkyl groups. In another preferred example, R2 and R3 are independently H, halogen, and C, respectively. 1-6 Alkyl alkyl groups, C halogenated compounds 1-6 Alkyl groups, deuterated C 1-6 Alkyl alkyl group, C 1-6 Alkoxy group, halogenated C 1-6 Alkoxy group, deuterated C 1-6 The group is selected from the group consisting of alkoxy groups, C3 cycloalkyl groups, and halogenated C3 cycloalkyl groups.

[0063] In another preferred example, R2 is H, halogen, C 1-6 Alkyl alkyl groups, C halogenated compounds 1-6 Alkyl groups, deuterated C 1-6 Alkyl alkyl group, C 1-6 Alkoxy group, halogenated C 1-6 Alkoxy group, deuterated C1-6 The group is selected from the group consisting of an alkoxy group, a C3 cycloalkyl group, and a halogenated C3 cycloalkyl group, and R3 is H. In another preferred example, R2 is H, halogen, C 1-3 Alkyl alkyl groups, C halogenated compounds 1-3 Alkyl groups, deuterated C 1-3 Alkyl alkyl group, C 1-3 Alkoxy group, halogenated C 1-3 Alkoxy group, deuterated C 1-3 Selected from the group consisting of alkoxy groups, R3 is H.

[0064] In another preferred example, R2 is H, halogen, C 1-3 Alkyl alkyl groups, C halogenated compounds 1-3 Alkyl groups, deuterated C 1-3 Selected from the group consisting of alkyl groups, R3 is H. In another preferred example, ring A has a structure selected from the group consisting of the following: [ka]

[0065] Here, each R6 is H, deuterium, halogen, -CN, -NO2, C 1-6 Alkyl alkyl groups, C halogenated compounds 1-6 Alkyl groups, deuterated C 1-3 Alkyl alkyl group, C 1-6 Alkoxy group, halogenated C 1-6 Independently selected from the group consisting of alkoxy groups, -C(O)R8, -C(O)OR8, -C(O)NR8R9, -SO2R8, -S(O)(NR8)R9, -SO2NR8R9, and -P(O)R8R9, Each of R8 and R9 is as defined above, and m is selected from 0, 1, 2, 3, 4, and 5.

[0066] In another preferred example, ring A has a structure selected from the group consisting of the following: [ka] In another preferred example, ring A has a structure selected from the group consisting of the following: [ka]

[0067] In another preferred example, R4 has a structure selected from the group consisting of the following: [ka] Here, L and L1 are independently either a combination or C 1-6 Selected from the group consisting of alkylene groups, -C(O)-, -C(O)NH-, -C(O)O-, -(SO2)-, and -SO2NH-,

[0068] Each R7 represents hydrogen, deuterium, halogen, oxo (=O), -CN, -OH, -NO2, and C. 1-6 Alkyl alkyl group, C 1-6 Alkoxy group, halogenated C 1-6 Alkyl alkyl groups, C halogenated compounds 1-6 Alkoxy group, deuterated C 1-6 C containing 1 to 4 heteroatoms selected from alkyl groups, N, O, or S 1-6 C halogens containing 1 to 4 heteroatoms selected from heteroalkyl groups, N, O, or S. 1-6 Heteroalkyl groups, -NR8R9, =NR8, -C(O)R8, -C(O)OR8, -C(O)NR8R9, -NR8C(O)R9, -SR8, -SO2R8, -NR8SO2R9, -SO2NR8R9, -NR8SO2NR9R 10 -P(O)R8R9, -L1-(C 1-6 Alkyl), -L1- (saturated or partially unsaturated C 3-10 Cycloalkyl), -L1-(C 6-10 A C is independently selected from the group consisting of aryl, -L1- (saturated or partially unsaturated 3-12 member heterocyclic alkyl containing 1-4 heteroatoms selected from N, O, or S), and -L1- (5-10 member heteroaryl containing 1-4 heteroatoms selected from N, O, or S), where the C 1-6 Alkyl alkyl group, C1-6 Heteroalkyl groups, C 3-10 Cycloalkyl groups, C 6-10 Aryl groups, 3-12 membered heterocyclic alkyl groups, and 5-10 membered heteroaryl groups are composed of deuterium, halogens, =O, -CN, -OH, -NH2, and C. 1-6 Alkyl alkyl groups, C halogenated compounds 1-6 Alkyl alkyl group, C 1-6 Alkoxy group, halogenated C 1-6 Alkoxy group, C 3-6 Cycloalkyl groups, halogenated C 3-6 It is optionally substituted by 0 to 6 substitutions selected from the group consisting of cycloalkyl groups, 3 to 6 membered heterocyclic alkyl groups containing 1 to 4 heteroatoms selected from N, O, or S, -SO2R8, -C(O)R8, -C(O)OR8, -C(O)NR8R9, and -NR8R9.

[0069] Alternatively, the two R7 atoms, together with the atom they are bonded to, become C 3-6 Cycloalkyl groups, C 6-10 A 3-6 member heterocyclic alkyl group containing an aryl group, 1-4 heteroatoms selected from N, O, or S, or a 5-6 member heteroaryl group containing 1-4 heteroatoms selected from N, O, or S is formed, where the C 3-6 Cycloalkyl groups, C 6-10 Aryl groups, 3-6 member heterocyclic alkyl groups, and 5-6 member heteroaryl groups are composed of deuterium, halogens, =O, -CN, -OH, -NR8R9, =NR8, -C(O)R8, -C(O)OR8, -C(O)NR8R9, -NR8C(O)R9, -SR8, -SO2R8, -NR8SO2R9, -SO2NR8R9, and -NR8SO2NR9R. 10 ,-P(O)R8R9,C 1-6 Alkyl alkyl group, C 1-6 C containing 1 to 4 heteroatoms selected from an alkoxy group, N, O, or S 1-6 Heteroalkyl groups, halogenated C 1-6 Alkyl alkyl groups, C halogenated compounds 1-6 C halogenated carbon containing 1 to 4 heteroatoms selected from an alkoxy group, N, O, or S. 1-6 Heteroalkyl groups, C 3-6It is optionally substituted by 0 to 6 substitutions selected from the group consisting of cycloalkyl groups, 3 to 6-membered heterocyclic alkyl groups containing 1 to 4 heteroatoms selected from N, O, or S,

[0070] Each R8, R9, R 10 As defined above, n is selected from the group consisting of 0, 1, 2, 3, 4, and 5. In another preferred example, each R7 is hydrogen, deuterium, halogen, oxo (=O), -CN, -OH, -NO2, C 1-6 Alkyl alkyl group, C 1-6 Alkoxy group, halogenated C 1-6 Alkyl alkyl groups, C halogenated compounds 1-6 Alkoxy group, deuterated C 1-6 C containing 1 to 4 heteroatoms selected from alkyl groups, N, O, or S 1-6 C halogens containing 1 to 4 heteroatoms selected from heteroalkyl groups, N, O, or S. 1-6 Heteroalkyl groups, -L1-(C 1-6 Alkyl), -L1- (saturated or partially unsaturated C 3-10 Cycloalkyl), -L1-(C 6-10 A C is independently selected from the group consisting of aryl, -L1- (saturated or partially unsaturated 3-12 member heterocyclic alkyl containing 1-4 heteroatoms selected from N, O, or S), and -L1- (5-10 member heteroaryl containing 1-4 heteroatoms selected from N, O, or S), where the C 1-6 Alkyl alkyl group, C 1-6 Heteroalkyl groups, C 3-10 Cycloalkyl groups, C 6-10 Aryl groups, 3-12 membered heterocyclic alkyl groups, and 5-10 membered heteroaryl groups are composed of deuterium, halogens, =O, -CN, -OH, -NH2, and C. 1-6 Alkyl alkyl groups, C halogenated compounds 1-6 Alkyl alkyl group, C 1-6 Alkoxy group, halogenated C 1-6 Alkoxy group, C 3-6 Cycloalkyl groups, halogenated C 3-6 It is optionally substituted by 0 to 6 substitutions selected from the group consisting of cycloalkyl groups.

[0071] In another preferred example, each R7 is hydrogen, deuterium, halogen, oxo (=O), -CN, -OH, -NO2, C 1-6 Alkyl alkyl group, C 1-6 Alkoxy group, halogenated C 1-6 Alkyl alkyl groups, C halogenated compounds 1-6 Alkoxy group, deuterated C 1-6 Alkyl group, -L1-(C 1-6 Independently selected from the group consisting of alkyl, where the C 1-6 Alkyl groups include deuterium, halogen, =O, -CN, -OH, -NH2, and C. 1-6 Alkyl alkyl groups, C halogenated compounds 1-6 Alkyl alkyl group, C 1-6 Alkoxy group, halogenated C 1-6 Alkoxy group, C 3-6 Cycloalkyl groups, halogenated C 3-6 It is optionally substituted by 0 to 6 substitutions selected from the group consisting of cycloalkyl groups.

[0072] In another preferred example, each R7 is hydrogen, deuterium, halogen, oxo (=O), -CN, -OH, -NO2, C 1-6 Alkyl alkyl groups, C halogenated compounds 1-6 Alkyl groups, deuterated C 1-6 Alkyl group, -L1-(C 1-6 Independently selected from the group consisting of alkyl, where the C 1-6 Alkyl groups include deuterium, halogen, =O, -CN, -OH, -NH2, and C. 1-6 Alkyl alkyl groups, C halogenated compounds 1-6 Alkyl alkyl group, C 1-6 Alkoxy group, halogenated C 1-6 It is optionally substituted by 0 to 6 substitutions selected from the group consisting of alkoxy groups.

[0073] In another preferred example, each R8, R9, R 10 These are H and C, respectively, independently. 1-6 Alkyl alkyl groups, C halogenated compounds 1-6 Alkyl alkyl group, C 3-6Selected from the group consisting of cycloalkyl groups, 3-6 membered heterocyclic alkyl groups containing 1-4 heteroatoms selected from N, O, or S, where the C 3-6 Cycloalkyl groups, 3- to 6-membered heterocyclic alkyl groups, are composed of deuterium, halogens, =O, -CN, -OH, -NH2, and C. 1-6 Alkyl alkyl groups, C halogenated compounds 1-6 Alkyl alkyl group, C 1-6 Alkoxy group, halogenated C 1-6 It is optionally substituted by 0 to 6 substitutions selected from the group consisting of alkoxy groups.

[0074] In another preferred example, each R8, R9, R 10 These are H and C, respectively, independently. 1-6 Alkyl alkyl groups, C halogenated compounds 1-6 Alkyl alkyl group, C 3-4 Selected from the group consisting of cycloalkyl groups, 3-4 heterocyclic alkyl groups containing 1 to 4 heteroatoms selected from N, O, or S, where the C 3-6 Cycloalkyl groups, 3- to 6-membered heterocyclic alkyl groups, are composed of deuterium, halogens, =O, -CN, -OH, -NH2, and C. 1-3 Alkyl alkyl groups, C halogenated compounds 1-3 Alkyl alkyl group, C 1-3 Alkoxy group, halogenated C 1-3 It is optionally substituted by 0 to 6 substitutions selected from the group consisting of alkoxy groups. In another preferred example, each R8, R9, R 10 These are H and C, respectively, independently. 1-6 Alkyl alkyl groups, C halogenated compounds 1-6 Selected from the group consisting of alkyl groups.

[0075] In another preferred example, the compound has a structure selected from the group consisting of the following: [ka] Here, R1, R2, R3, R4, Y1, Y2, Y3 are as defined herein, X8 is CR6 or N,

[0076] Each R6 represents H, deuterium, halogen, -CN, -NO2, C 1-6 Alkyl alkyl groups, C halogenated compounds 1-6 Alkyl groups, deuterated C 1-3 Alkyl alkyl group, C 1-6 Alkoxy group, halogenated C 1-6 Independently selected from the group consisting of alkoxy groups, -C(O)R8, -C(O)OR8, -C(O)NR8R9, -SO2R8, -S(O)(NR8)R9, -SO2NR8R9, and -P(O)R8R9, m is selected from the group consisting of 0, 1, 2, 3, and 4. In another preferred example, X1, X2, X3, X4, R1, R2, R3, R4, R5, R6, R7, R8, R9, R 10 L, L1, ring A, and ring B are, independently, the corresponding groups of compounds C1-C2 in the examples.

[0077] In another preferred example, the compound is selected from the group consisting of the following: [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka]

[0078] In another preferred example, the compound is selected from the group consisting of the following: [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka]

[0079] A second aspect of the present invention provides a pharmaceutical composition comprising one or more compounds described in the first aspect of the present invention, or pharmaceutically acceptable salts, stereoisomers, deuterides, solvates or prodrugs thereof, and a pharmaceutically acceptable carrier. A third aspect of the present invention provides the use of the compound described in the first aspect of the present invention, or a pharmaceutically acceptable salt, stereoisomer, deuteride, solvate, or prodrug thereof, 1) Preparation of selective PI3Kα inhibitors, 2) Used in applications selected from the group consisting of preparing drugs to modulate PI3Kα activity or to treat PI3Kα-related diseases.

[0080] In another preferred example, the PI3Kα has one or more mutations selected from the group consisting of H1047R, E542K, and E545K. In another preferred example, the PI3Kα-related disease is cancer or a tumor.

[0081] In another preferred example, the cancer or tumor is a selection of acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), adrenocortical carcinoma, HIV-related cancer, HIV-related lymphoma, anal cancer, astrocytoma, basal cell carcinoma, cholangiocarcinoma, bladder cancer, bone cancer, osteosarcoma, malignant fibrous histiocytoma, brain tumor, breast cancer, bronchial tumor, Burkitt lymphoma, carcinoid tumor, cancer of unknown primary origin, some of cardiac tumors, atypical teratoma / rhabdoid tumor, primary central nervous system lymphoma, cervical cancer, cholangiocarcinoma, chordal cancer, chronic lymphocytic leukemia (CLL), chronic myeloid Leukemia (CML), colorectal cancer, craniopharyngioma, cutaneous T-cell lymphoma, fungal diseases, scleral lymphoma syndrome, ductal carcinoma in situ (DCIS), embryonal tumors, medulloblastoma, endometrial cancer, ependymoma, esophageal cancer, sensory blastoma, Ewing's sarcoma, extracranial germ cell tumors, extragonadal germ cell tumors, fallopian tube cancer, gallbladder cancer, gastric cancer, gastrointestinal carcinoid tumors, malignant gastrointestinal stromal tumors (GIST), germ cell tumors, gestational trophoblastic disease, hairy cell leukemia, head and neck cancer, hepatocellular carcinoma, Langerhans cell histiocytosis, Hodgkin lymphoma, islet cell tumors, pancreatic neuroendocrine tumors, Kaposi's sarcoma, kidney cancer, laryngeal cancer Leukemia, liver cancer, lung cancer, lymphoma, male breast cancer, intraocular melanoma, Merkel cell carcinoma, malignant mesothelioma, metastatic cancer, metastatic squamous cell carcinoma of the neck, median duct cancer with nut gene mutation, oral cancer, multiple endocrine neoplasia syndrome, multiple myeloma / plasmacytic neoplasm, myelodysplastic syndrome, myelodysplastic tumor, myeloproliferative neoplasm, chronic myeloproliferative neoplasm, nasal cavity and paranasal sinus cancer, nasopharyngeal cancer, neuroblastoma, non-Hodgkin lymphoma, non-small cell lung cancer, oral cancer, lip and oral cancer, oropharyngeal cancer, malignant fibrous histiocytoma of bone, ovarian cancer, pancreatic cancer, pancreatic neuroendocrine neoplasm (islet cell tumor), papilloma Paraganglioma, sinus and nasal cavity cancer, parathyroid cancer, penile cancer, pharyngeal cancer, pheochromocytoma, pituitary adenoma, plasmacytoma, multiple myeloma, pleuropulmonary blastoma, primary central nervous system lymphoma, primary peritoneal cancer, prostate cancer, rectal cancer, recurrent cancer, renal cell (kidney) cancer, retinoblastoma, rhabdomyosarcoma, salivary gland cancer, sarcoma, pediatric angiotum, skin cancer, small cell lung cancer, small intestine cancer, soft tissue sarcoma, cutaneous squamous cell carcinoma, testicular cancer, oropharyngeal cancer, hypopharyngeal cancer, thymoma, thymic cancer, thyroid cancer, tracheobronchial tumor, renal pelvis-ureter transitional cell carcinoma, urethral cancer, uterine sarcoma, vaginal cancer, angiotum, vulvar cancer,The patient is selected from a group consisting of nephroblastomas.

[0082] In another preferred example, the cancers are endometrial cancer, breast cancer, esophageal squamous cell carcinoma, cervical squamous cell carcinoma, cervical adenocarcinoma, colorectal adenocarcinoma, bladder urothelial carcinoma, glioblastoma, ovarian cancer, non-small cell lung cancer, esophageal cancer / gastric cancer, schwannoma, head and neck squamous cell carcinoma, malignant melanoma, esophageal adenocarcinoma / gastric adenocarcinoma, soft tissue sarcoma, prostate cancer, fibrous laminaria carcinoma, hepatocellular carcinoma, diffuse glioma, colorectal cancer, pancreatic cancer, cholangiocarcinoma, B-cell lymphoma, mesothelioma, adrenocortical carcinoma, non-clear cell renal carcinoma, clear cell renal carcinoma, germ cell carcinoma, thymoma, pheochromocytoma, other neuroepithelial tumors, thyroid cancer, leukemia, or capsular glioma. In another preferred example, the cancer is breast cancer, prostate cancer, or brain tumor.

[0083] A fourth aspect of the present invention provides a method for preventing and / or treating PI3Kα activity modulation, or for treating PI3Kα-related diseases, the method comprising administering to a subject as needed a compound described in the first aspect of the present invention, or a pharmaceutically acceptable salt, stereoisomer, deuteride, solvate, or prodrug thereof. In another preferred example, the subject may be a human or a non-human mammal such as a rat, mouse, rabbit, pig, dog, or sheep. [Effects of the Invention]

[0084] It should be understood that, within the scope of the present invention, new or preferred technical solutions can be constructed by combining the above-described technical features of the present invention with the technical features specifically described below (e.g., in the examples). Due to space limitations, this will not be repeated here. [Modes for carrying out the invention]

[0085] Through extensive and meticulous research, the inventors unexpectedly prepared a compound with excellent PI3Kα mutation-selective inhibitory activity and a method for preparing the same. Specifically, through structural optimization, the inventors obtained a compound with excellent PI3Kα mutation-selective inhibitory activity. Based on this, the inventors completed the present invention.

[0086] term In this invention, unless otherwise specified, terms used have the general meanings well known to those skilled in the art. In this invention, the term "halogen" refers to F, Cl, Br, or I. In the present invention, "C 1-6 "Alkyl group" refers to a linear or branched alkyl group containing 1 to 6 carbon atoms, such as methyl group, ethyl group, propyl group, isopropyl group, butyl group, isobutyl group, tert-butyl group, neopentyl group, pteropentyl group, or similar groups. Preferably, C 1-3 It is an alkyl group. Other similar terms have similar meanings.

[0087] In the present invention, "C 1-6 The term "alkoxy group" refers to a linear or branched alkoxy group having 1 to 6 carbon atoms, and non-limitedly includes methoxy, ethoxy, propoxy, isopropoxy, and butoxy groups. Preferably, C 1-3 It is an alkoxy group. Other similar terms have similar meanings. In the present invention, "Deuterated C 1-6 The term "alkyl group" refers to an alkyl group in which hydrogen atoms on a linear or branched chain containing 1 to 6 carbon atoms are optionally substituted with one, more, or all deuterium atoms, such as -CD3, -CH2CD3, -CH(CH3)CD3, etc. 1-3 The term "alkyl group" has a similar meaning.

[0088] In the present invention, "Deuterated C 1-6An "alkoxy group" refers to an alkoxy group in which hydrogen atoms on a linear or branched chain containing 1 to 6 carbon atoms are arbitrarily substituted with one, more, or all deuterium atoms, such as -OCD3, -OCH2CD3, -OCH(CH3)CD3, etc. 1-3 The term "alkoxy group" has a similar meaning. In the present invention, "C 1-6 The term "heteroalkyl group" refers to a linear or branched alkyl group having 1 to 6 carbon atoms, including 1 to 4 heteroatoms arbitrarily selected from N, O, or S, and non-limitingly includes methoxymethyl group, ethoxymethyl group, propoxymethyl group, isopropoxymethyl group, butoxymethyl group, -CH2OH, -CH2NH2, -CH2NHCH3, -CH2N(CH3)2, -CH2CH2OCH3, -CH2CH2NHCH3, -CH2CH2N(CH3)2, etc.

[0089] In the present invention, "C 1-6 The term "alkylene group" refers to a linear or branched alkylene group structure containing 1 to 6 carbon atoms, and non-limited includes -CH2-, -CH2CH2-, -CH2CH2CH2-, -CH(CH3)CH2-, -CH(CH3)CH2CH2-, -CH2CH(CH3)CH2-, -CH2CH2CH2CH2-, -CH2CH2CH2CH2CH2CH2-, and -CH2CH2CH2CH2CH2CH2-. Other similar terms have similar meanings.

[0090] In the present invention, "saturated or partially unsaturated C 3-10 The term "cycloalkyl group" refers to a cyclic alkyl group having 3 to 10 carbon atoms on the ring, C 5-10 Spirocyclic alkyl group, C 5-10 Crosslinked cyclic alkyl group, C 3-8 Monocyclic alkyl group, C 4-12 It contains a fused cyclic alkyl group, where some carbon atoms on the ring can form an unsaturated structure in the form of a double bond with adjacent carbon atoms, and not limited to, [ka] This includes, etc. "Saturated or partially unsaturated C 3-6 "Cycloalkyl group" has a similar meaning.

[0091] In the present invention, the term "saturated or partially unsaturated 3-12 member heterocyclic alkyl group" refers to a cyclic alkyl group comprising 1 to 4 heteroatoms optionally selected from N, O, or S, wherein the ring may be a saturated ring or a partially unsaturated ring, and includes, but is not limited to, a 5-12 member spirocyclic alkyl group comprising 1 to 4 heteroatoms optionally selected from N, O, or S, a 5-12 member bridging cyclic alkyl group comprising 1 to 4 heteroatoms optionally selected from N, O, or S, a 3-8 member monocyclic alkyl group comprising 1 to 4 heteroatoms optionally selected from N, O, or S, and a 4-12 member fused cyclic alkyl group comprising 1 to 4 heteroatoms optionally selected from N, O, or S. [ka] Includes. The terms "4-6 member heterocyclic alkyl group" and "5-7 member heterocyclic alkyl group" have the same meaning. In this invention, the terms "aromatic ring" and "aryl group" have the same meaning. 6-10 The term "aryl group" refers to an aromatic structure containing aryl groups that do not contain heteroatoms and have 6 to 10 carbon atoms, including monocyclic aryl groups and bicyclic C groups. 8-10 It contains an aryl group, and is not limited to, [ka] This includes the following. The aryl group may or may not be substituted. The part attached to the parent compound is an aromatic ring.

[0092] In the present invention, the terms "aromatic heterocyclic" and "heteroaryl group" have the same meaning and refer to monocyclic or polycyclic heteroaromatic groups containing 1 to 4 heteroatoms arbitrarily selected from N, O, or S. For example, "5-10 membered heteroaryl group" refers to an aromatic heterocyclic group containing 1 to 4 heteroatoms selected from N, O, or S and 1 to 9 carbon atoms, and includes 5-6 membered monocyclic heteroaryl groups and 8-10 membered polycyclic heteroaryl groups. Here, "5-6 membered monocyclic heteroaryl groups" include, but are not limited to, furanyl groups, thiophenyl groups, pyridinyl groups, pyrazolyl groups, pyrrolyl groups, N-alkylpyrrolyl groups, pyrimidinyl groups, pyrazinyl groups, imidazolyl groups, tetrazolyl groups, etc., and "8-10 membered polycyclic heteroaryl groups" include, but are not limited to, these. [ka]

[0093] The heteroaryl group may be substituted or unsubstituted. Here, the part attached to the parent compound is the aromatic ring. In this invention, the term "halogenation" refers to substitution with a halogen. In the present invention, the term "substitution" refers to the substitution of one or more hydrogen atoms of a particular group with a particular substituent. The particular substituent is either a substituent equipped in accordance with the above, or a substituent appearing in each example. Unless otherwise specified, the substituted particular group may have substituents selected from the particular group at any of its substitutable positions, and such substituents may be the same or different at each position. Those skilled in the art will understand that the substituent combinations intended by the present invention are stable or chemically achievable combinations. The substituents include deuterium, halogen, hydroxyl group, cyano group, amino group, alkylamine group, =O, C 1-6 Alkyl alkyl group, C 1-6 Alkoxy group, C 3-10 Cycloalkyl groups, halogenated C 1-6 Alkyl alkyl groups, C halogenated compounds 1-6Alkoxy group, halogenated C 3-10 Cycloalkyl groups, alkylamine halogenated groups, 3-10 membered heterocyclic groups, aryl groups, heteroaryl groups, C 2-10 Acyl group, C 2-10 Ester group, C 2-6 Alkynyl group, C 2-6 This includes (but is not limited to) alkenyl groups.

[0094] In this invention, the term "0 to 6" refers to 0, 1, 2, 3, 4, 5, or 6. Other similar terms have similar meanings. In this invention, the term "one or more" refers to 1, 2, 3, 4, 5, or 6. Other similar terms have similar meanings. When a group exists simultaneously at multiple different positions in a compound, it should be understood that its definition at each position is independent and may be the same or different. That is, the phrase "selected from the group consisting of:" has the same meaning as "each independently selected from the group consisting of:" or "independently selected from the group consisting of:".

[0095] compound The present invention provides a compound, which is a compound of formula (I), or a pharmaceutically acceptable salt, stereoisomer, deuteride, solvate, or prodrug thereof. [ka] Here, R2, R3, R4, X1, X2, X3, X4, X5, X6, X7, ring A, and ring B are as defined above. In another preferred example, in the compound, one of R2, R3, R4, X1, X2, X3, X4, X5, X6, X7, ring A, or ring B is independently a corresponding specific group in the specific compound.

[0096] As used herein, the term “pharmaceutically acceptable salt” refers to a salt that is suitable as a drug when formed with an acid or base of the compound of the present invention. pharmaceutically acceptable salts include inorganic salts and organic salts. A preferred class of salts is one formed with an acid of the compound of the present invention. Acids suitable for salt formation include, but are not limited to, inorganic acids such as hydrochloric acid, hydrobromic acid, hydrofluoric acid, sulfuric acid, nitric acid, and phosphoric acid; organic acids such as formic acid, acetic acid, trifluoroacetic acid, propionic acid, oxalic acid, malonic acid, succinic acid, fumaric acid, maleic acid, lactic acid, malic acid, tartaric acid, citric acid, picric acid, benzoic acid, methanesulfonic acid, ethanesulfonic acid, p-toluenesulfonic acid, benzenesulfonic acid, and naphthalenesulfonic acid; and amino acids such as proline, phenylalanine, aspartic acid, and glutamic acid.

[0097] Other preferred salts are salts formed with the compound of the present invention and a base, such as alkali metal salts (e.g., sodium or potassium salts), alkaline earth metal salts (e.g., magnesium or calcium salts), ammonium salts (e.g., lower alkanolammonium salts and other pharmaceutically acceptable amine salts), such as methylamine salt, ethylamine salt, propylamine salt, dimethylamine salt, trimethylamine salt, diethylamine salt, triethylamine salt, t-butylamine salt, ethylenediamine salt, hydroxyethylamine salt, dihydroxyethylamine salt, trihydroxyethylamine salt, and amine salts formed from morpholine, piperazine, and lysine, respectively.

[0098] The compounds of the present invention also include prodrugs of the compounds represented by formula (I). The term "prodrug" includes being biologically active or inactive in itself, and being metabolized or chemically reacted in the human body after being administered in an appropriate manner to be converted into the compound of formula (I), or a salt or solution comprising the compound of formula (I). The prodrug includes, but is not limited to, forms of the compound such as carboxylic acid esters, carbonate esters, phosphate esters, nitrate esters, sulfate esters, sulfone esters, sulfoxide esters, amino compounds, carbamates, azo compounds, phosphoramides, glucosides, ethers, and acetals.

[0099] The term "solvate" refers to a complex formed by the coordination of the compound of the present invention with a solvent molecule to create a specific ratio. It should be understood that the specific preparation methods for the compounds of formula (I) of the present invention do not limit the present invention. The compounds of the present invention can also be easily prepared by any combination of the various synthesis methods described herein or known in the art, and such combinations can be easily carried out by those skilled in the art. Typically, the compounds of the present invention can be prepared by the process flow shown in the examples, where all raw materials and reagents used are purchased through commercial channels unless otherwise specified.

[0100] Pharmaceutical composition and administration method The present invention further provides a pharmaceutical composition comprising one or more of the aforementioned compounds in a therapeutically effective amount and a pharmaceutically acceptable carrier. Because the compounds of the present invention possess excellent antitumor activity, the compounds of the present invention, their various crystalline forms, pharmaceutically acceptable inorganic or organic salts, hydrates or solvates, and pharmaceutical compositions containing the compounds of the present invention as the main active ingredient are used to treat, prevent, and alleviate tumor-related diseases. The pharmaceutical composition of the present invention comprises the compound of the present invention or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable excipient or carrier in a safe and effective amount. Here, “safe and effective amount” means an amount of the compound sufficient to significantly improve the condition without causing serious side effects. Typically, the pharmaceutical composition contains 1 to 2000 mg of the compound / agent of the present invention, more preferably 10 to 1000 mg of the compound / agent of the present invention. Preferably, “one agent” is one capsule or tablet.

[0101] "Pharmacochemically acceptable carrier" means one or more compatible solid or liquid fillers or gels that are suitable for human use and must have sufficient purity and sufficiently low toxicity. "Compatibility" means that each component of the composition can be blended with each other in relation to the compounds of the present invention and among them without significantly reducing the potency of the compounds. Some examples of pharmaceutically acceptable carriers include cellulose and its derivatives (e.g., sodium carboxymethylcellulose, sodium ethylcellulose, cellulose acetate, etc.), gelatin, talc, solid lubricants (e.g., stearic acid, magnesium stearate), calcium sulfate, vegetable oils (e.g., soybean oil, sesame oil, peanut oil, olive oil, etc.), polyols (e.g., propylene glycol, glycerin, mannitol, sorbitol, etc.), emulsifiers (e.g., Tween®), wetting agents (e.g., sodium dodecyl sulfate), colorants, flavorings, stabilizers, antioxidants, preservatives, pyrogen-free water, etc.

[0102] The aforementioned pharmaceutical composition is in the form of an injection, capsule, tablet, pill, powder, or granule. The method of administration of the compound or pharmaceutical composition of the present invention is not particularly limited, and typical methods of administration include (but are not limited to) oral, intratumoral, rectal, parenteral (intravenous, intramuscular, or subcutaneous), and topical administration. Solid dosage forms for oral administration include capsules, tablets, pills, powders, and granules. In these solid dosage forms, the active compound is mixed with at least one conventional inactive excipient (or carrier), such as sodium citrate or dicalcium phosphate, or (a) fillers or compatibilizers such as starch, lactose, sucrose, glucose, mannitol, and silicic acid; (b) binders such as hydroxymethylcellulose, alginates, gelatin, polyvinylpyrrolidone, sucrose, and gum arabic; (c) humectants such as glycerin; (d) agar, calcium carbonate, potato starch. It is mixed with components such as potato starch or tapioca starch, alginic acid, certain complex silicates, and disintegrants such as sodium carbonate, (e) dissolution retarders such as paraffin, (f) absorption enhancers such as quaternary amine compounds, (g) wetting agents such as cetyl alcohol and glyceryl monostearate, (h) adsorbents such as kaolin, and (i) lubricants such as talc, calcium stearate, magnesium stearate, solid polyethylene glycol, sodium dodecyl sulfate, or mixtures thereof. In capsules, tablets, and pills, the dosage form may also include a buffer.

[0103] Solid dosage forms such as tablets, sugar pills, capsules, pills, and granules can be prepared using coating and shell materials, such as enteric coatings and other materials known in the art. They may contain opacifiers, and the release of the active compound or compound from such compositions can be delayed in specific parts of the digestive tract. Examples of usable embedding components are polymers and waxes. If necessary, the active compound can form microcapsules with one or more of the above excipients.

[0104] Liquid dosage forms for oral administration include pharmaceutically acceptable emulsions, solutions, suspensions, syrups, or tinctures. In addition to the active compound, the liquid dosage form may contain inert diluents conventionally used in the art, such as water or other solvents, and solubilizers and emulsifiers such as ethanol, isopropanol, ethyl carbonate, ethyl acetate, propylene glycol, 1,3-butanediol, dimethylformamide, and oils, particularly cottonseed oil, peanut oil, corn germ oil, olive oil, sesame oil, and sesame oil, or mixtures thereof. In addition to these inert diluents, the composition may also include auxiliary agents such as wetting agents, emulsifiers and suspending agents, sweeteners, flavoring agents and fragrances. In addition to the active compound, the suspension may include suspending agents such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol and dehydrated sorbitan esters, microcrystalline cellulose, aluminum methoxide and agar, or mixtures thereof.

[0105] Compositions for parenteral injection may include physiologically acceptable sterile aqueous or aqueous solutions, dispersions, suspensions or emulsions, and sterile powders for reconstitution into sterile injectable solutions or dispersions. Suitable aqueous and non-aqueous carriers, diluents, solvents or excipients include water, ethanol, polyols, and suitable mixtures thereof. Dosage forms of the compounds of the present invention used for topical administration include ointments, powders, patches, sprays, and inhalants. The active ingredient is mixed under sterile conditions with a physiologically acceptable carrier and any preservatives, buffers, or propellants as needed. The compounds of the present invention can be administered alone or in combination with other pharmaceutically acceptable compounds (e.g., antitumor drugs). The therapeutic method of the present invention can be used alone or in combination with other therapeutic means or therapeutic agents.

[0106] When the pharmaceutical composition is used, a safe and effective amount of the compound of the present invention is applied to a mammal (e.g., human) in need of treatment, where the dose at the time of administration is the effective dose to be considered, and for a person weighing 60 kg, the daily dose is usually 1 to 2000 mg, preferably 50 to 1000 mg. Of course, the specific dose must also take into account factors such as the route of administration and the patient's health condition, all of which are within the scope of the skills of a skilled physician.

[0107] Compared to the prior art, the present invention has the following main advantages. (1) The compound has excellent selective inhibitory activity against PI3Kα mutations. (2) The compound has excellent antitumor effects. (3) The compound has excellent safety. (4) The compound has excellent pharmacokinetic properties. The present invention will be further described below in conjunction with specific embodiments. It should be understood that these embodiments are used solely for illustrative purposes and do not limit the scope of the invention. In the following embodiments, experimental methods that do not specify conditions generally follow conventional conditions or conditions proposed by the manufacturer. Unless otherwise specified, percentages and parts are calculated by weight.

[0108] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as those well known to those skilled in the art. Furthermore, any methods and materials similar or equivalent to those described herein can all be applied to the methods of the present invention. Preferred methods and materials described herein are for demonstration purposes only.

[0109] Synthesis route of the example Unless otherwise specified, the absolute stereochemical definitions for all chiral atoms are as follows: The symbol "or1" indicates that the compound is a single-configuration compound but its absolute configuration is unknown; the symbol "or2" indicates that the compound is a single-configuration compound and an enantiomer of the "or1" structure but its absolute configuration is unknown; the symbol "abs" indicates that the compound has a structure in which its absolute configuration is shown; the symbol "rac" indicates that the compound is a racemate; and the symbols "S" or "R" indicate that the chirality of the carbon atom in the compound at that position is a known configuration in which it is indicated.

[0110] Synthesis of intermediates Synthesis of intermediate int1: The synthesis route and experimental process are as follows: [ka]

[0111] 1. Synthesis of compound int1-2: In a 100 ml bottle, int1-1 (2 g, 1 eq), sodium carbonate (4.2 g, 2 eq), water (20 mL), and 1,4-dioxane (60 mL) were added, and the mixture was cooled to 0°C. Fmoc-Cl (5.7 g, 1.1 eq) was added, and the mixture was allowed to rise naturally to room temperature. After stirring for 4 hours, the mixture was diluted with saturated saline solution (200 mL). The mixture was extracted with ethyl acetate, the organic phases were combined, dried, and concentrated to obtain 6.7 g of product.

[0112] 2. Synthesis of compounds int1-3: In a 100 mL three-necked bottle, int1-2 (5 g, 1 eq), toluene (100 ml), 2-amino-3-bromo-5-fluorobenzoic acid (4.7 g, 1.3 eq), and thionyl chloride (2.58 g, 1.4 eq) were added and stirred at 80°C for 1 hour, then heated to 120°C and reacted with stirring for 3 hours. After the reaction was complete, the mixture was purified by direct column chromatography to obtain 2.2 g of product. 1 H NMR(DMSO-d6,400MHz)δ 8.22(s,1H),7.94-7.86(m,2H),7.75(s,1H),7.69-7.62(m,2H),7.34(qd,J=7.9,7.3, 1.2Hz,4H),4.68-4.38(m,4H),4.33(t,J=6.2Hz,1H),4.14-3.96(m,2H),3.69(s,2H).

[0113] 3. Synthesis of compounds int1-4: int1-3 (2.2g, 1eq), dioxane (30ml), tributyl(1-ethoxyethylene)tin (1.82g, 1.2eq), and Pd(PPh3)2Cl2 (0.59g, 0.2eq) were added to a reaction bottle, and the mixture was reacted at 80°C for 3 hours under nitrogen gas protection. After the reaction, the reaction system was cooled to room temperature, 100ml of 2M hydrochloric acid was added, and the mixture was stirred for 30 minutes. Then, 100ml of saturated potassium fluoride solution was added, and the mixture was stirred for 30 minutes. The pH was adjusted to near neutral with saturated sodium bicarbonate, extracted with ethyl acetate, dried, concentrated, and purified by column chromatography to obtain 1.7g of the product.

[0114] 4. Synthesis of compounds int1-5: Add the above int1-4 (1.7g, 1eq), methanol (3mL), and dichloromethane (30ml) to a 500mL bottle, cool to 0°C, add NaBH4 (0.2g, 1.5eq), and stir at 0°C for 1 hour after the addition is complete. Monitor the completeness of the reaction by liquid chromatography-mass spectrometry, add saturated ammonium chloride (10ml), stir for 30 minutes, extract with dichloromethane (20ml x 3), dry, concentrate, and purify by column chromatography to obtain 1.22g of product. 1H NMR(400MHz,Methanol-d4)δ 7.74(d,J=9.3Hz,3H),7.62(t,J=7.1Hz,3H),7.38-7.23(m,4H),5.67(s,1H),4.62(s,2H),4. 29(d,J=23.7Hz,2H),4.02(s,1H),3.79(d,J=44.0Hz,1H),3.60(s,1H),1.50(d,J=6.3Hz,3H).

[0115] 5. Synthesis of compound int1: In a 25 mL three-necked bottle, add int1-5 (1.22 g, 1 eq) and dichloromethane (60 mL). Cool to 0°C under nitrogen gas protection, then add phosphorus tribromide (1 mL) dropwise and stir for 16 hours. After the reaction is complete, concentrate to obtain 2.2 g of crude product. Use directly in the next step of the reaction. 1 H NMR(400MHz,Chloroform-d)δ 7.88(d,J=7.9Hz,1H),7.77(s,3H),7.58(s,2H),7.45-7.29(m,4H),6.30(d,J=7.3Hz,1H),4.60(q, J=21.5,21.0Hz,4H),4.27(t,J=6.0Hz,1H),4.17-4.02(m,2H),3.68(s,2H),2.06(d,J=13.4Hz,3H).

[0116] Synthesis of the intermediate int2: The synthesis route and experimental process are as follows: [ka] In a 100 mL three-necked bottle, int2-1 (300 mg, 1.0 eq), DHP (234 mg, 2 eq), and dichloromethane (50 ml) were added, followed by the addition of p-toluenesulfonic acid (64 mg, 0.2 eq). The mixture was then reacted at room temperature for 1 hour under nitrogen gas protection. After the reaction was complete, the mixture was washed with saturated sodium chloride aqueous solution, extracted with dichloromethane, concentrated, and purified to obtain 300 mg of the product.

[0117] Synthesis of the intermediate int3: The synthesis route and experimental process are as follows: [ka]

[0118] 1. Synthesis of compound int3-2: Compound int3-1 (8.25 g, 43.2 mmol) is dissolved in 150 mL of N,N-dimethylformamide, and 3-chloro-4-cyanopyridine (5 g, 36 mmol) and cesium carbonate (23.5 g, 72 mmol) are added. After the addition is complete, the temperature is raised to 110°C and the mixture is reacted for 2 hours until the starting materials are completely reacted. Water is slowly added to quench the mixture, then it is extracted with dichloromethane to separate the organic phase, dried over anhydrous sodium sulfate, and the filtrate is concentrated under reduced pressure and purified to obtain 12 g of product. 1 H NMR (400MHz, Chloroform-d) δ 8.48 (d, J = 4.8 Hz, 1H), 8.11 (s, 1H), 7.56 (d, J = 4.8 Hz, 1H), 7.45 (dd, J = 7.6, 2.8 Hz, 1H), 7.24-7.09 (m, 2H).

[0119] 2. Synthesis of compound int3-3: Dissolve int3-2 (12 g, 41 mmol) in 120 g of polyphosphate and slowly raise the temperature to 220°C, stirring for 3 hours. After the starting materials have completely reacted, cool the reaction mixture to room temperature, dissolve it in water, adjust the pH to basic with saturated sodium bicarbonate aqueous solution, then extract three times with ethyl acetate, combine the organic phases, dry over anhydrous sodium sulfate, concentrate under reduced pressure, and purify to obtain 9.69 g of product. 1 H NMR (400MHz, Chloroform-d) δ 9.17(s,1H),8.71(d,J=5.1Hz,1H),8.09(d,J=5.1Hz,1H),7.97(dd,J=7.6,3.2Hz,1H),7.83(dd,J=7.2,3.2Hz,1H).

[0120] 3. Synthesis of compounds int3-4: Int3-3 (9g, 30.6 mmol), potassium iodide (11.2g, 67.32 mmol), and benzyl chloride (9.6g, 61.2 mmol) are added to 360 mL of acetonitrile, and the reaction mixture is slowly heated to 80°C and stirred overnight. After the starting materials have completely reacted, the reaction mixture is concentrated under reduced pressure to obtain 17 g of crude product, which is used directly in the next step of the reaction.

[0121] 4. Synthesis of compounds int3-5: Compound int3-4 (17 g, 30.9 mmol) is dissolved in 200 mL of anhydrous ethanol, sodium borohydride cyanohydride (15.5 g, 247.2 mmol) and acetic acid (1.8 g, 30.6 mmol) are added, and the mixture is stirred for 30 minutes while maintaining room temperature. After the starting materials have completely reacted, the reaction solution is diluted with water, then extracted three times with dichloromethane, the organic phases are combined, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and purified to obtain 6 g of product. 1 H NMR(400MHz,Chloroform-d)δ 7.81(dd,J=8.0,3.2Hz,1H),7.61(dd,J=7.2,3.2Hz,1H),7.32-7.27(m,2H),6.95-6.86(m,2H ),3.82(s,3H),3.69(s,2H),3.53(t,J=1.6Hz,2H),2.77(t,J=5.8Hz,2H),2.71-2.62(m,2H).

[0122] 5. Synthesis of compounds int3-6: Compound int3-5 (6g, 14.4 mmol), tributyl(1-ethoxyethylene)tin (6.2g, 17.2 mmol), and Pd(PPh3)2Cl2 (1g, 1.44 mmol) were dissolved in dry dioxane (250 mL) and stirred at 80°C for 12 hours. Then, under room temperature conditions, potassium fluoride solution was added, the mixture was stirred for 0.5 hours, filtered, and the mother liquor was extracted three times with ethyl acetate to separate the organic phase. The organic phase was spin-dried, dissolved in dichloromethane, 2 ml of concentrated hydrochloric acid was added, and the mixture was stirred at 25°C for 10 minutes. After the reaction was complete, the mixture was purified by column chromatography to obtain 4 g of product. 1H NMR(400MHz,Chloroform-d)δ 8.03(dd,J=7.6,3.2Hz,1H),7.80(dd,J=8.0,3.2Hz,1H),7.31-7.27(m,2H),6.93-6.87(m,2H),3.82( s,3H),3.69(s,2H),3.53(d,J=1.6Hz,2H),2.78(t,J=5.8Hz,2H),2.71(s,3H),2.68(d,J=6.8Hz,2H).

[0123] 6. Synthesis of compound int3-7: Compound int3-6 (1 g, 2.62 mmol) is dissolved in a mixed solvent consisting of 10 mL of dichloromethane and 10 mL of methanol. Under nitrogen gas protection, sodium borohydride (50 mg, 1.31 mmol) is slowly added, and the reaction mixture is stirred at room temperature for 10 minutes. After the starting materials have completely reacted, the reaction mixture is diluted with water, then extracted three times with dichloromethane, the organic phases are combined, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and purified to obtain 600 mg of the product. 1 H NMR(400MHz,Chloroform-d)δ 7.67(dd,J=7.9,3.2Hz,1H),7.52(dd,J=8.8,3.2Hz,1H),7.36-7.29(m,2H),6.97-6.86(m,2H),5.28(q,J=6.1Hz, 1H),3.83(s,3H),3.76-3.63(m,2H),3.40(s,2H),2.86-2.70(m,2H),2.66(d,J=5.8Hz,2H),1.47(d,J=6.4Hz,3H).

[0124] 7. Synthesis of compound int3-8: Compound int3-7 (600 mg, 1.56 mmol) is dissolved in 50 mL of anhydrous dichloromethane, and phosphorus tribromide (1.3 g, 4.68 mmol) is slowly added under nitrogen gas protection. The mixture is stirred at room temperature for 12 hours until the starting materials have completely reacted, and then concentrated under reduced pressure to obtain 600 mg of the product.

[0125] 8. Synthesis of compounds int3-9: Compound int3-8 (600 mg, 1.35 mmol) is dissolved in 20 mL of anhydrous N,N-dimethylformamide, and 2-tert-butyl 2-aminobenzoate (782 mg, 4.05 mmol) is slowly added at room temperature. The temperature is slowly raised to 60°C, and the mixture is reacted with stirring for 12 hours until the starting materials have completely reacted. The reaction mixture is then diluted with water, extracted three times with ethyl acetate, the organic phases are combined, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and purified to obtain 400 mg of the product. 1 H NMR(400MHz,Chloroform-d)δ 8.27(d,J=6.0Hz,1H),7.88(dd,J=8.0,1.6Hz,1H),7.70(dd,J=8.0,3.2Hz,1H),7.38(dd ,J=8.8,3.2Hz,1H),7.31(d,J=8.4Hz,2H),7.19-7.08(m,1H),6.94-6.87(m,2H),6.56(t, J=7.6Hz,1H),6.21(d,J=8.4Hz,1H),5.05(t,J=6.4Hz,1H),3.82(s,3H),3.74-3.64(m,2H ),3.55(d,J=6.9Hz,2H),2.78(dt,J=9.6,5.6Hz,2H),2.71(d,J=6.0Hz,2H),1.62(s,9H).

[0126] 9. Synthesis of compound int3: Compound int3-9 (180 mg, 0.32 mmol) is dissolved in 20 mL of 1,2-dichloroethane, and 1-chloroethyl chloroformate (92 mg, 0.64 mmol) is slowly added at room temperature. The temperature is slowly raised to 83°C, and the mixture is reacted with stirring for 3 hours until the starting materials have completely reacted. The reaction mixture is then concentrated to dryness, methanol is added, the temperature is raised to 65°C, and the mixture is reacted with stirring for 1 hour. The mixture is then concentrated and slurryed with methyl tert-butyl ether to obtain 140 mg of the product. 1H NMR(400MHz,Methanol-d4)δ 7.87(dd,J=8.0,1.6Hz,1H),7.70(dd,J=8.0,3.2Hz,1H),7.55(dd,J=8.8,3.2Hz,1H),7.19(m,1H),6.59(ddd,J=8.0,7.2,1.2Hz,1H),6.4 6(d,J=8.4Hz,1H),5.23(q,J=6.8Hz,1H),4.54-4.39(m,2H),3.58(t,J=6.0Hz,2H),2.96-2.86(m,2H),1.71(d,J=6.8Hz,3H),1.66(s,9H).

[0127] Synthesis of the intermediate int4: The synthesis route and experimental process are as follows: [ka]

[0128] 1. Composition of int4-1: Compound int3-6 (9 g, 23.6 mmol) is dissolved in 200 ml of tetrahydrofuran, then R-tert-butylsulfinamide (5.7 g, 47.2 mmol) and tetraethyl titanate (21.5 g, 94.4 mmol) are added, and the mixture is stirred overnight at 70°C. After the reaction is complete, water is added, the mixture is filtered, the filter cake is washed with ethyl acetate, the aqueous phase is extracted with ethyl acetate, the organic phase is combined and concentrated, and 10 g of the product is obtained by column chromatography.

[0129] 2. Composition of int4-2: Compound int4-1 (10 g, 20.6 mmol) was dissolved in 400 ml of methanol, and then cerium chloride heptahydrate (3.8 g, 10.3 mmol) was added. After the addition was complete, sodium borohydride (1.17 g, 30.9 mmol) was added to the reaction system in batches, and the reaction was carried out at room temperature for 10 minutes. After the reaction was complete, the mixture was concentrated, and 8.87 g of the product was obtained by column chromatography.

[0130] 3. Composition of int4-3: Compound int4-2 (12 g, 24.6 mmol) is dissolved in 120 ml of methanol / hydrogen chloride solution and reacted at room temperature for 10 minutes. After the reaction is complete, the solution is directly spin-dried, adjusted to basic conditions with saturated sodium bicarbonate aqueous solution, extracted with ethyl acetate, dried, concentrated, and obtained 10 g of product by column chromatography.

[0131] 4. Composition of int4-4: Compound int4-3 (5 g, 13.1 mmol) is dissolved in 100 ml of dimethyl sulfoxide, and N,N-diisopropylethylamine (8.5 g, 65.5 mmol) is added. After the addition is complete, 6-chloro-3-fluoropyridine-2-carboxylic acid tert-butyl ester (18.1 g, 78.6 mmol) is added to the reaction system, and the reaction is carried out at 70°C for 4 hours under nitrogen gas protection. After the reaction is complete, water is added, the mixture is extracted with ethyl acetate, dried, concentrated, and 3.4 g of the product is obtained by column chromatography.

[0132] 5. Composition of int4: Compound int4-4 (3.4 g, 5.72 mmol) is dissolved in 300 ml of 1,2-dichloroethane, and 1-chloroethyl chloroformate (1.63 g, 11.44 mmol) is added. After the addition is complete, the mixture is reacted at 83°C for 0.5 hours. After the reaction is complete, the mixture is directly spin-dried, and after spin-drying, it is dissolved in 300 ml of methanol. Triethylamine (2.3 g, 22.88 mmol) is immediately added, and after the addition is complete, the mixture is reacted at 65°C for 2 hours. After the reaction is complete, the mixture is concentrated, and 2.3 g of the product is obtained by column chromatography.

[0133] Synthesis of the intermediate int5: The synthesis route and experimental process are as follows: [ka] 1. Composition of int5-1: Compound int4-3 (930 mg, 2.43 mmol) was dissolved in 40 ml of dry toluene, and then tert-butyl o-iodobenzoate (888.1 mg, 2.92 mmol), cesium carbonate (2.14 g, 6.56 mmol), palladium acetate (54.5 mg, 0.25 mmol), and Xantphos (281 mg, 0.5 mmol) were added sequentially. After the addition was complete, the mixture was reacted overnight at 60°C under nitrogen gas protection. The mixture was filtered, the filter cake was washed with ethyl acetate, the sample was stirred, passed through column chromatography, dried, concentrated, and column chromatography was performed to obtain 710 mg of the product.

[0134] 2. Composition of int5: Compound int5-1 (710 mg, 1.27 mmol) was dissolved in 50 ml of 1,2-dichloroethane, and 1-chloroethyl chloroformate (365 mg, 2.54 mmol) was added. After the addition was complete, the mixture was reacted at 83°C for 1 hour. After the reaction was complete, the mixture was directly spin-dried, and after spin-drying, it was dissolved in 50 ml of methanol. Triethylamine (600 mg, 5.08 mmol) was immediately added, and the mixture was reacted at 65°C for 3 hours. After the reaction was complete, the mixture was spin-dried, concentrated, and the product was obtained by column chromatography to obtain 710 mg of the product.

[0135] Synthesis of the intermediate int6: The synthesis route and experimental process are as follows: [ka]

[0136] 1. Synthesis of compound int6-2: Compound int6-1 (3.8g, 20 mmol) and int6-0 (6g, 20 mmol) were dissolved in 1,2-dichloroethane (20 mL). Then, the above solution was added to a sealed tube containing 18 g of polyphosphate, stirred at 85°C for 12 hours, cooled to room temperature, and after the reaction was complete, saturated sodium bicarbonate aqueous solution was added to the reaction mixture to adjust it to basicity, extracted three times with ethyl acetate, spin-dried, and purified by column chromatography to obtain 1.7 g of product. 1 HNMR: (CDCl3,400Hz), δ 8.90~8.88(m,1H),7.94~7.92(m,1H),7.39~7.28(m,5H),3.75(s,2H),3.68(s,2H),2.84~2.80(m,4H).

[0137] 2. Synthesis of compound int6-3: Compound int6-2 (1.2 g, 3.1 mmol), tributyl(1-ethoxyethylene)tin (1.57 g, 4.3 mmol), and Pd(PPh3)2Cl2 (200 mg, 0.31 mmol) were dissolved in dry dioxane (50 mL) and stirred at 80°C for 12 hours. Then, under room temperature conditions, potassium fluoride solution was added and the mixture was stirred for 0.5 hours, filtered, and the mother liquor was extracted three times with ethyl acetate to separate the organic phase, which was then spin-dried. 10 mL of dioxane and concentrated hydrochloric acid (10 mL) were added and the mixture was stirred at 25°C for 1 hour. After the reaction was complete, saturated sodium bicarbonate aqueous solution was added, extracted with ethyl acetate, spin-dried, and purified by column chromatography to obtain 0.88 g of product. 1 HNMR: (CDCl3,400Hz), δ8.99~8.97(m,1H),7.87~7.85(m,1H),7.38~7.28(m,5H),3.75(s,2H),3.63(s,2H),2.84~2.80(m,7H).

[0138] 3. Synthesis of compound int6-4: Dissolve compound int6-3 (465 mg, 13.3 mmol) in 1,2-dichloroethane (10 mL), and under room temperature and nitrogen gas protection, add 1-chloroethyl chloroformate (0.29 mg, 26.5 mmol) and stir at 83°C for 2 hours. After the reaction is complete, concentrate the mixture and use it directly in the next step of the reaction.

[0139] 4. Synthesis of compound int6-5 Compound int6-4 (650 mg, crude product) is dissolved in methanol (10 mL) and reacted at 65°C under nitrogen gas protection for 1 hour. After the reaction is complete, the mixture is spin-dried and slurryed with methyl tert-butyl ether to obtain 360 mg of the product. 1 HNMR: (DMSO-d6,400Hz)δ9.75(s,2H),9.03~9.01(m,1H),8.23~8.21(m,1H),4.22(s,2H),3.38~3.35(m,2H),2.87~2.84(m,2H),2.71(s,2H),.

[0140] 5. Synthesis of compound int6-6: Compound int6-5 (150 mg, 0.5 mmol) is dissolved in dioxane / H2O (3 mL / 1 mL), and sodium carbonate (160 mg, 1.5 mmol) and Fmoc-Cl (142 mg, 0.55 mmol) are added under nitrogen gas protection at 0°C. The mixture is slowly heated to room temperature and stirred for 12 hours. After the reaction is complete, saturated brine is added, the mixture is extracted three times with dichloromethane, and the mixture is spin-dried to form a slurry to obtain 120 mg of the product. 1 HNMR:(CDCl3,400Hz),δ9.00~8.97(m,1H),7.95~7.94(m,1H),7.78~7.58(m,4H),7.40~7.36 (m,4H),4.62~4.54(m,2H),4.42~4.28(m,2H),3.71~3.70(m,3H),2.86(s,3H),2.77(s,2H).

[0141] 6. Synthesis of compounds int6-7: Compound int6-6 (120 mg, 0.25 mmol) is dissolved in methanol / dichloromethane (3 mL / 3 mL), and sodium borohydride (9.4 mg, 0.25 mmol) is added under nitrogen gas protection at room temperature. The mixture is stirred at 25°C for 10 minutes. After the reaction is complete, water is added to quench the mixture, it is spin-dried, and separated by column chromatography to obtain 80 mg of the product.

[0142] 7. Synthesis of compounds int6-8: Dissolve compound int6-7 (80 mg, 0.165 mmol) in dry dichloromethane (10 mL), add phosphorus tribromide (134 mg, 0.494 mmol) at room temperature under nitrogen gas protection, and stir at 25°C for 12 hours. Concentrate and use directly in the next step of the reaction.

[0143] 8. Synthesis of compounds int6-9: Compound int6-8 (180 mg of crude product) is dissolved in dry N,N-dimethylformamide (1 mL), and added to a solution of 2-tert-butyl 2-aminobenzoate (191 mg, 0.989 mmol) in N,N-dimethylformamide (2 mL) at 25°C. The mixture is reacted at 60°C with stirring for 12 hours. After the reaction is complete, saturated brine is added, the mixture is extracted three times with ethyl acetate, concentrated, and separated by column chromatography to obtain 15 mg of the product.

[0144] 9. Synthesis of compound int6: Compound int6-9 (15 mg, 0.223 mmol) is dissolved in dry dichloromethane (5 mL) and diethylamine (0.5 mL), and the mixture is stirred at room temperature under nitrogen gas protection for 12 hours. After the reaction is complete, the mixture is separated by column chromatography to obtain 6 mg of the product. 1 HNMR:(CDCl3,400Hz)δ8.82~8.80(m,1H),8.33~8.30(m,1H),7.92~7.90(m,1H),7.65~7.63(m,1H),7.16~7.12(m, 1H), 6.61~6.57(m,1H),6.21~6.19(m,1H),5.44~5.32(m,2H),3.38~3.36(m,2H),3.00~2.91(m,4H),1.65(s,9H).

[0145] Synthesis of the intermediate int7: The synthesis route and experimental process are as follows: [ka]

[0146] 1. Synthesis of compound int7-2: Compound int7-1 (4.48 g, 24 mmol) is dissolved in 60 mL of N,N-dimethylformamide, and 3-chloro-4-cyanopyridine (2.78 g, 20 mmol) and cesium carbonate (13 g, 40 mmol) are added. After the addition is complete, the temperature is raised to 110°C and the mixture is reacted for 3 hours until the starting materials are completely reacted. Water is slowly added to quench the mixture, then it is extracted with dichloromethane to separate the organic phase, dried over anhydrous sodium sulfate, and the filtrate is concentrated under reduced pressure and purified by column chromatography to obtain 4.5 g of product. 1 H NMR(400MHz,Chloroform-d)δ 8.47(d,J=4.8Hz,1H),8.12(s,1H),7.56~7.52(m,2H),7.23~7.20(m,1H),7.11~7.09(m,1H),2.41(s,3H),

[0147] 2. Synthesis of compound int7-3: Dissolve int7-2 (4.5 g, 15.5 mmol) in 40 g of polyphosphate and slowly raise the temperature to 220°C, stirring for 3 hours. After the starting materials have completely reacted, cool the reaction mixture to room temperature, dissolve it in water, adjust the pH to basic with saturated sodium bicarbonate aqueous solution, then extract three times with ethyl acetate, combine the organic phases, dry over anhydrous sodium sulfate, concentrate under reduced pressure, form a slurry, and purify to obtain 3.5 g of product. 1 H NMR (400MHz, Chloroform-d) δ 9.17(s,1H),8.71(d,J=5.1Hz,1H),8.12(s,1H),8.03(d,J=5.2Hz,1H),7.99(s,1H).

[0148] 3. Synthesis of compound int7-4: Int7-3 (2.5 g, 8.6 mmol), potassium iodide (3.15 g, 19 mmol), and benzyl chloride (2.7 g, 17.2 mmol) are added to 40 mL of acetonitrile, and the reaction mixture is slowly heated to 80°C and stirred for 2 hours. After the starting materials have completely reacted, the reaction mixture is concentrated under reduced pressure to obtain 8.2 g of crude product, which is used directly in the next step.

[0149] 4. Synthesis of compound int7-5: Compound int7-4 (8.2 g, 20 mmol) is dissolved in 200 mL of anhydrous ethanol, sodium borohydride cyanohydride (10.8 g, 160 mmol) and acetic acid (1.2 g, 20 mmol) are added, and the mixture is stirred for 30 minutes while maintaining room temperature. After the starting materials have completely reacted, the reaction mixture is diluted with water, then extracted three times with dichloromethane, the organic phases are combined, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and purified to obtain 3.8 g of product.

[0150] 5. Synthesis of compound int7-6: Compound int7-5 (3g, 7.24 mmol), tributyl(1-ethoxyethylene)tin (3.14g, 8.7 mmol), and Pd(PPh3)2Cl2 (510 mg, 0.724 mmol) were dissolved in dry dioxane (50 mL) and stirred at 80°C for 12 hours. Then, under room temperature conditions, potassium fluoride solution was added, the mixture was stirred for 0.5 hours, filtered, and the mother liquor was extracted three times with ethyl acetate to separate the organic phase. The organic phase was spin-dried, dissolved in dichloromethane, and 2 ml of concentrated hydrochloric acid was added. The mixture was stirred at 25°C for 10 minutes, and after the reaction was complete, 2.5 g of the product was obtained by column chromatography. 1 H NMR(400MHz,Chloroform-d)δ 8.20(s,1H),7.91(s,1H),7.32(d,J=8.4Hz,2H),6.93(d,J=8.4Hz,2H),3.84(s,3 H),3.71(s,2H),3.54(s,2H),2.79~2.77(m,2H),2.71~2.68(m,5H),2.48(s,3H).

[0151] 6. Synthesis of compound int7-7: Compound int7-6 (2.5 g, 6.63 mmol) is dissolved in a mixed solvent consisting of 30 mL of dichloromethane and 30 mL of methanol. Under nitrogen gas protection, sodium borohydride (251 mg, 6.63 mmol) is slowly added, and the reaction mixture is stirred at room temperature for 10 minutes. After the starting materials have completely reacted, the reaction mixture is diluted with water, then extracted three times with dichloromethane, the organic phases are combined, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and purified to obtain 1.5 g of product. 1 H NMR(400MHz,Chloroform-d)δ 7.90(s,1H),7.61(s,1H),7.34(d,J=8.4Hz,2H),6.94(d,J=8.4Hz,2H),5.35~5.32(m,1H),3.85 (s,3H),3.71~3.68(m,2H),3.43(s,2H),2.78~2.68(m,4H),2.44(s,3H),1.27(d,J=6.4Hz,2H).

[0152] 7. Synthesis of compounds int7-8: Compound int7-7 (1.5 g, 3.95 mmol) is dissolved in 50 mL of anhydrous dichloromethane, and phosphorus tribromide (3.21 g, 11.9 mmol) is slowly added under nitrogen gas protection. The mixture is stirred at room temperature for 12 hours until the starting materials have completely reacted, and then concentrated under reduced pressure to obtain 3.5 g of the product.

[0153] 8. Synthesis of compounds int7-9: Compound int7-8 (3.5 g, 3.95 mmol) is dissolved in 100 mL of anhydrous N,N-dimethylformamide. At room temperature, 2-tert-butyl 2-aminobenzoate (4.57 g, 23.7 mmol) is slowly added, and the mixture is slowly heated to 60°C and reacted with stirring for 12 hours. After the starting materials have completely reacted, the reaction mixture is diluted with water, then extracted three times with ethyl acetate, the organic phases are combined, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and purified to obtain 1.1 g of product.

[0154] 9. Synthesis of compound int7: Compound int7-9 (90 mg, 1.65 mmol) is dissolved in 5 mL of 1,2-dichloroethane, and 1-chloroethyl chloroformate (47.1 mg, 3.3 mmol) is slowly added at room temperature. The temperature is slowly raised to 83°C, and the mixture is reacted with stirring for 3 hours until the starting materials have completely reacted. The reaction mixture is then concentrated to dryness, methanol is added, the temperature is raised to 65°C, and the mixture is reacted with stirring for 1 hour. The mixture is then concentrated and slurryed with methyl tert-butyl ether to obtain 51 mg of product.

[0155] Synthesis of the intermediate int8: The synthesis route and experimental process are as follows: [ka] 1. Composition of int-8-1: int7-8 (260 mg, 0.59 mmol) is dissolved in N,N-dimethylformamide (5 ml), 3-amino-6-chloropyridine-2-carboxylic acid (507.0 mg, 2.95 mmol) is added, and the mixture is reacted at 80°C for 16 hours. After the reaction is complete, the reaction mixture is diluted with ethyl acetate, adjusted to a basic state with sodium bicarbonate solution, washed three times with saturated ammonium chloride, the organic phase is dried, concentrated, and purified by column chromatography to obtain 90 mg of the product.

[0156] 2. Composition of int8: Dissolve int8-1 (90 mg, 0.17 mmol) in 1,2-dichloroethane (4 ml), add 1-chloroethyl chloroformate (72.5 mg, 0.51 mmol), and react at 83°C for 3 hours. After the reaction is complete, spin-dry the reaction mixture, add methanol, and react at 65°C for 1 hour. Concentrate the reaction mixture to obtain 70 mg of the product.

[0157] Synthesis of the intermediate int9: The synthesis route and experimental process are as follows: [ka]

[0158] 1. Composition of int9-1: Compound int7-6 (10 g) was dissolved in 210 ml of tetrahydrofuran, then R-tert-butylsulfinamide (6.0 g) and tetraethyl titanate (22.3 g) were added, and the mixture was stirred overnight at 70°C. After the reaction was complete, water was added, the mixture was filtered, the filter cake was washed with ethyl acetate, the aqueous phase was extracted with ethyl acetate, the organic phase was combined and concentrated, and 11.2 g of the product was obtained by column chromatography.

[0159] 2. Composition of int9-2: Compound int9-1 (11.2g) was dissolved in 400ml of methanol, then cerium chloride heptahydrate (3.9g) was added. After the addition was complete, sodium borohydride (1.3g) was added in batches to the reaction system and the reaction was allowed to proceed at room temperature for 10 minutes. After the reaction was complete, the mixture was concentrated and 9.1g of the product was obtained by column chromatography.

[0160] 3. Synthesis of int9-3: Compound int9-2 (9.1g) was dissolved in 120ml of methanol / hydrogen chloride solution and reacted at room temperature for 10 minutes. After the reaction was complete, the solution was directly spin-dried, adjusted to basic conditions with saturated sodium bicarbonate aqueous solution, extracted with ethyl acetate, dried, concentrated, and obtained 7.2g of product by column chromatography.

[0161] 4. Synthesis of int9-4: Compound int9-3 (7.0 g) is dissolved in 100 ml of dimethyl sulfoxide, and N,N-diisopropylethylamine (9.3 g) is added. After the addition is complete, 6-chloro-3-fluoropyridine-2-carboxylic acid tert-butyl ester (20.1 g) is added to the reaction system, and the reaction is carried out at 70°C for 4 hours under nitrogen gas protection. After the reaction is complete, water is added, the mixture is extracted with ethyl acetate, dried, concentrated, and the product is obtained by column chromatography to obtain 4.3 g.

[0162] 5. Composition of int9: Compound int9-4 (4.3g) is dissolved in 300 ml of 1,2-dichloroethane, and 1-chloroethyl chloroformate (2.33g) is added. After the addition is complete, the mixture is reacted at 85°C for 0.5 hours. After the reaction is complete, the mixture is directly spin-dried, and after spin-drying, it is dissolved in 300 ml of methanol. Triethylamine (3.5g) is immediately added, and after the addition is complete, the mixture is reacted at 65°C for 2 hours. After the reaction is complete, the mixture is concentrated, and 3.1 g of the product is obtained by column chromatography.

[0163] Synthesis of the intermediate int10: The synthesis route and experimental process are as follows: [ka] 1. Composition of int10-1: Compound int9-3 (3.78 g) was dissolved in 150 ml of dry toluene, and then o-iodobenzoate tert-butyl ester (3.34 g), cesium carbonate (8.14 g), palladium acetate (216.5 mg), and Xantphos (964 mg) were added sequentially. After the addition was complete, the mixture was reacted overnight at 60°C under nitrogen gas protection. The mixture was filtered, the filter cake was washed with ethyl acetate, the sample was stirred, passed through column chromatography, dried, concentrated, and column chromatography was performed to obtain 2.84 g of the product.

[0164] 2. Composition of int10: Compound int10-1 (2.84 g) is dissolved in 150 ml of 1,2-dichloroethane, and 1-chloroethyl chloroformate (1.46 g) is added. After the addition is complete, the mixture is reacted at 85°C for 1 hour. After the reaction is complete, the mixture is directly spin-dried, and after spin-drying, it is dissolved in 150 ml of methanol. Triethylamine (2.43 g) is immediately added, and after the addition is complete, the mixture is reacted at 65°C for 3 hours. After the reaction is complete, the mixture is spin-dried, concentrated, and 1.78 g of the product is obtained by column chromatography.

[0165] Synthesis of the intermediate int11: The synthesis route and experimental process are as follows: [ka] 1. Synthesis of int11-2 Dissolve int11-1 (800 mg) in 1,4-dioxane (25 mL), and sequentially add benzyl mercaptan (500 mg), N,N-diisopropylethylamine (2.1 mL), Xantphos (465 mg), and Pd2(dba)3 (368 mg) at room temperature. Then, react the mixture at 100 °C with stirring under a nitrogen atmosphere for 18 hours until the starting materials are completely reacted. After adding a small amount of ethyl acetate to the reaction mixture, concentrate it under reduced pressure and purify it by column chromatography to obtain 603 mg of the product.

[0166] 2. Composition of int11 Dissolve int11-2 (603 mg) in a mixed solvent of acetonitrile (9 mL) and water (1 mL). Add trifluoroacetic acid (7.79 g) and N-chlorosuccinimide (667 mg) under ice water bath, and react at room temperature with stirring for 18 hours. The next day, add N-chlorosuccinimide (667 mg) and react at room temperature with stirring for 4 hours until the starting materials are completely reacted. Concentrate the reaction mixture under reduced pressure, adjust the pH to basic by adding saturated sodium bicarbonate aqueous solution, extract the aqueous solution with dichloromethane, dry the organic phase with anhydrous sodium sulfate, filter, and concentrate the filtrate under reduced pressure to obtain 588 mg of crude product, which is used directly in the next step of the reaction.

[0167] Synthesis of the intermediate int12: The synthesis route and experimental process are as follows: [ka] 1. Synthesis of int12-2 int6-0 (10g, 53.47 mmol) and int12-1 (10g, 53.47 mmol), along with polyphosphate (25 mL) and 1,2-dichloroethane (50 mL), were added to a 250 mL bottle. The mixture was stirred at 85°C for 16 hours, after which the reaction mixture was cooled to room temperature. The pH was adjusted to 8 with saturated sodium carbonate solution, and the mixture was extracted with ethyl acetate (2 × 100 mL). The organic phases were combined, washed with saturated sodium chloride, dried over anhydrous sodium sulfate, filtered, concentrated, and purified by column chromatography to obtain 3.5 g of the product.

[0168] 2. Synthesis of int12-3 Compound int12-2 (7g, 18.3 mmol), tributyl(1-ethoxyethylene)tin (7.9g, 21.9 mmol), and Pd(PPh3)2Cl2 (1.26g, 1.83 mmol) were dissolved in dry dioxane (70 ml) and stirred at 80°C for 12 hours. Then, under room temperature conditions, 70 ml of potassium fluoride solution was added and stirred for 0.5 hours, filtered, and the mother liquor was extracted with ethyl acetate (50 ml x 3) to separate the organic phase, which was spin-dried, dissolved in ethyl acetate (70 ml), 6 M hydrochloric acid (130 ml) was added, and stirred at 25°C for 10 minutes. A large amount of solid precipitated, which was filtered, the filter cake was washed with ethyl acetate (100 ml x 2), the pH was adjusted to neutral with saturated sodium bicarbonate, extracted with dichloromethane (70 ml x 2), dried, concentrated, and purified by column chromatography to obtain 3.9 g of product.

[0169] 3. Synthesis of int12-4: Compound int12-3 (3.8 g, 10.95 mmol) is dissolved in 38 mL of tetrahydrofuran, and under nitrogen gas protection, R-tert-butylsulfinamide (2.65 g, 21.9 mmol) and tetraethyl titanate (9.98 g, 43.8 mmol) are added, and the mixture is reacted at 70°C for 16 hours under nitrogen gas protection. After the starting materials have completely reacted, 38 mL of water is added to the reaction mixture, then extracted with ethyl acetate (60 ml x 4), the organic phases are combined, washed with saturated sodium chloride (60 ml), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain 4.64 g of crude product.

[0170] 4. Synthesis of int12-5: Compound int12-4 (4.64 g, 10.3 mmol) is dissolved in 70 mL of methanol. Under nitrogen gas protection, cerium chloride heptahydrate (1.92 g, 5.16 mmol) is added, the mixture is heated to 50°C under nitrogen gas protection, stirred for 30 minutes, cooled to 15°C, and sodium borohydride (0.58 g, 15.5 mmol) is added in batches. After the addition is complete, the mixture is reacted for 30 minutes while maintaining the temperature at 15°C. After the starting materials have completely reacted, dichloromethane (140 ml) and water (70 ml) are added to the reaction mixture. After separation of the phases, the aqueous phase is extracted with dichloromethane (60 ml), the organic phases are combined, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and purified by column chromatography to obtain 3 g of the product.

[0171] 5. Composition of int12: Compound int12-5 (3g) is dissolved in 15ml of ethanol, and under nitrogen gas protection, 2M HCl (30ml) is added and the mixture is reacted at 30°C for 30 minutes. After the starting materials have completely reacted, the reaction solution is concentrated, 500ml of dichloromethane is added, and the solution is neutralized with saturated sodium bicarbonate. The aqueous phase is extracted once with dichloromethane (20ml), the organic phase is combined, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and purified by column chromatography to obtain 2.1g of the product.

[0172] Synthesis of the intermediate int13: The synthesis route and experimental process are as follows: [ka]

[0173] 1. Composition of int13-1: Compound int6-3 (4.2 g, 11.93 mmol) is dissolved in 50 mL of tetrahydrofuran, and R-tert-butylsulfinamide (2.88 g, 23.80 mmol) and tetraethyl titanate (10.8 g, 47.37 mmol) are added. The mixture is reacted at 70°C for 4 hours. After the starting materials have completely reacted, 100 mL of water is added to the reaction mixture, and the mixture is extracted with ethyl acetate (100 ml x 4). The organic phases are combined, washed with saturated sodium chloride (300 ml), dried over anhydrous sodium sulfate, concentrated under reduced pressure, and purified by column chromatography to obtain 4 g of product.

[0174] 2. Synthesis of int13-2: Compound int13-1 (4 g, 8.79 mmol) is dissolved in 60 mL of methanol. Under nitrogen gas protection, cerium chloride heptahydrate (1.64 g, 4.4 mmol) is added, and the mixture is heated to 50°C under nitrogen gas protection and stirred for 30 minutes. Then it is cooled to 15°C, and sodium borohydride (0.50 g, 13.2 mmol) is added in batches. After the addition is complete, the mixture is reacted for 30 minutes while maintaining the temperature at 15°C. After the starting materials have completely reacted, the mixture is concentrated under reduced pressure and purified by column chromatography to obtain 2.8 g of the product.

[0175] 3. Composition of int13: Compound int13-2 (2.8 g, 6.13 mmol) is added to 2 M HCl (30 ml) and reacted at room temperature for 10 minutes. After the starting materials have completely reacted, the mixture is concentrated, ethyl acetate (50 ml) is added to the reaction solution, the pH is adjusted to basic with saturated sodium bicarbonate, the mixture is separated into layers, the aqueous phase is extracted once with ethyl acetate (20 ml), the organic phases are combined, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain 2 g of product.

[0176] Synthesis of the intermediate int14: The synthesis route and experimental process are as follows: [ka] 1. Composition of int14-1: Compound int12-3 (3.47 g, 10 mmol) is dissolved in 50 mL of tetrahydrofuran, and R-tert-butylsulfinamide (2.42 g, 20 mmol) and tetraethyl titanate (9.12 g, 40 mmol) are added. The mixture is reacted at 70°C for 4 hours. After the starting materials have completely reacted, 100 mL of water is added to the reaction mixture, and the mixture is extracted with ethyl acetate (100 ml x 4). The organic phases are combined, washed with saturated sodium chloride solution, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and purified by column chromatography to obtain 4.1 g of product.

[0177] 2. Synthesis of int14-2: Compound int14-1 (4.1 g, 9.1 mmol) is dissolved in 80 ml of methanol. Under nitrogen gas protection, cerium chloride heptahydrate (1.65 g, 4.4 mmol) is added, and the mixture is heated to 50°C under nitrogen gas protection and stirred for 30 minutes. Then it is cooled to 15°C, and sodium borohydride (0.55 g) is added in batches. After the addition is complete, the mixture is reacted for 30 minutes while maintaining the temperature at 15°C. After the starting materials have completely reacted, the mixture is concentrated under reduced pressure and purified by column chromatography to obtain 2.73 g of product.

[0178] 3. Composition of int14: Compound int14-2 (2.73 g, 6.0 mmol) was added to 2 M HCl (30 ml) and reacted at room temperature for 10 minutes. After the starting materials had completely reacted, the mixture was concentrated, ethyl acetate (50 ml) was added to the reaction solution, the pH was adjusted to basic with saturated sodium bicarbonate, the mixture was separated into layers, the aqueous phase was extracted once with ethyl acetate (20 ml), the organic phases were combined, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain 2.08 g of product.

[0179] Synthesis of the intermediate int15: The synthesis route and experimental process are as follows: [ka]

[0180] 1. Synthesis of int15-1 Dissolve int12-1 (5.0 g, 26.88 mmol) and triethyl 1,1,2-ethanetricarboxylic acid (6.61 g, 26.88 mmol) in toluene (100 ml), raise the temperature to 110°C, and stir for 24 hours. The starting materials react completely. Cool the reaction mixture to room temperature, wash the solid with cold ethanol to obtain 3.6 g of crude product, and prepare Ms[M+H] + :341.0.

[0181] 2. Synthesis of int15-2 Dissolve int15-1 (3.5g, 10.29 mmol) in phosphorus oxychloride (50 mL), raise the temperature to 120°C, and allow to react overnight. Slowly pour the reaction mixture into water to quench the reaction, extract with ethyl acetate, dry over anhydrous sodium sulfate, concentrate under reduced pressure, and purify by column chromatography to obtain 1.81 g of product, Ms[M+H] + :359.0.

[0182] 3. Synthesis of int15-3 Dissolve int15-2 (1.7g, 4.74 mmol) in tetrahydrofuran solution (35 mL), add 4-methoxybenzylamine (0.58g, 5.69 mmol), cool to 0°C, add tert-butoxide potassium (0.80g, 7.12 mmol) in batches, and after addition is complete, raise the temperature to room temperature and stir for 3 hours. The starting materials react completely. Add water to the reaction system at low temperature, extract the reaction mixture with ethyl acetate, dry with anhydrous sodium sulfate, concentrate under reduced pressure, and purify by column chromatography to obtain 1.3 g of product, Ms[M+H] + :414.0.

[0183] 4. Synthesis of int15-4 Compound int15-3 (1.3 g, 3.14 mmol) is dissolved in tetrahydrofuran (25 mL), boranetetrahydrofuran complex (3.77 mL, 3.77 mmol) is added dropwise, and the mixture is heated to 60°C and reacted for 1 hour. The starting materials react completely. The reaction mixture is diluted with ethyl acetate, the organic phase is washed with saturated brine, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and purified by column chromatography to obtain 0.74 g of product, Ms[M+H] + :400.1.

[0184] 5. Synthesis of int15-5 Compound int15-4 (0.74 g, 1.85 mmol), tributyl(1-ethoxyethylene)tin (1.08 g, 2.23 mmol), and Pd(PPh3)2Cl2 (0.14 g, 0.19 mmol) were dissolved in dry dioxane (70 ml) and stirred at 80°C for 12 hours. Then, under room temperature conditions, 30 ml of potassium fluoride solution was added and stirred for 0.5 hours, filtered, and the mother liquor was extracted with ethyl acetate. The organic phase was dried over anhydrous sodium sulfate, concentrated under reduced pressure, dissolved in ethyl acetate (50 ml), 6 M hydrochloric acid (80 ml) was added, stirred at 25°C for 10 minutes, filtered, the filter cake was washed with ethyl acetate, the pH of the filtrate was adjusted to neutral with saturated sodium bicarbonate, extracted with dichloromethane, dried over anhydrous sodium sulfate, concentrated, and purified by column chromatography to obtain 0.55 g of product, Ms[M+H] + :364.2.

[0185] 6. Synthesis of int15-6: Compound int15-5 (0.55 g, 1.51 mmol) is dissolved in 20 mL of tetrahydrofuran, and under nitrogen gas protection, R-tert-butylsulfinamide (0.37 g, 3.02 mmol) and tetraethyl titanate (1.38 g, 6.04 mmol) are added, and the mixture is reacted at 70°C for 16 hours under nitrogen gas protection. After the starting materials have completely reacted, 20 mL of water is added to the reaction mixture, then extracted with ethyl acetate, the organic phases are combined, washed with saturated sodium chloride aqueous solution, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain 0.47 g of crude product, Ms[M+H] +:467.2.

[0186] 7. Composition of int15-7: Compound int15-64 (0.47 g, 1.18 mmol) is dissolved in 20 mL of methanol. Under nitrogen gas protection, cerium chloride heptahydrate (1.92 g, 0.59 mmol) is added, the mixture is heated to 50°C under nitrogen gas protection, stirred for 30 minutes, cooled to 15°C, and sodium borohydride (0.06 g, 1.77 mmol) is added in batches. After the addition is complete, the mixture is reacted for 30 minutes while maintaining the temperature at 15°C. After the starting materials have completely reacted, dichloromethane and water are added to the reaction mixture, extracted, separated, the aqueous phase is extracted with dichloromethane, the organic phase is combined, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and purified by column chromatography to obtain 0.28 g of product Ms[M+H] + :469.2.

[0187] 8. Synthesis of int15-8: Compound int15-7 (0.28 g, 0.60 mmol) is dissolved in 5 ml of dichloromethane, and under nitrogen gas protection, 2 ml of 2 M hydrogen chloride / ethanol solution is added and the mixture is reacted at room temperature for 30 minutes. After the starting materials have completely reacted, the reaction mixture is concentrated, dichloromethane is added, and the solution is neutralized with saturated sodium bicarbonate. The aqueous phase is extracted with dichloromethane, the organic phase is combined, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain 0.2 g of the product, Ms[M+H] + :365.2.

[0188] 9. Composition of int15-9: Compound int15-8 (0.2 g, 0.55 mmol), 2-brominated tert-butylbenzoate (0.17 g, 0.66 mmol), palladium acetate (12 mg, 0.055 mmol), 4,5-bisdiphenylphosphine-9,9-dimethyloxanthracene (63 mg, 0.11 mmol), and cesium carbonate (0.48 g, 1.48 mmol) were dissolved in dry toluene (10 mL) and stirred at 100 °C for 2 hours. After the reaction was complete, the mixture was filtered, the filter cake was washed with ethyl acetate, and the organic phase was then spin-dried and purified by column chromatography to obtain 0.26 g of product, Ms[M+H] + :541.3.

[0189] Composition of 10.int15: Compound int15-9 (0.26 g, 0.48 mmol) is dissolved in 10 ml of 1,2-dichloroethane, and 1-chloroethyl chloroformate (0.14 g, 0.96 mmol) is added. After addition, the mixture is reacted at 80°C for 1 hour. After the reaction is complete, the mixture is concentrated and dissolved in 20 ml of methanol. Triethylamine (0.19 g, 1.92 mmol) is added, and after addition, the mixture is reacted at 65°C for 3 hours. After the reaction is complete, the mixture is concentrated and purified by column chromatography to obtain 0.15 g of product, Ms[M+H] + :421.2.

[0190] Synthesis of the intermediate int16: The synthesis route and experimental process are as follows: [ka]

[0191] 1. Synthesis of compound int16-2 int16-1 (5.0 g, 34.2 mmol), 2-(benzylamino)methyl acetate (6.74 g, 37.7 mmol), and N,N-diisopropylethylamine (17.9 mL, 102.6 mmol) were dissolved in 60 mL of anhydrous N,N-dimethylformamide. Under an ice bath, O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (19.5 g, 51.3 mmol) was added in batches, and the mixture was heated to room temperature and reacted for 30 minutes. After the starting materials had completely reacted, water was added under an ice bath, the aqueous phase was extracted with ethyl acetate, and the organic phase was combined. The organic phase was washed multiple times with saturated sodium chloride, dried with anhydrous sodium sulfate, filtered, concentrated, and purified by column chromatography to obtain 11.5 g of product [M+H] + :308.

[0192] 2. Synthesis of compound int16-3 Dissolve int16-2 (5.0 g, 16.29 mmol) in 60 mL of anhydrous tetrahydrofuran, and under a nitrogen gas atmosphere and in an ice bath, slowly add bistrimethylsilylaminolithium (33 mL, 33 mmol). Allow to rise naturally to room temperature and react for 4 hours until the starting materials have completely reacted. Then, under an ice bath, add saturated aqueous ammonium chloride solution, extract the aqueous phase with ethyl acetate, dry the organic phase with anhydrous sodium sulfate, filter and concentrate, and purify by column chromatography to obtain 2.18 g of product [M+H] + :276.

[0193] 3. Synthesis of compound int16-4 int16-3 (1.0 g, 3.64 mmol), 2-amino-3-bromo-5-methylpyridine (680 mg, 3.64 mmol), and 4-methylbenzenesulfonate pyridine (1.10 g, 4.37 mmol) were added to a 50 ml glass bottle and stirred at 120°C for 16 hours. The reaction mixture was then cooled to room temperature. The pH was adjusted to basic with saturated sodium bicarbonate solution, and the mixture was extracted with ethyl acetate. The organic phases were combined, washed with saturated sodium chloride, dried over anhydrous sodium sulfate, filtered, and concentrated. The mixture was purified by column chromatography to obtain 878 mg of product [M+H]. + :412 / 414.

[0194] 4. Synthesis of compound int16-5 Compound int16-4 (878 mg, 2.14 mmol), tributyl(1-ethoxyethylene)tin (1.16 g, 3.20 mmol), and Pd(PPh3)2Cl2 (150 mg, 0.21 mmol) were dissolved in dry dioxane (15 mL) and stirred at 85°C for 2 hours. Then, under room temperature conditions, 15 mL of potassium fluoride solution was added and stirred for 0.5 hours, filtered, and the reaction mixture was extracted with ethyl acetate to separate the organic phase. After spin drying, it was redissolved in 5 mL of ethyl acetate, 1 mL of 6 M hydrochloric acid was added, and the mixture was stirred at 25°C for 10 minutes. After the reaction was complete, the aqueous phase was extracted with ethyl acetate, the aqueous phase was neutralized with saturated sodium bicarbonate, extracted with ethyl acetate, dried, concentrated, and 500 mg of the product was obtained by column chromatography [M+H] + :376.

[0195] 3. Synthesis of compound int16-6: Compound int16-5 (500 mg, 1.33 mmol) was dissolved in 20 mL of tetrahydrofuran, and R-tert-butylsulfinamide (323 mg, 2.67 mmol) and tetraethyl titanate (1.21 g, 5.32 mmol) were added. The reaction mixture was then allowed to react at 70°C for 18 hours. After the starting materials had completely reacted, 5 mL of water was added to the reaction mixture, and then the mixture was filtered. The filter cake was washed multiple times with ethyl acetate, the organic phases were combined, washed with saturated sodium chloride, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and the product was obtained by column chromatography to obtain 460 mg of [M+H]. + :479.

[0196] 4. Synthesis of compound int16-7: Compound int16-6 (460 mg, 0.96 mmol) is dissolved in 10 mL of methanol, and under nitrogen gas protection, cerium chloride heptahydrate (179 mg, 0.48 mmol) is added. Under nitrogen gas protection, sodium borohydride (54 mg, 1.44 mmol) is added in batches in an ice bath, and the mixture is then reacted for 30 minutes. After the starting materials have completely reacted, the mixture is directly concentrated under reduced pressure and purified by column chromatography to obtain 286 mg of product [M+H]. + :481.

[0197] 5. Synthesis of compound int16: Compound int16-7 (286 mg, 0.59 mmol) is dissolved in dichloromethane, and 2 mL of 2 M hydrogen chloride / ethanol solution is added. The mixture is then reacted at room temperature for 10 minutes. After the starting materials have completely reacted, the ethanol is removed using a rotary evaporator. The reaction mixture is redissolved in ethyl acetate, adjusted to basicity with saturated sodium bicarbonate, the aqueous phase is separated, the organic phase is combined, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain 220 mg of product [M+H]. + :377.

[0198] Synthesis of the intermediate int17: The synthesis route and experimental process are as follows: [ka]

[0199] 1. Synthesis of int17-2 int17-1 (16.34 g, 83.80 mmol), benzylglycine tert-butyl ester (10 g, 55.87 mmol), and triethylamine (8.46 g, 83.80 mmol) were dissolved in acetonitrile (200 mL) and reacted overnight at 80°C. The reaction mixture was cooled to room temperature, concentrated, and purified by column chromatography to obtain 11.4 g of product. [M+H] + :294.

[0200] 2. Synthesis of int17-3 Dissolve int17-2 (11.4 g, 38.91 mmol) in ultra-dried tetrahydrofuran (300 mL), cool to -30°C, slowly add bistrimethylsilylaminolithium (97.28 mL, 97.28 mmol) dropwise, slowly raise the reaction mixture to 5°C, and stir until the starting materials disappear. Quench the reaction by adding aqueous ammonium chloride under ice bath. Extract the aqueous phase with ethyl acetate, and dry and concentrate the organic phase over anhydrous sodium sulfate. Purify by column chromatography to obtain 950 mg of product. [M+H] + :262. 1 H NMR(400MHz,DMSO)δ ppm7.39-7.30(m,4H),7.30-7.24(m,1H),3.90(d,J=6.0Hz,1H),3.67(s,2H),3.63(s,3H),3. 31-3.24(m,2H),2.63-2.55(m,1H),2.50-2.43(m,1H),1.97-1.81(m,2H),1.73-1.51(m,2H).

[0201] 3. Synthesis of int17-4 int17-3 (950 mg, 3.64 mmol), 2-amino-3-bromo-5-methylpyridine (680 mg, 3.64 mmol), and 4-methylbenzenesulfonate pyridine (1.10 g, 4.37 mmol) were stirred at 120°C for 16 hours, and the reaction mixture was cooled to room temperature. The pH was adjusted to basic with saturated sodium bicarbonate solution, and the mixture was extracted with ethyl acetate. The organic phases were combined, washed with saturated sodium chloride, dried over anhydrous sodium sulfate, filtered and concentrated, and purified by column chromatography to obtain 380 mg of product [M+H] + :398 / 400. 1 H NMR(400MHz,DMSO-d6)δ ppm8.27-8.23(m,1H),8.01-7.96(m,1H),7.43-7.36(m,2H),7.33-7.26(m,3H),4.52(s,2H) ,4.41(s,2H),3.21(t,J=5.6Hz,2H),2.30(s,3H),2.14(t,J=6.0Hz,2H),1.88-1.72(m,2H).

[0202] 4. Synthesis of int17-5 Compound int17-4 (380 mg, 0.96 mmol), tributyl(1-ethoxyethylene)tin (415 mg, 1.15 mmol), and Pd(PPh3)2Cl2 (150 mg, 0.09 mmol) were dissolved in dry dioxane (15 mL) and stirred at 90°C for 16 hours. Then, under room temperature conditions, 15 mL of potassium fluoride solution was added and stirred for 0.5 hours, filtered, the reaction mixture was extracted with ethyl acetate, the organic phase was separated and concentrated, redissolved in 5 mL of ethyl acetate, 6 M hydrochloric acid (1 mL) was added, and stirred at 25°C for 10 minutes. After the reaction was complete, the aqueous phase was extracted with ethyl acetate, the aqueous phase was neutralized with saturated sodium bicarbonate, extracted with ethyl acetate, dried, concentrated, and purified by column chromatography to obtain 250 mg of product [M+H] + :362.

[0203] 5. Synthesis of int17-6 Compound int17-5 (250 mg, 0.69 mmol) is dissolved in 20 mL of tetrahydrofuran, and R-tert-butylsulfinamide (167 mg, 1.38 mmol) and tetraethyl titanate (629 mg, 2.76 mmol) are added. The reaction mixture is then allowed to react at 75°C for 18 hours. After the starting materials have completely reacted, 5 mL of water is added to the reaction mixture, then it is filtered, the filter cake is washed multiple times with ethyl acetate, the organic phases are combined, washed with saturated sodium chloride, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and 200 mg of the product is obtained by column chromatography [M+H] + :465.

[0204] 6. Synthesis of int17-7 Compound int17-6 (200 mg, 0.43 mmol) is dissolved in 10 mL of methanol, and under nitrogen gas protection, cerium chloride heptahydrate (82 mg, 0.22 mmol) is added. Under nitrogen gas protection, sodium borohydride (25 mg, 0.65 mmol) is added in batches in an ice bath and the mixture is reacted for 30 minutes. After the starting materials have completely reacted, the mixture is concentrated under reduced pressure and purified by column chromatography to obtain 120 mg of product [M+H]. + :467.

[0205] 7. Composition of int17 Compound int17-7 (120 mg, 0.26 mmol) is dissolved in dichloromethane, 2 M HCl / EtOH (2 mL) is added, and the mixture is reacted at room temperature for 10 minutes. After the starting materials have completely reacted, the ethanol is removed using a rotary evaporator, the reaction mixture is redissolved in ethyl acetate, the solution is made basic with saturated sodium bicarbonate, the aqueous phase is separated, the organic phase is combined, the mixture is dried over anhydrous sodium sulfate, concentrated under reduced pressure, and purified by column chromatography to obtain 80 mg of product [M+H]. + :363.

[0206] Example 1 The compound of the present invention [ka] The synthesis route and experimental process are as follows: [ka]

[0207] 1. Synthesis of compound C1-1: In a 100 mL three-necked bottle, add the above int1 (2.2 g), dried N,N-dimethylformamide (60 mL), and tert-butyl 2-aminobenzoate (2.9 g, 6 eq), and react at 80°C for 8 hours under nitrogen gas protection. After the reaction is complete, add saturated ammonium chloride, extract with ethyl acetate, and then dry and concentrate to obtain 1.7 g of crude product.

[0208] 2. Synthesis of Compound C1-2 Add C1-1 (1.7g, 1.0eq), diethylamine (5ml), and dichloromethane (50ml) to a 100mL three-necked bottle and react at room temperature for 8 hours under nitrogen gas protection. After the reaction is complete, wash with saturated ammonium chloride aqueous solution, extract with dichloromethane, concentrate, and purify by column chromatography to obtain 258mg of product. 1 1H NMR (400MHz, Chloroform-d)δ 8.30(d,J=6.2Hz,1H),7.86(dd,J=8.0,1.7Hz,1H),7.75(dd,J=8.2,3.0Hz,1 H),7.48(dd,J=9.2,3.0Hz,1H),7.08(ddd,J=8.7,7.1,1.7Hz,1H),6.51(ddd ,J=8.1,7.0,1.1Hz,1H),6.28(d,J=8.4Hz,1H),5.50(t,J=6.5Hz,1H),4.17( s, 2H), 4.04 (td, J=5.6, 1.4Hz, 2H), 3.34 (q, J=7.6, 6.7Hz, 2H), 1.63 (s, 9H). 1.60 (d, J=6.7Hz, 3H).

[0209] 3. Compound C 1-3 synthesis Add C1-2 (100 mg, 1.0 eq), Pd2(dba)3 (41.73 mg, 0.2 eq), RuPhos (42.75 mg, 0.4 eq), tert-butoxide potassium (77.4 mg, 3 eq), int2 (112 mg, 2 eq), and toluene (5 ml) to a 20 mL sealed bottle and react at 100 °C for 0.5 hours. After the reaction is complete, filter, concentrate, and purify by column chromatography to obtain 60 mg of the product.

[0210] 4. Synthesis of compounds C1-4 Add C1-3 (110 mg, 1.0 eq), dichloromethane (5 mL), and trifluoroacetic acid (2.5 mL) to a 50 mL three-necked bottle and react at 40°C for 6 hours. After the reaction is complete, concentrate the solution and purify it by thin-layer chromatography to obtain 72 mg of the product.

[0211] 5. Synthesis of compounds C1 and C2 Compounds C1-4 were separated by chiral preparative chromatography under the following chiral resolution conditions: Instrument: Agilent 1260 InfinityII, chromatographic column: phenomenex Lux® 5μm Amylose-1 (250×21.2mm), mobile phase: n-hexane:isopropanol = 7:3, column temperature: 25°C. The following compounds were obtained by separation. C1 (Peak time 8.2 min, 9.54 mg) 1 1H NMR (400MHz, DMSO-d6)δ 12.71(s,1H),11.86(s,1H),8.60(s,1H),7.88-7.78(m,1H),7.68(dd,J=8.4, 3.0Hz,1H),7.56(d,J=8.6Hz,1H),7.42(s,1H),7.18(d,J=8.1Hz,1H),6.51(t ,J=7.5Hz,1H),6.42(d,J=8.6Hz,1H),5.44(d,J=7.1Hz,1H),4.43(s,2H),3.9 4(q,J=5.4Hz,2H),3.58(t,J=5.7Hz,2H),2.03(s,3H),1.59(d,J=6.6Hz,3H), C2 (peak time 16.2 min, 2 mg) 11H NMR (400MHz, DMSO-d6)δ 12.73(s,1H),11.88(s,1H),8.61(s,1H),7.86-7.77(m,1H),7.66(dd,J=8.4, 3.0Hz,1H),7.54(d,J=8.6Hz,1H),7.42(s,1H),7.18(d,J=8.1Hz,1H),6.51(t ,J=7.5Hz,1H),6.40(d,J=8.6Hz,1H),5.41(d,J=7.1Hz,1H),4.43(s,2H),3.9 4(q,J=5.4Hz,2H),3.58(t,J=5.7Hz,2H),2.03(s,3H),1.59(d,J=6.6Hz,3H).

[0212] Example 2 The compound of the present invention [ka] The synthesis route and experimental process are as follows: [ka]

[0213] 1. Synthesis of compound C3-1: Compound C1-2 (100 mg, 0.23 mmol) was dissolved in 5 mL of dichloromethane, and potassium carbonate (95 mg, 0.69 mmol) and methyl chloroformate (28 mg, 0.3 mmol) were added under cooling in an ice bath. The mixture was reacted at room temperature with stirring for 2 hours. After the reaction was complete, saturated brine was added, and the mixture was extracted three times with ethyl acetate. The organic phase was washed three times with saturated brine, dried, spin-dried, and purified by column chromatography to obtain 46 mg of the product.

[0214] 2. Synthesis of compound C3-2: Compound C3-1 (46 mg, 0.09 mmol) was dissolved in dichloromethane (4 mL) / trifluoroacetic acid (2 mL), stirred for 12 hours under nitrogen gas protection at 23°C, and after the reaction was complete, the mixture was spin-dried to obtain 35 mg of the product.

[0215] 3. Synthesis of compounds C3 and C4: Compound C3-2 (35 mg, 0.08 mmol) is separated using the following reconstitution method. Instrument: Agilent 1260 InfinityII, chromatographic column: phenomenex Lux® 5μm Amylose-1 (250×21.2mm), mobile phase: n-hexane:isopropanol = 7:3, column temperature: 25℃. The following compounds were obtained by separation. C3 (6.5 min, 15 mg) [M+H] + :441.2 C4 (8.8 min, 10 mg) [M+H] + :441.2

[0216] Example 3 The compound of the present invention [ka] The synthesis route and experimental process are as follows: [ka]

[0217] 1. Synthesis of compound C5-1: Compound C1-2 (100 mg, 0.23 mmol) was dissolved in 5 mL of dichloromethane, potassium carbonate (96 mg, 0.69 mmol) was added, and the mixture was stirred for 10 minutes. Isobutylamide chloride (30 mg, 0.27 mmol) was then added, and the mixture was reacted at room temperature with stirring for 3 hours. After the reaction was complete, the mixture was filtered, spin-dried, and purified by column chromatography to obtain 40 mg of the product. [M+H] + :509.0

[0218] 2. Synthesis of compound C5-2: Compound C5-1 (40 mg, 0.08 mmol) was dissolved in dichloromethane (3 mL) / trifluoroacetic acid (1.5 mL), stirred at 25°C for 16 hours, and after the reaction was complete, it was spin-dried to obtain 25 mg of the product.

[0219] 3. Synthesis of compounds C5 and C6: Compound C5-2 (25 mg, 0.06 mmol) is separated using the following reconstitution method. Instrument: Agilent 1260 InfinityII, Chromatography column: phenomenex Lux® 5μm Amylose-1 (250×21.2mm), Mobile phase: n-hexane:ethanol = 4:6, Column temperature: 25℃. The following compounds were obtained by separation. C5 (5.8 min, 8.7 mg) [M+H] + :453.3 1 1H NMR (400MHz, DMSO-d6)δ 12.73(s,1H),8.47(d,J=6.3Hz,1H),7.80(dd,J=7.9,1.7Hz,1H),7.70(dd,J=8 .3,3.1Hz,1H),7.61-7.51(m,1H),7.17(t,J=7.9Hz,1H),6.53(t,J=7.5Hz,1H), 6.38(d,J=8.5Hz,1H),5.47(s,1H),4.95-4.67(m,2H),4.16(s,2H),3.97(s,1H) ),3.81(s,1H),3.06-2.88(m,1H),1.58(d,J=6.6Hz,3H),1.06(d,J=6.7Hz,6H). C6 (9.8 min, 6.6 mg) [M+H] + :453.3 1 H NMR(400MHz,DMSO-d6)δ 12.74(s,1H),8.54-8.41(m,1H),7.80(dd,J=7.9,1.7Hz,1H),7.70(dd,J=8.4,3.0H z,1H),7.55(dd,J=9.3,3.3Hz,1H),7.17(t,J=7.9Hz,1H),6.53(t,J=7.5Hz,1H),6.3 8(d,J=8.5Hz,1H),5.47(s,1H),4.89(s,1H),4.82-4.67(m,1H),4.17(s,2H),3.97( s,1H),3.81(s,1H),3.05-2.87(m,1H),1.58(d,J=6.6Hz,3H),1.06(d,J=6.6Hz,6H).

[0220] Example 4 The compound of the present invention [ka] The synthesis route and experimental process are as follows: [ka]

[0221] 1. Synthesis of C9-1: Add C1-2 (200 mg, 0.46 mmol), tetrahydropyranone (60 mg, 0.59 mmol), sodium triacetoxyborohydride (155 mg, 0.73 mmol), and 20 ml of dichloromethane to a 10 mL bottle. After adding all the raw materials, stir overnight at room temperature under nitrogen gas protection. Process and purify by column chromatography to obtain 170 mg of the product.

[0222] 2. Synthesis of C9-2: Compound C9-1 (170 mg) is dissolved in 4 mL of anhydrous dichloromethane and 2 mL of trifluoroacetic acid, and the mixture is stirred overnight at room temperature under nitrogen gas protection. The reaction mixture is added dropwise to a saturated sodium bicarbonate solution, extracted, dried, concentrated, and 100 mg of the product is obtained by column chromatography.

[0223] 3. Synthesis of C9 and C10: First, compound C9-2 (100 mg) is separated using the following division method. Instrument: Agilent 1260 InfinityII, chromatographic column: CHIRALPAK IA 5μm (250×20mm), mobile phase: n-hexane:ethanol = 95:5, column temperature: 25℃. The following compounds were obtained by separation. C9 (14.1 min, 9.33 mg) [M+H] + :467.3; 1¹H NMR (400 MHz, DMSO-d₆) δ 8.52 (m, 1H), 7.81 (d, J=7.8 Hz, 1H), 7.74 (dd, J=8.2, 2.9 Hz, 1H), 7.62 (dd, J=9.4, 3.1 Hz, 1H), 7.18 (dd, J=8.6, 6.9 Hz, 1H), 6.54 (t, J=7.5 Hz, 1H), 6.37 (d, J=8.5 Hz, 1H), 5.45 (m, 1H), 4.47 (m, 2H), 4.23-3.31 (m, 9H), 2.03 (d, J=12.2 Hz, 2H), 1.81-1.64 (m, 2H), 1.59 (d, J=6.6 Hz, 2H). C₁₀ (16.2 min, 10.53 mg) [M+H] + : 467.3; 1 ¹H NMR (400 MHz, DMSO-d₆) δ 8.52 (m, 1H), 7.81 (d, J=7.8 Hz, 1H), 7.74 (dd, J=8.2, 2.9 Hz, 1H), 7.62 (dd, J=9.4, 3.1 Hz, 1H), 7.18 (dd, J=8.6, 6.9 Hz, 1H), 6.54 (t, J=7.5 Hz, 1H), 6.37 (d, J=8.5 Hz, 1H), 5.45 (m, 1H), 4.47 (m, 2H), 4.23-3.31 (m, 9H), 2.03 (d, J=12.2 Hz, 2H), 1.81-1.64 (m, 2H), 1.59 (d, J=6.6 Hz, 2H).

[0224] Example 5 Compound of the present invention

Chemical Formula

Chemical Formula

[0225] 1. Synthesis of compound C11-1: Compound int3 (110 mg, 0.25 mmol) is dissolved in 5 mL of N,N-dimethylformamide, potassium carbonate (103 mg, 0.75 mmol) is added at room temperature, and then methyl chloroformate (28.5 mg, 0.3 mmol) is slowly added dropwise. After the addition is complete, the mixture is reacted at room temperature with stirring for 3 hours until the starting materials have completely reacted. Water is then added to quench the mixture, and it is extracted three times with dichloromethane. The organic phases are combined, then concentrated, dried, and purified by column chromatography to obtain 80 mg of the product.

[0226] 2. Synthesis of compound C11-2: Compound C11-1 (80 mg, 0.16 mmol) was dissolved in a mixed solvent of dichloromethane (5 mL) and trifluoroacetic acid (5 mL), and the mixture was reacted at 25°C with stirring for 12 hours. After the reaction was complete, the mixture was spin-dried and separated by preparative plate to obtain 40 mg of the product.

[0227] 3. Synthesis of compounds C11 and C12: Compound C11-2 (40 mg) is separated using the following reconstitution method. Instrument: Agilent 1260 InfinityII, Chromatography column: phenomenex Lux® 5μm cellulose-4 (250×21.2mm), Mobile phase: n-hexane:ethanol = 9:1, Column temperature: 25℃. The following compounds were obtained by separation. C11 (5.5 min, 14 mg) [M+H] + :441.2 1 H NMR(400MHz,DMSO-d6)δ 12.81(s,1H),8.45(d,J=7.2Hz,1H),7.81(dd,J=7.8,1.6Hz,1H),7.59(m,2H),7.24(m,1H),6.60-6.51(m ,2H),5.21(t,J=6.8Hz,1H),4.68-4.52(m,2H),3.70(s,5H),2.54(d,J=5.6Hz,2H),1.64(d,J=6.8Hz,3H). C12 (8.2 min, 13 mg) [M+H] + :441.2 1 H NMR(400MHz,DMSO-d6)δ 12.81(s,1H),8.45(d,J=7.2Hz,1H),7.81(dd,J=7.8,1.6Hz,1H),7.59(m,2H),7.24(m,1H),6.60-6.51(m ,2H),5.21(t,J=6.8Hz,1H),4.68-4.52(m,2H),3.70(s,5H),2.54(d,J=5.6Hz,2H),1.64(d,J=6.8Hz,3H).

[0228] Example 6 The compound of the present invention [ka] The synthesis route and experimental process are as follows: [ka]

[0229] 1. Synthesis of compound C13-1: Compound int6 (17 mg, 0.039 mmol) and potassium carbonate (16 mg, 0.117 mmol) are dissolved in dry dichloromethane (10 mL), and methyl chloroformate (8.8 mg, 0.092 mmol) is added at room temperature under nitrogen gas protection, and the mixture is stirred at 25°C for 12 hours. The mixture is then concentrated, dried, and purified by column chromatography to obtain 9 mg of the product.

[0230] 2. Synthesis of compound C13-2: Compound C13-1 (13 mg, 0.026 mmol) was dissolved in dichloromethane (2 mL) / trifluoroacetic acid (2 mL), stirred for 12 hours under nitrogen gas protection at 23°C, and after the reaction was complete, the mixture was spin-dried to obtain 14 mg of the product.

[0231] 3. Synthesis of compounds C13 and C14 Compound C13-2 (50 mg, 0.113 mmol) is separated using the following reconstitution method. Instrument: Agilent 1260 InfinityII, Chromatography column: phenomenex Lux® 5μm cellulose-4 (250×21.2mm), Mobile phase: n-hexane:ethanol = 2:8, Column temperature: 25℃. The following compounds were obtained by separation. C13 (11.2 min, 20.73 mg) [M+H] + :441.2, 1 H NMR(DMSO-d6,400MHz)δ ppm 12.78(br,1H),8.80(dd,J=4.8,2.8Hz,1H),8.50(s,1H),7.86(dd,J=8.4,2.8Hz,1H),7.82(dd,J=8.0,2.0Hz,1H),7.24-7.19(m,1H),6 .57(t,J=8.0Hz,1H),6.38(d,J=8.8Hz,1H),5.32(s,1H),4.59(s,2H),3.74-3.62(m,5H),2.69(t,J=5.6Hz,2H),1.63(d,J=6.8Hz,3H). C14 (13.1 min, 21.16 mg) [M+H] + :441.2, 1 HNMR:(DMSO-d6,400Hz)δ12.81(s,1H),8.80~8.78(m,1H),8.50(s,1H),7.87~7.80(m,2H),7.23~7.19(m,1H),6.58~6.5 5(m,1H),6.39~6.37(m,1H),5.33~5.30(m,1H),4.58(s,2H),3.71~3.68(m,5H),2.70~2.67(m,2H),1.63(d,J=7.8Hz,3H)

[0232] Example 7 The compound of the present invention [ka] The synthesis route and experimental process are as follows: [ka]

[0233] 1. Synthesis of compound C19-1: Compound C1-2 (100 mg, 0.23 mmol) is dissolved in 5 mL of tetrahydrofuran, and carbonyldiimidazole (370 mg, 2.3 mmol) is added. After the addition is complete, the temperature is raised and the mixture is reacted at 60°C for 24 hours. Cyclopentylamine (387 mg, 4.6 mmol) is then added, and the mixture is reacted at 60°C for 16 hours. Water is added, and the mixture is extracted with ethyl acetate to separate the organic phase. The mixture is dried over anhydrous sodium sulfate, and the filtrate is concentrated under reduced pressure and then purified to obtain 50 mg of the product.

[0234] 2. Synthesis of compound C19-2: Compound C19-1 (50 mg, 0.09 mmol) was dissolved in a mixed solvent of dichloromethane (5 mL) and trifluoroacetic acid (5 mL), and the mixture was reacted at 25°C with stirring for 12 hours. After the reaction was complete, the mixture was spin-dried and separated by preparative plate to obtain 40 mg of the product.

[0235] 3. Synthesis of compounds C19 and C20: Compound C19-2 (40 mg) is separated using the following reconstitution method. Instrument: Agilent 1260 InfinityII, Chromatography column: phenomenex Lux® 5μm cellulose-4 (250×21.2mm), Mobile phase: n-hexane:ethanol = 4:6, Column temperature: 25℃. The following compounds were obtained by separation. C19 (4.4 min, 15 mg) [M+H] + :494.4 1¹H NMR (400 MHz, DMSO-d₆) δ ppm 12.79 (br, 1H), 8.46 (s, 1H), 7.81 (dd, J=8.0, 2.0 Hz, 1H), 7.70 (dd, J=8.0, 3.2 Hz, 1H), 7.53 (dd, J=9.6, 3.2 Hz, 1H), 7.22-7.14 (m, 1H), 6.63-6.49 (m, 2H), 6.34 (d, J=8.4 Hz, 1H), 5.53-5.41 (m, 1H), 4.77-4.60 (m, 2H), 4.10 (t, J=5.6 Hz, 2H), 4.03-3.90 (m, 1H), 3.83-3.65 (m, 2H), 1.88-1.76 (m, 2H), 1.72-1.62 (m, 2H), 1.58 (d, J=7.6 Hz, 3H), 1.54-1.39 (m, 4H). C20 (7.4 min, 15 mg) [M+H] + : 494.4 1 ¹H NMR (400 MHz, DMSO-d₆) δ ppm 12.76 (br, 1H), 8.46 (s, 1H), 7.81 (dd, J=8.0, 2.0 Hz, 1H), 7.70 (dd, J=8.0, 3.2 Hz, 1H), 7.53 (dd, J=9.6, 3.2 Hz, 1H), 7.21-7.11 (m, 1H), 6.63-6.48 (m, 2H), 6.34 (d, J=8.0 Hz, 1H), 5.53-5.40 (m, 1H), 4.77-4.60 (m, 2H), 4.10 (t, J=5.6 Hz, 2H), 4.03-3.91 (m, 1H), 3.83-3.66 (m, 2H), 1.88-1.76 (m, 2H), 1.72-1.62 (m, 2H), 1.58 (d, J=7.2 Hz, 3H), 1.54-1.38 (m, 4H).

[0236] Example 8 Compound of the present invention

Chemical Formula

Chemical Formula

[0237] 1. Synthesis of compound C44-1: Compound int7 (51 mg, 0.11 mmol) is dissolved in 5 mL of dichloromethane, and triethylamine (56 mg, 0.55 mmol) is added at 0°C, followed by the slow addition of isopropylsulfonyl chloride (37 mg, 0.26 mmol). After the addition is complete, the temperature is allowed to rise naturally, and the mixture is reacted with stirring for 12 hours. Once the starting materials have completely reacted, water is added to quench the mixture, and it is extracted three times with dichloromethane. The organic phases are combined, concentrated, and purified by column chromatography to obtain 20 mg of the product.

[0238] 2. Synthesis of compounds C44 and C45: Compound C44-1 (20 mg) was separated using the following separation method: Instrument: Agilent 1260 InfinityII, chromatographic column: phenomenex Lux® 5 μm cellulose-4 (250 × 21.2 mm), mobile phase: n-hexane:ethanol = 9:1, column temperature: 25°C. The mixture was then concentrated, dichloromethane (4 mL) / trifluoroacetic acid (2 mL) was added, and the mixture was stirred at 23°C for 12 hours under nitrogen gas protection. After the reaction was complete, the mixture was concentrated again and separated and purified by thin-layer preparative chromatography to obtain the product. C45 (17.4 min, 2.18 mg) [M+H] + :485.3 1 HNMR:(DMSO-d6,400Hz),δ8.59(s,1H),7.81~7.79(m,1H),7.73(s,1H),7.54(s,1H),7.18~7.16(m,1H),6.54~6.47(m,2H),5.21~ .5.13(m,1H),4.50~4.46(m,2H),3.59~3.54(m,3H),2.59~2.57(m,2H),2.35(s,3H),1.60(d,J=6.4Hz,3H),1.28(d,J=6.5Hz,6H). C44 (20.3 min, 2.74 mg) [M+H] + :485.3 1HNMR:(DMSO-d6,400Hz),δ8.59(s,1H),7.81~7.79(m,1H),7.73(s,1H),7.54(s,1H),7.18~7.16(m,1H),6.54~6.47(m,2H),5.21~ .5.13(m,1H),4.50~4.46(m,2H),3.59~3.54(m,3H),2.59~2.57(m,2H),2.35(s,3H),1.60(d,J=6.4Hz,3H),1.28(d,J=6.5Hz,6H).

[0239] Example 9 The compound of the present invention [ka] The synthesis route and experimental process are as follows: [ka]

[0240] 1. Synthesis of compound C54-1: Int7 (80 mg, 0.18 mmol) was dissolved in dichloromethane (10 ml), triethylamine (60 mg, 0.54 mmol) was added, and morpholine sulfonyl chloride (103 mg, 0.54 mmol) was added dropwise under ice bath. The reaction was carried out at 30°C for 12 hours. After the reaction was complete, the reaction solution was concentrated, diluted with ethyl acetate, washed twice with saturated saline, dried, concentrated, and separated using the following separation method: Instrument: Agilent 1260 InfinityII, chromatographic column: phenomenex Lux® 5 μm cellulose-4 (250 × 21.2 mm), mobile phase: n-hexane:ethanol = 8:2, column temperature: 25°C. Products C54-2 (21.0 min, 25 mg) and C55-1 (26.7 min, 25 mg) were obtained.

[0241] 2. Synthesis of compounds C54 and C55: Dissolve C54-2 and C55-1 in 5 ml of dichloromethane, add 5 ml of trifluoroacetic acid, and react at 30°C for 24 hours. After the reaction is complete, concentrate the mixture and purify it by column chromatography to obtain the product. C54 (16.5 min, 10 mg) 1 H NMR(400MHz,DMSO-d6),12.79(m,1H)8.47(d,J=7.2Hz,1H),7.80(dd,J=8.0,1.6Hz,1H ),7.73(d,J=2.4Hz,1H),7.55(d,J=2.4Hz,1H),7.22(m,1H),6.57-6.49(m,2H),5.17( t,J=6.8Hz,1H),4.44(d,J=8.0Hz,2H),3.64(t,J=4.8Hz,4H),3.53(q,J=6.0Hz,2H),3 .19(dd,J=5.6,3.6Hz,4H),2.59(t,J=5.6Hz,2H),2.35(s,3H),1.60(d,J=6.4Hz,3H). C55 (18.1 min, 10 mg) 1 1H NMR (400MHz, DMSO-d6)δ 12.79(m,1H),8.47(d,J=7.2Hz,1H),7.80(dd,J=8.0,1.6Hz,1H),7.73(d,J=2.4 Hz,1H),7.55(d,J=2.4Hz,1H),7.22(m,1H),6.57-6.49(m,2H),5.17(t,J=6.8Hz ,1H),4.44(d,J=8.0Hz,2H),3.64(t,J=4.8Hz,4H),3.53(q,J=6.0Hz,2H),3.19( dd,J=5.6,3.6Hz,4H),2.59(t,J=5.6Hz,2H),2.35(s,3H),1.60(d,J=6.4Hz,3H).

[0242] Example 10 The compound of the present invention [ka] The synthesis route and experimental process are as follows: [ka]

[0243] 1. Synthesis of compound C62-2: Compound C62-1 (25 g, 113.6 mmol) is dissolved in 400 mL of methanol, and thionyl chloride (54 g, 454.5 mmol) is added dropwise under ice bath. After the addition is complete, the temperature is raised to 70°C and the mixture is reacted for 4 hours until the starting materials are completely reacted. The mixture is directly spin-dried, adjusted to basicity with saturated sodium bicarbonate aqueous solution, extracted with ethyl acetate, dried over anhydrous sodium sulfate, filtered, and the filtrate is concentrated under reduced pressure to obtain 26 g of product. 1 H NMR (400MHz, Chloroform-d) δ 8.41 (d, J = 2.0 Hz, 1H), 7.89 (dd, J = 56.8, 5.2 Hz, 1H), 4.00 (d, J = 1.2 Hz, 3H).

[0244] 2. Synthesis of compound C62-3: C62-2 (26 g, 111.1 mmol) is dissolved in 350 ml of dry dioxane, then potassium carbonate (22.9 g, 166.7 mmol), Pd(dppf)Cl2 (8.1 g, 11.1 mmol), and a tetrahydrofuran solution of trimethylcyclotriboloxane (3.5 M, 80 ml, 277.8 mmol) are added. After the addition is complete, the mixture is stirred overnight at 105°C under nitrogen gas protection. After the starting materials have completely reacted, the reaction mixture is cooled to room temperature, water is added, and then the mixture is extracted three times with ethyl acetate. The organic phases are combined, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and purified to obtain 13.7 g of product. 1 H NMR (400MHz, Chloroform-d) δ 8.49 (d, J = 2.4 Hz, 1H), 7.62 (d, J = 5.6 Hz, 1H), 3.98 (s, 3H), 2.60 (d, J = 1.2 Hz, 3H). 3. Synthesis of compound C62-4: Add C62-3 (13.7 g, 80.6 mmol) to 120 mL of aqueous ammonia and stir in an iron bottle at 80°C for 5 hours. After the raw materials have completely reacted, concentrate the reaction solution under reduced pressure, then slurry it with dichloromethane and petroleum ether to obtain 12 g of product. 1 H NMR (400MHz, DMSO-d6) δ 8.51 (d, J = 1.6 Hz, 1H), 7.94 (d, J = 43.2 Hz, 2H), 7.44 (d, J = 5.6 Hz, 1H), 2.49 (s, 3H).

[0245] 4. Synthesis of compound C62-5: Compound C62-4 (4 g, 25.8 mmol) is dissolved in 80 mL of dichloromethane, triethylamine (7.82 g, 77.4 mmol) is added, and then anhydrous trifluoroacetic acid (10.8 g, 51.6 mmol) is added dropwise. The mixture is stirred for 2 hours while maintaining room temperature until the starting materials have completely reacted. After the reaction is complete, the mixture is diluted with water, then extracted three times with ethyl acetate, the organic phases are combined, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and then purified to obtain 3 g of product. 1 H NMR (400MHz, Chloroform-d) δ 8.58 (s, 1H), 7.39 (d, J = 4.8Hz, 1H), 2.62 (d, J = 1.2Hz, 3H).

[0246] 5. Synthesis of compound C62-6: Compound C62-5 (3 g, 21.9 mmol) is dissolved in 60 mL of N,N-dimethylformamide, and 2-bromo-4-fluorophenol (6.3 g, 32.9 mmol) and cesium carbonate (14.4 g, 43.8 mmol) are added. After the addition is complete, the temperature is raised to 130°C and the mixture is reacted for 1 hour until the starting materials are completely reacted. Water is slowly added to quench the mixture, then it is extracted with ethyl acetate, the organic phase is separated, dried over anhydrous sodium sulfate, and the filtrate is concentrated under reduced pressure and purified to obtain 5.7 g of product. 1 H NMR (400MHz, Chloroform-d) δ 8.02 (s, 1H), 7.51-7.45 (m, 1H), 7.42 (s, 1H), 7.20-7.09 (m, 2H), 2.59 (s, 3H).

[0247] 6. Synthesis of compound C62-7: Dissolve C62-6 (5.7 g, 41 mmol) in 57 g of polyphosphate and slowly raise the temperature to 220°C, stirring for 3 hours. After the starting materials have completely reacted, cool the reaction mixture to room temperature, dissolve it in water, adjust the pH to basic with saturated sodium bicarbonate aqueous solution, then extract three times with ethyl acetate, combine the organic phases, dry over anhydrous sodium sulfate, concentrate under reduced pressure, and purify to obtain 4 g of product. 1 H NMR (400MHz, Chloroform-d) δ 9.08 (s, 1H), 8.02-7.92 (m, 2H), 7.84 (dd, J = 7.2, 3.2Hz, 1H), 2.74 (s, 3H).

[0248] 7. Synthesis of compound C62-8: Add C62-7 (4g, 13 mmol), potassium iodide (9.5g, 57.2 mmol), and benzyl chloride (8.15g, 52 mmol) to 150 mL of acetonitrile, slowly raise the temperature of the reaction mixture to 80°C, and stir overnight. After the starting materials have completely reacted, concentrate the reaction mixture under reduced pressure to obtain 9 g of crude product, which is used directly in the next step of the reaction.

[0249] 8. Synthesis of compound C62-9: Compound C62-8 (9 g, 15.9 mmol) is dissolved in 100 mL of anhydrous ethanol, sodium borohydride cyanohydride (8 g, 127.4 mmol) and acetic acid (0.9 g, 15.9 mmol) are added, and the mixture is stirred for 30 minutes while maintaining room temperature. After the starting materials have completely reacted, the reaction solution is diluted with water, then extracted three times with dichloromethane, the organic phases are combined, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and then purified to obtain 2.5 g of product. 1H NMR(400MHz,Chloroform-d)δ 7.85(dd,J=8.0,3.2Hz,1H),7.64(dd,J=7.2,3.2Hz,1H),7.32(dd,J=8.8,3.2Hz,2H),6.93-6.91(m,2H),3.84(s,3H),3.7 9(dd,J=3.6,1.2Hz,2H),3.60(m,2H),3.18(h,J=6.4Hz,1H),2.85-2.74(m,1H),2.55-2.44(m,1H),1.22(d,J=6.4Hz,3H).

[0250] 9. Synthesis of compound C62-10: Compound C62-9 (2g, 4.63 mmol), tributyl(1-ethoxyethylene)tin (2g, 5.56 mmol), and Pd(PPh3)2Cl2 (0.33g, 0.46 mmol) were dissolved in dry dioxane (80 mL) and stirred at 80°C for 12 hours. Then, under room temperature conditions, potassium fluoride solution was added, the mixture was stirred for 0.5 hours, filtered, and the mother liquor was extracted three times with ethyl acetate to separate the organic phase. The organic phase was spin-dried, dissolved in dichloromethane, 2 mL of concentrated hydrochloric acid was added, and the mixture was stirred at 25°C for 10 minutes. After the reaction was complete, the mixture was purified by column chromatography to obtain 1.4 g of product. 1 H NMR(400MHz,Chloroform-d)δ 8.06(dd,J=7.6,3.2Hz,1H),7.83(dd,J=8.2,3.4Hz,1H),7.31(s,2H),6.94-6.89(m,2H),3.84(s,3H),3.80(m,2) H),3.64-3.55(m,2H),3.21(q,J=6.0Hz,1H),2.86-2.77(m,1H),2.71(s,3H),2.53(m,1H),1.22(d,J=6.4Hz,3H).

[0251] 10. Synthesis of compound C62-11: Compound C62-10 (0.7 g, 1.77 mmol) is dissolved in a mixed solvent consisting of 10 mL of dichloromethane and 10 mL of methanol. Under nitrogen gas protection, sodium borohydride (40 mg, 0.88 mmol) is slowly added, and the reaction mixture is stirred at room temperature for 10 minutes. After the starting materials have completely reacted, the reaction mixture is diluted with water, then extracted three times with dichloromethane, the organic phases are combined, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and purified to obtain 600 mg of product.

[0252] 11. Synthesis of compound C62-12: Compound C62-11 (600 mg, 1.5 mmol) is dissolved in 30 mL of 1,2-dichloroethane, and phosphorus tribromide (1.25 g, 4.5 mmol) is slowly added under nitrogen gas protection. The mixture is stirred at 50°C for 4 hours until the starting materials have completely reacted. After this, the mixture is concentrated under reduced pressure and slurryed with dichloromethane and petroleum ether to obtain 600 mg of the product.

[0253] 12. Synthesis of compound C62-13: Compound C62-12 (600 mg, 1.3 mmol) is dissolved in 20 mL of anhydrous N,N-dimethylformamide. At room temperature, 2-tert-butyl 2-aminobenzoate (1.6 g, 7.8 mmol) is slowly added, and the mixture is slowly heated to 60°C and reacted with stirring for 12 hours. After the starting materials have completely reacted, the reaction mixture is diluted with water, then extracted three times with ethyl acetate. The organic phases are combined, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and purified to obtain 350 mg of the product.

[0254] 13. Synthesis of compound C62-14: Compound C62-13 (350 mg, 0.61 mmol) is dissolved in 40 mL of 1,2-dichloroethane, and 1-chloroethyl chloroformate (174 mg, 1.22 mmol) is slowly added at room temperature. The temperature is slowly raised to 83°C, and the mixture is reacted with stirring for 3 hours until the starting materials have completely reacted. The reaction mixture is then concentrated to dryness, methanol is added, the temperature is raised to 65°C, and the mixture is reacted with stirring for 1 hour. The mixture is then made basic with triethylamine, and the mixture is spin-dried and purified to obtain 200 mg of the product.

[0255] 14. Synthesis of compound C62-15: Compound C62-14 (100 mg, 0.22 mmol) is dissolved in 5 mL of dichloromethane, and DBU (100 mg, 0.66 mmol) is added at room temperature. Then, a dichloromethane solution of isopropylsulfonyl chloride (78.3 mg, 0.55 mmol) is slowly added dropwise. After the addition is complete, the mixture is reacted at 30°C with stirring for 2 hours. Once the starting materials have completely reacted, water is added to quench the mixture, and it is extracted three times with dichloromethane. The organic phases are combined, then concentrated, dried, and purified by column chromatography to obtain 80 mg of the product.

[0256] 15. Synthesis of compound C62-16: Compound C62-15 (80 mg, 0.16 mmol) was dissolved in a mixed solvent of dichloromethane (5 mL) and trifluoroacetic acid (5 mL), and the mixture was reacted at 25°C with stirring for 12 hours. After the reaction was complete, the mixture was spin-dried and separated by thin-layer plate to obtain 70 mg of the product.

[0257] 16. Synthesis of compounds C62, C63, C64, and C65: Separation was performed using a division method of C62-16 (70 mg) or less. Instrument: Agilent 1260 InfinityII, chromatographic column: phenomenex Lux® 5 μm cellulose-4 (250 × 21.2 mm), mobile phase: n-hexane:ethanol = 9:1, column temperature: 25°C. C62 (19.2 min, 12.32 mg) [M+H] +:503.2 1 H NMR(400MHz,DMSO-d6)δ 12.86(m,1H),8.53(m,1H),7.81(dd,J=8.2,1.6Hz,1H),7.58(m,2H),7.23(t,J=7.6Hz,1H),6.57(dd,J=8.4,5.6Hz,2H),5.23(t,J=6.8Hz,1H),4.65-4.28(m,3H),3.51(p,J=6.8Hz,1H),2.72-2.56(m,2H),1.66(d,J=6.8Hz,3H),1.29-1.19(m,9H)。 C63(29.5min、4.42mg)[M+H] + :503.2 1 H NMR(400MHz,DMSO-d6)δ12.86(m,1H),8.53(m,1H),7.81(dd,J=8.2,1.6Hz,1H),7.58(m,2H),7.23(t,J=7.6Hz,1H),6.57(dd,J=8.4,5.6Hz,2H),5.23(t,J=6.8Hz,1H),4.65-4.28(m,3H),3.51(p,J=6.8Hz,1H),2.72-2.56(m,2H),1.66(d,J=6.8Hz,3H),1.29-1.19(m,9H)。 C64(34.7min、1.72mg)[M+H] + :503.2 1 H NMR(400MHz,DMSO-d6)δ12.86(m,1H),8.53(m,1H),7.81(dd,J=8.2,1.6Hz,1H),7.58(m,2H),7.23(t,J=7.6Hz,1H),6.57(dd,J=8.4,5.6Hz,2H),5.23(t,J=6.8Hz,1H),4.65-4.28(m,3H),3.51(p,J=6.8Hz,1H),2.72-2.56(m,2H),1.66(d,J=6.8Hz,3H),1.29-1.19(m,9H)。 C65(46.7min、8.72mg)[M+H] + :503.2 1H NMR(400MHz,DMSO-d6)δ12.86(m,1H),8.53(m,1H),7.81(dd,J=8.2,1.6Hz,1H),7.58(m,2H),7.23(t,J=7.6Hz,1H),6.57(dd,J=8.4,5. 6Hz,2H), 5.23(t,J=6.8Hz,1H),4.65-4.28(m,3H),3.51(p,J=6.8Hz,1H),2.72-2.56(m,2H),1.66(d,J=6.8Hz,3H),1.29-1.19(m,9H).

[0258] Example 11 The compound of the present invention [ka] The synthesis route and experimental process are as follows: [ka]

[0259] 1. Synthesis of compound C66-2: Compound C66-1 (4.48 g, 24 mmol) is dissolved in 60 mL of N,N-dimethylformamide, and 3-chloro-4-cyanopyridine (2.78 g, 20 mmol) and cesium carbonate (13 g, 40 mmol) are added. After the addition is complete, the temperature is raised to 110°C and the mixture is reacted for 3 hours until the starting materials are completely reacted. Water is slowly added to quench the mixture, then it is extracted with ethyl acetate to separate the organic phase, dried over anhydrous sodium sulfate, and the filtrate is concentrated under reduced pressure and purified by column chromatography to obtain 4.5 g of the product. 1 H NMR(400MHz,Chloroform-d)δ 8.53(d,J=4.8Hz,1H),8.16(s,1H),7.74(d,J=5.6Hz,1H),7.60(d,J=4.8Hz,1H),7.42~7.40(m,1H),7.16(d,J=8.8Hz,1H),

[0260] 2. Synthesis of compound C66-3: Dissolve C66-2 (4.5 g, 15.5 mmol) in 40 g of polyphosphate and slowly raise the temperature to 220°C, stirring for 3 hours. After the starting materials have completely reacted, cool the reaction mixture to room temperature, dissolve it in water, adjust the pH to basic with saturated sodium bicarbonate aqueous solution, then extract three times with ethyl acetate, combine the organic phases, dry over anhydrous sodium sulfate, concentrate under reduced pressure, form a slurry, and purify to obtain 3.5 g of product. 1 H NMR (400MHz, Chloroform-d) δ 9.19(s,1H),8.74(s,1H),8.28(d,J=2.4Hz,1H),8.12(s,1H),8.05(d,J=2.8Hz,1H).

[0261] 3. Synthesis of compound C66-4: Add C66-3 (2.5 g, 8.6 mmol), potassium iodide (3.15 g, 19 mmol), and benzyl chloride (2.7 g, 17.2 mmol) to 40 mL of acetonitrile. Slowly raise the temperature of the reaction mixture to 80°C and stir for 2 hours. After the starting materials have completely reacted, concentrate the reaction mixture under reduced pressure to obtain 8.2 g of crude product, which is used directly in the next step of the reaction.

[0262] 4. Synthesis of compound C66-5: Compound C66-4 (8.2 g, 20 mmol) is dissolved in 200 mL of anhydrous ethanol, sodium borohydride cyanohydride (10.8 g, 160 mmol) and acetic acid (1.2 g, 20 mmol) are added, and the mixture is stirred for 30 minutes while maintaining room temperature. After the starting materials have completely reacted, the reaction solution is diluted with water, then extracted three times with dichloromethane, the organic phases are combined, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and purified to obtain 3.8 g of product.

[0263] 5. Synthesis of compound C66-6: Compound C66-5 (3 g, 7.24 mmol), tributyl(1-ethoxyethylene)tin (3.14 g, 8.7 mmol), and Pd(PPh3)2Cl2 (510 mg, 0.724 mmol) were dissolved in dry dioxane (50 mL) and stirred at 80°C for 12 hours. Then, under room temperature conditions, potassium fluoride solution was added, the mixture was stirred for 0.5 hours, filtered, and the mother liquor was extracted three times with ethyl acetate to separate the organic phase. The organic phase was spin-dried, dissolved in dichloromethane, 2 ml of concentrated hydrochloric acid was added, and the mixture was stirred at 25°C for 10 minutes. After the reaction was complete, the mixture was purified by column chromatography to obtain 2.5 g of product. 1 H NMR(400MHz,Chloroform-d)δ 8.35(s,1H),8.03(s,1H),7.31(d,J=8.4Hz,2H),6.93(d,J=8.4Hz,2H),3.84(s,3 H),3.71(s,2H),3.54(s,2H),2.79~2.77(m,2H),2.71~2.68(m,5H),2.48(s,3H).

[0264] 6. Synthesis of compound C66-7: Compound C66-6 (1.13 g, 3 mmol) is dissolved in 50 mL of tetrahydrofuran, and under nitrogen gas protection, (R)-(+)-tert-butylsulfinamide (726 mg, 6 mmol) and Ti(OEt)4 (2.73 g, 1.2 mmol) are added sequentially, and the reaction mixture is stirred at 70°C for 12 hours. After the starting materials have completely reacted, the reaction mixture is diluted with water, filtered through diatomaceous earth, then washed with ethyl acetate, the filtrate is separated into layers, the mother liquor is extracted twice with ethyl acetate, the organic phases are combined, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and then purified to obtain 1.1 g of product.

[0265] 7. Synthesis of compound C66-8: Compound C66-7 (0.4 g, 0.8 mmol) is dissolved in 20 mL of methanol, and under nitrogen gas protection, CeCl3.7H2O (148 mg, 0.4 mmol) and sodium borohydride (45.6 mg, 1.2 mmol) are added sequentially and slowly, and the mixture is stirred at room temperature for 20 minutes. After the starting materials have completely reacted, aqueous ammonium chloride solution is added, and the mixture is extracted three times with ethyl acetate. The organic phases are combined, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and then purified to obtain 0.38 g of product.

[0266] 8. Synthesis of compound C66-9: Compound C66-8 (320 mg, 0.64 mmol) is dissolved in 25 mL of methanol, and 4N HCl / MeOH (5 mL) is slowly added at room temperature. The mixture is reacted for 1 hour with stirring until the starting materials have completely reacted. The reaction mixture is then concentrated to dryness, water (8 mL) is added, and the pH of the aqueous phase is adjusted to 12 with 10% aqueous ammonia. The mixture is then extracted three times with ethyl acetate, the organic phases are combined, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain 250 mg of the product.

[0267] 9. Synthesis of compound C66-10: Compound C66-9 (80 mg, 0.2 mmol) is dissolved in dimethyl sulfoxide (5 mL), and under conditions of 25°C, 6-chloro-3-fluoropyridine-2-carboxylate tert-butyl ester (56 mg, 0.24 mmol) and N,N-diisopropylethylamine (129 mg, 1 mmol) are added. The mixture is reacted at 100°C with stirring for 10 hours. After the reaction is complete, saturated brine is added, and the mixture is extracted three times with ethyl acetate. The mixture is spin-dried and purified by column chromatography to obtain 40 mg of the product. 1H NMR(400MHz,Chloroform-d)δ 8.31(br,1H),8.08(s,1H),7.51(s,1H),7.31(d,J=8.4Hz,2H),7.09(d,J=8.8Hz,2H),6.93(d,J=8.4Hz,2H),6.63 (d,J=8.8Hz,1H),5.01~4.96(m,1H),3.73~3.67(m,2H),3.54~3.50(m,2H),2.82~2.72(m,4H),1.69~1.65(m,12H).

[0268] 10. Synthesis of compound C66-11: Dissolve compound C66-10 (240 mg, 0.4 mmol) in 1,2-dichloroethane (24 mL), add 1-chloroethyl chloroformate (112 mg, 0.8 mmol) under nitrogen gas protection at room temperature, and stir at 83°C for 2 hours. After the reaction is complete, spin dry and use directly in the next step. Dissolve the crude product from the previous step in methanol (24 mL) and react at 65°C under nitrogen gas protection for 1 hour. After the reaction is complete, add triethylamine, adjust the pH of the reaction solution to basic, spin dry directly, and use in the next step of the reaction.

[0269] 11. Synthesis of compound C66-12: Compound C66-11 (19.2 mg, 0.04 mmol) is dissolved in 5 mL of 1,2-dichloroethane, and triethylamine (60 mg, 0.6 mmol) is added at room temperature. Then 4-morpholine sulfonyl chloride (74.4 mg, 0.4 mmol) is slowly added dropwise. After the addition is complete, the mixture is reacted at 30°C with stirring for 12 hours. After the starting materials have completely reacted, aqueous sodium bicarbonate is added to quench the mixture, and the mixture is extracted three times with dichloromethane. The organic phases are combined, and then washed once each with 10% aqueous citric acid solution and saturated brine. The mixture is dried, concentrated, and purified by preparative plate to obtain 8 mg of the product.

[0270] 12. Synthesis of compound C66: Compound C66-12 (40 mg, 0.06 mmol) was dissolved in dichloromethane (6 mL) / trifluoroacetic acid (3 mL), stirred for 12 hours under nitrogen gas protection at 30°C, and after the reaction was complete, it was spin-dried and purified by thin-layer preparative plate to obtain 5.64 mg of the product. [M+H] + :583.2 1 HNMR(DMSO-d6,400Hz),δ9.74(br,1H),7.86~7.81(m,2H),7.45~7.25(m,2H),5.21~5.19(m,1H), 4.55~4.39(m,2H),3.53~3.50(m,6H),3.14~3.10(m,4H),2.57~2.50(m,2H),1.64(d,J=2.4Hz,3H)

[0271] Example 12 The compound of the present invention [ka] The synthesis route and experimental process are as follows: [ka]

[0272] 1. Synthesis of compound C111-1: Compound int7-6 (0.5 g, 1.33 mmol) is dissolved in a mixed solvent consisting of 10 mL of dichloromethane and 10 mL of methanol. Under nitrogen gas protection, sodium borohydride (50 mg, 1.33 mmol) is slowly added, and the reaction mixture is stirred at room temperature for 10 minutes. After the starting materials have completely reacted, the mixture is processed and purified to obtain 0.3 g of product.

[0273] 2. Synthesis of compound C111-2: Compound C111-1 (0.3 g, 0.79 mmol) is dissolved in 20 mL of anhydrous dichloromethane, and phosphorus tribromide (0.64 g, 2.38 mmol) is slowly added under nitrogen gas protection. The mixture is stirred at room temperature for 12 hours, and after the reaction of the starting materials is complete, it is processed to obtain 0.7 g of product.

[0274] 3. Synthesis of compound C111-3: Compound C111-2 (0.7 g, 0.79 mmol) is dissolved in 20 mL of anhydrous N,N-dimethylformamide. At room temperature, 2-tert-butyl 2-aminobenzoate (0.89 g, 4.74 mmol) is slowly added, and the temperature is slowly raised to 60°C. The mixture is reacted with stirring for 36 hours. After the reaction is complete, the mixture is processed and purified to obtain 120 mg of the product.

[0275] 4. Synthesis of compound C111-4: Compound C111-3 (90 mg, 1.65 mmol) is dissolved in 5 mL of 1,2-dichloroethane, and 1-chloroethyl chloroformate (47.1 mg, 3.3 mmol) is slowly added at room temperature. The temperature is slowly raised to 83°C, and the mixture is reacted with stirring for 3 hours. After the reaction of the starting materials is complete, the mixture is processed and purified to obtain 51 mg of the product.

[0276] 5. Synthesis of compound C111-5: Compound C111-4 (51 mg, 0.11 mmol) is dissolved in 5 mL of dichloromethane, and triethylamine (56 mg, 0.55 mmol) is added at 0°C. Then phenylsulfonyl chloride (37 mg, 0.26 mmol) is slowly added dropwise. After the addition is complete, the temperature is allowed to rise naturally, and the mixture is reacted with stirring for 12 hours. After the reaction is complete, the mixture is processed and purified to obtain 28 mg of the product.

[0277] 6. Synthesis of compounds C111 and C112: Compound C111-5 (28 mg, 0.05 mmol) was separated using the following separation method: Instrument: Agilent 1260 InfinityII, chromatographic column: phenomenex Lux® 5 μm cellulose-4 (250 × 21.2 mm), mobile phase: n-hexane:ethanol = 1:9, column temperature: 25°C. C111 (9.5 min, 10.95 mg) [M+H] + :571.3 1HNMR:(DMSO-d6,400Hz),δ7.89~7.87(m,2H),7.71~7.68(m,2H),7.64~7.60(m,2H),7.43~7.41(m,1H),7.29~7.25(m,1H),6.74~.6.70(m ,1H),6.60~6.58(m,1H),5.13~5.10(m,1H),4.31~4.24(m,2H),3.44~3.39(m,1H),3.28~3.21(m,5H),2.35(s,3H),1.62(d,J=7.8Hz,3H) C112 (10.2 min, 11.94 mg) [M+H] + :571.3 1 HNMR:(DMSO-d6,400Hz),δ7.89~7.87(m,2H),7.71~7.68(m,2H),7.64~7.60(m,2H),7.43~7.41(m,1H),7.29~7.25(m,1H),6.74~.6.70( m,1H),6.60~6.58(m,1H),5.13~5.10(m,1H),4.31~4.24(m,2H),3.44~3.39(m,1H),3.28~3.21(m,5H),2.35(s,3H)1.62(d,J=7.8Hz,3H)

[0278] Example 13 The compound of the present invention [ka] The synthesis route and experimental process are as follows: [ka]

[0279] 1. Synthesis of compound C163-2 Dissolve C163-1 (1.01 g, 2.65 mmol) in 30 mL of dioxane, and add trimethylcyclotriboloxane in tetrahydrofuran solution (3.5 N, 5.4 mL), potassium carbonate (2.62 g, 7.95 mmol), and DPPF-PdCl2 (463 mg, 0.265 mmol). Raise the temperature of the reaction mixture to 105 °C and allow to react overnight. After the reaction is complete, purify by column chromatography to obtain 236 mg of the product. 1 H NMR (400MHz, Chloroform-d) δ 10.45 (s, 1H), 8.50 (d, J = 4.9Hz, 1H), 7.53 (t, J = 4.9Hz, 1H), 2.65 (d, J = 3.2Hz, 3H).

[0280] 2. Synthesis of compound C163-3 Dissolve C163-2 (54 mg, 0.39 mmol) in 1.5 mL of N,N-dimethylformamide, and add 2-bromo-4-fluorophenol (112 mg, 0.59 mmol) and cesium carbonate (198 mg, 0.78 mmol). Raise the temperature of the reaction mixture to 100°C and allow to react for 3 hours. After the reaction is complete, purify by column chromatography to obtain 24 mg of the product.

[0281] 3. Synthesis of compound C163-4 Dissolve C163-3 (24 mg, 0.078 mmol) in a mixed solvent of 0.5 mL of tetrahydrofuran and 0.5 mL of aqueous ammonia, add iodine (29.7 mg, 0.117 mmol), and react overnight at room temperature under nitrogen gas protection. After the reaction is complete, process to obtain 11 mg of the product. 1 H NMR (400MHz, Chloroform-d) δ 8.55(d,J=5.0Hz,1H),7.52-7.40(m,2H),6.98(ddd,J=9.1,7.5,3.0Hz,1H),6.54(dd,J=9.0,4.6Hz,1H),2.52(s,3H).

[0282] 4. Synthesis of compound C163-5 Add C163-4 (4.4g) to the reaction bottle, add polyphosphate (50g), and raise the temperature to 220°C to complete the reaction. Cool, add aqueous sodium bicarbonate solution to quench, adjust to basic conditions, extract three times with dichloromethane, dry, and concentrate to obtain 3.6g of crude product, which is used directly in the next step of the reaction.

[0283] 5. Synthesis of compound C163-6 Dissolve C163-5 (3.6g, 11.7 mmol) in acetonitrile, then add potassium iodide (4.28g, 25.8 mmol) and p-methoxybenzyl chloride (3.67g, 23.5 mmol). Increase the temperature to 80°C and react for 1 hour. After the reaction is complete, spin-dry the mixture directly and use it for the next step in the reaction.

[0284] 6. Synthesis of compound C163-7 Dissolve C163-6 in ethanol (150 ml), add acetic acid (211 mg, 3.5 mmol) and sodium borohydride cyanohydride (887 mg, 14.1 mmol), and react at room temperature for 10 minutes. After the reaction is complete, purify by column chromatography to obtain 1.3 g of product.

[0285] 7. Synthesis of compound C163-8 C163-7 (650 mg, 1.51 mmol) is dissolved in dioxane (10 ml), and tributyl(1-ethoxyethylene)tin (653.3 mg, 1.81 mmol) and Pd(PPh3)Cl2 (106 mg, 0.15 mmol) are added. The mixture is reacted overnight at 80°C under nitrogen gas protection. After the reaction is complete, the product is purified by column chromatography to obtain 540 mg of the product.

[0286] 8. Synthesis of compound C163-9 Dissolve C163-8 (540 mg, 1.37 mmol) in tetrahydrofuran (20 ml), and add R-tert-butylsulfinamide (331 mg, 2.73 mmol) and tetraethyl titanate (1.25 g, 5.47 mmol). Allow the reaction mixture to react overnight at 70°C under nitrogen gas protection. After the reaction is complete, 630 mg of the product is purified by column chromatography.

[0287] 9. Synthesis of compound C163-10 Add C163-9 (630 mg, 1.27 mmol) to 10 ml of methanol, add cerium chloride heptahydrate (236 mg, 0.63 mmol), stir for 5 minutes, and add sodium borohydride (72 mg, 1.90 mmol) in batches. After the reaction is complete, 540 mg of the product is purified by column chromatography.

[0288] 10. Synthesis of compound C163-11 Dissolve C163-10 (540 mg) in ethanol (5 ml), and add a 2 M ethanol solution of hydrochloric acid (5 ml). React at room temperature for 10 minutes. After the reaction is complete, purify by column chromatography to obtain 450 mg of the product.

[0289] 11. Synthesis of compound C163-12 Dissolve C163-11 (450 mg, 1.14 mmol) in toluene, and add 2-brominated tert-butylbenzoate (350 mg, 1.36 mmol), Pd(OAc)2 (25.5 mg, 0.11 mmol), Xantphos (131.6 mg, 0.23 mmol), and Cs2CO3 (1.00 g, 3.10 mmol). React overnight at 100°C under nitrogen gas protection. After the reaction is complete, 500 mg of the product is purified by column chromatography.

[0290] 12. Synthesis of compound C163-13 Dissolve C163-12 (500 mg, 0.87 mmol) in 1,2-dichloroethane, add 1-chloroethyl chloroformate (250 mg, 1.75 mmol), and react at 80°C for 1 hour. Concentrate the mixture, add methanol and triethylamine (353 mg, 3.50 mmol), and raise the temperature of the reaction to 65°C for 1 hour. After the reaction is complete, purify by column chromatography to obtain 300 mg of the product.

[0291] 13. Synthesis of compound C163-14 Dissolve C163-13 (150 mg, 0.33 mmol) in dichloromethane, add DBU (252 mg, 1.66 mmol) and isopropylsulfonyl chloride (142 mg, 1.00 mmol), and react at room temperature for 1 hour. After the reaction is complete, purify by column chromatography to obtain 100 mg of the product.

[0292] 14. Synthesis of compounds C163 and C164 Dissolve C163-14 in dichloromethane (4 ml), add trifluoroacetic acid (4 ml), and react overnight at room temperature. After the reaction is complete, concentrate and separate using the following separation method: Instrument: Agilent 1260 InfinityII, chromatographic column: phenomenex Lux® 5 μm cellulose-4 (250 × 21.2 mm), mobile phase: n-hexane:ethanol = 3:7, column temperature: 25°C. C163 (11.2 min, 23.26 mg) [M+H] + :502.6 1 H NMR(400MHz,DMSO-d6)δ 8.41(br,1H),7.84(dd,J=8.0,1.6Hz,1H),7.62-7.60(m,1H),7.51-7.48(m,1H),7.25-7.20(m,1H),6.58(t,J=7.6Hz,1H),6.50(d,J=8.4Hz, 1H),5.27(br,1H),4.91(q,J=6.8Hz,1H),3.87-3.82(m,1H),3.49-3.46(m,1H),2.66-2.54(m,2H),1.62(d,J=6.8Hz,6H),1.28-1.22(m,8H). C164 (13.4 min, 23.60 mg) [M+H] + :502.6 1 H NMR(400MHz,DMSO-d6)δ 8.48(br,1H),7.81(dd,J=8.0,1.6Hz,1H),7.66-7.60(m,2H),7.25-7.20(m,1H),6.56(t,J=7.6Hz,1H),6.50(d,J=8.4Hz,1H),5.21-5.18 (m,1H),4.87(q,J=6.8Hz,1H),3.87-3.82(m,1H),3.47-3.43(m,1H),2.68-2.52(m,2H),1.66-1.63(m,6H),1.23(dd,J=20.0,6.8Hz,8H).

[0293] Example 14 The compound of the present invention [ka] The synthesis route and experimental process are as follows: [ka]

[0294] 1. Synthesis of compound C166-1 Intermediate int7 (200 mg, 0.46 mmol) is dissolved in 5 mL of N,N-dimethylformamide, and methylbenzyl chloride (189 mg, 1.34 mmol), triethylamine (270 mg, 2.67 mmol), and potassium iodide (120 mg, 0.72 mmol) are added. The mixture is reacted overnight in a sealed tube at 80°C. After the reaction is complete, the product is purified by column chromatography to obtain 183 mg of the product. 2. Synthesis of compounds C166 and C167 Dissolve C166-1 (50 mg) in dichloromethane (10 mL), add trifluoroacetic acid (10 mL), and react overnight at room temperature. After the reaction is complete, concentrate and separate using the following separation method: Instrument: Agilent 1260 InfinityII, chromatographic column: phenomenex Lux® 5 μm cellulose-4 (250 × 21.2 mm), mobile phase: n-hexane:ethanol = 95:5, column temperature: 25 °C. C166 (10.4 min, 19.28 mg) [M+H] + :483.3 1 1H NMR (400MHz, DMSO-d6)δ 12.78(br,1H),8.42(d,J=7.0Hz,1H),7.82(dd,J=7.9,1.7Hz,1H),7.73(d, J=2.1Hz,1H),7.66-7.31(m,6H),7.24-7.17(m,1H),6.55(t,J=7.5Hz,1H), 6.46(d,J=8.5Hz,1H),5.15(t,J=6.6Hz,1H),4.75-4.04(m,3H),3.28-3.16 (m,2H),2.76-2.57(m,2H),2.35(s,3H),1.68(s,3H),1.59(d,J=6.6Hz,3H). C167 (13.6 min, 19.52 mg) [M+H] + :483.3 1 1H NMR (400MHz, DMSO-d6)δ 12.79(br,1H),8.42(d,J=6.9Hz,1H),7.82(dd,J=8.0,1.7Hz,1H),7.73(d, J=2.1Hz,1H),7.66-7.37(m,6H),7.25-7.17(m,1H),6.56(t,J=7.5Hz,1H), 6.47(d,J=8.5Hz,1H),5.17(t,J=6.7Hz,1H),4.87-4.02(m,3H),3.27-2.89 (m,2H),2.82-2.56(m,2H),2.35(s,3H),1.69(s,3H),1.59(d,J=6.7Hz,3H).

[0295] Example 15 The compound of the present invention [ka] The synthesis route and experimental process are as follows: [ka]

[0296] 1. Synthesis of C185-1 Compound int-12 (2.1 g, 6.03 mmol), 2-brominated tert-butylbenzoate (1.86 g, 7.24 mmol), palladium acetate (134 mg, 0.6 mmol), Xantphos (694 mg, 1.2 mmol), and cesium carbonate (5.9 g, 18.9 mmol) were dissolved in dry toluene (21 mL) and stirred at 100 °C for 12 hours. After the reaction was complete, the mixture was filtered, concentrated, and purified by column chromatography to obtain 2.4 g of the product.

[0297] 2. Synthesis of C185 and C186: Compound C185-1 (100 mg) was dissolved in dichloromethane (3 mL) / trifluoroacetic acid (3 mL), stirred for 12 hours under nitrogen gas protection at 30°C, and after the reaction was complete, 60 mg of crude product was purified by column chromatography and separated using the following separation method: Instrument: Agilent 1260 Infinity II, chromatographic column: phenomenex Lux® 5 μm Amylose-1 (250 × 21.2 mm), mobile phase: n-hexane:ethanol = 9:1, column temperature: 25°C. C185 (18.7 min, 15 mg) 1H NMR (400MHz, DMSO-d6)δ 8.63(s,1H),7.80(d,J=7.8Hz,1H),7.59(d,J=3.3Hz,1H),7.43-7.32(m,4H), 7.32-7.23(m,1H),7.23-7.09(m,1H),6.52(d,J=3.5Hz,1H),6.30(d,J=8.5Hz ,1H),5.30(d,J=6.6Hz,1H),3.73(s,2H),3.58(s,2H),3.14(d,J=3.4Hz,3H), 2.82-2.73(m,2H),2.68(d,J=5.6Hz,2H),2.28(s,3H),1.54(d,J=6.6Hz,3H). C186 (22 min, 5 mg) 1 H NMR (400MHz, DMSO-d6)δ 8.64(s,1H),8.45(d,J=6.5Hz,1H),7.80(d,J=7.9Hz,1H),7.61(d,J=2.1Hz,1H) ,7.46-7.32(m,4H),7.29(t,J=6.9Hz,1H),7.17(t,J=7.8Hz,1H),6.53(t,J=7.5 Hz,1H),6.30(d,J=8.5Hz,1H),5.30(q,J=6.1Hz,1H),3.73(s,2H),3.57(s,2H), 2.75(q,J=5.7Hz,2H),2.66(t,J=5.8Hz,2H),2.30(s,3H),1.54(d,J=6.6Hz,3H).

[0298] The synthesis method mentioned above is to use the following compounds to synthesize them. Table A-1 Table A-2 Table A-3 Table A-4 Table A-5 Table A-6 Table A-7 Table A-8 Table A-9 Table A-10 Table A-11 Table A-12 Table A-13 Table A-14 Table A-15 Table A-16 Table A-17 Table A-18 Table A-19 Table A-20 Table A-21 Table A-22 Table A-23 Table A-24 Table A-25 Table A-26 Table A-27 Table A-28 Table A-29 Table A-30 Table A-31 Table A-32 Table A-33 Table A-34 Table A-35 Table A-36 Table A-37 Table A-38 Table A-39 [Table A-40] [Table A-41] [Table A-42] [Table A-43] [Table A-44] [Table A-45] [Table A-46] [Table A-47] [Table A-48] [Table A-49] [Table A-50] [Table A-51]

[0299] Cell proliferation inhibition test 1. Experimental Materials [Table B]

[0300] 2. Experimental Protocol 1. Cell Plating a) Preparation of cell suspension b) Remove the culture medium from the culture bottle. c) Wash the cells once with PBS, d) After trypsin digestion, centrifuge and collect. e) Resuspend in culture medium, calculate, and adjust to the appropriate concentration. f) Add 100 µl of the cell suspension to each well of a 96-well plate, plate one plate for each cell type, and incubate overnight in a 37°C, 5% CO2 incubator.

[0301] 2. Treatment of the compound Dilution of the compound a) Preparation of serially diluted solutions of the test compound: The compound is prepared as a 10 mM stock solution. Then, 18 µl of the stock solution is dissolved in 982 µl of DMSO culture medium and sequentially diluted fourfold with 0.5% DMSO culture medium to prepare a total of nine concentrations. The concentrations of the compound after dilution are as follows: 180000nM, 45000nM, 11250nM, 2812.5nM, 703.13nM, 175.78nM, 43.95nM, 10.99nM, 2.75nM b) After thoroughly mixing the compounds uniformly, 20 µl of each compound solution was taken and added to a cell culture plate containing 100 µl of cells, with three duplicate wells for each concentration. The final concentrations of the compounds are as follows: 30000nM, 7500nM, 1875nM, 468.75nM, 117.188nM, 29.30nM, 7.32nM, 1.83nM, 0.46nM c) Transfer the cells to an incubator and incubate for 3 days.

[0302] 3. CTG detection Remove the cell culture plate, add 25 µl of CTG to a 96-well plate, incubate in a shaker at room temperature for 10 minutes, and read the plate. 4. Data Analysis The survival rate (% Cell Survival) is calculated using the following formula. Survival rate (% Cell Survival)=100%×(OD_Sample-OD_LCave) / (OD_HC-OD_LCave) OD_HC: 0.1‰ Number of cells read in the DMSO control group OD_Sample: Number of cells read after compound was added OD_LCave: Number of blank medium readings Analyed by Prizm:Dose-response-Inhibition-Log(inhibitor)vs response(three parameters for the best fit) The results of the cell proliferation inhibition test are shown in Table 1 below.

[0303] [Table 1-1] [Table 1-2] [Table 1-3] [Table 1-4] [Table 1-5] A is IC 50 This represents ≤500nM, and B is 500nM <IC 50 Represents ≤2000nM, C is 2000 nM <IC 50 This represents ≤5000nM, and D is 5000nM <IC 50 It represents.

[0304] This invention provides a series of compounds having selective inhibitory activity against the PI3Kα H1047R mutation, as well as a method for synthesizing them, and is expected to have a wide range of applications. All documents referenced in this invention are cited as references in this application, as if each document were cited individually. Furthermore, after reading the above teachings of this invention, persons skilled in the art can make various changes or modifications to the invention, and these equivalent forms are also included within the scope defined by the claims appended to this application.

Claims

1. A compound, wherein the compound is a compound of formula (I), or a pharmaceutically acceptable salt, stereoisomer, deuteride, solvate, or prodrug thereof. 【Chemistry 1】 Here, X １ N, O, S, NR １１ , C(R １１ ) ｑ Selected from the group consisting of, X ２ , X ３ Each is independently selected from the group consisting of N and C. X ４ is N or CR, X ５ does not exist, O, NR ５１ , C １－６ alkylene group, C ３－６ cycloalkylene group, a 3- to 6-membered heterocyclic alkylene group containing 1 to 4 heteroatoms selected from N, O or S, wherein said C １－６ alkylene group, C ３－６ cycloalkylene group, 3- to 6-membered heterocyclic alkylene group is substituted with 1, 2, 3, 4, 5 or 6 R ５２ is optionally substituted by, X ６ It does not exist, NR ６１ , C １－６ Selected from the group consisting of alkylene groups, where C １－６ The alkylene group consists of 1, 2, 3, 4, 5, or 6 R groups. ６２ It can be arbitrarily replaced by, X ７ is C=O, C=S, CR ７１ Selected from the group consisting of, The B ring contains one N atom and 0 to 3 heteroatoms selected from N, O, or S, and one or more R ５ A 5-7 member heterocyclic alkyl group that is optionally substituted by, Ring A is C ６－１０ Selected from the group consisting of an aryl group, a 5-10 membered heteroaryl group containing 1-4 heteroatoms selected from N, O, or S, and a 5-10 membered heterocyclic alkyl group containing 1-4 heteroatoms selected from N, O, or S, where the C ６－１０ The aryl group and the 5-10 membered heteroaryl group have m R ６ It can be arbitrarily replaced by, R, R ２ , R ３ , R １１ , R ５２ , R ６２ These are, independently, H, deuterium, halogen, oxo (=O), -CN, and -NO. ２ , C １－６ Alkyl alkyl groups, halogenated C １－６ Alkyl alkyl groups, deuterated C １－６ alkyl group, C １－６ Alkoxy group, halogenated C １－６ Alkoxy group, deuterated C １－６ Alkoxy group, C ３－６ Cycloalkyl groups, halogenated C ３－６ Cycloalkyl groups, deuterated C ３－６ Selected from the group consisting of cycloalkyl groups, Alternatively, R and R ２ Together with the atoms bonded to them, C ４－６ A cycloalkyl group or a 4-6 membered heterocyclic alkyl group comprising 1-4 heteroatoms selected from N, O, or S is formed, where the C ４－６ Cycloalkyl groups, 4- to 6-membered heterocyclic alkyl groups, have 1, 2, 3, 4, 5, or 6 R atoms. ６ It can be arbitrarily replaced by, Or, R ２ and R ３ Together with the atoms bonded to them, C ４－６ A cycloalkyl group or a 4-6 membered heterocyclic alkyl group comprising 1-4 heteroatoms selected from N, O, or S is formed, where the C ４－６ Cycloalkyl groups, 4- to 6-membered heterocyclic alkyl groups, have 1, 2, 3, 4, 5, or 6 R atoms. ６ It can be arbitrarily replaced by, R ５１ , R ６１ These are H, -CN, and -NO, respectively, independently. ２ , C １－６ Alkyl alkyl groups, halogenated C １－６ Alkyl alkyl groups, deuterated C １－６ alkyl group, C １－６ Alkoxy group, halogenated C １－６ Alkoxy group, deuterated C １－６ Alkoxy group, C ３－６ Cycloalkyl groups, halogenated C ３－６ Selected from the group consisting of cycloalkyl groups, R ７１ H, halogen, -CN, -NO ２ , C １－６ Alkyl alkyl groups, halogenated C １－６ alkyl group, C １－６ Alkoxy group, halogenated C １－６ Alkoxy group, C ３－６ Cycloalkyl groups, halogenated C ３－６ Cycloalkyl groups, -C(O)R ８ Selected from the group consisting of, R ４ is -L-(C １－６ Alkyl), -L-C ６－１０ Aryl group, -L- (5-10 membered heteroaryl containing 1-4 heteroatoms selected from N, O, or S), -L- (saturated or partially unsaturated C) ３－８ Selected from the group consisting of cycloalkyl, -L- (saturated or partially unsaturated 4-8 member heterocyclic alkyl containing 1-4 heteroatoms selected from N, O, or S), where the C １－６ alkyl group, C ６－１０ Aryl group, 5-10 membered heteroaryl group, C ３－８ Cycloalkyl groups, 4- to 8-membered heterocyclic alkyl groups, have n R ７ It can be arbitrarily replaced by, Each R ５ H, deuterium, halogen, -CN, oxo (=O), C １－６ Alkyl alkyl groups, halogenated C １－６ Alkyl alkyl groups, deuterated C １－６ alkyl group, C １－６ Alkoxy group, halogenated C １－６ Alkoxy group, deuterated C １－６ Alkoxy group, C ３－６ Cycloalkyl groups, halogenated C ３－６ Independently selected from the group consisting of cycloalkyl groups, 3- to 8-membered heterocyclic alkyl groups containing 1 to 3 heteroatoms selected from N, O, or S, Each R ６ is independently selected from the group consisting of H, deuterium, halogen, -CN, -NO ２ , C １－６ alkyl group, halogenated C １－６ alkyl group, deuterated C １－６ alkyl group, C １－６ alkoxy group, halogenated C １－６ alkoxy group, -C(O)R ８ , -C(O)OR ８ , -C(O)NR ８ R ９ , -SO ２ R ８ , -S(O)(NR ８ )R ９ , -SO ２ NR ８ R ９ , -P(O)R ８ R ９ , and is independently selected from the group consisting of, Each R ７ These are hydrogen, deuterium, halogens, oxo (=O), -CN, -OH, and -NO. ２ , C １－６ alkyl group, C １－６ Alkoxy group, halogenated C １－６ Alkyl alkyl groups, halogenated C １－６ Alkoxy group, deuterated C １－６ C containing 1 to 4 heteroatoms selected from alkyl groups, N, O, or S １－６ C halogenated with 1 to 4 heteroatoms selected from heteroalkyl groups, N, O, or S. １－６ Heteroalkyl groups, -NR ８ R ９ , = NR ８ , -C(O)R ８ , -C(O)OR ８ , -C(O)NR ８ R ９ , -NR ８ C(O)R ９ ,-SR ８ , -SO ２ R ８ , -NR ８ SO ２ R ９ , -SO ２ NR ８ R ９ , -NR ８ SO ２ NR ９ R １０ ,-P(O)R ８ R ９ , -L １ - (C １－６ Alkyl), -L １ - (Saturated or partially unsaturated C) ３－１０ Cycloalkyl), -L １ - (C ６－１０ Aryl), -L １ - (saturated or partially unsaturated 3-12 member heterocyclic alkyl group containing 1-4 heteroatoms selected from N, O, or S), -L １ - Independently selected from the group consisting of (5-10 membered heteroaryls containing 1-4 heteroatoms selected from N, O, or S), where C １－６ alkyl group, C １－６ Heteroalkyl groups, C ３－１０ Cycloalkyl groups, C ６－１０ Aryl groups, 3-12 membered heterocyclic alkyl groups, and 5-10 membered heteroaryl groups are composed of deuterium, halogens, =O, -CN, -OH, and -NH. ２ , C １－６ Alkyl alkyl groups, halogenated C １－６ alkyl group, C １－６ Alkoxy group, halogenated C １－６ Alkoxy group, C ３－６ Cycloalkyl groups, halogenated C ３－６ Cycloalkyl groups, 3-6 membered heterocyclic alkyl groups containing 1-4 heteroatoms selected from N, O, or S, -SO ２ R ８ , -C(O)R ８ , -C(O)OR ８ , -C(O)NR ８ R ９ , -NR ８ R ９ It is arbitrarily replaced by 0 to 6 permutations selected from the group consisting of the following: Alternatively, two R's ７ Together with the atoms to which they are bonded, C ３－６ Cycloalkyl groups, C ６－１０ A 3-6 member heterocyclic alkyl group containing an aryl group, 1-4 heteroatoms selected from N, O, or S, or a 5-6 member heteroaryl group containing 1-4 heteroatoms selected from N, O, or S is formed, where the C ３－６ Cycloalkyl groups, C ６－１０ Aryl groups, 3-6 membered heterocyclic alkyl groups, and 5-6 membered heteroaryl groups are associated with deuterium, halogens, =O, -CN, -OH, and -NR ８ R ９ , = NR ８ , -C(O)R ８ , -C(O)OR ８ , -C(O)NR ８ R ９ , -NR ８ C(O)R ９ ,-SR ８ , -SO ２ R ８ , -NR ８ SO ２ R ９ , -SO ２ NR ８ R ９ , -NR ８ SO ２ NR ９ R １０ ,-P(O)R ８ R ９ , C １－６ alkyl group, C １－６ C containing 1 to 4 heteroatoms selected from an alkoxy group, N, O, or S １－６ Heteroalkyl groups, halogenated C １－６ Alkyl alkyl groups, halogenated C １－６ C halogenated carbon containing alkoxy groups and 1 to 4 heteroatoms selected from N, O, or S １－６ Heteroalkyl groups, C ３－６ It is optionally substituted by 0 to 6 substitutions selected from the group consisting of cycloalkyl groups, 3 to 6-membered heterocyclic alkyl groups containing 1 to 4 heteroatoms selected from N, O, or S, L and L １ These are, independently, a combination, or C １－６ Alkylene group, C ２－６ Alkenylene group, C ２－６ Alkynylene group, 1-6 membered heteroalkylene group containing 1-4 heteroatoms selected from N, O, or S, -NR ８ -, -O-, -C(O)-, -C(O)NR ８ -, -C(O)O-, -NR ８ C(O)-,-(SO ２ ) -, -SO ２ NR ８ -, -NR ８ SO ２ -, -NR ８ SO ２ NR ９ -, -S(O)(NR ８ ) - Selected from the group consisting of, where C １－６ Alkylene group, C ２－６ Alkenylene group, C ２－６ Alkynylene groups and 1-6 membered heteroalkylene groups are composed of deuterium, halogen, =O, -CN, -OH, and -NR ８ R ９ , = NR ８ It is arbitrarily replaced by 0 to 6 permutations selected from the group consisting of the following: Each R ８ , R ９ , R １０ These are H and C, which are independent of each other. １－６ Alkyl alkyl groups, halogenated C １－６ alkyl group, C ３－６ Cycloalkyl groups, C ６－１０ Selected from the group consisting of an aryl group, a 3-6 membered heterocyclic alkyl group containing 1-4 heteroatoms selected from N, O, or S, and a 5-6 membered heteroaryl group containing 1-4 heteroatoms selected from N, O, or S, where the C ３－６ Cycloalkyl groups, C ６－１０ Aryl groups, 3-6 membered heterocyclic alkyl groups, and 5-6 membered heteroaryl groups are composed of deuterium, halogens, =O, -CN, -OH, and -NH. ２ , C １－６ Alkyl alkyl groups, halogenated C １－６ alkyl group, C １－６ Alkoxy group, halogenated C １－６ Alkoxy group, C １－６ Alkylamino group, halogenated C １－６ Alkylamino group, C １－６ Alkylthio group, halogenated C １－６ C containing 1 to 4 heteroatoms selected from alkylthio groups, N, O, or S １－６ C halogenated with 1 to 4 heteroatoms selected from heteroalkyl groups, N, O, or S. １－６ Heteroalkyl groups, C ３－６ Cycloalkyl groups, 3-6 member heterocyclic alkyl groups containing 1-4 heteroatoms selected from N, O, or S, and halogenated C ３－６ It is optionally substituted by 0 to 6 substitutions selected from the group consisting of cycloalkyl groups, 3 to 6-membered heterocyclic alkyl groups containing 1 to 4 heteroatoms selected from N, O, or S, Or, R ８ , R ９ These, together with the heteroatoms to which they are bonded, form a 3-6 member heterocyclic alkyl group containing 1-4 heteroatoms selected from N, O, or S, where the 3-6 member heterocyclic alkyl group is composed of deuterium, halogen, =O, -CN, -OH, -NH ２ , C １－６ Alkyl alkyl groups, halogenated C １－６ alkyl group, C １－６ Alkoxy group, halogenated C １－６ Alkoxy group, C １－６ Alkylamino group, halogenated C １－６ Alkylamino group, C １－６ Alkylthio group, halogenated C １－６ C containing 1 to 4 heteroatoms selected from alkylthio groups, N, O, or S １－６ C halogenated with 1 to 4 heteroatoms selected from heteroalkyl groups, N, O, or S. １－６ Heteroalkyl groups, C ３－６ Cycloalkyl groups, 3-6 member heterocyclic alkyl groups containing 1-4 heteroatoms selected from N, O, or S, and halogenated C ３－６ It is optionally substituted by 0 to 6 substitutions selected from the group consisting of cycloalkyl groups, 3 to 6-membered heterocyclic alkyl groups containing 1 to 4 heteroatoms selected from N, O, or S, Or, R ９ and R １０ These, together with the heteroatoms to which they are bonded, form a 3-6 member heterocyclic alkyl group containing 1-4 heteroatoms selected from N, O, or S, where the 3-6 member heterocyclic alkyl group is composed of deuterium, halogen, =O, -CN, -OH, -NH ２ , C １－６ Alkyl alkyl groups, halogenated C １－６ alkyl group, C １－６ Alkoxy group, halogenated C １－６ Alkoxy group, C １－６ Alkylamino group, halogenated C １－６ Alkylamino group, C １－６ Alkylthio group, halogenated C １－６ C containing 1 to 4 heteroatoms selected from alkylthio groups, N, O, or S １－６ C halogenated with 1 to 4 heteroatoms selected from heteroalkyl groups, N, O, or S. １－６ Heteroalkyl groups, C ３－６ Cycloalkyl groups, 3-6 member heterocyclic alkyl groups containing 1-4 heteroatoms selected from N, O, or S, and halogenated C ３－６ It is optionally substituted by 0 to 6 substitutions selected from the group consisting of cycloalkyl groups, 3 to 6-membered heterocyclic alkyl groups containing 1 to 4 heteroatoms selected from N, O, or S, each 【Chemistry 2】 Each of these is independently either a single bond or a double bond. The compound is characterized in that each m, n, and q is independently selected from the group consisting of 0, 1, 2, 3, 4, and 5.

2. A compound, wherein the compound is a compound of formula (I-a), or a pharmaceutically acceptable salt, stereoisomer, deuteride, solvate, or prodrug thereof. 【Transformation 3】 Here, X １ is N, O, C(R １１ ) ｑ Selected from the group consisting of, X ２ , X ３ Each is independently selected from the group consisting of N and C. X ４ is N or CR, The B ring contains one N atom and 0 to 3 heteroatoms selected from N, O, or S, and one or more R ５ A 5-7 member heterocyclic alkyl group that is optionally substituted by, Ring A is C ６－１０ Selected from the group consisting of a 5-8 membered heteroaryl group containing 1-4 heteroatoms selected from an aryl group, N, O, or S, where the C ６－１０ The aryl group and the 5- to 8-membered heteroaryl group have m R ６ It can be arbitrarily replaced by, R １ H, deuterium, halogen, -CN, C １－６ Alkyl alkyl groups, halogenated C １－６ Alkyl alkyl groups, deuterated C １－６ alkyl group, C １－６ Alkoxy group, halogenated C １－６ Selected from the group consisting of alkoxy groups, R, R ２ , R ３ , R １１ These are H, halogen, -CN, and C, respectively, independently. １－６ Alkyl alkyl groups, halogenated C １－６ Alkyl alkyl groups, deuterated C １－６ alkyl group, C １－６ Alkoxy group, halogenated C １－６ Alkoxy group, deuterated C １－６ Alkoxy group, C ３－６ Cycloalkyl groups, halogenated C ３－６ Selected from the group consisting of cycloalkyl groups, R ４ is -L-(C １－６ Alkyl), -L-C ６－１０ Aryl group, -L- (5- to 8-membered heteroaryl containing 1 to 4 heteroatoms selected from N, O, or S), -L- (saturated or partially unsaturated C) ３－８ Selected from the group consisting of cycloalkyl, -L- (saturated or partially unsaturated 4-8 member heterocyclic alkyl containing 1-4 heteroatoms selected from N, O, or S), where the C １－６ alkyl group, C ６－１０ Aryl group, 5-8 membered heteroaryl group, C ３－８ Cycloalkyl groups, 4- to 8-membered heterocyclic alkyl groups, have n R ７ It can be arbitrarily replaced by, Each R ５ H, deuterium, halogen, -CN, oxo (=O), C １－６ Alkyl alkyl groups, halogenated C １－６ Alkyl alkyl groups, deuterated C １－６ alkyl group, C １－６ Alkoxy group, halogenated C １－６ Alkoxy group, deuterated C １－６ Alkoxy group, C ３－６ Cycloalkyl groups, halogenated C ３－６ Independently selected from the group consisting of cycloalkyl groups, 3- to 8-membered heterocyclic alkyl groups containing 1 to 3 heteroatoms selected from N, O, or S, Each R ６ H, deuterium, halogen, -CN, -NO ２ , C １－６ Alkyl alkyl groups, halogenated C １－６ Alkyl alkyl groups, deuterated C １－６ alkyl group, C １－６ Alkoxy group, halogenated C １－６ Alkoxy group, -C(O)R ８ , -C(O)OR ８ , -C(O)NR ８ R ９ , -SO ２ R ８ , -S(O)(NR ８ ) R ９ , -SO ２ NR ８ R ９ ,-P(O)R ８ R ９ Independently selected from the group consisting of, Each R ７ These are hydrogen, deuterium, halogens, oxo (=O), -CN, -OH, and -NO. ２ , C １－６ alkyl group, C １－６ Alkoxy group, halogenated C １－６ Alkyl alkyl groups, halogenated C １－６ Alkoxy group, deuterated C １－６ C containing 1 to 4 heteroatoms selected from alkyl groups, N, O, or S １－６ C halogenated with 1 to 4 heteroatoms selected from heteroalkyl groups, N, O, or S. １－６ Heteroalkyl groups, -NR ８ R ９ , = NR ８ , -C(O)R ８ , -C(O)OR ８ , -C(O)NR ８ R ９ , -NR ８ C(O)R ９ ,-SR ８ , -SO ２ R ８ , -NR ８ SO ２ R ９ , -SO ２ NR ８ R ９ , -NR ８ SO ２ NR ９ R １０ ,-P(O)R ８ R ９ , -L １ - (C １－６ Alkyl), -L １ - (Saturated or partially unsaturated C) ３－１０ Cycloalkyl), -L １ - (C ６－１０ Aryl), -L １ - (saturated or partially unsaturated 3-12 member heterocyclic alkyl group containing 1-4 heteroatoms selected from N, O, or S), -L １ - Independently selected from the group consisting of (5-10 membered heteroaryls containing 1-4 heteroatoms selected from N, O, or S), where C １－６ alkyl group, C １－６ Heteroalkyl groups, C ３－１０ Cycloalkyl groups, C ６－１０ Aryl groups, 3-10 membered heterocyclic alkyl groups, and 5-10 membered heteroaryl groups are composed of deuterium, halogens, =O, -CN, -OH, and -NH. ２ , C １－６ Alkyl alkyl groups, halogenated C １－６ alkyl group, C １－６ Alkoxy group, halogenated C １－６ Alkoxy group, C ３－６ Cycloalkyl groups, halogenated C ３－６ Cycloalkyl groups, 3-6 membered heterocyclic alkyl groups containing 1-4 heteroatoms selected from N, O, or S, -SO ２ R ８ , -C(O)R ８ , -C(O)OR ８ , -C(O)NR ８ R ９ , -NR ８ R ９ It is arbitrarily replaced by 0 to 6 permutations selected from the group consisting of the following: Alternatively, two R's ７ Together with the atoms to which they are bonded, C ３－６ Cycloalkyl groups, C ６－１０ A 3-6 member heterocyclic alkyl group containing an aryl group, 1-4 heteroatoms selected from N, O, or S, or a 5-6 member heteroaryl group containing 1-4 heteroatoms selected from N, O, or S is formed, where the C ３－６ Cycloalkyl groups, C ６－１０ Aryl groups, 3-6 membered heterocyclic alkyl groups, and 5-6 membered heteroaryl groups are associated with deuterium, halogens, =O, -CN, -OH, and -NR ８ R ９ , = NR ８ , -C(O)R ８ , -C(O)OR ８ , -C(O)NR ８ R ９ , -NR ８ C(O)R ９ ,-SR ８ , -SO ２ R ８ , -NR ８ SO ２ R ９ , -SO ２ NR ８ R ９ , -NR ８ SO ２ NR ９ R １０ ,-P(O)R ８ R ９ , C １－６ alkyl group, C １－６ C containing 1 to 4 heteroatoms selected from an alkoxy group, N, O, or S １－６ Heteroalkyl groups, halogenated C １－６ Alkyl alkyl groups, halogenated C １－６ C halogenated carbon containing alkoxy groups and 1 to 4 heteroatoms selected from N, O, or S １－６ Heteroalkyl groups, C ３－６ It is optionally substituted by 0 to 6 substitutions selected from the group consisting of cycloalkyl groups, 3 to 6-membered heterocyclic alkyl groups containing 1 to 4 heteroatoms selected from N, O, or S, L and L １ These are, independently, a combination, or C １－６ Alkylene group, 1-6 membered heteroalkylene group containing 1-4 heteroatoms selected from N, O, or S, -NR ８ -, -O-, -C(O)-, -C(O)NR ８ -, -C(O)O-, -NR ８ C(O)-,-(SO ２ ) -, -SO ２ NR ８ -, -NR ８ SO ２ -, -NR ８ SO ２ NR ９ -, -S(O)(NR ８ Selected from the group consisting of ) Each R ８ , R ９ , R １０ These are H and C, which are independent of each other. １－６ Alkyl alkyl groups, halogenated C １－６ alkyl group, C ３－６ Cycloalkyl groups, C ６－１０ Selected from the group consisting of an aryl group, a 3-6 membered heterocyclic alkyl group containing 1-4 heteroatoms selected from N, O, or S, and a 5-6 membered heteroaryl group containing 1-4 heteroatoms selected from N, O, or S, where the C ３－６ Cycloalkyl groups, C ６－１０ Aryl groups, 3-6 membered heterocyclic alkyl groups, and 5-6 membered heteroaryl groups are composed of deuterium, halogens, =O, -CN, -OH, and -NH. ２ , C １－６ Alkyl alkyl groups, halogenated C １－６ alkyl group, C １－６ Alkoxy group, halogenated C １－６ C containing 1 to 4 heteroatoms selected from an alkoxy group, N, O, or S １－６ C halogenated with 1 to 4 heteroatoms selected from heteroalkyl groups, N, O, or S. １－６ It is optionally substituted by 0 to 6 substitutions selected from the group consisting of heteroalkyl groups. Or, R ８ and R ９ These, together with the heteroatoms to which they are bonded, form a 3-6 membered heterocyclic alkyl group containing 1-4 heteroatoms selected from N, O, or S. Or, R ９ and R １０ These, together with the heteroatoms to which they are bonded, form a 3-6 membered heterocyclic alkyl group containing 1-4 heteroatoms selected from N, O, or S. 【Chemistry 4】 These are single or double bonds, The compound is characterized in that each m, n, and q is independently selected from the group consisting of 0, 1, 2, 3, 4, and 5.

3. The aforementioned compound has a structure selected from the group consisting of the following: 【Transformation 5】 Here, X １ is N, O, C(R １１ ) ｑ Selected from the group consisting of, X ２ , X ３ Each is independently selected from the group consisting of N and C. Y １ , Y ２ , Y ３ , Y ４ These are, independently, O, C(R) ５ ) ２ _CHR ５ , C(=O), S(=O), S(=O) ２ NR ５ Selected from the group consisting of, Ring A is selected from the group consisting of a phenyl group and a 5-6 membered heteroaryl group containing 1 to 4 heteroatoms selected from N, O, or S, where the phenyl group and the 5-6 membered heteroaryl group have m R ６ It can be arbitrarily replaced by, R １ H, deuterium, halogen, -CN, C １－３ Alkyl alkyl groups, halogenated C １－３ Alkyl alkyl groups, deuterated C １－３ alkyl group, C １－３ Alkoxy group, halogenated C １－３ Selected from the group consisting of alkoxy groups, R ２ , R ３ , R １１ These are H, halogen, -CN, and C, respectively, independently. １－３ Alkyl alkyl groups, halogenated C １－３ Alkyl alkyl groups, deuterated C １－３ alkyl group, C １－３ Alkoxy group, halogenated C １－３ Alkoxy group, deuterated C １－３ Alkoxy group, C ３－５ Cycloalkyl groups, halogenated C ３－５ Selected from the group consisting of cycloalkyl groups, R ４ is -L-(C １－６ Alkyl), -L-phenyl group, -L-(5-6 membered heteroaryl containing 1-4 heteroatoms selected from N, O, or S), -L-(saturated or partially unsaturated C) ３－６ Selected from the group consisting of cycloalkyl, -L- (saturated or partially unsaturated 4-6 member heterocyclic alkyl containing 1-4 heteroatoms selected from N, O, or S), where the C １－６ Alkyl group, phenyl group, 5-6 membered heteroaryl group, C ３－６ Cycloalkyl groups, 4-6 member heterocyclic alkyl groups, have n R ７ It can be arbitrarily replaced by, Each R ５ H, deuterium, halogen, -CN, oxo (=O), C １－３ Alkyl alkyl groups, halogenated C １－３ Alkyl alkyl groups, deuterated C １－３ alkyl group, C １－３ Alkoxy group, halogenated C １－３ Alkoxy group, deuterated C １－３ Alkoxy group, C ３－５ Cycloalkyl groups, halogenated C ３－５ Independently selected from the group consisting of cycloalkyl groups, 3-5 heterocyclic alkyl groups containing 1 to 3 heteroatoms selected from N, O, or S, Each R ６ H, deuterium, halogen, -CN, -NO ２ , C １－６ Alkyl alkyl groups, halogenated C １－６ Alkyl alkyl groups, deuterated C １－３ alkyl group, C １－６ Alkoxy group, halogenated C １－６ Alkoxy group, -C(O)R ８ , -C(O)OR ８ , -C(O)NR ８ R ９ , -SO ２ R ８ , -S(O)(NR ８ ) R ９ , -SO ２ NR ８ R ９ ,-P(O)R ８ R ９ Independently selected from the group consisting of, Each R ７ These are hydrogen, deuterium, halogens, oxo (=O), -CN, -OH, and -NO. ２ , C １－６ alkyl group, C １－６ Alkoxy group, halogenated C １－６ Alkyl alkyl groups, halogenated C １－６ Alkoxy group, deuterated C １－６ C containing 1 to 4 heteroatoms selected from alkyl groups, N, O, or S １－６ C halogenated with 1 to 4 heteroatoms selected from heteroalkyl groups, N, O, or S. １－６ Heteroalkyl groups, -NR ８ R ９ , = NR ８ , -C(O)R ８ , -C(O)OR ８ , -C(O)NR ８ R ９ , -NR ８ C(O)R ９ , -SR ８ , -SO ２ R ８ , -NR ８ SO ２ R ９ , -SO ２ NR ８ R ９ , -NR ８ SO ２ NR ９ R １０ ,-P(O)R ８ R ９ , -L １ - (C １－６ Alkyl), -L １ - (Saturated or partially unsaturated C) ３－１０ Cycloalkyl), -L １ - (C ６－１０ Aryl), -L １ - (saturated or partially unsaturated 3-12 member heterocyclic alkyl group containing 1-4 heteroatoms selected from N, O, or S), -L １ - Independently selected from the group consisting of (5-10 membered heteroaryls containing 1-4 heteroatoms selected from N, O, or S), where C １－６ alkyl group, C １－６ Heteroalkyl groups, C ３－１０ Cycloalkyl groups, C ６－１０ Aryl groups, 3-10 membered heterocyclic alkyl groups, and 5-10 membered heteroaryl groups are composed of deuterium, halogens, =O, -CN, -OH, and -NH. ２ , C １－６ Alkyl alkyl groups, halogenated C １－６ alkyl group, C １－６ Alkoxy group, halogenated C １－６ Alkoxy group, C ３－６ Cycloalkyl groups, halogenated C ３－６ Cycloalkyl groups, 3-6 member heterocyclic alkyl groups containing 1-4 heteroatoms selected from N, O, or S, -SO ２ R ８ , -C(O)R ８ , -C(O)OR ８ , -C(O)NR ８ R ９ , -NR ８ R ９ It is arbitrarily replaced by 0 to 6 permutations selected from the group consisting of the following: Alternatively, two R's ７ Together with the atoms to which they are bonded, C ３－６ Cycloalkyl groups, C ６－１０ A 3-6 member heterocyclic alkyl group containing an aryl group, 1-4 heteroatoms selected from N, O, or S, or a 5-6 member heteroaryl group containing 1-4 heteroatoms selected from N, O, or S is formed, where the C ３－６ Cycloalkyl groups, C ６－１０ Aryl groups, 3-6 membered heterocyclic alkyl groups, and 5-6 membered heteroaryl groups are associated with deuterium, halogens, =O, -CN, -OH, and -NR ８ R ９ , = NR ８ , -C(O)R ８ , -C(O)OR ８ , -C(O)NR ８ R ９ , -NR ８ C(O)R ９ , -SR ８ , -SO ２ R ８ , -NR ８ SO ２ R ９ , -SO ２ NR ８ R ９ , -NR ８ SO ２ NR ９ R １０ ,-P(O)R ８ R ９ , C １－６ alkyl group, C １－６ C containing 1 to 4 heteroatoms selected from an alkoxy group, N, O, or S １－６ Heteroalkyl groups, halogenated C １－６ Alkyl alkyl groups, halogenated C １－６ C halogenated carbon containing alkoxy groups and 1 to 4 heteroatoms selected from N, O, or S １－６ Heteroalkyl groups, C ３－６ It is optionally substituted by 0 to 6 substitutions selected from the group consisting of cycloalkyl groups, 3 to 6-membered heterocyclic alkyl groups containing 1 to 4 heteroatoms selected from N, O, or S, L and L １ These are, independently, a combination, or C １－６ Alkylene group, 1-6 membered heteroalkylene group containing 1-4 heteroatoms selected from N, O, or S, -NR ８ -, -O-, -C(O)-, -C(O)NR ８ , -C(O)O-, -NR ８ C(O)-,-(SO ２ ) -, -SO ２ NR ８ -, -NR ８ SO ２ -, -NR ８ SO ２ NR ９ - Selected from the group consisting of, Each R ８ , R ９ , R １０ These are H and C, which are independent of each other. １－６ Alkyl alkyl groups, halogenated C １－６ alkyl group, C ３－６ Cycloalkyl groups, C ６－１０ Selected from the group consisting of an aryl group, a 3-6 membered heterocyclic alkyl group containing 1-4 heteroatoms selected from N, O, or S, and a 5-6 membered heteroaryl group containing 1-4 heteroatoms selected from N, O, or S, where the C ３－６ Cycloalkyl groups, C ６－１０ Aryl groups, 3-6 membered heterocyclic alkyl groups, and 5-6 membered heteroaryl groups are composed of deuterium, halogens, =O, -CN, -OH, and -NH. ２ , C １－６ Alkyl alkyl groups, halogenated C １－６ alkyl group, C １－６ Alkoxy group, halogenated C １－６ C containing 1 to 4 heteroatoms selected from an alkoxy group, N, O, or S １－６ C halogenated with 1 to 4 heteroatoms selected from heteroalkyl groups, N, O, or S. １－６ It is optionally substituted by 0 to 6 substitutions selected from the group consisting of heteroalkyl groups. Or, R ８ and R ９ These, together with the heteroatoms to which they are bonded, form a 3-6 membered heterocyclic alkyl group containing 1-4 heteroatoms selected from N, O, or S. Or, R ９ and R １０ These, together with the heteroatoms to which they are bonded, form a 3-6 membered heterocyclic alkyl group containing 1-4 heteroatoms selected from N, O, or S. 【Transformation 6】 These are single or double bonds, Each of m, n, and q is independently selected from 0, 1, 2, 3, 4, and 5. The compound described in claim 2, or a pharmaceutically acceptable salt, stereoisomer, deuteride, solvate, or prodrug thereof.

4. The aforementioned compound has a structure selected from the group consisting of the following: 【Transformation 7】 Here, R １ , R ２ , R ３ , R ４ , R １１ , Y １ , Y ２ , Y ３ , Y ４ Ring A is as defined in claim 1 or 2, structure 【Transformation 8】 teeth, 【Chemistry 9】 A feature that includes the arrangement of The compound described in claim 3, or a pharmaceutically acceptable salt, stereoisomer, deuteride, solvate, or prodrug thereof.

5. Ring A has a structure selected from the following group: 【Chemistry 10】 Here, each R ６ H, deuterium, halogen, -CN, -NO ２ , C １－６ Alkyl alkyl groups, halogenated C １－６ Alkyl alkyl groups, deuterated C １－３ alkyl group, C １－６ Alkoxy group, halogenated C １－６ Alkoxy group, -C(O)R ８ , -C(O)OR ８ , -C(O)NR ８ R ９ , -SO ２ R ８ , -S(O)(NR ８ ) R ９ , -SO ２ NR ８ R ９ ,-P(O)R ８ R ９ Independently selected from the group consisting of, Each R ８ , R ９ This is as defined in claim 1 or 2, m is selected from 0, 1, 2, 3, 4, 5. A compound according to claim 1 or 2, or a pharmaceutically acceptable salt, stereoisomer, deuteride, solvate, or prodrug thereof.

6. R ４ It has a structure selected from the following group: 【Chemistry 11】 Here, L and L １ These are, independently, a combination, or C １－６ Alkylene group, -C(O)-, -C(O)NH-, -C(O)O-, -(SO ２ ) -, -SO ２ Selected from the group consisting of NH-, Each R ７ These are hydrogen, deuterium, halogens, oxo (=O), -CN, -OH, and -NO. ２ , C １－６ alkyl group, C １－６ Alkoxy group, halogenated C １－６ Alkyl alkyl groups, halogenated C １－６ Alkoxy group, deuterated C １－６ C containing 1 to 4 heteroatoms selected from alkyl groups, N, O, or S １－６ C halogenated with 1 to 4 heteroatoms selected from heteroalkyl groups, N, O, or S. １－６ Heteroalkyl groups, -NR ８ R ９ , = NR ８ , -C(O)R ８ , -C(O)OR ８ , -C(O)NR ８ R ９ , -NR ８ C(O)R ９ , -SR ８ , -SO ２ R ８ , -NR ８ SO ２ R ９ , -SO ２ NR ８ R ９ , -NR ８ SO ２ NR ９ R １０ ,-P(O)R ８ R ９ , -L １ - (C １－６ Alkyl), -L １ - (Saturated or partially unsaturated C) ３－１０ Cycloalkyl), -L １ - (C ６－１０ Aryl), -L １ - (saturated or partially unsaturated 3-12 member heterocyclic alkyl group containing 1-4 heteroatoms selected from N, O, or S), -L １ - Independently selected from the group consisting of (5-10 membered heteroaryls containing 1-4 heteroatoms selected from N, O, or S), where C １－６ alkyl group, C １－６ Heteroalkyl groups, C ３－１０ Cycloalkyl groups, C ６－１０ Aryl groups, 3-12 membered heterocyclic alkyl groups, and 5-10 membered heteroaryl groups are composed of deuterium, halogens, =O, -CN, -OH, and -NH. ２ , C １－６ Alkyl alkyl groups, halogenated C １－６ alkyl group, C １－６ Alkoxy group, halogenated C １－６ Alkoxy group, C ３－６ Cycloalkyl groups, halogenated C ３－６ Cycloalkyl groups, 3-6 member heterocyclic alkyl groups containing 1-4 heteroatoms selected from N, O, or S, -SO ２ R ８ , -C(O)R ８ , -C(O)OR ８ , -C(O)NR ８ R ９ , -NR ８ R ９ It is arbitrarily replaced by 0 to 6 permutations selected from the group consisting of the following: Alternatively, two R's ７ Together with the atoms to which they are bonded, C ３－６ Cycloalkyl groups, C ６－１０ A 3-6 member heterocyclic alkyl group containing an aryl group, 1-4 heteroatoms selected from N, O, or S, or a 5-6 member heteroaryl group containing 1-4 heteroatoms selected from N, O, or S is formed, where the C ３－６ Cycloalkyl groups, C ６－１０ Aryl groups, 3-6 membered heterocyclic alkyl groups, and 5-6 membered heteroaryl groups are associated with deuterium, halogens, =O, -CN, -OH, and -NR ８ R ９ , = NR ８ , -C(O)R ８ , -C(O)OR ８ , -C(O)NR ８ R ９ , -NR ８ C(O)R ９ , -SR ８ , -SO ２ R ８ , -NR ８ SO ２ R ９ , -SO ２ NR ８ R ９ , -NR ８ SO ２ NR ９ R １０ ,-P(O)R ８ R ９ , C １－６ alkyl group, C １－６ C containing 1 to 4 heteroatoms selected from an alkoxy group, N, O, or S １－６ Heteroalkyl groups, halogenated C １－６ Alkyl alkyl groups, halogenated C １－６ C halogenated carbon containing alkoxy groups and 1 to 4 heteroatoms selected from N, O, or S １－６ Heteroalkyl groups, C ３－６ It is optionally substituted by 0 to 6 substitutions selected from the group consisting of cycloalkyl groups, 3 to 6-membered heterocyclic alkyl groups containing 1 to 4 heteroatoms selected from N, O, or S, Each R ８ , R ９ , R １０ This is as defined in claim 1 or 2, n is selected from the group consisting of 0, 1, 2, 3, 4, and 5. A compound according to claim 1 or 2, or a pharmaceutically acceptable salt, stereoisomer, deuteride, solvate, or prodrug thereof.

7. The aforementioned compound has a structure selected from the group consisting of the following: 【Chemistry 12】 Here, R １ , R ２ , R ３ , R ４ , Y １ , Y ２ , Y ３ This is as defined in claim 4, X ８ CR ６ or N, Each R ６ H, deuterium, halogen, -CN, -NO ２ , C １－６ Alkyl alkyl groups, halogenated C １－６ Alkyl alkyl groups, deuterated C １－３ alkyl group, C １－６ Alkoxy group, halogenated C １－６ Alkoxy group, -C(O)R ８ , -C(O)OR ８ , -C(O)NR ８ R ９ , -SO ２ R ８ , -S(O)(NR ８ ) R ９ , -SO ２ NR ８ R ９ ,-P(O)R ８ R ９ Independently selected from the group consisting of, m is characterized by being selected from the group consisting of 0, 1, 2, 3, and 4. The compound described in claim 3, or a pharmaceutically acceptable salt, stereoisomer, deuteride, solvate, or prodrug thereof.

8. The compound is characterized by being selected from the group consisting of the following, as described in claim 1 or 2, or a pharmaceutically acceptable salt, stereoisomer, deuteride, solvate, or prodrug thereof. 【Chemistry 13】 【Chemistry 14】 【Chemistry 15】 【Chemistry 16】 【Chemistry 17】 [Chemistry 18] 【Chemistry 19】 【Chemistry 20】 【Chemistry 21】 【Chemistry 22】 【Chemistry 23】 【Chemistry 24】 【Chemistry 25】 【Chemistry 26】 【Chemistry 27】 【Chemistry 28】 【Chemistry 29】 【Transformation 30】 【Chemistry 31】 【Chemistry 32】 【Transformation 33】 【Transformation 34】

9. A pharmaceutical composition comprising a safe and effective amount of the compound described in claim 1 or 2, or a pharmaceutically acceptable salt, stereoisomer, deuteride, solvate, or prodrug thereof, and a pharmaceutically acceptable carrier.

10. The use of the compound described in claim 1 or 2, or a pharmaceutically acceptable salt, stereoisomer, deuteride, solvate, or prodrug thereof, 1) Preparation of selective PI3Kα inhibitors, 2) Preparation of drugs for regulating PI3Kα activity or for treating PI3Kα-related diseases For applications selected from the group consisting of, Use of the compound described in claim 1 or 2, or a pharmaceutically acceptable salt, stereoisomer, deuteride, solvate, or prodrug thereof.

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