Yohimbine derivatives, processes for their preparation and use

Abstract

Yohimbine derivatives, methods of making and uses thereof. Disclosed are compounds of Formula I and pharmaceutical compositions comprising the compounds of Formula I. The compounds of Formula I of the present invention can be used to treat and / or prevent inflammatory bowel disease (IBD), particularly ulcerative colitis (UC), Crohn's disease (CD), or enteritis, as adrenergic receptor alpha 2A (ADRA2A) antagonists or partial antagonists.

Description

Technical Field

[0001] This invention relates to the field of medicinal chemistry. Specifically, this invention relates to yohimbine derivatives, pharmaceutical compositions comprising said derivatives, methods for preparing said derivatives, and the use of said derivatives or pharmaceutical compositions in the treatment and / or prevention of inflammatory bowel disease (IBD), preferably ulcerative colitis (UC), Crohn's disease (CD), and enteritis. Background Technology

[0002] The adrenergic system, composed of adrenaline and noradrenaline released by the sympathetic nervous system, regulates various physiological functions by acting on α and β adrenergic receptors (ARs). Recent studies have shown that adrenergic receptors are widely expressed in immune cells, including macrophages, monocytes, dendritic cells, T cells, and neutrophils, and their signaling pathways are closely related to the initiation, amplification, and regulation of inflammatory responses. Adrenergic receptors can be classified into subtypes such as α1, α2, β1, β2, and β3 based on their structure and signaling mechanisms. β receptors primarily activate the cAMP / PKA pathway, while α2 receptors mainly regulate adenylate cyclase activity through Gi proteins, and their downstream components can affect NF-κB, inflammasomes, and various key inflammatory factors.

[0003] Existing research indicates that adrenergic receptor antagonists can influence inflammatory responses in various inflammatory disease models by regulating immune cell activation, migration, and cytokine secretion. For example, β-receptor blockers (such as propranolol) can reduce inflammation levels and improve tissue damage under specific conditions in animal models of brain injury, ischemia-reperfusion, and post-traumatic systemic inflammation. Blockade or regulation of β2 receptors is also related to mechanisms such as changes in macrophage pro-inflammatory cytokine expression and regulation of NLRP3 inflammasome activation. Furthermore, α2 receptor-associated ligands have been reported to influence neutrophil migration, cytokine storms, and peripheral inflammation regulation. Overall, the role of adrenergic receptor antagonists in inflammation regulation is characterized by multi-target, subtype-dependent, and context-dependent effects.

[0004] Meanwhile, some clinical studies and registration trials have explored the role of β-blockers in acute stress, trauma, or systemic inflammatory responses in humans, suggesting their potential impact on inflammatory markers and immune activation. However, the adrenergic signaling pathway has a bidirectional regulatory effect on inflammation, and blocking β-receptors may exacerbate inflammatory responses in some animal models (Evans AK, et al. Beta-adrenergic receptor antagonism isproinflammatory and exacerbates pathology in some models. Neurobiology of Disease, 2020, 146, 105089. Maccari S, et al. Propranolol Promotes Monocyte-to-Macrophage Differentiation and Enhances Macrophage Anti-Inflammatory and Antioxidant Activities by NRF2 Activation. Int J Mol Sci, 2024, 25, 3683.). Therefore, current technologies still have shortcomings in terms of receptor subtype selectivity, dose dependence, controllability of immune effects, and safety.

[0005] Adrenaline receptor antagonists have shown potential application value as an anti-inflammatory mechanism in both basic and clinical research, but there is still a need to develop candidate compounds or treatment strategies with higher selectivity, clearer immunomodulatory mechanisms, and better safety to meet the needs of inflammatory disease treatment. Summary of the Invention

[0006] The purpose of this invention is to provide a yohimbine derivative, or a pharmaceutically acceptable salt, solvate, or prodrug thereof, which can be used as an adrenergic receptor α2A (ADRA2A) antagonist or partial antagonist.

[0007] Another object of the present invention is to provide a pharmaceutical composition comprising the yohimbine derivatives.

[0008] The present invention also aims to provide the use of the yohimbine derivatives, adrenergic receptor α2A (ADRA2A) antagonists or partial antagonists or pharmaceutical compositions in the treatment and / or prevention of inflammatory diseases, including but not limited to inflammatory bowel disease (IBD), preferably ulcerative colitis (UC), Crohn's disease (CD) or enteritis.

[0009] In a first aspect, the present invention provides compounds of Formula I, pharmaceutically acceptable salts thereof, solvates, or prodrugs thereof: (I) in, R 1 For non-existent, hydrogen, halogen, cyano, nitro, or optionally substituted groups: C 1-10 Straight-chain or branched alkyl groups, C 1-10 Straight-chain or branched alkoxy groups, C 3-10 Cycloalkyl, amino, amino C 1-6 Acyl, Ar 1 Ar 1 The aryl group is a 6- to 10-membered aryl group, a 5- to 10-membered heteroaryl group containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, or a 3- to 10-membered heterocyclic alkyl group containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, wherein "optional substitution" means optional substitution by one or more substituents selected from: halogen, cyano, C 1-6 Alkyl, hydroxyl C 1-6 Alkyl, Halogenated C 1-6 Alkyl, C 3-6 cycloalkyl, C 3-6 cycloalkyl C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, C containing 1, 2 or 3 heteroatoms independently selected from N, O or S. 1-6 Heteroalkyl groups, 3- to 6-membered heterocyclic groups containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, and 3- to 6-membered heterocyclic groups containing 1, 2, or 3 heteroatoms independently selected from N, O, or S. 1-6 Alkyl, 6- to 8-membered aryl, 6- to 8-membered aryl C 1-6 Alkyl group, containing 1, 2 or 3 independently selected from N, O or S, 6 to 8-membered heteroaryl group, C containing 1, 2 or 3 independently selected from N, O or S 1-6 Alkyl, hydroxyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 3-6 Cycloalkyloxy, 3- to 6-membered heterocyclic alkyloxy containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 6- to 8-membered aryloxy, amino, C 1-6 Alkylamino, amino C 1-6 Alkyl, C 1-6 Carboxyl group, C 1-6 alkoxycarbonyl, C 3-6Cycloalkyloxycarbonyl, 3- to 6-membered heterocyclic oxycarbonyl containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 6- to 8-membered aryloxycarbonyl, 6- to 8-membered heteroaryloxycarbonyl containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, C 1-6 alkyl carbonyloxy group, C 3-6 Cycloalkyl carbonyloxy group, 3- to 6-membered heterocyclic carbonyloxy group containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 6- to 8-membered aryl carbonyloxy group, 6- to 8-membered heteroaryl carbonyloxy group containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 6- to 8-membered aryl C 1-6 Alkoxy, C 1-6 Alkyl carbonyl amino, halogenated C 1-6 Alkyl carbonyl amino, C 3-6 Cycloalkylcarbonylamino, 3- to 6-membered heterocyclic carbonylamino containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 6- to 8-membered arylcarbonylamino, 6- to 8-membered heteroarylcarbonylamino containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, C 1-6 alkyl carbonyl amino C 1-6 Alkyl, amino C 1-3 Acyl, hydroxyl amino C 1-3 Acyl group, C 1-6 Alkylamino C 1-3 Acyl, 6- to 8-membered arylamino C 1-3 Acyl group, 6- to 8-membered heteroarylamino group containing 1, 2, or 3 heteroatoms independently selected from N, O, or S. 1-3 Acyl, amino C 1-3 Acyl C 1-6 Alkyl, amino C 1-3 Acylamino, C 1-6 Alkylamino C 1-3 Acylamino, C 1-6 Alkyl sulfonyl, halogenated C 1-6 alkylsulfonyl, C 3-6 Cycloalkylsulfonyl, 3- to 6-membered heterocyclic sulfonyl groups containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 6- to 8-membered arylsulfonyl groups, 6- to 8-membered heteroarylsulfonyl groups containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, aminosulfonyl, C 1-6 Alkylaminosulfonyl, 6- to 8-membered arylaminosulfonyl, 6- to 8-membered heteroarylaminosulfonyl containing 1, 2 or 3 heteroatoms independently selected from N, O or S, C 1-6 alkylsulfonylamino, C 3-6 Cycloalkylsulfonylamino, 3- to 6-membered heterocyclic sulfonylamino containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 6- to 8-membered arylsulfonylamino, 6- to 8-membered heteroarylsulfonylamino containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, halogenated C1-6 Alkylsulfonylamino, Alternatively, the two substituents may form an alkylene dioxy or a haloalkylene dioxy; or, the two substituents and the cycloalkyl or heterocycloalkyl group attached thereto may form a cycloalkyl or heterocycloalkyl moiety; or, the substituents may further fuse with an aryl, heteroaryl, cycloalkyl, or heterocycloalkyl group to form one or more fused cycloalkyl, aryl, heterocycloalkyl, or heteroaryl structural units. Each of the above substituents may optionally be substituted by one or more additional substituents selected from: halogen, cyano, C 1-6 Alkyl, hydroxyl C 1-6 Alkyl, Halogenated C 1-6 Alkyl, C 3-6 cycloalkyl, C 3-6 cycloalkyl C 1-3 Alkyl groups, C containing one, two, or three heteroatoms independently selected from N, O, or S. 1-6 heteroalkyl, hydroxyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 3-6 Cycloalkoxy, C 1-6 Alkylamino, C 1-6 Carboxyl group, C 1-6 Alkoxy C 1-6 carbonyl group, C 1-6 alkyl carbonyloxy group, C 3-6 Cycloalkylcarbonyloxy, C 1-6 Alkyl carbonyl amino, halogenated C 1-6 Alkyl carbonyl amino, C 3-6 cycloalkylcarbonylamino, C 1-6 alkyl carbonyl amino C 1-6 Alkyl, amino C 1-6 Acyl, hydroxyl amino C 1-6 Acyl group, C 1-6 Alkylamino C 1-6 Acyl, amino C 1-6 Acyl C 1-6 Alkyl, amino C 1-6 Acylamino, C 1-6 Alkylamino C 1-6 Acylamino, C 1-6 Alkyl sulfonyl, halogenated C 1-6 alkylsulfonyl, C 3-6 Cycloalkylsulfonyl, aminosulfonyl, C 1-6 Alkylaminosulfonyl, C 1-6 alkylsulfonylamino, C 3-6 Cycloalkylsulfonylamino, halogenated C 1-6 Alkylsulfonylamino or oxo; L 1For non-existent, single-bond, or arbitrarily substituted C 1-3 Alkylene, optionally substituted C 2-3 alkenyl, optionally substituted C 2-3 Ethyne group, optionally substituted C 3-6 Cycloalkylene, wherein the optional substitution refers to optional substitution by one or more substituents selected from: halogen, C 1-6 Alkyl, Halogenated C 1-6 Alkyl, hydroxyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, hydroxy C 1-6 Alkyl, C 1-6 Alkoxy C 1-6 alkyl; A 1 and A 2 Each can be represented independently as: non-existent, O, S, NR a1 , , , , , , Where R a1 and R a2 Each of the following groups is independently hydrogen, and can be optionally substituted: C 1-10 Straight-chain or branched alkyl groups, C 3-10 cycloalkyl, Ar a Ar a It is a 5- to 6-membered aryl group, containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, and a 3- to 8-membered heterocyclic alkyl group containing 1, 2, or 3 heteroatoms independently selected from N, O, or S. The optional substitution refers to optional substitution by one or more substituents selected from: halogen, cyano, C. 1-6 Alkyl, hydroxyl C 1-6 Alkyl, Halogenated C 1-6 Alkyl, C 3-6 cycloalkyl, C 3-6 cycloalkyl C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, C containing 1, 2 or 3 heteroatoms independently selected from N, O or S. 1-6 Heteroalkyl groups, 3- to 8-membered heterocyclic groups containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, and 3- to 8-membered heterocyclic groups containing 1, 2, or 3 heteroatoms independently selected from N, O, or S. 1-6 Alkyl, 5- to 6-membered aryl, 5- to 6-membered aryl C 1-6 Alkyl group, 5- to 6-membered heteroaryl group containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 5- to 6-membered heteroaryl group containing 1, 2, or 3 heteroatoms independently selected from N, O, or S C1-6 Alkyl, hydroxyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 3-6 Cycloalkoxy, 3- to 8-membered heterocyclic alkyl groups containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 5- to 6-membered aryloxy, amino, C 1-6 Alkylamino, amino C 1-6 Alkyl, C 1-6 Carboxyl group, C 1-6 alkoxycarbonyl, C 3-6 Cycloalkoxycarbonyl, 3- to 8-membered heterocyclic cycloalkoxycarbonyl containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 5- to 6-membered aryloxycarbonyl, 5- to 6-membered heteroaryloxycarbonyl containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, C 1-6 Alkyl carbonyloxy, C 3-6 Cycloalkyl carbonyloxy group, 3- to 8-membered heterocyclic carbonyloxy group containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 5- to 6-membered aryl carbonyloxy group, 5- to 6-membered heteroaryl carbonyloxy group containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 5- to 6-membered aryl C 1-6 Alkoxy, C 1-6 Alkyl carbonyl amino, halogenated C 1-6 Alkyl carbonyl amino, C 3-6 Cycloalkylcarbonylamino, 3- to 8-membered heterocyclic carbonylamino containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 5- to 6-membered arylcarbonylamino, 5- to 6-membered heteroarylcarbonylamino containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, C 1-6 alkyl carbonyl amino C 1-6 Alkyl, amino C 1-6 Acyl, hydroxyl amino C 1-6 Acyl group, C 1-6 Alkylamino C 1-6 Acyl, 5- to 6-membered arylamino C 1-6 Acyl group, 5- to 6-membered heteroarylamino group containing 1, 2, or 3 heteroatoms independently selected from N, O, or S. 1-6 Acyl, amino C 1-6 Acyl C 1-6 Alkyl, amino C 1-6 Acylamino, C 1-6 Alkylamino C 1-6 Acylamino, C 1-6 Alkyl sulfonyl, halogenated C 1-6 alkylsulfonyl, C 3-6Cycloalkylsulfonyl, 3- to 8-membered heterocyclic sulfonyl groups containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 5- to 6-membered arylsulfonyl groups, 5- to 6-membered heteroarylsulfonyl groups containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, aminosulfonyl, C 1-6 Alkylaminosulfonyl, 5- to 6-membered arylaminosulfonyl, 5- to 6-membered heteroarylaminosulfonyl containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, C 1-6 alkylsulfonylamino, C 3-6 Cycloalkylsulfonylamino, 3- to 8-membered heterocyclic sulfonylamino containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 5- to 6-membered arylsulfonylamino, 5- to 6-membered heteroarylsulfonylamino containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, halogenated C 1-6 Alkylsulfonylamino, Alternatively, two of the above substituents may form an alkylene dioxy or a haloalkylene dioxy, or two of the above substituents and the cycloalkyl or heterocycloalkyl group attached thereto may together form a cycloalkyl or heterocycloalkyl moiety, or the above substituents may further fuse with an aryl, heteroaryl, cycloalkyl or heterocycloalkyl group to form one or more fused cycloalkyl, aryl, heterocycloalkyl or heteroaryl structural units. Each of the above substituents may optionally be substituted by one or more additional substituents selected from: halogen, cyano, C 1-6 Alkyl, hydroxyl C 1-6 Alkyl, Halogenated C 1-6 Alkyl, C 3-6 cycloalkyl, C 3-6 cycloalkyl C 1-6 Alkyl groups, C containing one, two, or three heteroatoms independently selected from N, O, or S. 1-6 heteroalkyl, hydroxyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 3-6 Cycloalkoxy, C 1-6 Alkylamino, C 1-6 Carboxyl group, C 1-6 alkoxycarbonyl, C 1-6 Alkyl carbonyloxy, C 3-6 Cycloalkylcarbonyloxy, C 1-6 Alkyl carbonyl amino, halogenated C 1-6 Alkyl carbonyl amino, C 3-6 cycloalkylcarbonylamino, C 1-6 alkyl carbonyl amino C 1-6 Alkyl, amino C 1-6 Acyl, hydroxyl amino C 1-6 Acyl group, C 1-6 Alkylamino C 1-6 Acyl, amino C 1-6 Acyl C1-6 Alkyl, amino C 1-6 Acylamino, C 1-6 Alkylamino C 1-6 Acylamino, C 1-6 Alkyl sulfonyl, halogenated C 1-6 alkylsulfonyl, C 3-6 Cycloalkylsulfonyl, aminosulfonyl, C 1-6 Alkylaminosulfonyl, C 1-6 alkylsulfonylamino, C 3-6 Cycloalkylsulfonylamino, halogenated C 1-6 Alkylsulfonylamino or oxo; R 2 For non-existent, hydrogen, halogen, cyano, nitro, or optionally substituted groups: C 1-10 Straight-chain or branched alkyl groups, C 1-10 Straight-chain or branched alkoxy groups, C 3-10 Cycloalkyl, amino, amino C 1-6 Acyl group, Ar 2 Ar 2 The aryl group is 6 to 10-membered aryl, 5 to 10-membered heteroaryl containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, or 3 to 10-membered heterocyclic alkyl containing 1, 2, or 3 heteroatoms independently selected from N, O, or S. The term "optional substitution" means optional substitution by one or more substituents selected from: halogen, cyano, C. 1-6 Alkyl, hydroxyl C 1-6 Alkyl, Halogenated C 1-6 Alkyl, C 3-6 cycloalkyl, C 3-6 cycloalkyl C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, C containing 1, 2 or 3 heteroatoms independently selected from N, O or S. 1-6 Heteroalkyl groups, 3- to 6-membered heterocyclic groups containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, and 3- to 6-membered heterocyclic groups containing 1, 2, or 3 heteroatoms independently selected from N, O, or S. 1-6 Alkyl, 6- to 8-membered aryl, 6- to 8-membered aryl C 1-6 Alkyl group, containing 1, 2 or 3 independently selected from N, O or S, 6 to 8-membered heteroaryl group, C containing 1, 2 or 3 independently selected from N, O or S 1-6 Alkyl, hydroxyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 3-6 Cycloalkyloxy, 3- to 6-membered heterocyclic alkyloxy containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 6- to 8-membered aryloxy, amino, C 1-6 Alkylamino, amino C1-6 Alkyl, C 1-6 Carboxyl group, C 1-6 alkoxycarbonyl, C 3-6 Cycloalkyloxycarbonyl, 3- to 6-membered heterocyclic oxycarbonyl containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 6- to 8-membered aryloxycarbonyl, 6- to 8-membered heteroaryloxycarbonyl containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, C 1-6 Alkyl carbonyloxy, C 3-6 Cycloalkyl carbonyloxy group, 3- to 6-membered heterocyclic carbonyloxy group containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 6- to 8-membered aryl carbonyloxy group, 6- to 8-membered heteroaryl carbonyloxy group containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 6- to 8-membered aryl C 1-6 Alkoxy, C 1-6 Alkyl carbonyl amino, halogenated C 1-6 Alkyl carbonyl amino, C 3-6 Cycloalkylcarbonylamino, 3- to 6-membered heterocyclic carbonylamino containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 6- to 8-membered arylcarbonylamino, 6- to 8-membered heteroarylcarbonylamino containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, C 1-6 alkyl carbonyl amino C 1-6 Alkyl, amino C 1-3 Acyl, hydroxyl amino C 1-3 Acyl group, C 1-6 Alkylamino C 1-3 Acyl, 6- to 8-membered arylamino C 1-3 Acyl group, 6- to 8-membered heteroarylamino group containing 1, 2, or 3 heteroatoms independently selected from N, O, or S. 1-3 Acyl, amino C 1-3 Acyl C 1-6 Alkyl, amino C 1-3 Acylamino, C 1-6 Alkylamino C 1-3 Acylamino, C 1-6 Alkyl sulfonyl, halogenated C 1-6 alkylsulfonyl, C 3-6 Cycloalkylsulfonyl, 3- to 6-membered heterocyclic sulfonyl groups containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 6- to 8-membered arylsulfonyl groups, 6- to 8-membered heteroarylsulfonyl groups containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, aminosulfonyl, C 1-6 Alkylaminosulfonyl, 6- to 8-membered arylaminosulfonyl, 6- to 8-membered heteroarylaminosulfonyl containing 1, 2 or 3 heteroatoms independently selected from N, O or S, C 1-6 alkylsulfonylamino, C 3-6Cycloalkylsulfonylamino, 3- to 6-membered heterocyclic sulfonylamino containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 6- to 8-membered arylsulfonylamino, 6- to 8-membered heteroarylsulfonylamino containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, halogenated C 1-6 Alkylsulfonylamino, Alternatively, the two substituents may form an alkylene dioxy or a haloalkylene dioxy; or, the two substituents and the cycloalkyl or heterocycloalkyl group attached thereto may form a cycloalkyl or heterocycloalkyl moiety; or, the substituents may further fuse with an aryl, heteroaryl, cycloalkyl, or heterocycloalkyl group to form one or more fused cycloalkyl, aryl, heterocycloalkyl, or heteroaryl structural units. Each of the above substituents may optionally be substituted by one or more additional substituents selected from: halogen, cyano, C 1-6 Alkyl, hydroxyl C 1-6 Alkyl, Halogenated C 1-6 Alkyl, C 3-6 cycloalkyl, C 3-6 cycloalkyl C 1-3 Alkyl groups, C containing one, two, or three heteroatoms independently selected from N, O, or S. 1-6 heteroalkyl, hydroxyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 3-6 Cycloalkoxy, C 1-6 Alkylamino, C 1-6 Carboxyl group, C 1-6 Alkoxy C 1-6 carbonyl group, C 1-6 Alkyl carbonyloxy, C 3-6 Cycloalkylcarbonyloxy, C 1-6 Alkyl carbonyl amino, halogenated C 1-6 Alkyl carbonyl amino, C 3-6 cycloalkylcarbonylamino, C 1-6 alkyl carbonyl amino C 1-6 Alkyl, amino C 1-6 Acyl, hydroxyl amino C 1-6 Acyl group, C 1-6 Alkylamino C 1-6 Acyl, amino C 1-6 Acyl C 1-6 Alkyl, amino C 1-6 Acylamino, C 1-6 Alkylamino C 1-6 Acylamino, C 1-6 Alkyl sulfonyl, halogenated C 1-6 alkylsulfonyl, C 3-6 Cycloalkylsulfonyl, aminosulfonyl, C 1-6 Alkylaminosulfonyl, C 1-6alkylsulfonylamino, C 3-6 Cycloalkylsulfonylamino, halogenated C 1-6 Alkylsulfonylamino or oxo; L 2 For non-existent, single-bond, or optional substitution C 1-3 Alkylene, optionally substituted C 2-3 alkenyl, optionally substituted C 2-3 Ethyne group, optionally substituted C 3-6 Cycloalkylene, wherein the optional substitution refers to optional substitution by one or more substituents selected from: halogen, C 1-6 Alkyl, Halogenated C 1-6 Alkyl, hydroxyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, hydroxy C 1-6 Alkyl, C 1-6 Alkoxy C 1-6 alkyl; B 1 and B 2 Each can be categorized independently as: non-existent, O, S, NR b1 , , , , , , , where R b1 and R b2 Each of the following groups is independently hydrogen, and can be optionally substituted: C 1-10 Straight-chain or branched alkyl groups, C 3-10 cycloalkyl, Ar b Ar b It is a 5- to 6-membered aryl group, containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, and a 3- to 8-membered heterocyclic alkyl group containing 1, 2, or 3 heteroatoms independently selected from N, O, or S. The optional substitution refers to optional substitution by one or more substituents selected from: halogen, cyano, C. 1-6 Alkyl, hydroxyl C 1-6 Alkyl, Halogenated C 1-6 Alkyl, C 3-6 cycloalkyl, C 3-6 cycloalkyl C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, C containing 1, 2 or 3 heteroatoms independently selected from N, O or S. 1-6 Heteroalkyl groups, 3- to 8-membered heterocyclic groups containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, and 3- to 8-membered heterocyclic groups containing 1, 2, or 3 heteroatoms independently selected from N, O, or S. 1-6Alkyl, 5- to 6-membered aryl, 5- to 6-membered aryl C 1-6 Alkyl group, 5- to 6-membered heteroaryl group containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 5- to 6-membered heteroaryl group containing 1, 2, or 3 heteroatoms independently selected from N, O, or S C 1-6 Alkyl, hydroxyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 3-6 Cycloalkoxy, 3- to 8-membered heterocyclic alkyl groups containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 5- to 6-membered aryloxy, amino, C 1-6 Alkylamino, amino C 1-6 Alkyl, C 1-6 Carboxyl group, C 1-6 alkoxycarbonyl, C 3-6 Cycloalkoxycarbonyl, 3- to 8-membered heterocyclic cycloalkoxycarbonyl containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 5- to 6-membered aryloxycarbonyl, 5- to 6-membered heteroaryloxycarbonyl containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, C 1-6 alkyl carbonyloxy group, C 3-6 Cycloalkyl carbonyloxy group, 3- to 8-membered heterocyclic carbonyloxy group containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 5- to 6-membered aryl carbonyloxy group, 5- to 6-membered heteroaryl carbonyloxy group containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 5- to 6-membered aryl C 1-6 Alkoxy, C 1-6 Alkyl carbonyl amino, halogenated C 1-6 Alkyl carbonyl amino, C 3-6 Cycloalkylcarbonylamino, 3- to 8-membered heterocyclic carbonylamino containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 5- to 6-membered arylcarbonylamino, 5- to 6-membered heteroarylcarbonylamino containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, C 1-6 alkyl carbonyl amino C 1-6 Alkyl, amino C 1-6 Acyl, hydroxyl amino C 1-6 Acyl group, C 1-6 Alkylamino C 1-6 Acyl, 5- to 6-membered arylamino C 1-6 Acyl group, 5- to 6-membered heteroarylamino group containing 1, 2, or 3 heteroatoms independently selected from N, O, or S. 1-6 Acyl, amino C 1-6 Acyl C 1-6 Alkyl, amino C 1-6 Acylamino, C 1-6 Alkylamino C 1-6 Acylamino, C 1-6 Alkyl sulfonyl, halogenated C 1-6 alkylsulfonyl, C3-6 Cycloalkylsulfonyl, 3- to 8-membered heterocyclic sulfonyl groups containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 5- to 6-membered arylsulfonyl groups, 5- to 6-membered heteroarylsulfonyl groups containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, aminosulfonyl, C 1-6 Alkylaminosulfonyl, 5- to 6-membered arylaminosulfonyl, 5- to 6-membered heteroarylaminosulfonyl containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, C 1-6 alkylsulfonylamino, C 3-6 Cycloalkylsulfonylamino, 3- to 8-membered heterocyclic sulfonylamino containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 5- to 6-membered arylsulfonylamino, 5- to 6-membered heteroarylsulfonylamino containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, halogenated C 1-6 Alkylsulfonylamino, Alternatively, two of the above substituents may form an alkylene dioxy or a haloalkylene dioxy, or two of the above substituents and the cycloalkyl or heterocycloalkyl group attached thereto may together form a cycloalkyl or heterocycloalkyl moiety, or the above substituents may further fuse with an aryl, heteroaryl, cycloalkyl or heterocycloalkyl group to form one or more fused cycloalkyl, aryl, heterocycloalkyl or heteroaryl structural units. Each of the above substituents may optionally be substituted by one or more additional substituents selected from: halogen, cyano, C 1-6 Alkyl, hydroxyl C 1-6 Alkyl, Halogenated C 1-6 Alkyl, C 3-6 cycloalkyl, C 3-6 cycloalkyl C 1-6 Alkyl groups, C containing one, two, or three heteroatoms independently selected from N, O, or S. 1-6 heteroalkyl, hydroxyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 3-6 Cycloalkoxy, C 1-6 Alkylamino, C 1-6 Carboxyl group, C 1-6 alkoxycarbonyl, C 1-6 alkyl carbonyloxy group, C 3-6 Cycloalkylcarbonyloxy, C 1-6 Alkyl carbonyl amino, halogenated C 1-6 Alkyl carbonyl amino, C 3-6 cycloalkylcarbonylamino, C 1-6 alkyl carbonyl amino C 1-6 Alkyl, amino C 1-6 Acyl, hydroxyl amino C 1-6 Acyl group, C 1-6 Alkylamino C 1-6 Acyl, amino C1-6 Acyl C 1-6 Alkyl, amino C 1-6 Acylamino, C 1-6 Alkylamino C 1-6 Acylamino, C 1-6 Alkyl sulfonyl, halogenated C 1-6 alkylsulfonyl, C 3-6 Cycloalkylsulfonyl, aminosulfonyl, C 1-6 Alkylaminosulfonyl, C 1-6 alkylsulfonylamino, C 3-6 Cycloalkylsulfonylamino, halogenated C 1-6 Alkylsulfonylamino or oxo; R 3 It is hydrogen, or optionally substituted with the following groups: C 1-10 Straight-chain or branched alkyl groups, C 3-10 cycloalkyl, C 1-6 Acyl, Ar 3 Ar 3 It is a 5- to 6-membered aryl group, a 5- to 6-membered heteroaryl group containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, or a 3- to 8-membered heterocyclic alkyl group containing 1, 2, or 3 heteroatoms independently selected from N, O, or S. The term "optional substitution" means optional substitution by one or more substituents selected from: halogen, cyano, C. 1-6 Alkyl, hydroxyl C 1-6 Alkyl, Halogenated C 1-6 Alkyl, C 3-6 cycloalkyl, C 3-6 cycloalkyl C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, C containing 1, 2 or 3 heteroatoms independently selected from N, O or S. 1-6 Heteroalkyl groups, 3- to 6-membered heterocyclic groups containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, and 3- to 6-membered heterocyclic groups containing 1, 2, or 3 heteroatoms independently selected from N, O, or S. 1-6 Alkyl, 6- to 8-membered aryl, 6- to 8-membered aryl C 1-6 Alkyl group, containing 1, 2 or 3 independently selected from N, O or S, 6 to 8-membered heteroaryl group, C containing 1, 2 or 3 independently selected from N, O or S 1-6 Alkyl, hydroxyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 3-6 Cycloalkoxy, 3- to 6-membered heterocyclic hydroxyl groups containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 6- to 8-membered aryloxy, amino, C 1-6 Alkylamino, amino C 1-6 Alkyl, C 1-6 Carboxyl group, C1-6 alkoxycarbonyl, C 3-6 Cycloalkoxycarbonyl, heterocyclic oxycarbonyl containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 6- to 8-membered aryloxycarbonyl, 6- to 8-membered heteroaryloxycarbonyl containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, C 1-6 alkyl carbonyloxy group, C 3-6 Cycloalkyl carbonyloxy group, 3- to 6-membered heterocyclic carbonyloxy group containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 6- to 8-membered aryl carbonyloxy group, 6- to 8-membered heteroaryl carbonyloxy group containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 6- to 8-membered aryl C 1-6 Alkoxy, C 1-6 Alkyl carbonyl amino, halogenated C 1-6 Alkyl carbonyl amino, C 3-6 Cycloalkylcarbonylamino, 3- to 6-membered heterocyclic carbonylamino containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 6- to 8-membered arylcarbonylamino, 6- to 8-membered heteroarylcarbonylamino containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, C 1-6 alkyl carbonyl amino C 1-6 Alkyl, amino C 1-3 Acyl, hydroxyl amino C 1-3 Acyl group, C 1-6 Alkylamino C 1-3 Acyl, 6- to 8-membered arylamino C 1-3 Acyl group, 6- to 8-membered heteroarylamino group containing 1, 2, or 3 heteroatoms independently selected from N, O, or S. 1-3 Acyl, amino C 1-3 Acyl C 1-6 Alkyl, amino C 1-3 Acylamino, C 1-6 Alkylamino C 1-3 Acylamino, C 1-6 Alkyl sulfonyl, halogenated C 1-6 alkylsulfonyl, C 3-6 Cycloalkylsulfonyl, 3- to 6-membered heterocyclic sulfonyl groups containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 6- to 8-membered arylsulfonyl groups, 6- to 8-membered heteroarylsulfonyl groups containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, aminosulfonyl, C 1-6 Alkylaminosulfonyl, 6- to 8-membered arylaminosulfonyl, 6- to 8-membered heteroarylaminosulfonyl containing 1, 2 or 3 heteroatoms independently selected from N, O or S, C 1-6 alkylsulfonylamino, C 3-6Cycloalkylsulfonylamino, 3- to 6-membered heterocyclic sulfonylamino containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 6- to 8-membered arylsulfonylamino, 6- to 8-membered heteroarylsulfonylamino containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, halogenated C 1-6 Alkylsulfonylamino, Alternatively, the two substituents may form an alkylene dioxy or a haloalkylene dioxy; or, the two substituents and the cycloalkyl or heterocycloalkyl group attached thereto may form a cycloalkyl or heterocycloalkyl moiety; or, the substituents may further fuse with an aryl, heteroaryl, cycloalkyl, or heterocycloalkyl group to form one or more fused cycloalkyl, aryl, heterocycloalkyl, or heteroaryl structural units. Each of the above substituents may optionally be substituted by one or more additional substituents selected from: halogen, cyano, C 1-6 Alkyl, hydroxyl C 1-6 Alkyl, Halogenated C 1-6 Alkyl, C 3-6 cycloalkyl, C 3-6 cycloalkyl C 1-6 Alkyl groups, C containing one, two, or three heteroatoms independently selected from N, O, or S. 1-6 heteroalkyl, hydroxyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 3-6 Cycloalkoxy, C 1-6 Alkylamino, C 1-6 Carboxyl group, C 1-6 alkoxycarbonyl, C 1-6 Alkyl carbonyloxy, C 3-6 Cycloalkylcarbonyloxy, C 1-6 Alkyl carbonyl amino, halogenated C 1-6 Alkyl carbonyl amino, C 3-6 cycloalkylcarbonylamino, C 1-6 alkyl carbonyl amino C 1-6 Alkyl, amino C 1-3 Acyl, hydroxyl amino C 1-3 Acyl group, C 1-6 Alkylamino C 1-3 Acyl, amino C 1-3 Acyl C 1-6 Alkyl, amino C 1-3 Acylamino, C 1-6 Alkylamino C 1-3 Acylamino, C 1-6 Alkyl sulfonyl, halogenated C 1-6 alkylsulfonyl, C 3-6 Cycloalkylsulfonyl, aminosulfonyl, C 1-6 Alkylaminosulfonyl, C 1-6 alkylsulfonylamino, C3-6 Cycloalkylsulfonylamino, halogenated C 1-6 Alkylsulfonylamino or oxo; Or it could be a group like the one shown below: , , , , Where R 3a R 3b Each group is hydrogen, and the following groups may be optionally substituted: C 1-10 Straight-chain or branched alkyl groups, C 3-10 cycloalkyl, Ar 3a Ar 3a It is a 5- to 6-membered aryl group, containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, and a 3- to 8-membered heterocyclic alkyl group containing 1, 2, or 3 heteroatoms independently selected from N, O, or S. The optional substitution refers to optional substitution by one or more substituents selected from: halogen, cyano, C. 1-6 Alkyl, hydroxyl C 1-6 Alkyl, Halogenated C 1-6 Alkyl, C 3-6 cycloalkyl, C 3-6 cycloalkyl C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 alkynyl group, C 1-6 Heteroalkyl, heterocyclic, heterocyclic C 1-6 Alkyl, aryl, aralkyl, heteroaryl, heteroaryl C 1-6 Alkyl, hydroxyl, C 1-6 Alkoxy, halogenated C 1-6 Alkyloxy, cycloalkoxy, heterocyclic alkoxy, aryloxy, amino, C 1-6 Alkylamino, amino C 1-6 Alkyl, C 1-6 Carboxyl group, C 1-6 Alkoxycarbonyl, cycloalkoxycarbonyl, heterocyclic carbonyl, aryloxycarbonyl, heteroaryloxycarbonyl, C 1-6 Alkyl carbonyloxy, C 3-6 Cycloalkyl carbonyloxy, heterocyclic carbonyloxy, aryl carbonyloxy, heteroaryl carbonyloxy, aryl C 1-6 Alkoxy, C 1-6 Alkyl carbonyl amino, halogenated C 1-6 Alkyl carbonyl amino, C 3-6 Cycloalkylcarbonylamino, heterocyclic carbonylamino, arylcarbonylamino, heteroarylcarbonylamino, C 1-6 alkyl carbonyl amino alkyl, amino C 1-3 Acyl, hydroxyl amino C 1-3 Acyl, alkylamino C 1-3Acyl, arylamino C 1-3 Acyl, heteroarylamino C 1-3 Acyl, amino C 1-3 Acyl C 1-6 Alkyl, amino C 1-3 Acylamino, C 1-6 Alkylamino C 1-3 Acylamino, C 1-6 Alkyl sulfonyl, halogenated C 1-6 alkylsulfonyl, C 3-6 Cycloalkylsulfonyl, heterocyclic sulfonyl, arylsulfonyl, heteroarylsulfonyl, aminosulfonyl, C 1-6 Alkylaminosulfonyl, arylaminosulfonyl, heteroarylaminosulfonyl, C 1-6 alkylsulfonylamino, C 3-6 Cycloalkylsulfonylamino, heterocyclic sulfonylamino, arylsulfonylamino, heteroarylsulfonylamino, halogenated C 1-6 Alkylsulfonylamino, Alternatively, two substituents may form an alkylene dioxy or a haloalkylene dioxy, or two substituents together with the cycloalkyl or heterocycloalkyl group attached thereto may form a cycloalkyl or heterocycloalkyl moiety, or the fused to an aryl, heteroaryl, cycloalkyl, or heterocycloalkyl group may be one or more cycloalkyl, aryl, heterocycloalkyl, or heteroaryl moiety, each of which may optionally be substituted by one or more additional substituents selected from: halogen, cyano, alkyl, hydroxyalkyl, haloalkyl, cycloalkyl, cycloalkylalkyl, heteroalkyl, hydroxy, alkoxy, haloalkoxy, cycloalkoxy, alkylamino, C 1-6 Carboxyl, alkoxycarbonyl, alkylcarbonyloxy, cycloalkylcarbonyloxy, alkylcarbonylamino, haloalkylcarbonylamino, cycloalkylcarbonylamino, alkylcarbonylaminoalkyl, carbamoyl, hydroxycarbamoyl, alkylcarbamoyl, carbamoylalkyl, carbamoylamino, alkylcarbamoylamino, alkylsulfonyl, haloalkylsulfonyl, cycloalkylsulfonyl, aminosulfonyl, alkylaminosulfonyl, alkylsulfonylamino, cycloalkylsulfonylamino, haloalkylsulfonylamino or oxo; R 4 It is hydrogen, halogen, or optionally substituted with the following groups: C 1-10 Straight-chain or branched alkyl groups, C 3-10 cycloalkyl, C 1-10 alkoxy, amino, or Ar 4 Ar 4 The aryl group is 5 to 10-membered aryl, a 5 to 10-membered heteroaryl group containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, or a 3 to 8-membered heterocyclic alkyl group containing 1, 2, or 3 heteroatoms independently selected from N, O, or S. The term "optionally substituted" means optionally substituted by one or more groups selected from: halogen, cyano, C.1-6 Alkyl, hydroxyl C 1-6 Alkyl, Halogenated C 1-6 Alkyl, C 3-6 cycloalkyl, C 3-6 cycloalkyl C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, SF5, C containing 1, 2 or 3 heteroatoms independently selected from N, O or S 1-6 Heteroalkyl groups, 3- to 6-membered heterocyclic groups containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, and 3- to 6-membered heterocyclic groups containing 1, 2, or 3 heteroatoms independently selected from N, O, or S. 1-6 Alkyl, 6- to 8-membered aryl, 6- to 8-membered aryl C 1-6 Alkyl group, containing 1, 2 or 3 independently selected from N, O or S, 6 to 8-membered heteroaryl group, C containing 1, 2 or 3 independently selected from N, O or S 1-6 Alkyl, hydroxyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 3-6 Cycloalkyloxy, 3- to 6-membered heterocyclic alkyloxy containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 6- to 8-membered aryloxy, amino, C 1-6 Alkylamino, amino C 1-6 Alkyl, C 1-6 Carboxyl group, C 1-6 alkoxycarbonyl, C 3-6 Cycloalkyloxycarbonyl, 3- to 6-membered heterocyclic oxycarbonyl containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 6- to 8-membered aryloxycarbonyl, 6- to 8-membered heteroaryloxycarbonyl containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, C 1-6 Alkyl carbonyloxy, C 3-6 Cycloalkyl carbonyloxy group, 3- to 6-membered heterocyclic carbonyloxy group containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 6- to 8-membered aryl carbonyloxy group, 6- to 8-membered heteroaryl carbonyloxy group containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 6- to 8-membered aryl C 1-6 Alkoxy, C 1-6 Alkyl carbonyl amino, halogenated C 1-6 Alkyl carbonyl amino, C 3-6 Cycloalkylcarbonylamino, 3- to 6-membered heterocyclic carbonylamino containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 6- to 8-membered arylcarbonylamino, 6- to 8-membered heteroarylcarbonylamino containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, C 1-6 alkyl carbonyl amino C 1-6 Alkyl, amino C 1-3 Acyl, hydroxyl amino C 1-3Acyl group, C 1-6 Alkylamino C 1-3 Acyl, 6- to 8-membered arylamino C 1-3 Acyl group, 6- to 8-membered heteroarylamino group containing 1, 2, or 3 heteroatoms independently selected from N, O, or S. 1-3 Acyl, amino C 1-3 Acyl C 1-6 Alkyl, amino C 1-3 Acylamino, C 1-6 Alkylamino C 1-3 Acylamino, C 1-6 Alkyl sulfonyl, halogenated C 1-6 alkylsulfonyl, C 3-6 Cycloalkylsulfonyl, 3- to 6-membered heterocyclic sulfonyl groups containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 6- to 8-membered arylsulfonyl groups, 6- to 8-membered heteroarylsulfonyl groups containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, aminosulfonyl, C 1-6 Alkylaminosulfonyl, 6- to 8-membered arylaminosulfonyl, 6- to 8-membered heteroarylaminosulfonyl containing 1, 2 or 3 heteroatoms independently selected from N, O or S, C 1-6 alkylsulfonylamino, C 3-6 Cycloalkylsulfonylamino, 3- to 6-membered heterocyclic sulfonylamino containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 6- to 8-membered arylsulfonylamino, 6- to 8-membered heteroarylsulfonylamino containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, halogenated C 1-6 Alkylsulfonylamino, Alternatively, the two substituents may form an alkylene dioxy or a haloalkylene dioxy; or, the two substituents and the cycloalkyl or heterocycloalkyl group attached thereto may form a cycloalkyl or heterocycloalkyl moiety; or, the substituents may further fuse with an aryl, heteroaryl, cycloalkyl, or heterocycloalkyl group to form one or more fused cycloalkyl, aryl, heterocycloalkyl, or heteroaryl structural units. Each of the above substituents may optionally be substituted by one or more additional substituents selected from: halogen, cyano, C 1-6 Alkyl, hydroxyl C 1-6 Alkyl, Halogenated C 1-6 Alkyl, C 3-6 cycloalkyl, C 3-6 cycloalkyl C 1-3 Alkyl groups, C containing one, two, or three heteroatoms independently selected from N, O, or S. 1-6 heteroalkyl, hydroxyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 3-6 Cycloalkoxy, C 1-6 Alkylamino, C 1-6Carboxyl group, C 1-6 Alkoxy C 1-6 carbonyl group, C 1-6 Alkyl carbonyloxy, C 3-6 Cycloalkylcarbonyloxy, C 1-6 Alkyl carbonyl amino, halogenated C 1-6 Alkyl carbonyl amino, C 3-6 cycloalkylcarbonylamino, C 1-6 alkyl carbonyl amino C 1-6 Alkyl, amino C 1-6 Acyl, hydroxyl amino C 1-6 Acyl group, C 1-6 Alkylamino C 1-6 Acyl, amino C 1-6 Acyl C 1-6 Alkyl, amino C 1-6 Acylamino, C 1-6 Alkylamino C 1-6 Acylamino, C 1-6 Alkyl sulfonyl, halogenated C 1-6 alkylsulfonyl, C 3-6 Cycloalkylsulfonyl, aminosulfonyl, C 1-6 Alkylaminosulfonyl, C 1-6 alkylsulfonylamino, C 3-6 Cycloalkylsulfonylamino, halogenated C 1-6 alkylsulfonylamino or oxo; or L 4 R 4a , where L 4 For non-existent, single-bond, or optional substitution C 1-3 Alkylene, optionally substituted C 2-3 alkenyl, optionally substituted C 2-3 Ethyne group, optionally substituted C 3-6 Cycloalkylene, wherein the optional substitution refers to optional substitution by one or more substituents selected from: halogen, C 1-6 Alkyl, Halogenated C 1-6 Alkyl, hydroxyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, hydroxy C 1-6 Alkyl, C 1-6 Alkoxy C 1-6 Alkyl, or O, N, , , , , , , , , , , , , , where R 4a R 4b Each of the following groups is independently hydrogen, and optionally substituted: C 1-10 Straight-chain or branched alkyl groups, C 3-10 cycloalkyl, or Ar 4a Ar 4a It is a 5- to 6-membered aryl group, containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, and a 3- to 8-membered heterocyclic alkyl group containing 1, 2, or 3 heteroatoms independently selected from N, O, or S. The optional substitution refers to optional substitution by one or more substituents selected from: halogen, cyano, C. 1-6 Alkyl, hydroxyl C 1-6 Alkyl, Halogenated C 1-6 Alkyl, C 3-6 cycloalkyl, C 3-6 cycloalkyl C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, C containing 1, 2 or 3 heteroatoms independently selected from N, O or S. 1-6 Heteroalkyl groups, 3- to 8-membered heterocyclic groups containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, and 3- to 8-membered heterocyclic groups containing 1, 2, or 3 heteroatoms independently selected from N, O, or S. 1-6 Alkyl, 5- to 6-membered aryl, 5- to 6-membered aryl C 1-6 Alkyl group, 5- to 6-membered heteroaryl group containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 5- to 6-membered heteroaryl group containing 1, 2, or 3 heteroatoms independently selected from N, O, or S C 1-6 Alkyl, hydroxyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 3-6 Cycloalkoxy, 3- to 8-membered heterocyclic alkyl groups containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 5- to 6-membered aryloxy, amino, C 1-6 Alkylamino, amino C 1-6 Alkyl, C 1-6 Carboxyl group, C 1-6 alkoxycarbonyl, C 3-6 Cycloalkoxycarbonyl, 3- to 8-membered heterocyclic cycloalkoxycarbonyl containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 5- to 6-membered aryloxycarbonyl, 5- to 6-membered heteroaryloxycarbonyl containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, C 1-6 Alkyl carbonyloxy, C 3-6Cycloalkyl carbonyloxy group, 3- to 8-membered heterocyclic carbonyloxy group containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 5- to 6-membered aryl carbonyloxy group, 5- to 6-membered heteroaryl carbonyloxy group containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 5- to 6-membered aryl C 1-6 Alkoxy, C 1-6 Alkyl carbonyl amino, halogenated C 1-6 Alkyl carbonyl amino, C 3-6 Cycloalkylcarbonylamino, 3- to 8-membered heterocyclic carbonylamino containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 5- to 6-membered arylcarbonylamino, 5- to 6-membered heteroarylcarbonylamino containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, C 1-6 alkyl carbonyl amino C 1-6 Alkyl, amino C 1-6 Acyl, hydroxyl amino C 1-6 Acyl group, C 1-6 Alkylamino C 1-6 Acyl, 5- to 6-membered arylamino C 1-6 Acyl group, 5- to 6-membered heteroarylamino group containing 1, 2, or 3 heteroatoms independently selected from N, O, or S. 1-6 Acyl, amino C 1-6 Acyl C 1-6 Alkyl, amino C 1-6 Acylamino, C 1-6 Alkylamino C 1-6 Acylamino, C 1-6 Alkyl sulfonyl, halogenated C 1-6 alkylsulfonyl, C 3-6 Cycloalkylsulfonyl, 3- to 8-membered heterocyclic sulfonyl groups containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 5- to 6-membered arylsulfonyl groups, 5- to 6-membered heteroarylsulfonyl groups containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, aminosulfonyl, C 1-6 Alkylaminosulfonyl, 5- to 6-membered arylaminosulfonyl, 5- to 6-membered heteroarylaminosulfonyl containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, C 1-6 alkylsulfonylamino, C 3-6 Cycloalkylsulfonylamino, 3- to 8-membered heterocyclic sulfonylamino containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 5- to 6-membered arylsulfonylamino, 5- to 6-membered heteroarylsulfonylamino containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, halogenated C 1-6 Alkylsulfonylamino, Alternatively, two of the above substituents may form an alkylene dioxy or a haloalkylene dioxy, or two of the above substituents and the cycloalkyl or heterocycloalkyl group attached thereto may together form a cycloalkyl or heterocycloalkyl moiety, or the above substituents may further fuse with an aryl, heteroaryl, cycloalkyl or heterocycloalkyl group to form one or more fused cycloalkyl, aryl, heterocycloalkyl or heteroaryl structural units. Each of the above substituents may optionally be substituted by one or more additional substituents selected from: halogen, cyano, C 1-6 Alkyl, hydroxyl C 1-6 Alkyl, Halogenated C 1-6 Alkyl, C 3-6 cycloalkyl, C 3-6 cycloalkyl C 1-6 Alkyl groups, C containing one, two, or three heteroatoms independently selected from N, O, or S. 1-6 heteroalkyl, hydroxyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 3-6 Cycloalkoxy, C 1-6 Alkylamino, C 1-6 Carboxyl group, C 1-6 alkoxycarbonyl, C 1-6 Alkyl carbonyloxy, C 3-6 Cycloalkylcarbonyloxy, C 1-6 Alkyl carbonyl amino, halogenated C 1-6 Alkyl carbonyl amino, C 3-6 cycloalkylcarbonylamino, C 1-6 alkyl carbonyl amino C 1-6 Alkyl, amino C 1-6 Acyl, hydroxyl amino C 1-6 Acyl group, C 1-6 Alkylamino C 1-6 Acyl, amino C 1-6 Acyl C 1-6 Alkyl, amino C 1-6 Acylamino, C 1-6 Alkylamino C 1-6 Acylamino, C 1-6 Alkyl sulfonyl, halogenated C 1-6 alkylsulfonyl, C 3-6 Cycloalkylsulfonyl, aminosulfonyl, C 1-6 Alkylaminosulfonyl, C 1-6 alkylsulfonylamino, C 3-6 Cycloalkylsulfonylamino, halogenated C 1-6 Alkylsulfonylamino or oxo; R 5 It is hydrogen, halogen, nitro, or optionally substituted with the following groups: C 1-10 Straight-chain or branched alkyl groups, C 3-10Cycloalkyl, amino, C 1-10 alkoxy or Ar 5 Ar 5 The aryl group is a 5- to 6-membered aryl group, a 5- to 6-membered heteroaryl group containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, or a 3- to 8-membered heterocyclic alkyl group containing 1, 2, or 3 heteroatoms independently selected from N, O, or S. The term "optionally substituted" means optionally substituted by one or more groups selected from: halogen, cyano, C. 1-6 Alkyl, hydroxyl C 1-6 Alkyl, Halogenated C 1-6 Alkyl, C 3-6 cycloalkyl, C 3-6 cycloalkyl C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, C containing 1, 2 or 3 heteroatoms independently selected from N, O or S. 1-6 Heteroalkyl groups, 3- to 6-membered heterocyclic groups containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, and 3- to 6-membered heterocyclic groups containing 1, 2, or 3 heteroatoms independently selected from N, O, or S. 1-6 Alkyl, 6- to 8-membered aryl, 6- to 8-membered aryl C 1-6 Alkyl group, containing 1, 2 or 3 independently selected from N, O or S, 6 to 8-membered heteroaryl group, C containing 1, 2 or 3 independently selected from N, O or S 1-6 Alkyl, hydroxyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 3-6 Cycloalkyloxy, 3- to 6-membered heterocyclic alkyloxy containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 6- to 8-membered aryloxy, amino, C 1-6 Alkylamino, amino C 1-6 Alkyl, C 1-6 Carboxyl group, C 1-6 alkoxycarbonyl, C 3-6 Cycloalkyloxycarbonyl, 3- to 6-membered heterocyclic oxycarbonyl containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 6- to 8-membered aryloxycarbonyl, 6- to 8-membered heteroaryloxycarbonyl containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, C 1-6 Alkyl carbonyloxy, C 3-6 Cycloalkyl carbonyloxy group, 3- to 6-membered heterocyclic carbonyloxy group containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 6- to 8-membered aryl carbonyloxy group, 6- to 8-membered heteroaryl carbonyloxy group containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 6- to 8-membered aryl C 1-6 Alkoxy, C 1-6 Alkyl carbonyl amino, halogenated C 1-6 Alkyl carbonyl amino, C 3-6Cycloalkylcarbonylamino, 3- to 6-membered heterocyclic carbonylamino containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 6- to 8-membered arylcarbonylamino, 6- to 8-membered heteroarylcarbonylamino containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, C 1-6 alkyl carbonyl amino C 1-6 Alkyl, amino C 1-3 Acyl, hydroxyl amino C 1-3 Acyl group, C 1-6 Alkylamino C 1-3 Acyl, 6- to 8-membered arylamino C 1-3 Acyl group, 6- to 8-membered heteroarylamino group containing 1, 2, or 3 heteroatoms independently selected from N, O, or S. 1-3 Acyl, amino C 1-3 Acyl C 1-6 Alkyl, amino C 1-3 Acylamino, C 1-6 Alkylamino C 1-3 Acylamino, C 1-6 Alkyl sulfonyl, halogenated C 1-6 alkylsulfonyl, C 3-6 Cycloalkylsulfonyl, 3- to 6-membered heterocyclic sulfonyl groups containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 6- to 8-membered arylsulfonyl groups, 6- to 8-membered heteroarylsulfonyl groups containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, aminosulfonyl, C 1-6 Alkylaminosulfonyl, 6- to 8-membered arylaminosulfonyl, 6- to 8-membered heteroarylaminosulfonyl containing 1, 2 or 3 heteroatoms independently selected from N, O or S, C 1-6 alkylsulfonylamino, C 3-6 Cycloalkylsulfonylamino, 3- to 6-membered heterocyclic sulfonylamino containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 6- to 8-membered arylsulfonylamino, 6- to 8-membered heteroarylsulfonylamino containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, halogenated C 1-6 Alkylsulfonylamino, Alternatively, the two substituents may form an alkylene dioxy or a haloalkylene dioxy; or, the two substituents and the cycloalkyl or heterocycloalkyl group attached thereto may form a cycloalkyl or heterocycloalkyl moiety; or, the substituents may further fuse with an aryl, heteroaryl, cycloalkyl, or heterocycloalkyl group to form one or more fused cycloalkyl, aryl, heterocycloalkyl, or heteroaryl structural units. Each of the above substituents may optionally be substituted by one or more additional substituents selected from: halogen, cyano, C 1-6 Alkyl, hydroxyl C 1-6 Alkyl, Halogenated C 1-6 Alkyl, C 3-6 cycloalkyl, C3-6 cycloalkyl C 1-3 Alkyl groups, C containing one, two, or three heteroatoms independently selected from N, O, or S. 1-6 heteroalkyl, hydroxyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 3-6 Cycloalkoxy, C 1-6 Alkylamino, C 1-6 Carboxyl group, C 1-6 Alkoxy C 1-6 carbonyl group, C 1-6 alkyl carbonyloxy group, C 3-6 Cycloalkylcarbonyloxy, C 1-6 Alkyl carbonyl amino, halogenated C 1-6 Alkyl carbonyl amino, C 3-6 cycloalkylcarbonylamino, C 1-6 alkyl carbonyl amino C 1-6 Alkyl, amino C 1-6 Acyl, hydroxyl amino C 1-6 Acyl group, C 1-6 Alkylamino C 1-6 Acyl, amino C 1-6 Acyl C 1-6 Alkyl, amino C 1-6 Acylamino, C 1-6 Alkylamino C 1-6 Acylamino, C 1-6 Alkyl sulfonyl, halogenated C 1-6 alkylsulfonyl, C 3-6 Cycloalkylsulfonyl, aminosulfonyl, C 1-6 Alkylaminosulfonyl, C 1-6 alkylsulfonylamino, C 3-6 Cycloalkylsulfonylamino, halogenated C 1-6 Alkylsulfonylamino or oxo; or L 5 R 5a , where L 5 For non-existent, single-bond, or arbitrarily substituted C 1-3 Alkylene, optionally substituted C 2-3 alkenyl, optionally substituted C 2-3 Ethyne group, optionally substituted C 3-6 Cycloalkylene, wherein the optional substitution refers to optional substitution by one or more substituents selected from: halogen, C 1-6 Alkyl, Halogenated C 1-6 Alkyl, hydroxyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, hydroxy C 1-6 Alkyl, C 1-6 Alkoxy C 1-6Alkyl, or O, N, , , , , , , , , , , , , , where R 5a R 5b Each of the following groups is independently hydrogen, and may be optionally substituted: C 1-10 Straight-chain or branched alkyl groups, C 3-10 cycloalkyl, or Ar 5a Ar 5a It is a 5- to 6-membered aryl group, containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, and a 3- to 8-membered heterocyclic alkyl group containing 1, 2, or 3 heteroatoms independently selected from N, O, or S. The optional substitution refers to optional substitution by one or more substituents selected from: halogen, cyano, C. 1-6 Alkyl, hydroxyl C 1-6 Alkyl, Halogenated C 1-6 Alkyl, C 3-6 cycloalkyl, C 3-6 cycloalkyl C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, C containing 1, 2 or 3 heteroatoms independently selected from N, O or S. 1-6 Heteroalkyl groups, 3- to 8-membered heterocyclic groups containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, and 3- to 8-membered heterocyclic groups containing 1, 2, or 3 heteroatoms independently selected from N, O, or S. 1-6 Alkyl, 5- to 6-membered aryl, 5- to 6-membered aryl C 1-6 Alkyl group, 5- to 6-membered heteroaryl group containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 5- to 6-membered heteroaryl group containing 1, 2, or 3 heteroatoms independently selected from N, O, or S C 1-6 Alkyl, hydroxyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 3-6 Cycloalkoxy, 3- to 8-membered heterocyclic alkyl groups containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 5- to 6-membered aryloxy, amino, C 1-6 Alkylamino, amino C 1-6 Alkyl, C 1-6 Carboxyl group, C 1-6 alkoxycarbonyl, C 3-6Cycloalkoxycarbonyl, 3- to 8-membered heterocyclic cycloalkoxycarbonyl containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 5- to 6-membered aryloxycarbonyl, 5- to 6-membered heteroaryloxycarbonyl containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, C 1-6 Alkyl carbonyloxy, C 3-6 Cycloalkyl carbonyloxy group, 3- to 8-membered heterocyclic carbonyloxy group containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 5- to 6-membered aryl carbonyloxy group, 5- to 6-membered heteroaryl carbonyloxy group containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 5- to 6-membered aryl C 1-6 Alkoxy, C 1-6 Alkyl carbonyl amino, halogenated C 1-6 Alkyl carbonyl amino, C 3-6 Cycloalkylcarbonylamino, 3- to 8-membered heterocyclic carbonylamino containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 5- to 6-membered arylcarbonylamino, 5- to 6-membered heteroarylcarbonylamino containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, C 1-6 alkyl carbonyl amino C 1-6 Alkyl, amino C 1-6 Acyl, hydroxyl amino C 1-6 Acyl group, C 1-6 Alkylamino C 1-6 Acyl, 5- to 6-membered arylamino C 1-6 Acyl group, 5- to 6-membered heteroarylamino group containing 1, 2, or 3 heteroatoms independently selected from N, O, or S. 1-6 Acyl, amino C 1-6 Acyl C 1-6 Alkyl, amino C 1-6 Acylamino, C 1-6 Alkylamino C 1-6 Acylamino, C 1-6 Alkyl sulfonyl, halogenated C 1-6 alkylsulfonyl, C 3-6 Cycloalkylsulfonyl, 3- to 8-membered heterocyclic sulfonyl groups containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 5- to 6-membered arylsulfonyl groups, 5- to 6-membered heteroarylsulfonyl groups containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, aminosulfonyl, C 1-6 Alkylaminosulfonyl, 5- to 6-membered arylaminosulfonyl, 5- to 6-membered heteroarylaminosulfonyl containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, C 1-6 alkylsulfonylamino, C 3-6 Cycloalkylsulfonylamino, 3- to 8-membered heterocyclic sulfonylamino containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 5- to 6-membered arylsulfonylamino, 5- to 6-membered heteroarylsulfonylamino containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, halogenated C1-6 Alkylsulfonylamino, Alternatively, two of the above substituents may form an alkylene dioxy or a haloalkylene dioxy, or two of the above substituents and the cycloalkyl or heterocycloalkyl group attached thereto may together form a cycloalkyl or heterocycloalkyl moiety, or the above substituents may further fuse with an aryl, heteroaryl, cycloalkyl or heterocycloalkyl group to form one or more fused cycloalkyl, aryl, heterocycloalkyl or heteroaryl structural units. Each of the above substituents may optionally be substituted by one or more additional substituents selected from: halogen, cyano, C 1-6 Alkyl, hydroxyl C 1-6 Alkyl, Halogenated C 1-6 Alkyl, C 3-6 cycloalkyl, C 3-6 cycloalkyl C 1-6 Alkyl groups, C containing one, two, or three heteroatoms independently selected from N, O, or S. 1-6 heteroalkyl, hydroxyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 3-6 Cycloalkoxy, C 1-6 Alkylamino, C 1-6 Carboxyl group, C 1-6 alkoxycarbonyl, C 1-6 Alkyl carbonyloxy, C 3-6 Cycloalkylcarbonyloxy, C 1-6 Alkyl carbonyl amino, halogenated C 1-6 Alkyl carbonyl amino, C 3-6 cycloalkylcarbonylamino, C 1-6 alkyl carbonyl amino C 1-6 Alkyl, amino C 1-6 Acyl, hydroxyl amino C 1-6 Acyl group, C 1-6 Alkylamino C 1-6 Acyl, amino C 1-6 Acyl C 1-6 Alkyl, amino C 1-6 Acylamino, C 1-6 Alkylamino C 1-6 Acylamino, C 1-6 Alkyl sulfonyl, halogenated C 1-6 alkylsulfonyl, C 3-6 Cycloalkylsulfonyl, aminosulfonyl, C 1-6 Alkylaminosulfonyl, C 1-6 alkylsulfonylamino, C 3-6 Cycloalkylsulfonylamino, halogenated C 1-6 Alkylsulfonylamino or oxo; R 6 It is hydrogen, halogen, hydroxyl, or optionally substituted with the following groups: C1-10 Straight-chain or branched alkyl groups, C 3-10 cycloalkyl, C 1-10 alkoxy, amino, or Ar 6 Ar 6 The aryl group is 5 to 10-membered aryl, a 5 to 10-membered heteroaryl group containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, or a 3 to 8-membered heterocyclic alkyl group containing 1, 2, or 3 heteroatoms independently selected from N, O, or S. The term "optionally substituted" means optionally substituted by one or more groups selected from: halogen, cyano, C. 1-6 Alkyl, hydroxyl C 1-6 Alkyl, Halogenated C 1-6 Alkyl, C 3-6 cycloalkyl, C 3-6 cycloalkyl C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, SF5, C containing 1, 2 or 3 heteroatoms independently selected from N, O or S 1-6 Heteroalkyl groups, 3- to 6-membered heterocyclic groups containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, and 3- to 6-membered heterocyclic groups containing 1, 2, or 3 heteroatoms independently selected from N, O, or S. 1-6 Alkyl, 6- to 8-membered aryl, 6- to 8-membered aryl C 1-6 Alkyl group, containing 1, 2 or 3 independently selected from N, O or S, 6 to 8-membered heteroaryl group, C containing 1, 2 or 3 independently selected from N, O or S 1-6 Alkyl, hydroxyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 3-6 Cycloalkyloxy, 3- to 6-membered heterocyclic alkyloxy containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 6- to 8-membered aryloxy, amino, C 1-6 Alkylamino, amino C 1-6 Alkyl, C 1-6 Carboxyl group, C 1-6 alkoxycarbonyl, C 3-6 Cycloalkyloxycarbonyl, 3- to 6-membered heterocyclic oxycarbonyl containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 6- to 8-membered aryloxycarbonyl, 6- to 8-membered heteroaryloxycarbonyl containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, C 1-6 Alkyl carbonyloxy, C 3-6 Cycloalkyl carbonyloxy group, 3- to 6-membered heterocyclic carbonyloxy group containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 6- to 8-membered aryl carbonyloxy group, 6- to 8-membered heteroaryl carbonyloxy group containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 6- to 8-membered aryl C 1-6 Alkoxy, C 1-6Alkyl carbonyl amino, halogenated C 1-6 Alkyl carbonyl amino, C 3-6 Cycloalkylcarbonylamino, 3- to 6-membered heterocyclic carbonylamino containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 6- to 8-membered arylcarbonylamino, 6- to 8-membered heteroarylcarbonylamino containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, C 1-6 alkyl carbonyl amino C 1-6 Alkyl, amino C 1-3 Acyl, hydroxyl amino C 1-3 Acyl group, C 1-6 Alkylamino C 1-3 Acyl, 6- to 8-membered arylamino C 1-3 Acyl group, 6- to 8-membered heteroarylamino group containing 1, 2, or 3 heteroatoms independently selected from N, O, or S. 1-3 Acyl, amino C 1-3 Acyl C 1-6 Alkyl, amino C 1-3 Acylamino, C 1-6 Alkylamino C 1-3 Acylamino, C 1-6 Alkyl sulfonyl, halogenated C 1-6 alkylsulfonyl, C 3-6 Cycloalkylsulfonyl, 3- to 6-membered heterocyclic sulfonyl groups containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 6- to 8-membered arylsulfonyl groups, 6- to 8-membered heteroarylsulfonyl groups containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, aminosulfonyl, C 1-6 Alkylaminosulfonyl, 6- to 8-membered arylaminosulfonyl, 6- to 8-membered heteroarylaminosulfonyl containing 1, 2 or 3 heteroatoms independently selected from N, O or S, C 1-6 alkylsulfonylamino, C 3-6 Cycloalkylsulfonylamino, 3- to 6-membered heterocyclic sulfonylamino containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 6- to 8-membered arylsulfonylamino, 6- to 8-membered heteroarylsulfonylamino containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, halogenated C 1-6 Alkylsulfonylamino, Alternatively, the two substituents may form an alkylene dioxy or a haloalkylene dioxy; or, the two substituents and the cycloalkyl or heterocycloalkyl group attached thereto may form a cycloalkyl or heterocycloalkyl moiety; or, the substituents may further fuse with an aryl, heteroaryl, cycloalkyl, or heterocycloalkyl group to form one or more fused cycloalkyl, aryl, heterocycloalkyl, or heteroaryl structural units. Each of the above substituents may optionally be substituted by one or more additional substituents selected from: halogen, cyano, C 1-6 Alkyl, hydroxyl C 1-6Alkyl, Halogenated C 1-6 Alkyl, C 3-6 cycloalkyl, C 3-6 cycloalkyl C 1-3 Alkyl groups, C containing one, two, or three heteroatoms independently selected from N, O, or S. 1-6 heteroalkyl, hydroxyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 3-6 Cycloalkoxy, C 1-6 Alkylamino, C 1-6 Carboxyl group, C 1-6 Alkoxy C 1-6 carbonyl group, C 1-6 Alkyl carbonyloxy, C 3-6 Cycloalkylcarbonyloxy, C 1-6 Alkyl carbonyl amino, halogenated C 1-6 Alkyl carbonyl amino, C 3-6 cycloalkylcarbonylamino, C 1-6 alkyl carbonyl amino C 1-6 Alkyl, amino C 1-6 Acyl, hydroxyl amino C 1-6 Acyl group, C 1-6 Alkylamino C 1-6 Acyl, amino C 1-6 Acyl C 1-6 Alkyl, amino C 1-6 Acylamino, C 1-6 Alkylamino C 1-6 Acylamino, C 1-6 Alkyl sulfonyl, halogenated C 1-6 alkylsulfonyl, C 3-6 Cycloalkylsulfonyl, aminosulfonyl, C 1-6 Alkylaminosulfonyl, C 1-6 alkylsulfonylamino, C 3-6 Cycloalkylsulfonylamino, halogenated C 1-6 Alkylsulfonylamino or oxo; or L 6 R 6a , where L 6 For non-existent, single-bond, or optional substitution C 1-3 Alkylene, optionally substituted C 2-3 alkenyl, optionally substituted C 2-3 Ethyne group, optionally substituted C 3-6 Cycloalkylene, wherein the optional substitution refers to optional substitution by one or more substituents selected from: halogen, C 1-6 Alkyl, Halogenated C 1-6 Alkyl, hydroxyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, hydroxy C1-6 Alkyl, C 1-6 Alkoxy C 1-6 Alkyl, or O, N, , , , , , , , , , , , , , where R 6a R 6b Each of the following groups is independently hydrogen, and may be optionally substituted: C 1-10 Straight-chain or branched alkyl groups, C 3-10 cycloalkyl, or Ar 6a Ar 6a It is a 5- to 6-membered aryl group, containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, and a 3- to 8-membered heterocyclic alkyl group containing 1, 2, or 3 heteroatoms independently selected from N, O, or S. The optional substitution refers to optional substitution by one or more substituents selected from: halogen, cyano, C. 1-6 Alkyl, hydroxyl C 1-6 Alkyl, Halogenated C 1-6 Alkyl, C 3-6 cycloalkyl, C 3-6 cycloalkyl C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, C containing 1, 2, or 3 heteroatoms independently selected from N, O, or S. 1-6 Heteroalkyl groups, 3- to 8-membered heterocyclic groups containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, and 3- to 8-membered heterocyclic groups containing 1, 2, or 3 heteroatoms independently selected from N, O, or S. 1-6 Alkyl, 5- to 6-membered aryl, 5- to 6-membered aryl C 1-6 Alkyl group, 5- to 6-membered heteroaryl group containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 5- to 6-membered heteroaryl group containing 1, 2, or 3 heteroatoms independently selected from N, O, or S C 1-6 Alkyl, hydroxyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 3-6 Cycloalkoxy, 3- to 8-membered heterocyclic alkyl groups containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 5- to 6-membered aryloxy, amino, C 1-6 Alkylamino, amino C 1-6 Alkyl, C 1-6 Carboxyl group, C 1-6alkoxycarbonyl, C 3-6 Cycloalkoxycarbonyl, 3- to 8-membered heterocyclic cycloalkoxycarbonyl containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 5- to 6-membered aryloxycarbonyl, 5- to 6-membered heteroaryloxycarbonyl containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, C 1-6 Alkyl carbonyloxy, C 3-6 Cycloalkyl carbonyloxy group, 3- to 8-membered heterocyclic carbonyloxy group containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 5- to 6-membered aryl carbonyloxy group, 5- to 6-membered heteroaryl carbonyloxy group containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 5- to 6-membered aryl C 1-6 Alkoxy, C 1-6 Alkyl carbonyl amino, halogenated C 1-6 Alkyl carbonyl amino, C 3-6 Cycloalkylcarbonylamino, 3- to 8-membered heterocyclic carbonylamino containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 5- to 6-membered arylcarbonylamino, 5- to 6-membered heteroarylcarbonylamino containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, C 1-6 alkyl carbonyl amino C 1-6 Alkyl, amino C 1-6 Acyl, hydroxyl amino C 1-6 Acyl group, C 1-6 Alkylamino C 1-6 Acyl, 5- to 6-membered arylamino C 1-6 Acyl group, 5- to 6-membered heteroarylamino group containing 1, 2, or 3 heteroatoms independently selected from N, O, or S. 1-6 Acyl, amino C 1-6 Acyl C 1-6 Alkyl, amino C 1-6 Acylamino, C 1-6 Alkylamino C 1-6 Acylamino, C 1-6 Alkyl sulfonyl, halogenated C 1-6 alkylsulfonyl, C 3-6 Cycloalkylsulfonyl, 3- to 8-membered heterocyclic sulfonyl groups containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 5- to 6-membered arylsulfonyl groups, 5- to 6-membered heteroarylsulfonyl groups containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, aminosulfonyl, C 1-6 Alkylaminosulfonyl, 5- to 6-membered arylaminosulfonyl, 5- to 6-membered heteroarylaminosulfonyl containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, C 1-6 alkylsulfonylamino, C 3-6Cycloalkylsulfonylamino, 3- to 8-membered heterocyclic sulfonylamino containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 5- to 6-membered arylsulfonylamino, 5- to 6-membered heteroarylsulfonylamino containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, halogenated C 1-6 Alkylsulfonylamino, Alternatively, two of the above substituents may form an alkylene dioxy or a haloalkylene dioxy, or two of the above substituents and the cycloalkyl or heterocycloalkyl group attached thereto may together form a cycloalkyl or heterocycloalkyl moiety, or the above substituents may further fuse with an aryl, heteroaryl, cycloalkyl or heterocycloalkyl group to form one or more fused cycloalkyl, aryl, heterocycloalkyl or heteroaryl structural units. Each of the above substituents may optionally be substituted by one or more additional substituents selected from: halogen, cyano, C 1-6 Alkyl, hydroxyl C 1-6 Alkyl, Halogenated C 1-6 Alkyl, C 3-6 cycloalkyl, C 3-6 cycloalkyl C 1-6 Alkyl groups, C containing one, two, or three heteroatoms independently selected from N, O, or S. 1-6 heteroalkyl, hydroxyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 3-6 Cycloalkoxy, C 1-6 Alkylamino, C 1-6 Carboxyl group, C 1-6 alkoxycarbonyl, C 1-6 Alkyl carbonyloxy, C 3-6 Cycloalkylcarbonyloxy, C 1-6 Alkyl carbonyl amino, halogenated C 1-6 Alkyl carbonyl amino, C 3-6 cycloalkylcarbonylamino, C 1-6 alkyl carbonyl amino C 1-6 Alkyl, amino C 1-6 Acyl, hydroxyl amino C 1-6 Acyl group, C 1-6 Alkylamino C 1-6 Acyl, amino C 1-6 Acyl C 1-6 Alkyl, amino C 1-6 Acylamino, C 1-6 Alkylamino C 1-6 Acylamino, C 1-6 Alkyl sulfonyl, halogenated C 1-6 alkylsulfonyl, C 3-6 Cycloalkylsulfonyl, aminosulfonyl, C 1-6 Alkylaminosulfonyl, C 1-6 alkylsulfonylamino, C3-6 Cycloalkylsulfonylamino, halogenated C 1-6 Alkylsulfonylamino or oxo; R 7 It is hydrogen, halogen, nitro, or optionally substituted with the following groups: C 1-10 Straight-chain or branched alkyl groups, C 3-10 cycloalkyl, C 1-10 alkoxy, amino, or Ar 7 Ar 7 The aryl group is a 5- to 6-membered aryl group, a 5- to 6-membered heteroaryl group containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, or a 3- to 8-membered heterocyclic alkyl group containing 1, 2, or 3 heteroatoms independently selected from N, O, or S. The term "optionally substituted" means optionally substituted by one or more groups selected from: halogen, cyano, C. 1-6 Alkyl, hydroxyl C 1-6 Alkyl, Halogenated C 1-6 Alkyl, C 3-6 cycloalkyl, C 3-6 cycloalkyl C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, C containing 1, 2, or 3 heteroatoms independently selected from N, O, or S. 1-6 Heteroalkyl groups, 3- to 6-membered heterocyclic groups containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, and 3- to 6-membered heterocyclic groups containing 1, 2, or 3 heteroatoms independently selected from N, O, or S. 1-6 Alkyl, 6- to 8-membered aryl, 6- to 8-membered aryl C 1-6 Alkyl group, containing 1, 2 or 3 independently selected from N, O or S, 6 to 8-membered heteroaryl group, C containing 1, 2 or 3 independently selected from N, O or S 1-6 Alkyl, hydroxyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 3-6 Cycloalkyloxy, 3- to 6-membered heterocyclic alkyloxy containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 6- to 8-membered aryloxy, amino, C 1-6 Alkylamino, amino C 1-6 Alkyl, C 1-6 Carboxyl group, C 1-6 alkoxycarbonyl, C 3-6 Cycloalkyloxycarbonyl, 3- to 6-membered heterocyclic oxycarbonyl containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 6- to 8-membered aryloxycarbonyl, 6- to 8-membered heteroaryloxycarbonyl containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, C 1-6 Alkyl carbonyloxy, C 3-6Cycloalkyl carbonyloxy group, 3- to 6-membered heterocyclic carbonyloxy group containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 6- to 8-membered aryl carbonyloxy group, 6- to 8-membered heteroaryl carbonyloxy group containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 6- to 8-membered aryl C 1-6 Alkoxy, C 1-6 Alkyl carbonyl amino, halogenated C 1-6 Alkyl carbonyl amino, C 3-6 Cycloalkylcarbonylamino, 3- to 6-membered heterocyclic carbonylamino containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 6- to 8-membered arylcarbonylamino, 6- to 8-membered heteroarylcarbonylamino containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, C 1-6 alkyl carbonyl amino C 1-6 Alkyl, amino C 1-3 Acyl, hydroxyl amino C 1-3 Acyl group, C 1-6 Alkylamino C 1-3 Acyl, 6- to 8-membered arylamino C 1-3 Acyl group, 6- to 8-membered heteroarylamino group containing 1, 2, or 3 heteroatoms independently selected from N, O, or S. 1-3 Acyl, amino C 1-3 Acyl C 1-6 Alkyl, amino C 1-3 Acylamino, C 1-6 Alkylamino C 1-3 Acylamino, C 1-6 Alkyl sulfonyl, halogenated C 1-6 alkylsulfonyl, C 3-6 Cycloalkylsulfonyl, 3- to 6-membered heterocyclic sulfonyl groups containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 6- to 8-membered arylsulfonyl groups, 6- to 8-membered heteroarylsulfonyl groups containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, aminosulfonyl, C 1-6 Alkylaminosulfonyl, 6- to 8-membered arylaminosulfonyl, 6- to 8-membered heteroarylaminosulfonyl containing 1, 2 or 3 heteroatoms independently selected from N, O or S, C 1-6 alkylsulfonylamino, C 3-6 Cycloalkylsulfonylamino, 3- to 6-membered heterocyclic sulfonylamino containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 6- to 8-membered arylsulfonylamino, 6- to 8-membered heteroarylsulfonylamino containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, halogenated C 1-6 Alkylsulfonylamino, Alternatively, the two substituents may form an alkylene dioxy or a haloalkylene dioxy; or, the two substituents and the cycloalkyl or heterocycloalkyl group attached thereto may form a cycloalkyl or heterocycloalkyl moiety; or, the substituents may further fuse with an aryl, heteroaryl, cycloalkyl, or heterocycloalkyl group to form one or more fused cycloalkyl, aryl, heterocycloalkyl, or heteroaryl structural units. Each of the above substituents may optionally be substituted by one or more additional substituents selected from: halogen, cyano, C 1-6 Alkyl, hydroxyl C 1-6 Alkyl, Halogenated C 1-6 Alkyl, C 3-6 cycloalkyl, C 3-6 cycloalkyl C 1-3 Alkyl groups, C containing one, two, or three heteroatoms independently selected from N, O, or S. 1-6 heteroalkyl, hydroxyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 3-6 Cycloalkoxy, C 1-6 Alkylamino, C 1-6 Carboxyl group, C 1-6 Alkoxy C 1-6 carbonyl group, C 1-6 alkyl carbonyloxy group, C 3-6 Cycloalkylcarbonyloxy, C 1-6 Alkyl carbonyl amino, halogenated C 1-6 Alkyl carbonyl amino, C 3-6 cycloalkylcarbonylamino, C 1-6 alkyl carbonyl amino C 1-6 Alkyl, amino C 1-6 Acyl, hydroxyl amino C 1-6 Acyl group, C 1-6 Alkylamino C 1-6 Acyl, amino C 1-6 Acyl C 1-6 Alkyl, amino C 1-6 Acylamino, C 1-6 Alkylamino C 1-6 Acylamino, C 1-6 Alkyl sulfonyl, halogenated C 1-6 alkylsulfonyl, C 3-6 Cycloalkylsulfonyl, aminosulfonyl, C 1-6 Alkylaminosulfonyl, C 1-6 alkylsulfonylamino, C 3-6 Cycloalkylsulfonylamino, halogenated C 1-6 Alkylsulfonylamino or oxo; or L 7 R 7a , where L 7For non-existent, single-bond, or arbitrarily substituted C 1-3 Alkylene, optionally substituted C 2-3 alkenyl, optionally substituted C 2-3 Ethyne group, optionally substituted C 3-6 Cycloalkylene, wherein the optional substitution refers to optional substitution by one or more substituents selected from: halogen, C 1-6 Alkyl, Halogenated C 1-6 Alkyl, hydroxyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, hydroxy C 1-6 Alkyl, C 1-6 Alkoxy C 1-6 Alkyl, or O, N, , , , , , , , , , , , , , where R 7a R 7b Each of the following groups is independently hydrogen, and may be optionally substituted: C 1-10 Straight-chain or branched alkyl groups, C 3-10 cycloalkyl, or Ar 7a Ar 7a It is a 5- to 6-membered aryl group, containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, and a 3- to 8-membered heterocyclic alkyl group containing 1, 2, or 3 heteroatoms independently selected from N, O, or S. The optional substitution refers to optional substitution by one or more substituents selected from: halogen, cyano, C. 1-6 Alkyl, hydroxyl C 1-6 Alkyl, Halogenated C 1-6 Alkyl, C 3-6 cycloalkyl, C 3-6 cycloalkyl C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, C containing 1, 2 or 3 heteroatoms independently selected from N, O or S. 1-6 Heteroalkyl groups, 3- to 8-membered heterocyclic groups containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, and 3- to 8-membered heterocyclic groups containing 1, 2, or 3 heteroatoms independently selected from N, O, or S. 1-6 Alkyl, 5- to 6-membered aryl, 5- to 6-membered aryl C 1-6Alkyl group, 5- to 6-membered heteroaryl group containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 5- to 6-membered heteroaryl group containing 1, 2, or 3 heteroatoms independently selected from N, O, or S C 1-6 Alkyl, hydroxyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 3-6 Cycloalkoxy, 3- to 8-membered heterocyclic alkyl groups containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 5- to 6-membered aryloxy, amino, C 1-6 Alkylamino, amino C 1-6 Alkyl, C 1-6 Carboxyl group, C 1-6 alkoxycarbonyl, C 3-6 Cycloalkoxycarbonyl, 3- to 8-membered heterocyclic cycloalkoxycarbonyl containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 5- to 6-membered aryloxycarbonyl, 5- to 6-membered heteroaryloxycarbonyl containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, C 1-6 alkyl carbonyloxy group, C 3-6 Cycloalkyl carbonyloxy group, 3- to 8-membered heterocyclic carbonyloxy group containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 5- to 6-membered aryl carbonyloxy group, 5- to 6-membered heteroaryl carbonyloxy group containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 5- to 6-membered aryl C 1-6 Alkoxy, C 1-6 Alkyl carbonyl amino, halogenated C 1-6 Alkyl carbonyl amino, C 3-6 Cycloalkyl carbonylamino, 3- to 8-membered heterocyclic carbonylamino containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 5- to 6-membered aryl carbonylamino, 5- to 6-membered heteroaryl carbonylamino containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, C 1-6 alkyl carbonyl amino C 1-6 Alkyl, amino C 1-6 Acyl, hydroxyl amino C 1-6 Acyl group, C 1-6 Alkylamino C 1-6 Acyl, 5- to 6-membered arylamino C 1-6 Acyl group, 5- to 6-membered heteroarylamino group containing 1, 2, or 3 heteroatoms independently selected from N, O, or S. 1-6 Acyl, amino C 1-6 Acyl C 1-6 Alkyl, amino C 1-6 Acylamino, C 1-6 Alkylamino C 1-6 Acylamino, C 1-6 Alkyl sulfonyl, halogenated C 1-6 alkylsulfonyl, C 3-6Cycloalkylsulfonyl, 3- to 8-membered heterocyclic sulfonyl groups containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 5- to 6-membered arylsulfonyl groups, 5- to 6-membered heteroarylsulfonyl groups containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, aminosulfonyl, C 1-6 Alkylaminosulfonyl, 5- to 6-membered arylaminosulfonyl, 5- to 6-membered heteroarylaminosulfonyl containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, C 1-6 alkylsulfonylamino, C 3-6 Cycloalkylsulfonylamino, 3- to 8-membered heterocyclic sulfonylamino containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 5- to 6-membered arylsulfonylamino, 5- to 6-membered heteroarylsulfonylamino containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, halogenated C 1-6 Alkylsulfonylamino, Alternatively, two of the above substituents may form an alkylene dioxy or a haloalkylene dioxy, or two of the above substituents and the cycloalkyl or heterocycloalkyl group attached thereto may together form a cycloalkyl or heterocycloalkyl moiety, or the above substituents may further fuse with an aryl, heteroaryl, cycloalkyl or heterocycloalkyl group to form one or more fused cycloalkyl, aryl, heterocycloalkyl or heteroaryl structural units. Each of the above substituents may optionally be substituted by one or more additional substituents selected from: halogen, cyano, C 1-6 Alkyl, hydroxyl C 1-6 Alkyl, Halogenated C 1-6 Alkyl, C 3-6 cycloalkyl, C 3-6 cycloalkyl C 1-6 Alkyl groups, C containing one, two, or three heteroatoms independently selected from N, O, or S. 1-6 heteroalkyl, hydroxyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 3-6 Cycloalkoxy, C 1-6 Alkylamino, C 1-6 Carboxyl group, C 1-6 alkoxycarbonyl, C 1-6 alkyl carbonyloxy group, C 3-6 Cycloalkylcarbonyloxy, C 1-6 Alkyl carbonyl amino, halogenated C 1-6 Alkyl carbonyl amino, C 3-6 cycloalkylcarbonylamino, C 1-6 alkyl carbonyl amino C 1-6 Alkyl, amino C 1-6 Acyl, hydroxyl amino C 1-6 Acyl group, C 1-6 Alkylamino C 1-6 Acyl, amino C 1-6 Acyl C1-6 Alkyl, amino C 1-6 Acylamino, C 1-6 Alkylamino C 1-6 Acylamino, C 1-6 Alkyl sulfonyl, halogenated C 1-6 alkylsulfonyl, C 3-6 Cycloalkylsulfonyl, aminosulfonyl, C 1-6 Alkylaminosulfonyl, C 1-6 alkylsulfonylamino, C 3-6 Cycloalkylsulfonylamino, halogenated C 1-6 Alkylsulfonylamino or oxo; R 8 R 9 Each can be independently hydrogen, halogen, or optionally substituted C 1-10 Straight-chain or branched alkyl groups, C 3-10 cycloalkyl or Ar 8 Ar 8 The aryl group is a 5- to 6-membered aryl group, a 5- to 6-membered heteroaryl group containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, or a 3- to 8-membered heterocyclic alkyl group containing 1, 2, or 3 heteroatoms independently selected from N, O, or S. The term "optionally substituted" means optionally substituted by one or more groups selected from: halogen, cyano, C. 1-6 Alkyl, hydroxyl C 1-6 Alkyl, Halogenated C 1-6 Alkyl, C 3-6 cycloalkyl, C 3-6 cycloalkyl C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, C containing 1, 2 or 3 heteroatoms independently selected from N, O or S. 1-6 Heteroalkyl groups, 3- to 6-membered heterocyclic groups containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, and 3- to 6-membered heterocyclic groups containing 1, 2, or 3 heteroatoms independently selected from N, O, or S. 1-6 Alkyl, 6- to 8-membered aryl, 6- to 8-membered aryl C 1-6 Alkyl group, containing 1, 2 or 3 independently selected from N, O or S, 6 to 8-membered heteroaryl group, C containing 1, 2 or 3 independently selected from N, O or S 1-6 Alkyl, hydroxyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 3-6 Cycloalkyloxy, 3- to 6-membered heterocyclic alkyloxy containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 6- to 8-membered aryloxy, amino, C 1-6 Alkylamino, amino C 1-6 Alkyl, C 1-6 Carboxyl group, C 1-6alkoxycarbonyl, C 3-6 Cycloalkyloxycarbonyl, 3- to 6-membered heterocyclic oxycarbonyl containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 6- to 8-membered aryloxycarbonyl, 6- to 8-membered heteroaryloxycarbonyl containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, C 1-6 Alkyl carbonyloxy, C 3-6 Cycloalkyl carbonyloxy group, 3- to 6-membered heterocyclic carbonyloxy group containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 6- to 8-membered aryl carbonyloxy group, 6- to 8-membered heteroaryl carbonyloxy group containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 6- to 8-membered aryl C 1-6 Alkoxy, C 1-6 Alkyl carbonyl amino, halogenated C 1-6 Alkyl carbonyl amino, C 3-6 Cycloalkylcarbonylamino, 3- to 6-membered heterocyclic carbonylamino containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 6- to 8-membered arylcarbonylamino, 6- to 8-membered heteroarylcarbonylamino containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, C 1-6 alkyl carbonyl amino C 1-6 Alkyl, amino C 1-3 Acyl, hydroxyl amino C 1-3 Acyl group, C 1-6 Alkylamino C 1-3 Acyl, 6- to 8-membered arylamino C 1-3 Acyl group, 6- to 8-membered heteroarylamino group containing 1, 2, or 3 heteroatoms independently selected from N, O, or S. 1-3 Acyl, amino C 1-3 Acyl C 1-6 Alkyl, amino C 1-3 Acylamino, C 1-6 Alkylamino C 1-3 Acylamino, C 1-6 Alkyl sulfonyl, halogenated C 1-6 alkylsulfonyl, C 3-6 Cycloalkylsulfonyl, 3- to 6-membered heterocyclic sulfonyl groups containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 6- to 8-membered arylsulfonyl groups, 6- to 8-membered heteroarylsulfonyl groups containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, aminosulfonyl, C 1-6 Alkylaminosulfonyl, 6- to 8-membered arylaminosulfonyl, 6- to 8-membered heteroarylaminosulfonyl containing 1, 2 or 3 heteroatoms independently selected from N, O or S, C 1-6 alkylsulfonylamino, C 3-6Cycloalkylsulfonylamino, 3- to 6-membered heterocyclic sulfonylamino containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 6- to 8-membered arylsulfonylamino, 6- to 8-membered heteroarylsulfonylamino containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, halogenated C 1-6 Alkylsulfonylamino, Alternatively, the two substituents may form an alkylene dioxy or a haloalkylene dioxy; or, the two substituents and the cycloalkyl or heterocycloalkyl group attached thereto may form a cycloalkyl or heterocycloalkyl moiety; or, the substituents may further fuse with an aryl, heteroaryl, cycloalkyl, or heterocycloalkyl group to form one or more fused cycloalkyl, aryl, heterocycloalkyl, or heteroaryl structural units. Each of the above substituents may optionally be substituted by one or more additional substituents selected from: halogen, cyano, C 1-6 Alkyl, hydroxyl C 1-6 Alkyl, Halogenated C 1-6 Alkyl, C 3-6 cycloalkyl, C 3-6 cycloalkyl C 1-3 Alkyl groups, C containing one, two, or three heteroatoms independently selected from N, O, or S. 1-6 heteroalkyl, hydroxyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 3-6 Cycloalkoxy, C 1-6 Alkylamino, C 1-6 Carboxyl group, C 1-6 Alkoxy C 1-6 carbonyl group, C 1-6 Alkyl carbonyloxy, C 3-6 Cycloalkylcarbonyloxy, C 1-6 Alkyl carbonyl amino, halogenated C 1-6 Alkyl carbonyl amino, C 3-6 cycloalkylcarbonylamino, C 1-6 alkyl carbonyl amino C 1-6 Alkyl, amino C 1-6 Acyl, hydroxyl amino C 1-6 Acyl group, C 1-6 Alkylamino C 1-6 Acyl, amino C 1-6 Acyl C 1-6 Alkyl, amino C 1-6 Acylamino, C 1-6 Alkylamino C 1-6 Acylamino, C 1-6 Alkyl sulfonyl, halogenated C 1-6 alkylsulfonyl, C 3-6 Cycloalkylsulfonyl, aminosulfonyl, C 1-6 Alkylaminosulfonyl, C 1-6alkylsulfonylamino, C 3-6 Cycloalkylsulfonylamino, halogenated C 1-6 Alkylsulfonylamino or oxo; or L 8 R 8a , where L 8 For non-existent, single-bond, or optional substitution C 1-3 Alkylene, optionally substituted C 2-3 alkenyl, optionally substituted C 2-3 Ethyne group, optionally substituted C 3-6 Cycloalkylene, wherein the optional substitution refers to optional substitution by one or more substituents selected from: halogen, C 1-6 Alkyl, Halogenated C 1-6 Alkyl, hydroxyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, hydroxy C 1-6 Alkyl, C 1-6 Alkoxy C 1-6 Alkyl, or O, N, , , , , , , , , , , , , , where R 8a R 8b Each of the following groups is independently hydrogen, and may be optionally substituted: C 1-10 Straight-chain or branched alkyl groups, C 3-10 cycloalkyl, or Ar 8a Ar 8a It is a 5- to 6-membered aryl group, containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, and a 3- to 8-membered heterocyclic alkyl group containing 1, 2, or 3 heteroatoms independently selected from N, O, or S. The optional substitution refers to optional substitution by one or more substituents selected from: halogen, cyano, C. 1-6 Alkyl, hydroxyl C 1-6 Alkyl, Halogenated C 1-6 Alkyl, C 3-6 cycloalkyl, C 3-6 cycloalkyl C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, C containing 1, 2 or 3 heteroatoms independently selected from N, O or S. 1-6Heteroalkyl groups, 3- to 8-membered heterocyclic groups containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, and 3- to 8-membered heterocyclic groups containing 1, 2, or 3 heteroatoms independently selected from N, O, or S. 1-6 Alkyl, 5- to 6-membered aryl, 5- to 6-membered aryl C 1-6 Alkyl group, 5- to 6-membered heteroaryl group containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 5- to 6-membered heteroaryl group containing 1, 2, or 3 heteroatoms independently selected from N, O, or S C 1-6 Alkyl, hydroxyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 3-6 Cycloalkoxy, 3- to 8-membered heterocyclic alkyl groups containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 5- to 6-membered aryloxy, amino, C 1-6 Alkylamino, amino C 1-6 Alkyl, C 1-6 Carboxyl group, C 1-6 alkoxycarbonyl, C 3-6 Cycloalkoxycarbonyl, 3- to 8-membered heterocyclic cycloalkoxycarbonyl containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 5- to 6-membered aryloxycarbonyl, 5- to 6-membered heteroaryloxycarbonyl containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, C 1-6 Alkyl carbonyloxy, C 3-6 Cycloalkyl carbonyloxy group, 3- to 8-membered heterocyclic carbonyloxy group containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 5- to 6-membered aryl carbonyloxy group, 5- to 6-membered heteroaryl carbonyloxy group containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 5- to 6-membered aryl C 1-6 Alkoxy, C 1-6 Alkyl carbonyl amino, halogenated C 1-6 Alkyl carbonyl amino, C 3-6 Cycloalkylcarbonylamino, 3- to 8-membered heterocyclic carbonylamino containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 5- to 6-membered arylcarbonylamino, 5- to 6-membered heteroarylcarbonylamino containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, C 1-6 alkyl carbonyl amino C 1-6 Alkyl, amino C 1-6 Acyl, hydroxyl amino C 1-6 Acyl group, C 1-6 Alkylamino C 1-6 Acyl, 5- to 6-membered arylamino C 1-6 Acyl group, 5- to 6-membered heteroarylamino group containing 1, 2, or 3 heteroatoms independently selected from N, O, or S. 1-6 Acyl, amino C 1-6 Acyl C 1-6 Alkyl, amino C 1-6 Acylamino, C1-6 Alkylamino C 1-6 Acylamino, C 1-6 Alkyl sulfonyl, halogenated C 1-6 alkylsulfonyl, C 3-6 Cycloalkylsulfonyl, 3- to 8-membered heterocyclic sulfonyl groups containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 5- to 6-membered arylsulfonyl groups, 5- to 6-membered heteroarylsulfonyl groups containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, aminosulfonyl, C 1-6 Alkylaminosulfonyl, 5- to 6-membered arylaminosulfonyl, 5- to 6-membered heteroarylaminosulfonyl containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, C 1-6 alkylsulfonylamino, C 3-6 Cycloalkylsulfonylamino, 3- to 8-membered heterocyclic sulfonylamino containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 5- to 6-membered arylsulfonylamino, 5- to 6-membered heteroarylsulfonylamino containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, halogenated C 1-6 Alkylsulfonylamino, Alternatively, two of the above substituents may form an alkylene dioxy or a haloalkylene dioxy, or two of the above substituents and the cycloalkyl or heterocycloalkyl group attached thereto may together form a cycloalkyl or heterocycloalkyl moiety, or the above substituents may further fuse with an aryl, heteroaryl, cycloalkyl or heterocycloalkyl group to form one or more fused cycloalkyl, aryl, heterocycloalkyl or heteroaryl structural units. Each of the above substituents may optionally be substituted by one or more additional substituents selected from: halogen, cyano, C 1-6 Alkyl, hydroxyl C 1-6 Alkyl, Halogenated C 1-6 Alkyl, C 3-6 cycloalkyl, C 3-6 cycloalkyl C 1-6 Alkyl groups, C containing one, two, or three heteroatoms independently selected from N, O, or S. 1-6 heteroalkyl, hydroxyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 3-6 Cycloalkoxy, C 1-6 Alkylamino, C 1-6 Carboxyl group, C 1-6 alkoxycarbonyl, C 1-6 Alkyl carbonyloxy, C 3-6 Cycloalkylcarbonyloxy, C 1-6 Alkyl carbonyl amino, halogenated C 1-6 Alkyl carbonyl amino, C 3-6 cycloalkylcarbonylamino, C 1-6 alkyl carbonyl amino C 1-6 Alkyl, amino C1-6 Acyl, hydroxyl amino C 1-6 Acyl group, C 1-6 Alkylamino C 1-6 Acyl, amino C 1-6 Acyl C 1-6 Alkyl, amino C 1-6 Acylamino, C 1-6 Alkylamino C 1-6 Acylamino, C 1-6 Alkyl sulfonyl, halogenated C 1-6 alkylsulfonyl, C 3-6 Cycloalkylsulfonyl, aminosulfonyl, C 1-6 Alkylaminosulfonyl, C 1-6 alkylsulfonylamino, C 3-6 Cycloalkylsulfonylamino, halogenated C 1-6 Alkylsulfonylamino or oxo; Or, R 3 With R 4 The connected ring structure shown is as follows: D 1 and D 2 Each group is hydrogen, and the following groups may be substituted: C 1-10 Straight-chain or branched alkyl groups, C 3-10 cycloalkyl, Ar d Ar d The aryl group is a 5- to 6-membered aryl group, a 5- to 6-membered heteroaryl group containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, or a 3- to 8-membered heterocyclic alkyl group containing 1, 2, or 3 heteroatoms independently selected from N, O, or S. The term "optionally substituted" means optionally substituted by one or more groups selected from: halogen, cyano, C. 1-6 Alkyl, hydroxyl C 1-6 Alkyl, Halogenated C 1-6 Alkyl, C 3-6 cycloalkyl, C 3-6 cycloalkyl C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, C containing 1, 2 or 3 heteroatoms independently selected from N, O or S. 1-6 Heteroalkyl groups, 3- to 6-membered heterocyclic groups containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, and 3- to 6-membered heterocyclic groups containing 1, 2, or 3 heteroatoms independently selected from N, O, or S. 1-6 Alkyl, 6- to 8-membered aryl, 6- to 8-membered aryl C 1-6 Alkyl group, containing 1, 2 or 3 independently selected from N, O or S, 6 to 8-membered heteroaryl group, C containing 1, 2 or 3 independently selected from N, O or S 1-6 Alkyl, hydroxyl, C 1-6 Alkoxy, halogenated C1-6 Alkoxy, C 3-6 Cycloalkyloxy, 3- to 6-membered heterocyclic alkyloxy containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 6- to 8-membered aryloxy, amino, C 1-6 Alkylamino, amino C 1-6 Alkyl, C 1-6 Carboxyl group, C 1-6 alkoxycarbonyl, C 3-6 Cycloalkyloxycarbonyl, 3- to 6-membered heterocyclic oxycarbonyl containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 6- to 8-membered aryloxycarbonyl, 6- to 8-membered heteroaryloxycarbonyl containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, C 1-6 alkyl carbonyloxy group, C 3-6 Cycloalkyl carbonyloxy group, 3- to 6-membered heterocyclic carbonyloxy group containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 6- to 8-membered aryl carbonyloxy group, 6- to 8-membered heteroaryl carbonyloxy group containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 6- to 8-membered aryl C 1-6 Alkoxy, C 1-6 Alkyl carbonyl amino, halogenated C 1-6 Alkyl carbonyl amino, C 3-6 Cycloalkylcarbonylamino, 3- to 6-membered heterocyclic carbonylamino containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 6- to 8-membered arylcarbonylamino, 6- to 8-membered heteroarylcarbonylamino containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, C 1-6 alkyl carbonyl amino C 1-6 Alkyl, amino C 1-3 Acyl, hydroxyl amino C 1-3 Acyl group, C 1-6 Alkylamino C 1-3 Acyl, 6- to 8-membered arylamino C 1-3 Acyl group, 6- to 8-membered heteroarylamino group containing 1, 2, or 3 heteroatoms independently selected from N, O, or S 1-3 Acyl, amino C 1-3 Acyl C 1-6 Alkyl, amino C 1-3 Acylamino, C 1-6 Alkylamino C 1-3 Acylamino, C 1-6 Alkyl sulfonyl, halogenated C 1-6 alkylsulfonyl, C 3-6 Cycloalkylsulfonyl, 3- to 6-membered heterocyclic sulfonyl groups containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 6- to 8-membered arylsulfonyl groups, 6- to 8-membered heteroarylsulfonyl groups containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, aminosulfonyl, C 1-6Alkylaminosulfonyl, 6- to 8-membered arylaminosulfonyl, 6- to 8-membered heteroarylaminosulfonyl containing 1, 2 or 3 heteroatoms independently selected from N, O or S, C 1-6 alkylsulfonylamino, C 3-6 Cycloalkylsulfonylamino, 3- to 6-membered heterocyclic sulfonylamino containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 6- to 8-membered arylsulfonylamino, 6- to 8-membered heteroarylsulfonylamino containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, halogenated C 1-6 Alkylsulfonylamino, Alternatively, the two substituents may form an alkylene dioxy or a haloalkylene dioxy; or, the two substituents and the cycloalkyl or heterocycloalkyl group attached thereto may form a cycloalkyl or heterocycloalkyl moiety; or, the substituents may further fuse with an aryl, heteroaryl, cycloalkyl, or heterocycloalkyl group to form one or more fused cycloalkyl, aryl, heterocycloalkyl, or heteroaryl structural units. Each of the above substituents may optionally be substituted by one or more additional substituents selected from: halogen, cyano, C 1-6 Alkyl, hydroxyl C 1-6 Alkyl, Halogenated C 1-6 Alkyl, C 3-6 cycloalkyl, C 3-6 cycloalkyl C 1-3 Alkyl groups, C containing one, two, or three heteroatoms independently selected from N, O, or S. 1-6 heteroalkyl, hydroxyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 3-6 Cycloalkoxy, C 1-6 Alkylamino, C 1-6 Carboxyl group, C 1-6 Alkoxy C 1-6 carbonyl group, C 1-6 alkyl carbonyloxy group, C 3-6 Cycloalkylcarbonyloxy, C 1-6 Alkyl carbonyl amino, halogenated C 1-6 Alkyl carbonyl amino, C 3-6 cycloalkylcarbonylamino, C 1-6 alkyl carbonyl amino C 1-6 Alkyl, amino C 1-6 Acyl, hydroxyl amino C 1-6 Acyl group, C 1-6 Alkylamino C 1-6 Acyl, amino C 1-6 Acyl C 1-6 Alkyl, amino C 1-6 Acylamino, C 1-6 Alkylamino C 1-6 Acylamino, C 1-6Alkyl sulfonyl, halogenated C 1-6 alkylsulfonyl, C 3-6 Cycloalkylsulfonyl, aminosulfonyl, C 1-6 Alkylaminosulfonyl, C 1-6 alkylsulfonylamino, C 3-6 Cycloalkylsulfonylamino, halogenated C 1-6 Alkylsulfonylamino or oxo; L 3a and L 3b Each can be considered independently as a non-existent, single-bond, or arbitrarily substituted C. 1-3 Alkylene, optionally substituted C 2-3 alkenyl, optionally substituted C 2-3 Ethyne group, optionally substituted C 3-6 Cycloalkylene, wherein the optional substitution refers to optional substitution by one or more substituents selected from: halogen, C 1-6 Alkyl, Halogenated C 1-6 Alkyl, hydroxyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, hydroxy C 1-6 Alkyl, C 1-6 Alkoxy C 1-6 Alkyl, or L 3a and L 3b Formation C 3-10 cycloalkyl, Ar 3b Ar 3b The aryl group is a 5- to 6-membered aryl group, a 5- to 6-membered heteroaryl group containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, or a 3- to 8-membered heterocyclic alkyl group containing 1, 2, or 3 heteroatoms independently selected from N, O, or S. The term "optionally substituted" means optionally substituted by one or more groups selected from: halogen, cyano, C. 1-6 Alkyl, hydroxyl C 1-6 Alkyl, Halogenated C 1-6 Alkyl, C 3-6 cycloalkyl, C 3-6 cycloalkyl C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, C containing 1, 2 or 3 heteroatoms independently selected from N, O or S. 1-6 Heteroalkyl groups, 3- to 6-membered heterocyclic groups containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, and 3- to 6-membered heterocyclic groups containing 1, 2, or 3 heteroatoms independently selected from N, O, or S. 1-6 Alkyl, 6- to 8-membered aryl, 6- to 8-membered aryl C 1-6 Alkyl group, containing 1, 2 or 3 independently selected from N, O or S, 6 to 8-membered heteroaryl group, C containing 1, 2 or 3 independently selected from N, O or S 1-6Alkyl, hydroxyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 3-6 Cycloalkyloxy, 3- to 6-membered heterocyclic alkyloxy containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 6- to 8-membered aryloxy, amino, C 1-6 Alkylamino, amino C 1-6 Alkyl, C 1-6 Carboxyl group, C 1-6 alkoxycarbonyl, C 3-6 Cycloalkyloxycarbonyl, 3- to 6-membered heterocyclic oxycarbonyl containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 6- to 8-membered aryloxycarbonyl, 6- to 8-membered heteroaryloxycarbonyl containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, C 1-6 alkyl carbonyloxy group, C 3-6 Cycloalkyl carbonyloxy group, 3- to 6-membered heterocyclic carbonyloxy group containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 6- to 8-membered aryl carbonyloxy group, 6- to 8-membered heteroaryl carbonyloxy group containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 6- to 8-membered aryl C 1-6 Alkoxy, C 1-6 Alkyl carbonyl amino, halogenated C 1-6 Alkyl carbonyl amino, C 3-6 Cycloalkylcarbonylamino, 3- to 6-membered heterocyclic carbonylamino containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 6- to 8-membered arylcarbonylamino, 6- to 8-membered heteroarylcarbonylamino containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, C 1-6 alkyl carbonyl amino C 1-6 Alkyl, amino C 1-3 Acyl, hydroxyl amino C 1-3 Acyl group, C 1-6 Alkylamino C 1-3 Acyl, 6- to 8-membered arylamino C 1-3 Acyl group, 6- to 8-membered heteroarylamino group containing 1, 2, or 3 heteroatoms independently selected from N, O, or S 1-3 Acyl, amino C 1-3 Acyl C 1-6 Alkyl, amino C 1-3 Acylamino, C 1-6 Alkylamino C 1-3 Acylamino, C 1-6 Alkyl sulfonyl, halogenated C 1-6 alkylsulfonyl, C 3-6 Cycloalkylsulfonyl, 3- to 6-membered heterocyclic sulfonyl groups containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 6- to 8-membered arylsulfonyl groups, 6- to 8-membered heteroarylsulfonyl groups containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, aminosulfonyl, C1-6 Alkylaminosulfonyl, 6- to 8-membered arylaminosulfonyl, 6- to 8-membered heteroarylaminosulfonyl containing 1, 2 or 3 heteroatoms independently selected from N, O or S, C 1-6 alkylsulfonylamino, C 3-6 Cycloalkylsulfonylamino, 3- to 6-membered heterocyclic sulfonylamino containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 6- to 8-membered arylsulfonylamino, 6- to 8-membered heteroarylsulfonylamino containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, halogenated C 1-6 Alkylsulfonylamino, Alternatively, the two substituents may form an alkylene dioxy or a haloalkylene dioxy; or, the two substituents and the cycloalkyl or heterocycloalkyl group attached thereto may form a cycloalkyl or heterocycloalkyl moiety; or, the substituents may further fuse with an aryl, heteroaryl, cycloalkyl, or heterocycloalkyl group to form one or more fused cycloalkyl, aryl, heterocycloalkyl, or heteroaryl structural units. Each of the above substituents may optionally be substituted by one or more additional substituents selected from: halogen, cyano, C 1-6 Alkyl, hydroxyl C 1-6 Alkyl, Halogenated C 1-6 Alkyl, C 3-6 cycloalkyl, C 3-6 cycloalkyl C 1-3 Alkyl groups, C containing one, two, or three heteroatoms independently selected from N, O, or S. 1-6 heteroalkyl, hydroxyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 3-6 Cycloalkoxy, C 1-6 Alkylamino, C 1-6 Carboxyl group, C 1-6 Alkoxy C 1-6 carbonyl group, C 1-6 alkyl carbonyloxy group, C 3-6 Cycloalkylcarbonyloxy, C 1-6 Alkyl carbonyl amino, halogenated C 1-6 Alkyl carbonyl amino, C 3-6 cycloalkylcarbonylamino, C 1-6 alkyl carbonyl amino C 1-6 Alkyl, amino C 1-6 Acyl, hydroxyl amino C 1-6 Acyl group, C 1-6 Alkylamino C 1-6 Acyl, amino C 1-6 Acyl C 1-6 Alkyl, amino C 1-6 Acylamino, C 1-6 Alkylamino C 1-6 Acylamino, C1-6 Alkyl sulfonyl, halogenated C 1-6 alkylsulfonyl, C 3-6 Cycloalkylsulfonyl, aminosulfonyl, C 1-6 Alkylaminosulfonyl, C 1-6 alkylsulfonylamino, C 3-6 Cycloalkylsulfonylamino, halogenated C 1-6 Alkylsulfonylamino or oxo; Or, R 4 With R 5 Forming the ring structure shown: E 1 and E 2 Each group is hydrogen, and the following groups may be substituted: C 1-10 Straight-chain or branched alkyl groups, C 3-10 cycloalkyl, Ar e Ar e The aryl group is a 5- to 6-membered aryl group, a 5- to 6-membered heteroaryl group containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, or a 3- to 8-membered heterocyclic alkyl group containing 1, 2, or 3 heteroatoms independently selected from N, O, or S. The term "optionally substituted" means optionally substituted by one or more groups selected from: halogen, cyano, C. 1-6 Alkyl, hydroxyl C 1-6 Alkyl, Halogenated C 1-6 Alkyl, C 3-6 cycloalkyl, C 3-6 cycloalkyl C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, C containing 1, 2, or 3 heteroatoms independently selected from N, O, or S. 1-6 Heteroalkyl groups, 3- to 6-membered heterocyclic groups containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, and 3- to 6-membered heterocyclic groups containing 1, 2, or 3 heteroatoms independently selected from N, O, or S. 1-6 Alkyl, 6- to 8-membered aryl, 6- to 8-membered aryl C 1-6 Alkyl group, containing 1, 2 or 3 independently selected from N, O or S, 6 to 8-membered heteroaryl group, C containing 1, 2 or 3 independently selected from N, O or S 1-6 Alkyl, hydroxyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 3-6 Cycloalkyloxy, 3- to 6-membered heterocyclic alkyloxy containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 6- to 8-membered aryloxy, amino, C 1-6 Alkylamino, amino C 1-6 Alkyl, C 1-6 Carboxyl group, C 1-6 alkoxycarbonyl, C 3-6Cycloalkyloxycarbonyl, 3- to 6-membered heterocyclic oxycarbonyl containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 6- to 8-membered aryloxycarbonyl, 6- to 8-membered heteroaryloxycarbonyl containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, C 1-6 Alkyl carbonyloxy, C 3-6 Cycloalkyl carbonyloxy group, 3- to 6-membered heterocyclic carbonyloxy group containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 6- to 8-membered aryl carbonyloxy group, 6- to 8-membered heteroaryl carbonyloxy group containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 6- to 8-membered aryl C 1-6 Alkoxy, C 1-6 Alkyl carbonyl amino, halogenated C 1-6 Alkyl carbonyl amino, C 3-6 Cycloalkylcarbonylamino, 3- to 6-membered heterocyclic carbonylamino containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 6- to 8-membered arylcarbonylamino, 6- to 8-membered heteroarylcarbonylamino containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, C 1-6 alkyl carbonyl amino C 1-6 Alkyl, amino C 1-3 Acyl, hydroxyl amino C 1-3 Acyl group, C 1-6 Alkylamino C 1-3 Acyl, 6- to 8-membered arylamino C 1-3 Acyl group, 6- to 8-membered heteroarylamino group containing 1, 2, or 3 heteroatoms independently selected from N, O, or S 1-3 Acyl, amino C 1-3 Acyl C 1-6 Alkyl, amino C 1-3 Acylamino, C 1-6 Alkylamino C 1-3 Acylamino, C 1-6 Alkyl sulfonyl, halogenated C 1-6 alkylsulfonyl, C 3-6 Cycloalkylsulfonyl, 3- to 6-membered heterocyclic sulfonyl groups containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 6- to 8-membered arylsulfonyl groups, 6- to 8-membered heteroarylsulfonyl groups containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, aminosulfonyl, C 1-6 Alkylaminosulfonyl, 6- to 8-membered arylaminosulfonyl, 6- to 8-membered heteroarylaminosulfonyl containing 1, 2 or 3 heteroatoms independently selected from N, O or S, C 1-6 alkylsulfonylamino, C 3-6 Cycloalkylsulfonylamino, 3- to 6-membered heterocyclic sulfonylamino containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 6- to 8-membered arylsulfonylamino, 6- to 8-membered heteroarylsulfonylamino containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, halogenated C1-6 Alkylsulfonylamino, Alternatively, the two substituents may form an alkylene dioxy or a haloalkylene dioxy; or, the two substituents and the cycloalkyl or heterocycloalkyl group attached thereto may form a cycloalkyl or heterocycloalkyl moiety; or, the substituents may further fuse with an aryl, heteroaryl, cycloalkyl, or heterocycloalkyl group to form one or more fused cycloalkyl, aryl, heterocycloalkyl, or heteroaryl structural units. Each of the above substituents may optionally be substituted by one or more additional substituents selected from: halogen, cyano, C 1-6 Alkyl, hydroxyl C 1-6 Alkyl, Halogenated C 1-6 Alkyl, C 3-6 cycloalkyl, C 3-6 cycloalkyl C 1-3 Alkyl groups, C containing one, two, or three heteroatoms independently selected from N, O, or S. 1-6 heteroalkyl, hydroxyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 3-6 Cycloalkoxy, C 1-6 Alkylamino, C 1-6 Carboxyl group, C 1-6 Alkoxy C 1-6 carbonyl group, C 1-6 Alkyl carbonyloxy, C 3-6 Cycloalkylcarbonyloxy, C 1-6 Alkyl carbonyl amino, halogenated C 1-6 Alkyl carbonyl amino, C 3-6 cycloalkylcarbonylamino, C 1-6 alkyl carbonyl amino C 1-6 Alkyl, amino C 1-6 Acyl, hydroxyl amino C 1-6 Acyl group, C 1-6 Alkylamino C 1-6 Acyl, amino C 1-6 Acyl C 1-6 Alkyl, amino C 1-6 Acylamino, C 1-6 Alkylamino C 1-6 Acylamino, C 1-6 Alkyl sulfonyl, halogenated C 1-6 alkylsulfonyl, C 3-6 Cycloalkylsulfonyl, aminosulfonyl, C 1-6 Alkylaminosulfonyl, C 1-6 alkylsulfonylamino, C 3-6 Cycloalkylsulfonylamino, halogenated C 1-6 Alkylsulfonylamino or oxo; L 4a and L4b Each can be considered independently as a non-existent, single-bond, or arbitrarily substituted C. 1-3 Alkylene, optionally substituted C 2-3 alkenyl, optionally substituted C 2-3 Ethyne group, optionally substituted C 3-6 Cycloalkylene, wherein the optional substitution refers to optional substitution by one or more substituents selected from: halogen, C 1-6 Alkyl, Halogenated C 1-6 Alkyl, hydroxyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, hydroxy C 1-6 Alkyl, C 1-6 Alkoxy C 1-6 Alkyl, or L 3a and L 3b Formation C 3-10 cycloalkyl, Ar 3b Ar 3b The aryl group is a 5- to 6-membered aryl group, a 5- to 6-membered heteroaryl group containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, or a 3- to 8-membered heterocyclic alkyl group containing 1, 2, or 3 heteroatoms independently selected from N, O, or S. The term "optionally substituted" means optionally substituted by one or more groups selected from: halogen, cyano, C. 1-6 Alkyl, hydroxyl C 1-6 Alkyl, Halogenated C 1-6 Alkyl, C 3-6 cycloalkyl, C 3-6 cycloalkyl C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, C containing 1, 2 or 3 heteroatoms independently selected from N, O or S. 1-6 Heteroalkyl groups, 3- to 6-membered heterocyclic groups containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, and 3- to 6-membered heterocyclic groups containing 1, 2, or 3 heteroatoms independently selected from N, O, or S. 1-6 Alkyl, 6- to 8-membered aryl, 6- to 8-membered aryl C 1-6 Alkyl group, containing 1, 2 or 3 independently selected from N, O or S, 6 to 8-membered heteroaryl group, C containing 1, 2 or 3 independently selected from N, O or S 1-6 Alkyl, hydroxyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 3-6 Cycloalkyloxy, 3- to 6-membered heterocyclic alkyloxy containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 6- to 8-membered aryloxy, amino, C 1-6 Alkylamino, amino C 1-6 Alkyl, C 1-6 Carboxyl group, C 1-6 alkoxycarbonyl, C3-6 Cycloalkyloxycarbonyl, 3- to 6-membered heterocyclic oxycarbonyl containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 6- to 8-membered aryloxycarbonyl, 6- to 8-membered heteroaryloxycarbonyl containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, C 1-6 Alkyl carbonyloxy, C 3-6 Cycloalkyl carbonyloxy group, 3- to 6-membered heterocyclic carbonyloxy group containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 6- to 8-membered aryl carbonyloxy group, 6- to 8-membered heteroaryl carbonyloxy group containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 6- to 8-membered aryl C 1-6 Alkoxy, C 1-6 Alkyl carbonyl amino, halogenated C 1-6 Alkyl carbonyl amino, C 3-6 Cycloalkylcarbonylamino, 3- to 6-membered heterocyclic carbonylamino containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 6- to 8-membered arylcarbonylamino, 6- to 8-membered heteroarylcarbonylamino containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, C 1-6 alkyl carbonyl amino C 1-6 Alkyl, amino C 1-3 Acyl, hydroxyl amino C 1-3 Acyl group, C 1-6 Alkylamino C 1-3 Acyl, 6- to 8-membered arylamino C 1-3 Acyl group, 6- to 8-membered heteroarylamino group containing 1, 2, or 3 heteroatoms independently selected from N, O, or S 1-3 Acyl, amino C 1-3 Acyl C 1-6 Alkyl, amino C 1-3 Acylamino, C 1-6 Alkylamino C 1-3 Acylamino, C 1-6 Alkyl sulfonyl, halogenated C 1-6 alkylsulfonyl, C 3-6 Cycloalkylsulfonyl, 3- to 6-membered heterocyclic sulfonyl groups containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 6- to 8-membered arylsulfonyl groups, 6- to 8-membered heteroarylsulfonyl groups containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, aminosulfonyl, C 1-6 Alkylaminosulfonyl, 6- to 8-membered arylaminosulfonyl, 6- to 8-membered heteroarylaminosulfonyl containing 1, 2 or 3 heteroatoms independently selected from N, O or S, C 1-6 alkylsulfonylamino, C 3-6Cycloalkylsulfonylamino, 3- to 6-membered heterocyclic sulfonylamino containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 6- to 8-membered arylsulfonylamino, 6- to 8-membered heteroarylsulfonylamino containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, halogenated C 1-6 Alkylsulfonylamino, Alternatively, the two substituents may form an alkylene dioxy or a haloalkylene dioxy; or, the two substituents and the cycloalkyl or heterocycloalkyl group attached thereto may form a cycloalkyl or heterocycloalkyl moiety; or, the substituents may further fuse with an aryl, heteroaryl, cycloalkyl, or heterocycloalkyl group to form one or more fused cycloalkyl, aryl, heterocycloalkyl, or heteroaryl structural units. Each of the above substituents may optionally be substituted by one or more additional substituents selected from: halogen, cyano, C 1-6 Alkyl, hydroxyl C 1-6 Alkyl, Halogenated C 1-6 Alkyl, C 3-6 cycloalkyl, C 3-6 cycloalkyl C 1-3 Alkyl groups, C containing one, two, or three heteroatoms independently selected from N, O, or S. 1-6 heteroalkyl, hydroxyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 3-6 Cycloalkoxy, C 1-6 Alkylamino, C 1-6 Carboxyl group, C 1-6 Alkoxy C 1-6 carbonyl group, C 1-6 Alkyl carbonyloxy, C 3-6 Cycloalkylcarbonyloxy, C 1-6 Alkyl carbonyl amino, halogenated C 1-6 Alkyl carbonyl amino, C 3-6 cycloalkylcarbonylamino, C 1-6 alkyl carbonyl amino C 1-6 Alkyl, amino C 1-6 Acyl, hydroxyl amino C 1-6 Acyl group, C 1-6 Alkylamino C 1-6 Acyl, amino C 1-6 Acyl C 1-6 Alkyl, amino C 1-6 Acylamino, C 1-6 Alkylamino C 1-6 Acylamino, C 1-6 Alkyl sulfonyl, halogenated C 1-6 alkylsulfonyl, C 3-6 Cycloalkylsulfonyl, aminosulfonyl, C 1-6 Alkylaminosulfonyl, C 1-6alkylsulfonylamino, C 3-6 Cycloalkylsulfonylamino, halogenated C 1-6 Alkylsulfonylamino or oxo; or R 5 With R 6 Forming the ring structure shown: G 1 and G 2 Each group is hydrogen, and the following groups may be substituted: C 1-10 Straight-chain or branched alkyl groups, C 3-10 cycloalkyl, Ar g Ar g The aryl group is a 5- to 6-membered aryl group, a 5- to 6-membered heteroaryl group containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, or a 3- to 8-membered heterocyclic alkyl group containing 1, 2, or 3 heteroatoms independently selected from N, O, or S. The term "optionally substituted" means optionally substituted by one or more groups selected from: halogen, cyano, C. 1-6 Alkyl, hydroxyl C 1-6 Alkyl, Halogenated C 1-6 Alkyl, C 3-6 cycloalkyl, C 3-6 cycloalkyl C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, C containing 1, 2 or 3 heteroatoms independently selected from N, O or S. 1-6 Heteroalkyl groups, 3- to 6-membered heterocyclic groups containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, and 3- to 6-membered heterocyclic groups containing 1, 2, or 3 heteroatoms independently selected from N, O, or S. 1-6 Alkyl, 6- to 8-membered aryl, 6- to 8-membered aryl C 1-6 Alkyl group, containing 1, 2 or 3 independently selected from N, O or S, 6 to 8-membered heteroaryl group, C containing 1, 2 or 3 independently selected from N, O or S 1-6 Alkyl, hydroxyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 3-6 Cycloalkyloxy, 3- to 6-membered heterocyclic alkyloxy containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 6- to 8-membered aryloxy, amino, C 1-6 Alkylamino, amino C 1-6 Alkyl, C 1-6 Carboxyl group, C 1-6 alkoxycarbonyl, C 3-6 Cycloalkyloxycarbonyl, 3- to 6-membered heterocyclic oxycarbonyl containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 6- to 8-membered aryloxycarbonyl, 6- to 8-membered heteroaryloxycarbonyl containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, C 1-6Alkyl carbonyloxy, C 3-6 Cycloalkyl carbonyloxy group, 3- to 6-membered heterocyclic carbonyloxy group containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 6- to 8-membered aryl carbonyloxy group, 6- to 8-membered heteroaryl carbonyloxy group containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 6- to 8-membered aryl C 1-6 Alkoxy, C 1-6 Alkyl carbonyl amino, halogenated C 1-6 Alkyl carbonyl amino, C 3-6 Cycloalkylcarbonylamino, 3- to 6-membered heterocyclic carbonylamino containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 6- to 8-membered arylcarbonylamino, 6- to 8-membered heteroarylcarbonylamino containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, C 1-6 alkyl carbonyl amino C 1-6 Alkyl, amino C 1-3 Acyl, hydroxyl amino C 1-3 Acyl group, C 1-6 Alkylamino C 1-3 Acyl, 6- to 8-membered arylamino C 1-3 Acyl group, 6- to 8-membered heteroarylamino group containing 1, 2, or 3 heteroatoms independently selected from N, O, or S 1-3 Acyl, amino C 1-3 Acyl C 1-6 Alkyl, amino C 1-3 Acylamino, C 1-6 Alkylamino C 1-3 Acylamino, C 1-6 Alkyl sulfonyl, halogenated C 1-6 alkylsulfonyl, C 3-6 Cycloalkylsulfonyl, 3- to 6-membered heterocyclic sulfonyl groups containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 6- to 8-membered arylsulfonyl groups, 6- to 8-membered heteroarylsulfonyl groups containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, aminosulfonyl, C 1-6 Alkylaminosulfonyl, 6- to 8-membered arylaminosulfonyl, 6- to 8-membered heteroarylaminosulfonyl containing 1, 2 or 3 heteroatoms independently selected from N, O or S, C 1-6 alkylsulfonylamino, C 3-6 Cycloalkylsulfonylamino, 3- to 6-membered heterocyclic sulfonylamino containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 6- to 8-membered arylsulfonylamino, 6- to 8-membered heteroarylsulfonylamino containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, halogenated C 1-6 Alkylsulfonylamino, Alternatively, the two substituents may form an alkylene dioxy or a haloalkylene dioxy; or, the two substituents and the cycloalkyl or heterocycloalkyl group attached thereto may form a cycloalkyl or heterocycloalkyl moiety; or, the substituents may further fuse with an aryl, heteroaryl, cycloalkyl, or heterocycloalkyl group to form one or more fused cycloalkyl, aryl, heterocycloalkyl, or heteroaryl structural units. Each of the above substituents may optionally be substituted by one or more additional substituents selected from: halogen, cyano, C 1-6 Alkyl, hydroxyl C 1-6 Alkyl, Halogenated C 1-6 Alkyl, C 3-6 cycloalkyl, C 3-6 cycloalkyl C 1-3 Alkyl groups, C containing one, two, or three heteroatoms independently selected from N, O, or S. 1-6 heteroalkyl, hydroxyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 3-6 Cycloalkoxy, C 1-6 Alkylamino, C 1-6 Carboxyl group, C 1-6 Alkoxy C 1-6 carbonyl group, C 1-6 Alkyl carbonyloxy, C 3-6 Cycloalkylcarbonyloxy, C 1-6 Alkyl carbonyl amino, halogenated C 1-6 Alkyl carbonyl amino, C 3-6 cycloalkylcarbonylamino, C 1-6 alkyl carbonyl amino C 1-6 Alkyl, amino C 1-6 Acyl, hydroxyl amino C 1-6 Acyl group, C 1-6 Alkylamino C 1-6 Acyl, amino C 1-6 Acyl C 1-6 Alkyl, amino C 1-6 Acylamino, C 1-6 Alkylamino C 1-6 Acylamino, C 1-6 Alkyl sulfonyl, halogenated C 1-6 alkylsulfonyl, C 3-6 Cycloalkylsulfonyl, aminosulfonyl, C 1-6 Alkylaminosulfonyl, C 1-6 alkylsulfonylamino, C 3-6 Cycloalkylsulfonylamino, halogenated C 1-6 Alkylsulfonylamino or oxo; L 5a and L 5b Each is an independent C that does not exist, has a single bond, or can be arbitrarily replaced.1-3 Alkylene, optionally substituted C 2-3 alkenyl, optionally substituted C 2-3 Ethyne group, optionally substituted C 3-6 Cycloalkylene, wherein the optional substitution refers to optional substitution by one or more substituents selected from: halogen, C 1-6 Alkyl, Halogenated C 1-6 Alkyl, hydroxyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, hydroxy C 1-6 Alkyl, C 1-6 Alkoxy C 1-6 Alkyl, or L 3a and L 3b Formation C 3-10 cycloalkyl, Ar 3b Ar 3b The aryl group is a 5- to 6-membered aryl group, a 5- to 6-membered heteroaryl group containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, or a 3- to 8-membered heterocyclic alkyl group containing 1, 2, or 3 heteroatoms independently selected from N, O, or S. The term "optionally substituted" means optionally substituted by one or more groups selected from: halogen, cyano, C. 1-6 Alkyl, hydroxyl C 1-6 Alkyl, Halogenated C 1-6 Alkyl, C 3-6 cycloalkyl, C 3-6 cycloalkyl C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, C containing 1, 2 or 3 heteroatoms independently selected from N, O or S. 1-6 Heteroalkyl groups, 3- to 6-membered heterocyclic groups containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, and 3- to 6-membered heterocyclic groups containing 1, 2, or 3 heteroatoms independently selected from N, O, or S. 1-6 Alkyl, 6- to 8-membered aryl, 6- to 8-membered aryl C 1-6 Alkyl group, containing 1, 2 or 3 independently selected from N, O or S, 6 to 8-membered heteroaryl group, C containing 1, 2 or 3 independently selected from N, O or S 1-6 Alkyl, hydroxyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 3-6 Cycloalkyloxy, 3- to 6-membered heterocyclic alkyloxy containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 6- to 8-membered aryloxy, amino, C 1-6 Alkylamino, amino C 1-6 Alkyl, C 1-6 Carboxyl group, C 1-6 alkoxycarbonyl, C 3-6Cycloalkyloxycarbonyl, 3- to 6-membered heterocyclic oxycarbonyl containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 6- to 8-membered aryloxycarbonyl, 6- to 8-membered heteroaryloxycarbonyl containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, C 1-6 Alkyl carbonyloxy, C 3-6 Cycloalkyl carbonyloxy group, 3- to 6-membered heterocyclic carbonyloxy group containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 6- to 8-membered aryl carbonyloxy group, 6- to 8-membered heteroaryl carbonyloxy group containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 6- to 8-membered aryl C 1-6 Alkoxy, C 1-6 Alkyl carbonyl amino, halogenated C 1-6 Alkyl carbonyl amino, C 3-6 Cycloalkylcarbonylamino, 3- to 6-membered heterocyclic carbonylamino containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 6- to 8-membered arylcarbonylamino, 6- to 8-membered heteroarylcarbonylamino containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, C 1-6 alkyl carbonyl amino C 1-6 Alkyl, amino C 1-3 Acyl, hydroxyl amino C 1-3 Acyl group, C 1-6 Alkylamino C 1-3 Acyl, 6- to 8-membered arylamino C 1-3 Acyl group, 6- to 8-membered heteroarylamino group containing 1, 2, or 3 heteroatoms independently selected from N, O, or S. 1-3 Acyl, amino C 1-3 Acyl C 1-6 Alkyl, amino C 1-3 Acylamino, C 1-6 Alkylamino C 1-3 Acylamino, C 1-6 Alkyl sulfonyl, halogenated C 1-6 alkylsulfonyl, C 3-6 Cycloalkylsulfonyl, 3- to 6-membered heterocyclic sulfonyl groups containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 6- to 8-membered arylsulfonyl groups, 6- to 8-membered heteroarylsulfonyl groups containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, aminosulfonyl, C 1-6 Alkylaminosulfonyl, 6- to 8-membered arylaminosulfonyl, 6- to 8-membered heteroarylaminosulfonyl containing 1, 2 or 3 heteroatoms independently selected from N, O or S, C 1-6 alkylsulfonylamino, C 3-6 Cycloalkylsulfonylamino, 3- to 6-membered heterocyclic sulfonylamino containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 6- to 8-membered arylsulfonylamino, 6- to 8-membered heteroarylsulfonylamino containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, halogenated C1-6 Alkylsulfonylamino, Alternatively, the two substituents may form an alkylene dioxy or a haloalkylene dioxy; or, the two substituents and the cycloalkyl or heterocycloalkyl group attached thereto may form a cycloalkyl or heterocycloalkyl moiety; or, the substituents may further fuse with an aryl, heteroaryl, cycloalkyl, or heterocycloalkyl group to form one or more fused cycloalkyl, aryl, heterocycloalkyl, or heteroaryl structural units. Each of the above substituents may optionally be substituted by one or more additional substituents selected from: halogen, cyano, C 1-6 Alkyl, hydroxyl C 1-6 Alkyl, Halogenated C 1-6 Alkyl, C 3-6 cycloalkyl, C 3-6 cycloalkyl C 1-3 Alkyl groups, C containing one, two, or three heteroatoms independently selected from N, O, or S. 1-6 heteroalkyl, hydroxyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 3-6 Cycloalkoxy, C 1-6 Alkylamino, C 1-6 Carboxyl group, C 1-6 Alkoxy C 1-6 carbonyl group, C 1-6 Alkyl carbonyloxy, C 3-6 Cycloalkylcarbonyloxy, C 1-6 Alkyl carbonyl amino, halogenated C 1-6 Alkyl carbonyl amino, C 3-6 cycloalkylcarbonylamino, C 1-6 alkyl carbonyl amino C 1-6 Alkyl, amino C 1-6 Acyl, hydroxyl amino C 1-6 Acyl group, C 1-6 Alkylamino C 1-6 Acyl, amino C 1-6 Acyl C 1-6 Alkyl, amino C 1-6 Acylamino, C 1-6 Alkylamino C 1-6 Acylamino, C 1-6 Alkyl sulfonyl, halogenated C 1-6 alkylsulfonyl, C 3-6 Cycloalkylsulfonyl, aminosulfonyl, C 1-6 Alkylaminosulfonyl, C 1-6 alkylsulfonylamino, C 3-6 Cycloalkylsulfonylamino, halogenated C 1-6 Alkylsulfonylamino or oxo; Or R 6 With R7 Forming the ring structure shown: J 1 and J 2 Each group is hydrogen, and the following groups may be substituted: C 1-10 Straight-chain or branched alkyl groups, C 3-10 cycloalkyl, Ar j Ar j The aryl group is a 5- to 6-membered aryl group, a 5- to 6-membered heteroaryl group containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, or a 3- to 8-membered heterocyclic alkyl group containing 1, 2, or 3 heteroatoms independently selected from N, O, or S. The term "optionally substituted" means optionally substituted by one or more groups selected from: halogen, cyano, C. 1-6 Alkyl, hydroxyl C 1-6 Alkyl, Halogenated C 1-6 Alkyl, C 3-6 cycloalkyl, C 3-6 cycloalkyl C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, C containing 1, 2, or 3 heteroatoms independently selected from N, O, or S. 1-6 Heteroalkyl groups, 3- to 6-membered heterocyclic groups containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, and 3- to 6-membered heterocyclic groups containing 1, 2, or 3 heteroatoms independently selected from N, O, or S. 1-6 Alkyl, 6- to 8-membered aryl, 6- to 8-membered aryl C 1-6 Alkyl group, containing 1, 2 or 3 independently selected from N, O or S, 6 to 8-membered heteroaryl group, C containing 1, 2 or 3 independently selected from N, O or S 1-6 Alkyl, hydroxyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 3-6 Cycloalkyloxy, 3- to 6-membered heterocyclic alkyloxy containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 6- to 8-membered aryloxy, amino, C 1-6 Alkylamino, amino C 1-6 Alkyl, C 1-6 Carboxyl group, C 1-6 alkoxycarbonyl, C 3-6 Cycloalkyloxycarbonyl, 3- to 6-membered heterocyclic oxycarbonyl containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 6- to 8-membered aryloxycarbonyl, 6- to 8-membered heteroaryloxycarbonyl containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, C 1-6 Alkyl carbonyloxy, C 3-6Cycloalkyl carbonyloxy group, 3- to 6-membered heterocyclic carbonyloxy group containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 6- to 8-membered aryl carbonyloxy group, 6- to 8-membered heteroaryl carbonyloxy group containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 6- to 8-membered aryl C 1-6 Alkoxy, C 1-6 Alkyl carbonyl amino, halogenated C 1-6 Alkyl carbonyl amino, C 3-6 Cycloalkylcarbonylamino, 3- to 6-membered heterocyclic carbonylamino containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 6- to 8-membered arylcarbonylamino, 6- to 8-membered heteroarylcarbonylamino containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, C 1-6 alkyl carbonyl amino C 1-6 Alkyl, amino C 1-3 Acyl, hydroxyl amino C 1-3 Acyl group, C 1-6 Alkylamino C 1-3 Acyl, 6- to 8-membered arylamino C 1-3 Acyl group, 6- to 8-membered heteroarylamino group containing 1, 2, or 3 heteroatoms independently selected from N, O, or S. 1-3 Acyl, amino C 1-3 Acyl C 1-6 Alkyl, amino C 1-3 Acylamino, C 1-6 Alkylamino C 1-3 Acylamino, C 1-6 Alkyl sulfonyl, halogenated C 1-6 alkylsulfonyl, C 3-6 Cycloalkylsulfonyl, 3- to 6-membered heterocyclic sulfonyl groups containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 6- to 8-membered arylsulfonyl groups, 6- to 8-membered heteroarylsulfonyl groups containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, aminosulfonyl, C 1-6 Alkylaminosulfonyl, 6- to 8-membered arylaminosulfonyl, 6- to 8-membered heteroarylaminosulfonyl containing 1, 2 or 3 heteroatoms independently selected from N, O or S, C 1-6 alkylsulfonylamino, C 3-6 Cycloalkylsulfonylamino, 3- to 6-membered heterocyclic sulfonylamino containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 6- to 8-membered arylsulfonylamino, 6- to 8-membered heteroarylsulfonylamino containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, halogenated C 1-6 Alkylsulfonylamino, Alternatively, the two substituents may form an alkylene dioxy or a haloalkylene dioxy; or, the two substituents and the cycloalkyl or heterocycloalkyl group attached thereto may form a cycloalkyl or heterocycloalkyl moiety; or, the substituents may further fuse with an aryl, heteroaryl, cycloalkyl, or heterocycloalkyl group to form one or more fused cycloalkyl, aryl, heterocycloalkyl, or heteroaryl structural units. Each of the above substituents may optionally be substituted by one or more additional substituents selected from: halogen, cyano, C 1-6 Alkyl, hydroxyl C 1-6 Alkyl, Halogenated C 1-6 Alkyl, C 3-6 cycloalkyl, C 3-6 cycloalkyl C 1-3 Alkyl groups, C containing one, two, or three heteroatoms independently selected from N, O, or S. 1-6 heteroalkyl, hydroxyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 3-6 Cycloalkoxy, C 1-6 Alkylamino, C 1-6 Carboxyl group, C 1-6 Alkoxy C 1-6 carbonyl group, C 1-6 Alkyl carbonyloxy, C 3-6 Cycloalkylcarbonyloxy, C 1-6 Alkyl carbonyl amino, halogenated C 1-6 Alkyl carbonyl amino, C 3-6 cycloalkylcarbonylamino, C 1-6 alkyl carbonyl amino C 1-6 Alkyl, amino C 1-6 Acyl, hydroxyl amino C 1-6 Acyl group, C 1-6 Alkylamino C 1-6 Acyl, amino C 1-6 Acyl C 1-6 Alkyl, amino C 1-6 Acylamino, C 1-6 Alkylamino C 1-6 Acylamino, C 1-6 Alkyl sulfonyl, halogenated C 1-6 alkylsulfonyl, C 3-6 Cycloalkylsulfonyl, aminosulfonyl, C 1-6 Alkylaminosulfonyl, C 1-6 alkylsulfonylamino, C 3-6 Cycloalkylsulfonylamino, halogenated C 1-6 Alkylsulfonylamino or oxo; L 6a and L 6b Each is an independent C that does not exist, has a single bond, or can be arbitrarily replaced.1-3 Alkylene, optionally substituted C 2-3 alkenyl, optionally substituted C 2-3 Ethyne group, optionally substituted C 3-6 Cycloalkylene, wherein the optional substitution refers to optional substitution by one or more substituents selected from: halogen, C 1-6 Alkyl, Halogenated C 1-6 Alkyl, hydroxyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, hydroxy C 1-6 Alkyl, C 1-6 Alkoxy C 1-6 Alkyl, or L 3a and L 3b Formation C 3-10 cycloalkyl, Ar 3b Ar 3b The aryl group is a 5- to 6-membered aryl group, a 5- to 6-membered heteroaryl group containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, or a 3- to 8-membered heterocyclic alkyl group containing 1, 2, or 3 heteroatoms independently selected from N, O, or S. The term "optionally substituted" means optionally substituted by one or more groups selected from: halogen, cyano, C. 1-6 Alkyl, hydroxyl C 1-6 Alkyl, Halogenated C 1-6 Alkyl, C 3-6 cycloalkyl, C 3-6 cycloalkyl C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, C containing 1, 2, or 3 heteroatoms independently selected from N, O, or S. 1-6 Heteroalkyl groups, 3- to 6-membered heterocyclic groups containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, and 3- to 6-membered heterocyclic groups containing 1, 2, or 3 heteroatoms independently selected from N, O, or S. 1-6 Alkyl, 6- to 8-membered aryl, 6- to 8-membered aryl C 1-6 Alkyl group, containing 1, 2 or 3 independently selected from N, O or S, 6 to 8-membered heteroaryl group, C containing 1, 2 or 3 independently selected from N, O or S 1-6 Alkyl, hydroxyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 3-6 Cycloalkyloxy, 3- to 6-membered heterocyclic alkyloxy containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 6- to 8-membered aryloxy, amino, C 1-6 Alkylamino, amino C 1-6 Alkyl, C 1-6 Carboxyl group, C 1-6 alkoxycarbonyl, C 3-6Cycloalkyloxycarbonyl, 3- to 6-membered heterocyclic oxycarbonyl containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 6- to 8-membered aryloxycarbonyl, 6- to 8-membered heteroaryloxycarbonyl containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, C 1-6 Alkyl carbonyloxy, C 3-6 Cycloalkyl carbonyloxy group, 3- to 6-membered heterocyclic carbonyloxy group containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 6- to 8-membered aryl carbonyloxy group, 6- to 8-membered heteroaryl carbonyloxy group containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 6- to 8-membered aryl C 1-6 Alkoxy, C 1-6 Alkyl carbonyl amino, halogenated C 1-6 Alkyl carbonyl amino, C 3-6 Cycloalkylcarbonylamino, 3- to 6-membered heterocyclic carbonylamino containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 6- to 8-membered arylcarbonylamino, 6- to 8-membered heteroarylcarbonylamino containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, C 1-6 alkyl carbonyl amino C 1-6 Alkyl, amino C 1-3 Acyl, hydroxyl amino C 1-3 Acyl group, C 1-6 Alkylamino C 1-3 Acyl, 6- to 8-membered arylamino C 1-3 Acyl group, 6- to 8-membered heteroarylamino group containing 1, 2, or 3 heteroatoms independently selected from N, O, or S. 1-3 Acyl, amino C 1-3 Acyl C 1-6 Alkyl, amino C 1-3 Acylamino, C 1-6 Alkylamino C 1-3 Acylamino, C 1-6 Alkyl sulfonyl, halogenated C 1-6 alkylsulfonyl, C 3-6 Cycloalkylsulfonyl, 3- to 6-membered heterocyclic sulfonyl groups containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 6- to 8-membered arylsulfonyl groups, 6- to 8-membered heteroarylsulfonyl groups containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, aminosulfonyl, C 1-6 Alkylaminosulfonyl, 6- to 8-membered arylaminosulfonyl, 6- to 8-membered heteroarylaminosulfonyl containing 1, 2 or 3 heteroatoms independently selected from N, O or S, C 1-6 alkylsulfonylamino, C 3-6 Cycloalkylsulfonylamino, 3- to 6-membered heterocyclic sulfonylamino containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 6- to 8-membered arylsulfonylamino, 6- to 8-membered heteroarylsulfonylamino containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, halogenated C1-6 Alkylsulfonylamino, Alternatively, the two substituents may form an alkylene dioxy or a haloalkylene dioxy; or, the two substituents and the cycloalkyl or heterocycloalkyl group attached thereto may form a cycloalkyl or heterocycloalkyl moiety; or, the substituents may further fuse with an aryl, heteroaryl, cycloalkyl, or heterocycloalkyl group to form one or more fused cycloalkyl, aryl, heterocycloalkyl, or heteroaryl structural units. Each of the above substituents may optionally be substituted by one or more additional substituents selected from: halogen, cyano, C 1-6 Alkyl, hydroxyl C 1-6 Alkyl, Halogenated C 1-6 Alkyl, C 3-6 cycloalkyl, C 3-6 cycloalkyl C 1-3 Alkyl groups, C containing one, two, or three heteroatoms independently selected from N, O, or S. 1-6 heteroalkyl, hydroxyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 3-6 Cycloalkoxy, C 1-6 Alkylamino, C 1-6 Carboxyl group, C 1-6 Alkoxy C 1-6 carbonyl group, C 1-6 Alkyl carbonyloxy, C 3-6 Cycloalkylcarbonyloxy, C 1-6 Alkyl carbonyl amino, halogenated C 1-6 Alkyl carbonyl amino, C 3-6 cycloalkylcarbonylamino, C 1-6 alkyl carbonyl amino C 1-6 Alkyl, amino C 1-6 Acyl, hydroxyl amino C 1-6 Acyl group, C 1-6 Alkylamino C 1-6 Acyl, amino C 1-6 Acyl C 1-6 Alkyl, amino C 1-6 Acylamino, C 1-6 Alkylamino C 1-6 Acylamino, C 1-6 Alkyl sulfonyl, halogenated C 1-6 alkylsulfonyl, C 3-6 Cycloalkylsulfonyl, aminosulfonyl, C 1-6 Alkylaminosulfonyl, C 1-6 alkylsulfonylamino, C 3-6 Cycloalkylsulfonylamino, halogenated C 1-6 Alkylsulfonylamino or oxo; Or R 7 With R8 Forming the ring structure shown: K 1 and K 2 Each group is hydrogen, and the following groups may be substituted: C 1-10 Straight-chain or branched alkyl groups, C 3-10 cycloalkyl, Ar k Ar k The aryl group is a 5- to 6-membered aryl group, a 5- to 6-membered heteroaryl group containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, or a 3- to 8-membered heterocyclic alkyl group containing 1, 2, or 3 heteroatoms independently selected from N, O, or S. The term "optionally substituted" means optionally substituted by one or more groups selected from: halogen, cyano, C. 1-6 Alkyl, hydroxyl C 1-6 Alkyl, Halogenated C 1-6 Alkyl, C 3-6 cycloalkyl, C 3-6 cycloalkyl C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, C containing 1, 2, or 3 heteroatoms independently selected from N, O, or S. 1-6 Heteroalkyl groups, 3- to 6-membered heterocyclic groups containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, and 3- to 6-membered heterocyclic groups containing 1, 2, or 3 heteroatoms independently selected from N, O, or S. 1-6 Alkyl, 6- to 8-membered aryl, 6- to 8-membered aryl C 1-6 Alkyl group, containing 1, 2 or 3 independently selected from N, O or S, 6 to 8-membered heteroaryl group, C containing 1, 2 or 3 independently selected from N, O or S 1-6 Alkyl, hydroxyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 3-6 Cycloalkyloxy, 3- to 6-membered heterocyclic alkyloxy containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 6- to 8-membered aryloxy, amino, C 1-6 Alkylamino, amino C 1-6 Alkyl, C 1-6 Carboxyl group, C 1-6 alkoxycarbonyl, C 3-6 Cycloalkyloxycarbonyl, 3- to 6-membered heterocyclic oxycarbonyl containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 6- to 8-membered aryloxycarbonyl, 6- to 8-membered heteroaryloxycarbonyl containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, C 1-6 Alkyl carbonyloxy, C 3-6Cycloalkyl carbonyloxy group, 3- to 6-membered heterocyclic carbonyloxy group containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 6- to 8-membered aryl carbonyloxy group, 6- to 8-membered heteroaryl carbonyloxy group containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 6- to 8-membered aryl C 1-6 Alkoxy, C 1-6 Alkyl carbonyl amino, halogenated C 1-6 Alkyl carbonyl amino, C 3-6 Cycloalkylcarbonylamino, 3- to 6-membered heterocyclic carbonylamino containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 6- to 8-membered arylcarbonylamino, 6- to 8-membered heteroarylcarbonylamino containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, C 1-6 alkyl carbonyl amino C 1-6 Alkyl, amino C 1-3 Acyl, hydroxyl amino C 1-3 Acyl group, C 1-6 Alkylamino C 1-3 Acyl, 6- to 8-membered arylamino C 1-3 Acyl group, 6- to 8-membered heteroarylamino group containing 1, 2, or 3 heteroatoms independently selected from N, O, or S. 1-3 Acyl, amino C 1-3 Acyl C 1-6 Alkyl, amino C 1-3 Acylamino, C 1-6 Alkylamino C 1-3 Acylamino, C 1-6 Alkyl sulfonyl, halogenated C 1-6 alkylsulfonyl, C 3-6 Cycloalkylsulfonyl, 3- to 6-membered heterocyclic sulfonyl groups containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 6- to 8-membered arylsulfonyl groups, 6- to 8-membered heteroarylsulfonyl groups containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, aminosulfonyl, C 1-6 Alkylaminosulfonyl, 6- to 8-membered arylaminosulfonyl, 6- to 8-membered heteroarylaminosulfonyl containing 1, 2 or 3 heteroatoms independently selected from N, O or S, C 1-6 alkylsulfonylamino, C 3-6 Cycloalkylsulfonylamino, 3- to 6-membered heterocyclic sulfonylamino containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 6- to 8-membered arylsulfonylamino, 6- to 8-membered heteroarylsulfonylamino containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, halogenated C 1-6 Alkylsulfonylamino, Alternatively, the two substituents may form an alkylene dioxy or a haloalkylene dioxy; or, the two substituents and the cycloalkyl or heterocycloalkyl group attached thereto may form a cycloalkyl or heterocycloalkyl moiety; or, the substituents may further fuse with an aryl, heteroaryl, cycloalkyl, or heterocycloalkyl group to form one or more fused cycloalkyl, aryl, heterocycloalkyl, or heteroaryl structural units. Each of the above substituents may optionally be substituted by one or more additional substituents selected from: halogen, cyano, C 1-6 Alkyl, hydroxyl C 1-6 Alkyl, Halogenated C 1-6 Alkyl, C 3-6 cycloalkyl, C 3-6 cycloalkyl C 1-3 Alkyl groups, C containing one, two, or three heteroatoms independently selected from N, O, or S. 1-6 heteroalkyl, hydroxyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 3-6 Cycloalkoxy, C 1-6 Alkylamino, C 1-6 Carboxyl group, C 1-6 Alkoxy C 1-6 carbonyl group, C 1-6 Alkyl carbonyloxy, C 3-6 Cycloalkylcarbonyloxy, C 1-6 Alkyl carbonyl amino, halogenated C 1-6 Alkyl carbonyl amino, C 3-6 cycloalkylcarbonylamino, C 1-6 alkyl carbonyl amino C 1-6 Alkyl, amino C 1-6 Acyl, hydroxyl amino C 1-6 Acyl group, C 1-6 Alkylamino C 1-6 Acyl, amino C 1-6 Acyl C 1-6 Alkyl, amino C 1-6 Acylamino, C 1-6 Alkylamino C 1-6 Acylamino, C 1-6 Alkyl sulfonyl, halogenated C 1-6 alkylsulfonyl, C 3-6 Cycloalkylsulfonyl, aminosulfonyl, C 1-6 Alkylaminosulfonyl, C 1-6 alkylsulfonylamino, C 3-6 Cycloalkylsulfonylamino, halogenated C 1-6 Alkylsulfonylamino or oxo; L 7a and L 7b Each is an independent C that does not exist, has a single bond, or can be arbitrarily replaced.1-3 Alkylene, optionally substituted C 2-3 alkenyl, optionally substituted C 2-3 Ethyne group, optionally substituted C 3-6 Cycloalkylene, wherein the optional substitution refers to optional substitution by one or more substituents selected from: halogen, C 1-6 Alkyl, Halogenated C 1-6 Alkyl, hydroxyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, hydroxy C 1-6 Alkyl, C 1-6 Alkoxy C 1-6 Alkyl, or L 3a and L 3b Formation C 3-10 cycloalkyl, Ar 3b Ar 3b The aryl group is a 5- to 6-membered aryl group, a 5- to 6-membered heteroaryl group containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, or a 3- to 8-membered heterocyclic alkyl group containing 1, 2, or 3 heteroatoms independently selected from N, O, or S. The term "optionally substituted" means optionally substituted by one or more groups selected from: halogen, cyano, C. 1-6 Alkyl, hydroxyl C 1-6 Alkyl, Halogenated C 1-6 Alkyl, C 3-6 cycloalkyl, C 3-6 cycloalkyl C 1-6 Alkyl, C 2-6 alkenyl, C 2-6 Alkyne group, C containing 1, 2, or 3 heteroatoms independently selected from N, O, or S. 1-6 Heteroalkyl groups, 3- to 6-membered heterocyclic groups containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, and 3- to 6-membered heterocyclic groups containing 1, 2, or 3 heteroatoms independently selected from N, O, or S. 1-6 Alkyl, 6- to 8-membered aryl, 6- to 8-membered aryl C 1-6 Alkyl group, containing 1, 2 or 3 independently selected from N, O or S, 6 to 8-membered heteroaryl group, C containing 1, 2 or 3 independently selected from N, O or S 1-6 Alkyl, hydroxyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 3-6 Cycloalkyloxy, 3- to 6-membered heterocyclic alkyloxy containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 6- to 8-membered aryloxy, amino, C 1-6 Alkylamino, amino C 1-6 Alkyl, C 1-6 Carboxyl group, C 1-6 alkoxycarbonyl, C 3-6Cycloalkyloxycarbonyl, 3- to 6-membered heterocyclic oxycarbonyl containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 6- to 8-membered aryloxycarbonyl, 6- to 8-membered heteroaryloxycarbonyl containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, C 1-6 Alkyl carbonyloxy, C 3-6 Cycloalkyl carbonyloxy group, 3- to 6-membered heterocyclic carbonyloxy group containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 6- to 8-membered aryl carbonyloxy group, 6- to 8-membered heteroaryl carbonyloxy group containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 6- to 8-membered aryl C 1-6 Alkoxy, C 1-6 Alkyl carbonyl amino, halogenated C 1-6 Alkyl carbonyl amino, C 3-6 Cycloalkylcarbonylamino, 3- to 6-membered heterocyclic carbonylamino containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 6- to 8-membered arylcarbonylamino, 6- to 8-membered heteroarylcarbonylamino containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, C 1-6 alkyl carbonyl amino C 1-6 Alkyl, amino C 1-3 Acyl, hydroxyl amino C 1-3 Acyl group, C 1-6 Alkylamino C 1-3 Acyl, 6- to 8-membered arylamino C 1-3 Acyl group, 6- to 8-membered heteroarylamino group containing 1, 2, or 3 heteroatoms independently selected from N, O, or S. 1-3 Acyl, amino C 1-3 Acyl C 1-6 Alkyl, amino C 1-3 Acylamino, C 1-6 Alkylamino C 1-3 Acylamino, C 1-6 Alkyl sulfonyl, halogenated C 1-6 alkylsulfonyl, C 3-6 Cycloalkylsulfonyl, 3- to 6-membered heterocyclic sulfonyl groups containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 6- to 8-membered arylsulfonyl groups, 6- to 8-membered heteroarylsulfonyl groups containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, aminosulfonyl, C 1-6 Alkylaminosulfonyl, 6- to 8-membered arylaminosulfonyl, 6- to 8-membered heteroarylaminosulfonyl containing 1, 2 or 3 heteroatoms independently selected from N, O or S, C 1-6 alkylsulfonylamino, C 3-6 Cycloalkylsulfonylamino, 3- to 6-membered heterocyclic sulfonylamino containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, 6- to 8-membered arylsulfonylamino, 6- to 8-membered heteroarylsulfonylamino containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, halogenated C1-6 Alkylsulfonylamino, Alternatively, the two substituents may form an alkylene dioxy or a haloalkylene dioxy; or, the two substituents and the cycloalkyl or heterocycloalkyl group attached thereto may form a cycloalkyl or heterocycloalkyl moiety; or, the substituents may further fuse with an aryl, heteroaryl, cycloalkyl, or heterocycloalkyl group to form one or more fused cycloalkyl, aryl, heterocycloalkyl, or heteroaryl structural units. Each of the above substituents may optionally be substituted by one or more additional substituents selected from: halogen, cyano, C 1-6 Alkyl, hydroxyl C 1-6 Alkyl, Halogenated C 1-6 Alkyl, C 3-6 cycloalkyl, C 3-6 cycloalkyl C 1-3 Alkyl groups, C containing one, two, or three heteroatoms independently selected from N, O, or S. 1-6 heteroalkyl, hydroxyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 3-6 Cycloalkoxy, C 1-6 Alkylamino, C 1-6 Carboxyl group, C 1-6 Alkoxy C 1-6 carbonyl group, C 1-6 Alkyl carbonyloxy, C 3-6 Cycloalkylcarbonyloxy, C 1-6 Alkyl carbonyl amino, halogenated C 1-6 Alkyl carbonyl amino, C 3-6 cycloalkylcarbonylamino, C 1-6 alkyl carbonyl amino C 1-6 Alkyl, amino C 1-6 Acyl, hydroxyl amino C 1-6 Acyl group, C 1-6 Alkylamino C 1-6 Acyl, amino C 1-6 Acyl C 1-6 Alkyl, amino C 1-6 Acylamino, C 1-6 Alkylamino C 1-6 Acylamino, C 1-6 Alkyl sulfonyl, halogenated C 1-6 alkylsulfonyl, C 3-6 Cycloalkylsulfonyl, aminosulfonyl, C 1-6 Alkylaminosulfonyl, C 1-6 alkylsulfonylamino, C 3-6 Cycloalkylsulfonylamino, halogenated C 1-6 Alkylsulfonylamino or oxo.

[0010] In a specific implementation, R 1 For non-existent, hydrogen, or optionally substituted C 1-10 Straight-chain or branched alkyl groups; L 1 For non-existent, single-bond, or optional substitution C 1-3 Alkylene; A 1 and A 2 Each can be independently represented as: O, S, , ; R 2 The following groups are optional substitutions: C (for non-existent hydrogen groups) 1-10 Straight-chain or branched alkyl, C 1-10 Straight-chain or branched alkoxy groups, C 3-10 Cycloalkyl, amino, amino C 1-6 Acyl group; L 2 For non-existent, single-bond, or optional substitution C 1-3 Alkylene, optionally substituted C 2-3 alkenyl, optionally substituted C 3-6 Cycloalkylene; B 1 and B 2 Each can be represented independently as: non-existent, O, S. , ; R 3 It is hydrogen, or a group as shown below: , , , , Where R 3a R 3b Each is hydrogen, and the C atoms are optionally substituted. 1-10 Straight-chain or branched alkyl groups, C 3-10 cycloalkyl; R 4 It is hydrogen, halogen, or optionally substituted with the following groups: C 1-10 Straight-chain or branched alkyl, C 3-10 cycloalkyl, C 1-10 alkoxy, amino, or Ar 4 ; R 5 It is hydrogen, halogen, nitro, or optionally substituted with the following groups: C 1-10 Straight-chain or branched alkyl, amino, C 1-10 alkoxy or Ar 5 ; R 7 It is hydrogen, halogen, nitro, or optionally substituted with the following groups: C1-10 Straight-chain or branched alkyl groups, C 1-10 alkoxy, amino, or Ar 7 ; R 8 R 9 Each can be independently hydrogen, halogen, or optionally substituted C. 1-10 Straight-chain or branched alkyl groups.

[0011] In a specific implementation, -A 2 -A 1 -L 1 -R 1 The hydroxyl group is optionally substituted; R 2 Amino groups that are absent, hydrogen-containing, or optionally substituted; L 2 C is non-existent and can be arbitrarily substituted. 1-3 Alkylene, optionally substituted C 3-6 Cycloalkylene; B 1 and B 2 Each is independent as: O, ; R 3 It is hydrogen, or a group as shown below: , , where R 3a It is hydrogen, with optional substitution of C. 1-10 Straight-chain or branched alkyl groups; R 4 It is hydrogen, halogen, or optionally substituted with the following groups: C 1-10 Straight-chain or branched alkyl, C 3-10 cycloalkyl, C 1-10 alkoxy or Ar 4 ; R 5 It is hydrogen, halogen, nitro, or optionally substituted with the following groups: amino, C 1-10 alkoxy or Ar 5 Ar 5 It is a 5- to 6-membered aryl group, a 5- to 6-membered heteroaryl group containing 1, 2 or 3 heteroatoms independently selected from N, O or S, or a 3- to 8-membered heterocyclic alkyl group containing 1, 2 or 3 heteroatoms independently selected from N, O or S; R 7 It is hydrogen, halogen, nitro, or optionally substituted with the following groups: C 1-10 alkoxy, amino, or Ar 7 ; R 8 R 9 Each is hydrogen on its own.

[0012] In a specific implementation, R 4 It is hydrogen, halogen, or optionally substituted with the following groups: C 1-10 Straight-chain or branched alkyl, C 3-10 cycloalkyl or Ar 4 ; R 6 It is hydrogen, halogen, hydroxyl, or optionally substituted with the following groups: C 1-10 Straight-chain or branched alkyl groups, C 3-10 cycloalkyl, C 1-10 alkoxy or Ar 6 ; R 7 It is hydrogen, or Ar with optional substitution. 7 .

[0013] In a specific embodiment, the compound is any one of the compounds indicated by compound numbers 1-157.

[0014] In a specific embodiment, the compound is any of the compounds indicated by the following compound numbers: 1-5, 7, 9-10, 14-16, 18-22, 34-35, 44-45, 48-53, 57-58, 63-66, 68, 77, 83, 87-88, 91-96, 99-102, 105-108, 110-112, 114, 117, 119-120, 128, 130-131, 138, 142, 147, 155 and 157.

[0015] In a specific embodiment, the compound is any of the following compound numbers: 1, 9-10, 53, 57-58, 105-107, 117.

[0016] In a second aspect, the present invention provides a pharmaceutical composition comprising the compound described in the first aspect, a pharmaceutically acceptable salt, solvate or prodrug thereof, and optionally a pharmaceutically acceptable carrier or excipient.

[0017] In a third aspect, the present invention provides the use of the compounds described in the first aspect, pharmaceutically acceptable salts, solvates or prodrugs thereof, in the preparation of adrenergic receptor α2 antagonists or partial antagonists.

[0018] In a preferred embodiment, the adrenergic receptor α2 is adrenergic receptor α2A (ADRA2A).

[0019] In a preferred embodiment, the use includes scientific research purposes.

[0020] In a specific implementation, the adrenergic receptor α2A (ADRA2A) antagonist or partial antagonist is a drug for treating or preventing inflammatory bowel disease (IBD).

[0021] In a preferred embodiment, the inflammatory bowel disease is ulcerative colitis (UC), Crohn's disease (CD), or enteritis.

[0022] In a fourth aspect, the present invention provides the compounds described in the first aspect, pharmaceutically acceptable salts, solvates, or prodrugs thereof for the treatment or prevention of inflammatory bowel disease (IBD).

[0023] In a preferred embodiment, the inflammatory bowel disease is ulcerative colitis (UC), Crohn's disease (CD), or enteritis.

[0024] In a fifth aspect, the present invention provides a medicament comprising the compound described in the first aspect, a pharmaceutically acceptable salt thereof, a solvate thereof, or a prodrug thereof, for the treatment or prevention of inflammatory bowel disease (IBD).

[0025] In a preferred embodiment, the inflammatory bowel disease is ulcerative colitis (UC), Crohn's disease (CD), or enteritis.

[0026] In a sixth aspect, the present invention provides a method for treating or preventing inflammatory bowel disease (IBD), the method comprising the step of administering an effective amount of the compound of the first aspect, a pharmaceutically acceptable salt thereof, a solvate or a prodrug thereof, or a pharmaceutical composition of the second aspect to a subject in need of such treatment.

[0027] In a preferred embodiment, the inflammatory bowel disease is ulcerative colitis (UC), Crohn's disease (CD), or enteritis.

[0028] It should be understood that, within the scope of this invention, the above-described technical features of this invention and the technical features specifically described below (such as in the embodiments) can be combined with each other to form new or preferred technical solutions. Due to space limitations, they will not be described in detail here. Attached Figure Description

[0029] Figure 1 The process of establishing an acute DSS colitis model in mice was shown; Figure 2-5 The experimental results of the DSS model are shown (where, Figure 2 The changes in body weight of mice in each group were shown; Figure 3 The colon anatomy of each group of mice is shown; Figure 4 A statistical graph showing the colon length of mice in each group is displayed; Figure 5 The graph shows the disease activity scores of mice in each group on day 7 of the experiment. Detailed Implementation

[0030] Through extensive and in-depth research, the inventors unexpectedly discovered a series of yohimbine derivatives. These yohimbine derivatives not only possess novel structures but also exhibit improved receptor selectivity. Therefore, as α2-adrenergic receptor antagonists, the yohimbine derivatives of this invention demonstrate important scientific basis and innovative value in the treatment of inflammatory bowel disease. This invention was completed based on these findings.

[0031] Terminology Definition The scientific and technical terms used herein have the meanings conventionally understood by one of ordinary skill in the art to which this invention pertains. For clarity only, the terms used herein are defined as follows. However, it should be understood that the definitions of the terms do not constitute a limitation on the scope of protection of this invention, nor do they imply that the applicant / inventor acknowledges that these definitions constitute part of the prior art.

[0032] The terms used throughout this application, including the specification and claims, are defined and interpreted below. When describing the compounds of the invention, unless otherwise indicated, the terms used are interpreted according to the following definitions.

[0033] When a group can be substituted, such a group can be substituted by one or more substituents, and preferably by one, two or three substituents. Substituents can be selected from, but are not limited to, the group consisting of, for example, halogens, hydroxyl groups, oxo groups, cyano groups, nitro groups, amide groups, carboxyl groups, amino groups, cyanohaloalkoxy groups and haloalkyl groups.

[0034] As used herein, terms such as “alkyl, aryl or cycloalkyl, each optionally substituted with ...” or “alkyl, aryl or cycloalkyl, optionally substituted with ...” include “alkyl optionally substituted with ...”, “aryl optionally substituted with ...” and “cycloalkyl optionally substituted with ...”.

[0035] The term "halogen" refers to fluorine, chlorine, bromine, or iodine. Preferred halogen groups are fluorine, chlorine, and bromine.

[0036] The term "alkyl" itself, or as part of another substituent, refers to the formula C n H 2n+1 The alkyl group is a hydrocarbon group, where n is a number greater than or equal to 1. Typically, the alkyl group of the present invention comprises 1 to 8 carbon atoms, preferably 1 to 4 carbon atoms, more preferably 1 to 3 carbon atoms, and even more preferably 1 to 2 carbon atoms. The alkyl group can be straight-chain or branched and can be substituted as indicated herein. x-y -alkyl and C x -C y-alkyl refers to an alkyl group containing x to y carbon atoms. Suitable alkyl groups include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl and tert-butyl, pentyl and its isomers (e.g., n-pentyl, isopentyl), and hexyl and its isomers (e.g., n-hexyl, isohexyl). Preferred alkyl groups include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl and tert-butyl. When the suffix "ene" ("alkylene") is used in conjunction with alkyl, it is intended to indicate that the alkyl group as defined herein has two single bonds as connection points to other groups.

[0037] The term "alkylene" includes methylene, ethylene, methylmethylene, propylene, ethyl ethylene, and 1,2-dimethyl ethylene.

[0038] As used herein, the term "alkenyl" refers to an unsaturated hydrocarbon group, which may be straight-chain or branched, containing one or more carbon-carbon double bonds. Suitable alkenyl groups contain 2 to 6 carbon atoms, preferably 2 to 4 carbon atoms, and even more preferably 2 to 3 carbon atoms. Examples of alkenyl groups are vinyl, 2-propenyl, 2-butenyl, 3-butenyl, 2-pentenyl and its isomers, 2-hexenyl and its isomers, 2,4-pentadienyl, etc.

[0039] The term "alkynyl" refers to a class of monovalent unsaturated hydrocarbon groups, wherein the unsaturation originates from the presence of one or more carbon-carbon triple bonds. Alynyl groups typically and preferably have the same number of carbon atoms as described above with respect to alkenyl groups. Non-limiting examples of alkynyl groups include ethynyl, 2-propynyl, 2-butynyl, 3-butynyl, 2-pentynyl and its isomers, 2-hexynyl and its isomers, etc.

[0040] The terms “alkenylyl” and “alkynylylyl” refer to alkenyl or alkynyl groups as defined above, which have two single bonds as connection points to other groups.

[0041] The term "haloalkyl" alone or in combination refers to an alkyl group in which one or more hydrogen atoms are replaced by halogens as defined above, having the meaning as defined above. Non-limiting examples of such haloalkyl groups include chloromethyl, 1-bromoethyl, fluoromethyl, difluoromethyl, trifluoromethyl, 1,1,1-trifluoroethyl, etc.

[0042] The term "cycloalkyl" refers to a cyclic alkyl group, i.e., a monovalent, saturated, or unsaturated hydrocarbon group having one or two ring structures. Cycloalkyl groups include monocyclic or bicyclic hydrocarbon groups. A cycloalkyl group may contain three or more carbon atoms in the ring, and typically, according to the invention, contains 3 to 10 carbon atoms, more preferably 3 to 8 carbon atoms, and even more preferably 3 to 6 carbon atoms. Examples of cycloalkyl groups include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl, with cyclopropyl being particularly preferred. When the suffix "ene" is used in conjunction with a cyclic group, it refers to a cyclic group as defined herein having two single bonds as connection points to other groups. Therefore, "cycloalkylene" herein refers to the formula C n H 2n-2 A saturated allocyclic hydrocarbon divalent group. Suitable cycloalkylene groups are C10 and C20. 3-6 Cycloalkylene, preferably C 3-5 Cycloalkylene (i.e., 1,2-cyclopropylene, 1,1-cyclopropylene, 1,1-cyclobutylene, 1,2-cyclobutylene, 1,3-cyclobutylene, 1,3-cyclopentylene, or 1,1-cyclopentylene), more preferably C 3-4 Cycloalkylene compounds (i.e., 1,3-cyclopropylene, 1,1-cyclopropylene, 1,1-cyclobutylene, 1,2-cyclobutylene).

[0043] When at least one carbon atom in a cycloalkyl group is replaced by a heteroatom, the resulting ring is referred to herein as a "heterocycloalkyl" or "heterocyclic group". As used herein, the terms "heterocyclic group", "heterocycloalkyl", or "heterocycle" themselves or as part of another group refer to a non-aromatic, fully saturated, or partially unsaturated cyclic group (e.g., a 3- to 7-membered monocyclic ring, a 7- to 11-membered bicyclic ring, or containing a total of 3 to 10 ring atoms) having at least one heteroatom in at least one carbon-containing ring. Each ring of a heterocyclic group containing a heteroatom may have one, two, three, or four heteroatoms selected from nitrogen, oxygen, and / or sulfur atoms, wherein the nitrogen and sulfur heteroatoms may optionally be oxidized and the nitrogen heteroatom may optionally be quaternized. Any carbon atom of the heterocyclic group may be oxysubstituted (e.g., piperidinone, pyrrolidone). Heterocyclic groups may be linked at any heteroatom or carbon atom in the ring or ring system, provided that the valence allows. The rings of polycyclic heterocycles may be fused, bridged, and / or linked by one or more spiro atoms. Non-limiting exemplary heterocyclic groups include oxacyclobutyl, piperidinyl, aziridine, 2-imidazolinyl, pyrazolyl, imidazolinyl, isoxazolinyl, oxazolyl, isoxazolinyl, thiazolinyl, isothiazolyl, piperidinyl, 3H-indolyl, dihydroindolyl, isodihydroindolyl, 2-oxopiperazinyl, piperazinyl, homopiperazinyl, 2-pyrazolyl, 3-pyrazolyl, tetrahydro-2H-pyranyl, 2H-pyranyl, 4H-pyranyl, 3,4-dihydro-2H-pyranyl, 3-dioxolanecycloyl, and 1,4-dioxylalkyl. 2,5-Dioxoimidazolyl, 2-oxopiperidinyl, 2-oxopiperylyl, dihydroindolyl, tetrahydropyranyl, tetrahydrofuranyl, tetrahydroquinolinyl, tetrahydroisoquinolin-1-yl, tetrahydroisoquinolin-2-yl, tetrahydroisoquinolin-3-yl, tetrahydroisoquinolin-4-yl, thiomorpholin-4-yl, thiomorpholin-4-yl sulfoxide, thiomorpholin-4-yl sulfone, 1,3-dioxopentaneyl, 1,4-oxothiacyclohexyl, 1H-pyrrolazinyl, tetrahydro-1,1-dioxothiopheneyl, N-formylpiperazinyl, and morpholin-4-yl.

[0044] As used herein, the term "aryl" refers to a polyunsaturated aromatic hydrocarbon group having a single ring (i.e., phenyl) or multiple aromatic rings fused together (e.g., naphthyl) or covalently linked, typically containing 5 to 12 atoms; preferably 6 to 10 atoms, wherein at least one ring is aromatic. The aromatic ring may optionally include one or two additional rings (cycloalkyl, heterocyclic, or heteroaryl) fused thereto. Aryl groups are also intended to include partially hydrogenated derivatives of the carbocyclic systems listed herein. Non-limiting examples of aryl groups include phenyl, biphenyl, biphenylene, 5-tetrahydronaphthyl or 6-tetrahydronaphthyl, naphth-1-yl or naphth-2-yl, 4-indenyl, 5-indenyl, 6-indenyl or 7-indenyl, 1-acenaphthyl, 2-acenaphthyl, 3-acenaphthyl, 4-acenaphthyl or 5-acenaphthyl, 3-dihydroacenaphthyl, 4-dihydroacenaphthyl or 5- Dihydroacenaphthyl, 1-benzocyclopentadienyl or 2-benzocyclopentadienyl, 4-indanyl or 5-indanyl, 5-tetrahydronaphthyl, 6-tetrahydronaphthyl, 7-tetrahydronaphthyl or 8-tetrahydronaphthyl, 1,2,3,4-tetrahydronaphthyl, 1,4-dihydronaphthyl, 1-pyrene, 2-pyrene, 3-pyrene, 4-pyrene or 5-pyrene.

[0045] As used herein, the term "arylene" is intended to include divalent carbocyclic aromatic ring systems, such as phenylene, biphenylene, naphthylene, indenylene, cyclopentadienylene, azulene, etc. Arylene is also intended to include partially hydrogenated derivatives of the carbocyclic systems listed above. Non-limiting examples of such partially hydrogenated derivatives are 1,2,3,4-tetrahydronaphthylene, 1,4-dihydronaphthylene, etc.

[0046] The term "arylalkyl" or "aralkyl group" refers to a straight-chain or branched alkyl group in which one carbon atom is attached to an aryl ring. Non-limiting examples of arylalkyl groups include benzyl, phenethyl, (naphth-1-yl)methyl, or (naphth-2-yl)methyl. When an arylalkyl group is substituted, one or more substituents are attached either to the alkyl group or to the aryl ring. "x-membered arylalkyl" refers to a straight-chain or branched alkyl group in which one carbon atom is attached to an x-membered aryl ring. When at least one carbon atom in the aryl group is replaced by a heteroatom, the resulting ring is referred to herein as a heteroaryl ring.

[0047] As used herein, the term "heteroaryl" itself, or as part of another group, refers, but is not limited to, an aromatic ring or ring system of 5 to 12 carbon atoms containing fused or covalently linked 1 to 2 rings, typically containing 5 to 6 atoms; wherein at least one ring is aromatic, and wherein one or more carbon atoms in one or more of these rings are replaced by oxygen, nitrogen, and / or sulfur atoms, wherein the nitrogen and sulfur heteroatoms may optionally be oxidized and the nitrogen heteroatomium may optionally be quaternized. Such rings may be fused with aryl, cycloalkyl, heteroaryl, or heterocyclic rings. Non-limiting examples of such heteroaryl groups include: furanyl, thiophene, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, triazolyl, oxadiazolyl, thiadiazolyl, tetrazolyl, oxtriazolyl, thiatriazolyl, pyridinyl, pyrazinyl, pyridazinyl, oxazinyl, dioxazenyl, thiazinyl, triazinyl, imidazo[2,1-b][1,3]thiazolyl, thieno[3,2-b]furanyl, thieno[3,2-b]thienoyl, thieno[2,3-d][1,3]thiazolyl, thieno[2,3-d]imidazolyl, tetrazo[1,5-a]pyridinyl, indoleyl, indazinyl, isoindoleyl, benzofuranyl, isobenzofuranyl, benzothiopheneyl, isobenzothiopheneyl, inzolyl, benzyl Imidazolyl, 1,3-benzoxazolyl, 1,2-benzoisoxazolyl, 2,1-benzoisoxazolyl, 1,3-benzothiazolyl, 1,2-benzoisothiazolyl, 2,1-benzoisothiazolyl, benzotriazolyl, 1,2,3-benzoxadiazolyl, 2,1,3-benzoxadiazolyl, 1,2,3-benzothiadiazolyl, 2,1,3-benzothiadiazolyl Thiophene-pyridyl, purine, imidazo[1,2-a]pyridyl, 6-oxo-pyridazin-1(6H)-yl, 2-oxopyridazin-1(2H)-yl, 6-oxo-pyridazin-1(6H)-yl, 2-oxopyridazin-1(2H)-yl, 1,3-benzodioxanepentenyl, quinolinyl, isoquinolinyl, cycloazinyl, quinazolinyl, quinoxolinyl.

[0048] As used herein, the term "hybrid aryl" refers to a divalent carbon-cyclic aromatic ring system, including pyridyl groups, etc.

[0049] As used herein, the term "solvent complex" is used to describe a molecular complex comprising the compounds of the present invention and one or more pharmaceutically acceptable solvent molecules (e.g., ethanol). When the solvent is water, the term "hydrate" is used.

[0050] As used herein, the term "prodrug" refers to a pharmaceutically acceptable derivative, such as an ester, whose biotransformation in vivo yields an active pharmaceutical ingredient. Prodrugs are characterized by increased bioavailability and readily metabolized in vivo into an active compound. For the purposes of this invention, suitable prodrugs include carboxylic acid esters, particularly alkyl esters, aryl esters, acyloxyalkyl esters, and dioxacyclopentenyl carboxylic acid esters.

[0051] As used in this article, the term "prodrug" means any compound that will be modified to form a drug class, wherein the modification can be performed inside or outside the body, and before or after the prodrug is delivered to the indicated area of ​​the body to which the drug is administered.

[0052] yohimbine and its derivatives Yohimbine is a natural indole alkaloid with well-defined α2-adrenergic receptor antagonistic activity. Studies have shown that by regulating α2-AR, it can affect the degree of inflammation, modulate the infiltration of neutrophils and macrophages, and improve the expression of inflammatory markers such as iNOS in mucosal tissues. However, the mechanism of action and dosage range of yohimbine and its derivatives in IBD still lack systematic evaluation. Therefore, developing derivatives based on the yohimbine scaffold with higher α2 subtype selectivity, improved intestinal pharmacokinetic properties, and enhanced dual regulatory capabilities of the immune and mucosal barriers has significant potential for research and clinical application.

[0053] To address the problems existing in the prior art, this invention provides a class of yohimbine derivatives with novel structures. Specifically, this invention provides compounds of Formula I, their pharmaceutically acceptable salts, solvates, or prodrugs: (I) In the formula, R 1 L 1 A 1 A 2 R 2 L 2 B 1 B 2 R 3 R 4 R 5 R 6 R 7 R 8 R 9 Each as described above.

[0054] In specific embodiments, the present invention provides example compounds as shown in Table 1 below, including the following compounds and the corresponding covered compounds and their acceptable salts and solvated complexes.

[0055] Table 1 The compounds of the present invention can be in pharmaceutically acceptable salt form. Pharmaceutically acceptable salts of compounds of Formula I include their acid addition salts and base salts. Suitable acid addition salts are formed from acids that form non-toxic salts. Examples include acetates, adipic acid salts, aspartate salts, benzoates, benzenesulfonates, bicarbonates / carbonates, bisulfates / sulfates, borates, dextrorotatory camphor sulfonates, citrates, cyclohexylaminosulfonates, ethanedisulfonates, ethanesulfonates, formates, fumarates, glucohepanoates, glucuronates, hexafluorophosphates, hydroxybenzoylbenzoates, hydrochlorides / chlorides, hydrobromides / bromines, hydroiodides / iodides, hydroxyethylsulfonates, lactates, malates, maleates, malonates, methanesulfonates, methyl sulfates, naphthylates, 2-naphthylsulfonates, nicotinates, nitrates, orotates, oxalates, palmitates, dihydroxynaphthylates, phosphates / hydrogen phosphates / dihydrogen phosphates, pyroglutamates, sucrose salts, stearates, succinates, tannins, tartrates, toluenesulfonates, trifluoroacetates, and xinofoate. Suitable base salts are formed from bases that form non-toxic salts. Examples include aluminum, arginine, benzathine penicillin, calcium, choline, diethylamine, diethanolamine, glycine, lysine, magnesium, meglumine, ethanolamine, potassium, sodium, tromethamine, 2-(diethylamino)ethanol, ethanolamine, morpholine, 4-(2-hydroxyethyl)morpholine, and zinc salts. Hemisalts that form both acids and bases, such as hemisulfates and hemicalcium salts, can also be formed. Preferred pharmaceutically acceptable salts include hydrochlorides / chlorides, hydrobromines / bromines, hydrogen sulfates / sulfates, nitrates, citrates, and acetates.

[0056] When the compounds of the present invention contain both acidic and basic groups, they can also form internal salts, and such compounds are within the scope of the present invention. When the compounds of the present invention contain hydrogen-donating heteroatoms (e.g., NH), the present invention also covers salts and / or isomers formed by transferring said hydrogen atoms to basic groups or intramolecular atoms.

[0057] Pharmaceutically acceptable salts of compounds of formula I can be prepared by one or more of these methods: (i) By reacting a compound of formula I with a desired acid; (ii) By reacting a compound of formula I with a desired base; (iii) By removing an acid- or base-insecure protecting group from a suitable precursor of Formula I or by using a desired acid to open the ring of a suitable cyclic precursor, such as a lactone or lactam; or (iv) Convert one salt of a compound of formula I into another by reacting with a suitable acid or by using a suitable ion exchange column.

[0058] All these reactions typically take place in solution. Salts can precipitate from solution and be collected by filtration or recovered by evaporating the solvent. The degree of ionization in the salt can range from complete ionization to almost no ionization.

[0059] When referring to compounds of formula I, this includes referring to their salts, solvates, multicomponent complexes, and liquid crystals.

[0060] The compounds of the present invention include compounds of Formula I as defined above, including all their polymorphs and crystals, their prodrugs and isomers (including optical, geometric and tautomeric isomers), and isotopically labeled compounds of Formula I.

[0061] Furthermore, although pharmaceutically acceptable salts are generally preferred for the salts of the compounds of the present invention, it should be noted that the present invention also includes, in the broadest sense, non-pharmaceutical acceptable salts, which can be used, for example, for the separation and / or purification of the compounds of the present invention. For example, salts formed using optically active acids or bases can be used to form diastereomer salts that facilitate the separation of optically active isomers of compounds of Formula I above.

[0062] This invention also generally covers all pharmaceutically acceptable prodrugs and prodrugs of Formula I compounds.

[0063] Pharmaceutical Composition Based on the compound shown in Formula I, the present invention provides a pharmaceutical composition containing a therapeutically effective amount of the compound shown in Formula I or a pharmaceutically acceptable salt, solvate or prodrug thereof, and a pharmaceutically acceptable carrier or excipient.

[0064] The pharmaceutical compositions of the present invention can be formulated into dosage forms suitable for various routes of administration for the treatment of inflammatory bowel disease. A dosage is an amount of medicine that effectively improves or eliminates one or more symptoms. For the treatment of a specific disease, an effective amount is an amount sufficient to improve or, in some way, alleviate the symptoms associated with the disease. Such a dosage may be administered as a single dose or may be administered according to an effective treatment regimen. The dosage may cure the disease, but administration is usually intended to improve the symptoms of the disease. Repeated administration is generally required to achieve the desired symptom improvement. The dosage of the medicine will be determined based on the patient's age, health and weight, the type of concurrent treatment, the frequency of treatment, and the desired therapeutic benefit.

[0065] The pharmaceutical formulations of this invention can be administered to any mammal, provided they can obtain the therapeutic effects of the compounds of this invention. Humans are the most important of these mammals.

[0066] The compounds or pharmaceutical compositions thereof of the present invention can be used to treat inflammatory bowel disease. In specific embodiments, the inflammatory bowel disease includes, but is not limited to, ulcerative colitis (UC), Crohn's disease (CD), or enteritis.

[0067] The pharmaceutical formulations of the present invention can be manufactured using known methods. For example, they can be manufactured by conventional mixing, granulation, tableting, dissolving, or freeze-drying processes. When manufacturing oral formulations, solid excipients and active compounds can be combined, and the mixture can be selectively ground. If desired or necessary, appropriate excipients can be added, and the granular mixture can be processed to obtain tablets or tablet cores.

[0068] Suitable excipients, especially fillers, include sugars such as lactose or sucrose, mannitol or sorbitol; cellulose preparations or calcium phosphates, such as tricalcium phosphate or dicalcium phosphate; and binders, such as starch pastes, including corn starch, wheat starch, rice starch, potato starch, gelatin, astragalus gum, methylcellulose, hydroxypropyl methylcellulose, sodium carboxymethylcellulose, or polyvinylpyrrolidone. If necessary, disintegrants, such as the starches mentioned above, as well as carboxymethyl starch, croscarmellose, agar, or alginate or its salts, such as sodium alginate, can be added. Adjuvants, especially flow conditioners and lubricants, include silica, talc, stearates such as calcium magnesium stearate, stearic acid, or polyethylene glycol. If necessary, a suitable coating that resists gastric juices can be provided to the tablet core. For this purpose, a concentrated sugar solution can be applied. This solution may contain gum arabic, talc, polyvinylpyrrolidone, polyethylene glycol and / or titanium dioxide, varnish solutions, and suitable organic solvents or solvent mixtures. To prepare a coating resistant to gastric juice, a suitable cellulose solution, such as cellulose acetate phthalate or hydroxypropyl methylcellulose phthalate, can be used. Dyes or pigments can be added to the coating of the tablet or lozenge core, for example, to identify or characterize combinations of active ingredient dosages.

[0069] Based on the above-described compounds and pharmaceutical compositions, the present invention further provides a method for treating or preventing inflammatory bowel disease, the method comprising administering to a subject in need the compounds or pharmaceutical compositions of the present invention.

[0070] The administration method includes, but is not limited to, various administration methods known in the art, and can be determined according to the patient's actual condition.

[0071] Based on the teachings of this invention, those skilled in the art will recognize the use of the compounds of this invention in the preparation of medicaments for the prevention or treatment of inflammatory bowel disease. Of course, as α2-adrenergic receptor antagonists, the compounds of this invention can not only be prepared as therapeutic agents for inflammatory bowel disease, but also have various other applications, such as for research purposes.

[0072] Advantages of this invention: 1. The compound shown in Formula I of this invention is a novel yohimbine derivative; 2. As an α2-adrenergic receptor antagonist, the compound of Formula I of the present invention has important scientific basis and innovative value in the treatment of inflammatory bowel disease; 3. Compared with yohimbine, the compound of Formula I of the present invention has significantly improved antagonism and receptor selectivity of α2-adrenergic receptors, has a clear therapeutic mechanism, and has optimized safety.

[0073] The technical solution of the present invention is further described below with reference to specific implementation examples. However, the following implementation examples do not constitute a limitation on the present invention. All application methods based on the principles and technical means of the present invention are within the scope of the present invention. Experimental methods in the following embodiments that do not specify specific conditions are generally performed under conventional conditions or as recommended by the manufacturer. Unless otherwise stated, percentages and parts are by weight.

[0074] Example Materials and Methods Unless otherwise stated, all temperatures are expressed in °C, and all reactions are carried out at room temperature.

[0075] Analytical thin-layer chromatography (TLC) is used to monitor reactions, establish rapid chromatographic conditions, and confirm the purity of intermediates or final products. The TLC plates used are silica gel plates with a coating thickness of 0.2-0.25 mm, manufactured by Yu Cheng Chemical (Shanghai) Co., Ltd., and developed at room temperature using ultraviolet light (wavelength: 254 nm, 365 nm) or with iodine or a colorimetric reagent under the following conditions.

[0076] 1) Alizarin (2 grams of alizarin in 100 ml of ethanol); 2) Nitrophenylhydrazine (1 gram of nitrophenylhydrazine dissolves in 2 liters of 1N hydrochloric acid); 3) Potassium permanganate solution (1.5 g potassium permanganate and 1.5 mL of 10 wt% NaOH solution added to 200 mL of water); 4) Bromocresol green solution (0.1 wt% bromocresol green 2-propanol solution) HPLC-MS spectra were obtained using electrospray ionization (ESI) on Shimadzu or Agilent LCMS.

[0077] The specific requirements for the Shimadzu instrument are as follows: Shimadzu LC / MS determinations were performed on a Shimadzu PDA system equipped with a Shimadzu 2020 mass spectrometer, using a MERCK Chromolith Flash RP-18e (25 × 3 mm) column at 50 °C. The mobile phase consisted of 0.04% aqueous trifluoroacetic acid (A) and 0.02% trifluoroacetic acid acetonitrile solution (B). The flow rate was 1.5 mL / min.

[0078] Shimadzu LCMS determinations were performed on a Shimadzu PDA system using a WelCh Ultimate® XB-C18 (3.0 × 50 mm, 3 μm) column at 50 °C. The mobile phase consisted of 0.04% aqueous trifluoroacetic acid (A) and 0.02% trifluoroacetic acid acetonitrile solution (B). The flow rate was 1.2 mL / min.

[0079] Shimadzu LC / MS determinations were performed on a Shimadzu PDA system equipped with a Shimadzu 2020 mass spectrometer, using a ShimNex HE C18-AQ (30 × 3.0 mm, 3 μm) column at 50 °C. The mobile phase consisted of 0.04% aqueous trifluoroacetic acid (A) and 0.02% trifluoroacetic acid acetonitrile solution (B). The flow rate was 0.8 mL / min.

[0080] Shimadzu LC / MS determinations were performed on a Shimadzu PDA system equipped with a Shimadzu 2020 mass spectrometer, using a Chrom Core 120 C18 (3 μm, 3.0 × 30 mm) column at 50 °C. The mobile phase consisted of 0.04% aqueous trifluoroacetic acid (A) and 0.02% trifluoroacetic acid acetonitrile solution (B). The flow rate was 0.8 mL / min.

[0081] Shimadzu LC assays were performed on a Shimadzu PDA system using a Titank C18 (5 μm, 2.1 × 50 mm) column at 40 °C. The mobile phase consisted of 10 mM ammonium bicarbonate aqueous solution (A) and acetonitrile (B). The flow rate was 0.8 mL / min.

[0082] The specific requirements for Agilent instruments are as follows: The Agilent LC / MS determination was performed on an Agilent HPLC system equipped with a DAD / ELSD detector and an Agilent 6125B mass spectrometer, using an Agilent Poroshell 120 EC-C18 (2.7 μm, 3.0 × 30 mm) column at 50 °C. The mobile phase consisted of 0.04% aqueous trifluoroacetic acid (A) and 0.02% trifluoroacetic acid acetonitrile solution (B). The flow rate was 2.0 mL / min.

[0083] Purification was performed using a preparative HPLC system from Agilent, under the following conditions: The chromatography was performed on an Agilent 1260 Infinity system equipped with 6150 MSDa, using an Atlantis HILIC Silica (150 × 4.6 mm, 5 μm) column at 40 °C. The mobile phase consisted of 0.05% difluoroacetic acid (D-formic acid) aqueous solution (A) and 0.05% difluoroacetic acid acetonitrile solution (B). The flow rate was 1.0 mL / min.

[0084] Preparative HPLC was performed on an Agilent 1260 Infinity system equipped with a 6150 MSD, using an XSelect HSS T3 (100 × 3.0 mm, 3.5 μm) column at 40 °C. The mobile phase consisted of 0.05% aqueous difluoroacetic acid (A) and 0.05% difluoroacetic acid acetonitrile solution (B). The flow rate was 1.0 mL / min.

[0085] Nuclear magnetic resonance spectra were measured on Bruker Avance AV400 MHz and AV500 MHz NMR spectra. 1 HNMR, 13 C NMR, 19 F NMR and 31 P NMR). 1 ¹H NMR chemical shifts were recorded relative to tetramethylsilane (TMS) with the central peak of deuterated chloroform (CDCl₃) (δ = 7.27 ppm) as an internal standard. Data are presented as follows: chemical shift, peak type [s = singlet, d = doublet, t = triplet, q = quartet, m = multiplet, br = broad peak], coupling constant (Hz), and integral. 13 C10 NMR chemical shifts were expressed relative to the TMS record, with the central peak of CDCl3 (δ = 77.23 ppm) as an internal standard. All 13 All C NMR spectra were obtained under conditions of complete proton decoupling.

[0086] Solvents, reagents, and raw materials were purchased from common chemical suppliers such as Sigma Aldrich, Acros Organics, Nanjing Yaoshi Technology Co., Ltd., Shanghai Bid Pharmaceutical Technology Co., Ltd., Shaoyuan Technology (Shanghai) Co., Ltd., Anhui Zesheng Technology Co., Ltd., Shanghai Lingfeng Chemical Reagent Co., Ltd., and Keyuan Fine Chemicals Co., Ltd., and the following abbreviations were used: g: gram mg: milligram L: Lift, mL: milliliters μL: microliters mol: mole mmol: millimole, nm: nanometer TLC: Thin-layer chromatography Psi: pounds-force per square inch General synthesis scheme The method for synthesizing the compounds of the present invention is summarized in the following scheme.

[0087] Option 1: A method for preparing most of the compounds of this invention. Yohimbine derivative 1 was mixed with a halogenated compound and reacted at 0°C for 0.5–3 hours. The reaction solution was diluted with an organic solvent, washed successively with alkaline aqueous solution and reducing aqueous solution, dried over an inorganic salt, filtered, concentrated, and purified by silica gel column chromatography or preparative HPLC to obtain compound 2. Compound 2 was mixed with a metal catalyst, boric acid or borate ester or amino compound, and reacted at 60–140°C for 12–36 hours. After direct drying, filtration, and concentration, compound 3-a was obtained after purification by column chromatography or preparative HPLC.

[0088] Option 2: A method for preparing most of the compounds of this invention. Compound 2-a was obtained by reacting a yohimbine derivative 1 with a bis(binarinol) boronic acid ester and an iridium catalyst at 80-100°C for 10-48 hours, quenching the reaction solution with ice water, extracting with only organic solvents, concentrating and drying, and then purifying by silica gel column chromatography or preparative HPLC. Compound 2-a was then reacted with a halogenated compound at 60-100°C for 1-8 hours, filtered, dried, concentrated, and then purified by silica gel column chromatography or preparative HPLC. Compound 2 was then reacted with a metal catalyst, boric acid, boronic acid ester, or an amino compound at 60-140°C for 12-36 hours, directly dried, filtered, concentrated, and then purified by column chromatography or preparative HPLC. Compound 3-b1 was obtained by reacting compound 2-a with a halogenated compound at 60-140°C for 12-36 hours with a metal catalyst, directly dried, filtered, concentrated, and then purified by column chromatography or preparative HPLC.

[0089] Option 3: A method for preparing most of the compounds of this invention. Yohimbine derivative 1 was dissolved in an organic solvent with a molecular sieve, and ferric nitrate was added. The mixture was stirred at room temperature for 12-48 hours. The reaction solution was diluted with ice water and extracted with an organic solvent. The combined solutions were dried, filtered, and purified by silica gel column chromatography or preparative HPLC to obtain compound 3-a. Compound 3-a was dissolved in an organic solvent, and a metal catalyst was added. The mixture was stirred at room temperature under hydrogen at 20 psi for 12-36 hours. The reaction solution was concentrated and purified by silica gel column chromatography or preparative HPLC to obtain compound 3-b. Compound 3-b was mixed with a halide and a nitrite and stirred at 60°C for 12-36 hours. The reaction solution was mixed with ice water and extracted with an organic solvent. The combined organic phases were dried, filtered, and purified by silica gel column chromatography or preparative HPLC to obtain compound 2. Compound 2 was mixed with a metal catalyst, boric acid or borate ester or amino compound, and reacted at 60-140°C for 12-36 hours. The mixture was directly dried, filtered, concentrated, and purified by column chromatography or preparative HPLC to obtain compound 3-c.

[0090] Example 1 10 g of yohimbine (25.6 mmol) was dissolved in 240 mL of methanol, and 9.0 g of pyridinium hydrobromide (28.1 mmol) was added. The reaction mixture was stirred in an ice bath for 0.5 h. The reaction mixture was diluted with dichloromethane and extracted successively with 200 mL of saturated sodium bicarbonate and 200 mL of sodium thiosulfate aqueous solution. The organic phases were combined, washed with 300 mL of saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated. The crude product was purified by silica gel column chromatography (120 g silica gel column, ethyl acetate / petroleum ether system, ethyl acetate from 0% to 69%) and concentrated to give 9.9 g of compound 1 (brown solid, 89.3% yield).

[0091] LCMS (ESI) m / z 433.0, 435.0 [M+H] + ; 1 H NMR (400 MHz, DMSO) -d 6) d ppm11.00 (s, 1 H), 7.50 (d, J = 1.8 Hz, 1 H), 7.22 (d, J = 8.6 Hz, 1 H), 7.10 (m, 1 H), 4.64 (d, J = 4.6 Hz, 1 H), 4.09 (br s, 1 H), 3.65 (s, 3 H), 3.23 (br d, J = 10.6 Hz, 1 H), 2.97 (m, 1 H), 2.83 (m, 1 H), 2.64 - 2.78 (m, 1 H), 2.54 - 2.61 (m, 1 H), 2.42 - 2.48 (m, 1 H), 2.34 - 2.42 (m, 1 H), 2.26 (m, 1H), 2.04 - 2.17 (m, 1 H), 1.79 - 1.96 (m, 1 H), 1.69 - 1.76 (m, 1 H), 1.54 (br t, J = 12.6 Hz, 1 H), 1.32 - 1.46 (m, 2 H), 1.19 - 1.29 (m, 1 H), 0.97 (m, 1 H); HPLC: 100%@220 nm, 100%@254 nm; 98.9%ee Example 2 2.0 g of compound 1 (4.62 mmol), 1.14 g of sodium hydroxide (28.6 mmol), and 157 mg of tetrabutylammonium bisulfate (0.462 mmol) were dissolved in 80 mL of dichloromethane. 4.03 g of di-tert-butyl dicarbonate (18.5 mmol) was added, and the mixture was stirred at 20 °C for 3 hours. The reaction mixture was then added to 100 mL of ice water and extracted three times with 50 mL of dichloromethane. The combined organic phases were washed twice with 50 mL of saturated sodium chloride. The organic phase was dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (80 g silica gel column, methanol / dichloromethane system, methanol from 0% to 10%) to give 2.17 g of compound 2-1 (bright yellow solid, 79.9% yield). LCMS (ESI) m / z 535.1 [M+H] + 2.0 g of compound 2-1 (3.75 mmol), 2.86 g of bis(pinnatrol)boronic acid ester (11.3 mmol), and 1.47 g of potassium acetate (15.0 mmol) were dissolved in 100 mL of dioxane, and 411 mg of 1,1'-bis(diphenylphosphine)ferrocene palladium dichloride was added. (0.562 mmol), the reaction solution was stirred at 80 °C for 16 hours. The reaction solution was concentrated, poured into 100 mL of water, and extracted twice with 100 mL of ethyl acetate. The organic phases were combined, washed twice with 100 mL of saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain the crude product. The crude product was purified by silica gel column chromatography (40 g silica gel column, methanol / dichloromethane system, methanol from 0% to 10%) to give 1.4 g of compound 2-2 (brown solid, 56.6% yield). LCMS (ESI) m / z 581.2 [M+H] + 200 mg of compound 2-2 (0.345 mmol), 0.2 mL of triethylamine (1.44 mmol), and 10 mL of acetonitrile and 0.5 mL of methanol were dissolved in the same solution. 125 mg of copper acetate (0.688 mmol) was added, and the mixture was stirred at 80 °C for 16 hours under an oxygen atmosphere. The reaction mixture was concentrated under reduced pressure to obtain a crude product, which was then purified by silica gel column chromatography (12 g silica gel column, methanol / dichloromethane system, methanol from 0% to 10%) to give 130 mg of compound 2-3 (yellow oil, 32.9% yield). LCMS (ESI) m / z 485.2 [M+H] + 55 mg of compound 2-3 (0.114 mmol) was dissolved in 5 mL of 2 M dioxane hydrochloride, and the mixture was stirred at 20 °C for 12 hours. The reaction solution was directly concentrated to obtain the crude product. The crude product was purified by preparative high performance liquid chromatography (column: Phenomenex C18 150 * 40 mm; mobile phase: [water (0.225% formic acid)-acetonitrile]; gradient elution program: acetonitrile concentration increased from 8% to 28% within 10 minutes), and lyophilized to give 13.2 mg of compound 2 (white solid, 29.2% yield).

[0092] LCMS (ESI) m / z 385.3 [M+H] + ; 1 H NMR (400 MHz, DMSO- d 6) d ppm 10.57 (s,1 H), 8.18 (s, 0.5 H), 7.13 (d, J = 8.7 Hz, 1 H), 6.82 (d, J = 2.3 Hz, 1 H), 6.63 (dd, J = 8.7, 2.4 Hz, 1 H), 4.52 - 4.72 (m, 1 H), 4.09 (br d, J = 1.8Hz, 1H), 3.72 (s, 3H), 3.66 (s, 3H), 3.22 (br d, J = 11.2 Hz, 2 H), 2.98 (br dd, J = 11.1, 5.0 Hz, 1 H), 2.81 - 2.87 (m, 1 H), 2.67 - 2.78 (m, 1 H), 2.57 (br s, 1 H), 2.37 (br d, J = 12.2 Hz, 1 H), 2.26 (dd, J = 11.6, 2.5 Hz,1 H), 2.11 (br t, J = 10.5 Hz, 1 H), 1.80 - 1.91 (m, 1 H), 1.75 (br d, J =11.1 Hz, 1 H), 1.50 - 1.60 (m, 1 H), 1.33 - 1.47 (m, 2 H), 1.22 - 1.30 (m, 1H), 0.96 (q, J= 11.7 Hz, 1 H); HPLC:96.44%@220nm; 97.84%@254 nm; 99.6%ee Example 3 100 mg of compound 1 (0.231 mmol), 85 mg of phenylboronic acid (0.698 mmol), and 98 mg of potassium acetate (1.0 mmol) were dissolved in 5 mL of tetrahydrofuran. 25 mg of 1,1'-bis(diphenylphosphine)ferrocene palladium dichloride (0.0355 mmol) was added under nitrogen atmosphere, and the mixture was reacted at 70 °C for 12 h. The crude product was concentrated under reduced pressure and purified by preparative high-performance liquid chromatography (column: C18 150 × 30 mm; mobile phase: [water-acetonitrile]; gradient elution program: acetonitrile concentration increased from 48% to 68% within 2 minutes). After freeze-drying, 20.5 mg of compound 3 (white solid, 20.4% yield) was obtained.

[0093] LCMS (ESI) m / z 431.2 [M+H] + ; 1 H NMR (400 MHz, DMSO) -d 6) d ppm 10.85 (s,1 H), 7.64 (br d, J = 7.50 Hz, 2 H), 7.60 (s, 1 H), 7.42 (t, J = 7.69 Hz, 2H), 7.23 - 7.36 (m, 3 H), 4.63 (br s, 1 H), 4.10 (br s, 1 H), 3.67 (s, 3 H), 3.25 (br d, J = 11.13 Hz, 1 H), 3.01 (br dd, J = 10.76, 5.13 Hz, 1 H), 2.83 -2.91 (m, 1 H), 2.74 - 2.82 (m, 1 H), 2.62 - 2.70 (m, 1 H), 2.51 - 2.58 (m, 1H), 2.41 (br d, J = 12.26 Hz, 1 H), 2.28 (dd, J = 11.63, 2.38 Hz, 1 H), 2.13 (br t, J = 10.26 Hz, 1 H), 1.81 - 1.95 (m, 1 H), 1.75 (br d, J= 10.51 Hz, 1H), 1.50 - 1.63 (m, 1 H), 1.31 - 1.48 (m, 2 H), 1.27 (br d, J = 8.88 Hz, 1H), 0.99 (q, J = 11.63 Hz, 1 H); HPLC: 98.80%@220 nm; 99.66%@254 nm; 100.0%ee Example 4 The method was the same as in Example 3, except that phenylboronic acid was replaced with 4-fluorophenylboronic acid. The crude product was purified by preparative high performance liquid chromatography (column: Phenomenex C18 150 * 40 mm; mobile phase: [water (10% formic acid) - acetonitrile]; gradient elution program: acetonitrile concentration increased from 21% to 61% within 9 minutes, and 100% acetonitrile was maintained for 2 minutes). After freeze-drying, 34.6 mg of compound 4 (yellow solid, 32.1% yield) was obtained.

[0094] LCMS (ESI) m / z 449.2 [M+H] + ; 1 H NMR (400 MHz, DMSO- d 6) d ppm 10.86 (s,1 H), 8.19 (s, 0.30 H), 7.67 (dd, J = 8.8, 5.5 Hz, 2 H), 7.58 (s, 1 H), 7.32- 7.36 (m, 1 H), 7.21 - 7.30 (m, 3 H), 4.64 (br d, J = 1.5 Hz, 1 H), 4.11 (brs, 1 H), 3.68 (s, 3 H), 3.26 (br d, J = 11.9 Hz, 2 H), 3.02 (br dd, J = 10.2,5.2 Hz, 1 H), 2.86 (br d, J = 10.1 Hz, 1 H), 2.75 - 2.82 (m, 1 H), 2.63 -2.70 (m, 1 H), 2.39 - 2.45 (m, 1 H), 2.28 (dd, J = 11.6, 2.3 Hz, 1 H), 2.14 (br t, J= 10.2 Hz, 1 H), 1.83 - 1.93 (m, 1 H), 1.72 - 1.80 (m, 1 H), 1.51 -1.61 (m, 1 H), 1.36 - 1.47 (m, 2 H), 1.24 - 1.31 (m, 1 H), 0.95 - 1.05 (m, 1H); 19 F NMR (376 MHz, DMSO- d 6) d ppm -117.70; 98.84%@220 nm; 99.02%@254 nm.99.78%ee. Example 5 The method was the same as in Example 3, except that phenylboronic acid was replaced with 4-methoxyphenylboronic acid. The crude product was purified by preparative high performance liquid chromatography (column: C18 150 * 30 mm; mobile phase: [water-acetonitrile]; gradient elution program: acetonitrile concentration increased from 45% to 65% within 2 minutes, and 100% acetonitrile was maintained for 0 minutes). After freeze-drying, 29.3 mg of compound 5 (white solid, 27.0% yield) was obtained.

[0095] LCMS (ESI) m / z 461.0 [M+H] + ; 1 H NMR (400 MHz, DMSO-d 6) d ppm 10.80 (s,1 H), 7.57 (br d, J = 8.80 Hz, 2 H), 7.53 (s, 1 H), 7.29 - 7.36 (m, 1 H), 7.25 (dd, J = 8.36, 1.10 Hz, 1 H), 6.99 (d, J = 8.58 Hz, 2 H), 4.63 (d, J =4.62 Hz, 1 H), 4.11 (br s, 1 H), 3.79 (s, 3 H), 3.68 (s, 3 H), 3.25 (br d, J = 11.44 Hz, 1 H), 3.01 (br dd, J = 10.23, 5.39 Hz, 1 H), 2.85 (br d, J =10.56 Hz, 1 H), 2.79 (br d, J= 10.12 Hz, 1 H), 2.65 (br d, J = 14.75 Hz, 1H), 2.41 (br d, J = 12.54 Hz, 1 H), 2.28 (br dd, J = 11.55, 2.09 Hz, 1 H), 2.13 (br t, J = 9.57 Hz, 1 H), 1.82 - 1.96 (m, 1 H), 1.76 (br d, J = 12.10Hz, 1 H), 1.49 - 1.63 (m, 1 H), 1.33 - 1.49 (m, 2 H), 1.23 - 1.30 (m, 1 H), 0.99 (q, J = 11.37 Hz, 1 H); HPLC: 97.98 %@220 nm, 99.81%@254 nm; 99.1% ee. Example 6 The method was the same as in Example 3, except that phenylboronic acid was replaced with 4-pyridylphenylboronic acid. The crude product was purified by preparative high performance liquid chromatography (column: Phenomenex C18 150 * 40 mm; mobile phase: [water-acetonitrile]; gradient elution program: acetonitrile concentration increased from 33% to 53% within 2 minutes, and 100% acetonitrile was maintained for 2.5 minutes). After freeze-drying, 3.8 mg of compound 6 (white solid, 1.8% yield) was obtained.

[0096] LCMS (ESI) m / z 432.2 [M+H] + ; 1 H NMR (400 MHz, DMSO- d 6) d ppm 10.99 (s, 1 H), 8.52 - 8.59 (m, 2 H), 7.81 (s, 1 H), 7.68 - 7.74 (m, 2 H), 7.44 - 7.49 (m, 1 H), 7.36 - 7.41 (m, 1 H), 4.61 - 4.71 (m, 1 H), 4.10 (br s, 1 H), 3.67 (s, 3 H), 3.22 - 3.29 (m, 1 H), 3.01 (br dd, J = 11.0, 4.3 Hz, 1 H), 2.77 -2.89 (m, 2 H), 2.68 (br d,J = 12.2 Hz, 1 H), 2.41 (br d, J = 12.6 Hz, 1 H), 2.27 (dd, J = 11.4, 2.4 Hz, 1 H), 2.13 (br t, J = 10.2 Hz, 1 H), 1.81 - 1.93 (m, 1 H), 1.71 - 1.79 (m, 1 H), 1.51 - 1.61 (m, 1 H), 1.34 - 1.45 (m, 2 H), 1.27 (br d, J = 8.7 Hz, 1 H), 0.99 (q, J = 11.9 Hz, 1 H); HPLC:95.75%@220 nm; 94.04%@254 nm; 97.4%ee Example 7 The method was the same as in Example 3, except that phenylboronic acid was replaced with 1-methylpyrazole-3-phenazine borate. The crude product was purified by preparative high performance liquid chromatography (column: C18 150 * 30 mm; mobile phase: [water-acetonitrile]; gradient elution program: acetonitrile concentration increased from 28% to 48% within 2 minutes, and 100% acetonitrile was maintained for 0 minutes). After freeze-drying, 5.5 mg of compound 7 (white solid, 5.5% yield) was obtained.

[0097] LCMS (ESI) m / z 435.3 [M+H] + ; 1 H NMR (400 MHz, DMSO) -d 6) d ppm 10.78 (s,1 H), 7.75 (s, 1 H), 7.66 (d, J = 1.88 Hz, 1 H), 7.47 (dd, J = 8.38, 1.00 Hz, 1 H), 7.26 (d, J = 8.38 Hz, 1 H), 6.59 (d, J = 2.00 Hz, 1 H), 4.64 (d, J =4.50 Hz, 1 H), 4.11 (br s, 1 H), 3.86 (s, 3 H), 3.67 (s, 3 H), 3.24 (br d, J= 11.01 Hz, 1 H), 3.00 (br dd, J = 10.69, 5.32 Hz, 1 H), 2.85 (br d, J = 9.26Hz, 1 H), 2.73 - 2.81 (m, 1 H), 2.63 (br d, J = 14.01 Hz, 1 H), 2.45 - 2.49 (m, 1 H), 2.41 (br d, J = 12.26 Hz, 1 H), 2.27 (br dd, J = 11.44, 2.19 Hz, 1H), 2.07 - 2.18 (m, 1 H), 1.81 - 1.95 (m, 1 H), 1.76 (br d, J = 11.26 Hz, 1H), 1.55 (br t, J = 11.94 Hz, 1 H), 1.33 - 1.50 (m, 2 H), 1.27 (br d, J =9.38 Hz, 1 H), 0.99 (q, J = 11.76 Hz, 1 H); HPLC: 99.69%@220 nm; 99.56%@254nm; 100%ee. Example 8 The method was the same as in Example 3, except that phenylboronic acid was replaced with 1-methylpyrazole-4-phenazineboronic acid. The crude product was purified by preparative high performance liquid chromatography (column: Phenomenex C18 150 * 40 mm; mobile phase: [water-acetonitrile]; gradient elution program: acetonitrile concentration increased from 26% to 46% within 2 minutes, and 100% acetonitrile was maintained for 2.5 minutes). After freeze-drying, 14.0 mg of compound 8 (white solid, 13.4% yield) was obtained.

[0098] LCMS (ESI) m / z 435.2 [M+H] + ; 1 H NMR (400 MHz, DMSO- d 6) d ppm 10.72 (s, 1 H), 8.00 (s, 1 H), 7.75 (s, 1 H), 7.49 (s, 1 H), 7.16 - 7.25 (m, 2 H), 4.63 (br d, J= 4.0 Hz, 1 H), 4.10 (br s, 1 H), 3.84 (s, 3 H), 3.66 (s, 3 H), 3.22 (br d, J = 10.5 Hz, 1 H), 2.99 (br dd, J = 10.8, 4.9 Hz, 1 H), 2.81 - 2.87 (m, 1 H), 2.66 - 2.78 (m, 1 H), 2.57 - 2.64 (m, 1 H), 2.36 - 2.42 (m, 1 H), 2.27 (dd, J = 11.6, 2.5 Hz, 1 H), 2.11 (br t, J = 10.2 Hz, 1 H), 1.80 - 1.90 (m, 1 H), 1.72 - 1.78 (m, 1 H), 1.50 - 1.60 (m, 1 H), 1.34 - 1.44 (m, 2 H), 1.22 - 1.30 (m, 1 H), 0.93 - 1.03 (m, 1 H); HPLC: 96.07%@220 nm, 97.42%@254nm; 99.0%ee. Example 9 The method was the same as in Example 3, except that phenylboronic acid was replaced with furan-3-boronic acid linalool ester. The crude product was purified by preparative high performance liquid chromatography (column: C18 150 * 30 mm; mobile phase: [water-acetonitrile]; gradient elution program: acetonitrile concentration increased from 38% to 58% within 2 minutes, and 100% acetonitrile was maintained for 0 minutes). After freeze-drying, 19.5 mg of compound 9 (white solid, 19.2% yield) was obtained.

[0099] LCMS (ESI) m / z 421.2 [M+H] + ; 1 H NMR (400 MHz, DMSO) -d 6) d ppm 10.79 (s,1 H), 8.03 (s, 1 H), 7.68 (t, J = 1.44 Hz, 1 H), 7.55 (s, 1 H), 7.25 (s, 2H), 6.92 (d, J = 0.75 Hz, 1 H), 4.63 (d, J= 4.75 Hz, 1 H), 4.10 (br s, 1 H), 3.67 (s, 3 H), 3.23 (br d, J = 11.01 Hz, 1 H), 3.00 (br dd, J = 11.13, 5.13Hz, 1 H), 2.81 - 2.88 (m, 1 H), 2.77 (br d, J = 9.51 Hz, 1 H), 2.62 (br d, J = 14.26 Hz, 1 H), 2.46 (br d, J = 4.38 Hz, 1 H), 2.36 - 2.42 (m, 1 H), 2.27 (br dd, J = 11.57, 2.31 Hz, 1 H), 2.12 (br t, J = 10.32 Hz, 1 H), 1.80 - 1.92 (m, 1 H), 1.75 (br dd, J = 12.95, 2.19 Hz, 1 H), 1.55 (br t, J = 12.94 Hz, 1H), 1.32 - 1.48 (m, 2 H), 1.20 - 1.30 (m, 1 H), 0.98 (q, J = 11.63 Hz, 1 H); HPLC: 95.77%@220 nm; 99.48%@254 nm; 99.8% ee. Example 10 The method was the same as in Example 3, except that phenylboronic acid was replaced with furan-2-boronic acid benzoyl ester. The crude product was purified by preparative high performance liquid chromatography (column: Phenomenex C18 150 * 40 mm; mobile phase: [water-acetonitrile]; gradient elution program: acetonitrile concentration increased from 44% to 64% within 2 minutes, and 100% acetonitrile was maintained for 2.5 minutes). After freeze-drying, 32.5 mg of compound 10 was obtained (white solid, 29.5% yield).

[0100] LCMS (ESI) m / z 421.2 [M+H] + ; 1 H NMR (400 MHz, DMSO- d 6) dppm 10.89 (s,1 H), 7.63 - 7.70 (m, 2 H), 7.38 (dd, J =8.5, 1.2 Hz, 1H), 7.26 - 7.33 (m, 1H), 6.73 (d, J = 3.1 Hz, 1 H), 6.54 (dd, J = 3.2, 1.8 Hz, 1 H), 4.49 - 4.76 (m, 1 H), 4.10 (br d, J = 2.0 Hz, 1 H), 3.67 (s, 3 H), 3.22 - 3.26 (m, 1 H), 3.00 (br dd, J = 11.1, 5.0 Hz, 1 H), 2.85 (br d, J = 10.8 Hz, 1 H), 2.72 -2.80 (m, 1 H), 2.60 - 2.69 (m, 1 H), 2.40 (br d, J = 12.0 Hz, 1 H), 2.27 (dd, J = 11.5, 2.2 Hz, 1 H), 2.08 - 2.17 (m, 1 H), 1.81 - 1.92 (m, 1 H), 1.75 (brd, J = 11.9 Hz, 1 H), 1.51 - 1.60 (m, 1 H), 1.34 - 1.46 (m, 2 H), 1.27 (br d, J = 9.5 Hz, 1 H), 0.93 - 1.04 (m, 1 H); HPLC: 91.64%@220 nm; 88.12%@254 nm; 100%ee. Example 11 100 mg of compound 1 (0.231 mmol), 40 mg of morpholine (0.462 mmol), and 226 mg of cesium carbonate (0.692 mmol) were dissolved in 2 mL of dioxane. Under nitrogen atmosphere, 18 mg of [(2-dicyclohexylphosphino-2′,6′-bis(N,N-dimethylamino)-1,1′-biphenyl)-2-(2′-amino-1,1′-biphenyl)]palladium(II)methanesulfonate was added. (0.0231 mmol), the mixture was reacted at 110 °C for 12 h. The crude product was concentrated under reduced pressure and purified by preparative high performance liquid chromatography (column: Boston Prime C18 150 × 30 mm × 5 μm; mobile phase: [water (formic acid)-acetonitrile]; gradient elution program: acetonitrile concentration increased from 0% to 27% in 2 minutes, 100% acetonitrile was maintained for 0 minutes). After freeze-drying, 9.9 mg of compound 11 (white solid, 8.8% yield) was obtained.

[0101] LCMS (ESI) m / z 440.1 [M+H] + ; 1 H NMR (400 MHz, DMSO) -d 6) d ppm 10.50 (s,1 H), 7.14 (d, J = 8.63 Hz, 1 H), 6.82 (d, J = 1.88 Hz, 1 H), 6.76 (dd, J =8.63, 2.00 Hz, 1 H), 4.62 (br s, 1 H), 4.09 (br d, J = 1.38 Hz, 1 H), 3.71 -3.79 (m, 4 H), 3.66 (s, 3 H), 3.51 - 3.59 (m, 1 H), 3.19 (br d, J = 11.26 Hz, 1 H), 2.97 - 3.02 (m, 4 H), 2.95 (br d, J = 5.38 Hz, 1 H), 2.80 - 2.86 (m, 1H), 2.65 - 2.73 (m, 1 H), 2.55 (br s, 1 H), 2.41 - 2.47 (m, 1 H), 2.36 (br d, J = 12.38 Hz, 1 H), 2.26 (dd, J = 11.57, 2.56 Hz, 1 H), 2.09 (br t, J = 10.19Hz, 1H), 1.84 (qd, J = 10.67, 2.38 Hz, 1 H), 1.74 (br dd, J = 13.38, 1.63Hz, 1H), 1.54 (br t, J= 13.32 Hz, 1 H), 1.31 - 1.47 (m, 1 H), 1.22 - 1.28 (m, 1 H), 0.95 (q, J = 11.67 Hz, 1 H); HPLC: 99.79%@220 nm; 100.00%@254 nm; 94.3% ee. Example 12 The method was the same as in Example 11, except that morpholine was replaced with piperidine. The crude product was purified by preparative high performance liquid chromatography (column: Phenomenex C18 150 * 40 mm; mobile phase: [water (formic acid) - acetonitrile]; gradient elution program: acetonitrile concentration increased from 20% to 80% within 10 minutes, and 100% acetonitrile was maintained for 0 minutes). After freeze-drying, 77.8 mg of compound 12 (gray solid, 36.1% yield) was obtained.

[0102] LCMS (ESI) m / z 438.2 [M+H] + ; 1 H NMR (400 MHz, DMSO- d 6) d ppm 10.46 (s,1 H), 7.11 (d, J = 8.7 Hz, 1 H), 6.82 (d, J = 2.1 Hz, 1 H), 6.74 (dd, J =8.7, 2.2 Hz, 1 H), 4.61 (br d, J = 4.3 Hz, 1 H), 4.09 (br s, 1 H), 3.66 (s, 3H), 3.19 (br d, J = 11.5 Hz, 1 H), 2.94 - 3.01 (m, 5 H), 2.80 - 2.86 (m, 1H), 2.66 - 2.74 (m, 1 H), 2.55 (br s, 1 H), 2.31 - 2.39 (m, 1 H), 2.26 (dd, J = 11.6, 2.8 Hz, 1 H), 2.10 (br t, J = 10.4 Hz, 1 H), 1.85 (br d, J= 1.6 Hz, 1 H), 1.72 - 1.78 (m, 1 H), 1.62 - 1.69 (m, 4 H), 1.53 - 1.60 (m, 1 H), 1.47 - 1.53 (m, 2 H), 1.34 - 1.44 (m, 2 H), 1.23 - 1.29 (m, 1 H), 0.95 (q, J =11.4 Hz, 1 H); HPLC: 97.29%@220 nm; 93.70%@254 nm; 97.3%ee. Example 13 The method was the same as in Example 11, except that morpholine was replaced with N-methylpiperazine. The crude product was purified by preparative high performance liquid chromatography (column: Phenomenex Gemini NX C18 150 × 30 mm, 5 μm; mobile phase: [water (ammonia) - acetonitrile]; gradient elution program: acetonitrile concentration increased from 25% to 45% within 10 minutes, and 100% acetonitrile was maintained for 0 minutes). After freeze-drying, 3.5 mg of compound 13 (white solid, 3.2% yield) was obtained.

[0103] LCMS (ESI) m / z 453.3 [M+H] + ; 1 H NMR (400 MHz, DMSO) -d 6) d ppm 10.47 (s,1 H), 7.12 (d, J = 8.68 Hz, 1 H), 6.81 (d, J = 1.96 Hz, 1 H), 6.75 (dd, J =8.80, 2.20 Hz, 1 H), 4.62 (br s, 1 H), 4.09 (br d, J = 1.59 Hz, 1 H), 3.66 (s, 3 H), 3.19 (br d, J = 10.88 Hz, 1 H), 2.99 - 3.05 (m, 4 H), 2.93 - 2.98 (m, 1 H), 2.83 (br dd, J = 10.70, 2.26 Hz, 1 H), 2.63 - 2.75 (m, 1 H), 2.55 (br s, 1 H), 2.44 - 2.49 (m, 4 H), 2.41 - 2.44 (m, 1 H), 2.36 (dt,J = 12.53,2.90 Hz, 1 H), 2.24 - 2.29 (m, 1 H), 2.22 (s, 3 H), 2.10 (br t, J = 10.27 Hz, 1 H), 1.79 - 1.90 (m, 1 H), 1.75 (br d, J = 13.33 Hz, 1 H), 1.49 - 1.60 (m, 1H), 1.32 - 1.48 (m, 2 H), 1.26 (br d, J = 11.25 Hz, 1 H), 0.95 (q, J = 11.78Hz, 1 H); HPLC: 97.66%@220 nm, 95.99%@254 nm; 100% ee. Example 14 The method was the same as in Example 3, except that phenylboronic acid was replaced with trimethylcycloboroxane. The crude product was purified by preparative high performance liquid chromatography (column: Phenomenex C18 150 * 40 mm; mobile phase: [water-acetonitrile]; gradient elution program: acetonitrile concentration increased from 13% to 33% within 2 minutes, and 100% acetonitrile was maintained for 2.5 minutes). After freeze-drying, 7.0 mg of compound 14 (white solid, 7.3% yield) was obtained.

[0104] LCMS (ESI) m / z 369.2 [M+H] + ; 1 H NMR (400 MHz, DMSO- d 6) d ppm 10.60 (s, 1 H), 8.26 (m, 0.4 H), 7.08 - 7.17 (m, 2 H), 6.81 (br d, J = 8.3 Hz, 1 H), 4.51 - 4.69 (m, 1 H), 4.09 (br s, 1 H), 3.66 (s, 3 H), 3.21 (br d, J = 11.4Hz, 1H), 2.97 (br dd, J = 11.1, 5.1 Hz, 1 H), 2.80 - 2.86 (m, 1 H), 2.66 -2.78 (m, 1 H), 2.44 (br s, 1 H), 2.39 (br s, 1 H), 2.34 (s, 3 H), 2.26 (brdd,J = 11.5, 2.3 Hz, 1 H), 2.10 (br t, J = 10.4 Hz, 1H), 1.80 - 1.89 (m, 1H), 1.75 (br d, J = 10.9 Hz, 1 H), 1.50 - 1.60 (m, 1 H), 1.34 - 1.45 (m, 2H), 1.25 (br d, J = 10.0 Hz, 1 H), 0.96 (q, J = 11.3 Hz, 1 H); HPLC: 96.15%@220 nm; 88.96%@254 nm; 93.0%ee. Example 15 The method was the same as in Example 3, except that phenylboronic acid was replaced with cyclopropylboronic acid. The crude product was purified by preparative high performance liquid chromatography (column: Phenomenex C18 150 * 40 mm; mobile phase: [water (0.225% formic acid) - acetonitrile]; gradient elution program: acetonitrile concentration increased from 17% to 37% within 12 minutes, and 100% acetonitrile was maintained for 0 minutes). After freeze-drying, 38.4 mg of compound 15 (yellow solid, 13.4% yield) was obtained.

[0105] LCMS (ESI) m / z 395.1 [M+H] + ; 1 H NMR (400 MHz, DMSO- d 6) d ppm 10.59 (brs, 1 H), 8.15 (s, 1 H), 7.13 (d, J = 8.3 Hz, 1 H), 7.04 (s, 1 H), 6.73 (d, J = 8.6 Hz, 1 H), 4.55 - 4.66 (m, 1 H), 4.09 (br s, 1 H), 3.66 (s, 3 H), 3.20 -3.23 (m, 1 H), 2.95 - 3.02 (m, 1 H), 2.84 (br d, J = 10.9 Hz, 1 H), 2.68 -2.77 (m, 1 H), 2.57 (br s, 1 H), 2.37 (br d, J = 13.1 Hz, 1 H), 2.26 (dd, J=11.7, 2.1 Hz, 1 H), 2.09 - 2.17 (m, 1 H), 1.91 - 1.98 (m, 1 H), 1.81 - 1.89 (m, 1 H), 1.71 - 1.78 (m, 1 H), 1.50 - 1.59 (m, 1 H), 1.36 - 1.46 (m, 2 H),1.26 (br d, J = 9.9 Hz, 1 H), 0.93 - 1.02 (m, 1 H), 0.84 - 0.89 (m, 2 H), 0.57 - 0.62 (m, 2 H); HPLC: 99.43%@220 nm; 94.92%@254 nm; 96.1%ee. Example 16 1.2 g of compound 2-2 (2.07 mmol) and 750 mg of copper acetate (4.13 mmol) were dissolved in 50 mL of acetonitrile and 5 mL of water. 1.20 mL of triethylamine (8.62 mmol) was added, and the mixture was purged three times with oxygen, maintaining a nitrogen pressure of 15 psi. The mixture was stirred at 80 °C for 16 hours. The reaction mixture was filtered, and the filtrate was concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (40 g silica gel column, methanol / dichloromethane system, methanol from 0% to 15%) to give 130 mg of compound 16-1 (yellow oil, 13.4% yield). LCMS (ESI) m / z 471.3 [M+H] + 40 mg of compound 16-1 (0.085 mmol) was dissolved in 3 mL of 2 M dioxane hydrochloride, and the mixture was stirred at 20 °C for 12 hours. The reaction solution was directly concentrated to obtain the crude product. The crude product was purified by preparative high performance liquid chromatography (column: Phenomenex C18 150 * 40 mm; mobile phase: [water (0.225% formic acid)-acetonitrile]; gradient elution program: acetonitrile concentration increased from 0% to 30% within 10 minutes), and lyophilized to give 6.2 mg of compound 16 (white solid, 18.4% yield).

[0106] LCMS (ESI) m / z 371.2 [M+H] + ; 1 H NMR (400 MHz, DMSO- d 6) d ppm 10.40 (s,1 H), 8.17 (s, 0.9 H), 7.03 (d, J = 8.4 Hz, 1 H), 6.63 (d,J = 2.1 Hz, 1 H), 6.50 (dd, J = 8.6, 2.2 Hz, 1 H), 4.49 - 4.75 (m, 1 H), 4.09 (br d, J = 2.0Hz, 1 H), 3.66 (s, 3 H), 3.21 (br d, J = 11.5 Hz, 1 H), 2.97 (br dd, J =10.3, 4.8 Hz, 1 H), 2.80 - 2.87 (m, 1 H), 2.65 - 2.71 (m, 1 H), 2.47 (br s, 1H), 2.35 (br d, J = 12.8 Hz, 1 H), 2.25 (dd, J = 11.5, 2.6 Hz, 1 H), 2.11 (brt, J = 10.2 Hz, 1 H), 1.79 - 1.89 (m, 1 H), 1.75 (br d, J = 11.5 Hz, 1 H), 1.49 - 1.59 (m, 1 H), 1.34 - 1.46 (m, 2 H), 1.22 - 1.29 (m, 1 H), 0.95 (q, J= 11.9 Hz, 1 H); HPLC: 93.41%@220 nm; 96.54%@254 nm; 100%ee Example 17 200 mg of compound 10 (0.476 mmol) and 100 mg of wet palladium on carbon were dissolved in 10 mL of methanol. The mixture was reacted at 30 °C and 50 psi under hydrogen atmosphere for 48 h. The crude product was obtained by filtration and concentration under reduced pressure. The crude product was purified by preparative high performance liquid chromatography (column: Phenomenex Synergi C18 150 * 30 mm * 4 µm; mobile phase: [water (0.05% ammonia) - acetonitrile]; gradient elution program: acetonitrile concentration increased from 32% to 52% over 10 min, then 100% acetonitrile was maintained for 0 min). After lyophilization, 25.4 mg of compound 17 (white solid, 12.6% yield) was obtained.

[0107] LCMS (ESI) m / z 425.2 [M+H] + ; 1 H NMR (400 MHz, DMSO- d 6) d ppm 10.71 (s,1 H), 7.27 (s, 1 H), 7.20 (d, J = 8.1 Hz, 1 H), 6.95 (d, J = 9.2 Hz, 1 H), 4.80 (t, J = 7.4 Hz, 1 H), 4.63 (br s, 1 H), 4.09 (br s, 1 H), 3.98 (q, J =7.3 Hz, 1 H), 3.73 - 3.81 (m, 1 H), 3.66 (s, 3 H), 3.21 (br d, J = 10.6 Hz, 1H), 2.98 (br dd, J = 11.2, 5.1 Hz, 1 H), 2.83 (br d, J = 10.6 Hz, 1 H), 2.65- 2.79 (m, 1 H), 2.54 - 2.61 (m, 1 H), 2.35 - 2.42 (m, 1 H), 2.19 - 2.29 (m, 2 H), 2.10 (br t, J = 10.2 Hz, 1 H), 1.90 - 2.01 (m, 2 H), 1.79 - 1.89 (m, 1H), 1.63 - 1.78 (m, 2 H), 1.49 - 1.59 (m, 1 H), 1.32 - 1.48 (m, 2 H), 1.22 -1.30 (m, 1 H), 0.96 (q, J = 11.9 Hz, 1 H); HPLC: 99.51%@220 nm, 94.52%@254nm. Example 18 The method was the same as in Example 3, except that phenylboronic acid was replaced with vinylboronic acid ester. The crude product was purified by silica gel column chromatography (12 g silica gel column, methanol / dichloromethane system, methanol from 0% to 6%) to give 270 mg of compound 18-1 (yellow oil, crude product). LCMS (ESI) m / z 381.2 [M+H] + 150 mg of compound 18-1 (0.394 mmol) and 50 mg of wet palladium on carbon (0.047 mmol) were dissolved in 10 mL of methanol. The mixture was reacted at 20 °C and 15 psi under hydrogen atmosphere for 12 h. The crude product was obtained by filtration and concentration under reduced pressure. The crude product was purified by preparative high performance liquid chromatography (HPLC) (column: 40-WePure Biotech XP t C18 150 × 30 mm, 7 μm; mobile phase: [water (0.05% ammonia)-acetonitrile]; gradient elution program: acetonitrile concentration increased from 47% to 67% over 10 min, then 100% acetonitrile was maintained for 0 min). After lyophilization, 36.0 mg of compound 18 (white solid, 23.9% yield) was obtained.

[0108] LCMS (ESI) m / z 383.2 [M+H] + ; 1 H NMR (400 MHz, DMSO- d 6) d ppm 10.61 (s,1 H), 7.10 - 7.18 (m, 2 H), 6.84 (dd, J = 8.3, 1.1 Hz, 1 H), 4.62 (d, J = 4.6Hz, 1H), 4.09 (br d, J = 0.8 Hz, 1 H), 3.66 (s, 3 H), 3.20 (br d, J = 11.0Hz, 1H), 2.97 (br dd, J = 10.9, 5.3 Hz, 1 H), 2.83 (br dd, J = 10.8, 1.8 Hz, 1 H), 2.69 - 2.79 (m, 1 H), 2.63 (q, J = 7.5 Hz, 2 H), 2.55 (br d, J = 14.6Hz, 1 H), 2.42 - 2.47 (m, 1 H), 2.38 (br d, J = 12.1 Hz, 1 H), 2.26 (dd, J =11.5, 2.4 Hz, 1 H), 2.10 (br t, J= 10.3 Hz, 1 H), 1.79 - 1.90 (m, 1 H), 1.71 - 1.78 (m, 1 H), 1.50 - 1.59 (m, 1 H), 1.33 - 1.47 (m, 2 H), 1.25 (br d, J =9.6 Hz, 1 H), 1.19 (t, J = 7.6 Hz, 3 H), 0.95 (q, J = 11.5 Hz, 1 H); HPLC:99.95%@220 nm; 100%@254 nm. Example 19 The method was the same as in Example 3, except that phenylboronic acid was replaced with 2,5-dihydrofuran-3-phenanthrolborate. The crude product was purified by silica gel column chromatography (4 g silica gel column, methanol / dichloromethane system, methanol from 0% to 10%) to give 341 mg of compound 19-1 (white solid, yield 83.3%). LCMS (ESI) m / z 423.2 [M+H] + 105 mg of compound 19-1 (0.248 mmol) and 20 mg of wet palladium on carbon were dissolved in 10 mL of methanol. The mixture was reacted at 30 °C and 45 psi under hydrogen atmosphere for 5 h. The crude product was obtained by filtration and concentration under reduced pressure. The crude product was purified by preparative high performance liquid chromatography (column: 40-WePure Biotech XP t C18 150 × 30 mm, 7 μm; mobile phase: [water (0.05% ammonia)-acetonitrile]; gradient elution program: acetonitrile concentration increased from 31% to 51% over 10 min, then 100% acetonitrile was maintained for 0 min). After lyophilization, 36.0 mg of compound 19 (white solid, 15.4% yield) was obtained.

[0109] LCMS (ESI) m / z 425.2 [M+H] + ; 1 H NMR (400 MHz, DMSO) -d 6) d ppm 10.67 (s,1 H), 7.21 (br s, 1 H), 7.19 (d, J = 8.31 Hz, 1 H), 6.92 (dd, J = 8.31, 1.59Hz, 1H), 4.62 (d, J = 4.40 Hz, 1 H), 4.09 (br s, 1 H), 4.03 (t, J= 7.76 Hz, 1 H), 3.95 (td, J = 8.25, 4.28 Hz, 1 H), 3.79 (q, J = 8.07 Hz, 1 H), 3.66 (s, 3 H), 3.53 (td, J = 8.07, 1.34 Hz, 1 H), 3.36 - 3.45 (m, 1 H), 3.20 (br d, J = 11.49 Hz, 1 H), 2.97 (br dd, J = 10.88, 5.26 Hz, 1 H), 2.83 (dd, J = 11.00,2.32 Hz, 1 H), 2.65 - 2.80 (m, 1 H), 2.53 - 2.61 (m, 1 H), 2.45 (dd, J =11.25, 4.28 Hz, 1 H), 2.38 (dt, J = 12.35, 2.69 Hz, 1 H), 2.21 - 2.33 (m, 2H), 2.10 (t, J = 10.39 Hz, 1 H), 1.91 - 2.01 (m, 1 H), 1.79 - 1.90 (m, 1 H), 1.74 (br dd, J = 13.20, 2.45 Hz, 1 H), 1.49 - 1.61 (m, 1 H), 1.31 - 1.47 (m, 2 H), 1.26 (br d, J = 10.51 Hz, 1 H), 0.95 (q, J = 11.66 Hz, 1 H); HPLC:100.00%@220 nm; 100.00%@254 nm. Racemic. Example 20 The method was the same as in Example 3, except that phenylboronic acid was replaced with m-methoxyphenylboronic acid. The crude product was purified by preparative high performance liquid chromatography (column: 52-Welch Xtimate C18 150 × 30 mm, 5 μm; mobile phase: [water (0.55% ammonia)-acetonitrile]; gradient elution program: acetonitrile concentration increased from 44% to 74% within 9 minutes, and 100% acetonitrile was maintained for 0 minutes). After freeze-drying, 30 mg of compound 20 was obtained (white solid, 34.3% yield).

[0110] LCMS (ESI) m / z 461.3 [M+H] + ; 1 H NMR (DMSO- d 6, 400 MHz) d ppm 10.85 (s,1 H), 7.61 (s, 1 H), 7.37 - 7.27 (m, 3 H), 7.21 (d, J = 8.0 Hz, 1 H), 7.18 -7.10 (m, 1 H), 6.85 (dd, J = 1.6, 8.4 Hz, 1 H), 4.63 (d, J = 4.8 Hz, 1 H),4.10 (br s, 1 H), 3.82 (s, 3 H), 3.67 (s, 3 H), 3.25 (br d, J = 11.6 Hz, 1H), 3.01 (br dd, J = 4.8, 10.8 Hz, 1 H), 2.91 - 2.82 (m, 1 H), 2.82 - 2.74(m, 1 H), 2.72 - 2.61 (m, 1 H), 2.52 (br s, 1 H), 2.45 - 2.37 (m, 1 H), 2.28(dd, J = 2.4, 11.6 Hz, 1 H), 2.13 (br t, J = 10.4 Hz, 1 H), 1.95 - 1.81 (m, 1H), 1.80 - 1.70 (m, 1 H), 1.63 - 1.49 (m, 1H), 1.49 - 1.32 (m, 2 H), 1.31 -1.20 (m, 1 H), 0.99 (q, J = 11.6 Hz, 1 H); HPLC: 98.40%@220 nm, 99.84%@254nm. Example 21 The method was the same as in Example 3, except that phenylboronic acid was replaced with o-methoxyphenylboronic acid. The crude product was purified by preparative high performance liquid chromatography (column: 52-Welch Xtimate C18 150 × 30 mm, 5 μm; mobile phase: [water (0.55% ammonia)-acetonitrile]; gradient elution program: acetonitrile concentration increased from 12% to 42% within 10 minutes, and 100% acetonitrile was maintained for 0 minutes). After freeze-drying, 45.7 mg of compound 21 was obtained (white solid, 61.4% yield).

[0111] LCMS (ESI) m / z 461.2 [M+H] + ; 1 H NMR (400 MHz, DMSO- d 6) d ppm 10.79 (s, 1 H), 8.16 (s, 1 H), 7.38 (s, 1 H), 7.23 - 7.31 (m, 3 H), 7.11 (dd, J = 8.3,1.6 Hz, 1 H), 7.07 (d, J = 7.9 Hz, 1 H), 6.96 - 7.02 (m, 1 H), 4.50 - 4.71 (m, 1 H), 4.10 (br s, 1 H), 3.73 (s, 3 H), 3.67 (s, 3 H), 3.25 - 3.28 (m, 1H), 2.97 - 3.04 (m, 1 H), 2.86 (br d, J = 11.7 Hz, 1H), 2.72 - 2.82 (m, 1H), 2.60 (br d, J = 14.2 Hz, 1 H), 2.40 - 2.46 (m, 1 H), 2.28 (dd, J = 11.6,2.4 Hz, 1 H), 2.10 - 2.19 (m, 1 H), 1.82 - 1.93 (m, 1 H), 1.71 - 1.79 (m, 1H), 1.51 - 1.60 (m, 1 H), 1.36 - 1.48 (m, 2 H), 1.27 (br d, J = 8.2 Hz, 1 H), 0.99 (q, J = 11.6 Hz, 1 H); HPLC: 97.67%@220 nm; 99.87%@254 nm; 98.7%ee. Example 22 The method was the same as in Example 3, except that phenylboronic acid was replaced with o-methoxyphenylboronic acid. The crude product was purified by preparative high performance liquid chromatography (column: 50-Welch Xtimate C18 150 × 40 mm, 5 μm; mobile phase: [water (0.225% formic acid)-acetonitrile]; gradient elution program: acetonitrile concentration increased from 16% to 36% within 10 minutes, and 100% acetonitrile was maintained for 0 minutes). After freeze-drying, 23.0 mg of compound 22 (gray solid, 30.9% yield) was obtained.

[0112] LCMS (ESI) m / z 445.3 [M+H] + ; 1 H NMR (400 MHz, DMSO) -d 6) d ppm 10.82 (brs, 1 H), 7.48 - 7.59 (m, 3 H), 7.26 - 7.34 (m, 2 H), 7.22 (br d, J = 6.72 Hz, 2 H), 4.60 (br s, 1 H), 4.10 (br s, 1 H), 3.67 (br d, J = 1.47 Hz, 3 H), 3.26 (br d, J = 10.76 Hz, 1 H), 2.96 - 3.04 (m, 1 H), 2.82 - 2.91 (m, 1 H), 2.73 -2.81 (m, 1 H), 2.59 - 2.70 (m, 2 H), 2.52 - 2.56 (m, 1 H), 2.33 (br s, 3 H), 2.28 (br d, J = 12.23 Hz, 1 H), 2.13 (br t, J = 10.33 Hz, 1 H), 1.81 - 1.95 (m, 1 H), 1.70 - 1.80 (m, 1 H), 1.49 - 1.63 (m, 1 H), 1.31 - 1.48 (m, 2 H), 1.27 (br d, J = 7.34 Hz, 1 H), 0.91 - 1.07 (m, 1 H). HPLC: 96.49%@220 nm; 99.72%@254 nm.

[0113] Example 23 The method was the same as in Example 3, except that phenylboronic acid was replaced with p-chlorophenylboronic acid. The crude product was purified by preparative high performance liquid chromatography (column: 40-WePure Biotech XP tC18 150 × 30 mm, 7 μm; mobile phase: [water (0.05% ammonia) - acetonitrile]; gradient elution program: acetonitrile concentration increased from 60% to 80% within 10 minutes, and 100% acetonitrile was maintained for 0 minutes). After freeze-drying, 12.7 mg of compound 23 was obtained (white solid, 16.7% yield).

[0114] LCMS (ESI) m / z 465.2 [M+H] + ; 1 H NMR (400 MHz, DMSO- d 6) d ppm 10.89 (s, 1 H), 7.65 - 7.71 (m, 2 H), 7.63 (s, 1 H), 7.44 - 7.50 (m, 2 H), 7.28 - 7.38 (m, 2 H), 4.63 (br d, J = 3.4 Hz, 1 H), 4.11 (br s, 1 H), 3.68 (s, 3 H), 3.26 (br d, J = 10.4 Hz, 1 H), 3.01 (br dd, J = 10.8, 5.6 Hz, 1 H), 2.76 - 2.89 (m, 2 H), 2.62 - 2.71 (m, 1 H), 2.38 - 2.45 (m, 1 H), 2.28 (dd, J = 11.6, 2.6Hz, 1 H), 2.13 (br t, J = 10.3 Hz, 1 H), 1.82 - 1.94 (m, 1 H), 1.72 - 1.80 (m, 1 H), 1.51 - 1.63 (m, 1 H), 1.36 - 1.50 (m, 2 H), 1.28 (br d, J = 9.8 Hz, 1 H), 1.00 (q, J = 11.7 Hz, 1 H); HPLC: 98.56%@220 nm; 99.68%@254 nm. Example 24 The method was the same as in Example 3, except that phenylboronic acid was replaced with p-bromophenylboronic acid. The crude product was purified by preparative high performance liquid chromatography (column: 40-WePure Biotech XP tC18 150 × 30 mm, 7 μm; mobile phase: [water (0.05% ammonia) - acetonitrile]; gradient elution program: acetonitrile concentration increased from 58% to 78% within 10 minutes, and 100% acetonitrile was maintained for 0 minutes). After freeze-drying, 13.7 mg of compound 24 (white solid, 17.9% yield) was obtained.

[0115] LCMS (ESI) m / z 510.9 [M+H] + ; 1 H NMR (400 MHz, DMSO- d 6) d ppm 10.89 (s,1 H), 7.57 - 7.64 (m, 5 H), 7.28 - 7.36 (m, 2 H), 4.63 (d, J = 4.6 Hz, 1 H), 4.10 (br s, 1 H), 3.67 (s, 3 H), 3.25 (br d, J = 10.5 Hz, 1 H), 3.00 (br dd, J = 10.9, 5.2 Hz, 1 H), 2.75 - 2.88 (m, 2 H), 2.61 - 2.69 (m, 1 H), 2.41 (brd, J = 12.1 Hz, 1 H), 2.27 (dd, J = 11.4, 2.4 Hz, 1 H), 2.09 - 2.16 (m, 1 H), 1.82 - 1.91 (m, 1 H), 1.75 (br d, J = 11.4 Hz, 1 H), 1.55 (br t, J = 11.9 Hz, 1 H), 1.35 - 1.47 (m, 2 H), 1.23 - 1.30 (m, 1 H), 0.94 - 1.04 (m, 1 H); HPLC: 96.91%@220nm; 98.81%@254nm. Example 25 The method was the same as in Example 3, except that phenylboronic acid was replaced with p-ethoxyphenylboronic acid. The crude product was purified by preparative high performance liquid chromatography (column: 40-WePure Biotech XP tC18 150 × 30 mm, 7 μm; mobile phase: [water (0.05% ammonia) - acetonitrile]; gradient elution program: acetonitrile concentration increased from 58% to 78% within 10 minutes, and 100% acetonitrile was maintained for 0 minutes). After freeze-drying, 27.0 mg of compound 25 (white solid, 30.0% yield) was obtained.

[0116] LCMS (ESI) m / z 475.3 [M+H] + ; 1 H NMR (DMSO- d 6,400 MHz) d ppm 10.79 (s, 1 H), 7.71 - 7.40 (m, 3 H), 7.34 - 7.28 (m, 1 H), 7.27 - 7.21 (m, 1 H), 6.96 (br d, J = 8.4 Hz, 2 H), 4.63 (br d, J = 4.4 Hz, 1 H), 4.10 (br s, 1 H), 4.04 (q, J = 6.8 Hz, 2H), 3.67 (s, 3H), 3.24 (br d, J = 10.4 Hz, 1 H), 3.00 (brdd, J = 4.8, 10.4 Hz, 1 H), 2.90 - 2.72 (m, 2 H), 2.64 (br d, J = 13.2 Hz, 1H), 2.44 - 2.36 (m, 1H), 2.27 (br d, J = 11.6 Hz, 1 H), 2.18 - 2.05 (m, 1H), 1.93 - 1.79 (m, 1 H), 1.75 (br d, J = 11.6 Hz, 1 H), 1.55 (br t, J = 12.0Hz, 1H), 1.48 - 1.37 (m, 2H), 1.34 (br t, J = 6.8 Hz, 3 H), 1.26 (br d, J =9.6 Hz, 1H), 0.99 (q,J = 11.6 Hz, 1 H); HPLC: 98.98%@220 nm, 99.76%@254 nm. Example 26 The method is the same as in Example 3, except that phenylboronic acid is replaced with p-ethoxyphenylboronic acid. The crude product is purified by preparative high-performance liquid chromatography (column: 50-Welch Ultimate C). 18 150 × 40 mm × 5 μm; mobile phase: [water (0.225% formic acid) - acetonitrile]; gradient elution program: acetonitrile concentration increased from 15% to 55% over 10 minutes, 100% acetonitrile was maintained for 0 minutes), freeze-dried to give 42.5 mg of compound 26 (white solid, 53.9% yield).

[0117] LCMS (ESI) m / z 489.3 [M+H] + ; 1 H NMR (400 MHz, DMSO- d 6) d ppm 10.79 (s, 1 H), 8.15 (s, 1 H), 7.49 - 7.56 (m, 3 H), 7.28 - 7.33 (m, 1 H), 7.22 - 7.26 (m, 1 H), 6.95 (d, J = 8.7 Hz, 2 H), 4.62 (dt, J = 11.9, 5.9 Hz, 2 H), 4.10 (br d, J = 1.3 Hz, 1 H), 3.67 (s, 3 H), 3.29 (br s, 1 H), 3.02 (br dd, J =10.9, 5.4 Hz, 1 H), 2.86 (br d, J = 10.4 Hz, 1 H), 2.74 - 2.82 (m, 1 H), 2.61- 2.69 (m, 1 H), 2.41 (br d, J = 12.5 Hz, 1 H), 2.28 (dd, J = 11.4, 2.5 Hz, 1H), 2.14 (br t, J = 10.0 Hz, 1 H), 1.81 - 1.92 (m, 1 H), 1.75 (br d, J= 13.0Hz, 1 H), 1.50 - 1.59 (m, 1 H), 1.36 - 1.48 (m, 2 H), 1.29 (s, 3 H), 1.27 (s, 3 H), 1.24 - 1.26 (m, 1 H), 0.99 (q, J = 11.7 Hz, 1 H); HPLC: 99.83%@220 nm; 99.59%@254 nm; 100.0%ee. Example 27 The method is the same as in Example 3, except that phenylboronic acid is replaced with p-methylaminophenylboronic acid ester. The crude product is purified by preparative high-performance liquid chromatography (column: 50-Welch Ultimate C). 18 150 × 40 mm × 5 μm; mobile phase: [water (0.225% formic acid) - acetonitrile]; gradient elution program: acetonitrile concentration increased from 15% to 55% over 10 minutes, 100% acetonitrile was maintained for 0 minutes), freeze-dried to give 23.5 mg of compound 27 (white solid, 19.2% yield).

[0118] LCMS (ESI) m / z 460.2 [M+H] + ; 1 H NMR (400 MHz, DMSO) -d 6) d ppm 10.70 (s,1 H), 7.45 (s, 1 H), 7.39 (d, J = 8.56 Hz, 2 H), 7.24 - 7.29 (m, 1 H), 7.16 -7.22 (m, 1 H), 6.47 - 6.67 (m, 2 H), 5.60 (q, J = 5.14 Hz, 1 H), 4.62 (d, J =4.65 Hz, 1 H), 4.10 (br s, 1 H), 3.67 (s, 3 H), 3.23 (br d, J = 11.13 Hz, 1H), 3.00 (br dd, J = 11.07, 5.07 Hz, 1 H), 2.84 (br d, J = 10.64 Hz, 1 H), 2.76 (br dd, J = 11.25, 2.57 Hz, 1 H), 2.70 (d, J= 5.01 Hz, 3 H), 2.58 -2.66 (m, 1 H), 2.45 - 2.48 (m, 1 H), 2.40 (br d, J = 12.23 Hz, 1 H), 2.27 (dd, J = 11.49, 2.45 Hz, 1 H), 2.12 (br t, J = 10.33 Hz, 1 H), 1.81 - 1.93 (m, 1 H), 1.75 (br d, J = 12.47 Hz, 1 H), 1.50 - 1.62 (m, 1 H), 1.31 - 1.49 (m, 2 H), 1.26 (br d, J = 9.66 Hz, 1 H), 0.98 (q, J = 11.70 Hz, 1 H); HPLC:86.78%@220 nm; 98.76%@254 nm. Example 28 The method was the same as in Example 3, except that phenylboronic acid was replaced with p-dimethylaminophenylboronic acid. The crude product was purified by preparative high performance liquid chromatography (column: 40-WePure Biotech XP tC18 150 × 30 mm, 7 μm; mobile phase: [water (0.05% ammonia) - acetonitrile]; gradient elution program: acetonitrile concentration increased from 52% to 72% within 10 minutes, and 100% acetonitrile was maintained for 0 minutes). After freeze-drying, 46.2 mg of compound 28 was obtained (white solid, 41.3% yield).

[0119] LCMS (ESI) m / z 474.3 [M+H] + ; 1 H NMR (400 MHz, DMSO- d 6) d ppm 10.72 (s,1 H), 7.47 (d, J = 8.8 Hz, 3 H), 7.20 - 7.30 (m, 2 H), 6.78 (d, J = 8.9 Hz, 2H), 4.61 (d, J = 4.6 Hz, 1 H), 4.09 (br s, 1 H), 3.67 (s, 3 H), 3.23 (br d, J= 11.1 Hz, 1 H), 2.96 - 3.04 (m, 1 H), 2.91 (s, 6 H), 2.82 - 2.87 (m, 1 H), 2.73 - 2.80 (m, 1 H), 2.60 - 2.67 (m, 1 H), 2.36 - 2.43 (m, 1 H), 2.27 (dd, J = 11.5, 2.7 Hz, 1 H), 2.08 - 2.16 (m, 1 H), 1.81 - 1.91 (m, 1 H), 1.71 - 1.78 (m, 1 H), 1.50 - 1.60 (m, 1 H), 1.35 - 1.46 (m, 2 H), 1.23 - 1.30 (m, 1 H), 0.98 (q, J = 11.9 Hz, 1 H); HPLC: 97.80%@220 nm; 99.47%@254 nm.; 98.2% ee. Example 29 The method was the same as in Example 3, except that phenylboronic acid was replaced with 4-methoxycarbonylphenylboronic acid. The crude product was purified by preparative high performance liquid chromatography (column: 40-WePure Biotech XP tC18 150 × 30 mm, 7 μm; mobile phase: [water (0.05% ammonia) - acetonitrile]; gradient elution program: acetonitrile concentration increased from 48% to 68% within 10 minutes, and 100% acetonitrile was maintained for 0 minutes). After freeze-drying, 23.0 mg of compound 29 was obtained (white solid, 20.4% yield).

[0120] LCMS (ESI) m / z 489.3 [M+H] + ; 1 H NMR (400 MHz, DMSO- d 6) d ppm 10.94 (s,1 H), 8.00 (d, J = 8.6 Hz, 2 H), 7.82 (d, J = 8.6 Hz, 2 H), 7.73 (s, 1 H), 7.33 - 7.45 (m, 2 H), 4.62 (d, J = 4.2 Hz, 1 H), 4.10 (br s, 1 H), 3.87 (s, 3H), 3.67 (s, 3 H), 3.25 (br d, J= 10.5 Hz, 1 H), 3.01 (br dd, J = 10.4, 5.4Hz, 1 H), 2.75 - 2.90 (m, 2 H), 2.63 - 2.73 (m, 1 H), 2.37 - 2.45 (m, 1 H), 2.28 (dd, J = 11.6, 2.6 Hz, 1 H), 2.13 (br t, J = 10.4 Hz, 1 H), 1.82 - 1.94 (m, 1 H), 1.71 - 1.80 (m, 1 H), 1.50 - 1.62 (m, 1 H), 1.34 - 1.48 (m, 2 H), 1.23 - 1.31 (m, 1 H), 1.00 (q, J = 11.8 Hz, 1 H); HPLC: 99.92%@220 nm; 100%@254 nm. Example 30 The method was the same as in Example 3, except that phenylboronic acid was replaced with 4-carbamoylphenylboronic acid. The crude product was purified by preparative high performance liquid chromatography (column: 52-Welch Xtimate C18 150 × 30 mm, 5 μm; mobile phase: [water (0.05% ammonia) - acetonitrile]; gradient elution program: acetonitrile concentration increased from 22% to 52% within 9 minutes, 100% acetonitrile was maintained for 0 minutes). After freeze-drying, 30.0 mg of compound 30 was obtained (white solid, 33.4% yield).

[0121] LCMS (ESI) m / z 474.3 [M+H] + ; 1 H NMR (DMSO- d 6,400 MHz) d ppm 10.90 (s,1 H), 7.97 (br s, 1 H), 7.93 (d, J = 8.4 Hz, 2 H), 7.73 (d, J = 8.8 Hz, 2 H), 7.69 (s, 1H), 7.43 - 7.33 (m, 2 H), 7.31 (br s, 1 H), 4.63 (d, J = 4.4 Hz, 1H), 4.10 (br s, 1 H), 3.67 (s, 3 H), 3.25 (br d, J= 11.6 Hz, 1 H), 3.01 (brdd, J = 5.2, 10.8 Hz, 1 H), 2.91 - 2.83 (m, 1 H), 2.79 (br dd, J = 5.6, 9.6Hz, 1 H), 2.72 - 2.63 (m, 1 H), 2.54 (br s, 1 H), 2.42 (br d, J = 12.4 Hz, 1H), 2.28 (dd, J = 2.4, 11.6 Hz, 1 H), 2.13 (br t, J = 10.2 Hz, 1 H), 1.96 -1.82 (m, 1 H), 1.80 - 1.70 (m, 1 H), 1.62 - 1.51 (m, 1 H), 1.48 - 1.33 (m, 2H), 1.31 - 1.20 (m, 1 H), 1.09 - 0.89 (m, 1 H); HPLC: 99.16%@220 nm, 99.66%@254 nm. Example 31 The method is the same as in Example 3, except that phenylboronic acid is replaced with phenylboronic methanesulfonic acid. The crude product is purified by preparative high-performance liquid chromatography (column: 40-WePure Biotech XP tC). 18 150 × 30 mm × 7 μm; mobile phase: [water (0.05% ammonia) - acetonitrile]; gradient elution program: acetonitrile concentration increased from 35% to 55% over 10 minutes, 100% acetonitrile was maintained for 0 minutes), freeze-dried to give 13.0 mg of compound 31 (white solid, 18.5% yield).

[0122] LCMS (ESI) m / z 509.4 [M+H] + ; 1 H NMR (400 MHz, DMSO- d 6) d ppm 10.98 (s, 1 H), 7.94 (s, 4 H), 7.75 (s, 1 H), 7.35 - 7.44 (m, 2 H), 4.64 (br d, J= 3.2Hz, 1 H), 4.10 (br s, 1 H), 3.67 (s, 3 H), 3.27 (br s, 1 H), 3.23 (s, 3 H), 3.01 (br dd, J = 10.8, 5.1 Hz, 1 H), 2.76 - 2.89 (m, 2 H), 2.64 - 2.71 (m, 1H), 2.42 (br d, J = 12.1 Hz, 1 H), 2.28 (dd, J = 11.5, 2.6 Hz, 1 H), 2.08 -2.20 (m, 1 H), 1.81 - 1.93 (m, 1 H), 1.75 (br d, J = 10.4 Hz, 1 H), 1.50 -1.62 (m, 1 H), 1.32 - 1.48 (m, 2 H), 1.21 - 1.31 (m, 1 H), 1.00 (q, J = 11.7Hz, 1 H); HPLC: 94.18%@220 nm; 99.06%@254 nm; 99.4%ee. Example 32 The method was the same as in Example 3, except that phenylboronic acid was replaced with 4-acetamidophenylboronic acid. The crude product was purified by preparative high performance liquid chromatography (column: 55-Boston Prime C18 150 × 30 mm, 5 μm; mobile phase: [water (0.05% ammonia) - acetonitrile]; gradient elution program: acetonitrile concentration increased from 29% to 49% within 10 minutes, and 100% acetonitrile was maintained for 0 minutes). After freeze-drying, 13.8 mg of compound 32 was obtained (white solid, 17.2% yield).

[0123] LCMS (ESI) m / z 488.1 [M+H] + ; 1 H NMR (400 MHz, DMSO) -d 6) d ppm 10.80 (s, 1 H), 9.94 (s, 1 H), 7.48 - 7.67 (m, 5 H), 7.20 - 7.39 (m, 2 H), 4.62 (d, J =4.65 Hz, 1 H), 4.10 (br s, 1 H), 3.67 (s, 3 H), 3.24 (br d, J= 10.76 Hz, 1H), 3.00 (br dd, J = 10.64, 5.38 Hz, 1 H), 2.85 (br d, J = 10.27 Hz, 1 H), 2.78 (br d, J = 10.27 Hz, 1 H), 2.61 - 2.71 (m, 2 H), 2.41 (br d, J = 12.35Hz, 1H), 2.27 (br dd, J = 11.31, 2.02 Hz, 1 H), 2.12 (br t, J = 10.15 Hz, 1H), 2.05 (s, 3 H), 1.81 - 1.92 (m, 1 H), 1.75 (br d, J = 12.47 Hz, 1 H), 1.49- 1.62 (m, 1 H), 1.32 - 1.48 (m, 2 H), 1.22 - 1.31 (m, 1 H), 0.99 (q, J =11.66 Hz, 1 H); HPLC: 97.79%@220 nm; 99.78%@254 nm. Example 33 The method was the same as in Example 3, except that phenylboronic acid was replaced with 4-vinylphenylboronic acid. The crude product was purified by preparative high performance liquid chromatography (column: 40-WePure Biotech XP tC18 150 × 30 mm, 7 μm; mobile phase: [water (0.05% ammonia) - acetonitrile]; gradient elution program: acetonitrile concentration increased from 59% to 79% within 10 minutes, and 100% acetonitrile was maintained for 0 minutes). After freeze-drying, 20.6 mg of compound 33 was obtained (white solid, 27.8% yield).

[0124] LCMS (ESI) m / z 457.1 [M+H] + ; 1 H NMR (400 MHz, DMSO- d 6) d ppm 10.87 (s,1 H), 7.61 - 7.68 (m, 3 H), 7.52 (d, J = 8.4 Hz, 2 H), 7.34 (d, J = 0.9 Hz, 2H), 6.77 (dd, J= 17.6, 11.0 Hz, 1 H), 5.84 (d, J = 18.0 Hz, 1 H), 5.25 (d, J = 11.0 Hz, 1 H), 4.64 (d, J = 4.6 Hz, 1 H), 4.11 (br s, 1 H), 3.67 (s, 3 H), 3.25 (br d, J = 11.4 Hz, 1 H), 3.01 (br dd, J = 11.0, 5.3 Hz, 1 H), 2.76 -2.89 (m, 2 H), 2.63 - 2.71 (m, 1 H), 2.42 (br d, J = 12.1 Hz, 1 H), 2.28 (dd, J = 11.7, 2.4 Hz, 1 H), 2.13 (br t, J = 10.2 Hz, 1 H), 1.83 - 1.94 (m, 1 H), 1.70 - 1.80 (m, 1 H), 1.51 - 1.62 (m, 1 H), 1.36 - 1.47 (m, 2 H), 1.27 (br d, J = 9.9 Hz, 1 H), 1.00 (q, J = 11.9 Hz, 1 H); HPLC: 99.61%@220 nm; 99.94%@254nm; 98.12%ee. Example 34 The method was the same as in Example 3, except that phenylboronic acid was replaced with 2,4-difluorophenylboronic acid. The crude product was purified by preparative high-performance liquid chromatography (column: 40-WePure Biotech XP tC18 150 × 30 mm, 7 μm; mobile phase: [water (0.05% ammonia) - acetonitrile]; gradient elution program: acetonitrile concentration increased from 52% to 72% within 10 minutes, and 100% acetonitrile was maintained for 0 minutes). After freeze-drying, 30.7 mg of compound 34 was obtained (white solid, 40.6% yield).

[0125] LCMS (ESI) m / z 467.4 [M+H] + ; 1 H NMR (400 MHz, DMSO- d 6) dppm 10.93 (s, 1 H), 7.50 - 7.59 (m, 1 H), 7.46 (s, 1 H), 7.26 - 7.38 (m, 2 H), 7.11 - 7.18 (m, 2 H), 4.64 (d, J = 4.6 Hz, 1 H), 4.10 (br s, 1 H), 3.67 (s, 3 H), 3.25 (br d, J = 10.8 Hz, 1 H), 2.99 (br dd, J = 10.9, 5.2 Hz, 1 H), 2.84 (br d, J = 10.6 Hz, 1 H), 2.72 - 2.80 (m, 1 H), 2.58 - 2.65 (m, 1 H), 2.42 (br d, J =12.1 Hz, 1 H), 2.27 (dd, J = 11.3, 1.9 Hz, 1 H), 2.07 - 2.16 (m, 1 H), 1.81 -1.92 (m, 1 H), 1.75 (br d, J = 11.9 Hz, 1 H), 1.54 (br t, J = 12.1 Hz, 1 H), 1.34 - 1.48 (m, 2 H), 1.26 (br d, J = 9.5 Hz, 1 H), 0.99 (q, J = 11.7 Hz, 1H); 19 F NMR (376 MHz, DMSO- d 6) d ppm -113.15, -113.93; HPLC: 99.77%@220 nm; 99.92%@254 nm. Example 35 The method was the same as in Example 3, except that phenylboronic acid was replaced with 2,4,6-trifluorophenylboronic acid. The crude product was purified by preparative high-performance liquid chromatography (column: 40-WePure Biotech XP tC18 150 × 30 mm, 7 μm; mobile phase: [water (0.05% ammonia) - acetonitrile]; gradient elution program: acetonitrile concentration increased from 49% to 69% within 10 minutes, and 100% acetonitrile was maintained for 0 minutes). After freeze-drying, 13.8 mg of compound 35 was obtained (white solid, 15.5% yield).

[0126] LCMS (ESI) m / z 485.1 [M+H] + ; 1 H NMR (400 MHz, DMSO- d 6) d ppm 10.99 (s,1 H), 7.34 - 7.39 (m, 2 H), 7.23 - 7.31 (m, 2 H), 7.01 (d, J = 8.4 Hz, 1 H),4.64 (d, J = 4.6 Hz, 1 H), 4.10 (br s, 1 H), 3.67 (s, 3 H), 3.25 (br d, J =10.6 Hz, 1 H), 2.99 (br dd, J = 11.0, 5.0 Hz, 1 H), 2.85 (br dd, J = 10.7,1.4 Hz, 1 H), 2.71 - 2.80 (m, 1 H), 2.56 - 2.64 (m, 1 H), 2.43 (br d, J =13.0 Hz, 1 H), 2.28 (dd, J = 11.4, 2.5 Hz, 1 H), 2.12 (br t, J = 10.4 Hz, 1H), 1.82 - 1.91 (m, 1 H), 1.71 - 1.79 (m, 1 H), 1.50 - 1.61 (m, 1 H), 1.36 -1.46 (m, 2 H), 1.26 (br d, J = 8.4 Hz, 1 H), 0.99 (q, J = 11.5 Hz, 1 H); 19 FNMR (376 MHz, DMSO- d 6) d ppm -110.33, -111.41, -111.42; HPLC: 88.05%@220 nm;96.99%@254 nm. Example 36 The method was the same as in Example 3, except that phenylboronic acid was replaced with p-trifluorophenylboronic acid. The crude product was purified by preparative high performance liquid chromatography (column: 40-WePure Biotech XP tC18 150 × 30 mm, 7 μm; mobile phase: [water (0.05% ammonia) - acetonitrile]; gradient elution program: acetonitrile concentration increased from 59% to 79% within 10 minutes, and 100% acetonitrile was maintained for 0 minutes). After freeze-drying, 20.6 mg of compound 36 was obtained (white solid, 25.4% yield).

[0127] LCMS (ESI) m / z 499.2 [M+H] + ; 1 H NMR (400 MHz, DMSO) -d 6) d ppm 10.96 (s,1 H), 7.88 (d, J = 8.19 Hz, 2 H), 7.75 (d, J = 8.44 Hz, 2 H), 7.71 (s, 1 H), 7.38 (s, 2 H), 4.64 (d, J = 4.65 Hz, 1 H), 4.10 (br s, 1 H), 3.67 (s, 3 H), 3.25 (br d, J = 11.37 Hz, 1 H), 3.01 (br dd, J = 11.13, 5.01 Hz, 1 H), 2.75 -2.89 (m, 2 H), 2.63 - 2.72 (m, 1 H), 2.52 - 2.58 (m, 1 H), 2.42 (br dt, J =12.23, 2.45 Hz, 1 H), 2.28 (dd, J = 11.55, 2.38 Hz, 1 H), 2.13 (br t, J =10.33 Hz, 1 H), 1.81 - 1.95 (m, 1 H), 1.68 - 1.80 (m, 1 H), 1.50 - 1.64 (m, 1H), 1.31 - 1.50 (m, 2 H), 1.26 (br d, J = 8.93 Hz, 1 H), 1.00 (q, J = 11.82Hz, 1 H); HPLC: 99.29%@220 nm; 100.00%@254 nm. Example 37 The method was the same as in Example 3, except that phenylboronic acid was replaced with p-cyanobenonic acid. The crude product was purified by preparative high performance liquid chromatography (column: 55-Boston Prime C18 150 × 30 mm, 5 μm; mobile phase: [water (0.05% ammonia)-acetonitrile]; gradient elution program: acetonitrile concentration increased from 29% to 49% within 10 minutes, and 100% acetonitrile was maintained for 0 minutes). After freeze-drying, 26.1 mg of compound 37 was obtained (white solid, 35.5% yield).

[0128] LCMS (ESI) m / z 456.2 [M+H] + ; 1 H NMR (400 MHz, DMSO) -d 6) δ ppm 10.99 (s, 1 H), 7.82 - 7.98 (m, 4 H), 7.76 (s, 1 H), 7.30 - 7.47 (m, 2 H), 4.65 (d, J =4.65 Hz, 1 H), 4.11 (br s, 1 H), 3.68 (s, 3 H), 3.26 (br d, J = 11.25 Hz, 1H), 3.02 (br dd, J = 10.76, 5.14 Hz, 1 H), 2.75 - 2.91 (m, 2 H), 2.63 - 2.73 (m, 1 H), 2.38 - 2.45 (m, 2 H), 2.29 (dd, J = 11.49, 2.45 Hz, 1 H), 2.14 (brt, J = 10.09 Hz, 1 H), 1.81 - 1.98 (m, 1 H), 1.76 (br d, J = 10.51 Hz, 1 H), 1.51 - 1.62 (m, 1 H), 1.34 - 1.49 (m, 2 H), 1.24 - 1.32 (m, 1 H), 1.00 (q, J = 11.78 Hz, 1 H); HPLC: 100.00%@220 nm; 100.00%@254 nm. Example 38 The method was the same as in Example 3, except that phenylboronic acid was replaced with p-hydroxyphenylboronic acid. The crude product was purified by preparative high performance liquid chromatography (column: 40-WePure Biotech XP tC18 150 × 30 mm, 7 μm; mobile phase: [water (0.05% ammonia) - acetonitrile]; gradient elution program: acetonitrile concentration increased from 15% to 58% within 10 minutes, and 100% acetonitrile was maintained for 0 minutes). After freeze-drying, 20.0 mg of compound 38 was obtained (white solid, 27.7% yield).

[0129] LCMS (ESI) m / z 447.2 [M+H] + ; 1 H NMR (DMSO- d 6,400 MHz) d ppm 10.73 (s,1 H), 9.31 (br s, 1 H), 7.48 (s, 1 H), 7.43 (d, J = 8.4 Hz, 2 H), 7.32 - 7.26 (m, 1 H), 7.24 - 7.17 (m, 1 H), 6.81 (d, J = 8.8 Hz, 2 H), 4.59 (d, J = 4.4Hz, 1 H), 4.10 (br s, 1 H), 3.67 (s, 3 H), 3.24 (br d, J = 11.6 Hz, 1 H), 3.00 (br dd, J = 5.2, 10.8 Hz, 1 H), 2.89 - 2.82 (m, 1 H), 2.81 - 2.73 (m, 1H), 2.68 - 2.58 (m, 1 H), 2.40 (br d, J = 12.0 Hz, 1 H), 2.27 (dd, J = 2.4,11.6 Hz, 1 H), 2.12 (br t, J = 10.0 Hz, 1 H), 1.92 - 1.81 (m, 1 H), 1.80 -1.70 (m, 1 H), 1.55 (br t, J = 11.6 Hz, 1 H), 1.49 - 1.33 (m, 2 H), 1.32 -1.19 (m, 1 H), 0.99 (q, J= 11.6 Hz, 1 H); HPLC: 97.20%@220 nm, 99.78%@254nm. Example 39 The method was the same as in Example 3, except that phenylboronic acid was replaced with (4-aminosulfonyl)phenylboronic acid. The crude product was purified by preparative high performance liquid chromatography (column: 52-Welch Xtimate C18 150 × 30 mm, 5 μm; mobile phase: [water (0.05% ammonia)-acetonitrile]; gradient elution program: acetonitrile concentration increased from 25% to 55% within 10 minutes, and 100% acetonitrile was maintained for 0 minutes). After freeze-drying, 35.0 mg of compound 39 was obtained (white solid, 42.5% yield).

[0130] LCMS (ESI) m / z 510.3 [M+H] + ; 1 H NMR (DMSO- d 6,400 MHz) d ppm 10.95 (s, 1 H), 7.85 (s, 4 H), 7.71 (s, 1 H), 7.43 - 7.30 (m, 4 H), 4.64 (d, J = 4.8Hz, 1 H), 4.10 (br s, 1 H), 3.67 (s, 3 H), 3.28 - 3.19 (m, 1 H), 3.01 (br dd, J = 5.6, 10.8 Hz, 1 H), 2.90 - 2.75 (m, 2 H), 2.72 - 2.61 (m, 1 H), 2.42 (brd, J = 12.0 Hz, 1 H), 2.31 - 2.23 (m, 1 H), 2.19 - 2.09 (m, 1 H), 1.93 - 1.80 (m, 1 H), 1.75 (br d, J = 11.6 Hz, 1 H), 1.63 - 1.49 (m, 1 H), 1.48 - 1.34 (m, 2 H), 1.32 - 1.19 (m, 1 H), 1.00 (q, J = 11.2 Hz, 1 H); HPLC: 98.94%@220nm, 99.58%@254 nm. Example 40 The method is the same as in Example 3, except that phenylboronic acid is replaced with 1-(2-(4-boronicophenoxy)ethyl)pyrrolidine. The crude product is purified by preparative high-performance liquid chromatography (column: 40-WePure Biotech XP tC). 18 150 × 30 mm × 7 μm; mobile phase: [water (0.05% ammonia) - acetonitrile]; gradient elution program: acetonitrile concentration increased from 46% to 66% over 10 minutes, 100% acetonitrile was maintained for 0 minutes), freeze-dried to give 23.4 mg of compound 40 (white solid, 34.5% yield).

[0131] LCMS (ESI) m / z 544.3 [M+H] + ; 1 H NMR (400 MHz, DMSO- d 6) d ppm 10.79 (s, 1 H), 7.51 - 7.58 (m, 3 H), 7.27 - 7.32 (m, 1 H), 7.21 - 7.27 (m, 1 H), 6.98 (d, J = 8.8 Hz, 2 H), 4.63 (d, J = 4.8 Hz, 1 H), 4.05 - 4.13 (m, 3 H), 3.67 (s, 3 H), 3.24 (br d, J = 10.5 Hz, 1 H), 3.00 (br dd, J = 10.7, 5.1 Hz, 1 H), 2.84 (br d, J = 10.3 Hz, 1 H), 2.73 - 2.82 (m, 3 H), 2.59 - 2.68 (m, 1 H), 2.52 (br s, 4 H), 2.41 (br d, J = 12.0 Hz, 1 H), 2.27 (dd, J = 11.5, 2.3 Hz,1 H), 2.12 (br t, J = 10.2 Hz, 1 H), 1.81 - 1.92 (m, 1 H), 1.75 (br d, J=13.0 Hz, 1 H), 1.64 - 1.72 (m, 4 H), 1.49 - 1.59 (m, 1 H), 1.32 - 1.48 (m, 2H), 1.26 (br d, J = 9.4 Hz, 1 H), 0.98 (q, J = 11.6 Hz, 1 H); HPLC: 99.53%@220 nm; 99.33%@254 nm; 100.0%ee. Example 41 The method is the same as in Example 3, except that phenylboronic acid is replaced with 1-naphthoboronic acid. The crude product is purified by preparative high-performance liquid chromatography (column: 40-WePure Biotech XP tC). 18 150 × 30 mm × 7 μm; mobile phase: [water (0.05% ammonia) - acetonitrile]; gradient elution program: acetonitrile concentration increased from 61% to 81% over 10 minutes, 100% acetonitrile was maintained for 0 minutes), freeze-dried to give 30.1 mg of compound 41 (white solid, 45.2% yield).

[0132] LCMS (ESI) m / z 481.3 [M+H] + ; 1 H NMR (400 MHz, DMSO- d 6) d ppm 10.94 (s,1 H), 7.98 (d, J =7.7 Hz, 1 H), 7.89 (dd, J = 8.2, 5.0 Hz, 2 H), 7.48 - 7.60 (m, 2 H), 7.37 - 7.47 (m, 4 H), 7.08 - 7.14 (m, 1 H), 4.64 (d, J = 4.6 Hz, 1H), 4.11 (br s, 1 H), 3.68 (s, 3 H), 3.28 (br d, J = 11.1 Hz, 1 H), 2.99 (brdd, J = 10.6, 5.4 Hz, 1 H), 2.83 - 2.91 (m, 1 H), 2.73 - 2.82 (m, 1 H), 2.57 - 2.66 (m, 1 H), 2.43 - 2.48 (m, 1 H), 2.29 (dd, J = 11.6, 2.6 Hz, 1 H), 2.13 (br t,J = 10.1 Hz, 1 H), 1.82 - 1.95 (m, 1 H), 1.72 - 1.79 (m, 1 H), 1.51 -1.63 (m, 1 H), 1.33 - 1.49 (m, 2 H), 1.22 - 1.32 (m, 1 H), 1.02 (q, J = 11.7Hz, 1 H); HPLC: 99.60%@220 nm; 99.82%@254 nm; 99.5%ee. Example 42 The method is the same as in Example 3, except that phenylboronic acid is replaced with 6-methoxy-2-naphthoboronic acid. The crude product is purified by preparative high-performance liquid chromatography (column: 40-WePure Biotech XP tC). 18 150 × 30 mm × 7 μm; mobile phase: [water (0.05% ammonia) - acetonitrile]; gradient elution program: acetonitrile concentration increased from 57% to 77% over 10 minutes, 100% acetonitrile was maintained for 0 minutes), freeze-dried to give 14.4 mg of compound 42 (white solid, 17.2% yield).

[0133] LCMS (ESI) m / z 511.2 [M+H] + ; 1 H NMR (400 MHz, DMSO) -d 6) d ppm 10.87 (s, 1 H), 8.10 (s, 1 H), 7.81 - 7.96 (m, 3 H), 7.74 (s, 1 H), 7.42 - 7.55 (m, 1H), 7.35 - 7.40 (m, 1 H), 7.33 (br s, 1 H), 7.17 (br d, J = 8.93 Hz, 1 H), 4.65 (br d, J = 4.16 Hz, 1 H), 4.12 (br s, 1 H), 3.89 (s, 3 H), 3.69 (s, 3H), 3.27 (br d, J = 10.76 Hz, 1 H), 3.03 (br dd, J = 10.27, 4.77 Hz, 1 H), 2.78 - 2.93 (m, 2 H), 2.69 (br d, J= 13.33 Hz, 1 H), 2.53 - 2.59 (m, 1 H), 2.43 (br d, J = 11.74 Hz, 1 H), 2.29 (br d, J = 11.49 Hz, 1 H), 2.14 (br t, J = 9.84 Hz, 1 H), 1.81 - 2.00 (m, 1 H), 1.77 (br d, J = 12.72 Hz, 1 H), 1.52 -1.65 (m, 1 H), 1.35 - 1.50 (m, 2 H), 1.28 (br d, J = 9.29 Hz, 1 H), 1.02 (q, J = 11.94 Hz, 1 H); HPLC: 98.34%@220 nm; 99.35%@254 nm. Example 43 The method was the same as in Example 3, except that phenylboronic acid was replaced with 1H-indole-5-boronic acid. The crude product was purified by preparative high performance liquid chromatography (column: 52-Welch Xtimate C18 150 × 30 mm, 5 μm; mobile phase: [water (0.05% ammonia)-acetonitrile]; gradient elution program: acetonitrile concentration increased from 37% to 67% within 10 minutes, and 100% acetonitrile was maintained for 0 minutes). After freeze-drying, 35.0 mg of compound 43 was obtained (white solid, 46.1% yield).

[0134] LCMS (ESI) m / z 470.3 [M+H] + ; 1 H NMR (DMSO- d 6,400 MHz) d ppm 11.04 (brs, 1 H), 10.75 (s, 1 H), 7.75 (s, 1 H), 7.57 (s, 1 H), 7.45 - 7.40 (m, 1 H), 7.40 - 7.35 (m, 1 H), 7.33 (t, J = 2.8 Hz, 1 H), 7.31 (s, 2 H), 6.45 (br s, 1H), 4.64 (d, J = 4.8 Hz, 1 H), 4.10 (br s, 1 H), 3.67 (s, 3 H), 3.25 (br d,J = 11.2 Hz, 1 H), 3.01 (br dd, J = 5.6, 10.9 Hz, 1 H), 2.85 (br d, J = 10.2Hz, 1H), 2.79 (br d, J = 9.2 Hz, 1 H), 2.70 - 2.62 (m, 1 H), 2.53 (br d, J =4.8 Hz, 1 H), 2.42 (br d, J = 12.4 Hz, 1 H), 2.28 (dd, J = 2.4, 11.6 Hz, 1H), 2.13 (br t, J = 10.4 Hz, 1 H), 1.87 (br d, J = 9.6 Hz, 1 H), 1.75 (br d, J = 11.6 Hz, 1 H), 1.55 (br t, J = 11.6 Hz, 1 H), 1.49 - 1.33 (m, 2 H), 1.27- 1.27 (m, 1 H), 1.32 - 1.22 (m, 1 H), 1.00 (q, J = 11.6 Hz, 1 H); HPLC:95.82%@220 nm, 97.93%@254 nm. Example 44 The method was the same as in Example 3, except that phenylboronic acid was replaced with 3-fluoro-4-methoxyphenylboronic acid. The crude product was purified by preparative high performance liquid chromatography (column: 52-Welch Xtimate C18 150 × 30 mm, 5 μm; mobile phase: [water (0.05% ammonia)-acetonitrile]; gradient elution program: acetonitrile concentration increased from 43% to 73% within 10 minutes, and 100% acetonitrile was maintained for 0 minutes). After freeze-drying, 43.0 mg of compound 44 was obtained (white solid, 55.6% yield).

[0135] LCMS (ESI) m / z 479.3 [M+H] + ; 1 H NMR (DMSO- d 6,400 MHz) d ppm 10.84 (s,1 H), 7.58 (s, 1 H), 7.49 (dd,J = 2.0, 13.2 Hz, 1 H), 7.45 - 7.38 (m, 1 H), 7.34 - 7.25 (m, 2 H), 7.20 (t, J = 8.8 Hz, 1 H), 4.63 (d, J = 4.8 Hz, 1 H), 4.10 (br s, 1 H), 3.86 (s, 3 H), 3.67 (s, 3 H), 3.24 (br d, J = 10.8 Hz, 1H), 3.00 (br dd, J = 5.2, 10.8 Hz, 1 H), 2.84 (br d, J = 10.4 Hz, 1 H), 2.81- 2.74 (m, 1 H), 2.70 - 2.61 (m, 1 H), 2.40 (br d, J = 12.4 Hz, 1 H), 2.27 (dd, J = 2.4, 11.6 Hz, 1 H), 2.12 (br t, J = 10.4 Hz, 1 H), 1.86 (br d, J =9.6 Hz, 1 H), 1.75 (br dd, J = 2.4, 12.8 Hz, 1 H), 1.55 (br s, 1 H), 1.49 -1.32 (m, 2 H), 1.30 - 1.20 (m, 1 H), 1.06 - 0.92 (m, 1 H); HPLC: 99.52%@220nm, 100%@254 nm. Example 45 The method is the same as in Example 3, except that phenylboronic acid is replaced with 3-methyl-4-methoxyphenylboronic acid. The crude product is purified by preparative high-performance liquid chromatography (column: 40-WePure Biotech XP tC). 18 150 × 30 mm × 7 μm; mobile phase: [water (0.05% ammonia) - acetonitrile]; gradient elution program: acetonitrile concentration increased from 53% to 73% over 10 minutes, 100% acetonitrile was maintained for 0 minutes), freeze-dried to give 13.8 mg of compound 45 (white solid, 21.0% yield).

[0136] LCMS (ESI) m / z 475.3 [M+H] +; 1 H NMR (400 MHz, DMSO- d 6) d ppm 10.77 (s, 1 H), 7.52 (s, 1 H), 7.39 - 7.45 (m, 2 H), 7.27 - 7.33 (m, 1 H), 7.21 - 7.27 (m, 1 H), 6.97 (d, J = 8.6 Hz, 1 H), 4.61 (d, J = 4.8 Hz, 1 H), 4.10 (br s, 1H), 3.81 (s, 3 H), 3.67 (s, 3 H), 3.24 (br d, J = 10.8 Hz, 1 H), 3.00 (br dd, J = 10.6, 5.3 Hz, 1 H), 2.85 (br d, J = 10.1 Hz, 1 H), 2.71 - 2.81 (m, 1 H), 2.60 - 2.69 (m, 1 H), 2.41 (br d, J = 12.2 Hz, 1 H), 2.27 (dd, J = 11.6, 2.6Hz, 1H), 2.22 (s, 3H), 2.13 (br t, J = 10.3 Hz, 1 H), 1.81 - 1.91 (m, 1 H), 1.72 - 1.79 (m, 1 H), 1.50 - 1.61 (m, 1 H), 1.33 - 1.48 (m, 2 H), 1.27 (br d, J = 9.3 Hz, 1 H), 0.99 (q, J = 11.9 Hz, 1 H); HPLC: 99.69%@220 nm; 99.63%@254nm; 99.7%ee. Example 46 The method is the same as in Example 3, except that phenylboronic acid is replaced with 4-pentafluoride phenylboronic acid. The crude product is purified by preparative high-performance liquid chromatography (column: 40-WePure Biotech XP tC). 18150 × 30 mm × 7 μm; mobile phase: [water (0.05% ammonia) - acetonitrile]; gradient elution program: acetonitrile concentration increased from 63% to 83% over 10 minutes, 100% acetonitrile was maintained for 0 minutes), freeze-dried to give 14.1 mg of compound 46 (white solid, 20.3% yield).

[0137] LCMS (ESI) m / z 557.2 [M+H] + ; 1 H NMR (400 MHz, DMSO- d 6) d ppm 10.98 (s, 1 H), 7.85 - 7.94 (m, 4 H), 7.72 (s, 1 H), 7.39 (s, 2 H), 4.64 (d, J = 4.6Hz, 1 H), 4.10 (br s, 1 H), 3.67 (s, 3 H), 3.25 (br d, J = 10.8 Hz, 1 H), 3.01 (br dd, J = 10.5, 5.3 Hz, 1 H), 2.85 (br d, J = 10.5 Hz, 1 H), 2.74 -2.82 (m, 1 H), 2.63 - 2.71 (m, 1 H), 2.42 (br d, J = 12.3 Hz, 1 H), 2.28 (dd, J = 11.3, 2.4 Hz, 1 H), 2.13 (br t, J = 10.1 Hz, 1 H), 1.81 - 1.93 (m, 1 H), 1.75 (br d, J = 11.1 Hz, 1 H), 1.50 - 1.62 (m, 1 H), 1.32 - 1.48 (m, 2 H), 1.26 (br d, J = 9.6 Hz, 1 H), 0.99 (q, J = 11.5 Hz, 1 H); HPLC: 99.79%@220 nm; 100.0%@254 nm; 99.4%ee. Example 47 The method is the same as in Example 11, except that morpholine is replaced with tert-butyl carbamate. The crude product is dissolved in 5 mL of 2M dioxane hydrochloride solution, and the reaction is carried out at 20°C for 4 hours. The product is then concentrated under reduced pressure and purified by preparative high-performance liquid chromatography (HPLC) (column: 57-Phenomenex Gemini NX C). 18150 × 30 mm × 5 μm; mobile phase: [water (0.05% ammonia) - acetonitrile]; gradient elution program: acetonitrile concentration increased from 19% to 39% over 10 minutes, 100% acetonitrile was maintained for 0 minutes), freeze-dried to give 29.9 mg of compound 47 (white solid, 31.6% yield).

[0138] LCMS (ESI) m / z 370.2 [M+H] + ; 1 H NMR (400 MHz, DMSO- d 6) d ppm 10.20 (s,1 H), 6.94 (d, J = 8.4 Hz, 1 H), 6.49 (d, J = 1.6 Hz, 1 H), 6.37 (dd, J =8.4, 2.0 Hz, 1 H), 4.60 (d, J = 4.4 Hz, 1 H), 4.34 (br s, 2 H), 4.08 (br s, 1H), 3.65 (s, 3 H), 3.15 (br d, J = 11.1 Hz, 1 H), 2.94 (br dd, J = 10.6, 5.5Hz, 1H), 2.81 (dd, J = 10.9, 2.3 Hz, 1 H), 2.59 - 2.74 (m, 1 H), 2.39 - 2.48 (m, 2 H), 2.30 - 2.37 (m, 1 H), 2.25 (dd, J = 11.6, 2.5 Hz, 1 H), 2.08 (br t, J = 10.4 Hz, 1 H), 1.70 - 1.88 (m, 2 H), 1.54 (br t, J = 13.0 Hz, 1 H), 1.30- 1.47 (m, 2 H), 1.25 (br d, J = 9.4 Hz, 1 H), 0.93 (q, J = 11.5 Hz, 1 H); HPLC: 99.48%@220 nm, 95.11%@254 nm; 100%ee. Example 48 The method was the same as in Example 3, except that phenylboronic acid was replaced with 2,3-dimethoxyphenylboronic acid. The crude product was purified by preparative high performance liquid chromatography (column: 41-WePure Biotech XP tC18 150 × 40 mm, 7 μm; mobile phase: [water (formic acid)-acetonitrile]; gradient elution program: acetonitrile concentration increased from 14% to 34% within 10 minutes, 100% acetonitrile was maintained for 0 minutes). After freeze-drying, 24.4 mg of compound 48 was obtained (white solid, 29.6% yield).

[0139] LCMS (ESI) m / z 491.3 [M+H] + ; 1 H NMR (400 MHz, DMSO) -d 6) d ppm 10.85 (s,1 H), 7.41 (s, 1 H), 7.30 (d, J = 8.36 Hz, 1 H), 7.15 (d, J = 8.36 Hz, 1 H), 7.04 - 7.13 (m, 1 H), 6.96 - 7.01 (m, 1 H), 6.90 (d, J = 7.48 Hz, 1 H), 4.10 (br s, 1 H), 3.82 (s, 3 H), 3.67 (s, 3 H), 3.46 (s, 3 H), 3.35 (br d, J =11.22 Hz, 1 H), 3.04 (br dd, J = 10.45, 5.17 Hz, 1 H), 2.88 (br d, J = 9.90Hz, 1 H), 2.78 (br d, J = 10.34 Hz, 1 H), 2.52 - 2.67 (m, 2 H), 2.44 (br d, J = 12.10 Hz, 1 H), 2.28 (br d, J = 12.54 Hz, 1 H), 2.19 (br t, J = 10.01 Hz, 1H), 1.82 - 1.96 (m, 1H), 1.75 (br d, J = 11.88 Hz, 1 H), 1.50 - 1.63 (m, 1H), 1.35 - 1.48 (m, 2 H), 1.27 (br d,J = 5.94 Hz, 1 H), 1.02 (q, J = 11.74Hz, 1 H); HPLC: 99.02%@220 nm; 99.47%@254 nm; 87.8% ee. Example 49 The method was the same as in Example 3, except that phenylboronic acid was replaced with 2-fluoro-4-methoxyphenylboronic acid. The crude product was purified by preparative high performance liquid chromatography (column: 41-WePure Biotech XP tC18 150 × 40 mm, 7 μm; mobile phase: [water (formic acid)-acetonitrile]; gradient elution program: acetonitrile concentration increased from 6% to 36% within 10 minutes, 100% acetonitrile was maintained for 0 minutes). After freeze-drying, 18.8 mg of compound 49 was obtained (white solid, 25.1% yield).

[0140] LCMS (ESI) m / z 479.3 [M+H]+; 1 H NMR (400 MHz, DMSO- d 6) d ppm 10.91 (s, 1 H), 8.16 (s, 1 H), 7.51 (s, 1 H), 7.34 (d, J = 8.4 Hz, 1 H), 7.13 - 7.23 (m, 2 H), 6.98 - 7.01 (m, 1 H), 6.85 - 6.90 (m, 1 H), 4.62 (d, J = 2.4 Hz, 1H), 4.10 (s, 1 H), 3.79 (s, 3 H), 3.67 (s, 3 H), 3.25 (s, 1 H), 2.98 - 3.03 (m, 1 H), 2.86 (d, J = 9.4 Hz, 1 H), 2.72 - 2.81 (m, 1 H), 2.60 - 2.68 (m, 1H), 2.53 - 2.58 (m, 1 H), 2.42 (d, J = 12.4 Hz, 1 H), 2.26 - 2.30 (m, 1 H), 2.11 - 2.16 (m, 1 H), 1.81 - 1.93 (m, 1 H), 1.76 (d, J= 11.2 Hz, 1 H), 1.51- 1.63 (m, 1 H), 1.33 - 1.48 (m, 2 H), 1.20 - 1.32 (m, 1 H), 0.92 - 1.09 (m, 1 H); HPLC: 96.99%@220 nm, 99.69%@254 nm. Example 50 5.0 g of yohimbine (14.1 mmol), 17.9 g of bis(phenanthoxy)boronic acid ester (70.5 mmol), and 1.0 g of 3,4,7,8-tetramethyl-1,10-phenanthrolene (4.23 mmol) were dissolved in 125 mL of tetrahydrofuran, and 935 mg of cyclooctadiene methoxyiridium (1.41 mmol) were added. The mixture was stirred at 90 °C for 12 h. The reaction mixture was then added to 100 mL of ice water and extracted three times with 50 mL of dichloromethane. The combined organic phases were washed twice with 50 mL of saturated sodium chloride. The organic phase was dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (80 g silica gel column, methanol / dichloromethane system, methanol from 0% to 5%) to give 2.2 g of compound 50-1 (yellow solid, 32.5% yield). LCMS (ESI) m / z 481.2 [M+H] + 50 mg of compound 50-1 (0.0885 mmol) was dissolved in 1 mL of methanol and 0.2 mL of water, and 59.3 mg of copper bromide (0.266 mmol) was added. The mixture was stirred at 80 °C for 3 hours. The reaction solution was directly concentrated to obtain the crude product. The crude product was purified by preparative high performance liquid chromatography (column: Boston Prime C18 150 × 30 mm × 5 μm; mobile phase: [water (0.225% formic acid)-acetonitrile]; gradient elution program: acetonitrile concentration increased from 17% to 37% within 10 minutes), and lyophilized to give 6.2 mg of compound 50 (white solid, 16.0% yield).

[0141] LCMS (ESI) m / z 433.1 [M+H] + ; 1 H NMR (400 MHz, DMSO-d 6) δ ppm 10.87 (s,1 H), 7.36 (d, J = 7.63 Hz, 1 H), 7.21 (d, J = 7.38 Hz, 1 H), 6.89 (t, J=7.69 Hz, 1 H), 4.58 (s, 1 H), 4.08 (br s, 1 H), 3.67 (s, 3 H), 3.29 (br d, J = 11.63 Hz, 1 H), 2.99 (br dd, J = 10.94, 5.19 Hz, 1 H), 2.84 (br dd, J =11.07, 2.31 Hz, 1 H), 2.69 - 2.80 (m, 1 H), 2.63 - 2.68 (m, 1 H), 2.54 - 2.62 (m, 2 H), 2.25 (dd, J = 11.51, 2.63 Hz, 1 H), 2.17 (t, J = 10.26 Hz, 1 H), 1.80 - 1.92 (m, 1 H), 1.75 (br dd, J = 13.13, 2.63 Hz, 1 H), 1.49 - 1.60 (m, 1 H), 1.30 - 1.48 (m, 2 H), 1.19 - 1.29 (m, 1 H), 0.93 (q, J = 11.72 Hz, 1H); HPLC: 99.07%@220 nm, 100.00%@254 nm. Example 51 The method was the same as in Example 3, except that compound 1 was replaced with bromobenzene and phenylboronic acid was replaced with compound 50-1. The crude product was purified by preparative high performance liquid chromatography (column: C18 150 × 30 mm; mobile phase: [water (ammonia) - acetonitrile]; gradient elution program: the acetonitrile concentration increased from 39% to 79% within 2 minutes). After freeze-drying, 13.3 mg of compound 51 (white solid, 14.8% yield) was obtained.

[0142] LCMS (ESI) m / z 431.1 [M+H] + ; 1 H NMR (400 MHz, DMSO) -d 6) d ppm 10.45 (s,1 H), 7.57 - 7.65 (m, 2 H), 7.50 (t, J = 7.59 Hz, 2 H), 7.36 - 7.42 (m, 1 H), 7.34 (d, J= 7.04 Hz, 1 H), 7.02 - 7.07 (m, 1 H), 6.96 - 7.00 (m, 1 H), 4.56 (br s, 1 H), 4.07 (br d, J = 2.20 Hz, 1 H), 3.62 (s, 3 H), 3.21 - 3.31 (m, 2H), 3.00 (br dd, J = 11.33, 4.07 Hz, 1 H), 2.84 (br dd, J = 11.33, 2.09 Hz, 1H), 2.73 - 2.80 (m, 1 H), 2.52 - 2.65 (m, 2 H), 2.23 (dd, J = 11.44, 2.64 Hz,1 H), 2.16 (br t, J = 10.45 Hz, 1 H), 1.65 - 1.89 (m, 2 H), 1.48 - 1.59 (m, 1H), 1.31 - 1.46 (m, 2 H), 1.24 (br d, J = 8.36 Hz, 1 H), 0.92 (q, J = 11.52Hz, 1 H); HPLC: 98.39%@220 nm; 100.00%@254 nm. Example 52 The method was the same as in Example 3, except that compound 1 was replaced with p-fluorobromobenzene and phenylboronic acid was replaced with compound 50-1. The crude product was purified by preparative high performance liquid chromatography (column: Phenomenex C18 150 * 40 mm; mobile phase: [water (ammonia) - acetonitrile]; gradient elution program: the acetonitrile concentration increased from 53% to 73% within 2 minutes). After freeze-drying, 19.6 mg of compound 52 (white solid, 20.8% yield) was obtained.

[0143] LCMS (ESI) m / z 449.2 [M+H] + ; 1 H NMR (400 MHz, DMSO- d 6) d ppm 10.46 (s, 1 H), 7.58 - 7.64 (m, 2 H), 7.28 - 7.36 (m, 3 H), 7.00 - 7.07 (m, 1 H), 6.93- 6.99 (m, 1 H), 4.57 (d, J= 4.6 Hz, 1 H), 4.07 (br s, 1 H), 3.62 (s, 3 H), 3.26 (br d, J = 9.2 Hz, 1 H), 3.00 (br dd, J = 10.5, 4.7 Hz, 1 H), 2.84 (brd, J = 10.3 Hz, 1 H), 2.72 - 2.79 (m, 1 H), 2.61 (br d, J = 14.7 Hz, 1 H), 2.53 (br s, 1 H), 2.23 (dd, J = 11.2, 2.2 Hz, 1 H), 2.16 (br t, J = 10.6 Hz, 1 H), 1.77 - 1.87 (m, 1 H), 1.69 - 1.77 (m, 1 H), 1.49 - 1.57 (m, 1 H), 1.32 - 1.43 (m, 2 H), 1.20 - 1.29 (m, 1 H), 0.92 (q, J = 11.6 Hz, 1 H); 19 FNMR (400MHz, DMSO- d 6) d ppm 115.95; HPLC: 99.16%@220 nm; 99.35%@254 nm; 100%ee. Example 53 The method was the same as in Example 3, except that compound 1 was replaced with p-methoxybromobenzene and phenylboronic acid was replaced with compound 50-1. The crude product was purified by preparative high performance liquid chromatography (column: Boston Prime C18 150 × 30 mm × 5 μm; mobile phase: [water (formic acid)-acetonitrile]; gradient elution program: acetonitrile concentration increased from 26% to 46% within 2 minutes). After freeze-drying, 14.3 mg of compound 53 (white solid, 14.9% yield) was obtained.

[0144] LCMS (ESI) m / z 461.1 [M+H] + ; 1 H NMR (400 MHz, DMSO) -d 6) d ppm 10.39 (s,1 H), 7.53 (d, J= 8.80 Hz, 2 H), 7.31 (d, J = 7.48 Hz, 1 H), 7.07 (d, J =8.58 Hz, 2 H), 7.02 (t, J = 7.59 Hz, 1 H), 6.95 (dd, J = 7.26, 0.88 Hz, 1 H), 4.58 (br d, J = 1.98 Hz, 1 H), 4.08 (br s, 1 H), 3.83 (s, 3 H), 3.63 (s, 3H), 3.02 (br dd, J = 11.00, 4.84 Hz, 1 H), 2.86 (br dd, J = 10.89, 1.87 Hz, 1H), 2.72 - 2.81 (m, 1 H), 2.59 - 2.69 (m, 3 H), 2.52 - 2.58 (m, 1 H), 2.24 (dd, J = 11.66, 2.42 Hz, 1 H), 2.13 - 2.20 (m, 1 H), 1.78 - 1.93 (m, 1 H), 1.74 (br d, J- = 13.64 Hz, 1 H), 1.49 - 1.59 (m, 1 H), 1.31 - 1.45 (m, 2 H), 1.25 (br d, J = 10.34 Hz, 1 H), 0.94 (q, J = 11.44 Hz, 1 H); HPLC: 98.11%@220nm; 94.37%@254 nm. Example 54 The method was the same as in Example 3, except that compound 1 was replaced with 4-bromopyridine and phenylboronic acid was replaced with compound 50-1. The crude product was purified by preparative high performance liquid chromatography (column: Phenomenex C18 150 * 40 mm; mobile phase: [water (ammonia) - acetonitrile]; gradient elution program: the acetonitrile concentration increased from 33% to 53% within 10 minutes). After freeze-drying, 36.1 mg of compound 54 (white solid, 40.1% yield) was obtained.

[0145] LCMS (ESI) m / z 432.3 [M+H] + ; 1 H NMR (400 MHz, DMSO-d 6) d ppm 10.63 (s,1 H), 8.66 (d, J = 5.7 Hz, 2 H), 7.61 (d, J = 5.7 Hz, 2 H), 7.43 (t, J = 4.5Hz, 1 H), 7.09 (d, J = 4.5 Hz, 2 H), 4.57 (d, J = 4.4 Hz, 1 H), 4.07 (br s, 1H), 3.63 (s, 3 H), 3.28 (br d, J = 11.4 Hz, 1 H), 3.01 (br dd, J = 10.6, 4.9Hz, 1 H), 2.84 (br d, J = 10.1 Hz, 1 H), 2.73 - 2.81 (m, 1 H), 2.62 (br d, J = 14.7 Hz, 2 H), 2.55 (br d, J = 3.4 Hz, 1 H), 2.23 (dd, J = 11.4, 2.3 Hz, 1H), 2.11 - 2.17 (m, 1 H), 1.79 - 1.89 (m, 1 H), 1.74 (br d, J = 11.6 Hz, 1H), 1.48 - 1.59 (m, 1 H), 1.33 - 1.46 (m, 2 H), 1.21 - 1.27 (m, 1 H), 0.94 (q, J = 11.7 Hz, 1 H); HPLC: 99.91%@220nm; 99.80%@254 nm; 99.9%ee. Example 55 The method was the same as in Example 3, except that compound 1 was replaced with 3-bromo-1-methylpyrazole and phenylboronic acid was replaced with compound 50-1. The crude product was purified by preparative high performance liquid chromatography (column: Boston Prime C18 150 × 30 mm × 5 µm; mobile phase: [water (formic acid)-acetonitrile]; gradient elution program: acetonitrile concentration increased from 7% to 47% within 2 minutes). After freeze-drying, 21.3 mg of compound 55 (white solid, 23.1% yield) was obtained.

[0146] LCMS (ESI) m / z 435.2 [M+H] + ; 1 H NMR (400 MHz, DMSO- d 6) d ppm 10.12 (s,1 H), 7.82 (d, J = 2.3 Hz, 1 H), 7.47 (d, J = 7.3 Hz, 1 H), 7.34 (d, J = 7.6Hz, 1 H), 7.03 (t, J = 7.6 Hz, 1 H), 6.84 (d, J = 2.3 Hz, 1 H), 4.65 (br s, 1H), 4.12 (br s, 1 H), 3.96 (s, 3 H), 3.69 (s, 3 H), 3.32 (br s, 1 H), 3.02 (br dd, J = 10.9, 5.4 Hz, 1 H), 2.74 - 2.93 (m, 2 H), 2.60 - 2.71 (m, 1 H), 2.52 - 2.58 (m, 1 H), 2.26 - 2.38 (m, 2 H), 2.15 (br t, J = 10.3 Hz, 1 H), 1.83 - 1.98 (m, 1 H), 1.69 - 1.81 (m, 1 H), 1.51 - 1.61 (m, 1 H), 1.34 - 1.50 (m, 2 H), 1.22 - 1.32 (m, 1 H), 1.09 (q, J = 11.5 Hz, 1 H); HPLC: 98.24%@220nm, 98.04%@254 nm; 98.1%ee. Example 56 The method was the same as in Example 3, except that compound 1 was replaced with 4-bromo-1-methylpyrazole and phenylboronic acid was replaced with compound 50-1. The crude product was purified by preparative high performance liquid chromatography (column: C18 150 × 30 mm; mobile phase: [water (ammonia)-acetonitrile]; gradient elution program: acetonitrile concentration increased from 20% to 40% within 2 minutes). After freeze-drying, 35 mg of compound 56 (white solid, 38.7% yield) was obtained.

[0147] LCMS (ESI) m / z 435.2 [M+H] + ; 1 H NMR (400 MHz, DMSO- d 6) d ppm 10.14 (s, 1H), 8.15 (s, 1H), 7.84 (s, 1H), 7.24 (d, J = 7.7 Hz, 1H), 7.09 (d, J = 7.0Hz, 1H), 7.02 - 6.87 (m, 1H), 4.57 (d, J = 4.4 Hz, 1H), 4.08 (s, 1H), 3.92 (s, 3H), 3.66 (s, 3H), 3.30 (s, 1H), 3.00 (dd, J = 4.0, 10.4 Hz, 1H), 2.84 (d, J = 9.6 Hz, 1H), 2.80 - 2.69 (m, 1H), 2.64 - 2.53 (m, 3H), 2.29 - 2.14 (m, 2H), 1.93 - 1.80 (m, 1H), 1.75 (d, J = 11.2 Hz, 1H), 1.59 - 1.49 (m, 1H), 1.47 - 1.34 (m, 2H), 1.25 (d, J = 8.8 Hz, 1H), 0.95 (q, J = 12.0 Hz, 1H); HPLC: 99.40%@220 nm, 98.46%@254 nm. Example 57 The method was the same as in Example 3, except that compound 1 was replaced with 3-bromofuran and phenylboronic acid was replaced with compound 50-1. The crude product was purified by preparative high performance liquid chromatography (column: 57-Phenomenex Gemini NX C18 150 × 30 mm × 5 μm; mobile phase: [water (ammonia)-acetonitrile]; gradient elution program: acetonitrile concentration increased from 45% to 65% within 10 minutes). After freeze-drying, 15.9 mg of compound 57 (white solid, 18.2% yield) was obtained.

[0148] LCMS (ESI) m / z 421.2 [M+H] + ; 1 H NMR (400 MHz, DMSO-d 6) d ppm 10.11 (s,1 H), 8.25 (s, 1 H), 7.80 (t, J = 1.6 Hz, 1 H), 7.30 (d, J = 7.6 Hz, 1 H), 7.16 (d, J = 6.6 Hz, 1 H), 6.97 - 7.04 (m, 1 H), 6.95 (d, J = 1.0 Hz, 1 H), 4.57 (d, J = 4.4 Hz, 1 H), 4.08 (br s, 1 H), 3.66 (s, 3 H), 3.34 - 3.36 (m, 1H), 2.96 - 3.05 (m, 1 H), 2.82 - 2.90 (m, 1 H), 2.71 - 2.81 (m, 1 H), 2.53 -2.65 (m, 3 H), 2.14 - 2.29 (m, 2 H), 1.81 - 1.94 (m, 1 H), 1.71 - 1.80 (m, 1H), 1.49 - 1.60 (m, 1 H), 1.32 - 1.47 (m, 2 H), 1.21 - 1.30 (m, 1 H), 0.90 -1.02 (m, 1 H); HPLC: 98.99 %@220 nm, 97.86%@254 nm; 100%ee. Example 58 The method was the same as in Example 3, except that compound 1 was replaced with 2-bromofuran and phenylboronic acid was replaced with compound 50-1. The crude product was purified by preparative high performance liquid chromatography (column: 55-Boston Prime C18 150 × 30 mm × 5 μm; mobile phase: [water (formic acid)-acetonitrile]; gradient elution program: acetonitrile concentration increased from 17% to 37% within 10 minutes). After freeze-drying, 35 mg of compound 58 (white solid, 40.4% yield) was obtained.

[0149] LCMS (ESI) m / z 421.2 [M+H] + ; 1 H NMR (400 MHz, DMSO- d 6) d ppm 10.24 (s,1H), 8.16 (s,1H), 7.80 (d, J= 1.2 Hz, 1H), 7.39 (d, J = 7.6 Hz, 1H), 7.34 (d, J = 7.6 Hz, 1H), 7.05 (d, J = 3.6 Hz, 1H), 7.04 - 7.00 (m, 1H), 6.67 (dd, J = 2.0, 3.6 Hz, 1H), 4.73 - 4.40 (m, 1H), 4.09 (d, J = 2.0 Hz, 1H), 3.67 (s, 3H), 3.40 (d, J = 10.8 Hz, 2H), 3.07 - 2.98 (m, 1H), 2.91 - 2.84 (m, 1H), 2.83 - 2.72 (m, 1H), 2.66 - 2.54 (m, 3H), 2.29 - 2.20 (m, 2H), 1.97 - 1.84 (m, 1H), 1.80 - 1.69 (m, 1H), 1.54 (t, J = 11.6 Hz, 1H), 1.46 - 1.33 (m, 2H), 1.30 - 1.22 (m, 1H), 1.00 (q, J = 11.6 Hz, 1H); HPLC: 98.57%@220 nm, 99.60%@254 nm. Example 59 The method was the same as in Example 11, except that compound 1 was replaced with compound 50. The crude product was purified by preparative high performance liquid chromatography (column: 57-Phenomenex Gemini NX C18 150 × 30 mm × 5 μm; mobile phase: [water (formic acid)-acetonitrile]; gradient elution program: acetonitrile concentration increased from 34% to 54% within 10 minutes). After freeze-drying, 5.1 mg of compound 59 (white solid, 4.70% yield) was obtained.

[0150] LCMS (ESI) m / z 440.3 [M+H] + ; 1 H NMR (400 MHz, DMSO-d 6) d ppm 10.33 (s,1 H), 7.03 (d, J = 7.75 Hz, 1 H), 6.87 (t, J= 7.63 Hz, 1 H), 6.63 (d, J =7.38 Hz, 1 H), 4.57 (br s, 1 H), 4.08 (br s, 1 H), 3.80 - 3.87 (m, 4 H), 3.66 (s, 3 H), 3.24 - 3.31 (m, 1 H), 2.89 - 3.06 (m, 5 H), 2.79 - 2.87 (m, 1 H), 2.67 - 2.77 (m, 1 H), 2.53 - 2.61 (m, 3 H), 2.25 (dd, J = 11.38, 2.38 Hz, 1H), 2.17 (br t, J = 10.19 Hz, 1 H), 1.80 - 1.93 (m, 1 H), 1.70 - 1.78 (m, 1H), 1.48 - 1.60 (m, 1 H), 1.31 - 1.48 (m, 2 H), 1.25 (br d, J = 9.63 Hz, 1H), 0.95 (q, J = 11.67 Hz, 1 H); HPLC: 95.08%@220 nm, 93.39%@254 nm. Example 60 The method was the same as in Example 11, except that compound 1 was replaced with compound 50 and morpholine was replaced with piperidine. The crude product was purified by preparative high performance liquid chromatography (column: Phenomenex C18 150 * 40 mm; mobile phase: [water (ammonia) - acetonitrile]; gradient elution program: the acetonitrile concentration increased from 57% to 57% within 10 minutes). After freeze-drying, 12.6 mg of compound 60 (white solid, 12.3% yield) was obtained.

[0151] LCMS (ESI) m / z 438.1 [M+H] + ; 1 H NMR (400 MHz, DMSO- d 6) d ppm 10.22 (s,1 H), 8.19 (br s, 0.5 H), 7.00 (d, J = 7.7 Hz, 1 H), 6.85 (t, J = 7.6 Hz, 1H), 6.63 (d, J= 7.3 Hz, 1 H), 4.08 (br d, J = 2.1 Hz, 1 H), 3.66 (s, 3 H), 3.31 (br d, J = 10.6 Hz, 2 H), 2.94 (ddt, J = 16.5, 11.1, 5.7, 5.7 Hz, 5 H), 2.79 - 2.87 (m, 1 H), 2.67 - 2.78 (m, 1 H), 2.53 - 2.63 (m, 2 H), 2.25 (dd, J = 11.5, 2.4 Hz, 1 H), 2.18 (br t, J = 10.5 Hz, 1 H), 1.81 - 1.91 (m, 1 H), 1.70 - 1.80 (m, 5 H), 1.50 - 1.59 (m, 3 H), 1.34 - 1.47 (m, 2 H), 1.25 (br d, J = 8.6 Hz, 1 H), 0.96 (q, J = 11.7 Hz, 1 H); HPLC: 98.43%@220 nm; 100%@254nm; 100%ee. Example 61 The method was the same as in Example 11, except that compound 1 was replaced with compound 50 and morpholine was replaced with N-methylpiperazine. The crude product was purified by preparative high performance liquid chromatography (column: 57-Phenomenex Gemini NX C18 150 × 30 mm, 5 μm; mobile phase: [water (ammonia)-acetonitrile]; gradient elution program: acetonitrile concentration increased from 31% to 51% within 10 minutes). After freeze-drying, 13.5 mg of compound 61 (white solid, 12.1% yield) was obtained.

[0152] LCMS (ESI) m / z 453.3 [M+H] + ; 1 H NMR (400 MHz, DMSO-d 6) d ppm 10.25 (s,1 H), 7.01 (d, J = 7.63 Hz, 1 H), 6.86 (t, J = 7.63 Hz, 1 H), 6.62 (d, J=7.50 Hz, 1 H), 4.56 (br d, J = 3.38 Hz, 1 H), 4.08 (br s, 1 H), 3.66 (s, 3H), 3.25 - 3.30 (m, 2 H), 2.92 - 3.04 (m, 5 H), 2.80 - 2.86 (m, 1 H), 2.65 -2.77 (m, 1 H), 2.53 - 2.63 (m, 5 H), 2.47 (br d, J = 1.88 Hz, 1 H), 2.26 (s, 3 H), 2.20 - 2.24 (m, 1 H), 2.17 (br t, J = 10.38 Hz, 1 H), 1.85 (q, J =10.96 Hz, 1 H), 1.75 (br d, J = 10.88 Hz, 1 H), 1.54 (br t, J = 11.51 Hz, 1H), 1.32 - 1.47 (m, 2 H), 1.21 - 1.28 (m, 1 H), 0.94 (q, J = 11.67 Hz, 1 H).HPLC: 96.29%@220 nm, 93.49%@254 nm. Example 62 The method was the same as in Example 11, except that compound 1 was replaced with compound 50 and morpholine was replaced with NH2Boc. The crude product was purified by preparative high performance liquid chromatography (column: 57-Phenomenex Gemini NX C18 150 × 30 mm, 5 μm; mobile phase: [water (formic acid)-acetonitrile]; gradient elution program: acetonitrile concentration increased from 0% to 27% within 10 minutes). After freeze-drying, 13.4 mg of compound 62 (white solid, 9.6% yield) was obtained.

[0153] LCMS (ESI) m / z 370.2 [M+H] + ; 1 H NMR (400 MHz, DMSO) -d 6) d ppm 10.12 (s,1 H), 6.64 - 6.73 (m, 1 H), 6.53 - 6.61 (m, 1 H), 6.24 (d, J= 7.21 Hz, 1 H), 4.45 - 5.82 (m, 2 H), 4.11 (br s, 1 H), 3.66 (s, 3 H), 3.10 - 3.27 (m, 2 H), 2.97 (br dd, J = 10.82, 4.83 Hz, 1 H), 2.84 (br d, J = 10.03 Hz, 1 H), 2.63 -2.77 (m, 1 H), 2.52 - 2.57 (m, 2 H), 2.36 - 2.41 (m, 1 H), 2.29 (dd, J =11.37, 2.57 Hz, 1 H), 2.13 (br t, J = 10.03 Hz, 1 H), 1.81 - 1.95 (m, 1 H), 1.75 (br dd, J = 13.39, 2.26 Hz, 1 H), 1.50 - 1.61 (m, 1 H), 1.33 - 1.48 (m, 2 H), 1.21 - 1.30 (m, 1 H), 0.99 (q, J = 11.74 Hz, 1 H); HPLC: 99.07%@220 nm, 95.17%@254 nm. Example 63 The method was the same as in Example 3, except that compound 1 was replaced with 3-methoxybromobenzene and phenylboronic acid was replaced with compound 50-1. The crude product was purified by preparative high performance liquid chromatography (column: 55-Boston Prime C18 150 × 30 mm × 5 μm; mobile phase: [water (formic acid)-acetonitrile]; gradient elution program: the acetonitrile concentration increased from 18% to 58% within 10 minutes). After freeze-drying, 45 mg of compound 63 (white solid, 46.9% yield) was obtained.

[0154] LCMS (ESI) m / z 461.4 [M+H] + ; 1 H NMR (400 MHz, DMSO- d 6) dppm 10.54 (s,1H), 8.15 (s, 1H), 7.44 - 7.38 (m, 1H), 7.37 - 7.32 (m, 1H), 7.19 - 7.14 (m,2H), 7.07 - 7.01 (m, 2H), 6.97 - 6.91 (m, 1H), 4.71 - 4.43 (m, 1H), 4.07 (d, J = 2.0 Hz, 1H), 3.82 (s, 3H), 3.63 (s, 4H), 3.37 (d, J = 10.8 Hz, 1H), 3.06 (dd, J = 4.8, 9.6 Hz, 1H), 2.88 (d, J = 10.0 Hz, 1H), 2.84 - 2.74 (m, 1H), 2.68 - 2.53 (m, 3H), 2.28 - 2.18 (m, 2H), 1.92 - 1.79 (m, 1H), 1.78 - 1.69 (m, 1H), 1.60 - 1.49 (m, 1H), 1.48 - 1.32 (m, 2H), 1.25 (d, J = 8.4 Hz, 1H), 0.98 (q, J = 11.6 Hz, 1H); HPLC: 99.08%@220 nm, 99.85%@254 nm. Example 64 The method was the same as in Example 3, except that compound 1 was replaced with 2-methoxybromobenzene and phenylboronic acid was replaced with compound 50-1. The crude product was purified by preparative high performance liquid chromatography (column: 57-Phenomenex Gemini NX C18 150 × 30 mm × 5 μm; mobile phase: [water (ammonia) - acetonitrile]; gradient elution program: acetonitrile concentration increased from 45% to 65% within 10 minutes). After freeze-drying, 27.5 mg of compound 64 (white solid, 28.7% yield) was obtained.

[0155] LCMS (ESI) m / z 461.3 [M+H] + ; 1 H NMR (400 MHz, DMSO- d 6) d ppm 10.11 (s,1 H), 7.35 - 7.43 (m, 1 H), 7.31 (br dd,J = 10.6, 7.8 Hz, 2 H), 7.11 (d, J =8.3 Hz, 1 H), 6.94 - 7.07 (m, 2 H), 6.85 - 6.92 (m, 1 H), 4.51 (d, J = 4.4Hz, 1 H), 4.04 (br s, 1 H), 3.71 (s, 3 H), 3.57 - 3.66 (m, 3 H), 3.23 (br d, J = 10.4 Hz, 1 H), 3.00 (br dd, J = 10.8, 3.9 Hz, 1 H), 2.83 (br d, J = 10.3Hz, 1 H), 2.72 - 2.81 (m, 1 H), 2.54 - 2.69 (m, 2 H), 2.22 (br dd, J = 11.5,2.1 Hz, 1 H), 2.15 (br t, J = 10.2 Hz, 1 H), 1.70 - 1.87 (m, 2 H), 1.47 -1.59 (m, 1 H), 1.34 - 1.47 (m, 2 H), 1.25 (br d, J = 8.8 Hz, 1 H), 0.93 (q, J = 11.8 Hz, 1 H); HPLC: 96.62%@220 nm, 98.67%@254 nm; 100%ee. Example 65 The method was the same as in Example 3, except that compound 1 was replaced with 4-methylbromobenzene and phenylboronic acid was replaced with compound 50-1. The crude product was purified by preparative high performance liquid chromatography (column: Phenomenex Synergi C18 150 × 30 mm × 4 µm; mobile phase: [water (ammonia) - acetonitrile]; gradient elution program: the acetonitrile concentration increased from 56% to 76% within 10 minutes). After freeze-drying, 31.8 mg of compound 65 (white solid, 34.4% yield) was obtained.

[0156] LCMS (ESI) m / z 445.2 [M+H] + ; 1 H NMR (400 MHz, DMSO- d 6) dppm 10.38 (s,1 H), 7.49 (d, J = 7.9 Hz, 2 H), 7.22 - 7.38 (m, 3 H), 6.92 - 7.11 (m, 2 H), 4.55 (d, J = 4.6 Hz, 1 H), 4.07 (br s, 1 H), 3.63 (s, 3 H), 3.27 (br d, J =10.4 Hz, 1 H), 3.00 (br dd, J = 10.9, 4.1 Hz, 1 H), 2.83 (br d, J = 10.8 Hz, 1 H), 2.72 - 2.80 (m, 1 H), 2.57 - 2.65 (m, 1 H), 2.54 (br d, J =3.1 Hz, 1H), 2.38 (s, 3 H), 2.22 (dd, J = 11.5, 2.3 Hz, 1 H), 2.16 (br t, J = 10.4 Hz, 1 H), 1.70 - 1.88 (m, 2 H), 1.53 (br t, J = 11.6 Hz, 1 H), 1.30 - 1.46 (m, 2H), 1.24 (br d, J = 8.9 Hz, 1 H), 0.92 (q, J = 11.5 Hz, 1 H); HPLC: 99.88%@220 nm, 100.0%@254 nm. Example 66 The method was the same as in Example 3, except that compound 1 was replaced with 4-chlorobromobenzene and phenylboronic acid was replaced with compound 50-1. The crude product was purified by preparative high performance liquid chromatography (column: Phenomenex Synergi C18 150 × 30 mm × 4 µm; mobile phase: [water (ammonia) - acetonitrile]; gradient elution program: the acetonitrile concentration increased from 62% to 82% within 10 minutes). After freeze-drying, 38.1 mg of compound 66 (white solid, 39.4% yield) was obtained.

[0157] LCMS (ESI) m / z 465.2 [M+H] + ; 1 H NMR (400 MHz, DMSO- d 6) d ppm 10.50 (s,1 H), 7.57 - 7.64 (m, 2 H), 7.50 - 7.56 (m, 2 H), 7.36 (d, J = 7.6 Hz, 1 H), 7.01 - 7.09 (m, 1 H), 6.95 - 7.00 (m, 1 H), 4.56 (d, J = 4.6 Hz, 1 H), 4.07 (br s, 1 H), 3.63 (s, 3 H), 3.26 (br d, J = 10.9 Hz, 1 H), 3.00 (br dd, J =11.1, 4.6 Hz, 1 H), 2.73 - 2.89 (m, 2 H), 2.61 (br d, J = 15.0 Hz, 1 H), 2.54 (br d, J = 3.2 Hz, 1 H), 2.23 (dd, J = 11.5, 2.3 Hz, 1 H), 2.16 (br t, J =10.3 Hz, 1 H), 1.71 - 1.89 (m, 2 H), 1.53 (br t, J = 11.9 Hz, 1 H), 1.31 -1.46 (m, 2 H), 1.24 (br d, J = 8.7 Hz, 1 H), 0.93 (q, J = 11.7 Hz, 1 H); HPLC: 99.05 %@220 nm, 100.0%@254 nm. Example 67 The method was the same as in Example 3, except that compound 1 was replaced with 4-iodobromobenzene and phenylboronic acid was replaced with compound 50-1. The crude product was purified by preparative high performance liquid chromatography (column: Phenomenex Synergi C18 150 × 30 mm × 4 µm; mobile phase: [water (ammonia) - acetonitrile]; gradient elution program: acetonitrile concentration increased from 60% to 80% within 10 minutes). After freeze-drying, 6.5 mg of compound 67 (white solid, 6.1% yield) was obtained.

[0158] LCMS (ESI) m / z 509.1, 511.1 [M+H] + ; 1 H NMR (DMSO-d 6,400 MHz) d ppm10.51 (s, 1 H), 7.67 (br d, J = 8.0 Hz, 2 H), 7.54 (br d, J = 8.0 Hz, 2 H),7.37 (br d, J = 7.6 Hz, 1 H), 7.09 - 7.01 (m, 1 H), 7.00 - 6.93 (m, 1 H), 4.56 (br d, J = 4.4 Hz, 1 H), 4.07 (br s, 1 H), 3.63 (s, 3 H), 3.26 (br d, J = 11.6 Hz, 1 H), 3.00 (br d, J = 5.6 Hz, 1 H), 2.91 - 2.71 (m, 2 H), 2.61 (brd, J = 14.4 Hz, 1 H), 2.58 - 2.52 (m, 2 H), 2.23 (br d, J = 11.2 Hz, 1 H), 2.16 (br t, J = 10.0 Hz, 1 H), 1.89 - 1.69 (m, 2 H), 1.53 (br t, J = 11.6 Hz, 1 H), 1.46 - 1.31 (m, 2 H), 1.24 (br d, J = 7.8 Hz, 1 H), 1.03 - 0.86 (m, 1H); HPLC: 98.64%@220 nm, 98.73%@254 nm. Example 68 The method was the same as in Example 3, except that compound 1 was replaced with 4-ethoxybromobenzene and phenylboronic acid was replaced with compound 50-1. The crude product was purified by preparative high performance liquid chromatography (column: 57-Phenomenex Gemini NX C18 150 × 30 mm × 5 μm; mobile phase: [water (ammonia) - acetonitrile]; gradient elution program: the acetonitrile concentration increased from 61% to 71% within 10 minutes). After freeze-drying, 23.0 mg of compound 68 (white solid, 23.3% yield) was obtained.

[0159] LCMS (ESI) m / z 475.2 [M+H]+ ; 1 H NMR (DMSO- d 6,400 MHz) d ppm 10.36 (s,1 H), 7.51 (d, J = 8.8 Hz, 2 H), 7.30 (d, J = 7.6 Hz, 1 H), 7.08 - 6.97 (m, 3H), 6.96 - 6.89 (m, 1 H), 4.56 (br s, 1 H), 4.16 - 4.00 (m, 3 H), 3.63 (s, 3H), 3.27 (br d, J = 11.2 Hz, 1 H), 3.00 (br dd, J = 4.8, 10.4 Hz, 1 H), 2.87- 2.72 (m, 2 H), 2.60 (br d, J = 14.4 Hz, 1 H), 2.54 (br d, J = 3.1 Hz, 1 H), 2.22 (dd, J = 2.4, 11.6 Hz, 1 H), 2.16 (br t, J = 10.4 Hz, 1 H), 1.91 - 1.69 (m, 2 H), 1.61 - 1.47 (m, 1 H), 1.44 - 1.31 (m, 5 H), 1.24 (br d, J = 8.8 Hz, 1 H), 0.92 (q, J = 11.6 Hz, 1 H); HPLC: 99.74%@220 nm, 100%@254 nm. Example 69 The method was the same as in Example 3, except that compound 1 was replaced with 4-isopropoxybromobenzene and phenylboronic acid was replaced with compound 50-1. The crude product was purified by preparative high performance liquid chromatography (column: 57-Phenomenex Gemini NX C18 150× 30 mm × 5 μm; mobile phase: [water (ammonia)-acetonitrile]; gradient elution program: acetonitrile concentration increased from 40% to 80% within 10 minutes). After freeze-drying, 23.9 mg of compound 69 (yellow solid, 22.0% yield) was obtained.

[0160] LCMS (ESI) m / z 489.2 [M+H]+ ; 1 H NMR (400 MHz, DMSO -d 6) d ppm 10.43 (s,1 H), 7.46 - 7.51 (m, 2 H), 7.30 (d, J = 7.50 Hz, 1 H), 6.99 - 7.05 (m, 3 H),6.94 (dd, J = 7.25, 1.00 Hz, 1 H), 4.67 (dq, J = 12.02, 6.06, 6.06, 6.06,6.06 Hz, 1 H), 4.58 (br s, 1 H), 4.07 (br d, J = 1.63 Hz, 1 H), 3.63 (s, 3H), 3.35 (br d, J = 10.76 Hz, 2 H), 3.04 (br dd, J = 10.19, 4.57 Hz, 1 H),2.87 (br d, J = 9.38 Hz, 1 H), 2.73 - 2.83 (m, 1 H), 2.53 - 2.65 (m, 4 H),2.15 - 2.27 (m, 2 H), 1.79 - 1.91 (m, 1 H), 1.74 (br dd, J = 12.88, 2.38 Hz,1 H), 1.35 - 1.59 (m, 2 H), 1.31 (dd, J = 5.94, 0.81 Hz, 6 H), 1.22 - 1.27(m, 1 H), 0.95 (q, J = 11.76 Hz, 1 H); HPLC: 93.84%@220 nm, 97.82%@254 nm. Example 70 The method was the same as in Example 3, except that compound 1 was replaced with tert-butyl (4-bromophenyl)(methyl)carbamate and phenylboronic acid was replaced with compound 50-1. The crude product was purified by preparative high performance liquid chromatography (column: Phenomenex Synergi C18 150 × 30 mm × 4 µm; mobile phase: [water (ammonia)-acetonitrile]; gradient elution program: acetonitrile concentration increased from 45% to 65% within 10 minutes). After freeze-drying, 29.0 mg of compound 70 (white solid, 25.2% yield) was obtained.

[0161] LCMS (ESI) m / z 460.2 [M+H] + ; H NMR (400 MHz, DMSO) -d 6) d ppm 10.23 (s,1 H), 7.36 (d, J = 8.38 Hz, 2 H), 7.24 (d, J = 7.63 Hz, 1 H), 6.98 (t, J =7.38 Hz, 1 H), 6.91 (d, J = 7.25 Hz, 1 H), 6.67 (d, J = 8.50 Hz, 2 H), 5.75 (q, J = 4.75 Hz, 1 H), 4.55 (d, J = 4.50 Hz, 1 H), 4.08 (br s, 1 H), 3.64 (s, 3 H), 3.28 (br d, J = 10.51 Hz, 1 H), 3.00 (br dd, J = 10.38, 4.88 Hz, 1 H), 2.82 - 2.88 (m, 1 H), 2.74 (d, J = 5.00 Hz, 4 H), 2.54 - 2.63 (m, 3 H), 2.23 (dd, J = 11.51, 2.38 Hz, 1 H), 2.17 (br t, J = 10.51 Hz, 1 H), 1.78 - 1.92 (m, 1 H), 1.75 (br d, J= 10.88 Hz, 1 H), 1.50 - 1.61 (m, 1 H), 1.30 - 1.47 (m, 2 H), 1.18 - 1.29 (m, 1 H), 0.93 (q, J = 11.80 Hz, 1 H); HPLC: 99.46%@220nm, 99.66%@254 nm. Example 71 The method was the same as in Example 3, except that compound 1 was replaced with 4-bromo-N,N-dimethylaniline and phenylboronic acid was replaced with compound 50-1. The crude product was purified by preparative high performance liquid chromatography (column: 55-Boston Prime C18 150 × 30 mm, 5 μm; mobile phase: [water (ammonia)-acetonitrile]; gradient elution program: acetonitrile concentration increased from 13% to 33% within 10 minutes). After freeze-drying, 60.3 mg of compound 71 (yellow solid, 60.4% yield) was obtained.

[0162] LCMS (ESI) m / z 474.0 [M+H] + ; 1 H NMR (400 MHz, DMSO- d 6) d ppm 10.31 (s,1 H), 8.17 (s, 0.68 H), 7.45 (d, J = 8.8 Hz, 2 H), 7.26 (d, J = 7.1 Hz, 1 H), 6.97 - 7.02 (m, 1 H), 6.91 - 6.95 (m, 1 H), 6.87 (d, J = 8.9 Hz, 2 H), 4.40 -4.66 (m, 1 H), 4.08 (br d, J = 2.1 Hz, 1 H), 3.64 (s, 3 H), 3.33 (br d, J =10.6 Hz, 2 H), 3.03 (br dd, J = 10.9, 4.2 Hz, 1 H), 2.96 (s, 6 H), 2.86 (brd, J = 9.3 Hz, 1 H), 2.73 - 2.80 (m, 1 H), 2.61 (br d, J = 16.8 Hz, 1 H), 2.55 (br d, J= 9.2 Hz, 1 H), 2.16 - 2.26 (m, 2 H), 1.79 - 1.89 (m, 1 H), 1.75 (br dd, J = 13.1, 2.3 Hz, 1 H), 1.50 - 1.60 (m, 1 H), 1.33 - 1.46 (m, 2H), 1.21 - 1.29 (m, 1 H), 0.88 - 1.00 (m, 1 H); HPLC: 99.70%@220 nm; 98.77%@254 nm; 100%ee. Example 72 The method was the same as in Example 3, except that compound 1 was replaced with methyl 4-bromobenzoate and phenylboronic acid was replaced with compound 50-1. The crude product was purified by preparative high performance liquid chromatography (column: Phenomenex Synergi C18 150 * 30 mm * 4 μm; mobile phase: [water (ammonia) - acetonitrile]; gradient elution program: acetonitrile concentration increased from 55% to 75% within 10 minutes). After freeze-drying, 23.9 mg of compound 72 (white solid, 12.5% ​​yield) was obtained.

[0163] LCMS (ESI) m / z 489.2 [M+H] + ; 1 H NMR (400 MHz, DMSO- d 6) d ppm 10.57 (s,1 H), 8.03 - 8.11 (m, 2 H), 7.74 - 7.79 (m, 2 H), 7.41 (dd, J = 7.0, 1.8 Hz, 1 H), 7.03 - 7.12 (m, 2 H), 4.57 (br s, 1 H), 4.08 (br s, 1 H), 3.91 (s, 3H), 3.63 (s, 3 H), 3.24 - 3.31 (m, 2 H), 2.98 - 3.05 (m, 1 H), 2.74 - 2.89 (m, 2 H), 2.60 - 2.66 (m, 1 H), 2.54 - 2.57 (m, 1 H), 2.24 (dd, J= 11.5, 2.7Hz, 1 H), 2.15 - 2.20 (m, 1 H), 1.72 - 1.88 (m, 2 H), 1.50 - 1.60 (m, 1 H), 1.36 - 1.44 (m, 2 H), 1.24 - 1.28 (m, 1 H), 0.89 - 1.00 (m, 1 H); HPLC:93.56%@220 nm; 95.77%@254 nm; 100%ee Example 73 The method was the same as in Example 3, except that compound 1 was replaced with 4-bromobenzamide and phenylboronic acid was replaced with compound 50-1. The crude product was purified by preparative high performance liquid chromatography (column: Phenomenex Synergi C18 150 * 30 mm * 4 μm; mobile phase: [water (ammonia) - acetonitrile]; gradient elution program: the acetonitrile concentration increased from 29% to 49% within 10 minutes). After freeze-drying, 15.0 mg of compound 73 (white solid, 15.2% yield) was obtained.

[0164] LCMS (ESI) m / z 474.2 [M+H] + ; 1 H NMR (DMSO-d6, 400 MHz) d ppm 10.53 (brs, 1 H), 8.14 - 7.91 (m, 3 H), 7.67 (br d, J = 8.0 Hz, 2 H), 7.38 (br d, J =7.2 Hz, 2 H), 7.16 - 6.93 (m, 2 H), 4.56 (br d, J = 4.0 Hz, 1 H), 4.07 (br s,1 H), 3.63 (s, 3 H), 3.30 - 3.22 (m, 1 H), 3.01 (br d, J = 5.2 Hz, 1 H), 2.90- 2.73 (m, 2 H), 2.62 (br d, J = 14.8 Hz, 1 H), 2.55 (br s, 1 H), 2.28 - 2.11 (m, 2 H), 1.83 (br d, J= 10.0 Hz, 1 H), 1.78 - 1.69 (m, 1 H), 1.61 - 1.49 (m, 1 H), 1.47 - 1.33 (m, 2 H), 1.30 - 1.17 (m, 1 H), 0.94 (br d, J = 11.6Hz, 1 H); HPLC: 99.29%@220 nm, 98.75%@254 nm. Example 74 The method was the same as in Example 3, except that compound 1 was replaced with 4-bromophenylmethyl sulfone and phenylboronic acid was replaced with compound 50-1. The crude product was purified by preparative high performance liquid chromatography (column: Phenomenex Synergi C18 150 × 30 mm × 4 µm; mobile phase: [water (ammonia) - acetonitrile]; gradient elution program: the acetonitrile concentration increased from 44% to 64% within 10 minutes). After freeze-drying, 20.2 mg of compound 74 (white solid, 19.1% yield) was obtained.

[0165] LCMS (ESI) m / z 509.2 [M+H] + ; 1 H NMR (400 MHz, DMSO-d 6) d ppm 10.65 (s,1 H), 8.03 (d, J = 8.38 Hz, 2 H), 7.86 (d, J = 8.38 Hz, 2 H), 7.43 (dd, J =7.38, 1.00 Hz, 1 H), 7.10 (t, J = 7.38 Hz, 1 H), 7.06 (dd, J = 7.38, 1.38 Hz, 1 H), 4.58 (d, J = 4.63 Hz, 1 H), 4.08 (br s, 1 H), 3.63 (s, 3 H), 3.29 (s, 3H), 3.27 (br s, 1 H), 3.01 (br dd, J = 10.57, 4.82 Hz, 1 H), 2.85 (dd, J =11.63, 2.13 Hz, 1 H), 2.74 - 2.81 (m, 1 H), 2.63 (br d, J= 14.76 Hz, 1 H), 2.54 - 2.58 (m, 1 H), 2.24 (dd, J = 11.51, 2.50 Hz, 1 H), 2.17 (br t, J =10.32 Hz, 1 H), 1.78 - 1.90 (m, 1 H), 1.75 (dd, J = 13.01, 2.25 Hz, 1 H), 1.54 (br t, J = 11.94 Hz, 1 H), 1.31 - 1.47 (m, 2 H), 1.25 (br d, J = 8.63Hz, 1 H), 0.94 (q, J = 11.67 Hz, 1 H); HPLC: 99.80%@220 nm, 100.00%@254 nm. Example 75 The method was the same as in Example 3, except that compound 1 was replaced with 4-acetamidobromobenzene and phenylboronic acid was replaced with compound 50-1. The crude product was purified by preparative high performance liquid chromatography (column: Phenomenex Synergi C18 150 × 30 mm × 4 µm; mobile phase: [water (ammonia) - acetonitrile]; gradient elution program: the acetonitrile concentration increased from 37% to 57% within 10 minutes). After freeze-drying, 34.2 mg of compound 75 (white solid, 33.7% yield) was obtained.

[0166] LCMS (ESI) m / z 488.2 [M+H] + ; 1 H NMR (400 MHz, DMSO-d 6) d ppm 10.40 (s, 1 H), 10.04 (s, 1 H), 7.70 (d, J = 8.56 Hz, 2 H), 7.54 (d, J = 8.56 Hz, 2 H), 7.32 (d, J = 7.21 Hz, 1 H), 7.03 (t, J = 7.58 Hz, 1 H), 6.98 (dd, J = 7.21,0.98 Hz, 1 H), 4.56 (d, J= 4.65 Hz, 1 H), 4.08 (br s, 1 H), 3.64 (s, 3 H), 3.29 (br d, J = 11.25 Hz, 1 H), 3.01 (br dd, J = 10.82, 3.97 Hz, 1 H), 2.85 (br dd, J = 10.70, 1.41 Hz, 1 H), 2.72 - 2.81 (m, 1 H), 2.61 (br d, J = 15.28Hz, 1 H), 2.53 - 2.58 (m, 2 H), 2.23 (dd, J = 11.55, 2.51 Hz, 1 H), 2.18 (brt, J = 10.45 Hz, 1 H), 2.09 (s, 3 H), 1.79 - 1.95 (m, 1 H), 1.75 (br dd, J =12.59, 2.08 Hz, 1 H), 1.50 - 1.61 (m, 1 H), 1.32 - 1.47 (m, 2 H), 1.25 (br d, J = 8.93 Hz, 1 H), 0.93 (q, J = 11.53 Hz, 1 H); HPLC: 99.70%@220 nm, 100.00%@254 nm. Example 76 The method was the same as in Example 3, except that compound 1 was replaced with 4-vinylbromobenzene and phenylboronic acid was replaced with compound 50-1. The crude product was purified by preparative high performance liquid chromatography (column: Phenomenex Synergi C18 150 × 30 mm × 4 µm; mobile phase: [water (ammonia) - acetonitrile]; gradient elution program: the acetonitrile concentration increased from 61% to 81% within 10 minutes). After freeze-drying, 10.1 mg of compound 76 (white solid, 10.6% yield) was obtained.

[0167] LCMS (ESI) m / z 457.2 [M+H]+; 1 H NMR (400 MHz, DMSO) -d 6) d ppm 10.48 (s,1 H), 7.59 (s, 4 H), 7.35 (d, J= 7.26 Hz, 1 H), 7.05 (t, J = 7.26 Hz, 1 H), 7.00 (dd, J = 7.04, 0.88 Hz, 1 H), 6.82 (dd, J = 17.72, 10.89 Hz, 1 H), 5.90 (d, J = 17.61 Hz, 1 H), 5.30 (d, J = 11.00 Hz, 1 H), 4.57 (d, J = 4.40 Hz, 1H), 4.07 (br s, 1 H), 3.63 (s, 3 H), 3.28 (br d, J = 10.78 Hz, 1 H), 3.00 (brdd, J = 10.78, 4.62 Hz, 1 H), 2.83 (br d, J = 9.68 Hz, 1 H), 2.73 - 2.79 (m, 1 H), 2.53 - 2.67 (m, 3 H), 2.22 (dd, J = 11.44, 2.42 Hz, 1 H), 2.16 (br t, J = 10.45 Hz, 1 H), 1.78 - 1.90 (m, 1 H), 1.68 - 1.77 (m, 1 H), 1.53 (br t, J =11.88 Hz, 1 H), 1.31 - 1.45 (m, 2 H), 1.24 (br d, J = 8.80 Hz, 1 H), 0.93 (brq, J = 11.88 Hz, 1 H); HPLC: 98.64%@220 nm, 100.00%@254 nm. Example 77 The method was the same as in Example 3, except that compound 1 was replaced with 2,4-difluorobromobenzene and phenylboronic acid was replaced with compound 50-1. The crude product was purified by preparative high performance liquid chromatography (column: Phenomenex Synergi C18 150 × 30 mm × 4 µm; mobile phase: [water (ammonia) - acetonitrile]; gradient elution program: acetonitrile concentration increased from 54% to 74% within 10 minutes). After freeze-drying, 27.0 mg of compound 77 (white solid, 27.5% yield) was obtained.

[0168] LCMS (ESI) m / z 467.1 [M+H] + ; 1 H NMR (400 MHz, DMSO- d 6) d ppm 10.49 (s,1 H), 7.50 (td, J = 8.5, 6.9 Hz, 1 H), 7.40 (d, J = 7.8 Hz, 1 H), 7.33 (td, J = 9.9, 2.5 Hz, 1 H), 7.19 (td, J = 8.4, 2.4 Hz, 1 H), 7.03 (t, J = 7.5 Hz, 1H), 6.91 (d, J = 7.0 Hz, 1 H), 4.56 (d, J = 4.5 Hz, 1 H), 4.07 (br s, 1 H),3.62 (s, 3 H), 3.25 (br d, J = 10.5 Hz, 1 H), 3.00 (br dd, J = 10.6, 4.6 Hz,1 H), 2.82 - 2.87 (m, 1 H), 2.72 - 2.79 (m, 1 H), 2.57 - 2.68 (m, 1 H), 2.47(br d, J = 2.1 Hz, 1 H), 2.23 (dd, J = 11.4, 2.6 Hz, 1 H), 2.15 (br t, J =10.4 Hz, 1 H), 1.71 - 1.87 (m, 2 H), 1.49 - 1.59 (m, 1 H), 1.34 - 1.47 (m, 2H), 1.24 (br d, J = 8.4 Hz, 1 H), 0.91 (q, J = 11.7 Hz, 1 H); 19 F NMR (376MHz, DMSO- d 6) δ ppm -109.18, -112.25; HPLC: 99.10%@220 nm; 98.75%@254 nm;100%ee. Example 78 The method was the same as in Example 3, except that compound 1 was replaced with 1,3,5-trifluoro-2-bromobenzene and phenylboronic acid was replaced with compound 50-1. The crude product was purified by preparative high performance liquid chromatography (column: 40-WePure Biotech XP tC18 150× 30 mm, 7 μm; mobile phase: [water (formic acid)-acetonitrile]; gradient elution program: acetonitrile concentration increased from 13% to 53% within 10 minutes). After freeze-drying, 28.4 mg of compound 78 (white solid, 28.1% yield) was obtained.

[0169] LCMS (ESI) m / z 485.1 [M+H] + ; 1 H NMR (400 MHz, DMSO- d 6) d ppm 10.57 (s,1 H), 8.17 (s, 0.38 H), 7.43 (d, J = 7.8 Hz, 1 H), 7.25 - 7.33 (m, 2 H), 7.01- 7.06 (m, 1 H), 6.92 (d, J = 7.3 Hz, 1 H), 4.57 (br s, 1 H), 4.07 (br s, 1H), 3.61 (s, 3 H), 3.26 (br d, J = 10.9 Hz, 2 H), 3.01 (br dd, J = 10.8, 4.8Hz, 1 H), 2.82 - 2.89 (m, 1 H), 2.73 - 2.81 (m, 1 H), 2.59 - 2.70 (m, 1 H), 2.45 (br d, J = 2.4 Hz, 1 H), 2.24 (dd, J = 11.4, 2.6 Hz, 1 H), 2.16 (br t, J = 10.4 Hz, 1 H), 1.71 - 1.87 (m, 2 H), 1.49 - 1.58 (m, 1 H), 1.33 - 1.45 (m, 2 H), 1.24 (br d, J = 9.0 Hz, 1 H), 0.91 (q, J = 11.7 Hz, 1 H); 19F NMR (376MHz, DMSO-d6) δ ppm -108.69, -109.01, -109.87; HPLC: 99.76%@220 nm; 99.77%@254 nm; 95.76%ee. Example 79 The method was the same as in Example 3, except that compound 1 was replaced with 4-trifluoromethylbromobenzene and phenylboronic acid was replaced with compound 50-1. The crude product was purified by preparative high performance liquid chromatography (column: Phenomenex Synergi C18 150 * 30mm * 4 μm; mobile phase: [water (ammonia) - acetonitrile]; gradient elution program: the acetonitrile concentration increased from 63% to 83% within 10 minutes). After freeze-drying, 40.4 mg of compound 79 (white solid, 38.9% yield) was obtained.

[0170] LCMS (ESI) m / z 499.2 [M+H] + ; 1 H NMR (400 MHz, DMSO- d 6) d ppm 10.62 (s,1 H), 7.77 - 7.88 (m, 4 H), 7.41 (d, J = 7.3 Hz, 1 H), 7.02 - 7.11 (m, 2 H), 4.57 (d, J = 4.6 Hz, 1 H), 4.07 (br s, 1 H), 3.62 (s, 3 H), 3.27 (br d, J =11.3 Hz, 1 H), 3.01 (br dd, J = 10.4, 4.9 Hz, 1 H), 2.74 - 2.87 (m, 2 H), 2.60 - 2.69 (m, 1 H), 2.53 - 2.58 (m, 1 H), 2.23 (dd, J = 11.1, 2.3 Hz, 1 H), 2.16 (br t, J = 10.5 Hz, 1 H), 1.71 - 1.86 (m, 2 H), 1.49 - 1.59 (m, 1 H), 1.33 - 1.45 (m, 2 H), 1.22 - 1.29 (m, 1 H), 0.93 (q, J= 11.4 Hz, 1 H); HPLC:100%@220 nm; 100%@254 nm; 100%ee. Example 80 The method was the same as in Example 3, except that compound 1 was replaced with 4-cyanobromobenzene and phenylboronic acid was replaced with compound 50-1. The crude product was purified by preparative high performance liquid chromatography (column: 40-WePure Biotech XP tC18 150 × 30 mm, 7 μm; mobile phase: [water (formic acid)-acetonitrile]; gradient elution program: acetonitrile concentration increased from 9% to 49% within 10 minutes). After freeze-drying, 44.4 mg of compound 80 (white solid, 46.6% yield) was obtained.

[0171] LCMS (ESI) m / z 456.1 [M+H] + ; 1 H NMR (400 MHz, DMSO- d 6) d ppm 10.61 (s,1 H), 8.17 (s, 0.55 H), 7.96 (d, J = 8.3 Hz, 2 H), 7.80 (d, J = 8.4 Hz, 2 H), 7.43 (dd, J = 7.4, 1.0 Hz, 1 H), 7.04 - 7.13 (m, 2 H), 4.44 - 4.70 (m, 1 H), 4.09 (br d, J = 2.2 Hz, 1 H), 3.64 (s, 3 H), 3.32 (br d, J = 10.8 Hz, 2 H), 3.04 (br dd, J= 11.1, 4.4 Hz, 1 H), 2.84 - 2.90 (m, 1 H), 2.76 - 2.83 (m, 1H), 2.61 - 2.69 (m, 1 H), 2.54 - 2.58 (m, 1 H), 2.16 - 2.28 (m, 2 H), 1.80 -1.90 (m, 1 H), 1.71 - 1.78 (m, 1 H), 1.50 - 1.61 (m, 1 H), 1.34 - 1.47 (m, 2H), 1.26 (br d, J = 9.4 Hz, 1 H), 0.96 (q, J = 11.7 Hz, 1 H); HPLC: 99.81%@220 nm; 99.44%@254 nm; 100%ee. Example 81 The method was the same as in Example 3, except that compound 1 was replaced with 4-hydroxybromobenzene and phenylboronic acid was replaced with compound 50-1. The crude product was purified by preparative high performance liquid chromatography (column: Phenomenex Synergi C18 150 × 30 mm × 4 µm; mobile phase: [water (ammonia) - acetonitrile]; gradient elution program: acetonitrile concentration increased from 40% to 60% within 10 minutes). After freeze-drying, 43.2 mg of compound 81 (white solid, 38.7% yield) was obtained.

[0172] LCMS (ESI) m / z 447.2 [M+H] + ; 1 H NMR (400 MHz, DMSO- d 6) d ppm 10.31 (s,1 H), 9.48 (s, 1 H), 7.40 (d, J = 8.5 Hz, 2 H), 7.27 (d, J = 7.5 Hz, 1 H), 6.96 - 7.03 (m, 1 H), 6.91 (dd, J = 7.3, 0.9 Hz, 1 H), 6.88 (d, J = 8.5 Hz, 2H), 4.55 (d, J = 4.6 Hz, 1 H), 4.07 (br s, 1 H), 3.63 (s, 3 H), 3.27 (br d, J= 10.8 Hz, 1 H), 2.95 - 3.04 (m, 1 H), 2.84 (br d, J = 9.3 Hz, 1 H), 2.71 -2.79 (m, 1 H), 2.59 (br d, J = 15.8 Hz, 1 H), 2.52 - 2.56 (m, 1 H), 2.22 (dd, J = 11.5, 2.5 Hz, 1 H), 2.16 (br t, J = 10.4 Hz, 1 H), 1.71 - 1.88 (m, 2 H), 1.48 - 1.59 (m, 1 H), 1.31 - 1.46 (m, 2 H), 1.24 (br d, J = 8.6 Hz, 1 H), 0.92 (q, J = 11.7 Hz, 1 H); HPLC: 98.40%@220 nm, 100.0%@254 nm. Example 82 The method was the same as in Example 3, except that compound 1 was replaced with 4-bromobenzenesulfonamide and phenylboronic acid was replaced with compound 50-1. The crude product was purified by preparative high performance liquid chromatography (column: Phenomenex Synergi C18 150 × 30 mm × 4 µm; mobile phase: [water (ammonia) - acetonitrile]; gradient elution program: acetonitrile concentration increased from 37% to 57% within 10 minutes). After freeze-drying, 38.6 mg of compound 82 (white solid, 30.3% yield) was obtained.

[0173] LCMS (ESI) m / z 510.2 [M+H] + ; 1 H NMR (400 MHz, DMSO- d 6) d ppm 10.62 (s,1 H), 7.92 (d, J = 8.4 Hz, 2 H), 7.77 (d, J = 8.4 Hz, 2 H), 7.44 (s, 2 H), 7.40 (d, J = 7.1 Hz, 1 H), 7.05 - 7.10 (m, 1 H), 7.01 - 7.05 (m, 1 H), 4.57 (d, J= 4.5 Hz, 1 H), 4.07 (br s, 1 H), 3.63 (s, 3 H), 3.27 (br d, J = 11.0Hz, 1H), 3.01 (br dd, J = 10.4, 4.7 Hz, 1 H), 2.84 (br d, J = 10.3 Hz, 1 H), 2.74 - 2.81 (m, 1 H), 2.62 (br d, ...

Claims

1. The compound represented by Formula I and its pharmaceutically acceptable salt: （I） in, -A 2 -A 1 -L 1 -R 1 It is a hydroxyl group; R 2 It is hydrogen; L 2 C 1-3 Alkylene; B 1 It is O; B 2 for ; R 3 It is hydrogen; R 4 Ar is an optional replacement 4 Ar 4 A 6- to 10-membered aryl group containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, wherein "optionally substituted" means optionally substituted by one or more groups selected from: halogen, C 1-6 Alkyl, C 1-6 Alkoxy; R 6 It is hydrogen; or, R 6 Ar is an optional replacement 6 Ar 6 A 6- to 10-membered aryl group containing 1, 2, or 3 heteroatoms independently selected from N, O, or S, wherein "optionally substituted" means optionally substituted by one or more groups selected from: halogen, C 1-6 Alkyl, C 1-6 Alkoxy; R 4 It is hydrogen; R 5 It is hydrogen; R 7 It is hydrogen; R 8 R 9 Both are hydrogen.

2. The compound of claim 1, and its pharmaceutically acceptable salt, characterized in that, L 2 It is methylene; R 4 Ar is an optional replacement 4 Ar 4 It is a 6-membered aryl or furanyl group, and the term "optionally substituted" means that it is optionally substituted by one or more groups selected from the following: halogen, C 1-6 Alkoxy; R 6 It is hydrogen.

3. The compound of claim 1, and its pharmaceutically acceptable salt, characterized in that, L 2 It is methylene; R 4 It is hydrogen; R 6 Ar is an optional replacement 6 Ar 6 It is furanyl.

4. The compound of claim 2, and its pharmaceutically acceptable salt, characterized in that, R 4 It is an optionally substituted 6-membered aryl or unsubstituted furanyl, wherein "optionally substituted" means optionally substituted by one or more groups selected from: halogen, C 1-6 Alkyl group.

5. The compound of claim 3, and its pharmaceutically acceptable salt, characterized in that, R 6 It is furanyl.

6. A compound, and its pharmaceutically acceptable salt, characterized in that, The compounds are selected from the group consisting of: 、 、 、 、 、 、 、 、 。 7. A pharmaceutical composition comprising the compound of any one of claims 1-6, a pharmaceutically acceptable salt thereof, and optionally a pharmaceutically acceptable excipient.

8. Use of the compound of any one of claims 1-6, or a pharmaceutically acceptable salt thereof, in the preparation of an adrenergic receptor α2 antagonist or partial antagonist.

9. The use as described in claim 8, characterized in that, The aforementioned adrenergic receptor α2A antagonists or partial antagonists are drugs for the treatment or prevention of inflammatory bowel disease.

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