Pyridazinone heterocyclic compound Myosin II inhibitor and application thereof

Abstract

The invention discloses a pyridazinone ring compound as shown in a formula (I), a stereoisomer, a deuterated compound, a solvate, pharmaceutically acceptable salt or co-crystal of the pyridazinone ring compound, a pharmaceutical composition containing the pyridazinone ring compound and the stereoisomer, the deuterated compound, the solvate and the pharmaceutically acceptable salt or co-crystal of the pyridazinone ring compound, and application of the pyridazinone ring compound and the pharmaceutical composition to preparation of drugs for treating / preventing Myosin II mediated diseases, and all groups in the formula (I) are defined in the specification. # imgabs0 #

Description

A pyridazinone heterocyclic compound Myosin II inhibitor and its use Technical Field

[0001] The present invention relates to a Myosin II inhibitor, its stereoisomers, pharmaceutically acceptable salts, solvates, cocrystals or deuterated substances, and use thereof in preparing drugs for treating Myosin II-mediated related diseases. Background Art

[0002] Skeletal muscle plays two crucial roles in the human body: first, muscle contraction, which produces movement and maintains posture; and second, skeletal muscle is the site of glucose, fatty acid, and amino acid metabolism. During normal daily activities, skeletal muscle contraction is closely associated with muscle stress, breakdown, and remodeling, all of which are critical for muscle adaptation. However, in patients with progressive muscular dystrophies, such as Duchenne muscular dystrophy (DMD), muscle contraction leads to repeated rounds of irreparable, amplified muscle breakdown. As patients age, these changes eventually accumulate and develop into a pathological process, leading to excessive inflammation, fibrosis, and the accumulation of fat deposits in the muscles, which in turn progresses to a sharp decline in physical function and ultimately death.

[0003] DMD is a genetic disease affecting skeletal muscle. Becker muscular dystrophy (BMD), a variant of DMD, was first described by German physician Peter Emil Becker in the 1950s. Both are characterized by progressive muscle degeneration and weakness. Currently, there is a need for drugs that can treat patients with DMD or BMD.

[0004] Summary of the Invention

[0005] The present invention provides a compound of formula (I), formula (Ia), formula (Ib), formula (II), formula (III), formula (IV), formula (V), formula (VA), formula (VI), formula (VII), formula (VIII), and formula (IX), and a stereoisomer, deuterated form, solvate, or pharmaceutically acceptable salt or cocrystal thereof. The compound has the excellent effects of good activity, excellent physicochemical properties, ease of formulation, excellent pharmacokinetic properties, high bioavailability, and low toxic and side effects.

[0006] The compounds of formula (I), formula (Ia), formula (Ib), formula (II), formula (II-a), formula (III), formula (III-a), formula (IV), formula (V), formula (VA), formula (VI), formula (VII), formula (VIII), and formula (IX), stereoisomers, deuterated forms, solvates, or pharmaceutically acceptable salts or cocrystals thereof,

[0007]

[0008] in,

[0009] R 1 、R 2 、R 3 Each independently selected from H, deuterium, R A1 、-O-halogenated C 1-4 Alkyl, -NH-halogenated C 1-4 Alkyl, -OC 1-4 Alkyl, C 1-4 Alkoxy, halogen, cyano, nitro, OH, C 1-4 Alkyl, C 2-6 Alkenyl, -NH-C 1-4 Alkyl, -N(C 1-4 Alkyl)2, -NH-C 3-10 Cycloalkyl, -NHC(O)C 1-4 Alkyl, or 4-10 membered heterocycloalkyl containing 1-3 heteroatoms selected from N, O, S or selected from C 5-6 Alkoxy, the alkyl, alkoxy, cycloalkyl, heterocycloalkyl optionally further 1-3 selected from halogen, D, CN, OH, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, deuterated C 1-4 Alkoxy, C 3-10 Cycloalkyl, 4-6 membered heterocycloalkyl containing 1-3 heteroatoms selected from N, O, S, phenyl, and NH2, provided that R 1 、R 2 and R 3 Not selected from H at the same time;

[0010] In some embodiments, R 1 、R 2 、R 3 Each independently selected from H, deuterium, R A1 、-O-halogenated C 1-4 Alkyl, -NH-halogenated C 1-4 Alkyl, -OC 1-4 Alkyl, C 1-4 Alkoxy, halogen, cyano, nitro, C 1-4 Alkyl, C 2-6 Alkenyl, -NH-C 1-4 Alkyl, -N(C 1-4 Alkyl)2, -NH-C 3-10 Cycloalkyl, -NHC(O)C 1-4Alkyl, or 4-10 membered heterocycloalkyl containing 1-3 heteroatoms selected from N, O, S or selected from C 5-6 Alkoxy, the alkyl, alkoxy, cycloalkyl, heterocycloalkyl optionally further 1-3 selected from halogen, D, CN, OH, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, deuterated C 1-4 Alkoxy, C 3-10 Cycloalkyl, 4-6 membered heterocycloalkyl containing 1-3 heteroatoms selected from N, O, S, phenyl, and NH2, provided that R 1 、R 2 and R 3 Not selected from H at the same time;

[0011] In some embodiments, R 1 、R 2 、R 3 Each independently selected from H, deuterium, R A1 、-O-halogenated C 1-2 Alkyl, -NH-halogenated C 1-2 Alkyl, -OC 1-2 Alkyl, C 1-2 Alkoxy, halogen, cyano, nitro, OH, C 1-2 Alkyl, C 2-4 Alkenyl, -NH-C 1-2 Alkyl, -N(C 1-2 Alkyl)2, -NH-C 3-6 Monocyclic cycloalkyl, -NH-C 7-10 Bicyclic cycloalkyl, -NHC(O)C 1-2 alkyl, a 4-6 membered monocyclic heterocycloalkyl containing 1-3 heteroatoms selected from N, O, S, or a 7-10 membered bicyclic heterocycloalkyl containing 1-3 heteroatoms selected from N, O, S, or a C 5-6 Alkoxy, the alkyl, alkoxy, cycloalkyl, heterocycloalkyl optionally further 1, 2 or 3 selected from halogen, D, CN, OH, C 1-2 Alkyl, halogenated C 1-2 Alkyl, deuterated C 1-2 Alkyl, C 1-2 Alkoxy, halogenated C 1-2 Alkoxy, deuterated C 1-2 Alkoxy, C 3-5 Monocyclic cycloalkyl, C 7-10 Bicyclic cycloalkyl, 4-, 5-, or 6-membered heterocycloalkyl containing 1, 2, or 3 heteroatoms selected from N, O, or S, phenyl, and NH2;

[0012] In some embodiments, R 1 Selected from R A1 、-O-halogenated C 1-4 Alkyl; R 2 、R 3 Each independently selected from H, deuterium, C 2-4 Alkenyl, C 2-4 Alkynyl, halogen, cyano, nitro, OH, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 alkyl;

[0013] In some embodiments, R 1 Selected from R A1 、-O-halogenated C 1-4 Alkyl; R 2 、R 3 Each independently selected from H, deuterium, C 2-4 Alkenyl, C 2-4 Alkynyl, halogen, cyano, nitro, OH, C 1-2 Alkyl, halogenated C 1-2 Alkyl, deuterated C 1-2 alkyl;

[0014] In some embodiments, R 1 Selected from -O-halogenated C 1-4 Alkyl; R 2 、R 3 Each independently selected from H, deuterium, C 2-4 Alkenyl, C 2-4 Alkynyl, halogen, cyano, nitro, OH, C 1-2 Alkyl, halogenated C 1-2 Alkyl, deuterated C 1-2 alkyl;

[0015] In some embodiments, R 1 Selected from -O-halogenated C 1-4 Alkyl; R 2 、R 3 Each independently selected from H;

[0016] In some embodiments, R 1 Selected from -O-halogenated C 1-3 Alkyl; R 2 、R 3 Each independently selected from H;

[0017] In some embodiments, R 3 Selected from H;

[0018] In some embodiments, R 1 Selected from R A1 ; R2 、R 3 Each independently selected from H, deuterium, C 2-4 Alkenyl, C 2-4 Alkynyl, halogen, cyano, nitro, OH, C 1-2 Alkyl, halogenated C 1-2 Alkyl, deuterated C 1-2 alkyl;

[0019] In some embodiments, R 1 Selected from R A1 ; R 2 、R 3 Each is independently selected from H, deuterium, vinyl, and ethynyl;

[0020] In some embodiments, R 1 Selected from -CH2CH3, -CH2CH2CH3, R A1 ;

[0021] R A1 Selected from halogenated C 2-6 Alkenyl, C 2-6 Alkynyl, -O-(CH2) r -R a 、C 3-10 Cycloalkyl, 5-10 membered heteroaryl containing 1-3 heteroatoms selected from N, O, S, -C 1-4 Alkyl-R a 、-C 1-4 Alkyl-OR a 、-C 1-4 Alkyl-NR b R a 、-NR b -S(O)2-R a 、-NR b -S(O)2-NR b R a 、-O-NR b R a 、-NH-OR b 、-Se-(CH2) r -R a The alkynyl, heteroaryl, alkyl, cycloalkyl group may be further substituted by 1-3 groups selected from halogen, deuterium, CN, OH, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, deuterated C 1-4 Alkoxy and NH2 group substitution;

[0022] In some embodiments, R A1 Selected from halogenated C 2-6 Alkenyl, C 2-6 Alkynyl, -O-(CH2) r -R a 、C 3-10 Cycloalkyl, 5-10 membered heteroaryl containing 1-3 heteroatoms selected from N, O, S, -C 1-4 Alkyl-R a 、-C 1-4 Alkyl-OR a 、-C 1-4 Alkyl-NR b R a 、 -NR b -S(O)2-R a 、-NR b -S(O)2-NR b R a 、-O-NR b R a 、-NH-OR b 、-Se-(CH2) r -Ra, the alkynyl, heteroaryl, alkyl, cycloalkyl group is optionally further substituted by 1-3 groups selected from halogen, deuterium, CN, OH, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, deuterated C 1-4 Alkoxy and NH2 group substitution;

[0023] In some embodiments, R A1 Selected from halogenated C 2-6 Alkenyl, C 2-6 Alkynyl, -O-(CH2) r -R a 、C 3-10 Cycloalkyl, 5-10 membered heteroaryl containing 1-3 heteroatoms selected from N, O, S, -C 1-4 Alkyl-R a 、-C 1-4 Alkyl-OR a 、-C 1-4 Alkyl-NR b R a 、-NR b -S(O)2-R a 、-NR b -S(O)2-NR b R a 、-O-NRb R a 、-NH-OR b The alkynyl, heteroaryl, alkyl, cycloalkyl group may be further substituted by 1-3 groups selected from halogen, deuterium, CN, OH, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, deuterated C 1-4 Alkoxy and NH2 group substitution;

[0024] In some embodiments, R A1 Selected from halogenated C 2-6 Alkenyl, C 2-6 Alkynyl, 5-10 membered heteroaryl containing 1-3 heteroatoms selected from N, O, S, -C 1-4 Alkyl-R a 、-C 1-4 Alkyl-OR a 、-C 1-4 Alkyl-NR b R a 、-NR b -S(O)2-R a 、-NR b -S(O)2-NR b R a The alkynyl, heteroaryl, and alkyl groups are optionally further substituted by 1 to 3 groups selected from halogen, deuterium, CN, OH, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, deuterated C 1-4 Alkoxy and NH2 group substitution;

[0025] In some embodiments, R A1 Selected from halogenated C 2-4 Alkenyl, C 2-4 Alkynyl, -O-(CH2) r -R a 、C 3-6 Monocyclic cycloalkyl, 5-6 membered monocyclic heteroaryl containing 1-3 heteroatoms selected from N, O, S, 8-10 membered bicyclic heteroaryl containing 1-3 heteroatoms selected from N, O, S, -C 1-2 Alkyl-R a 、-C 1-2 Alkyl-OR a 、-C 1-2 Alkyl-NR b R a 、-NRb -S(O)2-R a 、-NR b -S(O)2-NR b R a 、-O-NR b R a 、-NH-OR b The alkynyl, heteroaryl, and alkyl groups are optionally further substituted by 1 to 3 groups selected from halogen, deuterium, CN, OH, C 1-2 Alkyl, halogenated C 1-2 Alkyl, deuterated C 1-2 Alkyl, C 1-2 Alkoxy, halogenated C 1-2 Alkoxy, deuterated C 1-2 Alkoxy and NH2 group substitution; r is selected from 0 or 1;

[0026] In some embodiments, R A1 Selected from halogenated C 2-4 Alkenyl, C 2-4 Alkynyl, 5-6 membered monocyclic heteroaryl containing 1-3 heteroatoms selected from N, O, S, 8-10 membered bicyclic heteroaryl containing 1-3 heteroatoms selected from N, O, S, -C 1-2 Alkyl-R a 、-C 1-2 Alkyl-OR a 、-C 1-2 Alkyl-NR b R a 、-NR b -S(O)2-R a 、-NR b -S(O)2-NR b R a 、-O-NR b R a 、-NH-OR b The alkynyl, heteroaryl, and alkyl groups are optionally further substituted by 1, 2, or 3 groups selected from halogen, deuterium, CN, OH, C 1-2 Alkyl, halogenated C 1-2 Alkyl, deuterated C 1-2 Alkyl, C 1-2 Alkoxy, halogenated C 1-2 Alkoxy, deuterated C 1-2 Alkoxy and NH2 group substitution;

[0027] In some embodiments, R A1 Selected from halogenated C 2-4 Alkenyl, C 2-4Alkynyl, 5-6 membered monocyclic heteroaryl containing 1-3 heteroatoms selected from N, O, S, 8-10 membered bicyclic heteroaryl containing 1-3 heteroatoms selected from N, O, S, -C 1-2 Alkyl-R a 、-C 1-2 Alkyl-OR a 、-C 1-2 Alkyl-NR b R a 、-NR b -S(O)2-R a 、-NR b -S(O)2-NR b R a The alkynyl, heteroaryl, and alkyl groups are optionally further substituted by 1, 2, or 3 groups selected from halogen, deuterium, CN, OH, C 1-2 Alkyl, halogenated C 1-2 Alkyl, deuterated C 1-2 Alkyl, C 1-2 Alkoxy, halogenated C 1-2 Alkoxy, deuterated C 1-2 Alkoxy and NH2 group substitution;

[0028] In some embodiments, R A1 Selected from halogenated C 2-4 Alkenyl, C 2-4 Alkynyl, 5-6 membered monocyclic heteroaryl containing 1-3 heteroatoms selected from N, O, S, -C 1-2 Alkyl-R a 、-C 1-2 Alkyl-OR a 、-C 1-2 Alkyl-NR b R a 、-NR b -S(O)2-R a 、-NR b -S(O)2-NR b R a The alkynyl, heteroaryl, and alkyl groups are optionally further substituted by 1, 2, or 3 groups selected from halogen, deuterium, CN, OH, C 1-2 Alkyl, halogenated C 1-2 Alkyl, deuterated C 1-2 Alkyl, C 1-2 Alkoxy, halogenated C 1-2 Alkoxy, deuterated C 1-2 Alkoxy and NH2 group substitution;

[0029] In some embodiments, R A1 Selected from halogenated C 2-4 Alkenyl, C 2-4Alkynyl, 5- or 6-membered monocyclic heteroaryl containing 1, 2, or 3 heteroatoms selected from N, O, or S, -CH2-R a 、-CH2-OR a 、-CH2-NR b R a 、-NR b -S(O)2-R a 、-NR b -S(O)2-NR b R a The alkynyl, heteroaryl, CH2 may be further substituted by 1, 2, or 3 halogens, deuterium, CN, OH, C 1-2 Alkyl, halogenated C 1-2 Alkyl, deuterated C 1-2 Alkyl, C 1-2 Alkoxy, halogenated C 1-2 Alkoxy, deuterated C 1-2 Alkoxy and NH2 group substitution;

[0030] In some embodiments, R A1 Selected from C 3-6 Monocyclic cycloalkyl, 4-6 membered monocyclic heteroaryl containing 1-3 heteroatoms selected from N, O, S, 8-10 membered benzo C containing 1-3 heteroatoms selected from N, O, S 3-6 Cycloalkyl, -OR a 、-O-CH2-R a , the cycloalkyl, heteroaryl, benzo C 3-6 The cycloalkyl group is optionally further substituted by 1, 2, or 3 groups selected from halogen, deuterium, CN, OH, C 1-2 Alkyl, halogenated C 1-2 Alkyl, deuterated C 1-2 Alkyl, C 1-2 Alkoxy, halogenated C 1-2 Alkoxy, deuterated C 1-2 Alkoxy and NH2 group substitution;

[0031] In some embodiments, R A1 Selected from halovinyl, halopropenyl, ethynyl, propynyl, pyrrolyl, furyl, thienyl, imidazolyl, oxazolyl, thiazolyl, pyrazolyl, isoxazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, -CH2-R a 、-CH2-OR a 、-CH2-NR b R a 、-NR b -S(O)2-R a 、-NR b -S(O)2-NR b R a, the ethynyl, propynyl, pyrrolyl, furyl, thienyl, imidazolyl, oxazolyl, thiazolyl, pyrazolyl, isoxazolyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, CH2 is optionally further substituted by 1, 2, or 3 groups selected from F, Cl, deuterium, CN, OH, methyl, ethyl, -CH2F, -CHF2, -CF3, -CH2CH2F, -CH2CHF2, -CH2CF3, -CHFCH2F, -CHFCHF2, -CHFCF3, -CF2CH2F, -CF2CHF2, -CF2CF3, -CH2D, -CHD2, -CD3, -CH2CH2D, -CH2CHD2, -CH2CD3, -CHDCH2D, -CHDCHD2, -CHDCD 3, -CD2CH2D, -CD2CHD2, -CD2CD3, methoxy, ethoxy, -OCHF2, -OCH2F, -OCF3, -OCH2CH2F, -OCH2CHF2, -OCH2CF3, -OCHFCH2F, -OCHFCHF2, -OCHFCF3, -OCF2CH2F, -OCF2CHF2, -OCF2CF3, -OCHD2, -OCH2D, -OCD3, -OCH2CH2D, -OCH2CHD2, -OCH2CD3, -OCHDCH2D, -OCHDCHD2, -OCHDCD3, -OCD2CH2D, -OCD2CHD2, -OCD2CD3 and NH2;

[0032] In some embodiments, R A1 Selected from

[0033] In some embodiments, R A1 Selected from

[0034] In some embodiments, R A1 Selected from Or selected from

[0035] In some embodiments, R A1 Selected from

[0036] In some embodiments, R A1 Selected from

[0037] Each R a Selected from CN, halogenated C 1-6 Alkyl, C 3-10Cycloalkyl, 4-10 membered heterocycloalkyl containing 1-3 heteroatoms selected from N, O, S, 6-10 membered aryl, 5-10 membered heteroaryl containing 1-3 heteroatoms selected from N, O, S, -C(O)-R a1 The alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl groups are optionally further substituted by 1-3 groups selected from halogen, =O, deuterium, CN, OH, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, deuterated C 1-4 Alkoxy and NH2 group substitution;

[0038] In certain embodiments, each R a Selected from CN, halogenated C 1-4 Alkyl, C 3-6 Monocyclic cycloalkyl, C 7-10 Spirocyclic cycloalkyl, C 4-8 Bridged ring cycloalkyl, C 4-9 cycloalkyl, 4-6 membered monocyclic heterocycloalkyl containing 1-3 heteroatoms selected from N, O, and S, 7-10 membered spirocyclic heterocycloalkyl containing 1-3 heteroatoms selected from N, O, and S, 4-8 membered bridged heterocycloalkyl containing 1-3 heteroatoms selected from N, O, and S, 4-6 membered cycloheterocycloalkyl containing 1-3 heteroatoms selected from N, O, and S, phenyl, 8-10 membered aryl, 5-6 membered monocyclic heteroaryl containing 1-3 heteroatoms selected from N, O, and S, 8-10 membered bicyclic heteroaryl containing 1-3 heteroatoms selected from N, O, and S, -C(O)-R a1 The alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl groups are optionally further substituted by 1-3 groups selected from halogen, =O, deuterium, CN, OH, C 1-2 Alkyl, halogenated C 1-2 Alkyl, deuterated C 1-2 Alkyl, C 1-2 Alkoxy, halogenated C 1-2 Alkoxy, deuterated C 1-2 Alkoxy and NH2 group substitution;

[0039] In certain embodiments, each R a Selected from CN, halogenated C 1-4 Alkyl, C 3-6Monocyclic cycloalkyl, 4-6 membered monocyclic heterocycloalkyl containing 1-3 heteroatoms selected from N, O, and S, 7-10 membered spirocyclic heterocycloalkyl containing 1-3 heteroatoms selected from N, O, and S, 4-8 membered bridged heterocycloalkyl containing 1-3 heteroatoms selected from N, O, and S, 4-6 membered cyclic heterocycloalkyl containing 1-3 heteroatoms selected from N, O, and S, phenyl, 8-10 membered aryl, 5-6 membered monocyclic heteroaryl containing 1-3 heteroatoms selected from N, O, and S, 8-10 membered bicyclic heteroaryl containing 1-3 heteroatoms selected from N, O, and S, -C(O)-R a1 The alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl groups are optionally further substituted by 1-3 groups selected from halogen, =O, deuterium, CN, OH, C 1-2 Alkyl, halogenated C 1-2 Alkyl, deuterated C 1-2 Alkyl, C 1-2 Alkoxy, halogenated C 1-2 Alkoxy, deuterated C 1-2 Alkoxy and NH2 group substitution;

[0040] In certain embodiments, each R a Selected from CN, -CH2F, -CHF2, -CF3, -CH2CH2F, -CH2CHF2, -CH2CF3, -CHFCH2F, -CHFCHF2, -CHFCF3, -CF2CH2F, -CF2CHF2, -CF2CF3, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, azetidinyl, azetyl, oxetanyl, oxetanyl, piperazinyl, piperidinyl, tetrahydropyranyl, morpholinyl, pyranyl, phenyl, pyrrolyl, furyl, thienyl, imidazolyl, oxazolyl, thiazolyl, pyrazolyl, isoxazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, -C(O)-R a1, wherein the above groups are optionally further replaced by 1, 2, or 3 groups selected from F, Cl, =O, deuterium, CN, OH, methyl, ethyl, -CH2F, -CHF2, -CF3, -CH2CH2F, -CH2CHF2, -CH2CF3, -CHFCH2F, -CHFCHF2, -CHFCF3, -CF2CH2F, -CF2CHF2, -CF2CF3, -CH2D, -CHD2, -CD3, -CH2CH2D, -CH2CHD2, -CH2CD3, -CHDCH2D, -CHDCHD2, -CHDCD3, -CD2CH2D, -CD2CHD2, -CD2CD 3. methoxy, ethoxy, -OCHF2, -OCH2F, -OCF3, -OCH2CH2F, -OCH2CHF2, -OCH2CF3, -OCHFCH2F, -OCHFCHF2, -OCHFCF3, -OCF2CH2F, -OCF2CHF2, -OCF2CF3, -OCHD2, -OCH2D, -OCD3, -OCH2CH2D, -OCH2CHD2, -OCH2CD3, -OCHDCH2D, -OCHDCHD2, -OCHDCD3, -OCD2CH2D, -OCD2CHD2, -OCD2CD3 and NH2;

[0041] Each R b Selected from H, deuterium, C 1-4 Alkyl, C 3-6 Cycloalkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl; in certain embodiments, each R b Selected from H, deuterium, C 1-4 Alkyl, C 3-6 Cycloalkyl; in certain embodiments, each R b Selected from H, deuterium, C 1-2 Alkyl, C 3-4 Cycloalkyl; in certain embodiments, each R b is selected from H, deuterium, and methyl;

[0042] R a1 Selected from OH, NH2, -NHC 1-4 Alkyl, -N(C 1-4 Alkyl)2, -NHC 3-10 Cycloalkyl, C 1-4 Alkoxy, C 1-6 Alkyl, C 3-10 Cycloalkyl, 6-10 membered aryl, 5-10 membered heteroaryl containing 1-3 heteroatoms selected from N, O, S; In certain embodiments, R a1 Selected from OH, NH2, -NHC 1-2Alkyl, -N(C 1-2 Alkyl)2, -NHC 3-7 Cycloalkyl, C 1-2 Alkoxy, C 1-2 Alkyl, C 3-7 Cycloalkyl, phenyl, 8-10 membered bicyclic aryl, 5-6 membered heteroaryl containing 1-3 heteroatoms selected from N, O, S, or 8-10 membered bicyclic heteroaryl containing 1-3 heteroatoms selected from N, O, S; in certain embodiments, R a1 Selected from OH, NH2, -NHC 1-2 Alkyl, -N(C 1-2 Alkyl)2, -NHC 3-4 Cycloalkyl, C 1-2 Alkoxy, C 1-2 Alkyl, C 3-4 Cycloalkyl, phenyl, piperazinyl, piperidinyl, tetrahydropyranyl, morpholinyl, pyranyl, phenyl, pyrrolyl, furanyl, thienyl, imidazolyl, oxazolyl, thiazolyl, pyrazolyl, isoxazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl; In certain embodiments, R a1 Selected from C 1-2 Alkyl, C 3-7 Cycloalkyl, phenyl, piperazinyl, piperidinyl, tetrahydropyranyl, morpholinyl, pyranyl, phenyl, pyrrolyl, furanyl, thienyl, imidazolyl, oxazolyl, thiazolyl, pyrazolyl, isoxazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl;

[0043] X is selected from CR 10 or N; in certain embodiments, X is selected from CH or N; in certain embodiments, X is selected from CH; in certain embodiments, X is selected from N;

[0044] X1 is selected from O, S; in certain embodiments, X1 is selected from O; in certain embodiments, X1 is selected from S;

[0045] R 4 、R 5 Each independently selected from H, deuterium, C 3-10 Cycloalkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, halogen, amino, -NH-C 1-4 Alkyl, -N(C 1-4 Alkyl)2, C 1-4 Alkyl, halogenated C 1-4 alkyl, 4-10 membered heterocycloalkyl containing 1-3 heteroatoms selected from N, O, S, 5-10 membered heteroaryl containing 1-3 heteroatoms selected from N, O, S, 6-10 membered aryl; in certain embodiments, R 4 、R 5 Each independently selected from H, deuterium, C3-4 Monocyclic cycloalkyl, C 7-8 Bicyclic cycloalkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, F, Cl, amino, -NH-C 1-2 Alkyl, -N(C 1-2 Alkyl)2, C 1-2 Alkyl, halogenated C 1-2 alkyl, 4-6 membered monocyclic heterocycloalkyl containing 1, 2, or 3 heteroatoms selected from N, O, and S, 7-10 membered bicyclic heterocycloalkyl containing 1, 2, or 3 heteroatoms selected from N, O, and S, 5-6 membered monocyclic heteroaryl containing 1-3 heteroatoms selected from N, O, and S, 8-10 membered bicyclic heteroaryl containing 1-3 heteroatoms selected from N, O, and S, phenyl, 8-10 membered bicyclic aryl; in certain embodiments, R 4 、R 5 Each independently selected from H, deuterium, C 3-4 Monocyclic cycloalkyl, C 7-8 Bicyclic cycloalkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, F, Cl, amino, -NH-C 1-2 Alkyl, -N(C 1-2 Alkyl)2, C 1-2 Alkyl, halogenated C 1-2 alkyl, 4-6 membered monocyclic heterocycloalkyl containing 1, 2, or 3 heteroatoms selected from N, O, and S; in certain embodiments, R 4 、R 5 Each independently selected from H, deuterium, C 3-4 Monocyclic cycloalkyl, C 7-8 Bicyclic cycloalkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, 4-5 membered monocyclic heterocycloalkyl containing 1, 2 or 3 heteroatoms selected from N, O or S; in certain embodiments, R 4 、R 5 Each independently selected from H, deuterium, C 3-4 Monocyclic cycloalkyl, C 2-4 Alkenyl, C 2-4 Alkynyl; in certain embodiments, R 4 、R 5 Each is independently selected from H, deuterium, cyclopropyl, cyclobutyl, vinyl, propenyl; in certain embodiments, R 4 、R 5 are each independently selected from H; in certain embodiments, R 5 Selected from H;

[0046] R 6 、R 7 、R 8 、R 9、R 10 Each independently selected from H, deuterium, R A2 , halogen, OH, CN, amino, C 1-4 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-4 Alkoxy, halogenated C 1-4 Alkyl, -NH-C 1-4 Alkyl, -N(C 1-4 Alkyl)2, -S(O)R c 、-S(O) 2 R c 、-C(O)R c 、-C(O)OR c 、-C(O)N(R c )2、-OC(O)R c The alkyl, alkenyl, alkynyl, and alkoxy groups are optionally further substituted by 1 to 3 groups selected from halogen, deuterium, CN, OH, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, deuterated C 1-4 Alkoxy and NH2 group substitution;

[0047] In certain embodiments, R 6 、R 7 、R 8 、R 9 、R 10 Each independently selected from H, deuterium, R A2 、F、Cl、OH、CN、amino、C 1-2 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-2 Alkoxy, halogenated C 1-2 Alkyl, -NH-C 1-2 Alkyl, -N(C 1-2 Alkyl)2, -S(O)R c 、-S(O) 2 R c 、-C(O)R c 、-C(O)OR c 、-C(O)N(R c )2、-OC(O)R c The alkyl, alkenyl, alkynyl, and alkoxy groups are optionally further substituted by 1, 2, or 3 groups selected from F, Cl, deuterium, CN, OH, C 1-2 Alkyl, halogenated C 1-2 Alkyl, deuterated C 1-2 Alkyl, C1-2 Alkoxy, halogenated C 1-2 Alkoxy, deuterated C 1-2 Alkoxy and NH2 group substitution;

[0048] In certain embodiments, R 7 、R 8 Each independently selected from H, deuterium, R A2 、F、Cl、OH、CN、amino、C 1-2 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-2 Alkoxy, halogenated C 1-2 Alkyl, -NH-C 1-2 Alkyl, -N(C 1-2 alkyl) 2, wherein the alkyl, alkenyl, alkynyl, alkoxy group is optionally further substituted by 1, 2, or 3 groups selected from F, Cl, deuterium, CN, OH, C 1-2 Alkyl, halogenated C 1-2 Alkyl, deuterated C 1-2 Alkyl, C 1-2 Alkoxy, halogenated C 1-2 Alkoxy, deuterated C 1-2 Alkoxy and NH2 group substitution; R 6 、R 9 、R 10 Each independently selected from H, deuterium, F, Cl, OH, CN, amino, C 1-2 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-2 Alkoxy, halogenated C 1-2 Alkyl, -NH-C 1-2 Alkyl, -N(C 1-2 alkyl) 2, wherein the alkyl, alkenyl, alkynyl, alkoxy group is optionally further substituted by 1, 2, or 3 groups selected from F, Cl, deuterium, CN, OH, C 1-2 Alkyl, halogenated C 1-2 Alkyl, deuterated C 1-2 Alkyl, C 1-2 Alkoxy, halogenated C 1-2 Alkoxy, deuterated C 1-2 Alkoxy and NH2 group substitution;

[0049] In certain embodiments, R 7 、R 8 Each independently selected from H, deuterium, R A2 、F、Cl、OH、CN、amino、C 1-2 Alkyl, C 1-2 Alkoxy, halogenated C 1-2 Alkyl, -NH-C 1-2Alkyl, -N(C 1-2 alkyl) 2, wherein the alkyl, alkenyl, alkynyl, alkoxy group is optionally further substituted by 1, 2, or 3 groups selected from F, Cl, deuterium, CN, OH, and NH2; R 6 、R 9 、R 10 Each independently selected from H, deuterium, F, Cl, OH, CN, amino, C 1-2 Alkyl, wherein the alkyl is optionally further substituted with 1, 2, or 3 groups selected from F, Cl, deuterium, and OH;

[0050] In certain embodiments, R 7 Each independently selected from R A2 ; R 6 、R 8 、R 9 、R 10 Each independently selected from H, deuterium, F, Cl, OH, CN, amino, C 1-2 Alkyl, wherein the alkyl is optionally further substituted with 1, 2, or 3 groups selected from F, Cl, deuterium, and OH;

[0051] In certain embodiments, R 8 Each independently selected from R A2 ; R 6 、R 7 、R 9 、R 10 Each independently selected from H, deuterium, F, Cl, OH, CN, amino, C 1-2 Alkyl, wherein the alkyl is optionally further substituted with 1, 2, or 3 groups selected from F, Cl, deuterium, and OH;

[0052] In certain embodiments, R 7 Each independently selected from R A2 ; R 6 、R 8 、R 9 、R 10 Each independently selected from H, deuterium, F, Cl, OH, CN, amino, C 1-2 alkyl;

[0053] In certain embodiments, R 8 Each independently selected from R A2 ; R 6 、R 7 、R 9 、R 10 Each independently selected from H, deuterium, F, Cl, OH, CN, amino, C 1-2 alkyl;

[0054] In certain embodiments, R 7 、R8 Each independently selected from H, deuterium, F, Cl, OH, CN, methyl, R A2 ; R 6 、R 9 、R 10 Each independently selected from H, deuterium, F, Cl, OH, CN, methyl;

[0055] In certain embodiments, R 6 、R 9 、R 10 Each independently selected from H, deuterium, halogen, C 1-6 Alkyl, halogenated C 1-6 Alkyl; in certain embodiments, R 6 、R 9 、R 10 Each independently selected from H, deuterium, halogen, C 1-3 Alkyl, halogenated C 1-3 Alkyl; in certain embodiments, R 6 、R 9 、R 10 Each independently selected from H, deuterium, F, Cl, methyl, trifluoromethyl, difluoromethyl;

[0056] R A2 Selected from -(CH2) r -(C 3-10 Cycloalkyl), -(CH2) r -(4-10 membered heterocycloalkyl containing 1-3 heteroatoms selected from N, O, S, Si), or -(CH2) r -(5-10 membered heteroaryl containing 1-3 heteroatoms selected from N, O, S), -P(O)(R c )2、-Si(R c )3, -SF5, N3, B(OH)2, or -S(O)(=NH)R c The cycloalkyl, heterocycloalkyl, and heteroaryl groups are optionally further substituted by 1 to 3 groups selected from halogen, =O, D, CN, OH, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, C 3-6 Cycloalkyl, 4-7 membered heterocycloalkyl containing 1-3 heteroatoms selected from N, O, S, deuterated C 1-4 Alkoxy and NH2 group substitution;

[0057] In certain embodiments, R A2 Selected from -(CH2) r-(4-10 membered heterocycloalkyl containing 1-3 heteroatoms selected from N, O, S, Si), or -(CH2) r -(5-10 membered heteroaryl containing 1-3 heteroatoms selected from N, O, S), -P(O)(R c )2、-Si(R c )3, -SF5, N3, B(OH)2, or -S(O)(=NH)R c The heterocycloalkyl and heteroaryl groups are optionally further substituted by 1-3 groups selected from halogen, =O, D, CN, OH, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, C 3-6 Cycloalkyl, 4-7 membered heterocycloalkyl containing 1-3 heteroatoms selected from N, O, S, deuterated C 1-4 Alkoxy and NH2 group substitution;

[0058] In certain embodiments, R A2 Selected from -(CH2) r -(4-10 membered heterocycloalkyl containing 1-3 heteroatoms selected from N, O, S), or -(CH2) r -(5-10 membered heteroaryl containing 1-3 heteroatoms selected from N, O, S), -P(O)(R c )2、-Si(R c )3、-SF5、-S(O)(=NH)R c The heterocycloalkyl and heterocycloaryl groups are optionally further substituted by 1-3 groups selected from halogen, D, CN, OH, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, deuterated C 1-4 Alkoxy and NH2 groups are substituted; in certain embodiments, R A2 Selected from -(CH2) r -(a 4-6 membered monocyclic heterocycloalkyl group containing 1-3 heteroatoms selected from N, O, and S), -(CH2) r -(7-10 membered spirocyclic heterocycloalkyl containing 1-3 heteroatoms selected from N, O, S), -(CH2) r -(5-6 membered monocyclic heteroaryl containing 1-3 heteroatoms selected from N, O, S), -(CH2) r -(8-10 membered bicyclic heteroaryl containing 1-3 heteroatoms selected from N, O, S), -P(O)(R c)2、-Si(R c )3、-SF5、-S(O)(=NH)R c The heterocycloalkyl and heterocycloaryl groups are optionally further substituted by 1-3 groups selected from halogen, D, CN, OH, C 1-2 Alkyl, halogenated C 1-2 Alkyl, deuterated C 1-2 Alkyl, C 1-2 Alkoxy, halogenated C 1-2 Alkoxy, deuterated C 1-2 Alkoxy and NH2 group substitution;

[0059] In certain embodiments, R A2 Selected from -(CH2) r -(a 4-6 membered monocyclic heterocycloalkyl group containing 1-3 heteroatoms selected from N, O, and S), -(CH2) r -(a 5-6 membered monocyclic heteroaryl group containing 1-3 heteroatoms selected from N, O, and S), -P(O)(R c )2、-Si(R c )3、-SF5、-S(O)(=NH)R c The heterocycloalkyl and heterocycloaryl groups are optionally further substituted by 1-3 groups selected from halogen, D, CN, OH, C 1-2 Alkyl, halogenated C 1-2 Alkyl, deuterated C 1-2 Alkyl, C 1-2 Alkoxy, halogenated C 1-2 Alkoxy, deuterated C 1-2 Alkoxy and NH2 groups are substituted; in certain embodiments, R A2 Selected from -(CH2) r -(a 4-6 membered monocyclic heterocycloalkyl group containing 1-3 heteroatoms selected from N, O, and S), -(CH2) r -(a 5-6 membered monocyclic heteroaryl containing 1-3 heteroatoms selected from N, O, and S), wherein the heterocycloalkyl and heteroaryl groups are optionally further substituted by 1-3 heteroatoms selected from halogen, D, CN, OH, C 1-2 Alkyl, halogenated C 1-2 Alkyl, deuterated C 1-2 Alkyl, C 1-2 Alkoxy, halogenated C 1-2 Alkoxy, deuterated C 1-2 Alkoxy and NH2 group substitution;

[0060] In certain embodiments, R A2 Selected from

[0061] In certain embodiments, R A2 Selected from

[0062] In certain embodiments, R A2 Selected from

[0063] Each R c Each independently selected from H, OH, C 1-4 Alkyl, C 3-7 Cycloalkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, deuterated C 1-4 alkoxy, or NH2; in certain embodiments, each R c Each independently selected from C 1-2 Alkyl, C 3-4 Cycloalkyl, halogenated C 1-2 Alkyl, deuterated C 1-2 Alkyl, C 1-2 Alkoxy, halogenated C 1-2 Alkoxy, deuterated C 1-2 Alkoxy or NH2; in certain embodiments, each R c Each independently selected from C 1-2 Alkyl, C 3-4 Cycloalkyl; in certain embodiments, each R c Each independently selected from C 1-2 alkyl;

[0064] Each r is independently selected from 0, 1, 2 or 3; in certain embodiments, each r is independently selected from 0, 1;

[0065] L1 is selected from a bond, O, NH, S, -CD2-, -CHD-, -CR L1 R L2 -、C 1-4 Alkyl, -C(O)-, S(O), S(O)2, wherein the alkyl group is optionally further R L1 substituted; in certain embodiments, L1 is selected from a bond, O; in certain embodiments, L1 is selected from a bond;

[0066] L2 is selected from O, NH, S, -CH2-, -CD2-, -CHD-, -CR L1 R L2 -、-CHR L2 -、-CDR L2 -、C 2-4 Alkyl, -C(O)-, S(O), S(O)2, wherein the alkyl group is optionally further substituted with 1-3 R L1In certain embodiments, L2 is selected from -CH2-, -CD2-, -CHD-, -CR L1 R L2 -、-CHR L2 -、-CDR L2 -、C 2-4 Alkyl, -C(O)-, S(O), S(O)2, wherein the alkyl group is optionally further substituted with 1-3 R L1 Substituted; In certain embodiments, L2 is selected from -CH2-, -CR L1 R L2 -、-CHR L2 -、-CDR L2 -, -C(O)-; In certain embodiments, L2 is selected from -CH2-; In certain embodiments, L2 is selected from -CR L1 R L2 -、-CHR L2 -、-CDR L2 -, -C(O)-;

[0067] R A4 Selected from -CH2-C 1-4 Alkyl-C 3-6 Cycloalkyl, -CH2-CR A4c =CR A4a R A4b 、-CH2-CH=CH-CH=CR A4a R A4b 、-CH(C 1-2 (alkyl)-CR A4c =CR A4a R A4b 、-C(C 1-2 alkyl)2-CR A4c =CR A4a R A4b 、L3-R A4’ In certain embodiments, R A4 Selected from -CH2-C 1-4 Alkyl-C 3-6 Cycloalkyl, -CH2-CH=CR A4a R A4b 、-CH2-CF=CR A4a R A4b 、-CH2-C(CN)=CR A4a R A4b 、-CH2-C(CH3)=CR A4a R A4b 、-CH2-CH=CH-CH=CR A4a R A4b 、-CHCH3-CR A4c =CRA4a R A4b 、-CH(CH2CH3)-CR A4c =CR A4a R A4b 、-C(CH3)2-CR A4c =CR A4a R A4b 、-C(CH2CH3)2-CR A4c =CR A4a R A4b 、L3-R A4’ In certain embodiments, R A4 Selected from -CH2-C 1-4 Alkyl-C 3-6 Cycloalkyl, -CH2-CR A4c =CR A4a R A4b 、-CH2-CH=CH-CH=CR A4a R A4b 、L3-R A4’ , or selected from -CHCH3-CR A4c =CR A4a R A4b In certain embodiments, R A4 Selected from -CH2-C 1-4 Alkyl-C 3-6 Cycloalkyl, -CH2-CH=CR A4a R A4b 、-CH2-CF=CR A4a R A4b 、-CH2-C(CH3)=CR A4a R A4b 、-CH2-CH=CH-CH=CR A4a R A4b 、L3-R A4’ or selected from -CHCH3-CH=CR A4a R A4b ;; In certain embodiments, R A4 Selected from -CH2-C 1-4 Alkyl-C 3-6 Cycloalkyl, -CH2-CF=CR A4a R A4b 、-CH2-CH=CH-CH=CR A4a R A4b 、L3-R A4’ or selected from -CHCH3-CH=CR A4a R A4b ;; In certain embodiments, R A4 Selected from -CH2-C 1-4 Alkyl-C3-6 Cycloalkyl, -CH2-C(CH3)=CR A4a R A4b 、-CH2-CH=CH-CH=CR A4a R A4b 、L3-R A4’ or selected from -CHCH3-CH=CR A4a R A4b In certain embodiments, R A4 Selected from -CH2-C 1-4 Alkyl-C 3-6 Cycloalkyl, -CH2-CH=CR A4a R A4b 、-CH2-CH=CH-CH=CR A4a R A4b 、L3-R A4’ or selected from -CHCH3-CH=CR A4a R A4b ;

[0068] In certain embodiments, R A4 Selected from -CH2-C 1-4 Alkyl-C 3-6 Cycloalkyl, -CH2-CF=CR A4a R A4b 、L3-R A4’ or selected from -CHCH3-CH=CR A4a R A4b In certain embodiments, R A4 Selected from -CH2-C 1-4 Alkyl-C 3-6 Cycloalkyl, -CH2-C(CH3)=CR A4a R A4b 、L3-R A4’ or selected from -CHCH3-CH=CR A4a R A4b In certain embodiments, R A4 Selected from -CH2-C 1-4 Alkyl-C 3-6 Cycloalkyl, -CH2-CH=CR A4a R A4b 、L3-R A4’ or selected from -CHCH3-CH=CR A4a R A4b In certain embodiments, R A4 Selected from -CH2-C 1-4 Alkyl-C 3-6 Cycloalkyl or selected from -CHCH3-CH=CR A4a R A4bIn certain embodiments, R A4 Selected from In certain embodiments, R A4 Selected from -CH2-CH=CR A4a R A4b 、L3-R A4’ or selected from -CHCH3-CH=CR A4a R A4b ;; In certain embodiments, R A4 Selected from Or choose In certain embodiments, R A4 Selected from Or choose

[0069] In certain embodiments, R A4 Selected from Or choose

[0070] R A4c Selected from H, halogen, deuterium, CN, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, deuterated C 1-4 Alkoxy and NH2; in certain embodiments, R A4c Selected from H, halogen, deuterium, C 1-4 Alkyl, halogenated C 1-4 Alkyl, C 1-4 Alkoxy; in certain embodiments, R A4c Selected from H, halogen, C 1-4 Alkyl; in certain embodiments, R A4c Selected from H;

[0071] R A4a 、R A4b Together with the carbon atom to which it is attached, it forms a 3-6 membered monocyclic carbon ring, C 7-10 Spirocarbon ring, C 7-10 Bridged carbon ring or C 7-10 A 4-7 membered heterocyclic ring containing 1-3 heteroatoms selected from N, O, and S, or a 6-membered 4-7 membered heterocyclic ring, wherein the carbocyclic ring or heterocyclic ring is optionally substituted by 1-3 heteroatoms selected from halogen, =O, deuterium, CN, OH, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4Alkyl, -COC 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, deuterated C 1-4 Alkoxy and NH2 groups are substituted; the carbocyclic ring includes cycloalkyl and aryl, and the heterocyclic ring includes heterocycloalkyl and heteroaryl;

[0072] In certain embodiments, R A4a 、R A4b Together with the carbon atom to which it is attached, it forms a 3-6 membered carbocyclic ring; in certain embodiments, R A4a 、R A4b Together with the carbon atom to which it is attached, it forms a 3-, 4-, 5-, or 6-membered carbocyclic ring; in certain embodiments, R A4a 、R A4b Together with the carbon atom to which it is attached, it forms a 3, 4, 5, or 6-membered cycloalkyl group; in certain embodiments, R A4a 、R A4b Together with the carbon atom to which it is attached, it forms a 4-, 5-, or 6-membered cycloalkyl group; in certain embodiments, R A4a 、R A4b Together with the carbon atom to which it is connected, it forms a 4, 5, or 6-membered monocyclic cycloalkyl group, C 7-10 Spirocarbon ring, C 7-10 cycloalkyl, cycloalkyl, heterocycloalkyl, ... 1-2 Alkyl, halogenated C 1-2 Alkyl, deuterated C 1-2 Alkyl, -COC 1-2 Alkyl, C 1-2 Alkoxy, halogenated C 1-2 Alkoxy, deuterated C 1-2 Alkoxy and NH2 group substitution;

[0073] In certain embodiments, R A4a 、R A4b Together with the carbon atom to which it is connected, it forms a 4, 5, or 6-membered monocyclic cycloalkyl group, C 7-10 Spirocarbon ring, C 7-10 A 5- or 6-membered heterocyclic cycloalkyl containing 1-3 heteroatoms selected from N, O, and S, wherein the cycloalkyl and heterocycloalkyl groups are optionally substituted by 1-3 heteroatoms selected from halogen, =O, deuterium, CN, OH, C 1-2 Alkyl, halogenated C 1-2 Alkyl, deuterated C 1-2 Alkyl, -COC 1-2 Alkyl, C 1-2 Alkoxy, halogenated C 1-2 Alkoxy, deuterated C1-2 Alkoxy and NH2 group substitution;

[0074] L3 is selected from C 3-6 Cycloalkyl, or -CH(C 1-2 alkyl)-C 1-4 Alkyl, the cycloalkyl group is optionally substituted by 1-3 R L3 replace;

[0075] In certain embodiments, L3 is selected from C 3-6 Cycloalkyl, -CH(C 1-2 alkyl)-C 1-4 Alkyl; in certain embodiments, L3 is selected from C 3-6 Cycloalkyl, -CH(C 1-2 alkyl)-C 1-2 Alkyl; In certain embodiments, L3 is selected from cyclobutyl, cyclopentyl, cyclohexyl, -CH(CH3)-CH2-*, wherein * represents the same as R 4A’ Linking site;

[0076] Each R L3 independently selected from halogen, =O, deuterium, CN, OH, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, -COC 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, deuterated C 1-4 Alkoxy and NH2;

[0077] Optionally, two R on adjacent ring atoms L3 and the atoms to which it is attached together form a 5-7 membered carbocyclic ring or a 5-7 membered heterocyclic ring containing 1-3 heteroatoms selected from N, O, and S; in certain embodiments, form a C4 cycloalkyl or C5 cycloalkyl; in certain embodiments, form a heteroaryl, such as pyrazolyl, imidazolyl, thiazolyl, thienyl, oxazolyl, furanyl, or form a 5-membered heterocycloalkyl containing 1-2 heteroatoms of N, O, and S; in certain embodiments, the carbocyclic ring or heterocyclic ring is optionally substituted;

[0078] R A4’ Selected from H, C 3-6 Cycloalkyl, 5-10 membered heteroaryl containing 1-3 heteroatoms selected from N, O, S, or 4-7 membered heterocycloalkyl containing 1-3 heteroatoms selected from N, O, S, wherein the cycloalkyl, heteroaryl and heterocycloalkyl are optionally further substituted by 1-3 halogen, deuterium, CN, OH, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, C 1-4Alkoxy, halogenated C 1-4 Alkoxy, deuterated C 1-4 Alkoxy and NH2 groups are substituted; in certain embodiments, R A4’ Selected from C 3-6 Cycloalkyl, 5-10 membered heteroaryl containing 1-3 heteroatoms selected from N, O, S, wherein the cycloalkyl and heteroaryl are optionally further substituted by 1-3 heteroatoms selected from halogen, deuterium, CN, OH, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, deuterated C 1-4 Alkoxy and NH2 groups are substituted; in certain embodiments, R A4’ Selected from C 4、5、6 Cycloalkyl, 5-6 membered monocyclic heteroaryl containing 1, 2, 3 heteroatoms selected from N, O, S, 8-10 membered bicyclic heteroaryl containing 1, 2, 3 heteroatoms selected from N, O, S, the cycloalkyl and heteroaryl groups are optionally further substituted by 1, 2, 3 heteroatoms selected from F, Cl, deuterium, CN, OH, C 1-2 Alkyl, halogenated C 1-2 Alkyl, deuterated C 1-2 Alkyl, C 1-2 Alkoxy, halogenated C 1-2 Alkoxy, deuterated C 1-2 Alkoxy and NH2 groups are substituted; in certain embodiments, R A4’ Selected from C 4、5 Cycloalkyl, 5-6 membered monocyclic heteroaryl containing 1, 2 or 3 heteroatoms selected from N, O and S, wherein the heteroaryl is optionally further substituted by 1, 2 or 3 heteroatoms selected from F, Cl, deuterium, CN, OH, C 1-2 Alkyl, halogenated C 1-2 Alkyl, deuterated C 1-2 Alkyl and NH2 group substitution;

[0079] R L1 、R L2 Each independently selected from halogen, OH, CN, amino, C 1-4 Alkyl, C 1-4 Alkoxy, C 3-6 Cycloalkyl, 4-6 membered heterocycloalkyl containing 1-3 heteroatoms selected from N, O, S; in certain embodiments, R L1 、R L2 Each independently selected from F, Cl, OH, CN, amino, C 1-2 Alkyl, C 1-2 Alkoxy, C 3-4Cycloalkyl, 4- or 5-membered heterocycloalkyl containing 1-3 heteroatoms selected from N, O, and S; in certain embodiments, R L1 、R L2 Each independently selected from F, Cl, OH, CN, amino, C 1-2 Alkyl, C 1-2 Alkoxy; in certain embodiments, R L1 、R L2 Each independently selected from F, Cl, OH, CN, C 1-2 Alkyl, C 1-2 Alkoxy; in certain embodiments, R L1 、R L2 Each independently selected from F, C 1-2 alkyl;

[0080] Alternatively, R 2 、R 4 , L1 and the atoms to which they are connected together form a 5-7 membered carbocyclic ring, a 5-7 membered heterocyclic ring containing 1-3 heteroatoms selected from N, O, and S, wherein the carbocyclic ring or heterocyclic ring is optionally further substituted by 1-3 heteroatoms selected from R A3 In certain embodiments, R 2 、R 4 , L1 and the atoms to which they are connected together form a 6-7 membered cycloalkyl, phenyl, wherein the cycloalkyl is optionally further substituted by 1-3 groups selected from R A3 In certain embodiments, R 2 、R 4 , L1 and the atoms to which they are connected together form a cyclohexyl group, a phenyl group, wherein the cyclohexyl group is optionally further substituted by 1 to 3 groups selected from R A3 In certain embodiments, R 2 、R 4 , L1 and the atoms to which they are attached together form a cyclohexyl group, a phenyl group; in certain embodiments, R 2 、R 4 Together with the atoms it is connected to form C 5-7 Cycloalkyl; in certain embodiments, R 2 、R 4 Together with the atoms to which they are attached, they form cyclopentyl, cyclohexyl, or cycloheptyl;

[0081] Alternatively, R 4 、R 5 Together with the atoms to which they are connected, they form a 5-7 membered monocyclic carbocyclic ring or a 5-7 membered heterocyclic ring containing 1-3 heteroatoms selected from N, O, and S, wherein the carbocyclic ring or heterocyclic ring is optionally substituted by 1-3 heteroatoms selected from R A3 In certain embodiments, R 4 、R 5Together with the atoms to which they are attached, they form a phenyl group, a 5-6 membered cycloalkyl group, a 5-6 membered heteroaryl group containing 1-3 heteroatoms selected from N, O, and S, wherein the cycloalkyl group is optionally substituted by 1-3 heteroatoms selected from R A3 In certain embodiments, R 4 、R 5 Together with the atoms to which it is attached, it forms phenyl, cyclopentyl, cyclohexyl, pyrrolyl, furyl, thienyl, imidazolyl, oxazolyl, thiazolyl, pyrazolyl, isoxazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl;

[0082] Alternatively, R L1 With R 9 Together with the atoms to which they are connected, they form a 5-7 membered carbocyclic ring or a 5-7 membered heterocyclic ring containing 1-3 heteroatoms selected from N, O, and S, wherein the carbocyclic ring or heterocyclic ring is optionally further surrounded by 1-3 heteroatoms selected from R A3 In certain embodiments, R L1 With R 9 Together with the atoms to which they are attached, they form a 5-6 membered cycloalkyl group, which is optionally further substituted by 1-3 groups selected from R A3 In certain embodiments, R L1 With R 9 Together with the atoms to which they are attached, they form cyclopentyl or cyclohexyl;

[0083] Alternatively, R L2 With R 9 Together with the atoms to which they are connected, they form a 5-7 membered carbocyclic ring or a 5-7 membered heterocyclic ring containing 1-3 heteroatoms selected from N, O, and S, wherein the carbocyclic ring or heterocyclic ring is optionally further surrounded by 1-3 heteroatoms selected from R A3 In certain embodiments, R L2 With R 9 Together with the atoms to which they are attached, they form a 5-6 membered cycloalkyl group, which is optionally further substituted by 1-3 groups selected from R A3 In certain embodiments, R L2 With R 9 Together with the atoms to which they are attached, they form cyclopentyl or cyclohexyl;

[0084] Each R A3 Each independently selected from =O, halogen, deuterium, CN, OH, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, deuterated C 1-4 Alkoxy and NH2 groups are substituted; in certain embodiments, each R A3Each independently selected from =O, F, Cl, deuterium, CN, OH, C 1-2 Alkyl, halogenated C 1-2 Alkyl, deuterated C 1-2 Alkyl, C 1-2 Alkoxy, halogenated C 1-2 Alkoxy, deuterated C 1-2 Alkoxy and NH2 groups are substituted; in certain embodiments, each R A3 each independently selected from =O, F, Cl, deuterium, CN, OH, methyl, ethyl, -CH2F, -CHF2, -CF3, -CH2CH2F, -CH2CHF2, -CH2CF3, -CHFCH2F, -CHFCHF2, -CHFCF3, -CF2CH2F, -CF2CHF2, -CF2CF3, -CH2D, -CHD2, -CD3, -CH2CH2D, -CH2CHD2, -CH2CD3, -CHDCH2D, -CHDCHD2, -CHDCD3, -CD2CH2D, -CD2CHD2, -CD2CD3, methoxy, ethoxy -OCHF2, -OCH2F, -OCF3, -OCH2CH2F, -OCH2CHF2, -OCH2CF3, -OCHFCH2F, -OCHFCHF2, -OCHFCF3, -OCF2CH2F, -OCF2CHF2, -OCF2CF3, -OCHD2, -OCH2D, -OCD3, -OCH2CH2D, -OCH2CHD2, -OCH2CD3, -OCHDCH2D, -OCHDCHD2, -OCHDCD3, -OCD2CH2D, -OCD2CHD2, -OCD2CD3 and NH2;

[0085] R 11a 、R 11b 、R 12a 、R 12b Each independently selected from H, deuterium, OH, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, deuterated C 1-4 Alkoxy, C 3-6 Cycloalkyl; or R 11a 、R 11b 、R 12a 、R 12b Any two atoms in the 3-6 Cycloalkyl, optionally further substituted by 1-3 groups selected from =O, Halogen, deuterium, CN, OH, C 1-3Alkyl, halogenated C 1-3 Alkyl, deuterated C 1-3 Alkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, deuterated C 1-3 Alkoxy group substitution;

[0086] In certain embodiments, R 11a 、R 11b 、R 12a 、R 12b Each independently selected from H, deuterium, OH, C 1-3 Alkyl, halogenated C 1-3 Alkyl; or R 11a and R 11b , or R 12a and R 12b and its connected atoms together form C 3-6 Cycloalkyl;

[0087] In certain embodiments, R 11a 、R 11b 、R 12a 、R 12b Each independently selected from H, deuterium, OH, C 1-3 Alkyl, halogenated C 1-3 Alkyl; or R 11a and R 11b , or R 12a and R 12b and the atoms to which they are attached together form a cyclopropyl group;

[0088] The conditions are: R 6 With R 10 、R 10 With R 7 、R 7 With R 8 、R 8 With R 9 A group of the carbon ring and the atoms connected thereto together form a 4-8 membered carbocyclic ring, a 5-7 membered heterocycloalkyl containing 1-3 heteroatoms selected from N, O, S, B, Si, wherein the carbon ring, the heterocycloalkyl is optionally further substituted by 1-3 heteroatoms selected from =O, Halogen, deuterium, CN, OH, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, deuterated C 1-4 Alkoxy, 5-7 membered heterocycloalkyl containing 1-3 heteroatoms selected from N, O, S, B, Si, 5-7 membered heteroaryl containing 1-3 heteroatoms selected from N, O, S, B, Si, and NH2;

[0089] In certain embodiments, the compounds of the present invention satisfy at least one of the following conditions, and the compounds of the present invention satisfy one, two, three, or four of the following conditions:

[0090] (1).R 1 、R 2 and R 3 At least one group is selected from R A1 ;

[0091] (2).R 4 and R 5 At least one group is selected from C 3-10 Cycloalkyl, C 2-6 Alkenyl, C 2-6 Alkynyl;

[0092] (3).R 4 、R 5 Together with the atoms to which they are attached, they form a 5-7 membered monocyclic carbocyclic ring or a 5-7 membered heterocyclic ring containing 1-3 heteroatoms selected from N, O, and S, wherein the carbocyclic ring or heterocyclic ring is optionally further substituted by 1-3 heteroatoms selected from R A3 substituted by a group, and R 1 Selected from R A1 or -O-halogenated C 1-4 alkyl;

[0093] (4).R 6 、R 7 、R 8 、R 9 、R 10 At least one group is selected from R A2 ; or R 6 With R 10 、R 10 With R 7 、R 7 With R 8 、R 8 With R 9 The group of and the atoms connected thereto together form a 4-7 membered carbocyclic ring or a 5-7 membered heterocycloalkyl containing 1-3 heteroatoms selected from N, O, S, B or an 8 membered carbocyclic ring or a 5-7 membered heterocycloalkyl containing 1 Si atom, wherein the carbocyclic ring or heterocycloalkyl is optionally further substituted by 1-3 atoms selected from =O, halogen, deuterium, CN, OH, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, deuterated C 1-4 Alkoxy and NH2 group substitution;

[0094] (5).R 2 、R 4 , L1 and the atoms to which they are connected together form a 5-7 membered carbocyclic ring or a 5-7 membered heterocyclic ring containing 1-3 heteroatoms selected from N, O, and S, wherein the carbocyclic ring or heterocyclic ring is optionally further surrounded by 1-3 heteroatoms selected from R A3 substituted by a group, and R 1 is not a heterocycloalkyl group;

[0095] (6) L1 is selected from O, NH, S, -CD2-, -CHD-, -CR L1 R L2 -、C 1-4 Alkyl, -C(O)-, S(O), S(O)2, wherein the alkyl group is optionally further R L1 replace;

[0096] (7) L2 is selected from O, NH, S, -CR L1 R L2 -、-CHR L2 -、-CDR L2 -, -C(O)-, S(O), S(O)2;

[0097] (8).R A4 Selected from -CH2-CR A4c =CR A4a R A4b 、-CH2-CH=CH-CH=CR A4a R A4b 、L3-R A4’ or selected from -CH(C 1-2 (alkyl)-CR A4c =CR A4a R A4b 、-C(C 1-2 alkyl)2-CR A4c =CR A4a R A4b ;

[0098] (9) X1 is selected from S;

[0099] (10).R L2 With R 9 Together with the atoms to which they are connected, they form a 5-7 membered carbocyclic ring or a 5-7 membered heterocyclic ring containing 1-3 heteroatoms selected from N, O, and S, wherein the carbocyclic ring or heterocyclic ring is optionally further surrounded by 1-3 heteroatoms selected from R A3 The group substitution;

[0100] In certain embodiments, the compounds of the present invention satisfy at least one of the following conditions. In certain embodiments, the compounds of the present invention satisfy one, two, three, or four of the following conditions:

[0101] (1).R 1 、R 2 and R 3 At least one group is selected from R A1 ;

[0102] (2).R 4 and R 5 At least one group is selected from C 3-10 Cycloalkyl, C 2-6 Alkenyl, C 2-6 Alkynyl;

[0103] (3).R 4 、R 5 Together with the atoms to which they are attached, they form a 5-7 membered monocyclic carbocyclic ring or a 5-7 membered heterocyclic ring containing 1-3 heteroatoms selected from N, O, and S, wherein the carbocyclic ring or heterocyclic ring is optionally further substituted by 1-3 heteroatoms selected from R A3 substituted by a group, and R 1 Selected from R A1 or -O-halogenated C 1-4 alkyl;

[0104] (4).R 6 、R 7 、R 8 、R 9 、R 10 At least one group is selected from R A2 ;

[0105] (5).R 2 、R 4 , L1 and the atoms to which they are connected together form a 5-7 membered carbocyclic ring, a 5-7 membered heterocyclic ring containing 1-3 heteroatoms selected from N, O, and S, wherein the carbocyclic ring or heterocyclic ring is optionally further substituted by 1-3 heteroatoms selected from R A3 substituted by a group, and R 1 is not a heterocycloalkyl group;

[0106] (6) L1 is selected from O, NH, S, -CD2-, -CHD-, -CR L1 R L2 -、C 1-4 Alkyl, -C(O)-, S(O), S(O)2, wherein the alkyl group is optionally further R L1 replace;

[0107] (7) L2 is selected from O, NH, S, -CR L1 R L2 -、-CHR L2 -、-CDR L2 -、-C(O)-、C 2-4 Alkyl, S(O), S(O)2, wherein the alkyl is 1-3 RL1 replace;

[0108] (8).R A4 Selected from -CH2-CR A4c =CR A4a R A4b 、L3-R A4’ or selected from -CH(C 1-2 (alkyl)-CR A4c =CR A4a R A4b 、-C(C 1-2 alkyl)2-CR A4c =CR A4a R A4b ;

[0109] (9).X1 is selected from S.

[0110] The compounds of the present invention satisfy at least one of the following conditions. In certain embodiments, the compounds of the present invention satisfy one, two, three or four of the following conditions:

[0111] (1).R 1 、R 2 and R 3 At least one group is selected from R A1 ;

[0112] (2).R 4 and R 5 At least one group is selected from C 3-10 Cycloalkyl, C 2-6 Alkenyl, C 2-6 Alkynyl;

[0113] (3).R 4 、R 5 Together with the atoms to which they are attached, they form a 5-7 membered monocyclic carbocyclic ring or a 5-7 membered heterocyclic ring containing 1-3 heteroatoms selected from N, O, and S, wherein the carbocyclic ring or heterocyclic ring is optionally further substituted by 1-3 heteroatoms selected from R A3 substituted by a group, and R 1 Selected from R A1 or -O-halogenated C 1-4 alkyl;

[0114] (4).R 6 、R 7 、R 8 、R 9 、R 10 At least one group is selected from R A2 ; or R 6 With R 10 、R 10 With R 7 、R7 With R 8 、R 8 With R 9 The group of and the atoms connected thereto together form a 4-7 membered carbocyclic ring or a 5-7 membered heterocycloalkyl containing 1-3 heteroatoms selected from N, O, S, B or an 8 membered carbocyclic ring or a 5-7 membered heterocycloalkyl containing 1 Si atom, wherein the carbocyclic ring or heterocycloalkyl is optionally further substituted by 1-3 atoms selected from =O, halogen, deuterium, CN, OH, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, deuterated C 1-4 Alkoxy and NH2 group substitution;

[0115] (5).R 2 、R 4 , L1 and the atoms to which they are connected together form a 5-7 membered carbocyclic ring or a 5-7 membered heterocyclic ring containing 1-3 heteroatoms selected from N, O, and S, wherein the carbocyclic ring or heterocyclic ring is optionally further surrounded by 1-3 heteroatoms selected from R A3 substituted by a group, and R 1 is not a heterocycloalkyl group;

[0116] (6) L1 is selected from O, NH, S, -CD2-, -CHD-, -CR L1 R L2 -、C 1-4 Alkyl, -C(O)-, S(O), S(O)2, wherein the alkyl group is optionally further R L1 replace;

[0117] (7) L2 is selected from O, NH, S, -CR L1 R L2 -、-CHR L2 -、-CDR L2 -, -C(O)-, S(O), S(O)2;

[0118] (8).R A4 Selected from -CH2-CH=CR A4a R A4b 、-CH2-CH=CH-CH=CR A4a R A4b 、L3-R A4’ or selected from -CH(C 1-2 (alkyl)-CR A4c =CR A4a R A4b 、-C(C 1-2 alkyl)2-CR A4c =CR A4a RA4b ;

[0119] (9) X1 is selected from S;

[0120] (10).R L2 With R 9 Together with the atoms to which they are connected, they form a 5-7 membered carbocyclic ring or a 5-7 membered heterocyclic ring containing 1-3 heteroatoms selected from N, O, and S, wherein the carbocyclic ring or heterocyclic ring is optionally further surrounded by 1-3 heteroatoms selected from R A3 The group substitution;

[0121] In certain embodiments, the compounds of the present invention satisfy at least one of the following conditions. In certain embodiments, the compounds of the present invention satisfy one, two, three, or four of the following conditions:

[0122] (1).R 1 、R 2 and R 3 At least one group is selected from R A1 ;

[0123] (2).R 4 and R 5 At least one group is selected from C 3-10 Cycloalkyl, C 2-6 Alkenyl, C 2-6 Alkynyl;

[0124] (3).R 4 、R 5 Together with the atoms to which they are attached, they form a 5-7 membered monocyclic carbocyclic ring or a 5-7 membered heterocyclic ring containing 1-3 heteroatoms selected from N, O, and S, wherein the carbocyclic ring or heterocyclic ring is optionally further substituted by 1-3 heteroatoms selected from R A3 substituted by a group, and R 1 Selected from R A1 or -O-halogenated C 1-4 alkyl;

[0125] (4).R 6 、R 7 、R 8 、R 9 、R 10 At least one group is selected from R A2 ;

[0126] (5).R 2 、R 4 , L1 and the atoms to which they are connected together form a 5-7 membered carbocyclic ring, a 5-7 membered heterocyclic ring containing 1-3 heteroatoms selected from N, O, and S, wherein the carbocyclic ring or heterocyclic ring is optionally further substituted by 1-3 heteroatoms selected from R A3 substituted by a group, and R 1 is not a heterocycloalkyl group;

[0127] (6) L1 is selected from O, NH, S, -CD2-, -CHD-, -CR L1 R L2 -、C 1-4 Alkyl, -C(O)-, S(O), S(O)2, wherein the alkyl group is optionally further R L1 replace;

[0128] (7) L2 is selected from O, NH, S, -CR L1 R L2 -、-CHR L2 -、-CDR L2 -、-C(O)-、C 2-4 Alkyl, S(O), S(O)2, wherein the alkyl is 1-3 R L1 replace;

[0129] (8).R A4 Selected from -CH2-CH=CR A4a R A4b 、L3-R A4’ or selected from -CH(C 1-2 (alkyl)-CR A4c =CR A4a R A4b 、-C(C 1-2 alkyl)2-CR A4c =CR A4a R A4b ;

[0130] (9) X1 is selected from S;

[0131] In certain embodiments, the compounds of the present invention satisfy at least one of the following conditions. In certain embodiments, the compounds of the present invention satisfy one, two, three, or four of the following conditions:

[0132] (1).R 1 、R 2 and R 3 At least one group is selected from R A1 ;

[0133] (2).R 4 and R 5 At least one group is selected from C 3-7 Cycloalkyl, C 2-4 Alkenyl, C 2-4 Alkynyl;

[0134] (3).R 7 、R 8 At least one group is selected from R A2 ;

[0135] (4) L2 is selected from -CR L1 R L2 -、-CHR L2 -、-CDR L2 -, -C(O)-;

[0136] (5).R 7 With R 8 、R 8 With R 9 The group of and the atoms connected thereto together form a 4-7 membered carbocyclic ring, a 5-7 membered heterocycloalkyl containing 1-3 heteroatoms selected from N, O, S, B, or an 8 membered carbocyclic ring or a 5-7 membered heterocycloalkyl containing 1 Si atom, wherein the carbocyclic ring or heterocycloalkyl is optionally further substituted by 1-3 atoms selected from =O, halogen, deuterium, CN, OH, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, deuterated C 1-4 Alkoxy and NH2 group substitution;

[0137] In certain embodiments, the compounds of the present invention satisfy at least one of the following conditions. In certain embodiments, the compounds of the present invention satisfy one, two, three, or four of the following conditions:

[0138] (1).R 1 、R 2 and R 3 At least one group is selected from R A1 ;

[0139] (2).R 7 、R 8 At least one group is selected from R A2 ;

[0140] (3).R 7 With R 8 、R 8 With R 9 A group of the group and the atoms connected thereto together form a 4-7 membered carbocyclic ring, a 5-7 membered heterocycloalkyl containing 1-3 heteroatoms selected from N, O, S, B, or an 8-membered carbocyclic ring or a 5-7 membered heterocycloalkyl containing 1 Si atom, wherein the carbocyclic ring or heterocycloalkyl is optionally further substituted by 1-3 atoms selected from =O, halogen, deuterium, CN, OH, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, deuterated C1-4 Alkoxy and NH2 group substitution;

[0141] In certain embodiments, the compounds of the present invention satisfy at least one of the following conditions. In certain embodiments, the compounds of the present invention satisfy one, two, three, or four of the following conditions:

[0142] (1).R 7 、R 8 At least one group is selected from R A2 ;

[0143] (2).R 4 and R 5 At least one group is selected from C 3-10 Cycloalkyl, C 2-6 Alkenyl, C 2-6 Alkynyl;

[0144] (3).R 4 、R 5 Together with the atoms to which they are attached, they form a 5-7 membered monocyclic carbocyclic ring or a 5-7 membered heterocyclic ring containing 1-3 heteroatoms selected from N, O, and S, wherein the carbocyclic ring or heterocyclic ring is optionally further substituted by 1-3 heteroatoms selected from R A3 The group substitution;

[0145] (4).R 2 、R 4 Together with the atoms to which they are connected, they form a 5-7 membered carbocyclic ring or a 5-7 membered heterocyclic ring containing 1-3 heteroatoms selected from N, O, and S, wherein the carbocyclic ring or heterocyclic ring is optionally further surrounded by 1-3 heteroatoms selected from R A3 The group substitution;

[0146] (5). L2 is selected from -CR L1 R L2 -、-CHR L2 -、-CDR L2 -、-C(O)-、C 2-4 Alkyl, the alkyl group is 1-3 R L1 replace;

[0147] (6).R 7 With R 8 、R 8 With R 9 The group of and the atoms connected thereto together form a 4-7 membered carbocyclic ring, a 5-7 membered heterocycloalkyl containing 1-3 heteroatoms selected from N, O, S, B, or an 8 membered carbocyclic ring or a 5-7 membered heterocycloalkyl containing 1 Si atom, wherein the carbocyclic ring or heterocycloalkyl is optionally further substituted by 1-3 atoms selected from =O, halogen, deuterium, CN, OH, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, deuterated C 1-4 Alkoxy and NH2 group substitution;

[0148] In certain embodiments, the compounds of the present invention satisfy at least one of the following conditions. In certain embodiments, the compounds of the present invention satisfy one, two, three, or four of the following conditions:

[0149] (1).R 1 Selected from R A1 ;

[0150] (2).R 4 and R 5 At least one group is selected from cyclopropyl, vinyl, and ethynyl;

[0151] (3).R 4 、R 5 Together with the atoms to which it is attached, it forms phenyl, cyclohexyl, cyclopentyl, thienyl, furanyl, pyrrolyl, pyrazolyl, isoxazolyl;

[0152] (4).R 7 、R 8 At least one group is selected from R A2 ;

[0153] (5).R 2 、R 4 , L1 and the atoms to which it is attached together form a cyclohexyl group or a phenyl group;

[0154] (6) L1 is selected from O;

[0155] (7) L2 is selected from -C(O)-, -CHF-, -CF2-, -C(CH3)2-;

[0156] (8).R 7 With R 8 、R 8 With R 9 A group of the group and the atoms connected thereto together form a 4-7 membered carbocyclic ring or an 8 membered carbocyclic ring or a 5-7 membered heterocycloalkyl containing 1 Si atom, wherein the carbocyclic ring or heterocycloalkyl is optionally further substituted by 1-3 atoms selected from =O, F, Cl, deuterium, OH, C 1-2 Alkyl, halogenated C 1-2 Alkyl radical substitution;

[0157] In certain embodiments, R 6 With R 10 、R 10 With R 7 、R 7 With R8 、R 8 With R 9 A group of atoms in the 4-8 Cycloalkyl, 5-7 membered heterocycloalkyl containing 1-3 heteroatoms selected from N, O, S, B, Si, wherein the cycloalkyl and heterocycloalkyl are optionally further substituted by 1-3 heteroatoms selected from =O, Halogen, deuterium, CN, OH, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, deuterated C 1-4 Alkoxy, 5-7 membered heterocycloalkyl containing 1-3 heteroatoms selected from N, O, S, B, Si, 5-7 membered heteroaryl containing 1-3 heteroatoms selected from N, O, S, B, Si, and NH2;

[0158] In certain embodiments, R 6 With R 10 、R 10 With R 7 、R 7 With R 8 、R 8 With R 9 A group of atoms in the 4-6 Monocyclic cycloalkyl, C 6-8 Bicyclic bridged cycloalkyl, C 6-8 Bicyclic and cycloalkyl, C 6-8 Bicyclic spiroalkyl, 5-7 membered heterocycloalkyl containing 1 Si heteroatom, the cycloalkyl and heterocycloalkyl are optionally further substituted by 1-3 groups selected from =O, Halogen, deuterium, CN, OH, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, deuterated C 1-4 Alkoxy and NH2 group substitution;

[0159] In certain embodiments, R 6 With R 10 、R 10 With R 7 、R 7 With R 8 、R 8 With R 9 A group of atoms in the 4-6 Monocyclic cycloalkyl, said cycloalkyl optionally further substituted by 1-3 groups selected from =O, Halogen, deuterium, CN, OH, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, deuterated C 1-4 Alkoxy and NH2 group substitution;

[0160] In certain embodiments, R 7 With R 8 and its connected atoms together form C 4-8 Cycloalkyl, said cycloalkyl optionally further substituted by 1-3 groups selected from =O, Halogen, deuterium, CN, OH, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, deuterated C 1-4 Alkoxy, 5-7 membered heterocycloalkyl containing 1-3 heteroatoms selected from N, O, S, B, Si, 5-7 membered heteroaryl containing 1-3 heteroatoms selected from N, O, S, B, Si, and NH2;

[0161] In certain embodiments, R 7 With R 8 and its connected atoms together form C 4-6 Monocyclic cycloalkyl, C 6-8 Bicyclic bridged cycloalkyl, C 6-8 Bicyclic and cycloalkyl, C 6-8 Bicyclic spirocycloalkyl, the cycloalkyl group is optionally further substituted by 1-3 groups selected from =O, Halogen, deuterium, CN, OH, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, deuterated C 1-4 Alkoxy and NH2 group substitution;

[0162] In certain embodiments, R 7 With R 8 and its connected atoms together form C 4-6 Monocyclic cycloalkyl, said cycloalkyl optionally further substituted by 1-3 groups selected from =O, Halogen, deuterium, CN, OH, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, C 1-4Alkoxy, halogenated C 1-4 Alkoxy, deuterated C 1-4 Alkoxy and NH2 group substitution;

[0163] In certain embodiments, R 6 With R 10 、R 10 With R 7 、R 7 With R 8 、R 8 With R 9 A group of and the atoms connected thereto together form cyclobutyl, cyclopentyl, cyclohexyl, cyclobutenyl, cyclopentenyl, cyclohexenyl, Optionally further substituted by 1-3 selected from halogen, deuterium, CN, OH, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, deuterated C 1-4 Alkoxy and NH2 group substitution;

[0164] In certain embodiments, R 7 With R 8 and the atoms to which they are attached together form cyclobutyl, cyclopentyl, cyclohexyl, cyclobutenyl, cyclopentenyl, cyclohexenyl, Optionally further substituted by 1-3 selected from halogen, deuterium, CN, OH, C 1-3 Alkyl, halogenated C 1-3 Alkyl, deuterated C 1-3 Alkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, deuterated C 1-3 Alkoxy and NH2 groups are substituted.

[0165] Specifically, in the first technical solution, the present invention provides a compound represented by formula (I) or (Ia), its stereoisomers, deuterated substances, solvates, or pharmaceutically acceptable salts,

[0166] in,

[0167] R 1 、R 2 、R 3 Each independently selected from H, deuterium, R A1 、-O-halogenated C 1-4 Alkyl, -NH-halogenated C 1-4 Alkyl, -OC1-4 Alkyl, C 1-4 Alkoxy, C 5-6 Alkoxy, halogen, cyano, nitro, C 1-4 Alkyl, C 2-6 Alkenyl, -NH-C 1-4 Alkyl, -N(C 1-4 Alkyl)2, -NH-C 3-10 Cycloalkyl, -NHC(O)C 1-4 Alkyl or 4-10 membered heterocycloalkyl containing 1-3 heteroatoms selected from N, O, S, wherein the alkyl, alkoxy, cycloalkyl, heterocycloalkyl is optionally further substituted by 1-3 heteroatoms selected from halogen, D, CN, OH, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, deuterated C 1-4 Alkoxy, C 3-10 Cycloalkyl, 4-6 membered heterocycloalkyl containing 1-3 heteroatoms selected from N, O, S, phenyl, and NH2, provided that R 1 、R 2 and R 3 Not selected from H at the same time;

[0168] R A1 Selected from halogenated C 2-6 Alkenyl, C 2-6 Alkynyl, -O-(CH2) r -R a 、C 3-10 Cycloalkyl, 5-10 membered heteroaryl containing 1-3 heteroatoms selected from N, O, S, -C 1-4 Alkyl-R a 、-C 1-4 Alkyl-OR a 、-C 1-4 Alkyl-NR b R a 、-NR b -S(O)2-R a 、-NR b -S(O)2-NR b R a 、-O-NR b R a 、-NH-OR b or -Se-(CH2) r -R a The alkynyl, heteroaryl, alkyl or cycloalkyl group is optionally further substituted by 1-3 halogen, deuterium, CN, OH, C 1-4 Alkyl, halogenated C 1-4Alkyl, deuterated C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, deuterated C 1-4 Alkoxy and NH2 group substitution;

[0169] Each R a Selected from CN, halogenated C 1-6 Alkyl, C 3-10 Cycloalkyl, 4-10 membered heterocycloalkyl containing 1-3 heteroatoms selected from N, O, S, 6-10 membered aryl, 5-10 membered heteroaryl containing 1-3 heteroatoms selected from N, O, S, -C(O)-R a1 The alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl groups are optionally further substituted by 1-3 groups selected from halogen, =O, deuterium, CN, OH, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, deuterated C 1-4 Alkoxy and NH2 group substitution;

[0170] Each R b Selected from H, deuterium, C 1-4 Alkyl, C 3-6 Cycloalkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 alkyl;

[0171] R a1 Selected from OH, NH2, -NHC 1-4 Alkyl, -N(C 1-4 Alkyl)2, -NHC 3-10 Cycloalkyl, C 1-4 Alkoxy, C 1-6 Alkyl, C 3-10 Cycloalkyl, 6-10 membered aryl, 5-10 membered heteroaryl containing 1-3 heteroatoms selected from N, O, S;

[0172] X is selected from CR 10 or N;

[0173] X1 is selected from O, S;

[0174] R 4 、R 5 Each independently selected from H, deuterium, C 3-10 Cycloalkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, halogen, amino, -NH-C 1-4 Alkyl, -N(C 1-4 Alkyl)2, C1-4 Alkyl, halogenated C 1-4 Alkyl, 4-10 membered heterocycloalkyl containing 1-3 heteroatoms selected from N, O, and S, 5-10 membered heteroaryl, and 6-10 membered aryl containing 1-3 heteroatoms selected from N, O, and S;

[0175] R 6 、R 7 、R 8 、R 9 、R 10 Each independently selected from H, deuterium, R A2 , halogen, OH, CN, amino, C 1-4 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-4 Alkoxy, halogenated C 1-4 Alkyl, -NH-C 1-4 Alkyl, -N(C 1-4 Alkyl)2, -S(O)R c 、-S(O) 2 R c 、-C(O)R c 、-C(O)OR c 、-C(O)N(R c )2、-OC(O)R c The alkyl, alkenyl, alkynyl, and alkoxy groups are optionally further substituted by 1 to 3 groups selected from halogen, deuterium, CN, OH, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, deuterated C 1-4 Alkoxy and NH2 group substitution;

[0176] R A2 Selected from -(CH2) r -(4-10 membered heterocycloalkyl containing 1-3 heteroatoms selected from N, O, S, Si), or -(CH2) r -(5-10 membered heteroaryl containing 1-3 heteroatoms selected from N, O, S), -P(O)(R c )2、-Si(R c )3, -SF5, N3, B(OH)2, or -S(O)(=NH)R c The heterocycloalkyl and heteroaryl groups are optionally further substituted by 1-3 groups selected from halogen, =O, D, CN, OH, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, C 1-4Alkoxy, halogenated C 1-4 Alkoxy, C 3-6 Cycloalkyl, 4-7 membered heterocycloalkyl containing 1-3 heteroatoms selected from N, O, S, deuterated C 1-4 Alkoxy and NH2 group substitution;

[0177] Each R c Each independently selected from H, OH, C 1-4 Alkyl, C 3-7 Cycloalkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, deuterated C 1-4 Alkoxy, or NH2;

[0178] Each r is independently selected from 0, 1, 2 or 3;

[0179] L1 is selected from a bond, O, NH, S, -CD2-, -CHD-, -CR L1 R L2 -、C 1-4 Alkyl, -C(O)-, S(O), S(O)2, wherein the alkyl group is optionally further R L1 replace;

[0180] L2 is selected from O, NH, S, -CH2-, -CD2-, -CHD-, -CR L1 R L2 -、-CHR L2 -、-CDR L2 -、C 2-4 Alkyl, -C(O)-, S(O), S(O)2, wherein the alkyl group is optionally further substituted with 1-3 R L1 replace;

[0181] R A4 Selected from -CH2-C 1-4 Alkyl-C 3-6 Cycloalkyl, -CH2-CR A4c =CR A4a R A4b 、-CH2-CH=CH-CH=CR A4a R A4b 、-CH(C 1-2 (alkyl)-CR A4c =CR A4a R A4b 、-C(C 1-2 alkyl)2-CR A4c =CR A4a R A4b 、L3-R A4’ ;

[0182] R A4c Selected from H, halogen, deuterium, CN, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, deuterated C 1-4 Alkoxy and NH2;

[0183] R A4a 、R A4b Together with the carbon atom to which it is attached, it forms a 3-6 membered monocyclic carbon ring, C 7-10 Spirocarbon ring, C 7-10 Bridged carbon ring, C 7-10 A 6-membered cyclic carbon ring, or a 4-7-membered heterocycle containing 1-3 heteroatoms selected from N, O, and S, wherein the carbon ring or heterocycle is optionally substituted by 1-3 heteroatoms selected from halogen, =O, deuterium, CN, OH, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, -COC 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, deuterated C 1-4 Alkoxy and NH2 group substituted; L3 is selected from C 3-6 Cycloalkyl, or -CH(C 1-2 alkyl)-C 1-4 Alkyl, the cycloalkyl group is optionally substituted by 1-3 R L3 replace;

[0184] Each R L3 independently selected from halogen, =O, deuterium, CN, OH, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, -COC 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, deuterated C 1-4 Alkoxy and NH2;

[0185] Optionally, two R on adjacent ring atoms L3 and the atoms to which they are attached together form a 5-7 membered carbocyclic ring or a 5-7 membered heterocyclic ring containing 1-3 heteroatoms selected from N, O, and S;

[0186] R A4’ Selected from H, C 3-6Cycloalkyl, 5-10 membered heteroaryl containing 1-3 heteroatoms selected from N, O, S, or 4-7 membered heterocycloalkyl containing 1-3 heteroatoms selected from N, O, S, wherein the cycloalkyl, heteroaryl and heterocycloalkyl are optionally further substituted by 1-3 halogen, deuterium, CN, OH, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, deuterated C 1-4 Alkoxy and NH2 group substitution;

[0187] R L1 、R L2 Each independently selected from halogen, OH, CN, amino, C 1-4 Alkyl, C 1-4 Alkoxy, C 3-6 Cycloalkyl, 4-6 membered heterocycloalkyl containing 1-3 heteroatoms selected from N, O, S;

[0188] Alternatively, R 2 、R 4 , L1 and the atoms to which they are connected together form a 5-7 membered carbocyclic ring, a 5-7 membered heterocyclic ring containing 1-3 heteroatoms selected from N, O, and S, wherein the carbocyclic ring or heterocyclic ring is optionally further substituted by 1-3 heteroatoms selected from R A3 The group substitution;

[0189] Alternatively, R 4 、R 5 Together with the atoms to which they are connected, they form a 5-7 membered monocyclic carbocyclic ring or a 5-7 membered heterocyclic ring containing 1-3 heteroatoms selected from N, O, and S, wherein the carbocyclic ring or heterocyclic ring is optionally substituted by 1-3 heteroatoms selected from R A3 The group substitution;

[0190] Alternatively, R L2 With R 9 Together with the atoms to which they are connected, they form a 5-7 membered carbocyclic ring or a 5-7 membered heterocyclic ring containing 1-3 heteroatoms selected from N, O, and S, wherein the carbocyclic ring or heterocyclic ring is optionally further surrounded by 1-3 heteroatoms selected from R A3 The group substitution;

[0191] Alternatively, R 6 With R 10 、R 10 With R 7 、R 7 With R 8 、R 8 With R 9The group of and the atoms connected thereto together form a 4-7 membered carbocyclic ring, a 5-7 membered heterocycloalkyl containing 1-3 heteroatoms selected from N, O, S, B, or an 8 membered carbocyclic ring or a 5-7 membered heterocycloalkyl containing 1 Si atom, wherein the carbocyclic ring or heterocycloalkyl is optionally further substituted by 1-3 atoms selected from =O, halogen, deuterium, CN, OH, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, deuterated C 1-4 Alkoxy and NH2 group substitution;

[0192] Each R A3 Each independently selected from =O, halogen, deuterium, CN, OH, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, deuterated C 1-4 Alkoxy and NH2 group substitution;

[0193] The condition is that the compound satisfies at least one of the following conditions:

[0194] (1).R 1 、R 2 and R 3 At least one group is selected from R A1 ;

[0195] (2).R 4 and R 5 At least one group is selected from C 3-10 Cycloalkyl, C 2-6 Alkenyl, C 2-6 Alkynyl;

[0196] (3).R 4 、R 5 Together with the atoms to which they are attached, they form a 5-7 membered monocyclic carbocyclic ring or a 5-7 membered heterocyclic ring containing 1-3 heteroatoms selected from N, O, and S, wherein the carbocyclic ring or heterocyclic ring is optionally further substituted by 1-3 heteroatoms selected from R A3 substituted by a group, and R 1 Selected from R A1 or -O-halogenated C 1-4 alkyl;

[0197] (4).R 6 、R 7 、R 8 、R 9 、R 10 At least one group is selected from R A2; or R 6 With R 10 、R 10 With R 7 、R 7 With R 8 、R 8 With R 9 The group of and the atoms connected thereto together form a 4-7 membered carbocyclic ring, a 5-7 membered heterocycloalkyl containing 1-3 heteroatoms selected from N, O, S, B, or an 8 membered carbocyclic ring or a 5-7 membered heterocycloalkyl containing 1 Si atom, wherein the carbocyclic ring or heterocycloalkyl is optionally further substituted by 1-3 atoms selected from =O, halogen, deuterium, CN, OH, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, deuterated C 1-4 Alkoxy and NH2 group substitution;

[0198] (5).R 2 、R 4 , L1 and the atoms to which they are connected together form a 5-7 membered carbocyclic ring or a 5-7 membered heterocyclic ring containing 1-3 heteroatoms selected from N, O, and S, wherein the carbocyclic ring or heterocyclic ring is optionally further surrounded by 1-3 heteroatoms selected from R A3 substituted by a group, and R 1 is not a heterocycloalkyl group;

[0199] (6) L1 is selected from O, NH, S, -CD2-, -CHD-, -CR L1 R L2 -、C 1-4 Alkyl, -C(O)-, S(O), S(O)2, wherein the alkyl group is optionally further R L1 replace;

[0200] (7) L2 is selected from O, NH, S, -CR L1 R L2 -、-CHR L2 -、-CDR L2 -, -C(O)-, S(O), S(O)2;

[0201] (8).R A4 Selected from -CH2-CR A4c =CR A4a R A4b 、-CH2-CH=CH-CH=CR A4a R A4b 、L3-R A4’ 、-CH(C 1-2 (alkyl)-CR A4c =CRA4a R A4b 、-C(C 1-2 alkyl)2-CR A4c =CR A4a R A4b ;

[0202] (9) X1 is selected from S;

[0203] (10).R L2 With R 9 Together with the atoms to which they are connected, they form a 5-7 membered carbocyclic ring or a 5-7 membered heterocyclic ring containing 1-3 heteroatoms selected from N, O, and S, wherein the carbocyclic ring or heterocyclic ring is optionally further surrounded by 1-3 heteroatoms selected from R A3 substituted by a group.

[0204] As an alternative to the first technical solution of the present invention, a compound represented by formula (I) or (Ia), a stereoisomer, deuterated substance, solvate, or pharmaceutically acceptable salt thereof is provided.

[0205] Among them, R 1 、R 2 、R 3 Each independently selected from H, deuterium, R A1 、-O-halogenated C 1-4 Alkyl, -NH-halogenated C 1-4 Alkyl, -OC 1-4 Alkyl, C 1-4 Alkoxy, halogen, cyano, nitro, C 1-4 Alkyl, C 2-6 Alkenyl, -NH-C 1-4 Alkyl, -N(C 1-4 Alkyl)2, -NH-C 3-10 Cycloalkyl, -NHC(O)C 1-4 Alkyl, or 4-10 membered heterocycloalkyl containing 1-3 heteroatoms selected from N, O, S or selected from C 5-6 Alkoxy, the alkyl, alkoxy, cycloalkyl, heterocycloalkyl optionally further 1-3 selected from halogen, D, CN, OH, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, deuterated C 1-4 Alkoxy, C 3-10 Cycloalkyl, 4-6 membered heterocycloalkyl containing 1-3 heteroatoms selected from N, O, S, phenyl, and NH2, provided that R 1 、R 2 and R 3Not selected from H at the same time;

[0206] R A1 Selected from halogenated C 2-6 Alkenyl, C 2-6 Alkynyl, 5-10 membered heteroaryl containing 1-3 heteroatoms selected from N, O, S, -C 1-4 Alkyl-R a 、-C 1-4 Alkyl-OR a 、-C 1-4 Alkyl-NR b R a 、-NR b -S(O)2-R a 、-NR b -S(O)2-NR b R a or R A1 Selected from -O-NR b R a 、-NH-OR b The alkynyl, heteroaryl, and alkyl groups are optionally further substituted by 1 to 3 groups selected from halogen, deuterium, CN, OH, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, deuterated C 1-4 Alkoxy and NH2 group substitution;

[0207] Each R a Selected from CN, halogenated C 1-6 Alkyl, C 3-10 Cycloalkyl, 4-10 membered heterocycloalkyl containing 1-3 heteroatoms selected from N, O, S, 6-10 membered aryl, 5-10 membered heteroaryl containing 1-3 heteroatoms selected from N, O, S, -C(O)-R a1 The alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl groups are optionally further substituted by 1-3 groups selected from halogen, =O, deuterium, CN, OH, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, deuterated C 1-4 Alkoxy and NH2 group substitution;

[0208] Each R b Selected from H, deuterium, C 1-4 Alkyl, C 3-6 Cycloalkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 alkyl;

[0209] R a1 Selected from OH, NH2, -NHC 1-4 Alkyl, -N(C 1-4 Alkyl)2, -NHC 3-10 Cycloalkyl, C 1-4 Alkoxy, C 1-6 Alkyl, C 3-10 Cycloalkyl, 6-10 membered aryl, 5-10 membered heteroaryl containing 1-3 heteroatoms selected from N, O, S;

[0210] X is selected from CR 10 or N;

[0211] X1 is selected from O, S;

[0212] R 4 、R 5 Each independently selected from H, deuterium, C 3-10 Cycloalkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, halogen, amino, -NH-C 1-4 Alkyl, -N(C 1-4 Alkyl)2, C 1-4 Alkyl, halogenated C 1-4 Alkyl, 4-10 membered heterocycloalkyl containing 1-3 heteroatoms selected from N, O, and S, 5-10 membered heteroaryl, and 6-10 membered aryl containing 1-3 heteroatoms selected from N, O, and S;

[0213] R 6 、R 7 、R 8 、R 9 、R 10 Each independently selected from H, deuterium, R A2 , halogen, OH, CN, amino, C 1-4 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-4 Alkoxy, halogenated C 1-4 Alkyl, -NH-C 1-4 Alkyl, -N(C 1-4 Alkyl)2, -S(O)R c 、-S(O) 2 R c 、-C(O)R c 、-C(O)OR c 、-C(O)N(R c )2、-OC(O)R c The alkyl, alkenyl, alkynyl, and alkoxy groups are optionally further substituted by 1 to 3 groups selected from halogen, deuterium, CN, OH, C 1-4Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, deuterated C 1-4 Alkoxy and NH2 group substitution;

[0214] R A2 Selected from -(CH2) r -(4-10 membered heterocycloalkyl containing 1-3 heteroatoms selected from N, O, S, Si), or -(CH2) r -(5-10 membered heteroaryl containing 1-3 heteroatoms selected from N, O, S), -P(O)(R c )2、-Si(R c )3, -SF5, N3, B(OH)2, or -S(O)(=NH)R c The heterocycloalkyl and heteroaryl groups are optionally further substituted by 1-3 groups selected from halogen, =O, D, CN, OH, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, C 3-6 Cycloalkyl, 4-7 membered heterocycloalkyl containing 1-3 heteroatoms selected from N, O, S, deuterated C 1-4 Alkoxy and NH2 group substitution;

[0215] Each R c Each independently selected from H, OH, C 1-4 Alkyl, C 3-7 Cycloalkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, deuterated C 1-4 Alkoxy, or NH2;

[0216] Each r is independently selected from 0, 1, 2 or 3;

[0217] L1 is selected from a bond, O, NH, S, -CD2-, -CHD-, -CR L1 R L2 -、C 1-4 Alkyl, -C(O)-, S(O), S(O)2, wherein the alkyl group is optionally further R L1 replace;

[0218] L2 is selected from O, NH, S, -CH2-, -CD2-, -CHD-, -CR L1 RL2 -、-CHR L2 -、-CDR L2 -、C 2-4 Alkyl, -C(O)-, S(O), S(O)2, wherein the alkyl group is optionally further substituted with 1-3 R L1 replace;

[0219] R A4 Selected from -CH2-C 1-4 Alkyl-C 3-6 Cycloalkyl, -CH2-CR A4c =CR A4a R A4b 、-CH2-CH=CH-CH=CR A4a R A4b 、L3-R A4’ or selected from -CH(C 1-2 (alkyl)-CR A4c =CR A4a R A4b 、-C(C 1-2 alkyl)2-CR A4c =CR A4a R A4b ; or R A4 Selected from -CH2-C 1-4 Alkyl-C 3-6 Cycloalkyl, -CH2-CF=CR A4a R A4b 、-CH2-C(CH3)=CR A4a R A4b 、-CH2-CH=CR A4a R A4b 、-CH2-CH=CH-CH=CR A4a R A4b 、L3-R A4’ or selected from -CHCH3-CH=CR A4a R A4b 、-C(C 1-2 alkyl)2-CH=CR A4a R A4b 、-CH2-C(CN)=CR A4a R A4b ; or R A4 Selected from -CH2-C 1-4 Alkyl-C 3-6 Cycloalkyl, -CH2-CH=CR A4a R A4b 、-CH2-CH=CH-CH=CR A4a R A4b 、L3-R A4’or selected from -CHCH3-CH=CR A4a R A4b ;

[0220] R A4c Selected from H, halogen, deuterium, CN, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, deuterated C 1-4 Alkoxy and NH2;

[0221] R A4a 、R A4b Together with the carbon atom to which it is attached, it forms a 3-6 membered monocyclic carbon ring, C 7-10 Spirocarbon ring, C 7-10 Bridged carbon ring, C 7-10 A 4-7 membered heterocyclic ring containing 1-3 heteroatoms selected from N, O, and S, or a 6-membered 4-7 membered heterocyclic ring, wherein the carbocyclic ring or heterocyclic ring is optionally substituted by 1-3 heteroatoms selected from halogen, =O, deuterium, CN, OH, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, -COC 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, deuterated C 1-4 Alkoxy and NH2 group substitution;

[0222] L3 is selected from C 3-6 Cycloalkyl, or -CH(C 1-2 alkyl)-C 1-4 Alkyl, the cycloalkyl group is optionally substituted by 1-3 R L3 replace;

[0223] Each R L3 independently selected from halogen, =O, deuterium, CN, OH, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, -COC 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, deuterated C 1-4 Alkoxy and NH2;

[0224] Optionally, two R on adjacent ring atoms L3 and the atoms to which they are attached together form a 5-7 membered carbocyclic ring or a 5-7 membered heterocyclic ring containing 1-3 heteroatoms selected from N, O, and S;

[0225] R A4’Selected from H, C 3-6 Cycloalkyl, 5-10 membered heteroaryl containing 1-3 heteroatoms selected from N, O, S, or 4-7 membered heterocycloalkyl containing 1-3 heteroatoms selected from N, O, S, wherein the cycloalkyl, heteroaryl and heterocycloalkyl are optionally further substituted by 1-3 halogen, deuterium, CN, OH, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, deuterated C 1-4 Alkoxy and NH2 group substitution;

[0226] R L1 、R L2 Each independently selected from halogen, OH, CN, amino, C 1-4 Alkyl, C 1-4 Alkoxy, C 3-6 Cycloalkyl, 4-6 membered heterocycloalkyl containing 1-3 heteroatoms selected from N, O, S;

[0227] Alternatively, R 2 、R 4 , L1 and the atoms to which they are connected together form a 5-7 membered carbocyclic ring, a 5-7 membered heterocyclic ring containing 1-3 heteroatoms selected from N, O, and S, wherein the carbocyclic ring or heterocyclic ring is optionally further substituted by 1-3 heteroatoms selected from R A3 The group substitution;

[0228] Alternatively, R 4 、R 5 Together with the atoms to which they are connected, they form a 5-7 membered monocyclic carbocyclic ring or a 5-7 membered heterocyclic ring containing 1-3 heteroatoms selected from N, O, and S, wherein the carbocyclic ring or heterocyclic ring is optionally substituted by 1-3 heteroatoms selected from R A3 The group substitution;

[0229] Alternatively, R L2 With R 9 Together with the atoms to which they are connected, they form a 5-7 membered carbocyclic ring or a 5-7 membered heterocyclic ring containing 1-3 heteroatoms selected from N, O, and S, wherein the carbocyclic ring or heterocyclic ring is optionally further surrounded by 1-3 heteroatoms selected from R A3 The group substitution;

[0230] Alternatively, R 6 With R 10 、R 10 With R 7 、R 7 With R 8 、R 8 With R 9The group of and the atoms connected thereto together form a 4-7 membered carbocyclic ring or a 5-7 membered heterocycloalkyl or 8 membered carbocyclic ring containing 1-3 heteroatoms selected from N, O, S, and B, wherein the carbocyclic ring or heterocycloalkyl is optionally further substituted by 1-3 heteroatoms selected from =O, halogen, deuterium, CN, OH, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, deuterated C 1-4 Alkoxy and NH2 group substitution;

[0231] Each R A3 Each independently selected from =O, halogen, deuterium, CN, OH, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, deuterated C 1-4 Alkoxy and NH2 group substitution;

[0232] The condition is that the compound satisfies at least one of the following conditions:

[0233] (1).R 1 、R 2 and R 3 At least one group is selected from R A1 ;

[0234] (2).R 4 and R 5 At least one group is selected from C 3-10 Cycloalkyl, C 2-6 Alkenyl, C 2-6 Alkynyl;

[0235] (3).R 4 、R 5 Together with the atoms to which they are attached, they form a 5-7 membered monocyclic carbocyclic ring or a 5-7 membered heterocyclic ring containing 1-3 heteroatoms selected from N, O, and S, wherein the carbocyclic ring or heterocyclic ring is optionally further substituted by 1-3 heteroatoms selected from R A3 substituted by a group, and R 1 Selected from R A1 or -O-halogenated C 1-4 alkyl;

[0236] (4).R 6 、R 7 、R 8 、R 9 、R 10 At least one group is selected from R A2 ; or R 6 With R10 、R 10 With R 7 、R 7 With R 8 、R 8 With R 9 A group of the group and the atoms connected thereto together form a 4-7 membered carbocyclic ring or a 5-7 membered heterocycloalkyl containing 1-3 heteroatoms selected from N, O, S, and B, wherein the carbocyclic ring or heterocycloalkyl is optionally further substituted by 1-3 heteroatoms selected from =O, halogen, deuterium, CN, OH, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, deuterated C 1-4 Alkoxy and NH2 group substitution;

[0237] (5).R 2 、R 4 , L1 and the atoms to which they are connected together form a 5-7 membered carbocyclic ring or a 5-7 membered heterocyclic ring containing 1-3 heteroatoms selected from N, O, and S, wherein the carbocyclic ring or heterocyclic ring is optionally further surrounded by 1-3 heteroatoms selected from R A3 substituted by a group, and R 1 is not a heterocycloalkyl group;

[0238] (6) L1 is selected from O, NH, S, -CD2-, -CHD-, -CR L1 R L2 -、C 1-4 Alkyl, -C(O)-, S(O), S(O)2, wherein the alkyl group is optionally further R L1 replace;

[0239] (7) L2 is selected from O, NH, S, -CR L1 R L2 -、-CHR L2 -、-CDR L2 -, -C(O)-, S(O), S(O)2;

[0240] (8).R A4 Selected from -CH2-CF=CR A4a R A4b 、-CH2-CH=CH-CH=CR A4a R A4b 、L3-R A4’ or selected from -CHCH3-CH=CR A4a R A4b 、-CH2-C(CN)=CR A4a R A4b 、-CH(CH2CH3)-CH=CRA4a R A4b 、-C(CH3)2-CH=CR A4a R A4b 、-C(CH2CH3)2-CH=CR A4a R A4b ; or R A4 Selected from -CH2-C(CH3)=CR A4a R A4b 、-CH2-CH=CH-CH=CR A4a R A4b 、L3-R A4’ or selected from -CHCH3-CH=CR A4a R A4b ; or R A4 Selected from -CH2-CH=CR A4a R A4b 、-CH2-CH=CH-CH=CR A4a R A4b 、L3-R A4’ or selected from -CHCH3-CH=CR A4a R A4b ;

[0241] (9) X1 is selected from S;

[0242] (10).R L2 With R 9 Together with the atoms to which they are connected, they form a 5-7 membered carbocyclic ring or a 5-7 membered heterocyclic ring containing 1-3 heteroatoms selected from N, O, and S, wherein the carbocyclic ring or heterocyclic ring is optionally further surrounded by 1-3 heteroatoms selected from R A3 substituted by a group.

[0243] As an alternative to the first technical solution of the present invention, a compound represented by formula (I) or (Ia), a stereoisomer, deuterated substance, solvate, or pharmaceutically acceptable salt thereof is provided.

[0244] in,

[0245] R 1 、R 2 、R 3 Each independently selected from H, deuterium, R A1 、-O-halogenated C 1-4 Alkyl, -NH-halogenated C 1-4 Alkyl, -OC 1-4 Alkyl, C 1-4 Alkoxy, halogen, cyano, nitro, OH, C 1-4 Alkyl, C 2-6 Alkenyl, -NH-C 1-4 Alkyl, -N(C1-4 Alkyl)2, -NH-C 3-10 Cycloalkyl, -NHC(O)C 1-4 Alkyl, or 4-10 membered heterocycloalkyl containing 1-3 heteroatoms selected from N, O, S or selected from C 5-6 Alkoxy, the alkyl, alkoxy, cycloalkyl, heterocycloalkyl optionally further 1-3 selected from halogen, D, CN, OH, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, deuterated C 1-4 Alkoxy, C 3-10 Cycloalkyl, 4-6 membered heterocycloalkyl containing 1-3 heteroatoms selected from N, O, S, phenyl, and NH2, provided that R 1 、R 2 and R 3 Not selected from H at the same time;

[0246] R A1 Selected from halogenated C 2-6 Alkenyl, C 2-6 Alkynyl, 5-10 membered heteroaryl containing 1-3 heteroatoms selected from N, O, S, -C 1-4 Alkyl-R a 、-C 1-4 Alkyl-OR a 、-C 1-4 Alkyl-NR b R a 、-NR b -S(O)2-R a 、-NR b -S(O)2-NR b R a or R A1 Selected from -O-NR b R a 、-NH-OR b The alkynyl, heteroaryl, and alkyl groups are optionally further substituted by 1 to 3 groups selected from halogen, deuterium, CN, OH, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, deuterated C 1-4 Alkoxy and NH2 group substitution;

[0247] Each R a Selected from CN, halogenated C 1-6 Alkyl, C 3-10Cycloalkyl, 4-10 membered heterocycloalkyl containing 1-3 heteroatoms selected from N, O, S, 6-10 membered aryl, 5-10 membered heteroaryl containing 1-3 heteroatoms selected from N, O, S, -C(O)-R a1 The alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl groups are optionally further substituted by 1-3 groups selected from halogen, =O, deuterium, CN, OH, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, deuterated C 1-4 Alkoxy and NH2 group substitution;

[0248] Each R b Selected from H, deuterium, C 1-4 Alkyl, C 3-6 Cycloalkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 alkyl;

[0249] R a1 Selected from OH, NH2, -NHC 1-4 Alkyl, -N(C 1-4 Alkyl)2, -NHC 3-10 Cycloalkyl, C 1-4 Alkoxy, C 1-6 Alkyl, C 3-10 Cycloalkyl, 6-10 membered aryl, 5-10 membered heteroaryl containing 1-3 heteroatoms selected from N, O, S;

[0250] X is selected from CR 10 or N;

[0251] X1 is selected from O, S;

[0252] R 4 、R 5 Each independently selected from H, deuterium, C 3-10 Cycloalkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, halogen, amino, -NH-C 1-4 Alkyl, -N(C 1-4 Alkyl)2, C 1-4 Alkyl, halogenated C 1-4 Alkyl, 4-10 membered heterocycloalkyl containing 1-3 heteroatoms selected from N, O, and S, 5-10 membered heteroaryl, and 6-10 membered aryl containing 1-3 heteroatoms selected from N, O, and S;

[0253] R 6 、R 7 、R 8 、R9 、R 10 Each independently selected from H, deuterium, R A2 , halogen, OH, CN, amino, C 1-4 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-4 Alkoxy, halogenated C 1-4 Alkyl, -NH-C 1-4 Alkyl, -N(C 1-4 Alkyl)2, -S(O)R c 、-S(O) 2 R c 、-C(O)R c 、-C(O)OR c 、-C(O)N(R c )2、-OC(O)R c The alkyl, alkenyl, alkynyl, and alkoxy groups are optionally further substituted by 1 to 3 groups selected from halogen, deuterium, CN, OH, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, deuterated C 1-4 Alkoxy and NH2 group substitution;

[0254] Alternatively, R 7 With R 8 and the atoms to which they are attached together form a 4-7 membered carbocyclic ring or a 5-7 membered heterocycloalkyl containing 1-3 heteroatoms selected from N, O, S, and B, wherein the carbocyclic ring or heterocycloalkyl is optionally further substituted by 1-3 heteroatoms selected from ═O, halogen, deuterium, CN, OH, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, deuterated C 1-4 Alkoxy and NH2 group substitution;

[0255] R A2 Selected from -(CH2) r -(4-10 membered heterocycloalkyl containing 1-3 heteroatoms selected from N, O, S), or -(CH2) r -(5-10 membered heteroaryl containing 1-3 heteroatoms selected from N, O, S), -P(O)(R c )2、-Si(R c )3、-SF5、-S(O)(=NH)R cThe heterocycloalkyl and heterocycloaryl groups are optionally further substituted by 1-3 groups selected from halogen, D, CN, OH, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, deuterated C 1-4 Alkoxy and NH2 group substitution;

[0256] Each R c Each independently selected from H, OH, C 1-4 Alkyl, C 3-7 Cycloalkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, deuterated C 1-4 Alkoxy, or NH2;

[0257] Each r is independently selected from 0, 1, 2 or 3;

[0258] L1 is selected from a bond, O, NH, S, -CD2-, -CHD-, -CR L1 R L2 -、C 1-4 Alkyl, -C(O)-, S(O), S(O)2, wherein the alkyl group is optionally further R L1 replace;

[0259] L2 is selected from O, NH, S, -CH2-, -CD2-, -CHD-, -CR L1 R L2 -、-CHR L2 -、-CDR L2 -、C 2-4 Alkyl, -C(O)-, S(O), S(O)2, wherein the alkyl group is optionally further substituted with 1-3 R L1 replace;

[0260] R A4 Selected from -CH2-C 1-4 Alkyl-C 3-6 Cycloalkyl, -CH2-CH=CR A4a R A4b 、L3-R A4’ or selected from -CH(C 1-2 (alkyl)-CR A4c =CR A4a R A4b 、-C(C 1-2 alkyl)2-CR A4c =CR A4a RA4b ;

[0261] R A4a 、R A4b Together with the carbon atom to which it is attached, it forms a 3-6 membered carbocyclic ring;

[0262] L3 is selected from C 3-6 Cycloalkyl, -CH(C 1-2 alkyl)-C 1-4 alkyl;

[0263] R A4’ Selected from C 3-6 Cycloalkyl, 5-10 membered heteroaryl containing 1-3 heteroatoms selected from N, O, S, wherein the cycloalkyl and heteroaryl are optionally further substituted by 1-3 heteroatoms selected from halogen, deuterium, CN, OH, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, deuterated C 1-4 Alkoxy and NH2 group substitution;

[0264] R L1 、R L2 Each independently selected from halogen, OH, CN, amino, C 1-4 Alkyl, C 1-4 Alkoxy, C 3-6 Cycloalkyl, 4-6 membered heterocycloalkyl containing 1-3 heteroatoms selected from N, O, S;

[0265] Alternatively, R 2 、R 4 , L1 and the atoms to which they are connected together form a 5-7 membered carbocyclic ring, a 5-7 membered heterocyclic ring containing 1-3 heteroatoms selected from N, O, and S, wherein the carbocyclic ring or heterocyclic ring is optionally further substituted by 1-3 heteroatoms selected from R A3 The group substitution;

[0266] Alternatively, R 4 、R 5 Together with the atoms to which they are connected, they form a 5-7 membered monocyclic carbocyclic ring or a 5-7 membered heterocyclic ring containing 1-3 heteroatoms selected from N, O, and S, wherein the carbocyclic ring or heterocyclic ring is optionally substituted by 1-3 heteroatoms selected from R A3 The group substitution;

[0267] Alternatively, R L1 With R 9 Together with the atoms to which they are connected, they form a 5-7 membered carbocyclic ring or a 5-7 membered heterocyclic ring containing 1-3 heteroatoms selected from N, O, and S, wherein the carbocyclic ring or heterocyclic ring is optionally further surrounded by 1-3 heteroatoms selected from R A3 The group substitution;

[0268] Each R A3 Each independently selected from =O, halogen, deuterium, CN, OH, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, deuterated C 1-4 Alkoxy and NH2 group substitution;

[0269] The condition is that the compound satisfies one of the following conditions:

[0270] (1).R 1 、R 2 and R 3 At least one group is selected from R A1 ;

[0271] (2).R 4 and R 5 At least one group is selected from C 3-10 Cycloalkyl, C 2-6 Alkenyl, C 2-6 Alkynyl;

[0272] (3).R 4 、R 5 Together with the atoms to which they are attached, they form a 5-7 membered monocyclic carbocyclic ring or a 5-7 membered heterocyclic ring containing 1-3 heteroatoms selected from N, O, and S, wherein the carbocyclic ring or heterocyclic ring is optionally further substituted by 1-3 heteroatoms selected from R A3 substituted by a group, and R 1 Selected from R A1 or -O-halogenated C 1-4 alkyl;

[0273] (4).R 6 、R 7 、R 8 、R 9 、R 10 At least one group is selected from R A2 ;

[0274] (5).R 2 、R 4 , L1 and the atoms to which they are connected together form a 5-7 membered carbocyclic ring, a 5-7 membered heterocyclic ring containing 1-3 heteroatoms selected from N, O, and S, wherein the carbocyclic ring or heterocyclic ring is optionally further substituted by 1-3 heteroatoms selected from R A3 substituted by a group, and R 1 is not a heterocycloalkyl group;

[0275] (6) L1 is selected from O, NH, S, -CD2-, -CHD-, -CR L1R L2 -、C 1-4 Alkyl, -C(O)-, S(O), S(O)2, wherein the alkyl group is optionally further R L1 replace;

[0276] (7) L2 is selected from O, NH, S, -CR L1 R L2 -、-CHR L2 -、-CDR L2 -、-C(O)-、C 2-4 Alkyl, S(O), S(O)2, wherein the alkyl is 1-3 R L1 replace;

[0277] (8).R A4 Selected from -CH2-CH=CR A4a R A4b 、L3-R A4’ or selected from -CH(C 1-2 (alkyl)-CR A4c =CR A4a R A4b 、-C(C 1-2 alkyl)2-CR A4c =CR A4a R A4b ;

[0278] (9).X1 is selected from S.

[0279] The second technical solution of the present invention provides a compound represented by formula (Ib), its stereoisomers, deuterated substances, solvates, deuterated substances, or pharmaceutically acceptable salts,

[0280] in,

[0281] R 1 、R 2 、R 3 Each independently selected from H, deuterium, R A1 、-O-halogenated C 1-4 Alkyl, -NH-halogenated C 1-4 Alkyl, -OC 1-4 Alkyl, C 1-4 Alkoxy, halogen, cyano, nitro, OH, C 1-4 Alkyl, C 2-6 Alkenyl, -NH-C 1-4 Alkyl, -N(C 1-4 Alkyl)2, -NH-C 3-10 Cycloalkyl, -NHC(O)C 1-4 Alkyl, or 4-10 membered heterocycloalkyl containing 1-3 heteroatoms selected from N, O, S or selected from C5-6 Alkoxy, the alkyl, alkoxy, cycloalkyl, heterocycloalkyl optionally further 1-3 selected from halogen, D, CN, OH, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, deuterated C 1-4 Alkoxy, C 3-10 Cycloalkyl, 4-6 membered heterocycloalkyl containing 1-3 heteroatoms selected from N, O, S, phenyl, and NH2, provided that R 1 、R 2 and R 3 Not selected from H at the same time;

[0282] R A1 Selected from halogenated C 2-6 Alkenyl, C 2-6 Alkynyl, 5-10 membered heteroaryl containing 1-3 heteroatoms selected from N, O, S, -C 1-4 Alkyl-R a 、-C 1-4 Alkyl-OR a 、-C 1-4 Alkyl-NR b R a 、-NR b -S(O)2-R a 、-NR b -S(O)2-NR b R a The alkynyl, heteroaryl, and alkyl groups are optionally further substituted by 1 to 3 groups selected from halogen, deuterium, CN, OH, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, deuterated C 1-4 Alkoxy and NH2 group substitution;

[0283] Each R a Selected from CN, halogenated C 1-6 Alkyl, C 3-10 Cycloalkyl, 4-10 membered heterocycloalkyl containing 1-3 heteroatoms selected from N, O, S, 6-10 membered aryl, 5-10 membered heteroaryl containing 1-3 heteroatoms selected from N, O, S, -C(O)-R a1 The alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl groups are optionally further substituted by 1-3 groups selected from halogen, =O, deuterium, CN, OH, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, deuterated C 1-4 Alkoxy and NH2 group substitution;

[0284] Each R b Selected from H, deuterium, C 1-4 Alkyl, C 3-6 Cycloalkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 alkyl;

[0285] R a1 Selected from OH, NH2, -NHC 1-4 Alkyl, -N(C 1-4 Alkyl)2, -NHC 3-10 Cycloalkyl, C 1-4 Alkoxy, C 1-6 Alkyl, C 3-10 Cycloalkyl, 6-10 membered aryl, 5-10 membered heteroaryl containing 1-3 heteroatoms selected from N, O, S;

[0286] X is selected from CR 10 or N;

[0287] R 4 、R 5 Each independently selected from H, deuterium, C 3-10 Cycloalkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, halogen, amino, -NH-C 1-4 Alkyl, -N(C 1-4 Alkyl)2, C 1-4 Alkyl, halogenated C 1-4 Alkyl, 4-10 membered heterocycloalkyl containing 1-3 heteroatoms selected from N, O, and S, 5-10 membered heteroaryl, and 6-10 membered aryl containing 1-3 heteroatoms selected from N, O, and S;

[0288] R 6 、R 7 、R 8 、R 9 、R 10 Each independently selected from H, deuterium, R A2 , halogen, OH, CN, amino, C 1-4 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-4 Alkoxy, halogenated C 1-4 Alkyl, -NH-C 1-4 Alkyl, -N(C 1-4 Alkyl)2, -S(O)R c、-S(O) 2 R c 、-C(O)R c 、-C(O)OR c 、-C(O)N(R c )2、-OC(O)R c The alkyl, alkenyl, alkynyl, and alkoxy groups are optionally further substituted by 1 to 3 groups selected from halogen, deuterium, CN, OH, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, deuterated C 1-4 Alkoxy and NH2 group substitution;

[0289] Alternatively, R 7 With R 8 and the atoms to which they are attached together form a 4-7 membered carbocyclic ring or a 5-7 membered heterocycloalkyl containing 1-3 heteroatoms selected from N, O, S, and B, or an 8 membered carbocyclic ring or a 5-7 membered heterocycloalkyl containing 1 Si atom, wherein the carbocyclic ring or heterocycloalkyl is optionally further substituted by 1-3 atoms selected from ═O, halogen, deuterium, CN, OH, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, deuterated C 1-4 Alkoxy and NH2 group substitution;

[0290] R A2 Selected from -(CH2) r -(4-10 membered heterocycloalkyl containing 1-3 heteroatoms selected from N, O, S), or -(CH2) r -(5-10 membered heteroaryl containing 1-3 heteroatoms selected from N, O, S), -P(O)(R c )2、-Si(R c )3、-SF5、-S(O)(=NH)R c The heterocycloalkyl and heterocycloaryl groups are optionally further substituted by 1-3 groups selected from halogen, D, CN, OH, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, deuterated C 1-4 Alkoxy and NH2 group substitution;

[0291] Each R c Each independently selected from H, OH, C1-4 Alkyl, C 3-7 Cycloalkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, deuterated C 1-4 Alkoxy, or NH2;

[0292] Each r is independently selected from 0, 1, 2 or 3;

[0293] L1 is selected from a bond, O, NH, S, -CD2-, -CHD-, -CR L1 R L2 -、C 1-4 Alkyl, -C(O)-, S(O), S(O)2, wherein the alkyl group is optionally further R L1 replace;

[0294] L2 is selected from O, NH, S, -CH2-, -CD2-, -CHD-, -CR L1 R L2 -、-CHR L2 -、-CDR L2 -、C 2-4 Alkyl, -C(O)-, S(O), S(O)2, wherein the alkyl group is optionally further substituted with 1-3 R L1 replace;

[0295] R L1 、R L2 Each independently selected from halogen, OH, CN, amino, C 1-4 Alkyl, C 1-4 Alkoxy, C 3-6 Cycloalkyl, 4-6 membered heterocycloalkyl containing 1-3 heteroatoms selected from N, O, S;

[0296] Alternatively, R 2 、R 4 , L1 and the atoms to which they are connected together form a 5-7 membered carbocyclic ring, a 5-7 membered heterocyclic ring containing 1-3 heteroatoms selected from N, O, and S, wherein the carbocyclic ring or heterocyclic ring is optionally further substituted by 1-3 heteroatoms selected from R A3 The group substitution;

[0297] Alternatively, R 4 、R 5 Together with the atoms to which they are connected, they form a 5-7 membered monocyclic carbocyclic ring or a 5-7 membered heterocyclic ring containing 1-3 heteroatoms selected from N, O, and S, wherein the carbocyclic ring or heterocyclic ring is optionally substituted by 1-3 heteroatoms selected from R A3 The group substitution;

[0298] Alternatively, R L1 With R9 Together with the atoms to which they are connected, they form a 5-7 membered carbocyclic ring or a 5-7 membered heterocyclic ring containing 1-3 heteroatoms selected from N, O, and S, wherein the carbocyclic ring or heterocyclic ring is optionally further surrounded by 1-3 heteroatoms selected from R A3 The group substitution;

[0299] Each R A3 Each independently selected from =O, halogen, deuterium, CN, OH, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, deuterated C 1-4 Alkoxy and NH2 group substitution;

[0300] The condition is that the compound satisfies one of the following conditions:

[0301] (1).R 1 、R 2 and R 3 At least one group is selected from R A1 ;

[0302] (2).R 4 and R 5 At least one group is selected from C 3-10 Cycloalkyl, C 2-6 Alkenyl, C 2-6 Alkynyl;

[0303] (3).R 4 、R 5 Together with the atoms to which they are attached, they form a 5-7 membered monocyclic carbocyclic ring or a 5-7 membered heterocyclic ring containing 1-3 heteroatoms selected from N, O, and S, wherein the carbocyclic ring or heterocyclic ring is optionally further substituted by 1-3 heteroatoms selected from R A3 substituted by a group, and R 1 Selected from R A1 or -O-halogenated C 1-4 alkyl;

[0304] (4).R 6 、R 7 、R 8 、R 9 、R 10 At least one group is selected from R A2 ;

[0305] (5).R 2 、R 4 , L1 and the atoms to which they are connected together form a 5-7 membered carbocyclic ring, a 5-7 membered heterocyclic ring containing 1-3 heteroatoms selected from N, O, and S, wherein the carbocyclic ring or heterocyclic ring is optionally further substituted by 1-3 heteroatoms selected from R A3substituted by a group, and R 1 is not a heterocycloalkyl group;

[0306] (6) L1 is selected from O, NH, S, -CD2-, -CHD-, -CR L1 R L2 -、C 1-4 Alkyl, -C(O)-, S(O), S(O)2, wherein the alkyl group is optionally further R L1 replace;

[0307] (7) L2 is selected from O, NH, S, -CR L1 R L2 -、-CHR L2 -、-CDR L2 -、-C(O)-、C 2-4 Alkyl, S(O), S(O)2, wherein the alkyl is 1-3 R L1 replace;

[0308] The definitions of other groups are consistent with those of any of the above technical solutions.

[0309] The third technical solution of the present invention is that the compound of the present invention, its stereoisomer, deuterated substance, solvate, or pharmaceutically acceptable salt has the structure of formula (II):

[0310] L2 is selected from -CH2-, -CR L1 R L2 -、-CHR L2 -、-CDR L2 -, -C(O)-;

[0311] X is selected from CR 10 or N;

[0312] R 4 、R 5 Each independently selected from H, deuterium, C 3-7 Cycloalkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, F, Cl, amino, -NH-C 1-2 Alkyl, -N(C 1-2 Alkyl)2, C 1-2 Alkyl, 4-7 membered heterocycloalkyl containing 1-3 heteroatoms selected from N, O, S;

[0313] R 7 、R 8 Each independently selected from H, deuterium, R A2 、F、Cl、OH、CN、amino、C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4Alkynyl, C 1-4 Alkoxy, halogenated C 1-4 Alkyl, -NH-C 1-2 Alkyl, -N(C 1-2 Alkyl)2, -S(O)R c 、-S(O) 2 R c 、-C(O)R c 、-C(O)OR c 、-C(O)N(R c )2、-OC(O)R c ;

[0314] R 9 、R 10 Each independently selected from H, deuterium, F, Cl, OH, CN, amino, C 1-2 alkyl;

[0315] R A2 Selected from -(CH2) r -(a 4-6 membered monocyclic heterocycloalkyl group containing 1-3 heteroatoms selected from N, O, and S), -(CH2) r -(7-10 membered spirocyclic heterocycloalkyl containing 1-3 heteroatoms selected from N, O, S), -(CH2) r -(5-6 membered monocyclic heteroaryl containing 1-3 heteroatoms selected from N, O, S), -(CH2) r -(8-10 membered bicyclic heteroaryl containing 1-3 heteroatoms selected from N, O, S), -P(O)(R c )2、-Si(R c )3、-SF5、-S(O)(=NH)R c The heterocycloalkyl and heteroaryl groups are optionally further substituted by 1-3 groups selected from halogen, D, CN, OH, C 1-2 Alkyl, halogenated C 1-2 Alkyl, deuterated C 1-2 Alkyl, C 1-2 Alkoxy, halogenated C 1-2 Alkoxy, deuterated C 1-2 Alkoxy and NH2 group substitution;

[0316] Alternatively, R 7 With R 8 、R 8 With R 9 The group of and the atoms connected thereto together form a 4-7 membered carbocyclic ring, a 5-7 membered heterocycloalkyl containing 1-3 heteroatoms selected from N, O, S, B, or an 8 membered carbocyclic ring or a 5-7 membered heterocycloalkyl containing 1 Si atom, wherein the carbocyclic ring or heterocycloalkyl is optionally further substituted by 1-3 atoms selected from =O, halogen, deuterium, CN, OH, C 1-4Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, deuterated C 1-4 Alkoxy and NH2 group substitution;

[0317] The condition is that the compound satisfies at least one of the following conditions:

[0318] (1).R 1 、R 2 and R 3 At least one group is selected from R A1 ;

[0319] (2).R 4 and R 5 At least one group is selected from C 3-7 Cycloalkyl, C 2-4 Alkenyl, C 2-4 Alkynyl;

[0320] (3).R 7 、R 8 At least one group is selected from R A2 ;

[0321] (4) L2 is selected from -CR L1 R L2 -、-CHR L2 -、-CDR L2 -, -C(O)-;

[0322] (5).R 7 With R 8 、R 8 With R 9 The group of and the atoms connected thereto together form a 4-7 membered carbocyclic ring, a 5-7 membered heterocycloalkyl ring containing 1-3 heteroatoms selected from N, O, S, B, or an 8-membered carbocyclic ring, wherein the carbocyclic ring or heterocycloalkyl ring is optionally further substituted by 1-3 heteroatoms selected from =O, halogen, deuterium, CN, OH, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, deuterated C 1-4 Alkoxy and NH2 group substitution;

[0323] The definitions of other groups are consistent with those of any of the above technical solutions.

[0324] As an alternative to the third technical solution of the present invention, the compound of the present invention, its stereoisomer, deuterated substance, solvate, or pharmaceutically acceptable salt has the structure of formula (II):

[0325] L2 is selected from -CH2-, -CR L1 R L2 -、-CHR L2 -、-CDR L2 -, -C(O)-;

[0326] X is selected from CR 10 or N;

[0327] R 4 、R 5 Each independently selected from H, deuterium, C 3-7 Cycloalkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, F, Cl, amino, -NH-C 1-2 Alkyl, -N(C 1-2 Alkyl)2, C 1-2 Alkyl, 4-7 membered heterocycloalkyl containing 1-3 heteroatoms selected from N, O, S;

[0328] R 7 、R 8 Each independently selected from H, deuterium, R A2 、F、Cl、OH、CN、amino、C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-4 Alkoxy, halogenated C 1-4 Alkyl, -NH-C 1-2 Alkyl, -N(C 1-2 Alkyl)2, -S(O)R c 、-S(O) 2 R c 、-C(O)R c 、-C(O)OR c 、-C(O)N(R c )2、-OC(O)R c ;

[0329] Alternatively, R 7 With R 8 and the atoms to which they are attached together form a 4-7 membered carbocyclic ring or a 5-7 membered heterocycloalkyl or 8 membered carbocyclic ring containing 1-3 heteroatoms selected from N, O, S, and B, wherein the carbocyclic ring or heterocycloalkyl is optionally further substituted by 1-3 heteroatoms selected from =O, halogen, deuterium, CN, OH, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, deuterated C1-4 Alkoxy and NH2 group substitution;

[0330] R 9 、R 10 Each independently selected from H, deuterium, F, Cl, OH, CN, amino, C 1-2 alkyl;

[0331] R A2 Selected from -(CH2) r -(a 4-6 membered monocyclic heterocycloalkyl group containing 1-3 heteroatoms selected from N, O, and S), -(CH2) r -(7-10 membered spirocyclic heterocycloalkyl containing 1-3 heteroatoms selected from N, O, S), -(CH2) r -(5-6 membered monocyclic heteroaryl containing 1-3 heteroatoms selected from N, O, S), -(CH2) r -(8-10 membered bicyclic heteroaryl containing 1-3 heteroatoms selected from N, O, S), -P(O)(R c )2、-Si(R c )3、-SF5、-S(O)(=NH)R c The heterocycloalkyl and heterocycloaryl groups are optionally further substituted by 1-3 groups selected from halogen, D, CN, OH, C 1-2 Alkyl, halogenated C 1-2 Alkyl, deuterated C 1-2 Alkyl, C 1-2 Alkoxy, halogenated C 1-2 Alkoxy, deuterated C 1-2 Alkoxy and NH2 group substitution;

[0332] The condition is that the compound satisfies one of the following conditions:

[0333] (1).R 1 、R 2 and R 3 At least one group is selected from R A1 ;

[0334] (2).R 4 and R 5 At least one group is selected from C 3-7 Cycloalkyl, C 2-4 Alkenyl, C 2-4 Alkynyl;

[0335] (3).R 7 、R 8 At least one group is selected from R A2 ;

[0336] (4) L2 is selected from -CR L1 R L2-、-CHR L2 -、-CDR L2 -, -C(O)-;

[0337] The definitions of other groups are consistent with those of any of the above technical solutions.

[0338] The fourth technical solution of the present invention relates to compounds of formula (I), (II), (Ib), stereoisomers, deuterated substances, solvates, or pharmaceutically acceptable salts or cocrystals thereof, wherein R 2 、R 4 , L1 and the atoms to which they are connected together form a 6-7 membered cycloalkyl, phenyl, wherein the cycloalkyl is optionally further substituted by 1-3 groups selected from R A3 substituted by a group, and R 1 It is not a heterocycloalkyl group; the definitions of other groups are consistent with those in any of the above technical solutions.

[0339] The fifth technical solution of the present invention is a compound of the present invention, a stereoisomer, a deuterated substance, a solvate, or a pharmaceutically acceptable salt or a cocrystal thereof, wherein R 4 、R 5 Together with the atoms to which they are attached, they form a phenyl group, a 5-6 membered cycloalkyl group, a 5-6 membered heteroaryl group containing 1-3 heteroatoms selected from N, O, and S, wherein the cycloalkyl group is optionally substituted by 1-3 heteroatoms selected from R A3 substituted by a group, and R 1 Selected from R A1 or -O-halogenated C 1-4 Alkyl; the definitions of other groups are consistent with those in any of the above technical solutions.

[0340] The sixth technical solution of the present invention is a compound of the present invention, a stereoisomer, a deuterated substance, a solvate, or a pharmaceutically acceptable salt or a cocrystal thereof, wherein R L1 With R 9 Together with the atoms to which they are attached, they form a 5-6 membered cycloalkyl group, which is optionally further substituted by 1-3 groups selected from R A3 The definitions of other groups are consistent with those of any of the above technical solutions.

[0341] The seventh technical solution of the present invention is a compound of the present invention, a stereoisomer, a deuterated substance, a solvate, or a pharmaceutically acceptable salt or a cocrystal thereof, wherein each R A3 Each independently selected from =O, halogen, deuterium, CN, OH, C 1-2 Alkyl, halogenated C 1-2 Alkyl, deuterated C 1-2 Alkyl, C 1-2 Alkoxy, halogenated C 1-2 Alkoxy, deuterated C 1-2 Alkoxy and NH2 group substitution; other group definitions are consistent with any of the above technical solutions.

[0342] The eighth technical solution of the present invention is a compound of the present invention, a stereoisomer, a deuterated substance, a solvate, or a pharmaceutically acceptable salt or a cocrystal thereof, wherein:

[0343] R 2 、R 4 , L1 and the atoms to which they are attached together form a 6-7 membered cycloalkyl, a phenyl group or a 5-7 membered cycloalkyl group, wherein the cycloalkyl group is optionally further substituted by 1-3 groups selected from R A3 substituted by a group, and R 1 is not a heterocycloalkyl group; or

[0344] R 4 、R 5 Together with the atoms to which they are attached, they form a phenyl group, a 5-6 membered cycloalkyl group, a 5-6 membered heteroaryl group containing 1-3 heteroatoms selected from N, O, and S, wherein the cycloalkyl group is optionally substituted by 1-3 heteroatoms selected from R A3 substituted by a group, and R 1 Selected from R A1 or -O-halogenated C 1-4 Alkyl; or

[0345] R L1 With R 9 Together with the atoms to which they are attached, they form a 5-6 membered cycloalkyl group, which is optionally further substituted by 1-3 groups selected from R A3 The group substitution;

[0346] Each R A3 Each independently selected from =O, halogen, deuterium, CN, OH, C 1-2 Alkyl, halogenated C 1-2 Alkyl, deuterated C 1-2 Alkyl, C 1-2 Alkoxy, halogenated C 1-2 Alkoxy, deuterated C 1-2 Alkoxy and NH2 group substitution;

[0347] The definitions of other groups are consistent with those of any of the above technical solutions.

[0348] The ninth technical solution of the present invention is a compound of the present invention, a stereoisomer, a deuterated substance, a solvate, or a pharmaceutically acceptable salt or a cocrystal thereof,

[0349] R 1 Selected from R A1 、-O-halogenated C 1-4 Alkyl, wherein the alkyl is optionally further substituted by 1-3 groups selected from halogen, D, CN, OH, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, C 1-4Alkoxy, halogenated C 1-4 Alkoxy, deuterated C 1-4 Alkoxy and NH2 group substitution;

[0350] R 2 、R 3 Each independently selected from H, deuterium, C 2-4 Alkenyl, C 2-4 Alkynyl, halogen, cyano, nitro, OH, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 alkyl;

[0351] R A1 Selected from halogenated C 2-4 Alkenyl, C 2-4 Alkynyl, -O-(CH2) r -R a 、C 3-6 Monocyclic cycloalkyl, 5-6 membered monocyclic heteroaryl containing 1-3 heteroatoms selected from N, O, S, 8-10 membered bicyclic heteroaryl containing 1-3 heteroatoms selected from N, O, S, -C 1-2 Alkyl-R a 、-C 1-2 Alkyl-OR a 、-C 1-2 Alkyl-NR b R a 、-NR b -S(O)2-R a 、-NR b -S(O)2-NR b R a 、-O-NR b R a 、 -NH-OR b or -Se-(CH2) r -Ra, the alkynyl, heteroaryl, alkyl group is optionally further substituted by 1-3 groups selected from halogen, deuterium, CN, OH, C 1-2 Alkyl, halogenated C 1-2 Alkyl, deuterated C 1-2 Alkyl, C 1-2 Alkoxy, halogenated C 1-2 Alkoxy, deuterated C 1-2 Alkoxy and NH2 group substitution;

[0352] r is selected from 0 or 1;

[0353] Each R a Selected from CN, halogenated C 1-4 Alkyl, C 3-6 Monocyclic cycloalkyl, C 7-10 Spirocyclic cycloalkyl, C4-8 Bridged ring cycloalkyl, C 4-9 cycloalkyl, 4-6 membered monocyclic heterocycloalkyl containing 1-3 heteroatoms selected from N, O, and S, 7-10 membered spirocyclic heterocycloalkyl containing 1-3 heteroatoms selected from N, O, and S, 4-8 membered bridged heterocycloalkyl containing 1-3 heteroatoms selected from N, O, and S, 4-6 membered cycloheterocycloalkyl containing 1-3 heteroatoms selected from N, O, and S, phenyl, 8-10 membered aryl, 5-6 membered monocyclic heteroaryl containing 1-3 heteroatoms selected from N, O, and S, 8-10 membered bicyclic heteroaryl containing 1-3 heteroatoms selected from N, O, and S, -C(O)-R a1 The alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl groups are optionally further substituted by 1-3 groups selected from halogen, =O, deuterium, CN, OH, C 1-2 Alkyl, halogenated C 1-2 Alkyl, deuterated C 1-2 Alkyl, C 1-2 Alkoxy, halogenated C 1-2 Alkoxy, deuterated C 1-2 Alkoxy and NH2 group substitution;

[0354] Each R b Selected from H, deuterium, C 1-2 Alkyl, C 3-4 Cycloalkyl;

[0355] The definitions of other groups are consistent with those of any of the above technical solutions.

[0356] The tenth technical solution of the present invention is a compound of the present invention, a stereoisomer, a deuterated substance, a solvate, or a pharmaceutically acceptable salt or a cocrystal thereof,

[0357] R 1 Selected from R A1 、-O-halogenated C 1-4 Alkyl, wherein the alkyl is optionally further substituted by 1-3 groups selected from halogen, D, CN, OH, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, deuterated C 1-4 Alkoxy and NH2 group substitution;

[0358] R 2 、R 3 Each independently selected from H, deuterium, C 2-4 Alkenyl, C 2-4 Alkynyl, halogen, cyano, nitro, OH, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 alkyl;

[0359] R A1 Selected from halogenated C 2-4 Alkenyl, C 2-4 Alkynyl, 5-6 membered monocyclic heteroaryl containing 1-3 heteroatoms selected from N, O, S, 8-10 membered bicyclic heteroaryl containing 1-3 heteroatoms selected from N, O, S, -C 1-2 Alkyl-R a 、-C 1-2 Alkyl-OR a 、-C 1-2 Alkyl-NR b R a 、-NR b -S(O)2-R a 、-NR b -S(O)2-NR b R a Or selected from -O-NR b R a 、-NH-OR b or selected from -Se-(CH2) r -Ra, the alkynyl, heteroaryl, alkyl group is optionally further substituted by 1-3 groups selected from halogen, deuterium, CN, OH, C 1-2 Alkyl, halogenated C 1-2 Alkyl, deuterated C 1-2 Alkyl, C 1-2 Alkoxy, halogenated C 1-2 Alkoxy, deuterated C 1-2 Alkoxy and NH2 group substitution;

[0360] Each R a Selected from CN, halogenated C 1-4 Alkyl, C 3-6 Monocyclic cycloalkyl, C 7-10 Spirocyclic cycloalkyl, C 4-8 Bridged ring cycloalkyl, C 4-9 cycloalkyl, 4-6 membered monocyclic heterocycloalkyl containing 1-3 heteroatoms selected from N, O, and S, 7-10 membered spirocyclic heterocycloalkyl containing 1-3 heteroatoms selected from N, O, and S, 4-8 membered bridged heterocycloalkyl containing 1-3 heteroatoms selected from N, O, and S, 4-6 membered cycloheterocycloalkyl containing 1-3 heteroatoms selected from N, O, and S, phenyl, 8-10 membered aryl, 5-6 membered monocyclic heteroaryl containing 1-3 heteroatoms selected from N, O, and S, 8-10 membered bicyclic heteroaryl containing 1-3 heteroatoms selected from N, O, and S, -C(O)-R a1 The alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl groups are optionally further substituted by 1-3 groups selected from halogen, =O, deuterium, CN, OH, C 1-2 Alkyl, halogenated C1-2 Alkyl, deuterated C 1-2 Alkyl, C 1-2 Alkoxy, halogenated C 1-2 Alkoxy, deuterated C 1-2 Alkoxy and NH2 group substitution;

[0361] Each R b Selected from H, deuterium, C 1-2 Alkyl, C 3-4 Cycloalkyl;

[0362] The definitions of other groups are consistent with those of any of the above technical solutions.

[0363] The eleventh technical solution of the present invention is that the compound of the present invention, its stereoisomer, deuterated substance, solvate, or pharmaceutically acceptable salt has the structure of formula (III):

[0364] X is selected from CR 10 or N;

[0365] R 9 、R 10 Each independently selected from H, deuterium, F, Cl, OH, CN, amino, C 1-2 alkyl;

[0366] The condition is that the compound satisfies one of the following conditions:

[0367] (1).R 1 、R 2 and R 3 At least one group is selected from R A1 ;

[0368] (2).R 7 、R 8 At least one group is selected from R A2 ;

[0369] (3).R 7 With R 8 、R 8 With R 9 The group of and the atoms connected thereto together form a 4-7 membered carbocyclic ring, a 5-7 membered heterocycloalkyl containing 1-3 heteroatoms selected from N, O, S, B, or an 8 membered carbocyclic ring or a 5-7 membered heterocycloalkyl containing 1 Si atom, wherein the carbocyclic ring or heterocycloalkyl is optionally further substituted by 1-3 atoms selected from =O, halogen, deuterium, CN, OH, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, deuterated C 1-4Alkoxy and NH2 group substitution;

[0370] The definitions of other groups are consistent with those of any of the above technical solutions.

[0371] The twelfth technical solution of the present invention is that the compound of the present invention, its stereoisomer, deuterated substance, solvate, or pharmaceutically acceptable salt has the structure of formula (III):

[0372] X is selected from CR 10 or N;

[0373] R 9 、R 10 Each independently selected from H, deuterium, F, Cl, OH, CN, amino, C 1-2 alkyl;

[0374] The condition is that the compound satisfies one of the following conditions:

[0375] (1).R 1 、R 2 and R 3 At least one group is selected from R A1 ;

[0376] (2).R 7 、R 8 At least one group is selected from R A2 ;

[0377] The definitions of other groups are consistent with those of any of the above technical solutions.

[0378] The thirteenth technical solution of the present invention is that the compound of the present invention, its stereoisomer, deuterated substance, solvate, or pharmaceutically acceptable salt has the structure of formula (IV) or (V):

[0379] X is selected from CR 10 or N;

[0380] R 9 、R 10 Each independently selected from H, deuterium, F, Cl, OH, CN, amino, C 1-2 alkyl;

[0381] L2 is selected from -CH2-, -CD2-, -CHD-, -CR L1 R L2 -、-CHR L2 -、-CDR L2 -、C 2-4 Alkyl, -C(O)-, wherein the alkyl group is optionally further substituted with 1-3 R L1 replace;

[0382] The condition is that the compound satisfies one of the following conditions:

[0383] (1).R 7 、R 8 At least one group is selected from R A2 ;

[0384] (2).R 4 and R 5 At least one group is selected from C 3-10 Cycloalkyl, C 2-6 Alkenyl, C 2-6 Alkynyl;

[0385] (3).R 4 、R 5 Together with the atoms to which they are attached, they form a 5-7 membered monocyclic carbocyclic ring or a 5-7 membered heterocyclic ring containing 1-3 heteroatoms selected from N, O, and S, wherein the carbocyclic ring or heterocyclic ring is optionally further substituted by 1-3 heteroatoms selected from R A3 The group substitution;

[0386] (4).R 2 、R 4 Together with the atoms to which they are connected, they form a 5-7 membered carbocyclic ring or a 5-7 membered heterocyclic ring containing 1-3 heteroatoms selected from N, O, and S, wherein the carbocyclic ring or heterocyclic ring is optionally further surrounded by 1-3 heteroatoms selected from R A3 The group substitution;

[0387] (5). L2 is selected from -CR L1 R L2 -、-CHR L2 -、-CDR L2 -、-C(O)-、C 2-4 Alkyl, the alkyl group is 1-3 R L1 replace;

[0388] (6).R 7 With R 8 、R 8 With R 9 The group of and the atoms connected thereto together form a 4-7 membered carbocyclic ring, a 5-7 membered heterocycloalkyl containing 1-3 heteroatoms selected from N, O, S, B, or an 8 membered carbocyclic ring or a 5-7 membered heterocycloalkyl containing 1 Si atom, wherein the carbocyclic ring or heterocycloalkyl is optionally further substituted by 1-3 atoms selected from =O, halogen, deuterium, CN, OH, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, deuterated C 1-4 Alkoxy and NH2 group substitution;

[0389] The definitions of other groups are consistent with those of any of the above technical solutions.

[0390] The fourteenth technical solution of the present invention is that the compound of the present invention, its stereoisomer, deuterated substance, solvate, or pharmaceutically acceptable salt has the structure of formula (IV) or (V):

[0391] X is selected from CR 10 or N;

[0392] R 9 、R 10 Each independently selected from H, deuterium, F, Cl, OH, CN, amino, C 1-2 alkyl;

[0393] L2 is selected from -CH2-, -CD2-, -CHD-, -CR L1 R L2 -、-CHR L2 -、-CDR L2 -、C 2-4 Alkyl, -C(O)-, wherein the alkyl group is optionally further substituted with 1-3 R L1 replace;

[0394] The condition is that the compound satisfies one of the following conditions:

[0395] (1).R 7 、R 8 At least one group is selected from R A2 ;

[0396] (2).R 4 and R 5 At least one group is selected from C 3-10 Cycloalkyl, C 2-6 Alkenyl, C 2-6 Alkynyl;

[0397] (3).R 4 、R 5 Together with the atoms to which they are attached, they form a 5-7 membered monocyclic carbocyclic ring or a 5-7 membered heterocyclic ring containing 1-3 heteroatoms selected from N, O, and S, wherein the carbocyclic ring or heterocyclic ring is optionally further substituted by 1-3 heteroatoms selected from R A3 The group substitution;

[0398] (4).R 2 、R 4 Together with the atoms to which they are connected, they form a 5-7 membered carbocyclic ring or a 5-7 membered heterocyclic ring containing 1-3 heteroatoms selected from N, O, and S, wherein the carbocyclic ring or heterocyclic ring is optionally further surrounded by 1-3 heteroatoms selected from R A3 The group substitution;

[0399] (5). L2 is selected from -CR L1 R L2 -、-CHR L2 -、-CDR L2 -、-C(O)-、C 2-4 Alkyl, the alkyl group is 1-3 R L1 replace;

[0400] The definitions of other groups are consistent with those of any of the above technical solutions.

[0401] The fifteenth technical solution of the present invention is that the compound of the present invention, its stereoisomer, deuterated substance, solvate, or pharmaceutically acceptable salt has the structure of formula (VI), (VII), (VIII), or (IX):

[0402] X is selected from CR 10 or N;

[0403] L2 is selected from -CH2-, -CD2-, -CHD-, -CR L1 R L2 -、-CHR L2 -、-CDR L2 -、C 2-4 Alkyl, -C(O)-, wherein the alkyl group is optionally further substituted with 1-3 R L1 replace;

[0404] R 9 、R 10 Each independently selected from H, deuterium, OH, CN, amino, C 1-4 Alkyl, halogenated C 1-4 alkyl;

[0405] R 1 Selected from R A1 ;

[0406] R 2 、R 3 Each independently selected from H, deuterium, C 2-4 Alkenyl, C 2-4 Alkynyl, halogen, cyano, nitro, OH, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 alkyl;

[0407] The definitions of other groups are consistent with those of any of the above technical solutions.

[0408] The sixteenth technical solution of the present invention relates to the compound of formula (Ia) described in the present invention, its stereoisomers, deuterated substances, solvates, or pharmaceutically acceptable salts or cocrystals, wherein

[0409] RA4 Selected from -CH2-CF=CR A4a R A4b 、-CH2-CH=CH-CH=CR A4a R A4b 、L3-R A4’ 、-CH(C 1-2 (alkyl)-CR A4c =CR A4a R A4b 、-C(C 1-2 alkyl)2-CR A4c =CR A4a R A4b 、-CH2-C(CN)=CR A4a R A4b ; or R A4 Selected from -CH2-C(CH3)=CR A4a R A4b 、-CH2-CH=CH-CH=CR A4a R A4b 、L3-R A4’ 、-CH(C 1-2 (alkyl)-CR A4c =CR A4a R A4b 、-C(C 1-2 alkyl)2-CR A4c =CR A4a R A4b 、-CH2-C(CN)=CR A4a R A4b ; or R A4 Selected from -CH2-CH=CR A4a R A4b 、-CH2-CH=CH-CH=CR A4a R A4b 、L3-R A4’ 、-CH(C 1-2 (alkyl)-CR A4c =CR A4a R A4b 、-C(C 1-2 alkyl)2-CR A4c =CR A4a R A4b 、-CH2-C(CN)=CR A4a R A4b ;

[0410] R A4a 、R A4b Together with the carbon atom to which it is connected, it forms a 4, 5, or 6-membered monocyclic cycloalkyl group, C 7-10 Spirocarbon ring, C 7-10A 5-membered or 6-membered heterocyclic cycloalkyl containing 1-3 heteroatoms selected from N, O, and S, or a 6-membered 5-membered or 6-membered heterocyclic cycloalkyl, wherein the cycloalkyl or heterocycloalkyl is optionally substituted by 1-3 halogens, =O, deuterium, CN, OH, C 1-2 Alkyl, halogenated C 1-2 Alkyl, deuterated C 1-2 Alkyl, -COC 1-2 Alkyl, C 1-2 Alkoxy, halogenated C 1-2 Alkoxy, deuterated C 1-2 Alkoxy and NH2 group substitution;

[0411] L3 is selected from C 3-6 Cycloalkyl, -CH(C 1-2 alkyl)-C 1-2 alkyl;

[0412] R A4’ Selected from C 3-6 Cycloalkyl, 5-10 membered heteroaryl containing 1-3 heteroatoms selected from N, O, S, wherein the cycloalkyl and heteroaryl are optionally further substituted by 1-3 heteroatoms selected from halogen, deuterium, CN, OH, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, deuterated C 1-4 Alkoxy and NH2 group substitution;

[0413] The definitions of other groups are consistent with any of the above technical solutions.

[0414] The seventeenth technical solution of the present invention relates to the compound of formula (Ia) according to the present invention, its stereoisomers, deuterated substances, solvates, or pharmaceutically acceptable salts or cocrystals, wherein

[0415] R A4 Selected from -CH2-CF=CR A4a R A4b 、-CH2-CH=CH-CH=CR A4a R A4b 、L3-R A4’ ; or R A4 Selected from -CH2-C(CH3)=CR A4a R A4b 、-CH2-CH=CH-CH=CR A4a R A4b 、L3-R A4’ ; or R A4 Selected from -CH2-CH=CR A4a R A4b、-CH2-CH=CH-CH=CR A4a R A4b 、L3-R A4’ ;

[0416] R A4a 、R A4b Together with the carbon atom to which it is connected, it forms a 4, 5, or 6-membered monocyclic cycloalkyl group, C 7-10 Spirocarbon ring, C 7-10 A 5-membered or 6-membered heterocyclic cycloalkyl containing 1-3 heteroatoms selected from N, O, and S, or a 6-membered 5-membered or 6-membered heterocyclic cycloalkyl, wherein the cycloalkyl or heterocycloalkyl is optionally substituted by 1-3 halogens, =O, deuterium, CN, OH, C 1-2 Alkyl, halogenated C 1-2 Alkyl, deuterated C 1-2 Alkyl, -COC 1-2 Alkyl, C 1-2 Alkoxy, halogenated C 1-2 Alkoxy, deuterated C 1-2 Alkoxy and NH2 group substitution;

[0417] L3 is selected from C 3-6 Cycloalkyl, -CH(C 1-2 alkyl)-C 1-2 alkyl;

[0418] R A4’ Selected from C 3-6 Cycloalkyl, 5-10 membered heteroaryl containing 1-3 heteroatoms selected from N, O, S, wherein the cycloalkyl and heteroaryl are optionally further substituted by 1-3 heteroatoms selected from halogen, deuterium, CN, OH, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, deuterated C 1-4 Alkoxy and NH2 group substitution;

[0419] The definitions of other groups are consistent with any of the above technical solutions.

[0420] The eighteenth technical solution of the present invention relates to the compound of formula (Ia) described in the present invention, its stereoisomers, deuterated substances, solvates, or pharmaceutically acceptable salts or cocrystals, wherein

[0421] R A4 Selected from -CH2-CH2-C 3-6 Cycloalkyl, -CH2-CF=CR A4a R A4b 、L3-R A4’ 、-CH(C 1-2 (alkyl)-CRA4c =CR A4a R A4b 、-C(C 1-2 alkyl)2-CR A4c =CR A4a R A4b 、-CH2-C(CN)=CR A4a R A4b ; or R A4 Selected from -CH2-CH2-C 3-6 Cycloalkyl, -CH2-C(CH3)=CR A4a R A4b 、L3-R A4’ 、-CH(C 1-2 (alkyl)-CR A4c =CR A4a R A4b 、-C(C 1-2 alkyl)2-CR A4c =CR A4a R A4b 、-CH2-C(CN)=CR A4a R A4b ; or R A4 Selected from -CH2-CH2-C 3-6 Cycloalkyl, -CH2-CH=CR A4a R A4b 、L3-R A4 、-CH(C 1-2 (alkyl)-CR A4c =CR A4a R A4b 、-C(C 1-2 alkyl)2-CR A4c =CR A4a R A4b 、-CH2-C(CN)=CR A4a R A4b ;

[0422] R A4a 、R A4b Together with the carbon atom to which it is attached, it forms a 4-, 5-, or 6-membered cycloalkyl group;

[0423] L3 is selected from C 3-6 Cycloalkyl, -CH(C 1-2 alkyl)-C 1-2 alkyl;

[0424] R A4’ Selected from C 3-6 Cycloalkyl, 5-10 membered heteroaryl containing 1-3 heteroatoms selected from N, O, S, wherein the cycloalkyl and heteroaryl are optionally further substituted by 1-3 heteroatoms selected from halogen, deuterium, CN, OH, C1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, deuterated C 1-4 Alkoxy and NH2 group substitution;

[0425] The condition is that the compound satisfies R A4 Selected from -CH2-CF=CR A4a R A4b 、L3-R A4’ ; or satisfy R A4 Selected from -CH2-C(CH3)=CR A4a R A4b 、L3-R A4’ ; or satisfy R A4 Selected from -CH2-CH=CR A4a R A4b 、L3-R A4’ ;

[0426] The definitions of other groups are consistent with any of the above technical solutions.

[0427] The nineteenth technical solution of the present invention relates to the compound of formula (Ia) described in the present invention, its stereoisomers, deuterated substances, solvates, or pharmaceutically acceptable salts or cocrystals, wherein

[0428] R A4 Selected from -CH2-CH2-C 3-6 Cycloalkyl, -CH2-CF=CR A4a R A4b 、L3-R A4’ ; or R A4 Selected from -CH2-CH2-C 3-6 Cycloalkyl, -CH2-C(CH3)=CR A4a R A4b 、L3-R A4’ ; or R A4 Selected from -CH2-CH2-C 3-6 Cycloalkyl, -CH2-CH=CR A4a R A4b 、L3-R A4 ;

[0429] R A4a 、R A4b Together with the carbon atom to which it is attached, it forms a 4-, 5-, or 6-membered cycloalkyl group;

[0430] L3 is selected from C 3-6 Cycloalkyl, -CH(C 1-2 alkyl)-C1-2 alkyl;

[0431] R A4’ Selected from C 3-6 Cycloalkyl, 5-10 membered heteroaryl containing 1-3 heteroatoms selected from N, O, S, wherein the cycloalkyl and heteroaryl are optionally further substituted by 1-3 heteroatoms selected from halogen, deuterium, CN, OH, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, deuterated C 1-4 Alkoxy and NH2 group substitution;

[0432] The condition is that the compound satisfies R A4 Selected from -CH2-CF=CR A4a R A4b 、L3-R A4’ ; or satisfy R A4 Selected from -CH2-C(CH3)=CR A4a R A4b 、L3-R A4’ ; or satisfy R A4 Selected from -CH2-CH=CR A4a R A4b 、L3-R A4’ ;

[0433] The definitions of other groups are consistent with any of the above technical solutions.

[0434] The twentieth technical solution of the present invention relates to the compound of formula (Ia) described in the present invention, its stereoisomers, deuterated substances, solvates, or pharmaceutically acceptable salts or cocrystals, wherein

[0435] R 1 Selected from R A1 、-O-halogenated C 1-2 Alkyl, -NH-halogenated C 1-2 Alkyl, -OC 1-2 Alkyl, C 1-2 Alkoxy, halogen, cyano, nitro, OH, C 1-2 Alkyl, C 2-4 Alkenyl, -NH-C 1-2 Alkyl, -N(C 1-2 Alkyl)2, -NH-C 3-10 Cycloalkyl, -NHC(O)C 1-2 Alkyl, or 4-10 membered heterocycloalkyl containing 1-3 heteroatoms selected from N, O, S, wherein the alkyl, alkoxy, cycloalkyl, heterocycloalkyl is optionally further substituted by 1-3 heteroatoms selected from halogen, D, CN, OH, C1-2 Alkyl, halogenated C 1-2 Alkyl, deuterated C 1-2 Alkyl, C 1-2 Alkoxy, halogenated C 1-2 Alkoxy, deuterated C 1-2 Alkoxy, C 3-8 Cycloalkyl, 4-6 membered heterocycloalkyl containing 1-3 heteroatoms selected from N, O, S, phenyl, and NH2;

[0436] R 2 、R 3 Each independently selected from H, deuterium, C 1-4 Alkoxy, halogen, cyano, nitro, OH, C 1-2 Alkyl, C 2-4 Alkenyl, -NH-C 1-2 Alkyl, -N(C 1-2 Alkyl) 2, wherein the alkyl and alkoxy groups are optionally further substituted by 1-3 groups selected from halogen, D, CN, OH, C 1-2 Alkyl, halogenated C 1-2 Alkyl, deuterated C 1-2 Alkyl, C 1-2 Alkoxy, halogenated C 1-2 Alkoxy, deuterated C 1-2 Alkoxy, and NH2 group substitution;

[0437] X1 is selected from O, S;

[0438] R 4 、R 5 Each independently selected from H, deuterium, C 3-7 Cycloalkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, F, Cl, amino, -NH-C 1-2 Alkyl, -N(C 1-2 Alkyl)2, C 1-2 Alkyl, 4-7 membered heterocycloalkyl containing 1-3 heteroatoms selected from N, O, S;

[0439] L1 is selected from a bond;

[0440] The definitions of other groups are consistent with those of any of the above technical solutions.

[0441] The twenty-first technical solution of the present invention relates to the compound of formula (Ia) described in the present invention, its stereoisomers, deuterated substances, solvates, or pharmaceutically acceptable salts or cocrystals, wherein

[0442] R A4 Selected from Or choose Further, R A4 Selected from Or choose

[0443] The definitions of other groups are consistent with any of the above technical solutions.

[0444] The twenty-second technical solution of the present invention relates to the compound of formula (Ia) described in the present invention, its stereoisomers, deuterated substances, solvates, or pharmaceutically acceptable salts or cocrystals, wherein

[0445] R A4 Selected from Or choose Further, R A4 Selected from Or choose

[0446] The definitions of other groups are consistent with any of the above technical solutions.

[0447] The twenty-third technical solution of the present invention is a compound of the present invention, a stereoisomer, a deuterated substance, a solvate, or a pharmaceutically acceptable salt or a cocrystal thereof, wherein

[0448] L1 is selected from a bond, O;

[0449] L2 is selected from -CH2-, -C(O)-, -CHF-, -CF2-, C(CH3)2-;

[0450] R L1 、R L2 Each independently selected from H, deuterium, and F;

[0451] R 6 、R 9 、R 10 Each independently selected from H, deuterium, F, Cl, OH, CN, methyl;

[0452] R 7 、R 8 Each independently selected from H, deuterium, F, Cl, OH, CN, methyl, R A2 ;

[0453] R A2 Selected from

[0454] R 2 、R 3 Each is independently selected from H, deuterium, vinyl, and ethynyl;

[0455] R 4 、R 5 Each is independently selected from H, deuterium, cyclopropyl, vinyl, and ethynyl;

[0456] Alternatively, R 4 、R 5 Together with the atoms to which it is attached, it forms phenyl, cyclohexyl, cyclopentyl, thienyl, furanyl, pyrrolyl, pyrazolyl, isoxazolyl;

[0457] Alternatively, R 2 、R 4 , L1 and the atoms to which it is attached together form a cyclohexyl group or a phenyl group;

[0458] Alternatively, R L1 With R 9 Together with the atoms to which they are attached, they form cyclopentyl or cyclohexyl;

[0459] Alternatively, R 7 With R 8 and the atoms to which they are attached together form a 4-7 membered carbocyclic ring, a 5-7 membered heterocycloalkyl ring containing 1-3 heteroatoms selected from N, O, S, and B, or an 8 membered carbocyclic ring, wherein the carbocyclic ring or heterocycloalkyl ring is optionally further substituted by 1-3 heteroatoms selected from =O, halogen, deuterium, CN, OH, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, deuterated C 1-4 Alkoxy and NH2 group substitution;

[0460] R 1 Selected from -CH2CH3, -CH2CH2CH3,

[0461] R A1 Selected from

[0462] The condition is that the compound satisfies one of the following conditions:

[0463] (1).R 1 Selected from R A1 ;

[0464] (2).R 4 and R 5 At least one group is selected from cyclopropyl, vinyl, and ethynyl;

[0465] (3).R4 、R 5 Together with the atoms to which it is attached, it forms phenyl, cyclohexyl, cyclopentyl, thienyl, furanyl, pyrrolyl, pyrazolyl, isoxazolyl;

[0466] (4).R 7 、R 8 At least one group is selected from R A2 ;

[0467] (5).R 2 、R 4 , L1 and the atoms to which it is attached together form a cyclohexyl group or a phenyl group;

[0468] (6) L1 is selected from O;

[0469] (7) L2 is selected from -C(O)-, -CHF-, -CF2-, -C(CH3)2-;

[0470] (8).R 7 With R 8 、R 8 With R 9 A group of the group and the atoms connected thereto together form a 4-7 membered carbocyclic ring or an 8 membered carbocyclic ring or a 5-7 membered heterocycloalkyl containing 1 Si atom, wherein the carbocyclic ring or heterocycloalkyl is optionally further substituted by 1-3 atoms selected from =O, F, Cl, deuterium, OH, C 1-2 Alkyl, halogenated C 1-2 Alkyl radical substitution;

[0471] The definitions of other groups are consistent with any of the above technical solutions.

[0472] The twenty-fourth technical solution of the present invention is a compound of the present invention, a stereoisomer, a deuterated substance, a solvate, or a pharmaceutically acceptable salt or a cocrystal thereof, wherein

[0473] L1 is selected from a bond, O;

[0474] L2 is selected from -CH2-, -C(O)-, -CHF-, -CF2-, C(CH3)2-;

[0475] R L1 、R L2 Each independently selected from H, deuterium, and F;

[0476] R 6 、R 9 、R 10 Each independently selected from H, deuterium, F, Cl, OH, CN, methyl;

[0477] R 7 、R 8 Each independently selected from H, deuterium, F, Cl, OH, CN, methyl, RA2 ;

[0478] Alternatively, R 7 With R 8 and the atoms to which they are attached together form a 4-7 membered carbocyclic ring or a 5-7 membered heterocycloalkyl containing 1-3 heteroatoms selected from N, O, S, and B, or an 8 membered carbocyclic ring or a 5-7 membered heterocycloalkyl containing 1 Si atom, wherein the carbocyclic ring or heterocycloalkyl is optionally further substituted by 1-3 atoms selected from ═O, halogen, deuterium, CN, OH, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, deuterated C 1-4 Alkoxy and NH2 group substitution;

[0479] R A2 Selected from

[0480] R 2 、R 3 Each is independently selected from H, deuterium, vinyl, and ethynyl;

[0481] R 4 、R 5 Each is independently selected from H, deuterium, cyclopropyl, vinyl, and ethynyl;

[0482] Alternatively, R 4 、R 5 Together with the atoms to which it is attached, it forms phenyl, cyclohexyl, cyclopentyl, thienyl, furanyl, pyrrolyl, pyrazolyl, isoxazolyl;

[0483] Alternatively, R 2 、R 4 , L1 and the atoms to which it is attached together form a cyclohexyl group or a phenyl group;

[0484] Alternatively, R L1 With R 9 Together with the atoms to which they are attached, they form cyclopentyl or cyclohexyl;

[0485] R 1 Selected from R A1 ; or R 1 Selected from

[0486] R A1 Selected from Or choose Or choose

[0487] The condition is that the compound satisfies one of the following conditions:

[0488] (1).R 1 Selected from R A1 ;

[0489] (2).R 4 and R 5 At least one group is selected from cyclopropyl, vinyl, and ethynyl;

[0490] (3).R 4 、R 5 Together with the atoms to which it is attached, it forms phenyl, cyclohexyl, cyclopentyl, thienyl, furanyl, pyrrolyl, pyrazolyl, isoxazolyl;

[0491] (4).R 7 、R 8 At least one group is selected from R A2 ;

[0492] (5).R 2 、R 4 , L1 and the atoms to which it is attached together form a cyclohexyl group or a phenyl group;

[0493] (6) L1 is selected from O;

[0494] (7).(7) L2 is selected from -C(O)-, -CHF-, -CF2-, C(CH3)2-.

[0495] The twenty-fifth technical solution of the present invention is a compound of the present invention, a stereoisomer, a deuterated substance, a solvate, or a pharmaceutically acceptable salt thereof.

[0496] A pharmaceutically acceptable salt or co-crystal, wherein

[0497] L1 is selected from a bond, O;

[0498] L2 is selected from -CH2-, -C(O)-, -CHF-, -CF2-, C(CH3)2-;

[0499] R L1 、R L2 Each independently selected from H, deuterium, and F;

[0500] R 6 、R 9 、R 10 Each independently selected from H, deuterium, F, Cl, OH, CN, methyl;

[0501] R 7 、R 8 Each independently selected from H, deuterium, F, Cl, OH, CN, methyl, R A2 ;

[0502] Alternatively, R 7 With R 8 and the atoms to which they are attached together form a 4-7 membered carbocyclic ring or a 5-7 membered heterocycloalkyl containing 1-3 heteroatoms selected from N, O, S, and B, or an 8 membered carbocyclic ring or a 5-7 membered heterocycloalkyl containing 1 Si atom, wherein the carbocyclic ring or heterocycloalkyl is optionally further substituted by 1-3 atoms selected from ═O, halogen, deuterium, CN, OH, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, deuterated C 1-4 Alkoxy and NH2 group substitution;

[0503] R A2 Selected from

[0504] R 2 、R 3 Each is independently selected from H, deuterium, vinyl, and ethynyl;

[0505] R 4 、R 5 Each is independently selected from H, deuterium, cyclopropyl, vinyl, and ethynyl;

[0506] Alternatively, R 4 、R 5 Together with the atoms to which it is attached, it forms phenyl, cyclohexyl, cyclopentyl, thienyl, furanyl, pyrrolyl, pyrazolyl, isoxazolyl;

[0507] Alternatively, R 2 、R 4 , L1 and the atoms to which it is attached together form a cyclohexyl group or a phenyl group;

[0508] Alternatively, R L1 With R 9 Together with the atoms to which they are attached, they form cyclopentyl or cyclohexyl;

[0509] R 1 Selected from R A1 ; or R 1 Selected from

[0510] R A1 Selected from Or choose Or choose

[0511] The condition is that the compound satisfies one of the following conditions:

[0512] (1).R 1 Selected from R A1 ;

[0513] (2).R 4 and R 5 At least one group is selected from cyclopropyl, vinyl, and ethynyl;

[0514] (3).R 4 、R 5 Together with the atoms to which it is attached, it forms phenyl, cyclohexyl, cyclopentyl, thienyl, furanyl, pyrrolyl, pyrazolyl, isoxazolyl;

[0515] (4).R 7 、R 8 At least one group is selected from R A2 ;

[0516] (5).R 2 、R 4 , L1 and the atoms to which it is attached together form a cyclohexyl group or a phenyl group;

[0517] (6) L1 is selected from O;

[0518] (7) L2 is selected from -C(O)-, -CHF-, -CF2-, and C(CH3)2-.

[0519] The twenty-sixth technical solution of the present invention is a compound of the present invention, a stereoisomer, a deuterated substance, a solvate, or a pharmaceutically acceptable salt or a cocrystal thereof, wherein

[0520] L1 is selected from a bond, O;

[0521] L2 is selected from -CH2-, -C(O)-, -CHF-, -CF2-, C(CH3)2-;

[0522] R L1 、R L2 Each independently selected from H, deuterium, and F;

[0523] R 6 、R 9 、R 10 Each independently selected from H, deuterium, F, Cl, OH, CN, methyl;

[0524] R 7 、R 8 Each independently selected from H, deuterium, F, Cl, OH, CN, methyl, R A2 ;

[0525] Alternatively, R 7 With R 8and the atoms to which they are attached together form a 4-7 membered carbocyclic ring or a 5-7 membered heterocycloalkyl containing 1-3 heteroatoms selected from N, O, S, and B, or an 8 membered carbocyclic ring or a 5-7 membered heterocycloalkyl containing 1 Si atom, wherein the carbocyclic ring or heterocycloalkyl is optionally further substituted by 1-3 atoms selected from ═O, halogen, deuterium, CN, OH, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, deuterated C 1-4 Alkoxy and NH2 group substitution;

[0526] R A2 Selected from

[0527] R 2 、R 3 Each is independently selected from H, deuterium, vinyl, and ethynyl;

[0528] R 4 、R 5 Each is independently selected from H, deuterium, cyclopropyl, vinyl, and ethynyl;

[0529] Alternatively, R 4 、R 5 Together with the atoms to which it is attached, it forms phenyl, cyclohexyl, cyclopentyl, thienyl, furanyl, pyrrolyl, pyrazolyl, isoxazolyl;

[0530] Alternatively, R 2 、R 4 , L1 and the atoms to which it is attached together form a cyclohexyl group or a phenyl group;

[0531] Alternatively, R L1 With R 9 Together with the atoms to which they are attached, they form cyclopentyl or cyclohexyl;

[0532] R 1 Selected from R A1 ; or R 1 Selected from

[0533] R A1 Selected from

[0534] Or choose Or choose

[0535] The condition is that the compound satisfies one of the following conditions:

[0536] (1).R 1Selected from R A1 ;

[0537] (2).R 4 and R 5 At least one group is selected from cyclopropyl, vinyl, and ethynyl;

[0538] (3).R 4 、R 5 Together with the atoms to which it is attached, it forms phenyl, cyclohexyl, cyclopentyl, thienyl, furanyl, pyrrolyl, pyrazolyl, isoxazolyl;

[0539] (4).R 7 、R 8 At least one group is selected from R A2 ;

[0540] (5).R 2 、R 4 , L1 and the atoms to which it is attached together form a cyclohexyl group or a phenyl group;

[0541] (6) L1 is selected from O;

[0542] (7).(7) L2 is selected from -C(O)-, -CHF-, -CF2-, C(CH3)2-.

[0543] The twenty-seventh technical solution of the present invention is a compound of the present invention, a stereoisomer, a deuterated substance, a solvate, or a pharmaceutically acceptable salt or a cocrystal thereof, wherein

[0544] L1 is selected from a bond, O;

[0545] L2 is selected from -CH2-, -C(O)-, -CHF-, -CF2-, C(CH3)2-;

[0546] R L1 、R L2 Each independently selected from H, deuterium, and F;

[0547] R 6 、R 9 、R 10 Each independently selected from H, deuterium, F, Cl, OH, CN, methyl;

[0548] R 7 、R 8 Each independently selected from H, deuterium, F, Cl, OH, CN, methyl, R A2 ;

[0549] Alternatively, R 7 With R 8and the atoms to which they are attached together form a 4-7 membered carbocyclic ring or a 5-7 membered heterocycloalkyl containing 1-3 heteroatoms selected from N, O, S, and B, or an 8 membered carbocyclic ring or a 5-7 membered heterocycloalkyl containing 1 Si atom, wherein the carbocyclic ring or heterocycloalkyl is optionally further substituted by 1-3 atoms selected from ═O, halogen, deuterium, CN, OH, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, deuterated C 1-4 Alkoxy and NH2 group substitution;

[0550] R A2 Selected from

[0551] R 2 、R 3 Each is independently selected from H, deuterium, vinyl, and ethynyl;

[0552] R 4 、R 5 Each is independently selected from H, deuterium, cyclopropyl, vinyl, and ethynyl;

[0553] Alternatively, R 4 、R 5 Together with the atoms to which it is attached, it forms phenyl, cyclohexyl, cyclopentyl, thienyl, furanyl, pyrrolyl, pyrazolyl, isoxazolyl;

[0554] Alternatively, R 2 、R 4 , L1 and the atoms to which it is attached together form a cyclohexyl group or a phenyl group;

[0555] Alternatively, R L1 With R 9 Together with the atoms to which they are attached, they form cyclopentyl or cyclohexyl;

[0556] R 1 Selected from R A1 ; or R 1 Selected from

[0557] R A1 Selected from Or choose Or choose

[0558] The condition is that the compound satisfies one of the following conditions:

[0559] (1).R 1 Selected from R A1 ;

[0560] (2).R 4 and R 5 At least one group is selected from cyclopropyl, vinyl, and ethynyl;

[0561] (3).R 4 、R 5 Together with the atoms to which it is attached, it forms phenyl, cyclohexyl, cyclopentyl, thienyl, furanyl, pyrrolyl, pyrazolyl, isoxazolyl;

[0562] (4).R 7 、R 8 At least one group is selected from R A2 ;

[0563] (5).R 2 、R 4 , L1 and the atoms to which it is attached together form a cyclohexyl group or a phenyl group;

[0564] (6) L1 is selected from O;

[0565] (7) L2 is selected from -C(O)-, -CHF-, -CF2-, and C(CH3)2-.

[0566] The twenty-eighth technical solution of the present invention relates to a compound of formula (Ia), a stereoisomer, deuterated substance, solvate, or pharmaceutically acceptable salt or cocrystal thereof, wherein

[0567] L1 is selected from a bond, O;

[0568] R 2 、R 3 Each is independently selected from H, deuterium, vinyl, and ethynyl;

[0569] R 4 、R 5 Each is independently selected from H, deuterium, cyclopropyl, vinyl, and ethynyl;

[0570] Alternatively, R 4 、R 5 Together with the atoms to which it is attached, it forms phenyl, cyclohexyl, cyclopentyl, thienyl, furanyl, pyrrolyl, pyrazolyl, isoxazolyl;

[0571] R 1 Selected from R A1 ; or R 1 Selected from

[0572] R A1 Selected from

[0573] X1 is selected from O, S;

[0574] R A4 Selected from Or choose

[0575] As an optional technical solution, the compound represented by formula (I) or (Ia), its stereoisomer, deuterated substance, solvate, or pharmaceutically acceptable salt, wherein R 1 -O-halogenated C 1-4 Alkyl, R 2 、R 3 is H, X1 is S or R 6 、R 7 、R 8 、R 9 At least one of them is R A2 , R A2 -(a 4-10 membered heterocycloalkyl containing 1-3 heteroatoms selected from N, O, S, Si), or -(a 5-10 membered heteroaryl containing 1-3 heteroatoms selected from N, O, S), -P(O)(R c )2、-Si(R c )3, -SF5, B(OH)2, or -S(O)(=NH)R c The heterocycloalkyl and heteroaryl groups are optionally further substituted by 1-3 groups selected from halogen, =O, D, CN, OH, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, C 3-6 Cycloalkyl, 4-7 membered heterocycloalkyl containing 1-3 heteroatoms selected from N, O, S, deuterated C 1-4 Alkoxy and NH2 group substitution;

[0576] or R 1 R A1 , R 2 、R 3 is H, X1 is O, R A1 C 2-6 Alkynyl, -C 1-4 Alkyl-OR a 、-NR b -S(O)2-R a , each R a Selected from C 3-10Cycloalkyl or 4-10 membered heterocycloalkyl containing 1-3 heteroatoms selected from N, O, S, wherein the cycloalkyl and heterocycloalkyl are optionally further substituted by 1-3 heteroatoms selected from halogen, =O, deuterium, CN, OH, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, deuterated C 1-4 The alkoxy group and the NH2 group are substituted; the remaining groups are as described in any of the above technical solutions.

[0577] The twenty-ninth technical solution of the present invention relates to a compound of formula (Ia), its stereoisomers, deuterated substances, solvates,

[0578] or a pharmaceutically acceptable salt or cocrystal, wherein

[0579] L1 is selected from a bond, O;

[0580] R 2 、R 3 Each is independently selected from H, deuterium, vinyl, and ethynyl;

[0581] R 4 、R 5 Each is independently selected from H, deuterium, cyclopropyl, vinyl, and ethynyl;

[0582] Alternatively, R 4 、R 5 Together with the atoms to which it is attached, it forms phenyl, cyclohexyl, cyclopentyl, thienyl, furanyl, pyrrolyl, pyrazolyl, isoxazolyl;

[0583] R 1 Selected from R A1 ; or R 1 Selected from

[0584] R A1 Selected from

[0585] X1 is selected from O, S;

[0586] R A4 Selected from Or choose

[0587] As an optional technical solution, the compound represented by formula (I) or (Ia), its stereoisomer, deuterated substance, solvate, or pharmaceutically acceptable salt, wherein R 1 -O-halogenated C 1-4 Alkyl, R 2、R 3 is H, X1 is S or R 6 、R 7 、R 8 、R 9 At least one of them is R A2 , R A2 -(a 4-10 membered heterocycloalkyl containing 1-3 heteroatoms selected from N, O, S, Si), or -(a 5-10 membered heteroaryl containing 1-3 heteroatoms selected from N, O, S), -P(O)(R c )2、-Si(R c )3, -SF5, B(OH)2, or -S(O)(=NH)R c The heterocycloalkyl and heteroaryl groups are optionally further substituted by 1-3 groups selected from halogen, =O, D, CN, OH, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, C 3-6 Cycloalkyl, 4-7 membered heterocycloalkyl containing 1-3 heteroatoms selected from N, O, S, deuterated C 1-4 Alkoxy and NH2 group substitution;

[0588] or R 1 R A1 , R 2 、R 3 is H, X1 is O, R A1 C 2-6 Alkynyl, -C 1-4 Alkyl-OR a 、-NR b -S(O)2-R a , each R a Selected from C 3-10 Cycloalkyl or 4-10 membered heterocycloalkyl containing 1-3 heteroatoms selected from N, O, S, wherein the cycloalkyl and heterocycloalkyl are optionally further substituted by 1-3 heteroatoms selected from halogen, =O, deuterium, CN, OH, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, deuterated C 1-4 The alkoxy group and the NH2 group are substituted; the remaining groups are as described in any of the above technical solutions.

[0589] The 30th technical solution of the present invention is a compound of the present invention, a stereoisomer, a deuterated substance, a solvate, or a pharmaceutically

[0590] An acceptable salt having the structure of formula (I):

[0591] in,

[0592] R 1 、R 2 、R 3 Each independently selected from H, deuterium, R A1 、-O-halogenated C 1-4 Alkyl, -NH-halogenated C 1-4 Alkyl, -OC 1-4 Alkyl, C 1-4 Alkoxy, C 5-6 Alkoxy, halogen, cyano, nitro, C 1-4 Alkyl, C 2-6 Alkenyl, -NH-C 1-4 Alkyl, -N(C 1-4 Alkyl)2, -NH-C 3-10 Cycloalkyl, -NHC(O)C 1-4 Alkyl or 4-10 membered heterocycloalkyl containing 1-3 heteroatoms selected from N, O, S, wherein the alkyl, alkoxy, cycloalkyl, heterocycloalkyl is optionally further substituted by 1-3 heteroatoms selected from halogen, D, CN, OH, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, deuterated C 1-4 Alkoxy, C 3-10 Cycloalkyl, 4-6 membered heterocycloalkyl containing 1-3 heteroatoms selected from N, O, S, phenyl, and NH2, provided that R 1 、R 2 and R 3 Not selected from H at the same time;

[0593] R A1 Selected from halogenated C 2-6 Alkenyl, C 2-6 Alkynyl, -O-(CH2) r -R a 、C 3-10 Cycloalkyl, 5-10 membered heteroaryl containing 1-3 heteroatoms selected from N, O, S, -C 1-4 Alkyl-R a 、-C 1-4 Alkyl-OR a 、-C 1-4 Alkyl-NR b R a 、-NR b -S(O)2-R a 、-NRb -S(O)2-NR b R a 、-O-NR b R a 、-NH-OR b 、-Se-(CH2) r -R a The alkynyl, heteroaryl, and alkyl groups are optionally further substituted by 1 to 3 groups selected from halogen, deuterium, CN, OH, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, deuterated C 1-4 Alkoxy and NH2 group substitution;

[0594] Each R a Selected from CN, halogenated C 1-6 Alkyl, C 3-10 Cycloalkyl, 4-10 membered heterocycloalkyl containing 1-3 heteroatoms selected from N, O, S, 6-10 membered aryl, 5-10 membered heteroaryl containing 1-3 heteroatoms selected from N, O, S, -C(O)-R a1 The alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl groups are optionally further substituted by 1-3 groups selected from halogen, =O, deuterium, CN, OH, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, deuterated C 1-4 Alkoxy and NH2 group substitution;

[0595] Each R b Selected from H, deuterium, C 1-4 Alkyl, C 3-6 Cycloalkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 alkyl;

[0596] R a1 Selected from OH, NH2, -NHC 1-4 Alkyl, -N(C 1-4 Alkyl)2, -NHC 3-10 Cycloalkyl, C 1-4 Alkoxy, C 1-6 Alkyl, C 3-10 Cycloalkyl, 6-10 membered aryl, 5-10 membered heteroaryl containing 1-3 heteroatoms selected from N, O, S;

[0597] X is selected from CR 10 or N;

[0598] X1 is selected from O, S;

[0599] R 4 、R 5 Each independently selected from H, deuterium, C 3-10 Cycloalkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, halogen, amino, -NH-C 1-4 Alkyl, -N(C 1-4 Alkyl)2, C 1-4 Alkyl, halogenated C 1-4 Alkyl, 4-10 membered heterocycloalkyl containing 1-3 heteroatoms selected from N, O, and S, 5-10 membered heteroaryl, and 6-10 membered aryl containing 1-3 heteroatoms selected from N, O, and S;

[0600] R 6 、R 7 、R 8 、R 9 、R 10 Each independently selected from H, deuterium, R A2 , halogen, OH, CN, amino, C 1-4 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-4 Alkoxy, halogenated C 1-4 Alkyl, -NH-C 1-4 Alkyl, -N(C 1-4 Alkyl)2, -S(O)R c 、-S(O) 2 R c 、-C(O)R c 、-C(O)OR c 、-C(O)N(R c )2、-OC(O)R c The alkyl, alkenyl, alkynyl, and alkoxy groups are optionally further substituted by 1 to 3 groups selected from halogen, deuterium, CN, OH, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, deuterated C 1-4 Alkoxy and NH2 groups substituted; provided that, R 7 With R 8 、R 8 With R 9At least one group of the carbon ring and the atoms connected thereto together form a 4-8 membered carbocyclic ring, a 5-7 membered heterocycloalkyl containing 1-3 heteroatoms selected from N, O, S, B, Si, wherein the carbon ring and heterocycloalkyl are optionally further substituted by 1-3 heteroatoms selected from =O, halogen, deuterium, CN, OH, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, deuterated C 1-4 Alkoxy and NH2 group substitution;

[0601] R A2 Selected from -(CH2) r -(4-10 membered heterocycloalkyl containing 1-3 heteroatoms selected from N, O, S, Si), or -(CH2) r -(5-10 membered heteroaryl containing 1-3 heteroatoms selected from N, O, S), -P(O)(R c )2、-Si(R c )3, -SF5, N3, B(OH)2, or -S(O)(=NH)R c The heterocycloalkyl and heteroaryl groups are optionally further substituted by 1-3 groups selected from halogen, =O, D, CN, OH, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, C 3-6 Cycloalkyl, 4-7 membered heterocycloalkyl containing 1-3 heteroatoms selected from N, O, S, deuterated C 1-4 Alkoxy and NH2 group substitution;

[0602] Each R c Each independently selected from H, OH, C 1-4 Alkyl, C 3-7 Cycloalkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, deuterated C 1-4 Alkoxy, or NH2;

[0603] Each r is independently selected from 0, 1, 2 or 3;

[0604] L1 is selected from a bond, O, NH, S, -CD2-, -CHD-, -CR L1 R L2 -、C 1-4Alkyl, -C(O)-, S(O), S(O)2, wherein the alkyl group is optionally further R L1 replace;

[0605] L2 is selected from O, NH, S, -CH2-, -CD2-, -CHD-, -CR L1 R L2 -、-CHR L2 -、-CDR L2 -、C 2-4 Alkyl, -C(O)-, S(O), S(O)2, wherein the alkyl group is optionally further substituted with 1-3 R L1 replace;

[0606] R L1 、R L2 Each independently selected from halogen, OH, CN, amino, C 1-4 Alkyl, C 1-4 Alkoxy, C 3-6 Cycloalkyl, 4-6 membered heterocycloalkyl containing 1-3 heteroatoms selected from N, O, S;

[0607] Alternatively, R 2 、R 4 , L1 and the atoms to which they are connected together form a 5-7 membered carbocyclic ring, a 5-7 membered heterocyclic ring containing 1-3 heteroatoms selected from N, O, and S, wherein the carbocyclic ring or heterocyclic ring is optionally further substituted by 1-3 heteroatoms selected from R A3 The group substitution;

[0608] Alternatively, R 4 、R 5 Together with the atoms to which they are connected, they form a 5-7 membered monocyclic carbocyclic ring or a 5-7 membered heterocyclic ring containing 1-3 heteroatoms selected from N, O, and S, wherein the carbocyclic ring or heterocyclic ring is optionally substituted by 1-3 heteroatoms selected from R A3 The group substitution;

[0609] Alternatively, R L2 With R 9 Together with the atoms to which they are connected, they form a 5-7 membered carbocyclic ring or a 5-7 membered heterocyclic ring containing 1-3 heteroatoms selected from N, O, and S, wherein the carbocyclic ring or heterocyclic ring is optionally further surrounded by 1-3 heteroatoms selected from R A3 The group substitution;

[0610] Alternatively, R 6 With R 10 and the atoms to which they are attached together form a 4-7 membered carbocyclic ring, a 5-7 membered heterocycloalkyl containing 1-3 heteroatoms selected from N, O, S, and B, an 8 membered carbocyclic ring, or a 5-7 membered heterocycloalkyl containing 1 Si atom, wherein the carbocyclic ring or heterocycloalkyl is optionally further substituted by 1-3 atoms selected from ═O, halogen, deuterium, CN, OH, C 1-4Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, deuterated C 1-4 Alkoxy and NH2 group substitution;

[0611] Each R A3 Each independently selected from =O, halogen, deuterium, CN, OH, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, deuterated C 1-4 Alkoxy and NH2 groups are substituted.

[0612] The thirty-first technical solution of the present invention is that the compound of the present invention, its stereoisomer, deuterated substance, solvate, or pharmaceutically acceptable salt or cocrystal has the structure of formula (I):

[0613] in,

[0614] R 1 、R 2 、R 3 Each independently selected from H, deuterium, R A1 、-O-halogenated C 1-4 Alkyl, -NH-halogenated C 1-4 Alkyl, -OC 1-4 Alkyl, C 1-6 Alkoxy, halogen, cyano, nitro, C 1-4 Alkyl, -NH-C 1-4 Alkyl, -N(C 1-4 Alkyl)2, -NH-C 3-10 Cycloalkyl, -NHC(O)C 1-4 Alkyl or 4-10 membered heterocycloalkyl containing 1-3 heteroatoms selected from N, O, S, wherein the alkyl, alkoxy, cycloalkyl, heterocycloalkyl is optionally further substituted by 1-3 heteroatoms selected from halogen, D, CN, OH, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, deuterated C 1-4 Alkoxy, C 3-10 Cycloalkyl, 4-6 membered heterocycloalkyl containing 1-3 heteroatoms selected from N, O, S, phenyl, and NH2, provided that R 1 、R 2 and R 3Not selected from H at the same time;

[0615] R A1 Selected from halogenated C 2-6 Alkenyl, C 2-6 Alkynyl, -O-(CH2) r -R a 、C 3-10 Cycloalkyl, 5-10 membered heteroaryl containing 1-3 heteroatoms selected from N, O, S, -C 1-4 Alkyl-R a 、-C 1-4 Alkyl-OR a 、-C 1-4 Alkyl-NR b R a 、-NR b -S(O)2-R a 、-NR b -S(O)2-NR b R a 、-O-NR b R a 、-NH-OR b 、-Se-(CH2) r -R a The alkynyl, heteroaryl, alkyl, cycloalkyl group may be further substituted by 1-3 groups selected from halogen, deuterium, CN, OH, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, deuterated C 1-4 Alkoxy and NH2 group substitution;

[0616] Each R a Selected from CN, halogenated C 1-6 Alkyl, C 3-10 Cycloalkyl, 4-10 membered heterocycloalkyl containing 1-3 heteroatoms selected from N, O, S, 6-10 membered aryl, 5-10 membered heteroaryl containing 1-3 heteroatoms selected from N, O, S, -C(O)-R a1 The alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl groups are optionally further substituted by 1-3 groups selected from halogen, =O, deuterium, CN, OH, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, deuterated C 1-4 Alkoxy and NH2 group substitution;

[0617] Each R bSelected from H, deuterium, C 1-4 Alkyl, C 3-6 Cycloalkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 alkyl;

[0618] R a1 Selected from OH, NH2, -NHC 1-4 Alkyl, -N(C 1-4 Alkyl)2, -NHC 3-10 Cycloalkyl, C 1-4 Alkoxy, C 1-6 Alkyl, C 3-10 Cycloalkyl, 6-10 membered aryl, 5-10 membered heteroaryl containing 1-3 heteroatoms selected from N, O, S;

[0619] X is selected from CR 10 or N;

[0620] X1 is selected from O, S;

[0621] R 4 、R 5 Each independently selected from H, deuterium, C 3-10 Cycloalkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, halogen, amino, -NH-C 1-4 Alkyl, -N(C 1-4 Alkyl)2, C 1-4 Alkyl, halogenated C 1-4 Alkyl, 4-10 membered heterocycloalkyl containing 1-3 heteroatoms selected from N, O, and S, 5-10 membered heteroaryl, and 6-10 membered aryl containing 1-3 heteroatoms selected from N, O, and S;

[0622] R 6 、R 7 、R 8 、R 9 、R 10 Each independently selected from H, deuterium, R A2 , halogen, OH, CN, amino, C 1-4 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-4 Alkoxy, halogenated C 1-4 Alkyl, -NH-C 1-4 Alkyl, -N(C 1-4 Alkyl)2, -S(O)R c 、-S(O) 2 R c 、-C(O)R c 、-C(O)OR c 、-C(O)N(Rc )2、-OC(O)R c The alkyl, alkenyl, alkynyl, and alkoxy groups are optionally further substituted by 1 to 3 groups selected from halogen, deuterium, CN, OH, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, deuterated C 1-4 Alkoxy and NH2 group substitution;

[0623] R A2 Selected from -(CH2) r -(C 3-10 Cycloalkyl), -(CH2) r -(4-10 membered heterocycloalkyl containing 1-3 heteroatoms selected from N, O, S, Si), or -(CH2) r -(5-10 membered heteroaryl containing 1-3 heteroatoms selected from N, O, S), -P(O)(R c )2、-Si(R c )3, -SF5, N3, B(OH)2, or -S(O)(=NH)R c The cycloalkyl, heterocycloalkyl, and heteroaryl groups are optionally further substituted by 1 to 3 groups selected from halogen, =O, D, CN, OH, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, C 3-6 Cycloalkyl, 4-7 membered heterocycloalkyl containing 1-3 heteroatoms selected from N, O, S, deuterated C 1-4 Alkoxy and NH2 group substitution;

[0624] Each R c Each independently selected from H, OH, C 1-4 Alkyl, C 3-7 Cycloalkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, deuterated C 1-4 Alkoxy or NH2;

[0625] Each r is independently selected from 0, 1, 2 or 3;

[0626] L1 is selected from a bond, O, NH, S, -CD2-, -CHD-, -CR L1 R L2 -、C 1-4Alkyl, -C(O)-, S(O), S(O)2, wherein the alkyl group is optionally further R L1 replace;

[0627] L2 is selected from a bond, O, NH, S, -CH2-, -CD2-, -CHD-, -CR L1 R L2 -、-CHR L2 -、-CDR L2 -、C 2-4 Alkyl, -C(O)-, S(O), S(O)2, wherein the alkyl group is optionally further substituted with 1-3 R L1 replace;

[0628] R L1 、R L2 Each independently selected from halogen, OH, CN, amino, C 1-4 Alkyl, C 1-4 Alkoxy, C 3-6 Cycloalkyl, 4-6 membered heterocycloalkyl containing 1-3 heteroatoms selected from N, O, S;

[0629] Alternatively, R 2 、R 4 , L1 and the atoms to which they are connected together form a 5-7 membered carbocyclic ring, a 5-7 membered heterocyclic ring containing 1-3 heteroatoms selected from N, O, and S, wherein the carbocyclic ring or heterocyclic ring is optionally further substituted by 1-3 heteroatoms selected from R A3 The group substitution;

[0630] Alternatively, R 4 、R 5 Together with the atoms to which they are connected, they form a 5-7 membered monocyclic carbocyclic ring or a 5-7 membered heterocyclic ring containing 1-3 heteroatoms selected from N, O, and S, wherein the carbocyclic ring or heterocyclic ring is optionally substituted by 1-3 heteroatoms selected from R A3 The group substitution;

[0631] Alternatively, R L2 With R 9 Together with the atoms to which they are connected, they form a 5-7 membered carbocyclic ring or a 5-7 membered heterocyclic ring containing 1-3 heteroatoms selected from N, O, and S, wherein the carbocyclic ring or heterocyclic ring is optionally further surrounded by 1-3 heteroatoms selected from R A3 The group substitution;

[0632] Each R A3 Each independently selected from =O, halogen, deuterium, CN, OH, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, deuterated C 1-4Alkoxy and NH2 group substitution;

[0633] The conditions are: R 6 With R 10 、R 10 With R 7 、R 7 With R 8 、R 8 With R 9 A group of the carbon ring and the atoms connected thereto together form a 4-8 membered carbocyclic ring, a 5-7 membered heterocycloalkyl containing 1-3 heteroatoms selected from N, O, S, B, Si, wherein the carbon ring, the heterocycloalkyl is optionally further substituted by 1-3 heteroatoms selected from =O, Halogen, deuterium, CN, OH, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, deuterated C 1-4 The alkyl group may be substituted with an alkoxy group, a 5-7 membered heterocycloalkyl group containing 1-3 heteroatoms selected from N, O, S, B, Si, a 5-7 membered heteroaryl group containing 1-3 heteroatoms selected from N, O, S, B, Si, and NH2.

[0634] As an alternative to the thirty-first technical solution of the present invention, the compound of the present invention, its stereoisomer, deuterated substance, solvate, or pharmaceutically acceptable salt or cocrystal has the structure of formula (I):

[0635] in,

[0636] R 1 、R 2 、R 3 Each independently selected from H, deuterium, R A1 、-O-halogenated C 1-4 Alkyl, -NH-halogenated C 1-4 Alkyl, -OC 1-4 Alkyl, C 1-6 Alkoxy, halogen, cyano, nitro, C 1-4 Alkyl, -NH-C 1-4 Alkyl, -N(C 1-4 Alkyl)2, -NH-C 3-10 Cycloalkyl, -NHC(O)C 1-4 Alkyl or 4-10 membered heterocycloalkyl containing 1-3 heteroatoms selected from N, O, S, wherein the alkyl, alkoxy, cycloalkyl, heterocycloalkyl is optionally further substituted by 1-3 heteroatoms selected from halogen, D, CN, OH, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, C1-4 Alkoxy, halogenated C 1-4 Alkoxy, deuterated C 1-4 Alkoxy, C 3-10 Cycloalkyl, 4-6 membered heterocycloalkyl containing 1-3 heteroatoms selected from N, O, S, phenyl, and NH2, provided that R 1 、R 2 and R 3 Not selected from H at the same time;

[0637] R A1 Selected from halogenated C 2-6 Alkenyl, C 2-6 Alkynyl, -O-(CH2) r -R a 、C 3-10 Cycloalkyl, 5-10 membered heteroaryl containing 1-3 heteroatoms selected from N, O, S, -C 1-4 Alkyl-R a 、-C 1-4 Alkyl-OR a 、-C 1-4 Alkyl-NR b R a 、-NR b -S(O)2-R a 、-NR b -S(O)2-NR b R a 、-O-NR b R a 、-NH-OR b 、-Se-(CH2) r -R a The alkynyl, heteroaryl, alkyl, cycloalkyl group may be further substituted by 1-3 groups selected from halogen, deuterium, CN, OH, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, deuterated C 1-4 Alkoxy and NH2 group substitution;

[0638] Each R a Selected from CN, halogenated C 1-6 Alkyl, C 3-10 Cycloalkyl, 4-10 membered heterocycloalkyl containing 1-3 heteroatoms selected from N, O, S, 6-10 membered aryl, 5-10 membered heteroaryl containing 1-3 heteroatoms selected from N, O, S, -C(O)-R a1 The alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl groups are optionally further substituted by 1-3 groups selected from halogen, =O, deuterium, CN, OH, C1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, deuterated C 1-4 Alkoxy and NH2 group substitution;

[0639] Each R b Selected from H, deuterium, C 1-4 Alkyl, C 3-6 Cycloalkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 alkyl;

[0640] R a1 Selected from OH, NH2, -NHC 1-4 Alkyl, -N(C 1-4 Alkyl)2, -NHC 3-10 Cycloalkyl, C 1-4 Alkoxy, C 1-6 Alkyl, C 3-10 Cycloalkyl, 6-10 membered aryl, 5-10 membered heteroaryl containing 1-3 heteroatoms selected from N, O, S;

[0641] X is selected from CR 10 or N;

[0642] X1 is selected from O, S;

[0643] R 4 、R 5 Each independently selected from H, deuterium, C 3-10 Cycloalkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, halogen, amino, -NH-C 1-4 Alkyl, -N(C 1-4 Alkyl)2, C 1-4 Alkyl, halogenated C 1-4 Alkyl, 4-10 membered heterocycloalkyl containing 1-3 heteroatoms selected from N, O, and S, 5-10 membered heteroaryl, and 6-10 membered aryl containing 1-3 heteroatoms selected from N, O, and S;

[0644] R 6 、R 7 、R 8 、R 9 、R 10 Each independently selected from H, deuterium, R A2 , halogen, OH, CN, amino, C 1-4 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-4 Alkoxy, halogenated C1-4 Alkyl, -NH-C 1-4 Alkyl, -N(C 1-4 Alkyl)2, -S(O)R c 、-S(O) 2 R c 、-C(O)R c 、-C(O)OR c 、-C(O)N(R c )2、-OC(O)R c The alkyl, alkenyl, alkynyl, and alkoxy groups are optionally further substituted by 1 to 3 groups selected from halogen, deuterium, CN, OH, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, deuterated C 1-4 Alkoxy and NH2 group substitution;

[0645] R A2 Selected from -(CH2) r -(4-10 membered heterocycloalkyl containing 1-3 heteroatoms selected from N, O, S, Si), or -(CH2) r -(5-10 membered heteroaryl containing 1-3 heteroatoms selected from N, O, S), -P(O)(R c )2、-Si(R c )3, -SF5, N3, B(OH)2, or -S(O)(=NH)R c The heterocycloalkyl and heteroaryl groups are optionally further substituted by 1-3 groups selected from halogen, =O, D, CN, OH, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, C 3-6 Cycloalkyl, 4-7 membered heterocycloalkyl containing 1-3 heteroatoms selected from N, O, S, deuterated C 1-4 Alkoxy and NH2 group substitution;

[0646] Each R c Each independently selected from H, OH, C 1-4 Alkyl, C 3-7 Cycloalkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, deuterated C 1-4 Alkoxy or NH2;

[0647] Each r is independently selected from 0, 1, 2 or 3;

[0648] L1 is selected from a bond, O, NH, S, -CD2-, -CHD-, -CR L1 R L2 -、C 1-4 Alkyl, -C(O)-, S(O), S(O)2, wherein the alkyl group is optionally further R L1 replace;

[0649] L2 is selected from a bond, O, NH, S, -CH2-, -CD2-, -CHD-, -CR L1 R L2 -、-CHR L2 -、-CDR L2 -、C 2-4 Alkyl, -C(O)-, S(O), S(O)2, wherein the alkyl group is optionally further substituted with 1-3 R L1 replace;

[0650] R L1 、R L2 Each independently selected from halogen, OH, CN, amino, C 1-4 Alkyl, C 1-4 Alkoxy, C 3-6 Cycloalkyl, 4-6 membered heterocycloalkyl containing 1-3 heteroatoms selected from N, O, S;

[0651] Alternatively, R 2 、R 4 , L1 and the atoms to which they are connected together form a 5-7 membered carbocyclic ring, a 5-7 membered heterocyclic ring containing 1-3 heteroatoms selected from N, O, and S, wherein the carbocyclic ring or heterocyclic ring is optionally further substituted by 1-3 heteroatoms selected from R A3 The group substitution;

[0652] Alternatively, R 4 、R 5 Together with the atoms to which they are connected, they form a 5-7 membered monocyclic carbocyclic ring or a 5-7 membered heterocyclic ring containing 1-3 heteroatoms selected from N, O, and S, wherein the carbocyclic ring or heterocyclic ring is optionally substituted by 1-3 heteroatoms selected from R A3 The group substitution;

[0653] Alternatively, R L2 With R 9 Together with the atoms to which they are connected, they form a 5-7 membered carbocyclic ring or a 5-7 membered heterocyclic ring containing 1-3 heteroatoms selected from N, O, and S, wherein the carbocyclic ring or heterocyclic ring is optionally further surrounded by 1-3 heteroatoms selected from R A3 The group substitution;

[0654] Each R A3 Each independently selected from =O, halogen, deuterium, CN, OH, C1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, deuterated C 1-4 Alkoxy and NH2 group substitution;

[0655] The conditions are: R 6 With R 10 、R 10 With R 7 、R 7 With R 8 、R 8 With R 9 A group of the carbon ring and the atoms connected thereto together form a 4-8 membered carbocyclic ring, a 5-7 membered heterocycloalkyl containing 1-3 heteroatoms selected from N, O, S, B, Si, wherein the carbon ring, the heterocycloalkyl is optionally further substituted by 1-3 heteroatoms selected from =O, Halogen, deuterium, CN, OH, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, deuterated C 1-4 substituted with an alkoxy group, a 5-7 membered heterocycloalkyl group containing 1-3 heteroatoms selected from N, O, S, B, and Si, a 5-7 membered heteroaryl group containing 1-3 heteroatoms selected from N, O, S, B, and Si, and NH2; in some embodiments, provided that: R 6 With R 10 、R 10 With R 7 、R 7 With R 8 、R 8 With R 9 A group of the group and the atoms connected thereto together form a 4-8 membered cycloalkyl, a 5-7 membered heterocycloalkyl containing 1-3 heteroatoms selected from N, O, S, B, Si, wherein the cycloalkyl and heterocycloalkyl are optionally further substituted by 1-3 heteroatoms selected from =O, halogen, deuterium, CN, OH, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, deuterated C 1-4 The alkyl group may be substituted with an alkoxy group, a 5-7 membered heterocycloalkyl group containing 1-3 heteroatoms selected from N, O, S, B, Si, a 5-7 membered heteroaryl group containing 1-3 heteroatoms selected from N, O, S, B, Si, and NH2.

[0656] The thirty-second technical solution of the present invention is a compound of the present invention, a stereoisomer, a deuterated substance, a solvate, or a pharmaceutically acceptable salt or a cocrystal thereof, wherein

[0657] R 6 、R 7 、R 8 、R 9 、R 10 Each independently selected from H, deuterium, -SF5, N3, halogen, OH, CN, amino, C 1-2 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-2 Alkoxy, halogenated C 1-2 Alkyl, -NH-C 1-2 Alkyl, -N(C 1-2 alkyl) 2, wherein the alkyl, alkenyl, alkynyl, alkoxy group is optionally further substituted by 1-3 groups selected from halogen, deuterium, CN, OH, C 1-2 Alkyl, halogenated C 1-2 Alkyl, deuterated C 1-2 Alkyl, C 1-2 Alkoxy, halogenated C 1-2 Alkoxy, deuterated C 1-2 Alkoxy and NH2 group substitution;

[0658] The remaining groups are as described in any of the above technical solutions.

[0659] The thirty-third technical solution of the present invention is that the compound of the present invention, its stereoisomer, deuterated substance, solvate, or pharmaceutically acceptable salt or cocrystal has the structure of formula (II) or (II-a):

[0660] L2 is selected from a bond, -CH2-, -CR L1 R L2 -、-CHR L2 -、-CDR L2 -, -C(O)-;

[0661] R L1 、R L2 Each independently selected from halogen, OH, CN, amino, C 1-2 Alkyl, C 1-2 Alkoxy, C 3-4 Cycloalkyl, 4-membered heterocycloalkyl containing 1-3 heteroatoms selected from N, O, and S;

[0662] R 2 、R 3 Each independently selected from H, deuterium, C 1-2 Alkoxy, halogen, cyano, nitro, C 1-2Alkyl, wherein the alkyl and alkoxy groups are optionally further substituted by 1-3 groups selected from halogen, D, CN, OH and NH2;

[0663] R 1 Selected from R A1 、-O-halogenated C 1-4 Alkyl, -NH-halogenated C 1-4 Alkyl, C 1-4 Alkoxy, halogen, cyano, nitro, C 1-4 Alkyl, -NH-C 1-4 Alkyl, -N(C 1-4 Alkyl)2, -NH-C 3-10 Cycloalkyl, -NHC(O)C 1-4 Alkyl or 4-10 membered heterocycloalkyl containing 1-3 heteroatoms selected from N, O, S, wherein the alkyl, alkoxy, cycloalkyl, heterocycloalkyl is optionally further substituted by 1-3 heteroatoms selected from halogen, D, CN, OH, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, deuterated C 1-4 Alkoxy, C 3-10 substituted by cycloalkyl, 4-6 membered heterocycloalkyl containing 1-3 heteroatoms selected from N, O, S, phenyl and NH2;

[0664] X is selected from CR 10 or N;

[0665] R 4 、R 5 Each independently selected from H, deuterium, C 3-7 Cycloalkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, F, Cl, amino, -NH-C 1-2 Alkyl, -N(C 1-2 Alkyl)2, C 1-2 Alkyl, 4-7 membered heterocycloalkyl containing 1-3 heteroatoms selected from N, O, S;

[0666] R 7 、R 8 Each independently selected from H, deuterium, F, Cl, OH, CN, amino, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-4 Alkoxy, halogenated C 1-4 Alkyl, -NH-C 1-2 Alkyl, -N(C 1-2 Alkyl)2, -S(O)R c、-S(O) 2 R c 、-C(O)R c 、-C(O)OR c 、-C(O)N(R c )2、-OC(O)R c ;

[0667] R 6 、R 9 、R 10 Each independently selected from H, deuterium, F, Cl, OH, CN, amino, C 1-2 alkyl;

[0668] Alternatively, R 2 、R 4 Together with the atoms to which they are connected, they form a 5-7 membered carbocyclic ring or a 5-7 membered heterocyclic ring containing 1-3 heteroatoms selected from N, O, and S, wherein the carbocyclic ring or heterocyclic ring is optionally further surrounded by 1-3 heteroatoms selected from R A3 The group substitution;

[0669] Each R A3 Each independently selected from =O, halogen, deuterium, CN, OH, C 1-2 Alkyl, halogenated C 1-2 Alkyl, deuterated C 1-2 Alkyl, C 1-2 Alkoxy, halogenated C 1-2 Alkoxy, deuterated C 1-2 Alkoxy and NH2 group substitution;

[0670] The conditions are: R 10 With R 7 、R 7 With R 8 、R 8 With R 9 A group of the group and the atoms connected thereto together form a 4-8 membered cycloalkyl, a 5-7 membered heterocycloalkyl containing 1-3 heteroatoms selected from N, O, S, B, Si, wherein the cycloalkyl and heterocycloalkyl are optionally further substituted by 1-3 heteroatoms selected from =O, Halogen, deuterium, CN, OH, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, deuterated C 1-4 substituted with an alkoxy group, a 5-7 membered heterocycloalkyl group containing 1-3 heteroatoms selected from N, O, S, B, and Si, a 5-7 membered heteroaryl group containing 1-3 heteroatoms selected from N, O, S, B, and Si, and NH2; in some embodiments, provided that: R 10 With R7 、R 7 With R 8 、R 8 With R 9 A group of the group and the atoms connected thereto together form a 4-8 membered cycloalkyl, a 5-7 membered heterocycloalkyl containing 1-3 heteroatoms selected from N, O, S, B, Si, wherein the cycloalkyl and heterocycloalkyl are optionally further substituted by 1-3 heteroatoms selected from =O, halogen, deuterium, CN, OH, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, deuterated C 1-4 Alkoxy, 5-7 membered heterocycloalkyl containing 1-3 heteroatoms selected from N, O, S, B, Si, 5-7 membered heteroaryl containing 1-3 heteroatoms selected from N, O, S, B, Si, and NH2;

[0671] The remaining groups are as described in any of the above technical solutions.

[0672] The thirty-fourth technical solution of the present invention is that the compound of the present invention, its stereoisomer, deuterated substance, solvate, or pharmaceutically acceptable salt or cocrystal has the structure of formula (III) or (III-a):

[0673] X is selected from CR 10 or N;

[0674] R 6 、R 7 、R 8 、R 9 、R 10 Each independently selected from H, deuterium, F, Cl, OH, CN, amino, C 1-2 alkyl;

[0675] Alternatively, R 2 、R 4 Together with the atoms to which they are connected, they form a 5-7 membered carbocyclic ring or a 5-7 membered heterocyclic ring containing 1-3 heteroatoms selected from N, O, and S, wherein the carbocyclic ring or heterocyclic ring is optionally further surrounded by 1-3 heteroatoms selected from R A3 The group substitution;

[0676] The conditions are: R 10 With R 7 、R 7 With R 8 、R 8 With R 9A group of the group and the atoms connected thereto together form a 4-8 membered cycloalkyl, a 5-7 membered heterocycloalkyl containing 1-3 heteroatoms selected from N, O, S, B, Si, wherein the cycloalkyl and heterocycloalkyl are optionally further substituted by 1-3 heteroatoms selected from =O, Halogen, deuterium, CN, OH, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, deuterated C 1-4 The alkyl group is substituted with an alkoxy group, a 5-7 membered heterocycloalkyl group containing 1-3 heteroatoms selected from N, O, S, B, and Si, a 5-7 membered heteroaryl group containing 1-3 heteroatoms selected from N, O, S, B, and Si, and an NH2 group; the remaining groups are as described in any of the aforementioned technical solutions.

[0677] The thirty-fifth technical solution of the present invention is a compound of the present invention, a stereoisomer, a deuterated substance, a solvate, or a pharmaceutically acceptable salt or a cocrystal thereof, wherein

[0678] R 1 Selected from R A1 、-O-halogenated C 1-4 Alkyl, C 1-4 Alkyl, wherein the alkyl is optionally further substituted by 1-3 groups selected from halogen, D, CN, OH, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, deuterated C 1-4 Alkoxy and NH2 group substitution;

[0679] R 2 、R 3 Each independently selected from H, deuterium, C 2-4 Alkenyl, C 2-4 Alkynyl, halogen, cyano, nitro, OH, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 alkyl;

[0680] R A1 Selected from halogenated C 2-4 Alkenyl, C 2-4 Alkynyl, -O-(CH2) r -R a 、C 3-6 Monocyclic cycloalkyl, C 5-8 Bicyclic bridged ring cycloalkyl, C 6-10Bicyclic spirocyclic cycloalkyl, 5-6 membered monocyclic heteroaryl containing 1-3 heteroatoms selected from N, O, S, 8-10 membered bicyclic heteroaryl containing 1-3 heteroatoms selected from N, O, S, -C 1-2 Alkyl-R a 、-C 1-2 Alkyl-OR a 、-C 1-2 Alkyl-NR b R a 、-NR b -S(O)2-R a 、-NR b -S(O)2-NR b R a 、-O-NR b R a 、-NH-OR b 、-Se-(CH2) r -R a The alkynyl, heteroaryl, alkyl, cycloalkyl group may be further substituted by 1-3 groups selected from halogen, deuterium, CN, OH, C 1-2 Alkyl, halogenated C 1-2 Alkyl, deuterated C 1-2 Alkyl, C 1-2 Alkoxy, halogenated C 1-2 Alkoxy, deuterated C 1-2 Alkoxy and NH2 group substitution;

[0681] Each R a Selected from CN, halogenated C 1-4 Alkyl, C 3-6 Monocyclic cycloalkyl, C 7-10 Spirocyclic cycloalkyl, C 4-8 Bridged ring cycloalkyl, C 4-9 cycloalkyl, 4-6 membered monocyclic heterocycloalkyl containing 1-3 heteroatoms selected from N, O, and S, 7-10 membered spirocyclic heterocycloalkyl containing 1-3 heteroatoms selected from N, O, and S, 4-8 membered bridged heterocycloalkyl containing 1-3 heteroatoms selected from N, O, and S, 4-6 membered cycloheterocycloalkyl containing 1-3 heteroatoms selected from N, O, and S, phenyl, 8-10 membered aryl, 5-6 membered monocyclic heteroaryl containing 1-3 heteroatoms selected from N, O, and S, 8-10 membered bicyclic heteroaryl containing 1-3 heteroatoms selected from N, O, and S, -C(O)-R a1 The alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl groups are optionally further substituted by 1-3 groups selected from halogen, =O, deuterium, CN, OH, C 1-2 Alkyl, halogenated C 1-2 Alkyl, deuterated C 1-2 Alkyl, C 1-2 Alkoxy, halogenated C1-2 Alkoxy, deuterated C 1-2 Alkoxy and NH2 group substitution;

[0682] Each R b Selected from H, deuterium, C 1-2 Alkyl, C 3-4 The remaining groups are as described in any of the above technical solutions.

[0683] The thirty-sixth technical solution of the present invention is a compound of the present invention, a stereoisomer, a deuterated substance, a solvate, or a pharmaceutically acceptable salt or a cocrystal thereof, wherein

[0684] R 1 Selected from R A1 、-O-halogenated C 1-4 Alkyl, C 1-4 Alkyl, wherein the alkyl is optionally further substituted by 1-3 groups selected from halogen, D, CN, OH, C 1-2 Alkyl, halogenated C 1-2 Alkyl, deuterated C 1-2 Alkyl, C 1-2 Alkoxy, halogenated C 1-2 Alkoxy, deuterated C 1-2 Alkoxy and NH2 group substitution;

[0685] R 2 、R 3 Each independently selected from H, deuterium, F, Cl, cyano, OH, C 1-2 Alkyl, halogenated C 1-2 Alkyl, deuterated C 1-2 alkyl;

[0686] R A1 Selected from -O-(CH2) r -R a 、C 3-6 Monocyclic cycloalkyl, C 5-8 Bicyclic bridged ring cycloalkyl, C 6-10 Bicyclic spirocyclic cycloalkyl, 5-6 membered monocyclic heteroaryl containing 1-3 heteroatoms selected from N, O, S, 8-10 membered bicyclic heteroaryl containing 1-3 heteroatoms selected from N, O, S, -C 1-2 Alkyl-R a 、-C 1-2 Alkyl-OR a 、-Se-(CH2) r -R a The heteroaryl, alkyl, cycloalkyl group may be further substituted by 1-3 groups selected from halogen, deuterium, CN, OH, C 1-2 Alkyl, halogenated C 1-2 Alkyl, deuterated C 1-2 Alkyl, C1-2 Alkoxy, halogenated C 1-2 Alkoxy, deuterated C 1-2 Alkoxy and NH2 group substitution;

[0687] Each R a Selected from halogenated C 1-4 Alkyl, C 3-6 Monocyclic cycloalkyl, C 7-10 Spirocyclic cycloalkyl, C 4-8 Bridged ring cycloalkyl, C 4-9 cycloalkyl, 4-6 membered monocyclic heterocycloalkyl containing 1-3 heteroatoms selected from N, O, and S, 7-10 membered spirocyclic heterocycloalkyl containing 1-3 heteroatoms selected from N, O, and S, 4-8 membered bridged heterocycloalkyl containing 1-3 heteroatoms selected from N, O, and S, 4-6 membered cycloheterocycloalkyl containing 1-3 heteroatoms selected from N, O, and S, phenyl, 8-10 membered aryl, 5-6 membered monocyclic heteroaryl containing 1-3 heteroatoms selected from N, O, and S, 8-10 membered bicyclic heteroaryl containing 1-3 heteroatoms selected from N, O, and S, wherein the alkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl are optionally further substituted by 1-3 halogens, =O, deuterium, CN, OH, C 1-2 Alkyl, halogenated C 1-2 Alkyl, deuterated C 1-2 Alkyl, C 1-2 Alkoxy, halogenated C 1-2 Alkoxy, deuterated C 1-2 The alkoxy group and the NH2 group are substituted; the remaining groups are as described in any of the above technical solutions.

[0688] The thirty-seventh technical solution of the present invention is that the compound of the present invention, its stereoisomer, deuterated substance, solvate, or pharmaceutically acceptable salt or cocrystal has the structure of formula (IV) or (V):

[0689] X is selected from CR 10 or N;

[0690] R 9 、R 10 Each independently selected from H, deuterium, F, Cl, OH, CN, amino, C 1-2 alkyl;

[0691] L2 is selected from a bond, -CH2-, -CD2-, -CHD-, -CR L1 R L2 -、-CHR L2 -、-CDR L2 -、C 2-4 Alkyl, -C(O)-, wherein the alkyl group is optionally further substituted with 1-3 R L1 replace;

[0692] The conditions are: R 10 With R 7 、R 7 With R 8 、R 8 With R 9 A group of the group and the atoms connected thereto together form a 4-8 membered cycloalkyl, a 5-7 membered heterocycloalkyl containing 1-3 heteroatoms selected from N, O, S, B, Si, wherein the cycloalkyl and heterocycloalkyl are optionally further substituted by 1-3 heteroatoms selected from =O, Halogen, deuterium, CN, OH, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, deuterated C 1-4 The alkoxy group and the NH2 group are substituted; the remaining groups are as described in any of the above technical solutions.

[0693] The thirty-eighth technical solution of the present invention is a compound of the present invention, a stereoisomer, a deuterated substance, a solvate, or a pharmaceutically acceptable salt or a cocrystal thereof, wherein

[0694] R 6 With R 10 、R 10 With R 7 、R 7 With R 8 、R 8 With R 9 A group of the carbon ring and the atoms connected thereto together form a 4, 5, 6, 7, 8-membered carbocyclic ring, a 5, 6, 7-membered heterocycloalkyl containing 1, 2, 3 heteroatoms selected from N, O, S, B, Si, wherein the carbon ring or heterocycloalkyl is optionally further substituted by 1, 2, 3 heteroatoms selected from =O, Halogen, deuterium, CN, OH, C 1-2 Alkyl, halogenated C 1-2 Alkyl, deuterated C 1-2 Alkyl, C 1-2 Alkoxy, halogenated C 1-2 Alkoxy, deuterated C 1-2 Alkoxy, 5-, 6-, or 7-membered heterocycloalkyl containing 1-3 heteroatoms selected from N, O, S, B, or Si, 5-, 6-, or 7-membered heteroaryl containing 1-3 heteroatoms selected from N, O, S, B, or Si, and NH2;

[0695] In some embodiments, R 6 With R 10 、R 10 With R 7 、R 7 With R8 、R 8 With R 9 A group of the group and the atoms connected thereto together form a 4, 5, 6, 7, 8-membered cycloalkyl, a 5, 6, 7-membered heterocycloalkyl containing 1, 2, 3 heteroatoms selected from N, O, S, B, Si, wherein the cycloalkyl and heterocycloalkyl are optionally further substituted by 1, 2, 3 heteroatoms selected from =O, Halogen, deuterium, CN, OH, C 1-2 Alkyl, halogenated C 1-2 Alkyl, deuterated C 1-2 Alkyl, C 1-2 Alkoxy, halogenated C 1-2 Alkoxy, deuterated C 1-2 Alkoxy, 5-, 6-, or 7-membered heterocycloalkyl containing 1-3 heteroatoms selected from N, O, S, B, or Si, 5-, 6-, or 7-membered heteroaryl containing 1-3 heteroatoms selected from N, O, S, B, or Si, and NH2;

[0696] In some embodiments, R 6 With R 10 、R 10 With R 7 、R 7 With R 8 、R 8 With R 9 A group of the cycloalkyl and the atoms connected thereto together form a 4, 5, 6, 7, 8-membered cycloalkyl, a 5, 6, 7-membered heterocycloalkyl containing 1, 2, 3 heteroatoms selected from N, O, S, B, Si, wherein the cycloalkyl and heterocycloalkyl are optionally further substituted by 1, 2, 3 heteroatoms selected from =O, halogen, deuterium, CN, OH, C 1-2 Alkyl, halogenated C 1-2 Alkyl, deuterated C 1-2 Alkyl, C 1-2 Alkoxy, halogenated C 1-2 Alkoxy, deuterated C 1-2 Alkoxy, 5-, 6-, or 7-membered heterocycloalkyl containing 1-3 heteroatoms selected from N, O, S, B, or Si, 5-, 6-, or 7-membered heteroaryl containing 1-3 heteroatoms selected from N, O, S, B, or Si, and NH2;

[0697] In some embodiments, R 7 With R 8 、R 8 With R 9 A group of the group and the atoms connected thereto together form a 4, 5, 6, 7, 8-membered cycloalkyl, a 5, 6-membered heterocycloalkyl containing 1, 2, 3 heteroatoms selected from N, O, S, B, Si, wherein the cycloalkyl and heterocycloalkyl are optionally further substituted by 1, 2, 3 heteroatoms selected from =O, halogen, deuterium, CN, OH, C 1-2 Alkyl, halogenated C1-2 Alkyl, deuterated C 1-2 Alkyl, C 1-2 Alkoxy, halogenated C 1-2 Alkoxy, deuterated C 1-2 Alkoxy and NH2 group substitution;

[0698] In some embodiments, R 7 With R 8 and the atoms to which they are attached together form a 4, 5, 6, 7, 8-membered cycloalkyl group, a 5, 6-membered heterocycloalkyl group containing 1, 2, 3 heteroatoms selected from N, O, S, B, Si, wherein the cycloalkyl group and the heterocycloalkyl group are optionally further substituted by 1, 2, 3 heteroatoms selected from =O, halogen, deuterium, CN, OH, C 1-2 Alkyl, halogenated C 1-2 Alkyl, deuterated C 1-2 Alkyl, C 1-2 Alkoxy, halogenated C 1-2 Alkoxy, deuterated C 1-2 Alkoxy and NH2 group substitution;

[0699] In some embodiments, R 7 With R 8 and the atoms to which they are attached together form a 4- or 5-membered cycloalkyl group, a 5-membered heterocycloalkyl group containing 1, 2, or 3 heteroatoms selected from N, O, S, B, or Si, wherein the cycloalkyl group or heterocycloalkyl group is optionally further substituted by 1, 2, or 3 heteroatoms selected from =O, halogen, deuterium, CN, OH, C 1-2 Alkyl, halogenated C 1-2 Alkyl, deuterated C 1-2 Alkyl, C 1-2 Alkoxy, halogenated C 1-2 Alkoxy, deuterated C 1-2 Alkoxy and NH2 group substitution;

[0700] The remaining groups are as described in any of the above technical solutions.

[0701] The thirty-ninth technical solution of the present invention is a compound of the present invention, a stereoisomer, a deuterated substance, a solvate, or a pharmaceutically acceptable salt or a cocrystal thereof, wherein

[0702] L1 is selected from a bond;

[0703] L2 is selected from a bond, -CH2-, -CD2-, -CHD-, -C(O)-, -CHF-, -CDF-, -CF2-, CH(CH3)-, CD(CH3)-, C(CH3)2-;

[0704] R 6 、R 9 、R 10Each independently selected from H, deuterium, F, Cl, OH, CN, methyl;

[0705] R 7 、R 8 Each independently selected from H, deuterium, F, Cl, OH, CN, methyl;

[0706] R 2 、R 3 Each is independently selected from H, deuterium, vinyl, and ethynyl;

[0707] R 4 、R 5 Each is independently selected from H, deuterium, cyclopropyl, vinyl, and ethynyl;

[0708] Alternatively, R 4 、R 5 Together with the atoms to which it is attached, it forms phenyl, cyclohexyl, cyclopentyl, thienyl, furanyl, pyrrolyl, pyrazolyl, isoxazolyl;

[0709] Alternatively, R 2 、R 4 , L1 and the atoms to which they are attached together form cyclohexyl, cycloheptyl, phenyl or cyclopentyl;

[0710] Alternatively, R L1 With R 9 Together with the atoms to which they are attached, they form cyclopentyl or cyclohexyl;

[0711] R 1 Selected from -CF3, -CH2CH3, -CH2CH2CH3,

[0712] In some embodiments, R 1 Selected from -CH2CH3, -CH2CH2CH3,

[0713] The conditions are: R 6 With R 10 、R 10 With R 7 、R 7 With R 8 、R 8 With R 9A group of the group and the atoms connected thereto together form a 4-8 membered cycloalkyl or a 5-7 membered heterocycloalkyl containing 1 Si atom, wherein the cycloalkyl or heterocycloalkyl is optionally further substituted by 1-3 atoms selected from =O, F, Cl, deuterium, OH, C 1-2 Alkyl, halogenated C 1-2 Alkyl, 5-6 membered heteroaryl containing 1-3 heteroatoms selected from N, O, S, B, Si;

[0714] In some embodiments, the proviso is: R 6 With R 10 、R 10 With R 7 、R 7 With R 8 、R 8 With R 9 A group of the group and the atoms connected thereto together form a 4-8 membered cycloalkyl or a 5-7 membered heterocycloalkyl containing 1 Si atom, wherein the cycloalkyl or heterocycloalkyl is optionally further substituted by 1-3 groups selected from =O, F, Cl, deuterium, OH, C 1-2 Alkyl, halogenated C 1-2 Alkyl, 5-6 membered heteroaryl containing 1-3 heteroatoms selected from N, O, S, B, Si;

[0715] In some embodiments, the proviso is: R 6 With R 10 、R 10 With R 7 、R 7 With R 8 、R 8 With R 9 A group of the group and the atoms connected thereto together form a 4, 5, 6-membered cycloalkyl group or a 5, 6-membered heterocycloalkyl group containing 1 Si atom, wherein the cycloalkyl group or heterocycloalkyl group is optionally further substituted by 1-3 groups selected from =O, F, Cl, deuterium, OH, C 1-2 Alkyl, halogenated C 1-2 Alkyl, 5-6 membered heteroaryl containing 1-3 heteroatoms selected from N, O, S, B, Si;

[0716] The remaining groups are as described in any of the above technical solutions.

[0717] Furthermore, the compound of the present invention, its stereoisomer, deuterated form, solvate, or pharmaceutically acceptable salt or cocrystal has the structure of formula (VA):

[0718] R 11a 、R 11b 、R 12a 、R12b Each independently selected from H, deuterium, OH, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, deuterated C 1-4 Alkoxy, C 3-6 Cycloalkyl; or R 11a 、R 11b 、R 12a 、R 12b Any two atoms in the 3-6 Cycloalkyl, optionally further substituted by 1-3 groups selected from =O, Halogen, deuterium, CN, OH, C 1-3 Alkyl, halogenated C 1-3 Alkyl, deuterated C 1-3 Alkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, deuterated C 1-3 Alkoxy group substitution;

[0719] In certain embodiments, R 11a 、R 11b 、R 12a 、R 12b Each independently selected from H, deuterium, OH, C 1-3 Alkyl, halogenated C 1-3 Alkyl; or R 11a and R 11b , or R 12a and R 12b and its connected atoms together form C 3-6 Cycloalkyl;

[0720] In certain embodiments, R 11a 、R 11b 、R 12a 、R 12b Each independently selected from H, deuterium, OH, C 1-3 Alkyl, halogenated C 1-3 Alkyl; or R 11a and R 11b , or R 12a and R 12b and the atoms to which they are attached together form a cyclopropyl group;

[0721] The remaining groups are as described in any of the above technical solutions.

[0722] The fortieth technical solution of the present invention is that the compound of the present invention, its stereoisomer, deuterated substance, solvate, or pharmaceutically acceptable salt or cocrystal has the structure of formula (I):

[0723] in,

[0724] R 1 、R 2 、R 3 Each independently selected from H, deuterium, R A1 、-O-halogenated C 1-4 Alkyl, -NH-halogenated C 1-4 Alkyl, -OC 1-4 Alkyl, C 1-4 Alkoxy, C 5-6 Alkoxy, halogen, cyano, nitro, C 1-4 Alkyl, C 2-6 Alkenyl, -NH-C 1-4 Alkyl, -N(C 1-4 Alkyl)2, -NH-C 3-10 Cycloalkyl, -NHC(O)C 1-4 Alkyl or 4-10 membered heterocycloalkyl containing 1-3 heteroatoms selected from N, O, S, wherein the alkyl, alkoxy, cycloalkyl, heterocycloalkyl is optionally further substituted by 1-3 heteroatoms selected from halogen, D, CN, OH, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, deuterated C 1-4 Alkoxy, C 3-10 Cycloalkyl, 4-6 membered heterocycloalkyl containing 1-3 heteroatoms selected from N, O, S, phenyl, and NH2, provided that R 1 、R 2 and R 3 Not selected from H at the same time;

[0725] R A1 Selected from halogenated C 2-6 Alkenyl, C 2-6 Alkynyl, -O-(CH2) r -R a 、C 3-10 Cycloalkyl, 5-10 membered heteroaryl containing 1-3 heteroatoms selected from N, O, S, -C 1-4 Alkyl-R a 、-C 1-4 Alkyl-OR a 、-C 1-4 Alkyl-NR b R a 、-NR b -S(O)2-R a 、-NR b -S(O)2-NR b Ra 、-O-NR b R a 、-NH-OR b 、-Se-(CH2) r -R a The alkynyl, heteroaryl, alkyl, cycloalkyl group may be further substituted by 1-3 groups selected from halogen, deuterium, CN, OH, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, deuterated C 1-4 Alkoxy and NH2 group substitution;

[0726] Each R a Selected from CN, halogenated C 1-6 Alkyl, C 3-10 Cycloalkyl, 4-10 membered heterocycloalkyl containing 1-3 heteroatoms selected from N, O, S, 6-10 membered aryl, 5-10 membered heteroaryl containing 1-3 heteroatoms selected from N, O, S, -C(O)-R a1 The alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl groups are optionally further substituted by 1-3 groups selected from halogen, =O, deuterium, CN, OH, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, deuterated C 1-4 Alkoxy and NH2 group substitution;

[0727] Each R b Selected from H, deuterium, C 1-4 Alkyl, C 3-6 Cycloalkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 alkyl;

[0728] R a1 Selected from OH, NH2, -NHC 1-4 Alkyl, -N(C 1-4 Alkyl)2, -NHC 3-10 Cycloalkyl, C 1-4 Alkoxy, C 1-6 Alkyl, C 3-10 Cycloalkyl, 6-10 membered aryl, 5-10 membered heteroaryl containing 1-3 heteroatoms selected from N, O, S;

[0729] X is selected from CR 10 or N;

[0730] X1 is selected from O, S;

[0731] R 4 、R 5 Each independently selected from H, deuterium, C 3-10 Cycloalkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, halogen, amino, -NH-C 1-4 Alkyl, -N(C 1-4 Alkyl)2, C 1-4 Alkyl, halogenated C 1-4 Alkyl, 4-10 membered heterocycloalkyl containing 1-3 heteroatoms selected from N, O, and S, 5-10 membered heteroaryl, and 6-10 membered aryl containing 1-3 heteroatoms selected from N, O, and S;

[0732] R 6 、R 7 、R 8 、R 9 、R 10 Each independently selected from H, deuterium, R A2 , halogen, OH, CN, amino, C 1-4 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-4 Alkoxy, halogenated C 1-4 Alkyl, -NH-C 1-4 Alkyl, -N(C 1-4 Alkyl)2, -S(O)R c 、-S(O) 2 R c 、-C(O)R c 、-C(O)OR c 、-C(O)N(R c )2、-OC(O)R c The alkyl, alkenyl, alkynyl, and alkoxy groups are optionally further substituted by 1 to 3 groups selected from halogen, deuterium, CN, OH, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, deuterated C 1-4 Alkoxy and NH2 group substitution;

[0733] R A2 Selected from -(CH2) r -(4-10 membered heterocycloalkyl containing 1-3 heteroatoms selected from N, O, S, Si), or -(CH2) r -(5-10 membered heteroaryl containing 1-3 heteroatoms selected from N, O, S), -P(O)(R c )2、-Si(Rc )3, -SF5, N3, B(OH)2, or -S(O)(=NH)R c The heterocycloalkyl and heteroaryl groups are optionally further substituted by 1-3 groups selected from halogen, =O, D, CN, OH, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, C 3-6 Cycloalkyl, 4-7 membered heterocycloalkyl containing 1-3 heteroatoms selected from N, O, S, deuterated C 1-4 Alkoxy and NH2 group substitution;

[0734] Each R c Each independently selected from H, OH, C 1-4 Alkyl, C 3-7 Cycloalkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, deuterated C 1-4 Alkoxy, or NH2;

[0735] Each r is independently selected from 0, 1, 2 or 3;

[0736] L1 is selected from a bond, O, NH, S, -CD2-, -CHD-, -CR L1 R L2 -、C 1-4 Alkyl, -C(O)-, S(O), S(O)2, wherein the alkyl group is optionally further R L1 replace;

[0737] L2 is selected from O, NH, S, -CH2-, -CD2-, -CHD-, -CR L1 R L2 -、-CHR L2 -、-CDR L2 -、C 2-4 Alkyl, -C(O)-, S(O), S(O)2, wherein the alkyl group is optionally further substituted with 1-3 R L1 replace;

[0738] R L1 、R L2 Each independently selected from halogen, OH, CN, amino, C 1-4 Alkyl, C 1-4 Alkoxy, C 3-6 Cycloalkyl, 4-6 membered heterocycloalkyl containing 1-3 heteroatoms selected from N, O, S;

[0739] Alternatively, R 2 、R 4 , L1 and the atoms to which they are connected together form a 5-7 membered carbocyclic ring, a 5-7 membered heterocyclic ring containing 1-3 heteroatoms selected from N, O, and S, wherein the carbocyclic ring or heterocyclic ring is optionally further substituted by 1-3 heteroatoms selected from R A3 The group substitution;

[0740] Alternatively, R 4 、R 5 Together with the atoms to which they are connected, they form a 5-7 membered monocyclic carbocyclic ring or a 5-7 membered heterocyclic ring containing 1-3 heteroatoms selected from N, O, and S, wherein the carbocyclic ring or heterocyclic ring is optionally substituted by 1-3 heteroatoms selected from R A3 The group substitution;

[0741] Alternatively, R L2 With R 9 Together with the atoms to which they are connected, they form a 5-7 membered carbocyclic ring or a 5-7 membered heterocyclic ring containing 1-3 heteroatoms selected from N, O, and S, wherein the carbocyclic ring or heterocyclic ring is optionally further surrounded by 1-3 heteroatoms selected from R A3 The group substitution;

[0742] Each R A3 Each independently selected from =O, halogen, deuterium, CN, OH, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, deuterated C 1-4 Alkoxy and NH2 group substitution;

[0743] The conditions are: R 6 With R 10 、R 10 With R 7 、R 7 With R 8 、R 8 With R 9 A group of the group and the atoms connected thereto together form a 4-8 membered carbocyclic ring, a 5-7 membered heterocycloalkyl containing 1-3 heteroatoms selected from N, O, S, B, Si, wherein the carbocyclic ring or heterocycloalkyl is optionally further substituted by 1-3 heteroatoms selected from =O, halogen, deuterium, CN, OH, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, deuterated C 1-4 Alkoxy and NH2 groups are substituted.

[0744] The forty-first technical solution of the present invention is that the compound of the present invention, its stereoisomer, deuterated substance, solvate, or pharmaceutically acceptable salt or cocrystal has the structure of formula (II):

[0745] L2 is selected from -CH2-, -CR L1 R L2 -、-CHR L2 -、-CDR L2 -, -C(O)-;

[0746] X is selected from CR 10 or N;

[0747] R 4 、R 5 Each independently selected from H, deuterium, C 3-7 Cycloalkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, F, Cl, amino, -NH-C 1-2 Alkyl, -N(C 1-2 Alkyl)2, C 1-2 Alkyl, 4-7 membered heterocycloalkyl containing 1-3 heteroatoms selected from N, O, S;

[0748] R 7 、R 8 Each independently selected from H, deuterium, R A2 、F、Cl、OH、CN、amino、C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-4 Alkoxy, halogenated C 1-4 Alkyl, -NH-C 1-2 Alkyl, -N(C 1-2 Alkyl)2, -S(O)R c 、-S(O) 2 R c 、-C(O)R c 、-C(O)OR c 、-C(O)N(R c )2、-OC(O)R c ;

[0749] R 9 、R 10 Each independently selected from H, deuterium, F, Cl, OH, CN, amino, C 1-2 alkyl;

[0750] R A2 Selected from -(CH2) r-(a 4-6 membered monocyclic heterocycloalkyl group containing 1-3 heteroatoms selected from N, O, and S), -(CH2) r -(7-10 membered spirocyclic heterocycloalkyl containing 1-3 heteroatoms selected from N, O, S), -(CH2) r -(5-6 membered monocyclic heteroaryl containing 1-3 heteroatoms selected from N, O, S), -(CH2) r -(8-10 membered bicyclic heteroaryl containing 1-3 heteroatoms selected from N, O, S), -P(O)(R c )2、-Si(R c )3、-SF5、-S(O)(=NH)R c The heterocycloalkyl and heteroaryl groups are optionally further substituted by 1-3 groups selected from halogen, D, CN, OH, C 1-2 Alkyl, halogenated C 1-2 Alkyl, deuterated C 1-2 Alkyl, C 1-2 Alkoxy, halogenated C 1-2 Alkoxy, deuterated C 1-2 Alkoxy and NH2 group substitution;

[0751] The conditions are: R 10 With R 7 、R 7 With R 8 、R 8 With R 9 A group of the group and the atoms connected thereto together form a 4-8 membered carbocyclic ring, a 5-7 membered heterocycloalkyl containing 1-3 heteroatoms selected from N, O, S, B, Si, wherein the carbocyclic ring or heterocycloalkyl is optionally further substituted by 1-3 heteroatoms selected from =O, halogen, deuterium, CN, OH, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, deuterated C 1-4 The alkoxy group and the NH2 group are substituted; the remaining groups are as described in any of the above technical solutions.

[0752] The forty-second technical solution of the present invention is a compound of the present invention, a stereoisomer, a deuterated substance, a solvate, or a pharmaceutically acceptable salt or a cocrystal thereof, wherein

[0753] R 2 、R 4 , L1 and the atoms to which they are connected together form a 5-7 membered cycloalkyl, phenyl, wherein the cycloalkyl is optionally further substituted by 1-3 groups selected from R A3 substituted by a group, and R 1 is not a heterocycloalkyl group; or

[0754] R4 、R 5 Together with the atoms to which they are attached, they form a phenyl group, a 5-6 membered cycloalkyl group, a 5-6 membered heteroaryl group containing 1-3 heteroatoms selected from N, O, and S, wherein the cycloalkyl group is optionally substituted by 1-3 heteroatoms selected from R A3 substituted by a group, and R 1 Selected from R A1 or -O-halogenated C 1-4 Alkyl; or

[0755] R L2 With R 9 Together with the atoms to which they are attached, they form a 5-6 membered cycloalkyl group, which is optionally further substituted by 1-3 groups selected from R A3 The group substitution;

[0756] Each R A3 Each independently selected from =O, halogen, deuterium, CN, OH, C 1-2 Alkyl, halogenated C 1-2 Alkyl, deuterated C 1-2 Alkyl, C 1-2 Alkoxy, halogenated C 1-2 Alkoxy, deuterated C 1-2 Alkoxy and NH2 group substitution;

[0757] The remaining groups are as described in any of the above technical solutions.

[0758] The forty-third technical solution of the present invention is a compound of the present invention, a stereoisomer, a deuterated substance, a solvate, or a pharmaceutically acceptable salt thereof, wherein

[0759] R 1 Selected from R A1 、-O-halogenated C 1-4 Alkyl, wherein the alkyl is optionally further substituted by 1-3 groups selected from halogen, D, CN, OH, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, deuterated C 1-4 Alkoxy and NH2 group substitution;

[0760] R 2 、R 3 Each independently selected from H, deuterium, C 2-4 Alkenyl, C 2-4 Alkynyl, halogen, cyano, nitro, OH, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 alkyl;

[0761] RA1 Selected from halogenated C 2-4 Alkenyl, C 2-4 Alkynyl, -O-(CH2) r -R a 、C 3-6 Monocyclic cycloalkyl, 5-6 membered monocyclic heteroaryl containing 1-3 heteroatoms selected from N, O, S, 8-10 membered bicyclic heteroaryl containing 1-3 heteroatoms selected from N, O, S, -C 1-2 Alkyl-R a 、-C 1-2 Alkyl-OR a 、-C 1-2 Alkyl-NR b R a 、-NR b -S(O)2-R a 、-NR b -S(O)2-NR b R a 、-O-NR b R a 、-NH-OR b 、-Se-(CH2) r -R a The alkynyl, heteroaryl, alkyl, cycloalkyl group may be further substituted by 1-3 groups selected from halogen, deuterium, CN, OH, C 1-2 Alkyl, halogenated C 1-2 Alkyl, deuterated C 1-2 Alkyl, C 1-2 Alkoxy, halogenated C 1-2 Alkoxy, deuterated C 1-2 Alkoxy and NH2 group substitution;

[0762] r is selected from 0 or 1;

[0763] Each R a Selected from CN, halogenated C 1-4 Alkyl, C 3-6 Monocyclic cycloalkyl, C 7-10 Spirocyclic cycloalkyl, C 4-8 Bridged ring cycloalkyl, C 4-9 cycloalkyl, 4-6 membered monocyclic heterocycloalkyl containing 1-3 heteroatoms selected from N, O, and S, 7-10 membered spirocyclic heterocycloalkyl containing 1-3 heteroatoms selected from N, O, and S, 4-8 membered bridged heterocycloalkyl containing 1-3 heteroatoms selected from N, O, and S, 4-6 membered cycloheterocycloalkyl containing 1-3 heteroatoms selected from N, O, and S, phenyl, 8-10 membered aryl, 5-6 membered monocyclic heteroaryl containing 1-3 heteroatoms selected from N, O, and S, 8-10 membered bicyclic heteroaryl containing 1-3 heteroatoms selected from N, O, and S, -C(O)-R a1The alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl groups are optionally further substituted by 1-3 groups selected from halogen, =O, deuterium, CN, OH, C 1-2 Alkyl, halogenated C 1-2 Alkyl, deuterated C 1-2 Alkyl, C 1-2 Alkoxy, halogenated C 1-2 Alkoxy, deuterated C 1-2 Alkoxy and NH2 group substitution;

[0764] Each R b Selected from H, deuterium, C 1-2 Alkyl, C 3-4 Cycloalkyl;

[0765] The remaining groups are as described in any of the above technical solutions.

[0766] The forty-fourth technical solution of the present invention is that the compound of the present invention, its stereoisomer, deuterated substance, solvate, or pharmaceutically acceptable salt or cocrystal has the structure of formula (III):

[0767] X is selected from CR 10 or N;

[0768] R 9 、R 10 Each independently selected from H, deuterium, F, Cl, OH, CN, amino, C 1-2 alkyl;

[0769] The conditions are: R 10 With R 7 、R 7 With R 8 、R 8 With R 9 A group of the group and the atoms connected thereto together form a 4-8 membered carbocyclic ring, a 5-7 membered heterocycloalkyl containing 1-3 heteroatoms selected from N, O, S, B, Si, wherein the carbocyclic ring or heterocycloalkyl is optionally further substituted by 1-3 heteroatoms selected from =O, halogen, deuterium, CN, OH, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, deuterated C 1-4 Alkoxy and NH2 group substitution;

[0770] The remaining groups are as described in any of the above technical solutions.

[0771] The forty-fifth technical solution of the present invention is that the compound of the present invention, its stereoisomer, deuterated substance, solvate, or pharmaceutically acceptable salt or cocrystal has the structure of formula (IV) or (V):

[0772] X is selected from CR 10 or N;

[0773] R 9 、R 10 Each independently selected from H, deuterium, F, Cl, OH, CN, amino, C 1-2 alkyl;

[0774] L2 is selected from -CH2-, -CD2-, -CHD-, -CR L1 R L2 -、-CHR L2 -、-CDR L2 -、C 2-4 Alkyl, -C(O)-, wherein the alkyl group is optionally further substituted with 1-3 R L1 replace;

[0775] The conditions are: R 10 With R 7 、R 7 With R 8 、R 8 With R 9 A group of the group and the atoms connected thereto together form a 4-8 membered carbocyclic ring, a 5-7 membered heterocycloalkyl containing 1-3 heteroatoms selected from N, O, S, B, Si, wherein the carbocyclic ring or heterocycloalkyl is optionally further substituted by 1-3 heteroatoms selected from =O, halogen, deuterium, CN, OH, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, deuterated C 1-4 The alkoxy group and the NH2 group are substituted; the remaining groups are as described in any of the above technical solutions.

[0776] The forty-sixth technical solution of the present invention is a compound of the present invention, a stereoisomer, a deuterated substance, a solvate, or a pharmaceutically acceptable salt or cocrystal thereof, R A2 Selected from -(CH2) r -(a 4-6 membered monocyclic heterocycloalkyl group containing 1-3 heteroatoms selected from N, O, and S), -(CH2) r -(a 5-6 membered monocyclic heteroaryl containing 1-3 heteroatoms selected from N, O, and S), wherein the heterocycloalkyl and heteroaryl groups are optionally further substituted by 1-3 heteroatoms selected from halogen, D, CN, OH, C 1-2 Alkyl, halogenated C 1-2 Alkyl, deuterated C 1-2 Alkyl, C 1-2 Alkoxy, halogenated C 1-2 Alkoxy, deuterated C1-2 Alkoxy and NH2 group substitution;

[0777] r is selected from 0 and 1;

[0778] The remaining groups are as described in any of the above technical solutions.

[0779] The forty-seventh technical solution of the present invention is a compound of the present invention, a stereoisomer, a deuterated substance, a solvate, or a pharmaceutically acceptable salt or a cocrystal thereof, wherein

[0780] L1 is selected from a bond, O;

[0781] L2 is selected from -CH2-, -C(O)-, -CHF-, -CF2-, C(CH3)2-;

[0782] R L1 、R L2 Each independently selected from H, deuterium, and F;

[0783] R 6 、R 9 、R 10 Each independently selected from H, deuterium, F, Cl, OH, CN, methyl;

[0784] R 7 、R 8 Each independently selected from H, deuterium, F, Cl, OH, CN, methyl, R A2 ;

[0785] R A2 Selected from

[0786] R 2 、R 3 Each is independently selected from H, deuterium, vinyl, and ethynyl;

[0787] R 4 、R 5 Each is independently selected from H, deuterium, cyclopropyl, vinyl, and ethynyl;

[0788] Alternatively, R 4 、R 5 Together with the atoms to which it is attached, it forms phenyl, cyclohexyl, cyclopentyl, thienyl, furanyl, pyrrolyl, pyrazolyl, isoxazolyl;

[0789] Alternatively, R 2 、R 4 , L1 and the atoms to which they are attached together form a cyclohexyl, phenyl or cyclopentyl group;

[0790] Alternatively, R L1 With R 9Together with the atoms to which they are attached, they form cyclopentyl or cyclohexyl;

[0791] R 1 Selected from -CH2CH3, -CH2CH2CH3, R A1 ;

[0792] R A1 Selected from

[0793] The conditions are: R 6 With R 10 、R 10 With R 7 、R 7 With R 8 、R 8 With R 9 A group of the group and the atoms connected thereto together form a 4-8 membered carbocyclic ring or a 5-7 membered heterocyclic alkyl containing 1 Si atom, wherein the carbocyclic ring or heterocyclic alkyl is optionally further substituted by 1-3 atoms selected from =O, F, Cl, deuterium, OH, C 1-2 Alkyl, halogenated C 1-2 The remaining groups are as described in any of the above technical solutions.

[0794] Furthermore, the compounds of formula (I), formula (Ia), formula (Ib), formula (II), formula (II-a), formula (III), formula (III-a), formula (IV), formula (V), and formula (VA), their stereoisomers, deuterated substances, solvates, or pharmaceutically acceptable salts or cocrystals, wherein R 7 With R 8 and its connected atoms together form C 4-8 Cycloalkyl, said cycloalkyl optionally further substituted by 1-3 groups selected from =O, Halogen, deuterium, CN, OH, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, deuterated C 1-4 The alkyl group may be substituted with an alkoxy group, a 5-7 membered heterocycloalkyl group containing 1-3 heteroatoms selected from N, O, S, B, Si, a 5-7 membered heteroaryl group containing 1-3 heteroatoms selected from N, O, S, B, Si, and NH2.

[0795] Furthermore, the compounds of formula (I), formula (Ia), formula (Ib), formula (II), formula (II-a), formula (III), formula (III-a), formula (IV), formula (V), and formula (VA), their stereoisomers, deuterated substances, solvates, or pharmaceutically acceptable salts or cocrystals, wherein R 7 With R 8 and its connected atoms together form C 4-6 Monocyclic cycloalkyl, C 6-8 Bicyclic bridged cycloalkyl, C 6-8 Bicyclic and cycloalkyl, C 6-8 Bicyclic spirocycloalkyl, the cycloalkyl group is optionally further substituted by 1-3 groups selected from =O, Halogen, deuterium, CN, OH, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, deuterated C 1-4 Alkoxy and NH2 groups are substituted.

[0796] Furthermore, the compounds of formula (I), formula (Ia), formula (Ib), formula (II), formula (II-a), formula (III), formula (III-a), formula (IV), formula (V), and formula (VA), their stereoisomers, deuterated substances, solvates, or pharmaceutically acceptable salts or cocrystals, wherein R 7 With R 8 and its connected atoms together form C 4-6 Monocyclic cycloalkyl, said cycloalkyl optionally further substituted by 1-3 groups selected from =O, Halogen, deuterium, CN, OH, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, deuterated C 1-4 Alkoxy and NH2 groups are substituted.

[0797] Furthermore, the compounds of formula (I), formula (Ia), formula (Ib), formula (II), formula (II-a), formula (III), formula (III-a), formula (IV), formula (V), and formula (VA), their stereoisomers, deuterated substances, solvates, or pharmaceutically acceptable salts or cocrystals, wherein R 7 With R 8 and the atoms to which they are attached together form cyclobutyl, cyclopentyl, cyclohexyl, cyclobutenyl, cyclopentenyl, cyclohexenyl, Optionally further substituted by 1-3 selected from halogen, deuterium, CN, OH, C 1-3 Alkyl, halogenated C 1-3 Alkyl, deuterated C 1-3 Alkyl, C 1-3 Alkoxy, halogenated C 1-3 Alkoxy, deuterated C 1-3 Alkoxy and NH2 groups are substituted.

[0798] The compounds of Formula (I), Formula (Ia), Formula (Ib), Formula (II), Formula (II-a), Formula (III), Formula (III-a), Formula (IV), Formula (V), Formula (VA), Formula (VI), Formula (VII), Formula (VIII), and Formula (IX) of the present invention, and their stereoisomers, deuterated forms, solvates, or pharmaceutically acceptable salts or cocrystals, are selected from but not limited to the structures in Tables 1 and 2 below:

[0799] Table 1:

[0800] Table 2: Note: abs means absolute configuration.

[0801] Secondly, the present invention also provides a pharmaceutical composition, which contains the compound described in any one of the aforementioned technical solutions, its stereoisomers, solvates, deuterated substances, or pharmaceutically acceptable salts, and pharmaceutically acceptable carriers and / or excipients.

[0802] Furthermore, the pharmaceutical composition or pharmaceutical preparation comprises 1-1500 mg of the compound described in any of the aforementioned technical solutions, its stereoisomers, deuterated substances, solvates, or pharmaceutically acceptable salts or cocrystals, and pharmaceutically acceptable carriers and / or excipients.

[0803] Furthermore, the present invention also provides the use of a compound according to any of the preceding embodiments, a stereoisomer, solvate, deuterated form, or pharmaceutically acceptable salt, or a pharmaceutical composition thereof, in the preparation of a medicament for treating / preventing Myosin II-mediated diseases. Furthermore, Myosin II-mediated diseases include, but are not limited to, muscular dystrophy.

[0804] The present invention also provides a method for treating a disease in a mammal, comprising administering to a subject a therapeutically effective amount of a compound according to any one of the aforementioned technical solutions, its stereoisomers, deuterated forms, solvates, or pharmaceutically acceptable salts or cocrystals, and a pharmaceutically acceptable carrier and / or excipient, wherein the therapeutically effective amount is preferably 1-1500 mg, and the disease is preferably muscular dystrophy.

[0805] The present invention also provides a method for treating a disease in a mammal, comprising administering to the mammal a therapeutically effective amount of a compound of the present invention, or a stereoisomer, deuterated form, solvate, pharmaceutically acceptable salt, cocrystal, or pharmaceutical composition thereof. In some embodiments, the mammal of the present invention includes a human.

[0806] As used herein, an "effective amount" or "therapeutically effective amount" refers to administering a sufficient amount of a compound disclosed herein that will alleviate one or more symptoms of the disease or condition being treated to some extent. In some embodiments, the result is a reduction and / or alleviation of the signs, symptoms or causes of the disease, or any other desired change in a biological system. For example, an "effective amount" for therapeutic use is the amount of a compound disclosed herein required to provide a clinically significant reduction in disease symptoms. Examples of therapeutically effective amounts include, but are not limited to, 1-1500 mg, 1-1400 mg, 1-1300 mg, 1-1200 mg, 1-1000 mg, 1-900 mg, 1-800 mg, 1-700 mg, 1-600 mg, 1-500 mg, 1-400 mg, 1-300 mg, 1-250 mg, 1-200 mg, 1-150 mg, 1-125 mg, 1-100 mg, 1-80 mg, 1-60 mg, 1-50mg, 1-40mg, 1-25mg, 1-20mg, 5-1500mg, 5-1000mg, 5-900mg, 5-800mg, 5-700mg, 5-600mg, 5-500mg , 5-400mg, 5-300mg, 5-250mg, 5-200mg, 5-150mg, 5-125mg, 5-100mg, 5-90mg, 5-70mg, 5-80mg, 5-60mg, 5-50mg, 5-40mg, 5-30mg, 5-25mg, 5-20mg, 10-1500mg, 10-1000mg, 10-900mg, 10-800mg, 10-700mg, 10-600mg, 10-500mg, 10-450m g, 10-400mg, 10-300mg, 10-250mg, 10-200mg, 10-150mg, 10-125mg, 10-100mg, 10-90mg, 10-80mg, 10-70mg, 10-60mg, 10-50mg, 10 -40mg, 10-30mg, 10-20mg; 20-1500mg, 20-1000mg, 20-900mg, 20-800mg, 20-700mg, 20-600mg, 20-500mg, 20-400mg, 20-350mg, 20 -300mg, 20-250mg, 20-200mg, 20-150mg, 20-125mg, 20-100mg, 20-90mg, 20-80mg, 20-70mg, 20-60mg, 20-50mg, 20-40mg, 20-30mg;50-1500mg, 50-1000mg, 50-900mg, 50-800mg, 50-700mg, 50-600mg, 50-500mg, 50-400mg, 50-300mg, 50-250mg, 50-200mg, 50-150mg, 50-125mg, 5 0-100mg; 100-1500mg, 100-1000mg, 100-900mg, 100-800mg, 100-700mg, 100-600mg, 100-500mg, 100-400mg, 100-300mg, 100-250mg, 100-200mg. ;

[0807] The present invention relates to a pharmaceutical composition or pharmaceutical formulation comprising a therapeutically effective amount of a compound of the present invention, or a stereoisomer, deuterated form, solvate, pharmaceutically acceptable salt, or cocrystal thereof, and a carrier and / or excipient. The pharmaceutical composition may be in the form of a unit dosage form (the amount of the active ingredient in a unit dosage form is also referred to as the "drug strength"). In some embodiments, the pharmaceutical composition includes but is not limited to 1-1500 mg, 5-1000 mg, 10-800 mg, 20-600 mg, 25-500 mg, 40-200 mg, 50-100 mg, 1 mg, 1.25 mg, 2.5 mg, 5 mg, 10 mg, 12.5 mg, 15 mg, 20 mg, 25 mg, 30 mg, 35 mg, 40 mg, 45 mg, 50 mg, 55 mg, 60 mg, 65 mg, 70 mg, 75 mg, 80 mg, 85 mg, 90 mg, 95 mg, 100 mg, 110 mg, 120 mg, 125 mg, 130 mg, 140 mg, 150 mg, 160 mg, 170 mg, 180 mg, 190 mg g, 200 mg, 210 mg, 220 mg, 230 mg, 240 mg, 250 mg, 275 mg, 300 mg, 325 mg, 350 mg, 375 mg, 400 mg, 425 mg, 450 mg, 475 mg, 500 mg, 525 mg, 550 mg, 575 mg, 600 mg, 625 mg, 650 mg, 675 mg, 700 mg, 725 mg, 750 mg, 775 mg, 800 mg, 850 mg, 900 mg, 950 mg, 1000 mg, 1100 mg, 1200 mg, 1300 mg, 1400 mg, 1500 mg of a compound of the present invention or a stereoisomer, deuterated form, solvate, pharmaceutically acceptable salt or cocrystal thereof.

[0808] A method for treating a disease in a mammal, comprising administering to a subject a therapeutically effective amount of a compound of the present invention, its stereoisomer, deuterated form, solvate, or pharmaceutically acceptable salt or cocrystal, and a pharmaceutically acceptable carrier and / or excipient, wherein the therapeutically effective amount is preferably 1-1500 mg, and the disease is preferably muscular dystrophy.

[0809] A method for treating a disease in a mammal, comprising administering a compound of the present invention, a stereoisomer, deuterated form, solvate, or pharmaceutically acceptable salt or cocrystal thereof, and a pharmaceutically acceptable carrier and / or excipient to a subject at a daily dose of 1-1500 mg / day, wherein the daily dose can be a single dose or divided doses. In some embodiments, the daily dose includes but is not limited to 10-1500 mg / day, 20-1500 mg / day, 25-1500 mg / day, 50-1500 mg / day, 75-1500 mg / day, 100-1500 mg / day, 200-1500 mg / day, 10-1000 mg / day, 20-1000 mg / day, 25-1000 mg / day, 50-1000 mg / day, 75-1000 mg / day In some embodiments, the daily dose includes but is not limited to 1 mg / day, 5 mg / day, 10 mg / day, 20 mg / day, 25 mg / day, 50 mg / day, 75 mg / day, 100 mg / day, 125 mg / day, 150 mg / day, 200 mg / day, 400 mg / day, 600 mg / day, 800 mg / day, 1000 mg / day, 1200 mg / day, 1400 mg / day, 1500 mg / day.

[0810] The present invention relates to a kit, which may include a composition in single-dose or multi-dose form, wherein the kit contains a compound of the present invention or a stereoisomer, deuterated form, solvate, pharmaceutically acceptable salt or cocrystal thereof, and the amount of the compound of the present invention or its stereoisomer, deuterated form, solvate, pharmaceutically acceptable salt or cocrystal is the same as that in the above-mentioned pharmaceutical composition.

[0811] The amount of the compound of the invention or its stereoisomer, deuterated form, solvate, pharmaceutically acceptable salt or cocrystal in the present invention is in each case calculated as the free base.

[0812] "Preparation specifications" refers to the weight of the main drug contained in each vial, tablet or other unit preparation.

[0813] Synthesis route

[0814] Those skilled in the art can prepare the compounds of the present invention by combining known organic synthesis techniques, using commercially available chemicals and / or compounds described in the chemical literature as starting materials. "Commercially available chemicals" are obtained from reputable commercial sources, including suppliers such as Titan Technology, Anage Chemical, Shanghai Demo, Chengdu Kelon Chemical, Shaoyuan Chemical Technology, Nanjing Yaoshi, WuXi AppTec, and J&K Technology.

[0815] Specific and similar reactants can be selectively identified by indexes of known chemical substances prepared by the American Chemical Society's Chemical Abstracts Service, which are available in most public and university libraries and online. Chemicals that are known but not commercially available in the catalog are optionally prepared by custom chemical synthesis facilities, many of which standard chemical supply facilities (e.g., those listed above) offer custom synthesis services.

[0816] the term

[0817] Unless otherwise specified in the present invention, the terms of the present invention have the following meanings:

[0818] The carbon, hydrogen, oxygen, sulfur, nitrogen or halogen involved in the groups and compounds of the present invention include their isotopes, and the carbon, hydrogen, oxygen, sulfur, nitrogen or halogen involved in the groups and compounds of the present invention are optionally further replaced by one or more of their corresponding isotopes, wherein the isotopes of carbon include 12 C. 13 C and 14 C, hydrogen isotopes include protium (H), deuterium (deuterium, also known as heavy hydrogen), tritium (T, also known as super tritium), oxygen isotopes include 16 O. 17 O and 18 O, sulfur isotopes include 32 S. 33 S. 34 S and 36 S, nitrogen isotopes include 14 N and 15 N, an isotope of fluorine 19 F, chlorine isotopes include 35 Cl and 37 Isotopes of Cl, bromine include 79 Br and 81 Br.

[0819] "Halogen" herein refers to F, Cl, Br, I, or isotopes thereof.

[0820] "Halo" or "halogen-substituted" refers to substitution with one or more halogens selected from F, Cl, Br, I, or isotopes thereof. The upper limit of the number of halogen substituents is equal to the sum of the number of hydrogen atoms that can be replaced by the substituted group. Unless otherwise specified, the number of halogen substituents is any integer between 1 and the upper limit. When the number of halogen substituents is greater than 1, they may be the same or different halogens. Typical examples include 1-5 halogen substitutions, 1-3 halogen substitutions, 1-2 halogen substitutions, and 1 halogen substitution.

[0821] "Deuterium" refers to the isotope of hydrogen (H) and is synonymous with "D".

[0822] "Deuterated" or "deuterated compound" refers to a situation where a hydrogen atom on an alkyl, cycloalkyl, alkylene, aryl, heteroaryl, thiol, heterocycloalkyl, alkenyl, alkynyl or other group is replaced by at least one deuterium atom. The upper limit of the number of deuterated groups is equal to the sum of the number of replaceable hydrogen atoms in the substituted group. Unless otherwise specified, the number of deuterated groups is any integer between 1 and the upper limit, for example, 1-20 deuterium atoms, 1-10 deuterium atoms, 1-6 deuterium atoms, 1-3 deuterium atoms, 1-2 deuterium atoms or 1 deuterium atom.

[0823] “C x-y " group refers to a group containing x to y carbon atoms, such as "C 1-6 "Alkyl" refers to an alkyl group containing 1 to 6 carbon atoms.

[0824] "Alkyl" refers to a monovalent straight-chain or branched saturated aliphatic hydrocarbon group. Typically, it is an alkyl group having 1 to 20 carbon atoms, or an alkyl group having 1 to 8 carbon atoms, or an alkyl group having 1 to 6 carbon atoms, or an alkyl group having 1 to 4 carbon atoms. Non-limiting examples include methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, neobutyl, tert-butyl, n-pentyl, isopentyl, neopentyl, n-hexyl, and the like. The alkyl group may be further substituted with a substituent.

[0825] "Alkylene" refers to a divalent straight-chain or branched saturated alkyl group. Examples of alkylene groups include, but are not limited to, methylene, ethylene, and the like.

[0826] "Haloalkyl" refers to a situation where one or more hydrogen atoms in an alkyl group are replaced by one or more halogen atoms (such as fluorine, chlorine, bromine, iodine, or their isotopes). The upper limit of the number of halogen substituents is equal to the sum of the number of replaceable hydrogen atoms in the alkyl group. Unless otherwise specified, the number of halogen substituents is any integer between 1 and the upper limit. Typically, an alkyl group is substituted with 1-5 halogens, or 1-3 halogens, or 1-2 halogens, or 1 halogen. When the number of halogen substituents is greater than 1, they can be the same or different halogens. Specific examples include, but are not limited to, -CF3, -CH2Cl, -CH2CF3, -CCl2, CF3, etc.

[0827] "Alkoxy" or "alkyloxy" refers to an -O-alkyl group. For example, -OC 1-8 Alkyl, -OC 1-6 Alkyl, -OC 1-4 Alkyl or -OC 1-2 Specific non-limiting examples include methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, sec-butoxy, tert-butoxy, n-pentoxy, n-hexyloxy, cyclopropyloxy, and cyclobutyloxy, and the like; the alkoxy groups may be optionally substituted with substituents.

[0828] "Haloalkoxy" refers to an -O-haloalkyl group. For example, -O-haloC 1-8 Alkyl, -O-halogenated C 1-6 Alkyl, -O-halogenated C 1-4 Alkyl or -O-halogenated C 1-2 Alkyl; the upper limit of the number of halogen substituents is equal to the sum of the number of hydrogen atoms that can be substituted by the substituted group. Unless otherwise specified, the number of halogen substituents is any integer between 1 and the upper limit, preferably 1-5 halogen substitutions, 1-3 halogen substitutions, 1-2 halogen substitutions, or 1 halogen substitution; when the number of halogen substituents is greater than 1, they may be the same or different halogen substitutions; non-limiting examples include monofluoromethoxy, difluoromethoxy, trifluoromethoxy, difluoroethyloxy, and the like.

[0829] "Alkenyl" refers to a straight or branched chain hydrocarbon group containing at least one carbon-carbon double bond (C=C), typically containing 2 to 18 carbon atoms, such as 2 to 8 carbon atoms, further such as 2 to 6 carbon atoms, and further such as 2 to 4 carbon atoms, examples of which include but are not limited to vinyl, allyl, 1-propenyl, 2-propenyl, 1-butenyl, 2-butenyl, 3-butenyl, 1-pentenyl, 2-pentenyl, 3-pentenyl, 4-pentenyl, 1-methyl-1-butenyl, 2-methyl-1-butenyl, 2-methyl-2-butenyl, 2-methyl-3-butenyl, 2-methyl-4-butenyl, 2-methyl-5-butenyl, 2-methyl-6-butenyl, 2-methyl-7-butenyl, 2-methyl-8-butenyl, 2-methyl-9-butenyl, 2-methyl-1-butenyl, 2-methyl-2-butenyl, 2-methyl-3 ... -methyl-3-butenyl, 1-hexenyl, 2-hexenyl, 3-hexenyl, 4-hexenyl, 5-hexenyl, 1-methyl-1-pentenyl, 2-methyl-1-pentenyl, 1-heptenyl, 2-heptenyl, 3-heptenyl, 4-heptenyl, 1-octenyl, 3-octenyl, 1-nonenyl, 3-nonenyl, 1-decenyl, 4-decenyl, 1,3-butadiene, 1,3-pentadiene, 1,4-pentadiene and 1,4-hexadiene, etc.; the alkenyl group may be optionally further substituted with a substituent.

[0830] "Alkenylene" refers to a straight or branched divalent unsaturated hydrocarbon group containing at least one carbon-carbon double bond (C=C), typically containing 2 to 18 carbon atoms, such as 2 to 8 carbon atoms, further such as 2 to 6 carbon atoms, and further such as 2 to 4 carbon atoms. Non-limiting examples include ethynylene, and the alkenylene group may be optionally substituted with a substituent.

[0831] "Alkynyl" refers to a straight-chain or branched hydrocarbon group containing at least one carbon-carbon triple bond (C≡C), typically containing 2 to 18 carbon atoms, further containing 2 to 8 carbon atoms, further containing 2 to 6 carbon atoms, and further containing 2 to 4 carbon atoms. Examples include, but are not limited to, ethynyl, 1-propynyl, 2-propynyl, butynyl, 2-butynyl, 3-butynyl, 1-methyl-2-propynyl, 4-pentynyl, 3-pentynyl, 1-methyl-2-butynyl, 2-hexynyl, 3-hexynyl, 2-heptynyl, 3-heptynyl, 4-heptynyl, 3-octynyl, 3-nonynyl, and 4-decynyl. The alkynyl group may be optionally substituted with a substituent.

[0832] "Alkynylene" refers to a straight or branched divalent unsaturated hydrocarbon group containing a carbon-carbon triple bond (C≡C), typically containing 2 to 18 carbon atoms, further containing 2 to 8 carbon atoms, further containing 2 to 6 carbon atoms, further containing 2-4 carbon atoms, non-limiting examples include ethynylene, propynylene, butynylene, and the alkynylene group may be optionally substituted with a substituent.

[0833] "Cycloalkyl" refers to a saturated or partially unsaturated, non-aromatic carbocyclic hydrocarbon group containing no ring heteroatoms. Cycloalkyl can be monocyclic, bicyclic or polycyclic. Bicyclic or polycyclic rings can be cyclic, spirocyclic, bridged or a combination thereof. Bicyclic or polycyclic rings can include one or more aromatic rings, but the ring system as a whole does not have aromaticity. The attachment site can be on the aromatic ring or on the non-aromatic ring. Usually, the cycloalkyl group contains 3 to 20 carbon atoms, further contains 3-8 carbon atoms, and further contains 3-6 carbon atoms; when it is a monocyclic cycloalkyl group, it contains 3-15 carbon atoms, or 3-10 carbon atoms, or 3-8 carbon atoms, or 3-6 carbon atoms; when it is a bicyclic or polycyclic cycloalkyl group, it contains 5-12 carbon atoms, or 5-11 carbon atoms, or 6-10 carbon atoms; non-limiting examples include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, butenyl, cyclopentenyl, cyclohexenyl, The cycloalkyl group may be optionally substituted with a substituent.

[0834] "Cycloalkylene" refers to a divalent radical of a cycloalkyl group.

[0835] "Aryl" refers to a carbon ring with aromaticity and no heteroatoms, including monocyclic aromatic groups and fused aromatic groups, and aromatic groups fused with cycloalkyl groups. When fused with cycloalkyl groups, the aromatic group is the linking point. It usually contains 6 to 14 carbon atoms, and further contains 6 to 10 carbon atoms. Non-limiting examples include phenyl, naphthyl, anthracenyl, phenanthrenyl, The aryl group may be optionally substituted with a substituent.

[0836] "Carbocycle" or "carbocyclyl" refers to a saturated, partially unsaturated, or aromatic carbocycle, including aryl and cycloalkyl. Carbocycles can be monocyclic, bicyclic, or polycyclic, including bridged, fused, and spirocyclic rings and combinations thereof. Carbocycles typically have 3 to 12 carbon atoms, or 3-10 carbon atoms, or 3-6 carbon atoms. In non-limiting examples, monocyclic carbocycles include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, or phenyl, and bicyclic bridged rings include etc., double ring and ring include etc., bicyclic spiro ring includes The carbocyclic ring may be optionally substituted with a substituent.

[0837] "Heterocycloalkyl" refers to a saturated or partially unsaturated non-aromatic carbocyclic ring containing 1, 2, 3, or 4 heteroatoms selected from N, S, and O. Heterocycloalkyl can be monocyclic, bicyclic, or polycyclic. Bicyclic or polycyclic rings can be bridged, fused, spirocyclic, or a combination thereof. Bicyclic or polycyclic rings can include one or more aromatic or heteroaromatic rings, but the ring system as a whole is not aromatic. The attachment point can be on the aromatic ring or on the non-aromatic ring. Heterocycloalkyl groups are usually 3 to 20-membered rings. When they are monocyclic heterocycloalkyl groups, they are usually 3 to 15-membered rings, or 3-10-membered rings, or 3-8-membered rings, or 3-6-membered rings; when they are bicyclic or polycyclic heterocycloalkyl groups, they are usually 5-12-membered rings, or 5-11-membered rings, or 6-9-membered rings. The heteroatoms N and S include their oxidation states. Non-limiting examples of heterocycloalkyl groups include azetidinyl, morpholinyl, piperazinyl, piperidinyl, tetrahydropyranyl, oxetanyl, pyranyl, azolidinyl, azolinyl, oxolanyl, oxekinyl, and the like. Heterocycloalkyl groups may be optionally substituted with substituents.

[0838] "Heteroaromatic ring" or "heteroaryl" unless otherwise specified refers to a ring containing 1 to 4 heteroatoms selected from N, O or S and their oxidation states and having aromatic properties, which may be monocyclic, bicyclic or polycyclic, and the bicyclic or polycyclic rings may be bridged, parallel, spirocyclic or combinations thereof; when bicyclic or polycyclic, it may be a fusion of a heteroaryl and an aryl, or a fusion of a heteroaryl and a heteroaryl, wherein either the heteroaryl or the aryl may be a connection site. Non-limiting examples include furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyrazolyl, pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, indolyl, purinyl, The heteroaryl group may be optionally substituted by a substituent.

[0839] "Heterocycle" or "heterocyclyl" refers to a saturated or unsaturated, aromatic or non-aromatic ring containing 1 to 4 heteroatoms selected from N, O, or S and their oxidation states, and includes heteroaryl and heterocycloalkyl. Heterocycles include monocyclic heterocycles, bicyclic bridged heterocycles, bicyclic fused heterocycles, and bicyclic spiro heterocycles, or combinations thereof. Heterocycles are typically 3- to 12-membered heterocycles, 5- to 12-membered heterocycles, or 5- to 7-membered heterocycles. The heterocyclic group may be attached to a heteroatom or a carbon atom, and non-limiting examples include oxirane, aziridine, oxetanyl, azetidinyl, 1,3-dioxolanyl, 1,4-dioxolanyl, 1,3-dioxanyl, piperazinyl, azepanyl, pyridinyl, furanyl, thienyl, pyranyl, N-alkylpyrrolyl, pyrimidinyl, pyrazinyl, pyrazolyl, pyridazinyl, imidazolyl, piperidinyl, piperidinyl, morpholinyl, thiomorpholinyl, 1,3-dithianyl , dihydrofuranyl, dihydropyranyl, dithiolanyl, tetrahydrofuranyl, tetrahydropyrrolyl, tetrahydroimidazolyl, oxazolyl, dihydrooxazolyl, tetrahydrooxazolyl, tetrahydrothiazolyl, tetrahydropyranyl, benzimidazolyl, benzopyridinyl, pyrrolopyridinyl, benzodihydrofuranyl, azabicyclo[3.2.1]octyl, azabicyclo[5.2.0]nonyl, oxatricyclo[5.3.1.1]dodecyl, azaadamantyl and oxaspiro[3.3]heptanyl, The heterocyclic ring may be optionally substituted with a substituent.

[0840] "Heterocyclylene" refers to a substituted or unsubstituted, saturated or unsaturated, aromatic or non-aromatic divalent heterocyclic group. Non-limiting examples include wait.

[0841] "Spiro" refers to a polycyclic group that shares a carbon atom (called a spiro atom) between the rings, which may contain 0 or more double bonds or triple bonds, and may contain 0 to 5 heteroatoms selected from N, O, S, P, Si and their oxidation states. Typically, the spiro ring is a 6- to 14-membered ring, or a 6- to 12-membered ring, or a 6- to 10-membered ring. Typically, the spiro ring is a trispirotri (representing a three-membered ring spirotricycle), a trispirotetra, a trispiropenta, a trispirohexa, a tetraspirotetra, a tetraspiropenta, a tetraspirohexa, a pentaspiropenta or a pentaspirohexa. Non-limiting examples of spiro rings include The spiro ring may be optionally substituted with a substituent.

[0842] "Parallel ring" or "condensed ring" refers to a polycyclic group in which the rings share two adjacent ring atoms and a chemical bond, and may contain one or more double bonds or triple bonds, and the rings may contain 0 to 5 heteroatoms selected from N, S, O, P, Si and their oxidation states. Usually, the cyclic ring is a 5- to 20-membered ring, or a 5- to 14-membered ring, or a 5- to 12-membered ring, or a 5- to 10-membered ring. Usually, the cyclic ring is a three- to four-membered ring (representing a cyclic ring formed by a three-membered ring and a four-membered ring. According to the IUPC naming rules, it is possible to have a three-membered ring as the basic ring or a four-membered ring as the basic ring. The same applies below), a three- to five-ring ring, a three- to six-ring ring, a four- to four-ring ring, a four- to five-ring ring, a four- to six-ring ring, a five- to five-ring ring, a five- to six-ring ring, and a six- to six-ring ring. Non-limiting examples of cyclic rings include purine, quinoline, isoquinoline, benzopyran, benzofuran, benzothiophene,

[0843] ; The ring may be aromatic or non-aromatic and optionally substituted by a substituent.

[0844] "Bridged ring" means two rings that share two non-adjacent ring atoms and may contain one or more double or triple bonds. A bridged ring may contain 0 to 5 heteroatoms selected from N, S, O, P, Si and their oxidation states. Typically, the number of ring atoms in a bridged ring is 5 to 20, or 5 to 14, or 5 to 12, or 5 to 10. Non-limiting examples of bridged rings include adamantane,

[0845] "Substitution" or "substituent" unless otherwise specified refers to any substitution at a position permitted by chemical theory, and the number of substituents complies with the chemical bond rules. Exemplary substituents include but are not limited to: C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Heteroalkyl, C 5-12 Aryl, 5-12 membered heteroaryl, hydroxyl, C 1-6 Alkoxy, C 5-12 Aryloxy, thiol, C 1-6 Alkylthio, cyano, halogen, C1-6 Alkylthiocarbonyl, C 1-6 Alkylcarbamoyl, N-carbamoyl, nitro, silyl, sulfinyl, sulfonyl, sulfoxide, halo 1-6 Alkyl, halogenated C 1-6 Alkoxy, amino, phosphonic acid, -CO2(C 1-6 alkyl), -OC(=O)(C 1-6 alkyl), -OCO2(C 1-6 alkyl), -C(=O)NH2, -C(=O)N(C 1-6 alkyl)2,-OC(=O)NH(C 1-6 alkyl), -NHC(=O)(C 1-6 alkyl), -N(C 1-6 alkyl)C(=O)(C 1-6 Alkyl), -NHCO2(C 1-6 alkyl), -NHC(=O)N(C 1-6 alkyl)2,-HC(=O)NH(C 1-6 alkyl), -NHC(=O)NH2, -NHSO2(C 1-6 alkyl), -SO2N(C 1-6 Alkyl)2,-SO2NH(C 1-6 alkyl), -SO2NH2, -SO2C 1-6 Alkyl, etc.

[0846] "Optional" or "optionally" means that the subsequently described event or circumstance may but need not occur, and the description includes instances where the event or circumstance occurs and instances where it does not. For example, "alkyl optionally substituted with F" means that the alkyl group may but need not be substituted with F, and the description includes instances where the alkyl group is substituted with F and instances where the alkyl group is not substituted with F.

[0847] "Pharmaceutically acceptable salts" refer to salts of the compounds of the present invention that retain the biological effectiveness and properties of the free acids or free bases, and the free acids are reacted with non-toxic inorganic or organic bases, or the free bases are reacted with non-toxic inorganic or organic acids.

[0848] A "pharmaceutical composition" refers to a mixture of one or more compounds described herein, or stereoisomers, deuterated forms, solvates, pharmaceutically acceptable salts, or cocrystals thereof, with other ingredients, wherein the other ingredients include physiologically / pharmaceutically acceptable carriers and / or excipients.

[0849] "Carrier" refers to a system that does not cause significant irritation to the organism and does not eliminate the biological activity and properties of the administered compound, and can change the way the drug enters the human body and its distribution in the body, control the release rate of the drug and deliver the drug to the target organ. Non-limiting examples include microcapsules and microspheres, nanoparticles, liposomes, etc.

[0850] An "excipient" is a substance that is not itself a therapeutic agent but serves as a diluent, adjuvant, binder, and / or vehicle that is added to a pharmaceutical composition to improve its handling or storage properties or to allow or facilitate the formation of a compound or pharmaceutical composition into a unit dosage form for administration. As known to those skilled in the art, excipients can serve a variety of functions and can be described as wetting agents, buffers, suspending agents, lubricants, emulsifiers, disintegrants, absorbents, preservatives, surfactants, colorants, flavoring agents, and sweeteners. Examples of excipients include, but are not limited to: (1) sugars such as lactose, glucose, and sucrose; (2) starches such as corn starch and potato starch; (3) cellulose and its derivatives such as sodium carboxymethylcellulose, ethylcellulose, cellulose acetate, hydroxypropyl methylcellulose, hydroxypropyl cellulose, microcrystalline cellulose, and cross-linked carboxymethylcellulose (e.g., cross-linked sodium carboxymethylcellulose); (4) tragacanth; (5) malt; (6) gelatin; (7) talc; (8) excipients such as cocoa butter and suppository waxes; (9) oils such as peanut oil, cottonseed oil, safflower oil, sesame oil, olive oil, corn oil, etc. and soybean oil; (10) glycols such as propylene glycol; (11) polyols such as glycerol, sorbitol, mannitol and polyethylene glycol; (12) esters such as ethyl oleate and ethyl laurate; (13) agar; (14) buffers such as magnesium hydroxide and aluminum hydroxide; (15) alginic acid; (16) pyrogen-free water; (17) isotonic saline; (18) Ringer's solution; (19) ethanol; (20) pH buffer solutions; (21) polyesters, polycarbonates and / or polyanhydrides; and (22) other non-toxic compatible substances used in pharmaceutical preparations.

[0851] The compounds of the present invention may exist in specific geometric or stereoisomeric forms. All such compounds of the present invention, including cis and trans isomers, (-)- and (+)-enantiomers, (R)- and (S)-enantiomers, diastereomers, (D)-isomers, (L)-isomers, and racemic mixtures and other mixtures thereof, such as enantiomerically or diastereomerically enriched mixtures, all of which are within the scope of the present invention. Additional asymmetric carbon atoms may be present in the substituents of the compounds of the present invention. All of these isomers and their mixtures are within the scope of the present invention. In certain embodiments, preferred compounds are those isomeric compounds that exhibit superior biological activity. Purified or partially purified isomers and stereoisomers of the compounds of the present invention, or racemic mixtures or diastereomeric mixtures, are also within the scope of the present invention. Purification and separation of such substances can be achieved by standard techniques known in the art.

[0852] The compounds of the present invention also include their tautomers. For example, when the present invention describes a compound on the left side in which the pyrimidine ring is substituted with OH, it also includes the tautomer compound on the right side.

[0853] "Solvate" refers to a substance formed by a compound of the present invention or a salt thereof and a stoichiometric or non-stoichiometric amount of a solvent bound to the compound or salt thereof by non-covalent forces between the molecules. When the solvent is water, the solvate is a hydrate.

[0854] A "cocrystal" is a crystal formed by the active pharmaceutical ingredient (API) and cocrystal former (CCF) bound together by hydrogen bonds or other non-covalent bonds. Both the API and CCF are solid in their pure form at room temperature, and the components exist in a fixed stoichiometric ratio. A cocrystal is a multi-component crystal, encompassing both binary cocrystals formed between two neutral solids and multi-component cocrystals formed between a neutral solid and a salt or solvate. DETAILED DESCRIPTION

[0855] The present invention will be described in detail below through examples. Where specific conditions are not specified in the examples, the experimental methods are carried out according to conventional conditions. The examples are provided to better illustrate the present invention, but it should not be understood that the present invention is limited to the examples. Any non-essential improvements and adjustments made by those skilled in the art to the embodiments based on the above invention are still within the scope of protection of the present invention.

[0856] Test Method

[0857] The structures of the compounds were determined by nuclear magnetic resonance (NMR) or / and mass spectrometry (MS). NMR shifts (δ) were expressed in 10 -6The unit of (ppm) is given. NMR measurements were performed using a Bruker Avance III 400 and Bruker Avance 300 NMR spectrometer. The solvents used were deuterated dimethyl sulfoxide (DMSO-d6), deuterated chloroform (CDCl3), and deuterated methanol (CD3OD). The internal standard was tetramethylsilane (TMS).

[0858] MS was determined using (Agilent 6120B (ESI) and Agilent 6120B (APCI));

[0859] HPLC determination was performed using an Agilent 1260DAD high pressure liquid chromatograph (Zorbax SB-C 18 100 × 4.6 mm, 3.5 μM);

[0860] Thin layer chromatography silica gel plates used were Yantai Huanghai HSGF254 or Qingdao GF254 silica gel plates. The specifications of the silica gel plates used for thin layer chromatography (TLC) were 0.15 mm to 0.20 mm, and the specifications used for thin layer chromatography separation and purification products were 0.4 mm to 0.5 mm.

[0861] Column chromatography generally uses Yantai Huanghai silica gel 200-300 mesh silica gel as the carrier.

[0862] Preparation of intermediate 1

[0863] Step 1: Dissolve 2,2-difluoroethanol-1-ol (16.5 g, 201.2 mmol) in tetrahydrofuran (50 mL). Add sodium hydride (7.44 g, 310 mmol) in portions at 0°C. Return to room temperature and stir for 40 minutes. Then, add 5-bromo-2-chloropyrimidine (Compound 1a) (30 g, 155.1 mmol) in tetrahydrofuran (50 mL) and continue stirring for 3 hours. Dilute with water and extract three times with ethyl acetate. The organic phase is collected, dried, and concentrated to yield Compound 1b (36 g crude product), which is used directly in the next step.

[0864] LC-MS (ESI): m / z = 239.1 [M+H] + .

[0865] Step 2: Dissolve compound 1b (38 g, 158.98 mmol), potassium acetate (39.01 g, 397.45 mmol), pinacol diboronate (52.48 g, 206.67 mmol), and chloro(2-dicyclohexylphosphino-2',4',6'-triisoporphyrinyl-1,1'-biphenyl)[2-(2'-amino-1,1'-biphenyl)]palladium(II) (12.51 g, 15.90 mmol) in 1,4-dioxane (500 mL). The mixture was purged with nitrogen three times and heated to 100°C under a nitrogen atmosphere with stirring for 3 hours. Filter the mixture while hot, and rinse the filter cake four times with ethyl acetate and dichloromethane. The filtrate was collected and concentrated to yield compound 1c (32 g crude product), which was used directly in the next reaction.

[0866] LC-MS (ESI): m / z = 205.2 [M+H] + .

[0867] Step 3: Compound 1c (30 g, 147.10 mmol), 6-bromo-3-pyridazinone (30.71 g, 176.52 mmol), tripotassium phosphate (40.59 g, 191.23 mmol), and (1,3-bis(2,6-diisopropylphenyl)imidazolylidene)(3-chloropyridyl)palladium(II) dichloride (10.02 g, 14.71 mmol) were dissolved in a mixed solvent of 1,4-dioxane (360 mL) and water (120 mL). The mixture was purged with nitrogen three times and heated to 90°C under a nitrogen atmosphere with stirring for 3 hours. After cooling, the mixture was filtered and the filter cake was rinsed with water, ethyl acetate, and dichloromethane, respectively. The filter cake was collected and dried to give intermediate 1 (27 g crude product), which was used directly.

[0868] LC-MS (ESI): m / z = 255.1 [M+H] + .

[0869] Example 56

[0870] Step 1: Dissolve compound 56A (0.7 g, 5.22 mmol) in dichloromethane (12 mL), add thionyl chloride (1.24 g, 10.44 mmol), and stir at room temperature for 2 hours. Directly concentrate under reduced pressure to obtain compound 56B (0.8 g crude product, 100%), which is used directly in the next reaction.

[0871] 1 H NMR (400MHz, DMSO-d6) δ7.24(d,1H),7.15(t,1H),7.07(d,1H),4.72(s,2H),3.12(s,4H).

[0872] Step 2: Compound 1D (0.6 g, 2.20 mmol, synthesis method reference: WO2020097258A1), compound 56B (0.34 g, 2.20 mmol), and cesium carbonate (2.15 g, 6.60 mmol) were dissolved in acetonitrile (20 mL) and stirred at 80°C for 2 hours. After cooling, the mixture was concentrated directly. The residue was added with water (10 mL) and extracted three times with ethyl acetate (15 mL × 3). The organic phase was collected, dried, and concentrated. The resulting residue was purified by reverse-phase column chromatography (acetonitrile:water (v:v) = 45:55) to obtain compound 56 (0.6 g, 70.23%).

[0873] 1 H NMR (400MHz, DMSO-d6) δ9.15(s,2H),8.10(d,1H),7.24(s,1H),7.16-7.10(m,2H),7.04(d,1H),5.27(s,2H),5.11(d,2H),3.09(s,4H);

[0874] LC-MS (ESI): m / z = 389.1 [M+H] + .

[0875] Example 57

[0876] Step 1: Dissolve (2,3-dihydro-1H-inden-5-yl)methanol (Compound 57A) (0.3 g, 2.04 mmol) in dichloromethane (6 mL). Slowly add thionyl chloride (0.49 g, 4.12 mmol) dropwise in an ice-water bath. Return the mixture to room temperature and continue the reaction for 2 hours. The reaction solution was concentrated to afford Compound 57B (0.5 g crude product), which was used directly in the next reaction.

[0877] 1 H NMR (400MHz, DMSO-d6)7.19-7.11(m,3H),4.60(s,2H),2.85-2.77(m,4H),2.04-1.88(m,2H).

[0878] Step 2: Compound 1D (0.25 g, 0.92 mmol), compound 57B (0.23 g, 1.38 mmol), and potassium carbonate (0.32 g, 2.32 mmol) were dissolved in N,N-dimethylformamide (8 mL), heated to 70°C, and stirred for 2 hours. The reaction mixture was diluted with water and extracted three times with ethyl acetate. The combined organic phases were concentrated, and the resulting residue was purified by preparative HPLC. Methods: 1. Apparatus: Waters 2767 Preparative HPLC; Column: SunFire@Prep C18 (19 mm × 250 mm). 2. The sample was filtered through a 0.45 μm filter to prepare a sample solution. 3. Preparative Chromatography Conditions: a. Mobile Phase A and B Composition: Mobile Phase A: Acetonitrile; Mobile Phase B: Water (containing 0.5% ammonium acetate); b. Gradient elution, mobile phase A content ranging from 50% to 80%; c. Flow rate: 20 mL / min; d. Elution time: 18 min. Retention time: 17 min. Compound 57 (160 mg, 43%) was obtained.

[0879] 1 H NMR(400MHz,DMSO-d6)δ9.15(s,2H),8.11(d,1H),7.25(s,1H),7.19-7.11(m ,3H),5.27(s,2H),5.16-5.06(m,2H),2.85-2.77(m,4H),2.04-1.88(m,2H);

[0880] LC-MS (ESI): m / z = 403.2 [M+H] + .

[0881] Example 60

[0882] Step 1: Dissolve intermediate 1 (0.25 g, 0.98 mmol), compound 56B (0.19 g, 1.24 mmol), and potassium carbonate (0.34 g, 2.46 mmol) in N,N-dimethylformamide (8 mL), heat to 70°C, and stir for 3 hours. The reaction mixture was diluted with water and extracted three times with ethyl acetate. The organic phases were combined and concentrated, and the residue was purified by preparative HPLC. Methods: 1. Apparatus: Waters 2767 Preparative HPLC; Column: SunFire@Prep C18 (19 mm × 250 mm). 2. Filter the sample through a 0.45 μm filter to prepare a sample solution. 3. Preparative Chromatography Conditions: a. Mobile Phase A and B Composition: Mobile Phase A: Acetonitrile; Mobile Phase B: Water (containing 0.5% ammonium acetate); b. Gradient elution, mobile phase A content ranging from 30% to 70%; c. Flow rate: 20 mL / min; d. Elution time: 20 min. Retention time: 18 min. Compound 60 (120 mg, 33%) was obtained.

[0883] 1 H NMR(400MHz,DMSO-d6)δ9.11(s,2H),8.08(d,1H),7.25(d,1H),7.15-7.10(m,2H ),7.04(d,1H),6.63-6.26(m,1H),5.27(s,2H),4.78-4.62(m,2H),3.08(s,4H);

[0884] LC-MS (ESI): m / z = 371.1 [M+H] + .

[0885] Example 61

[0886] Step 1: Compound 61A (2.0 g, 10.91 mmol) was dissolved in tetrahydrofuran (25 mL) and stirred under a nitrogen atmosphere. n-Butyllithium (8.7 mL, 13.09 mmol, 1.5 M solution in n-hexane) was added dropwise at -78°C. After addition, the mixture was stirred at the same temperature for 0.5 hour. Finally, N,N-dimethylformamide (1.04 g, 14.18 mmol) was added dropwise and stirring continued for 1 hour. Water was slowly added dropwise at -78°C to quench the reaction. The mixture was extracted with ethyl acetate (30 mL x 3). The organic phase was collected, dried, and concentrated to afford compound 61B (1.40 g crude product, 97.1%), which was used directly in the next step.

[0887] Step 2: Compound 61B (1.4 g, 10.59 mmol) was dissolved in tetrahydrofuran (25 mL). The mixture was stirred at 0°C and methylmagnesium bromide (10.6 mL, 21.2 mmol, 2 M in diethyl ether) was added dropwise. After complete addition, the mixture was allowed to react at room temperature for 2 h. The reaction was quenched by adding water under ice-cooling. The mixture was extracted with ethyl acetate (30 mL x 3). The organic phase was collected, dried, and concentrated to yield compound 61C (1.3 g, crude product, 82.83%), which was used directly in the next step.

[0888] Step 3: Compound 61C (0.60 g, 4.05 mmol) was dissolved in tetrahydrofuran (20 mL). Triphenylphosphine (1.59 g, 6.07 mmol) and compound 1D (1.21 g, 4.46 mmol) were added. Diisopropyl azodicarboxylate (1.23 g, 6.07 mmol) was slowly added dropwise at 0°C. The mixture was then slowly warmed to room temperature and allowed to react overnight. The reaction solution was concentrated, and the resulting residue was purified by silica gel column chromatography (petroleum ether:ethyl acetate (v:v) = 1:1) to afford compound 61 (700 mg, 42.96%).

[0889] 1H NMR((400MHz, CDCl3)δ8.94(s,2H),7.54(d,1H),7.33(d,1H),7.19(s,1H),7 .05-7.00(m,2H),6.41-6.36(m,1H),4.88(q,2H),3.14(s,4H),1.82(d,3H);

[0890] LC-MS (ESI): m / z = 403.1 [M+H] + .

[0891] Example 62

[0892] Step 1: Compound 62A (1.0 g, 5.46 mmol) and tetrahydrofuran (25 mL) were added to a three-necked flask and stirred at -78°C under nitrogen. Then, n-butyllithium (2.6 mL, 6.5 mmol, 2.5 M solution in n-hexane) was slowly added dropwise. After addition, the mixture was stirred at the same temperature for 0.5 h. Finally, N,N-dimethylformamide (0.52 g, 7.10 mmol) was slowly added dropwise and stirring continued for 1 h. The reaction was quenched by the slow addition of water, and extracted with ethyl acetate (30 mL x 2). The organic phase was collected, dried, and concentrated to yield compound 62B (0.50 g crude product, 69.3%), which was used directly in the next step.

[0893] Step 2: Compound 62B (0.22 g, 1.66 mmol) was dissolved in tetrahydrofuran (15 mL) and stirred at 0°C. Diisobutylaluminum hydride (2.5 mL, 2.5 mmol, 1 M solution in n-hexane) was then slowly added dropwise. After complete addition, the mixture was returned to room temperature and stirred for 2 h. The mixture was stirred in an ice bath. Water (0.2 mL), 15% aqueous sodium hydroxide solution (0.2 mL), and water (0.5 mL) were added sequentially. The mixture was stirred for 10 min and dried over anhydrous sodium sulfate. The mixture was filtered and the filter cake was washed with ethyl acetate. The resulting solution was concentrated to yield compound 62C (0.18 g, 80.8%), which was used directly in the next step.

[0894] Step 3: Compound 62C (0.18 g, 1.34 mmol) was dissolved in tetrahydrofuran (20 mL), and triphenylphosphine (0.53 g, 2.01 mmol) and compound 1D (0.40 g, 1.47 mmol) were added. Diisopropyl azodicarboxylate (0.41 g, 2.01 mmol) was slowly added dropwise at 0°C, and the mixture was slowly warmed to room temperature and stirred overnight. The mixture was concentrated directly, and the resulting residue was purified by silica gel column chromatography (petroleum ether:ethyl acetate (v:v) = 1:1) to afford compound 62 (55 mg, 10.57%).

[0895] 1H NMR((400MHz, CDCl3)δ8.94(s,2H),7.59(d,1H),7.24(d,1H),7.18(t,1H),7.07(d,1H),6.98(d,1H),5.36(s,2H),4.87(q,2H),3.14-3.10(m,4H);

[0896] LC-MS (ESI): m / z = 389.1 [M+H] + .

[0897] Example 63 and Example 64

[0898] Compound 61 (700.0 mg) was chirally resolved to give P1 (retention time: 1.855 min, designated as compound 63. SFC analysis method: instrument: SHIMADZU LC-30AD; chromatographic column: Chiralcel WHELK column; mobile phase: A for CO2; B for 0.05% DEA in MeOH; gradient: 5-40% B gradient elution; flow rate: 3 mL / min; column temperature: 35°C; column pressure: 100 bar; wavelength: 220 nm.) and P2 (retention time: 2.536 min, designated as compound 64). Preparation method: Instrument: Waters 150Prep-SFCA; Column: Chiralcel WHELK column; Mobile phase: A for CO2; B for 0.1% NH3·H2O in MeOH; Gradient: 45% B gradient elution; Flow rate: 100 mL / min; Column temperature: 25°C; Wavelength: 220 nm; Cycle time: 5.0 min; Sample preparation: Sample concentration: 10 mg / mL in acetonitrile; Injection: 10 mL per sample. After separation, the product was dried and concentrated by rotary evaporation at 35°C, and the solvent was then dried in a lyophilizer at -80°C to afford Compound 63 (260 mg, 37.1%) and Compound 64 (256 mg, 36.6%).

[0899] Compound 63: 1 H NMR((400MHz, CDCl3)δ8.94(s,2H),7.54(d,1H),7.32(d,1H),7.19(s,1H),7.04-7.00(m,2 H),6.41-6.36(m,1H),4.88(q,2H),3.14(s,4H),1.82(d,3H); LC-MS(ESI):m / z=403.1[M+H] + .

[0900] Compound 64:1 H NMR((400MHz, CDCl3)δ8.94(s,2H),7.54(d,1H),7.32(d,1H),7.19(s,1H),7.04-7.00(m,2 H),6.41-6.36(m,1H),4.88(q,2H),3.14(s,4H),1.82(d,3H); LC-MS(ESI):m / z=403.1[M+H] + .

[0901] Example 65

[0902] Step 1: Dissolve compound 56B (3.5 g, 20.00 mmol), 6-bromo-3-pyridazinol (3.94 g, 20.00 mmol), and cesium carbonate (19.55 g, 60.00 mmol) in acetonitrile (100 mL), heat to 80°C, and stir for 2.5 h. The mixture was concentrated directly, and the resulting residue was purified by silica gel column chromatography (petroleum ether:ethyl acetate (v:v) = 3:1) to afford compound 65A (4 g, 68.70%).

[0903] LC-MS (ESI): m / z = 291.1 [M+H] + .

[0904] Step 2: Compound 65A (4 g, 13.74 mmol), 2-chloropyrimidine-5-boronic acid (4.35 g, 27.48 mmol), potassium carbonate (5.70 g, 41.22 mmol), and 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene[3-chloropyridine]palladium dichloride (0.94 g, 1.37 mmol) were dissolved in 1,4-dioxane (50 mL) and water (10 mL). The mixture was heated to 90°C under nitrogen and stirred for 2.5 h. The residue was concentrated directly, and purified by silica gel column chromatography (petroleum ether:ethyl acetate (v:v) = 1:1) to provide compound 65B (3.5 g, 78.44%).

[0905] LC-MS (ESI): m / z = 325.5 [M+H] + .

[0906] Step 3: Dissolve trifluoropropanol (0.28 g, 2.48 mmol) in tetrahydrofuran (5 mL), then add sodium metal (0.043 g, 1.86 mmol). After the sodium disappears, add compound 65B (0.20 g, 0.62 mmol) and stir at room temperature for 1 h. Extract with water and ethyl acetate, collect the organic phase, dry it, and concentrate it. The resulting residue is purified by reverse-phase column chromatography (water:acetonitrile (v:v) = 40:60) to give compound 65 (0.1 g, 40.09%).

[0907] 1 H NMR(400MHz,DMSO-d6)δ9.09(s,2H),8.08(d,1H),7.24(d,1H),7.15-7.09(m,2H ),7.04(d,1H),5.27(s,2H),4.61-4.58(m,2H),3.09(s,4H),2.94-2.79(m,2H);

[0908] LC-MS (ESI): m / z = 403.4 [M+H] + .

[0909] Example 66

[0910] Step 1: 2-Fluoroethanol (0.20 g, 3.1 mmol) was dissolved in tetrahydrofuran (5 mL), and sodium metal (0.057 g, 2.48 mmol) was added. After the sodium disappeared, compound 65B (0.20 g, 0.62 mmol) was added and stirred at room temperature for 1 h. Water and ethyl acetate were added for extraction. The organic phase was collected, dried, and concentrated. The resulting residue was purified by reverse-phase column chromatography (water:acetonitrile (v:v) = 40:60) to provide compound 66 (0.1 g, 45.77%).

[0911] 1 H NMR (400MHz, DMSO-d6) δ9.08(s,2H),8.08(d,1H),7.24(d,1H),7.16-7.08(m,2H),7.04(d,1H),5.27(s,2H),4.92-4.51(m,4H),3.09(s,4H);

[0912] LC-MS (ESI): m / z = 353.4 [M+H] + .

[0913] Example 67

[0914] Step 1: Intermediate 1 (0.50 g, 1.97 mmol), compound 67A (0.50 g, 2.36 mmol), and cesium carbonate (1.30 g, 4.00 mmol) were added sequentially to acetonitrile (20 mL), heated to 80°C, and stirred for 2 hours. After cooling, the mixture was diluted with water and extracted three times with ethyl acetate. The combined organic phases were dried over anhydrous sodium sulfate and concentrated. The resulting residue was purified by reverse phase column chromatography (acetonitrile:water (v:v) = 10%-80%) to afford compound 67 (420 mg, 55%).

[0915] 1H NMR(400MHz, CDCl3)δ8.93(s,2H),7.56(d,1H),7.34(s,1H),7.27-7.25(m,1H),7.19-7.17(m,1H),7 .06(d,1H),6.32-6.02(m,1H),5.36(s,2H),4.69-4.61(m,2H),2.90-2.85(m,4H),2.90-2.00(m,2H);

[0916] LC-MS (ESI): m / z = 385.1 [M+H] + .

[0917] Example 68

[0918] 3,3-Difluoropropan-1-ol (0.24 g, 2.48 mmol) was dissolved in tetrahydrofuran (5 mL), and sodium metal (0.043 g, 1.87 mmol) was added. After the sodium disappeared, compound 65B (0.20 g, 0.62 mmol) was added and allowed to react at room temperature for 1 hour. Water and ethyl acetate were added to the system for extraction. The organic phase was collected and concentrated under reduced pressure. The resulting residue was purified by reverse-phase column chromatography (acetonitrile:water (v:v) = 10% to 80%) to obtain compound 69 (0.1 g, 41.96%).

[0919] 1 H NMR(400MHz,DMSO-d6)δ9.08(s,2H),8.07(d,1H),7.24(d,1H),7.15-7.08(m,2H),7.0 4(d,1H),6.42-6.11(m,1H),5.27(s,2H),4.52(t,2H),3.09(s,4H),2.46-2.29(m,2H);

[0920] LC-MS (ESI): m / z = 385.1 [M+H] + .

[0921] Example 69

[0922] 3-Fluoropropan-1-ol (0.19 g, 2.48 mmol) was dissolved in tetrahydrofuran (5 mL), and sodium metal (0.043 g, 1.87 mmol) was added. After the sodium disappeared, compound 65B (0.20 g, 0.62 mmol) was added and allowed to react at room temperature for 1 hour. Water and ethyl acetate were added to the system for extraction. The organic phase was collected and concentrated under reduced pressure. The resulting residue was purified by reverse-phase column chromatography (acetonitrile:water (v:v) = 10% to 80%) to obtain compound 69 (0.08 g, 35.22%).

[0923] 1 H NMR(400MHz,DMSO-d6)δ9.07(s,2H),8.07(d,1H),7.24(d,1H),7.14-7.07(m,2H),7.04(d ,1H),5.27(s,2H),4.67(t,1H),4.55(t,1H),4.47(t,2H),3.09(s,4H),2.23-2.06(m,2H);

[0924] LC-MS (ESI): m / z = 367.2 [M+H] + .

[0925] Example 70

[0926] 3-Chloropropan-1-ol (0.23 g, 2.48 mmol) was dissolved in tetrahydrofuran (5 mL), and sodium metal (0.043 g, 1.87 mmol) was added. After the sodium disappeared, compound 65B (0.20 g, 0.62 mmol) was added and allowed to react at room temperature for 1 hour. Water and ethyl acetate were added to the system for extraction. The organic phase was collected and concentrated under reduced pressure. The resulting residue was purified by reverse-phase column chromatography (acetonitrile:water (v:v) = 10% to 80%) to obtain compound 70 (0.09 g, 37.92%).

[0927] 1 H NMR(400MHz,DMSO-d6)δ9.07(s,2H),8.07(d,1H),7.24(d,1H),7.17-7.08(m,2H),7 .04(d,1H),5.27(s,2H),4.49(t,2H),3.80(t,2H),3.09(s,4H),2.28-2.15(m,2H);

[0928] LC-MS (ESI): m / z = 383.1 [M+H] + .

[0929] Example 71

[0930] Step 1: Dissolve compound 67A (2 g, 9.47 mmol), 6-bromo-3-pyridazinol (1.82 g, 10.42 mmol), and potassium carbonate (3.27 g, 23.68 mmol) in N,N-dimethylformamide (30 mL), heat to 70°C, and stir for 3 hours. After cooling, the mixture was diluted with water and extracted three times with ethyl acetate. The combined organic phases were concentrated under reduced pressure, and the resulting residue was purified by silica gel column chromatography (ethyl acetate:petroleum ether (v:v) = 15%) to afford compound 71B (2.5 g, 86%).

[0931] LC-MS (ESI): m / z = 305.2 [M+H] + .

[0932] Step 2: Compound 71B (2.5 g, 8.19 mmol), (2-chloropyrimidin-5-yl)boronic acid (1.95 g, 12.29 mmol), potassium phosphate (2.61 g, 12.29 mmol), and 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene](3-chloropyridyl)palladium(II) dichloride (0.56 g, 0.82 mmol) were dissolved in a mixed solvent of 1,4-dioxane (30 mL) and water (10 mL). The mixture was stirred at 90°C under nitrogen for 3 hours. After cooling, water was added directly to precipitate the solid, which was filtered and the filter cake was rinsed three times with ethyl acetate. The filter cake was collected and dried to obtain compound 71C (1.8 g, 65%).

[0933] LC-MS (ESI): m / z = 339.3 [M+H] + .

[0934] Step 3: Dissolve 3-fluoropropanol (0.46 g, 5.90 mmol) in tetrahydrofuran (10 mL) and add sodium metal (68 mg, 2.96 mmol). Stir at room temperature until the sodium metal disappears. Add compound 71C (200 mg, 0.59 mmol) to the reaction mixture and stir for 2 hours. Extract with water and ethyl acetate, wash the organic phase with saturated brine, and concentrate under reduced pressure. The resulting residue is purified by reverse-phase column chromatography (acetonitrile:water (v:v) = 10% to 80%) to obtain compound 71 (22 mg, 9.8%).

[0935] 1H NMR (400MHz, CDCl3) δ8.90(s,2H),7.55(d,1H),7.35(s,1H),7.28-7.25(m,1H),7.19-7.17(m,1H),7.05(d,1H) ),5.36(s,2H),4.74-4.72(m,1H),4.63-4.55(m,3H),2.90-2.85(m,4H),2.30-2.18(m,2H),2.09-2.00(m,2H);

[0936] LC-MS (ESI): m / z = 381.3 [M+H] + .

[0937] Example 72

[0938] Step 1: Compound 72A (1.00 g, 5.08 mmol), (tributyltin)methanol (1.96 g, 6.10 mmol) and chloro(2-dicyclohexylphosphino-2',4',6'-triisopropyl-1,1'-biphenyl)[2-(2'-amino-1,1'-biphenyl)]palladium(II) (0.40 g, 0.51 mmol) were added sequentially to 1,4-dioxane (30 mL) solvent, the atmosphere was replaced with nitrogen three times, the temperature was raised to 110°C and stirred for 2 hours. After completion of the reaction, the mixture was cooled to room temperature, and ethyl acetate (100 mL) and saturated brine (100 mL) were added for separation. The organic phase was collected and washed three times with saturated brine, then dried over anhydrous sodium sulfate. The filtrate was filtered and concentrated under reduced pressure. The resulting residue was purified by chromatography (ethyl acetate:petroleum ether (v:v) = 0-100%) to give compound 72B (0.24 g, yield: 31.89%).

[0939] LC-MS (ESI): m / z = 149.1 [M+H] + .

[0940] Step 2: Compound 72B (0.24 g, 1.62 mmol) was added to dichloromethane (10 mL), followed by triethylamine (0.16 g, 1.62 mmol). Methanesulfonyl chloride (0.19 g, 1.62 mmol) was slowly added dropwise under an ice bath. The mixture was stirred for 30 minutes. After completion of the reaction, ethyl acetate (100 mL) and aqueous sodium bicarbonate (100 mL) were added for separation. The organic phase was collected and washed three times with saturated brine, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The resulting residue was purified by column chromatography (ethyl acetate:petroleum ether (v:v) = 0-50%) to afford compound 72C (0.18 g, yield: 49.10%).

[0941] LC-MS (ESI): m / z = 227.20 [M+H] + .

[0942] Step 3: Compound 1D (90 mg, 0.33 mmol), compound 72C (75 mg, 0.33 mmol), and potassium carbonate (46 mg, 0.33 mmol) were added sequentially to acetonitrile (10 mL), and the mixture was heated to 70°C and stirred for 2 hours. After cooling to room temperature, ethyl acetate and saturated brine were added for separation. The organic phase was collected and washed three times with saturated brine, then concentrated under reduced pressure. The resulting residue was purified by reverse-phase column chromatography (acetonitrile:water (v:v) = 5%-80%) to obtain compound 72 (51 mg, yield: 38.41%).

[0943] 1 H NMR(400MHz, CDCl3)δ8.94(s,2H),7.70-7.59(m,2H),7.53-7.48(m,1H),7. 34-7.32(m,1H),7.11(d,1H),5.45(s,2H),4.91-4.85(m,2H),3.95(s,2H);

[0944] LC-MS (ESI): m / z = 403.50 [M+H] + .

[0945] Example 73

[0946] Step 1: Compound 74D (0.20 g, 1.20 mmol) and dichloromethane (15 mL) were added to a single-necked flask and stirred at 0°C. Thionyl chloride (0.29 g, 2.40 mmol) was then slowly added dropwise. After addition, the mixture was stirred at room temperature for 2 hours. The mixture was concentrated to afford compound 73A (0.22 g, 99.29%), which was used directly in the next step.

[0947] Step 2: Compound 73A (0.22 g, 1.19 mmol) was dissolved in acetonitrile (15 mL), followed by the addition of compound 1D (0.36 g, 1.31 mmol) and cesium carbonate (1.18 g, 3.62 mmol). The mixture was stirred at 80°C for 4 hours. After cooling, the mixture was filtered and the filtrate was concentrated. The resulting residue was purified by silica gel column chromatography (petroleum ether:ethyl acetate (v:v) = 1:1) to afford compound 73 (0.30 g, 59.97%).

[0948] 1H NMR((400MHz, CDCl3)δ8.94(s,2H),7.58(d,1H),7.11(s,1H),7.08(d,1H),6 .94(d,1H),6.34(s,2H),4.88(q,2H),2.93-2.88(m,4H),2.13-2.06(m,2H);

[0949] LC-MS (ESI): m / z = 421.1 [M+H] + .

[0950] Example 74

[0951] Step 1: To a 250 mL reaction flask, compound 74A (5 g, 21.83 mmol), triethylsilane (50 mL, 313.90 mmol), and trifluoroacetic acid (110 mL) were added sequentially and stirred at 45°C for 16 hours. The reaction mixture was concentrated under reduced pressure, and the resulting residue was extracted with ethyl acetate and water. The organic phase was collected and concentrated, and the resulting residue was purified by column chromatography (petroleum ether) to afford compound 74B (3.7 g, yield: 78.81%).

[0952] Step 2: To a 100 mL reaction flask, compound 74B (3.7 g, 17.20 mmol) and tetrahydrofuran (40 mL) were added sequentially. Under nitrogen protection, n-butyllithium (8.26 mL, 20.64 mmol, 2.5 M solution in hexane) was slowly added dropwise at -78°C. After stirring for half an hour, N,N-dimethylformamide (3 mL) was added dropwise, and the mixture was stirred at -78°C for 1 hour. The reaction solution was quenched with water and extracted with ethyl acetate. The organic phase was collected, washed, and concentrated. The resulting residue was separated by column chromatography (petroleum ether:ethyl acetate (v:v) = 1:0 to 0:1) to provide compound 74C (2.3 g, yield: 81.45%).

[0953] Step 3: To a 100 mL reaction flask, compound 74C (2.3 g, 14.01 mmol) and methanol (30 mL) were added sequentially, followed by sodium borohydride (1.59 g, 42.03 mmol). The reaction was stirred at room temperature for 1 hour. The reaction solution was quenched with water and extracted with ethyl acetate. The organic phase was collected, washed, and concentrated. The resulting residue was separated by column chromatography (petroleum ether:ethyl acetate (v:v) = 1:0 to 0:1) to provide compound 74D (2.2 g, yield: 94.49%).

[0954] Step 4: To a 100 mL reaction flask, compound 74D (100 mg, 0.60 mmol), intermediate 1 (0.18 g, 0.72 mmol), triphenylphosphine (0.24 g, 0.9 mmol), and tetrahydrofuran (4 mL) were added sequentially. After complete addition, the mixture was stirred at 0°C for 20 minutes. Under nitrogen, diisopropyl azodicarboxylate (0.18 g, 0.9 mmol) was slowly added dropwise. The reaction was stirred at room temperature for 3 hours. The reaction solution was concentrated, and the resulting residue was purified by preparative HPLC. Methods: 1. Apparatus: Waters 2767 Preparative HPLC; Column: SunFire@PrepC18 (19 mm × 250 mm). 2. The sample was filtered through a 0.45 μm filter to prepare a sample solution. 3. Preparative chromatography conditions: a. Mobile phase A, B composition: Mobile phase A: acetonitrile; Mobile phase B: water (containing 0.05% ammonia); b. Gradient elution, mobile phase A content from 25% to 75%; c. Flow rate: 15 mL / min; d. Elution time: 20 min. Retention time: 9.2 min. Compound 74 (95.8 mg, yield: 39.68%) was obtained.

[0955] 1 H NMR(400MHz,DMSO-d6)δ9.13(s,2H),8.10(d,1H),7.14(d,1H),7.09(s,1H),6.98(s,1H), 6.59-6.30(m,1H),5.28(s,2H),4.73-4.65(m,2H),2.89-2.82(m,4H),2.07-2.01(m,2H);

[0956] LCMS m / z=403.4[M+H] + .

[0957] Example 75

[0958] Step 1: 2-Fluoroethanol (0.38 g, 5.90 mmol) was added to tetrahydrofuran (10 mL) and sodium (68 mg, 2.96 mmol) was added. The mixture was stirred at room temperature until no sodium was visible. Compound 71C (200 mg, 0.59 mmol) was added to the reaction solution and stirred at room temperature for 2 hours. Water and ethyl acetate were added to separate the layers. The organic phase was collected, washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated. The resulting residue was purified by reverse-phase column chromatography (acetonitrile:water (v:v) = 10%-80%) to obtain compound 75 (100 mg, yield: 46.2%).

[0959] 1H NMR(400MHz, CDCl3)δ8.91(s,2H),7.56(d,1H),7.34(s,1H),7.27-7.24(m,1H),7.18(d,1H),7.04(d,1H),5 .35(s,2H),4.89-4.81(m,1H),4.75-4.72(m,2H),4.70-4.62(m,1H),2.90-2.85(m,4H),2.08-2.00(m,2H);

[0960] LC-MS (ESI): m / z = 367.40 [M+H] + .

[0961] Example 76

[0962] Step 1: Dissolve 3,3-difluoropropan-1-ol (0.17 g, 1.77 mmol) in tetrahydrofuran (10 mL). Slowly add sodium lumps (0.021 g, 0.90 mmol) in an ice-water bath. Heat to 60°C with stirring until the sodium lumps disappear. Cool to room temperature, add compound 71C (0.2 g, 0.59 mmol), and continue stirring for 3 hours. Dilute the reaction solution with water and extract three times with ethyl acetate. The combined organic phases are concentrated under reduced pressure, and the resulting residue is purified by preparative HPLC. Methods: 1. Apparatus: Waters 2767 Preparative HPLC; Column: SunFire@PrepC18 (19 mm × 250 mm). 2. Filter the sample through a 0.45 μm filter to prepare a sample solution. 3. Preparative chromatography conditions: a. Mobile phase A, B composition: Mobile phase A: acetonitrile; Mobile phase B: water (containing 0.5% ammonium acetate); b. Gradient elution, mobile phase A content from 40% to 70%; c. Flow rate: 20 mL / min; d. Elution time: 16 min. Retention time: 15 min. Compound 76 (20 mg, yield: 8.5%) was obtained.

[0963] 1 H NMR(400MHz,DMSO-d6)δ9.08(s,2H),8.08(d,1H),7.24(s,1H),7.19-7.11(m,3H),6.45-6.06(m ,1H),5.27(s,2H),4.55-4.48(m,2H),2.83-2.77(m,4H),2.44-2.30(m,2H),2.01-1.95(m,2H);

[0964] LC-MS (ESI): m / z = 399.40 [M+H] + .

[0965] Example 77

[0966] Step 1: Dissolve 3-chloropropan-1-ol (0.17 g, 1.80 mmol) in tetrahydrofuran (8 mL). Slowly add sodium lumps (0.021 g, 0.90 mmol) in an ice-water bath. Heat to 60°C with stirring until the sodium lumps disappear completely. Cool to room temperature, add compound 71C (0.2 g, 0.59 mmol), and continue stirring for 3 hours. Dilute the reaction solution with water and extract three times with ethyl acetate. The combined organic phases are concentrated under reduced pressure, and the resulting residue is purified by preparative HPLC. Methods: 1. Apparatus: Waters 2767 Preparative HPLC; Column: SunFire@PrepC18 (19 mm × 250 mm). 2. Filter the sample through a 0.45 μm filter to prepare a sample solution. 3. Preparative chromatography conditions: a. Mobile phase A, B composition: Mobile phase A: acetonitrile; Mobile phase B: water (containing 0.5% ammonium acetate); b. Gradient elution, mobile phase A content from 40% to 80%; c. Flow rate: 20 mL / min; d. Elution time: 16 min. Retention time: 15 min. Lyophilization afforded compound 77 (25 mg, yield: 10.6%).

[0967] 1 H NMR(400MHz,DMSO-d6)δ9.07(s,2H),8.07(d,1H),7.24(s,1H),7.19-7.08(m,3H),5.27(s,2H), 4.51-4.45(m,2H),3.88-3.76(m,2H),2.87-2.77(m,4H),2.27-2.19(m,2H),2.04-1.94(m,2H);

[0968] LC-MS (ESI): m / z = 397.40 [M+H] + .

[0969] Example 78

[0970] Step 1: Dissolve compound 71C (0.2 g, 0.59 mmol) and chloro(2-dicyclohexylphosphino-2',6'-di-isopropoxy-1,1'-biphenyl)(2-amino-1,1'-biphenyl-2-yl)palladium(II) (0.046 g, 0.059 mmol) in anhydrous dioxane (2 mL). After nitrogen purge, add a solution of cyclopropylmagnesium bromide in tetrahydrofuran (1.2 mL, 2.4 mmol). Stir and react at 100°C under nitrogen for 3 hours. After cooling, extract with water and ethyl acetate. The organic phase is collected and concentrated under reduced pressure. The resulting residue is purified by preparative HPLC. Methods: 1. Instrument: Waters 2767 Preparative HPLC; Column: SunFire@PrepC18 (19 mm × 250 mm). 2. Filter the sample through a 0.45 μm filter to prepare a sample solution. 3. Preparative Chromatography Conditions: a. Mobile Phase A, B Composition: Mobile Phase A: Acetonitrile; Mobile Phase B: Pure Water; b. Gradient Elution, Mobile Phase A Content from 10% to 70%; c. Flow Rate: 15 mL / min. d. Elution Time: 20 min. Retention Time: 9.2 min. Compound 78 (3.3 mg, Yield: 1.6%) was obtained.

[0971] 1 H NMR(400MHz,DMSO-d6)δ9.08(s,2H),8.08(d,1H),7.24(s,1H),7.16(s,2H),7.12(d,1H), 5.27(s,2H),2.83-2.78(m,4H),2.30-2.23(m,1H),2.01-1.94(m,2H),1.17-0.96(m,4H);

[0972] LC-MS (ESI): m / z = 345.1 [M+H] + .

[0973] Example 79

[0974] Step 1: Dissolve 5-bromo-2,3-dihydro-1H-inden-1-one (2.11 g, 10 mmol) in toluene (100 mL). Add 1,2-ethanedithiol (1.88 g, 20 mmol) and p-toluenesulfonic acid (172 mg, 1 mmol) sequentially. Heat to 110°C and react overnight. Cool to room temperature and concentrate. The resulting residue is separated by silica gel column chromatography (petroleum ether:ethyl acetate (v:v) = 10:1) to provide compound 79A (2.68 g, 93.4% yield).

[0975] Step 2: Weigh N-iodosuccinimide (1.57 g, 7 mmol) into a 50 mL plastic centrifuge tube, add dichloromethane (10 mL), and cool to -78°C. Add hydrogen fluoride pyridine solution (4 mL). Dissolve compound 79A (1 g, 3.5 mmol) in dichloromethane (10 mL) and add dropwise to the above system. Continue the reaction at this temperature for 2 h. Add saturated sodium bicarbonate solution until no bubbles are generated. Add petroleum ether (100 mL), shake thoroughly, collect the organic phase, dry over anhydrous sodium sulfate, and concentrate the resulting residue, which is purified by silica gel column chromatography (100% petroleum ether) to afford compound 79B (235 mg, yield: 28.9%).

[0976] 1 H NMR (400MHz, CDCl3) δ7.49-7.37(m,3H), 3.06-2.96(m,2H), 2.66-2.51(m,2H).

[0977] Step 3: Compound 79B (235 mg, 1 mmol) was dissolved in 1,4-dioxane (10 mL). (tributyltin)methanol (353 mg, 1.1 mmol) and chloro(2-dicyclohexylphosphino-2',4',6'-triisopropyl-1,1'-biphenyl)[2-(2'-amino-1,1'-biphenyl)]palladium(II) (Xphos-pd-G2) (78 mg, 0.1 mmol) were added. After nitrogen substitution, the reaction was carried out at 90°C for 4 h. After cooling and concentration, the resulting residue was purified by silica gel column chromatography (petroleum ether:ethyl acetate (v:v) = 1:0 to 5:1) to provide compound 79C (116 mg, yield: 63%).

[0978] LC-MS(ESI):m / z=165.2[M-HF+H] + ,167.1[M-OH - ] + .

[0979] Step 4: Compound 79C (116 mg, 0.6 mmol) was dissolved in dichloromethane (10 mL), followed by the addition of triphenylphosphine (471 mg, 1.8 mmol) and carbon tetrabromide (596 mg, 1.8 mmol). The mixture was stirred at room temperature for 2 h. The mixture was concentrated and the resulting residue was purified by column chromatography (100% petroleum ether) to afford compound 79D (128 mg, 82.1% yield).

[0980] Step 5: Compound 79D (128 mg, 0.52 mmol) was dissolved in DMF (10 mL), and compound 1D (163 mg, 0.6 mmol) and potassium carbonate (276 mg, 2 mmol) were added. The mixture was reacted at 70°C for 2 h. Water (50 mL) was added, and the mixture was extracted with ethyl acetate (50 mL x 2). The organic phase was collected, washed with saturated brine, dried over anhydrous sodium sulfate, and the filtrate was filtered and concentrated. The resulting residue was purified by column chromatography (petroleum ether:ethyl acetate (v:v) = 1:0 to 1:1) to afford compound 79 (69 mg, yield: 30.4%).

[0981] 1 H NMR(400MHz, CDCl3)δ8.94(s,2H),7.60(d,1H),7.52(d,1H),7.47-7.42(m,1H),7.40(s, 1H),7.09(d,1H),5.42(s,2H),4.92-4.84(m,2H),3.06-2.98(m,2H),2.65-2.49(m,2H);

[0982] LC-MS (ESI): m / z = 439.2 [M+H] + .

[0983] Example 80

[0984] Step 1: Dissolve cyclopropylmethanol (0.12 g, 1.73 mmol) in tetrahydrofuran (8 mL). Then, slowly add sodium hydride (0.064 g, 2.67 mmol) in portions under an ice-water bath. After stirring for half an hour, compound 71C (0.3 g, 0.89 mmol) is added. The mixture is then returned to room temperature and the reaction is continued for 2 hours. After completion, the reaction is diluted with water and extracted three times with ethyl acetate. The organic phases are combined and concentrated under reduced pressure. The resulting residue is purified by preparative HPLC. Methods: 1. Apparatus: Waters 2767 Preparative HPLC; Column: SunFire@PrepC18 (19 mm × 250 mm). 2. Filter the sample through a 0.45 μm filter to prepare a sample solution. 3. Preparative chromatography conditions: a. Mobile phase A, B composition: Mobile phase A: acetonitrile; Mobile phase B: water (containing 0.5% ammonium acetate); b. Gradient elution, mobile phase A content from 40% to 85%; c. Flow rate: 20 mL / min; d. Elution time: 18 min. Retention time: 17 min. Compound 80 (100 mg, yield: 30%) was obtained.

[0985] 1H NMR(400MHz,DMSO-d6)δ9.06(s,2H),8.07(d,1H),7.24(s,1H),7.21-7.15(m,2H),7.16-7.09(m,1H),5.26(s,2 H),4.21(d,2H),2.86-2.76(m,4H),2.02-1.90(m,2H),1.34-1.20(m,1H),0.66-0.53(m,2H),0.48-0.31(m,2H);

[0986] LC-MS (ESI): m / z = 375.10 [M+H] + .

[0987] Example 81

[0988] Step 1: Dissolve (2,2-difluorocyclopropyl)methanol (0.19 g, 1.76 mmol) in tetrahydrofuran (8 mL). Slowly add sodium h...

Claims

1. A compound represented by formula (I), its stereoisomer, deuterated form, solvate, or pharmaceutically acceptable salt or cocrystal, in, R 1 、R 2 、R 3 Each independently selected from H, deuterium, R A1 、-O-halogenated C 1-4 Alkyl, -NH-halogenated C 1-4 Alkyl, -OC 1-4 Alkyl, C 1-6 Alkoxy, halogen, cyano, nitro, C 1-4 Alkyl, -NH-C 1-4 Alkyl, -N(C 1-4 Alkyl)2, -NH-C 3-10 Cycloalkyl, -NHC(O)C 1-4 Alkyl or 4-10 membered heterocycloalkyl containing 1-3 heteroatoms selected from N, O, S, wherein the alkyl, alkoxy, cycloalkyl, heterocycloalkyl is optionally further substituted by 1-3 heteroatoms selected from halogen, D, CN, OH, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, deuterated C 1-4 Alkoxy, C 3-10 Cycloalkyl, 4-6 membered heterocycloalkyl containing 1-3 heteroatoms selected from N, O, S, phenyl, and NH2, provided that R 1 、R 2 and R 3 Not selected from H at the same time; R A1 Selected from halogenated C 2-6 Alkenyl, C 2-6 Alkynyl, -O-(CH2) r -R a 、C 3-10 Cycloalkyl, 5-10 membered heteroaryl containing 1-3 heteroatoms selected from N, O, S, -C 1-4 Alkyl-R a 、-C 1-4 Alkyl-OR a 、-C 1-4 Alkyl-NR b R a 、-NR b -S(O)2-R a 、-NR b -S(O)2-NR b R a 、-O-NR b R a 、-NH-OR b 、-Se-(CH2) r -R a The alkynyl, heteroaryl, alkyl, cycloalkyl group may be further substituted by 1-3 halogen, deuterium, CN, OH, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, deuterated C 1-4 Alkoxy and NH2 group substitution; Each R a Selected from CN, halogenated C 1-6 Alkyl, C 3-10 Cycloalkyl, 4-10 membered heterocycloalkyl containing 1-3 heteroatoms selected from N, O, S, 6-10 membered aryl, 5-10 membered heteroaryl containing 1-3 heteroatoms selected from N, O, S, -C(O)-R a1 The alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl groups are optionally further substituted by 1-3 groups selected from halogen, =O, deuterium, CN, OH, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, deuterated C 1-4 Alkoxy and NH2 group substitution; Each R b Selected from H, deuterium, C 1-4 Alkyl, C 3-6 Cycloalkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 alkyl; R a1 Selected from OH, NH2, -NHC 1-4 Alkyl, -N(C 1-4 Alkyl)2, -NHC 3-10 Cycloalkyl, C 1-4 Alkoxy, C 1-6 Alkyl, C 3-10 Cycloalkyl, 6-10 membered aryl, 5-10 membered heteroaryl containing 1-3 heteroatoms selected from N, O, S; X is selected from CR 10 or N; X1 is selected from O, S; R 4 、R 5 Each independently selected from H, deuterium, C 3-10 Cycloalkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, halogen, amino, -NH-C 1-4 Alkyl, -N(C 1-4 Alkyl)2, C 1-4 Alkyl, halogenated C 1-4 Alkyl, 4-10 membered heterocycloalkyl containing 1-3 heteroatoms selected from N, O, and S, 5-10 membered heteroaryl, 6-10 membered aryl containing 1-3 heteroatoms selected from N, O, and S; R 6 、R 7 、R 8 、R 9 、R 10 Each independently selected from H, deuterium, R A2 , halogen, OH, CN, amino, C 1-4 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-4 Alkoxy, halogenated C 1-4 Alkyl, -NH-C 1-4 Alkyl, -N(C 1-4 Alkyl)2, -S(O)R c 、 -S(O) 2 R c 、-C(O)R c 、-C(O)OR c 、-C(O)N(R c )2、-OC(O)R c The alkyl, alkenyl, alkynyl, and alkoxy groups are optionally further substituted by 1 to 3 groups selected from halogen, deuterium, CN, OH, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, deuterated C 1-4 Alkoxy and NH2 group substitution; R A2 Selected from -(CH2) r -(C 3-10 Cycloalkyl), -(CH2) r -(4-10 membered heterocycloalkyl containing 1-3 heteroatoms selected from N, O, S, Si), or -(CH2) r -(5-10 membered heteroaryl containing 1-3 heteroatoms selected from N, O, S), -P(O)(R c )2、-Si(R c )3, -SF5, N3, B(OH)2, or -S(O)(=NH)R c The cycloalkyl, heterocycloalkyl, and heteroaryl groups are optionally further substituted by 1 to 3 groups selected from halogen, =O, D, CN, OH, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, C 3-6 Cycloalkyl, 4-7 membered heterocycloalkyl containing 1-3 heteroatoms selected from N, O, S, deuterated C 1-4 Alkoxy and NH2 group substitution; Each R c Each independently selected from H, OH, C 1-4 Alkyl, C 3-7 Cycloalkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, deuterated C 1-4 Alkoxy or NH2; Each r is independently selected from 0, 1, 2 or 3; L1 is selected from a bond, O, NH, S, -CD2-, -CHD-, -CR L1 R L2 -、C 1-4 Alkyl, -C(O)-, S(O), S(O)2, wherein the alkyl group is optionally further R L1 replace; L2 is selected from a bond, O, NH, S, -CH2-, -CD2-, -CHD-, -CR L1 R L2 -、-CHR L2 -、-CDR L2 -、C 2-4 Alkyl, -C(O)-, S(O), S(O)2, wherein the alkyl group is optionally further substituted with 1-3 R L1 replace; R L1 、R L2 Each independently selected from halogen, OH, CN, amino, C 1-4 Alkyl, C 1-4 Alkoxy, C 3-6 Cycloalkyl, 4-6 membered heterocycloalkyl containing 1-3 heteroatoms selected from N, O, S; Alternatively, R 2 、R 4 , L1 and the atoms to which they are connected together form a 5-7 membered carbocyclic ring, a 5-7 membered heterocyclic ring containing 1-3 heteroatoms selected from N, O, and S, wherein the carbocyclic ring or heterocyclic ring is optionally further substituted by 1-3 heteroatoms selected from R A3 The group substitution; Alternatively, R 4 、R 5 Together with the atoms to which they are connected, they form a 5-7 membered monocyclic carbocyclic ring or a 5-7 membered heterocyclic ring containing 1-3 heteroatoms selected from N, O, and S, wherein the carbocyclic ring or heterocyclic ring is optionally substituted by 1-3 heteroatoms selected from R A3 The group substitution; Alternatively, R L2 With R 9 Together with the atoms to which they are connected, they form a 5-7 membered carbocyclic ring or a 5-7 membered heterocyclic ring containing 1-3 heteroatoms selected from N, O, and S, wherein the carbocyclic ring or heterocyclic ring is optionally further surrounded by 1-3 heteroatoms selected from R A3 The group substitution; Each R A3 Each independently selected from =O, halogen, deuterium, CN, OH, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, deuterated C 1-4 Alkoxy and NH2 group substitution; The conditions are: R 6 With R 10 、R 10 With R 7 、R 7 With R 8 、R 8 With R 9 A group of the carbon ring and the atoms connected thereto together form a 4-8 membered carbocyclic ring, a 5-7 membered heterocycloalkyl containing 1-3 heteroatoms selected from N, O, S, B, Si, wherein the carbon ring, the heterocycloalkyl is optionally further substituted by 1-3 heteroatoms selected from =O, Halogen, deuterium, CN, OH, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, deuterated C 1-4 The alkyl group may be substituted with an alkoxy group, a 5-7 membered heterocycloalkyl group containing 1-3 heteroatoms selected from N, O, S, B, Si, a 5-7 membered heteroaryl group containing 1-3 heteroatoms selected from N, O, S, B, Si, and NH2.

2. The compound according to claim 1, its stereoisomer, deuterated form, solvate, or pharmaceutically acceptable salt or cocrystal, R 6 、R 7 、R 8 、R 9 、R 10 Each independently selected from H, deuterium, -SF5, N3, halogen, OH, CN, amino, C 1-2 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-2 Alkoxy, halogenated C 1-2 Alkyl, -NH-C 1-2 Alkyl, -N(C 1-2 alkyl) 2, wherein the alkyl, alkenyl, alkynyl, alkoxy group is optionally further substituted by 1-3 groups selected from halogen, deuterium, CN, OH, C 1-2 Alkyl, halogenated C 1-2 alkyl, Deuterated C 1-2 Alkyl, C 1-2 Alkoxy, halogenated C 1-2 Alkoxy, deuterated C 1-2 Alkoxy and NH2 groups are substituted.

3. The compound according to claim 1, its stereoisomer, deuterated form, solvate, or pharmaceutically acceptable salt or cocrystal, having the structure of formula (II) or (II-a): L2 is selected from a bond, -CH2-, -CR L1 R L2 -、-CHR L2 -、-CDR L2 -, -C(O)-; R L1 、R L2 Each independently selected from halogen, OH, CN, amino, C 1-2 Alkyl, C 1-2 Alkoxy, C 3-4 Cycloalkyl, 4-membered heterocycloalkyl containing 1-3 heteroatoms selected from N, O, and S; R 2 、R 3 Each independently selected from H, deuterium, C 1-2 Alkoxy, halogen, cyano, nitro, C 1-2 Alkyl, wherein the alkyl and alkoxy groups are optionally further substituted by 1-3 groups selected from halogen, D, CN, OH and NH2; R 1 Selected from R A1 、-O-halogenated C 1-4 Alkyl, -NH-halogenated C 1-4 Alkyl, C 1-4 Alkoxy, halogen, cyano, nitro, C 1-4 Alkyl, -NH-C 1-4 Alkyl, -N(C 1-4 Alkyl)2, -NH-C 3-10 Cycloalkyl, -NHC(O)C 1-4 Alkyl or 4-10 membered heterocycloalkyl containing 1-3 heteroatoms selected from N, O, S, wherein the alkyl, alkoxy, cycloalkyl, heterocycloalkyl is optionally further substituted by 1-3 heteroatoms selected from halogen, D, CN, OH, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, deuterated C 1-4 Alkoxy, C 3-10 substituted by cycloalkyl, 4-6 membered heterocycloalkyl containing 1-3 heteroatoms selected from N, O, S, phenyl and NH2; X is selected from CR 10 or N; R 4 、R 5 Each independently selected from H, deuterium, C 3-7 Cycloalkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, F, Cl, amino, -NH-C 1-2 Alkyl, -N(C 1-2 Alkyl)2, C 1-2 Alkyl, 4-7 membered heterocycloalkyl containing 1-3 heteroatoms selected from N, O, S; R 7 、R 8 Each independently selected from H, deuterium, F, Cl, OH, CN, amino, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-4 Alkoxy, halogenated C 1-4 Alkyl, -NH-C 1-2 Alkyl, -N(C 1-2 Alkyl)2, -S(O)R c 、-S(O) 2 R c 、-C(O)R c 、-C(O)OR c 、-C(O)N(R c )2、-OC(O)R c ; R 6 、R 9 、R 10 Each independently selected from H, deuterium, F, Cl, OH, CN, amino, C 1-2 alkyl; Alternatively, R 2 、R 4 Together with the atoms to which they are connected, they form a 5-7 membered carbocyclic ring or a 5-7 membered heterocyclic ring containing 1-3 heteroatoms selected from N, O, and S, wherein the carbocyclic ring or heterocyclic ring is optionally further surrounded by 1-3 heteroatoms selected from R A3 The group substitution; Each R A3 Each independently selected from =O, halogen, deuterium, CN, OH, C 1-2 Alkyl, halogenated C 1-2 Alkyl, deuterated C 1-2 Alkyl, C 1-2 Alkoxy, halogenated C 1-2 Alkoxy, deuterated C 1-2 Alkoxy and NH2 group substitution; The conditions are: R 10 With R 7 、R 7 With R 8 、R 8 With R 9 A group of the group and the atoms connected thereto together form a 4-8 membered cycloalkyl, a 5-7 membered heterocycloalkyl containing 1-3 heteroatoms selected from N, O, S, B, Si, wherein the cycloalkyl and heterocycloalkyl are optionally further substituted by 1-3 heteroatoms selected from =O, Halogen, deuterium, CN, OH, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, deuterated C 1-4 The alkyl group may be substituted with an alkoxy group, a 5-7 membered heterocycloalkyl group containing 1-3 heteroatoms selected from N, O, S, B, Si, a 5-7 membered heteroaryl group containing 1-3 heteroatoms selected from N, O, S, B, Si, and NH2.

4. The compound according to claim 1, its stereoisomer, deuterated form, solvate, or pharmaceutically acceptable salt or cocrystal, having the structure of formula (III) or (III-a): X is selected from CR 10 or N; R 6 、R 7 、R 8 、R 9 、R 10 Each independently selected from H, deuterium, F, Cl, OH, CN, amino, C 1-2 alkyl; Alternatively, R 2 、R 4 Together with the atoms to which they are connected, they form a 5-7 membered carbocyclic ring or a 5-7 membered heterocyclic ring containing 1-3 heteroatoms selected from N, O, and S, wherein the carbocyclic ring or heterocyclic ring is optionally further surrounded by 1-3 heteroatoms selected from R A3 The group substitution; The conditions are: R 10 With R 7 、R 7 With R 8 、R 8 With R 9 A group of the group and the atoms connected thereto together form a 4-8 membered cycloalkyl, a 5-7 membered heterocycloalkyl containing 1-3 heteroatoms selected from N, O, S, B, Si, wherein the cycloalkyl and heterocycloalkyl are optionally further substituted by 1-3 heteroatoms selected from =O, Halogen, deuterium, CN, OH, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, deuterated C 1-4 The alkyl group may be substituted with an alkoxy group, a 5-7 membered heterocycloalkyl group containing 1-3 heteroatoms selected from N, O, S, B, Si, a 5-7 membered heteroaryl group containing 1-3 heteroatoms selected from N, O, S, B, Si, and NH2.

5. The compound according to any one of claims 1 to 4, its stereoisomer, deuterated form, solvate, or pharmaceutically acceptable salt or cocrystal, R 1 Selected from R A1 、-O-halogenated C 1-4 Alkyl, C 1-4 Alkyl, wherein the alkyl is optionally further substituted by 1-3 groups selected from halogen, D, CN, OH, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, deuterated C 1-4 Alkoxy and NH2 group substitution; R 2 、R 3 Each independently selected from H, deuterium, C 2-4 Alkenyl, C 2-4 Alkynyl, halogen, cyano, nitro, OH, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 alkyl; R A1 Selected from halogenated C 2-4 Alkenyl, C 2-4 Alkynyl, -O-(CH2) r -R a 、C 3-6 Monocyclic cycloalkyl, C 5-8 Bicyclic bridged ring cycloalkyl, C 6-10 Bicyclic spirocyclic cycloalkyl, 5-6 membered monocyclic heteroaryl containing 1-3 heteroatoms selected from N, O, S, 8-10 membered bicyclic heteroaryl containing 1-3 heteroatoms selected from N, O, S, -C 1-2 Alkyl-R a 、-C 1-2 Alkyl-OR a 、-C 1-2 Alkyl-NR b R a 、-NR b -S(O)2-R a 、-NR b -S(O)2-NR b R a 、-O-NR b R a 、-NH-OR b 、-Se-(CH2) r -R a The alkynyl, heteroaryl, alkyl, cycloalkyl group may be further substituted by 1-3 halogen, deuterium, CN, OH, C 1-2 Alkyl, halogenated C 1-2 Alkyl, deuterated C 1-2 Alkyl, C 1-2 Alkoxy, halogenated C 1-2 Alkoxy, deuterated C 1-2 Alkoxy and NH2 group substitution; Each R a Selected from CN, halogenated C 1-4 Alkyl, C 3-6 Monocyclic cycloalkyl, C 7-10 Spirocyclic cycloalkyl, C 4-8 Bridged ring cycloalkyl, C 4-9 cycloalkyl, 4-6 membered monocyclic heterocycloalkyl containing 1-3 heteroatoms selected from N, O, and S, 7-10 membered spirocyclic heterocycloalkyl containing 1-3 heteroatoms selected from N, O, and S, 4-8 membered bridged heterocycloalkyl containing 1-3 heteroatoms selected from N, O, and S, 4-6 membered cycloheterocycloalkyl containing 1-3 heteroatoms selected from N, O, and S, phenyl, 8-10 membered aryl, 5-6 membered monocyclic heteroaryl containing 1-3 heteroatoms selected from N, O, and S, 8-10 membered bicyclic heteroaryl containing 1-3 heteroatoms selected from N, O, and S, -C(O)-R a1 The alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl groups are optionally further substituted by 1-3 groups selected from halogen, =O, deuterium, CN, OH, C 1-2 Alkyl, halogenated C 1-2 Alkyl, deuterated C 1-2 Alkyl, C 1-2 Alkoxy, halogenated C 1-2 Alkoxy, deuterated C 1-2 Alkoxy and NH2 group substitution; Each R b Selected from H, deuterium, C 1-2 Alkyl, C 3-4 Cycloalkyl.

6. The compound according to claim 5, its stereoisomer, deuterated form, solvate, or pharmaceutically acceptable salt or cocrystal, R 1 Selected from R A1 、-O-halogenated C 1-4 Alkyl, C 1-4 Alkyl, wherein the alkyl is optionally further substituted by 1-3 groups selected from halogen, D, CN, OH, C 1-2 Alkyl, halogenated C 1-2 Alkyl, deuterated C 1-2 Alkyl, C 1-2 Alkoxy, halogenated C 1-2 Alkoxy, deuterated C 1-2 Alkoxy and NH2 group substitution; R 2 、R 3 Each independently selected from H, deuterium, F, Cl, cyano, OH, C 1-2 Alkyl, halogenated C 1-2 Alkyl, deuterated C 1-2 alkyl; R A1 Selected from -O-(CH2) r -R a 、C 3-6 Monocyclic cycloalkyl, C 5-8 Bicyclic bridged ring cycloalkyl, C 6-10 Bicyclic spirocyclic cycloalkyl, 5-6 membered monocyclic heteroaryl containing 1-3 heteroatoms selected from N, O, S, 8-10 membered bicyclic heteroaryl containing 1-3 heteroatoms selected from N, O, S, -C 1-2 Alkyl-R a 、-C 1-2 Alkyl-OR a 、-Se-(CH2) r -R a The heteroaryl, alkyl, cycloalkyl group may be further substituted by 1-3 groups selected from halogen, deuterium, CN, OH, C 1-2 Alkyl, halogenated C 1-2 Alkyl, deuterated C 1-2 Alkyl, C 1-2 Alkoxy, halogenated C 1-2 Alkoxy, deuterated C 1-2 Alkoxy and NH2 group substitution; Each R a Selected from halogenated C 1-4 Alkyl, C 3-6 Monocyclic cycloalkyl, C 7-10 Spirocyclic cycloalkyl, C 4-8 Bridged ring cycloalkyl, C 4-9 cycloalkyl, 4-6 membered monocyclic heterocycloalkyl containing 1-3 heteroatoms selected from N, O, and S, 7-10 membered spirocyclic heterocycloalkyl containing 1-3 heteroatoms selected from N, O, and S, 4-8 membered bridged heterocycloalkyl containing 1-3 heteroatoms selected from N, O, and S, 4-6 membered cycloheterocycloalkyl containing 1-3 heteroatoms selected from N, O, and S, phenyl, 8-10 membered aryl, 5-6 membered monocyclic heteroaryl containing 1-3 heteroatoms selected from N, O, and S, 8-10 membered bicyclic heteroaryl containing 1-3 heteroatoms selected from N, O, and S, wherein the alkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl are optionally further substituted by 1-3 halogens, =O, deuterium, CN, OH, C 1-2 Alkyl, halogenated C 1-2 Alkyl, deuterated C 1-2 Alkyl, C 1-2 Alkoxy, halogenated C 1-2 Alkoxy, deuterated C 1-2 Alkoxy and NH2 groups are substituted.

7. The compound according to claim 1, its stereoisomer, deuterated form, solvate, or pharmaceutically acceptable salt or cocrystal, having the structure of formula (IV) or (V): X is selected from CR 10 or N; R 9 、R 10 Each independently selected from H, deuterium, F, Cl, OH, CN, amino, C 1-2 alkyl; L2 is selected from a bond, -CH2-, -CD2-, -CHD-, -CR L1 R L2 -、-CHR L2 -、-CDR L2 -、C 2-4 Alkyl, -C(O)-, wherein the alkyl group is optionally further substituted with 1-3 R L1 replace; The conditions are: R 10 With R 7 、R 7 With R 8 、R 8 With R 9 A group of the group and the atoms connected thereto together form a 4-8 membered cycloalkyl, a 5-7 membered heterocycloalkyl containing 1-3 heteroatoms selected from N, O, S, B, Si, wherein the cycloalkyl and heterocycloalkyl are optionally further substituted by 1-3 heteroatoms selected from =O, Halogen, deuterium, CN, OH, C 1-4 Alkyl, halogenated C 1-4 Alkyl, deuterated C 1-4 Alkyl, C 1-4 Alkoxy, halogenated C 1-4 Alkoxy, deuterated C 1-4 Alkoxy and NH2 groups are substituted.

8. The compound according to claim 1, its stereoisomer, deuterated form, solvate, or pharmaceutically acceptable salt or cocrystal, wherein L1 is selected from a bond; L2 is selected from a bond, -CH2-, -CD2-, -CHD-, -C(O)-, -CHF-, -CDF-, -CF2-, CH(CH3)-, CD(CH3)-, C(CH3)2-; R 6 、R 9 、R 10 Each independently selected from H, deuterium, F, Cl, OH, CN, methyl; R 7 、R 8 Each independently selected from H, deuterium, F, Cl, OH, CN, methyl; R 2 、R 3 Each is independently selected from H, deuterium, vinyl, and ethynyl; R 4 、R 5 Each is independently selected from H, deuterium, cyclopropyl, vinyl, and ethynyl; Alternatively, R 4 、R 5 Together with the atoms to which it is attached, it forms phenyl, cyclohexyl, cyclopentyl, thienyl, furanyl, pyrrolyl, pyrazolyl, isoxazolyl; Alternatively, R 2 、R 4 , L1 and the atoms to which they are attached together form cyclohexyl, cycloheptyl, phenyl or cyclopentyl; Alternatively, R L1 With R 9 Together with the atoms to which they are attached, they form cyclopentyl or cyclohexyl; R 1 Selected from -CF3, -CH2CH3, -CH2CH2CH3, The conditions are: R 6 With R 10 、R 10 With R 7 、R 7 With R 8 、R 8 With R 9 A group of the group and the atoms connected thereto together form a 4-8 membered cycloalkyl or a 5-7 membered heterocycloalkyl containing 1 Si atom, wherein the cycloalkyl or heterocycloalkyl is optionally further substituted by 1-3 groups selected from =O, F, Cl, deuterium, OH, C 1-2 Alkyl, halogenated C 1-2 The alkyl group is substituted with a 5-6 membered heteroaryl group containing 1-3 heteroatoms selected from N, O, S, B, and Si.

9. The compound according to claim 1, its stereoisomer, deuterated form, solvate, pharmaceutically acceptable salt or cocrystal, wherein the compound is selected from one of the structures in Table 1 or Table 2.

10. A pharmaceutical composition or pharmaceutical preparation comprising the compound according to any one of claims 1 to 9, its stereoisomer, deuterated form, solvate, or pharmaceutically acceptable salt or cocrystal, and a pharmaceutically acceptable carrier and / or excipient.

11. The pharmaceutical composition or pharmaceutical formulation according to claim 10, comprising 1-1500 mg of the compound according to any one of claims 1-9, or a stereoisomer, deuterated form, solvate, or pharmaceutically acceptable salt or cocrystal thereof, and a pharmaceutically acceptable carrier and / or excipient.

12. Use of the compound according to any one of claims 1 to 9, its stereoisomer, deuterated form, solvate, pharmaceutically acceptable salt or cocrystal, or the composition according to claims 10 to 11 in the preparation of a medicament for treating / preventing a Myosin II-mediated disease.

13. The use according to claim 12, wherein the Myosin II-mediated disease is selected from muscular dystrophy.

14. A method for treating a disease in a mammal, the method comprising administering to a subject a therapeutically effective amount of a compound according to any one of claims 1 to 9, a stereoisomer, deuterated form, solvate, pharmaceutically acceptable salt or cocrystal thereof, preferably 1 to 1500 mg, wherein the disease is preferably muscular dystrophy.

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