CYP11a1 inhibitor, preparation method therefor, and use thereof

Abstract

The present application relates to a compound represented by formula (I), and the compound can inhibit steroid hormone-dependent disorders and diseases of CYP11A1. The present application further comprises a pharmaceutical composition comprising the compound represented by formula (I) and a method for treating a condition related to CYP11A1 activity.

Description

A CYP11A1 inhibitor, its preparation method and its application

[0001] Citation of relevant applications

[0002] This application claims priority to Chinese patent application CN202410495469.0, filed on April 23, 2024, the contents of which are incorporated herein by reference in their entirety and for all purposes. Technical Field

[0003] This application pertains to the pharmaceutical field, specifically relating to a CYP11A1 inhibitor, its preparation method, and its application. Background Technology

[0004] Treatment of steroid receptor-dependent diseases, such as androgen receptor (AR)-dependent and estrogen receptor (ER)-dependent cancers, has been extensively investigated. For example, prostate cancer is one of the most common cancers among men worldwide. While the 5-year survival rate is high for patients with localized prostate cancer, the prognosis is poor for those who develop castration-resistant prostate cancer (CRPC) within a 5-year follow-up period. The androgen receptor (AR) signaling axis is crucial at all stages of prostate cancer. In the CRPC stage (castration-resistant prostate cancer), the disease is characterized by high AR expression, AR amplification, and persistent activation of the AR signaling axis by residual tissue / tumor androgens and other steroid hormones and steroid biosynthetic intermediates. Therefore, treatment for advanced prostate cancer involves androgen deprivation therapy (ADT), such as hormonal control with gonadotropin-releasing hormone (GnRH) agonists / antagonists or surgical castration, AR antagonists, or CYP17A1 inhibitors (e.g., abiraterone acetate in combination with prednisone). Although therapy may initially lead to disease regression, most patients eventually develop a disease that is difficult to cure with currently available therapies. It is speculated that elevated progesterone levels in patients treated with abiraterone acetate are one of the mechanisms of resistance. Some non-clinical and clinical studies have shown that enzymes catalyzing steroid biosynthesis in the later stages of CRPC are upregulated. Recently, it has been reported that 11β-OH androstenedione can be metabolized into 11-ketotestosterone (11-KT) and 11-ketodehydrotestosterone (11-K-DHT), which can bind to and activate AR as efficiently as testosterone and dihydrotestosterone. Studies have shown that these steroids are present in high levels in the plasma and tissues of prostate cancer patients, suggesting their role as AR agonists in CRPC. Furthermore, it has been resolved that resistance to CYP17A1 inhibition in prostate cancer may remain steroid-dependent and respond to treatments that can further inhibit de novo intratumoral steroid synthesis upstream of CYP17A1, such as CYP11A1 inhibition therapy (Cai, C. et al., 1(20), 6503-6513, 2011).

[0005] CYP11A1, also known as cholesterol side-chain lyase, is a mitochondrial monooxygenase that catalyzes the conversion of cholesterol into pregnenolone, a precursor to all steroid hormones. By inhibiting CYP11A1, a key enzyme in steroid biosynthesis upstream of CYP17A1, complete blockade of the entire steroid biosynthesis can be achieved. Therefore, CYP11A1 inhibitors may have great potential for treating steroid hormone-dependent cancers, including prostate cancer, even in advanced stages of the disease, particularly in patients who appear refractory to hormone therapy. Summary of the Invention

[0006] Compounds of formula (I) have been found to be effective CYP11A1 inhibitors. Therefore, the compounds of the present invention are particularly useful as medicines for treating steroid hormone-dependent conditions and diseases that require inhibition of CYP11A1.

[0007] In one aspect, the present invention provides compounds of formula (I), or stereoisomers, tautomers, diastereomers, racemates, cis-trans isomers, isotopically labeled compounds (preferably deuterated), N-oxides, metabolites, esters, prodrugs, crystal forms, hydrates, solvates, or pharmaceutically acceptable salts thereof:

[0008] in:

[0009] Ring A is a 4-12 membered heterocyclic group; wherein the heteroatoms in the 4-12 membered heterocyclic group are selected from N, O and S, and the number of heteroatoms is 1, 2, 3 or 4;

[0010] Each R a Each can be independently represented by hydrogen, deuterium, halogen, cyano, nitro, hydroxyl, amino, mercapto, oxo, or -C(O)-R. a1 、-(CR a2 R a3 ) p -C(=O)-OR a4 -C(=O)-NR a5 R a6 、-C(=NR a7 )-(R a8 -S(O)2-R a9 -S(O)2-NR a10 R a11 -NR a12 S(O)2-R a13 -P(=O)-R a14 R a15The C1-6 alkyl, C2-6 alkenyl, C1-6 alkoxy, C1-6 alkylthio, -NH(C1-6 alkyl), -N(C1-6 alkyl)2, C3-10 cycloalkyl, 3-10 heterocyclic group may be substituted with one or more substituents selected from deuterium, halogen, cyano, hydroxyl, amino, oxo, C1-6 alkyl, C2-6 alkenyl, C1-6 alkoxy, C1-6 alkylthio, -NH(C1-6 alkyl), -N(C1-6 alkyl)2, C3-6 cycloalkyl, 3-10 heterocyclic group, C6-10 aryl, 5-10 heteroaryl group;

[0011] R a1 R a2 R a3 R a4 R a5 R a6 R a7 R a8 R a9 R a10 R a11 R a12 R a13 R a14 R a15 Each is independently hydrogen, C1-6 alkyl, C2-6 alkenyl, C2-6 ynyl, C3-10 cyclic hydrocarbon, 3-10 heterocyclic, C6-10 aryl, 5-10 heteroaryl, or R a5 and R a6 and the N atoms and R atoms connected to them a10 and R a11 The N atoms attached to them form 4-7 membered heterocyclic groups, namely C1-6 alkyl, C2-6 alkenyl, C2-6 ynyl, C3-10 cyclic hydrocarbon, 3-10 membered heterocyclic group, C6-10 aryl, 5-10 membered heteroaryl, or R a5 and R a6 and the N atoms and R atoms connected to them a10 and R a11 The N atoms connected to them form 4-7 membered heterocyclic groups, which may be optionally substituted by one or more substituents selected from deuterium, halogen, cyano, hydroxyl, amino, oxo, C1-6 alkyl, C1-6 alkoxy, -NH(C1-6 alkyl), -N(C1-6 alkyl)2;

[0012] Ring B is a 5-6 membered heteroaryl group;

[0013] Each R bEach of these can be independently hydrogen, deuterium, halogen, cyano, hydroxyl, amino, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, -NH(C1-6 alkyl), -N(C1-6 alkyl)2;

[0014] The ring C is C6-10 aryl, 5-10 heteroaryl, or 5-12 heterocyclic.

[0015] Each R c Each of these groups can be independently represented as hydrogen, deuterium, halogen, cyano, nitro, hydroxyl, amino, mercapto, oxo, or -C(O)NR. c1 R c2 -C(O)R c3 、-S(O)2R c4 C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkylthio, -NH (C1-6 alkyl), -N (C1-6 alkyl)2, C3-10 cycloalkyl, C3-10 cycloalkyloxy, 3-10 heterocyclic, C6-10 aryl, 5-10 heteroaryl, or two adjacent R groups c Together with the ring atoms they are attached to, they form a 5-6 membered ring; the C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkylthio, -NH(C1-6 alkyl), -N(C1-6 alkyl)2, C3-10 cycloalkyl, C3-10 cycloalkyloxy, 3-10 heterocyclic, C6-10 aryl, 5-10 heteroaryl, or two adjacent R groups c Together with the ring atoms they are attached to, they form a 5-6 membered ring which may be optionally substituted by one or more substituents selected from deuterium, halogen, cyano, hydroxyl, amino, oxo, C1-6 alkyl, C1-6 alkoxy, C3-6 cycloalkyl, 3-10 heterocyclic, C6-10 aryl, and 5-10 heteroaryl.

[0016] R c1 R c2 R c3 R c4 Each is independently selected from hydrogen, C1-6 alkyl, C1-6 alkoxy, C3-10 cycloalkyl, or R c1 R c2 Together with the N atoms attached to them, they form 4-7 membered heterocyclic groups; the C1-6 alkyl, C1-6 alkoxy, C3-10 cycloalkyl, or R c1 R c2 Together with the N atoms attached to them, they form 4-7 membered heterocyclic groups, which may be optionally replaced by one or more groups selected from deuterium, halogen, hydroxyl, amino, oxo, C1-6 alkyl, C1-6 alkoxy, and C3-10 cycloalkyl.

[0017] R1 R 2 Each is independently selected from hydrogen, deuterium, halogen, C1-6 alkyl, C1-6 haloalkyl, C1-6 deuteralkyl, C1-6 alkoxy, C1-6 haloalkoxy, or R 1 R 2 Together with the carbon atoms they are attached to, they form 3-10 membered rings;

[0018] Ring D is a 9-10 membered heterocyclic group or a 9-10 membered heteroaryl group;

[0019] Each R d Each is independently selected from hydrogen, deuterium, halogen, cyano, nitro, hydroxyl, mercapto, oxo, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C1-6 alkylthio, -NH(C1-6 alkyl), -N(C1-6 alkyl)2, hydroxyC1-6 alkyl, -C(O)(C1-6 alkyl), -C(O)O(C1-6 alkyl), -S(O)(C1-6 alkyl), -S(O)2(C1-6 alkyl), C3-10 cycloalkyl, 3-10 heterocyclic, C6-10 aryl, 5-10 heteroaryl;

[0020] a can be 0, 1, 2, 3, 4, 5, or 6;

[0021] p is 0, 1, 2, 3 or 4;

[0022] b can be 0, 1, 2, or 3;

[0023] c can be 0, 1, 2, 3, 4, 5, or 6;

[0024] d can be 0, 1, 2, 3 or 4.

[0025] In some implementation schemes, each R a Each can be independently represented by hydrogen, deuterium, halogen, cyano, hydroxyl, amino, mercapto, oxo, or -C(O)-R. a1 、-(CR a2 R a3 ) p -C(=O)-OR a4 -C(=O)-NR a5 R a6 、-C(=NR a7 )-(R a8 -S(O)2-R a9 -S(O)2-NR a10 R a11 -NR a12 S(O)2-R a13 -P(=O)-R a14 R a15C1-4 alkyl, C2-4 alkenyl, C1-4 alkoxy, C1-4 alkylthio, -NH(C1-4 alkyl), -N(C1-4 alkyl)2, C3-6 cycloalkyl, C5-10 cycloalkenyl, 3-10 membered heterocyclic groups; wherein the C1-4 alkyl, C2-4 alkenyl, C1-4 alkoxy, C1-4 alkylthio, -NH(C1-4 alkyl), -N(C1-4 alkyl)2, C3-6 cycloalkyl, C The 5-10 cycloalkenyl or 3-10 heterocyclic group is optionally substituted by one or more substituents selected from deuterium, halogen, cyano, hydroxyl, amino, oxo, C1-4 alkyl, C2-4 alkenyl, C1-4 alkoxy, C1-4 alkylthio, -NH(C1-4 alkyl), -N(C1-4 alkyl)2, C3-6 cycloalkyl, 3-10 heterocyclic, C6-10 aryl, and 5-10 heteroaryl; provided that at least one R a Selected from oxo groups, -C(O)-R a1 、-(CR a2 R a3 ) p -C(=O)-OR a4 -C(=O)-NR a5 R a6 、-C(=NR a7 )-(R a8 -S(O)2-R a9 -S(O)2-NR a10 R a11 -NR a12 S(O)2-R a13 -P(=O)-R a14 R a15 .

[0026] R a1 R a2 R a3 R a4 R a5 R a6 R a7 R a8 R a9 R a10 R a11 R a12 R a13 R a14 R a15 Each of the following is independently hydrogen, C1-4 alkyl, C2-4 alkenyl, C2-4 ynyl, C3-6 cycloalkyl, C5-10 cycloalkenyl, 3-10 heterocyclic, C6-10 aryl, 5-10 heteroaryl, or R a5 and R a6 and the N atoms and R atoms connected to them a10 and R a11The N atoms attached to them form 4-7 membered saturated or partially saturated heterocyclic groups, namely C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, C3-6 cycloalkyl, C5-10 cycloalkenyl, 3-10 membered heterocyclic groups, C6-10 aryl, 5-10 membered heteroaryl, or R a5 and R a6 and the N atoms and R atoms connected to them a10 and R a11 The N atoms connected to them form 4-7 member saturated or partially saturated heterocyclic groups, which may be optionally substituted by one or more substituents selected from deuterium, halogen, cyano, hydroxyl, amino, oxo, C1-4 alkyl, C1-4 alkoxy, -NH(C1-4 alkyl), -N(C1-4 alkyl)2.

[0027] In some implementation schemes, each R a Each of these groups can be independently represented as hydrogen, deuterium, F, Cl, Br, cyano, hydroxyl, amino, mercapto, oxo, or -C(O)-R. a1 -C(=O)-OR a4 -C(=O)-NR a5 R a6 、-C(=NR a7 )-(R a8 -S(O)2-R a9 -S(O)2-NR a10 R a11 -NR a12 S(O)2-R a13 -P(=O)-R a14 R a15 C1-4 alkyl, C1-4 alkoxy, C1-4 alkylthio, -NH(C1-4 alkyl), -N(C1-4 alkyl)2, C3-6 cycloalkyl, 4-7 membered heterocyclic group; wherein the C1-4 alkyl, C1-4 alkoxy, C1-4 alkylthio, -NH(C1-4 alkyl), -N(C1-4 alkyl)2, C3-6 cycloalkyl, 4-7 membered heterocyclic group is optionally substituted by one or more substituents selected from deuterium, halogen, cyano, hydroxyl, amino, oxo, C1-4 alkyl, C1-4 alkoxy, C1-4 alkylthio, -NH(C1-4 alkyl), -N(C1-4 alkyl)2; provided that at least one R a Selected from oxo groups, -C(O)-R a1 -C(=O)-OR a4 -C(=O)-NR a5 R a6 、-C(=NR a7 )-(R a8 -S(O)2-R a9 -S(O)2-NR a10 Ra11 -NR a12 S(O)2-R a13 -P(=O)-R a14 R a15 .

[0028] R a1 R a4 R a5 R a6 R a7 R a8 R a9 R a10 R a11 R a12 R a13 R a14 R a15 Each of the following is independently hydrogen, C1-4 alkyl, C2-4 alkenyl, C3-6 cycloalkyl, 4-7 heterocyclic, phenyl, 5-6 heteroaryl, or R a5 and R a6 and the N atoms and R atoms connected to them a10 and R a11 The N atoms attached to them form 4-6 membered saturated or partially saturated heterocyclic groups, namely C1-4 alkyl, C2-4 alkenyl, C3-6 cycloalkyl, 4-7 membered heterocyclic group, phenyl, 5-6 membered heteroaryl, or R a5 and R a6 and the N atoms and R atoms connected to them a10 and R a11 The N atoms connected to them form 4-6 member saturated or partially saturated heterocyclic groups, which may be optionally substituted by one or more substituents selected from deuterium, halogen, cyano, hydroxyl, amino, oxo, C1-4 alkyl, C1-4 alkoxy, -NH(C1-4 alkyl), -N(C1-4 alkyl)2.

[0029] In some implementation schemes, R aEach of these groups is independently hydrogen, deuterium, F, Cl, Br, cyano, hydroxyl, amino, oxo, -C(O)-(C1-4 alkyl), -C(O)-(C1-4 haloalkyl), -C(O)-(C1-4 alkyl)-CN, -C(O)-(C3-6 cycloalkyl), -C(=O)-OC1-4 alkyl, -C(=O)-OC3-6 cycloalkyl, -S(O)2-(C1-C4 alkyl), -S(O)2-(C1-C4 haloalkyl), -S(O)2-(C2-C4 alkenyl), -S(O)2-(C3-6 cycloalkyl), -S(O)2-phenyl-C1-4 alkyl. -S(O)2-5-6 heteroaryl, -C(=O)-NH(C1-4 alkyl), -C(=NH)(C1-4 alkyl), -P(=O)(C1-C4 alkyl)2, -NHS(O)2-(C1-C4 alkyl), C1-4 alkyl, C1-4 alkoxy, -NH(C1-4 alkyl), -N(C1-4 alkyl)2; wherein the C1-4 alkyl, C1-4 alkoxy, -NH(C1-4 alkyl), -N(C1-4 alkyl)2 is optionally substituted by one or more substituents selected from deuterium, halogen, cyano, hydroxyl, amino, oxo, C1-4 alkyl; provided that at least one R a Selected from -C(O)-(C1-4 alkyl), -C(O)-(C1-4 haloalkyl), -C(O)-(C1-4 alkyl)-CN, -C(O)-(C3-6 cycloalkyl), -C(=O)-OC1-4 alkyl, -C(=O)-OC3-6 cycloalkyl, -S(O)2-(C1-C4 alkyl), -S(O)2-(C1-C4 haloalkyl), -S(O)2-(C2-C4 alkenyl), -S(O)2-(C3-6 cycloalkyl), -S(O)2-phenyl-C1-4 alkyl, -S(O)2-5-6 heteroaryl, -C(=O)-NH(C1-4 alkyl), -C(=NH)(C1-4 alkyl), -P(=O)(C1-C4 alkyl)2, -NHS(O)2-(C1-C4 alkyl).

[0030] In some implementation schemes, R a Selected from -C(O)-R a1 or -S(O)2-R a9 .

[0031] In some implementation schemes, R a Selected from -S(O)2-R a9 .

[0032] In some implementation schemes, R a1 It is selected from C1-6 alkyl, C1-6 haloalkyl, cyanoC1-6 alkyl, or C3-6 cycloalkyl.

[0033] In some implementation schemes, Ra1 Selected from C1-6 alkyl or cyanoC1-6 alkyl-.

[0034] In some implementation schemes, R a9 It is selected from C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C3-6 cycloalkyl, phenyl, and 5-6 heteroaryl; wherein the phenyl and 5-6 heteroaryl are optionally substituted with one or more halogens or C1-6 alkyl groups.

[0035] In some implementation schemes, R a9 Selected from C1-6 alkyl groups.

[0036] In some implementation schemes, R a Selected from

[0037] In some implementation schemes, R a Selected from

[0038] In some embodiments, ring A is a 4-12 membered heterocyclic group; wherein the heteroatom in the 4-12 membered heterocyclic group is selected from N, O and S, and the number of heteroatoms is 1, 2, 3 or 4, wherein at least one heteroatom is N;

[0039] In some embodiments, ring A is a 4-7 member monocyclic heterocyclic group, a 7-12 member bridged ring heterocyclic group, a 6-12 member fused bicyclic heterocyclic group, or a 7-12 member spirocyclic heterocyclic group; wherein the heteroatoms in the 4-7 member monocyclic heterocyclic group, the 7-12 member bridged ring heterocyclic group, the 6-12 member fused bicyclic heterocyclic group, or the 7-12 member spirocyclic heterocyclic group are selected from N, O, and S, and the number of heteroatoms is 1, 2, or 3, wherein at least one heteroatom is N.

[0040] In some implementations, ring A is

[0041] In some implementations, ring A is selected from...

[0042] In some implementations, ring A is selected from...

[0043] In some embodiments, Selected from a1 can be 0, 1, 2, 3, 4 or 5.

[0044] In some embodiments, Selected from a1 is 0, 1, 2, 3 or 4; a2 is 0, 1 or 2; a3 is 0, 1 or 2.

[0045] In some embodiments, Selected from a1 is 0, 1, 2, 3, or 4; preferably, a1 is 0, 1, or 2; more preferably, a1 is 0; a2 is 0, 1, or 2; a3 is 0, 1, or 2; preferably, a2 is 0 and a3 is 0; wherein, each R a Each of the following is independently substituted with hydrogen, deuterium, halogen, cyano, hydroxyl, amino, mercapto, oxo, C1-6 alkyl, C2-6 alkenyl, C1-6 alkoxy, C1-6 alkylthio, -NH(C1-6 alkyl), or -N(C1-6 alkyl)2; wherein the C1-6 alkyl, C2-6 alkenyl, C1-6 alkoxy, C1-6 alkylthio, -NH(C1-6 alkyl), or -N(C1-6 alkyl)2 is optionally substituted with one or more substituents selected from deuterium, halogen, cyano, hydroxyl, amino, oxo, C1-6 alkyl, C2-6 alkenyl, C1-6 alkoxy, C1-6 alkylthio, -NH(C1-6 alkyl), or -N(C1-6 alkyl)2; preferably, each R a Each of the following groups is independently hydrogen, F, Cl, Br, cyano, hydroxyl, amino, oxo, C1-4 alkyl, C1-4 alkoxy, -NH(C1-4 alkyl), -N(C1-4 alkyl)2; the C1-4 alkyl, C1-4 alkoxy, -NH(C1-4 alkyl), -N(C1-4 alkyl)2 is optionally substituted by one or more substituents selected from deuterium, halogen, cyano, hydroxyl, amino, oxo, C1-4 alkyl, C1-4 alkoxy, -NH(C1-4 alkyl), -N(C1-4 alkyl)2; preferably, each R a Each of these can be independently represented as hydrogen, F, Cl, Br, cyano, ethyl cyano, hydroxyl, amino, oxo, methyl, ethyl, methoxy, ethoxy, fluoromethyl, fluoroethyl, fluoromethoxy, fluoroethoxy, methylamino, and dimethylamino.

[0046] In some embodiments, Selected from

[0047] In some embodiments, Selected from

[0048] In some embodiments, Selected from

[0049] In some embodiments, Selected from

[0050] In some embodiments, Selected from

[0051] In some embodiments, Selected from

[0052] In some embodiments, Selected from

[0053] In some implementations, ring B is a 5-membered heteroaryl group.

[0054] In some implementation schemes, ring B is

[0055] In some implementation schemes, ring B is Preferably, ring B is The key marked with "#" is connected to ring A, and the key marked with "$" is connected to ring C.

[0056] In some implementation schemes, each R b Each of these can be independently hydrogen, deuterium, halogen, cyano, hydroxyl, amino, C1-4 alkyl, C1-4 alkoxy, C1-4 haloalkyl, C1-4 haloalkoxy, -NH(C1-4 alkyl), -N(C1-4 alkyl)2.

[0057] In some implementation schemes, R b Each of these can be independently represented as hydrogen, deuterium, F, Cl, Br, cyano, hydroxyl, amino, methyl, ethyl, methoxy, ethoxy, fluoromethyl, fluoroethyl, fluoromethoxy, fluoroethoxy, methylamino, ethylamino, and dimethylamino.

[0058] In some implementations, b is 0, 1, or 2.

[0059] In some implementations, b is 0 or 1.

[0060] In some implementations, b is 0.

[0061] In some embodiments, the ring C is a C6-10 aryl, a 5-10 heteroaryl, or a 5-10 heterocyclic group; the heteroatoms in the 5-10 heteroaryl and 5-10 heterocyclic groups are selected from N, O, and S, and the number of heteroatoms is 1, 2, 3, or 4.

[0062] In some implementations, ring C is

[0063] In some implementations, ring C is

[0064] In some implementations, ring C is

[0065] In some implementations, ring C is

[0066] In some implementation schemes, R c Each can be independently represented by hydrogen, deuterium, halogen, cyano, nitro, hydroxyl, amino, mercapto, oxo, or -C(O)NR. c1 R c2 -C(O)R c3 、-S(O)2R c4 C1-4 alkyl, C1-4 alkoxy, C2-4 alkenyl, C2-4 alkynyl, C1-4 alkylthio, -NH(C1-4 alkyl), -N(C1-4 alkyl)2, C3-6 cycloalkyl, C5-10 cycloalkenyl, C3-6 cycloalkoxy, 4-7 membered heterocyclic, C6-10 aryl, 5-10 membered heteroaryl, or two adjacent R groups. c Together with the ring atoms they are attached to, they form a 5-6 membered carbon ring or heterocycle; the C1-4 alkyl, C1-4 alkoxy, C2-4 alkenyl, C2-4 alkynyl, C1-4 alkylthio, -NH(C1-4 alkyl), -N(C1-4 alkyl)2, C3-6 cycloalkyl, C5-10 cycloalkenyl, C3-6 cycloalkoxy, 4-7 membered heterocyclic, C6-10 aryl, 5-10 membered heteroaryl, or two adjacent R groups. c Together with the ring atoms attached to them, they form a 5-6 membered carbon ring or heterocycle, optionally substituted by one or more substituents selected from deuterium, halogen, cyano, hydroxyl, amino, oxo, C1-4 alkyl, C1-4 alkoxy, C3-6 cycloalkyl, 4-7 membered heterocyclic, C6-10 aryl, and 5-10 membered heteroaryl; R c1 R c2 R c3 R c4 Each is independently selected from hydrogen, C1-4 alkyl, C1-4 alkoxy, C3-6 cycloalkyl, or R c1 R c2Together with the N atoms attached to them, they form 4-7 membered heterocyclic groups; the C1-4 alkyl, C1-4 alkoxy, C3-6 cycloalkyl, or R c1 R c2 Together with the N atoms attached to them, they form 4-7 membered heterocyclic groups, which may be optionally replaced by one or more groups selected from deuterium, halogen, hydroxyl, amino, oxo, C1-4 alkyl, C1-4 alkoxy, and C3-6 cycloalkyl.

[0067] In some implementation schemes, R c Each of these groups can be independently represented as hydrogen, deuterium, halogen, cyano, hydroxyl, amino, mercapto, oxo, C1-4 alkyl, C1-4 alkoxy, C2-4 alkenyl, C1-4 alkylthio, -NH(C1-4 alkyl), -N(C1-4 alkyl)2, C3-6 cycloalkyl, C3-6 cycloalkoxy, 4-7 membered heterocyclic, C1-4 haloalkyl, C1-4 haloalkoxy, C1-4 deuterated alkyl, C3-6 cycloalkyl, and C1-4 alkylene-.

[0068] In some implementation schemes, R c Each of these can be independently halogen, C1-6 alkyl, C1-6 haloalkyl, C1-6 deuterated alkyl, C3-6 cycloalkyl, 4-7 heterocyclic alkyl, C3-6 cycloalkyl, C1-4 alkyl-.

[0069] In some implementation schemes, R c Each is independently a halogen, a C1-4 alkyl, a C1-4 haloalkyl, or a C1-4 deuterated alkyl.

[0070] In some implementation schemes, R c Each of these groups can be independently hydrogen, F, Cl, Br, cyano, hydroxyl, oxo, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, cyclopropyl, oxetane, azirone, cyclopropylmethylene, methoxy, trifluoromethoxy, difluoromethoxy, monofluoromethoxy, ethoxy, isopropoxy, cyclopropoxy, vinyl, propenyl, methylthio, fluoromethyl (e.g., monofluoromethyl, difluoromethyl, trifluoromethyl), fluoroethyl (e.g., -CH2CF3, -CH2CHF2), deuterated methyl (e.g., -CDH2, -CD2H, -CD3).

[0071] In some implementation schemes, R cEach of these groups can be independently hydrogen, F, Cl, Br, cyano, hydroxyl, oxo, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, cyclopropyl, oxetane, azirone, cyclopropylmethylene, methoxy, trifluoromethoxy, difluoromethoxy, monofluoromethoxy, ethoxy, isopropoxy, cyclopropoxy, vinyl, propenyl, methylthio, fluoromethyl (e.g., monofluoromethyl, difluoromethyl, trifluoromethyl), or deuterated methyl (e.g., -CD3).

[0072] In some embodiments, Selected from Where c is 0, 1, 2, 3, or 4; c2 is 0, 1, or 2; c3 is 0, 1, or 2; and the key marked "1" connects to ring B, and the key marked "2" connects to...

[0073] In some embodiments, Selected from Where c is 0, 1, 2, 3, or 4; c2 is 0, 1, or 2; c3 is 0, 1, or 2; and the key marked "1" connects to ring B, and the key marked "2" connects to...

[0074] In some embodiments, Selected from Where c is 0, 1, 2, 3, or 4; c1 is 0, 1, 2, or 3; preferably c1 is 1 or 2; wherein the key marked "1" is connected to ring B, and the key marked "2" is connected to...

[0075] In some embodiments, Selected from Wherein, c is 0, 1, 2, 3, or 4; preferably, c is 0, 1, 2, or 3; c1 is 0, 1, 2, or 3; preferably, c1 is 1 or 2; wherein the key marked "1" is connected to ring B, and the key marked "2" is connected to...

[0076] In some embodiments, Selected from Where c1 is 0, 1, 2, or 3; preferably c1 is 1 or 2; wherein the key marked "1" is connected to ring B, and the key marked "2" is connected to...

[0077] In some embodiments, Selected from

[0078] The key marked "1" connects to ring B, and the key marked "2" connects to... In some embodiments, Selected from The key marked "1" connects to ring B, and the key marked "2" connects to...

[0079] In some embodiments, Selected from The key marked "1" connects to ring B, and the key marked "2" connects to...

[0080] In some embodiments, Selected from The key marked "1" connects to ring B, and the key marked "2" connects to...

[0081] In some implementation schemes, R 1 R 2 Each is independently selected from hydrogen, deuterium, halogen, C1-4 alkyl, C1-4 haloalkyl, C1-4 deuteralkyl, C1-4 alkoxy, C1-4 haloalkoxy, or R 1 R 2 Together with the carbon atoms they are attached to, they form 3-7 membered carbon rings or heterocycles.

[0082] In some implementation schemes, R 1 R 2 Each is independently selected from hydrogen, deuterium, F, Cl, Br, methyl, ethyl, methoxy, ethoxy, or R. 1 R 2 Together with the carbon atoms they are attached to, they form cyclopropyl, cyclobutyl, oxocyclobutyl, and azircyclobutyl.

[0083] In some implementation schemes, R 1 R 2 All are hydrogen, or R 1 R 2One is hydrogen, and the other is deuterium, F, Cl, Br, methyl, ethyl, methoxy, or ethoxy.

[0084] In some implementation schemes, R 1 R 2 Both are hydrogen.

[0085] In some embodiments, ring D is a 5-6 nucleotide nitrogen-containing heterocyclic benzobenzene, a 5-6 nucleotide nitrogen-containing heterocyclic benzobenzene, a 5-6 nucleotide nitrogen-containing heterocyclic benzobenzene, or a 5-6 nucleotide nitrogen-containing heterocyclic benzobenzene.

[0086] In some implementations, ring D is Wherein, G1, G2, G3, and G4 are each independently selected from CH or N; G5 is selected from CH2, NH, O, or S; preferably, G1, G2, G3, and G4 are each independently selected from CH, or one of G1, G2, G3, and G4 is selected from N, and the rest are selected from CH; G5 is selected from CH2, NH, or O.

[0087] In some implementations, ring D is Wherein, G1, G2, G3, and G4 are each independently selected from CH or N; G5 is selected from CH2, NH, O, or S; preferably, G1, G2, G3, and G4 are each independently selected from CH, or one of G1, G2, G3, and G4 is selected from N, and the rest are selected from CH; G5 is selected from CH2, NH, or O.

[0088] In some implementations, ring D is

[0089] In some implementations, ring D is

[0090] In some implementations, ring D is

[0091] In some implementation schemes, R d Each is independently selected from hydrogen, deuterium, halogen, cyano, nitro, hydroxyl, mercapto, oxo, C1-4 alkyl, C1-4 alkoxy, C1-4 haloalkyl, C1-4 haloalkoxy, C1-4 alkylthio, -NH(C1-4 alkyl), -N(C1-4 alkyl)2, hydroxyC1-4 alkyl, -C(O)(C1-4 alkyl), -C(O)O(C1-4 alkyl), -S(O)(C1-4 alkyl), -S(O)2(C1-4 alkyl), C3-6 cycloalkyl, 4-7 heterocyclic, C6-10 aryl, 5-10 heteroaryl.

[0092] In some implementation schemes, Rd Each is independently selected from hydrogen, deuterium, F, Cl, Br, cyano, nitro, hydroxyl, mercapto, oxo, methyl, ethyl, propyl, butyl, methoxy, ethoxy, propoxy, fluoromethyl, fluoroethyl, fluoromethoxy, fluoroethoxy, methylthio, ethylthio, methylamino, ethylamino, dimethylamino, hydroxymethyl, hydroxyethyl, -C(O)CH3, -C(O)OCH3, -S(O)CH3, -S(O)2CH3, cyclopropyl, cyclobutyl, oxetanebutyl, azirone, phenyl, pyridinyl, pyrroleyl, pyrimidinyl, and pyrazinyl.

[0093] In some implementations, a is 0, 1, 2 or 3, preferably a is 1.

[0094] In some implementations, b is 0, 1, or 2; preferably, b is 0 or 1.

[0095] In some implementations, c is 0, 1, 2, 3 or 4, preferably c is 0, 1, 2 or 3.

[0096] In some implementations, d is 0, 1, 2 or 3, preferably d is 0, 1 or 2, more preferably d is 0.

[0097] In some embodiments, the present invention provides compounds of formula (I) as described above, wherein the compounds have the structure shown in formula (I-1):

[0098] In some embodiments, the present invention provides compounds of formula (I) as described above, wherein the compounds have structures as shown in any of formulas (I-1-1), (I-1-2), and (I-1-3):

[0099] In some embodiments, the present invention provides compounds of formula (I) as described above, wherein the compounds have the structure shown in any of formulas (I-1-1'), (I-1-2'), and (I-1-3'):

[0100] Z1, Z2, Z3, and Z4 are each independently selected from CH or N; preferably, one or two of Z1, Z2, Z3, and Z4 are N, and the rest are CH; c is 0, 1, 2, 3, or 4, preferably c is 0, 1, 2, or 3; c1 is 0, 1, 2, or 3, preferably c1 is 1 or 2.

[0101] In some embodiments, the present invention provides compounds of formula (I-1-1') as described above, wherein the compounds have any structure as shown in formulas (I-1-A), (I-1-B), (I-1-C), (I-1-D), (I-1-E), (I-1-F), (I-1-G), (I-1-H):

[0102] In some embodiments, the present invention provides compounds of formula (I) as described above, wherein the compounds have the structure shown in formula (I-2):

[0103] in, This indicates a 5-membered heteroaryl group, where Y1 and Y3 are independently C and N, and Y2, Y4, and Y5 are independently N, NH, O, S, or CH; and the groups connected to Y1, Y2, Y3, Y4, and Y5 are... Each can independently represent a single or double bond; two bonds connected to one atom They are not all double bonds at the same time; when Y2, Y4, and Y5 are O, S, or NH, the bonds they are connected to... It is a single key.

[0104] In some embodiments, the present invention provides compounds of formula (I) as described above, wherein the compounds have the structure shown in formula (I-2'):

[0105] In some embodiments, the present invention provides compounds of formula (I) as described above, wherein the compounds have structures as shown in any of formulas (I-2'-1), (I-2'-2), and (I-2'-3):

[0106] Z1, Z2, Z3, and Z4 are each independently selected from CH or N; preferably, one or two of Z1, Z2, Z3, and Z4 are N, and the rest are CH; c is 0, 1, 2, 3, or 4, preferably c is 0, 1, 2, or 3; c1 is 0, 1, 2, or 3, preferably c1 is 1 or 2.

[0107] In some embodiments, the present invention provides compounds of formula (I) as described above, wherein the compounds have structures as shown in either formula (I-3) or (I-4):

[0108] In some embodiments, the present invention provides compounds of formula (I) as described above, wherein the compounds have structures as shown in any of formulas (I-3-1), (I-3-2), (I-4-1), and (I-4-2):

[0109] In some embodiments, the present invention provides compounds of formula (I) as described above, wherein the compounds are represented by any structure of formula (I-3') or (I-4'):

[0110] Among them, R a9 The C1-6 alkyl, C2-6 alkenyl, C2-6 ynyl, C3-10 cycloalkyl, 3-10 heterocyclic, C6-10 aryl, and 5-10 heteroaryl groups are selected; the C1-6 alkyl, C2-6 alkenyl, C2-6 ynyl, C3-10 cycloalkyl, 3-10 heterocyclic, C6-10 aryl, and 5-10 heteroaryl groups are optionally substituted by one or more substituents selected from deuterium, halogen, cyano, hydroxyl, amino, oxo, C1-6 alkyl, C1-6 alkoxy, -NH(C1-6 alkyl), and -N(C1-6 alkyl)2; preferably, R a9 The C1-4 alkyl, C2-4 alkenyl, C3-6 cycloalkyl, 4-7 heterocyclic, C6-10 aryl, and 5-10 heteroaryl groups are selected; the C1-4 alkyl, C2-4 alkenyl, C3-6 cycloalkyl, 4-7 heterocyclic, C6-10 aryl, and 5-10 heteroaryl groups are optionally substituted by one or more substituents selected from deuterium, halogen, cyano, hydroxyl, amino, oxo, C1-4 alkyl, C1-4 alkoxy, -NH(C1-4 alkyl), and -N(C1-4 alkyl)2; preferably, R a9 The C1-4 alkyl, C2-4 alkenyl, C3-6 cycloalkyl, 4-6 heterocyclic, phenyl, and 5-6 heteroaryl groups are selected; the C1-4 alkyl, C2-4 alkenyl, C3-6 cycloalkyl, 4-6 heterocyclic, phenyl, and 5-6 heteroaryl groups are optionally substituted by one or more substituents selected from deuterium, halogen, cyano, hydroxyl, amino, oxo, C1-4 alkyl, C1-4 alkoxy, -NH(C1-4 alkyl), and -N(C1-4 alkyl)2; preferably, R a9 It is a C1-6 alkyl or C1-6 haloalkyl; preferably, R a9 The compounds are methyl, ethyl, trifluoromethyl, difluoromethyl, cyclopropyl, cyclobutane, oxetane, azirone, phenyl, methylphenylene, thiophene, and pyridyl.

[0111] Each R aEach of the following is independently substituted with hydrogen, deuterium, halogen, cyano, hydroxyl, amino, mercapto, oxo, C1-6 alkyl, C2-6 alkenyl, C1-6 alkoxy, C1-6 alkylthio, -NH(C1-6 alkyl), or -N(C1-6 alkyl)2; wherein the C1-6 alkyl, C2-6 alkenyl, C1-6 alkoxy, C1-6 alkylthio, -NH(C1-6 alkyl), or -N(C1-6 alkyl)2 is optionally substituted with one or more substituents selected from deuterium, halogen, cyano, hydroxyl, amino, oxo, C1-6 alkyl, C2-6 alkenyl, C1-6 alkoxy, C1-6 alkylthio, -NH(C1-6 alkyl), or -N(C1-6 alkyl)2; preferably, each R a Each of the following groups is independently hydrogen, F, Cl, Br, cyano, hydroxyl, amino, oxo, C1-4 alkyl, C1-4 alkoxy, -NH(C1-4 alkyl), -N(C1-4 alkyl)2; the C1-4 alkyl, C1-4 alkoxy, -NH(C1-4 alkyl), -N(C1-4 alkyl)2 is optionally substituted by one or more substituents selected from deuterium, halogen, cyano, hydroxyl, amino, oxo, C1-4 alkyl, C1-4 alkoxy, -NH(C1-4 alkyl), -N(C1-4 alkyl)2; preferably, each R a Each is independently hydrogen or C1-4 alkyl; preferably, each R a Each of these groups can be independently identified as hydrogen, F, Cl, Br, cyano, hydroxyl, amino, oxo, methyl, ethyl, methoxy, ethoxy, fluoromethyl, fluoroethyl, fluoromethoxy, fluoroethoxy, methylamino, and dimethylamino.

[0112] a1 is 0, 1, or 2; preferably, a1 is 0 or 1; more preferably, a1 is 0;

[0113] Ring A is a 4-7 member saturated or partially saturated monocyclic heterocyclic group or a 7-12 member bicyclic heterocyclic group; the 7-12 member bicyclic heterocyclic group is a fused ring, a spiro ring, or a bridged ring; the heteroatoms in the 4-7 member saturated or partially saturated monocyclic heterocyclic group or the 7-12 member bicyclic heterocyclic group are selected from N, O, and S, and the number of heteroatoms is 1, 2, or 3; preferably, ring A is a 5-7 member saturated monocyclic heterocyclic group, an 8-11 fused bicyclic heterocyclic group, or a 9-11 member spirocyclic heterocyclic group; the heteroatoms in the 5-7 member saturated monocyclic heterocyclic group, the 8-11 fused bicyclic heterocyclic group, or the 9-11 member spirocyclic heterocyclic group are selected from N, O, and S, and the number of heteroatoms is 1, 2, or 3, wherein at least one heteroatom is N; preferably, ring A is The key marked with "a" is connected to Keys marked with "b" are connected to

[0114] Each R bEach of the following is independently hydrogen, deuterium, halogen, cyano, hydroxyl, amino, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, -NH(C1-6 alkyl), -N(C1-6 alkyl)2; preferably, each R b Each of the following is independently hydrogen, deuterium, halogen, cyano, hydroxyl, amino, C1-4 alkyl, C1-4 alkoxy, C1-4 haloalkyl, C1-4 haloalkoxy, -NH(C1-4 alkyl), -N(C1-4 alkyl)2; preferably, each R b Each of these can be independently represented as hydrogen, deuterium, F, Cl, Br, cyano, hydroxyl, amino, methyl, ethyl, methoxy, ethoxy, fluoromethyl, fluoroethyl, fluoromethoxy, fluoroethoxy, methylamino, ethylamino, and dimethylamino.

[0115] b is 0, 1, or 2; preferably, b is 0 or 1; more preferably, b is 0;

[0116] This indicates a 5-membered heteroaryl group, where Y1 and Y3 are independently C and N, and Y2, Y4, and Y5 are independently N, NH, O, S, or CH; and the groups connected to Y1, Y2, Y3, Y4, and Y5 are... Each can independently represent a single or double bond; two bonds connected to one atom They are not all double bonds at the same time; when Y2, Y4, and Y5 are O, S, or NH, the bonds they are connected to... It is a single bond; preferably, one of Y1 and Y3 is selected from N and the other is selected from C, one of Y2, Y4 and Y5 is selected from N and the other two are selected from CH; more preferably, Y1 and Y5 are selected from N, Y3 is selected from C, and Y2 and Y4 are selected from CH.

[0117] R 1 R 2 Each is independently selected from hydrogen, deuterium, halogen, C1-6 alkyl, C1-6 haloalkyl, C1-6 deuteralkyl, C1-6 alkoxy, C1-6 haloalkoxy, or R 1 R 2 Together with the carbon atoms they are attached to, they form 3-7 membered rings; preferably, R 1 R 2 Each is independently selected from hydrogen, deuterium, halogen, C1-4 alkyl, C1-4 haloalkyl, C1-4 deuteralkyl, C1-4 alkoxy, C1-4 haloalkoxy, or R 1 R 2 Together with the carbon atoms they are attached to, they form 3-7 membered carbon rings or heterocycles; preferably, R 1 R 2Each is independently selected from hydrogen, deuterium, F, Cl, Br, methyl, ethyl, methoxy, ethoxy, fluoromethyl, fluoromethoxy, deuterated methyl, deuterated methoxy, or R. 1 R 2 Together with the carbon atoms they are attached to, they form cyclopropyl, cyclobutyl, oxacyclobutyl, and azirheycyclobutyl groups; preferably, R 1 R 2 All are hydrogen, or R 1 R 2 One is hydrogen, and the other is deuterium, F, Cl, Br, methyl, ethyl, methoxy, ethoxy, trifluoromethyl, difluoromethyl, -CD3, -OCD3; preferably, R 1 R 2 Both are hydrogen.

[0118] Each R d Each is independently selected from hydrogen, deuterium, halogen, cyano, hydroxyl, mercapto, oxo, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C1-6 alkylthio, -NH (C1-6 alkyl), -N (C1-6 alkyl)2; preferably, each R d Each is independently selected from hydrogen, deuterium, halogen, cyano, hydroxyl, mercapto, oxo, C1-4 alkyl, C1-4 alkoxy, C1-4 haloalkyl, C1-4 haloalkoxy, C1-4 alkylthio, -NH (C1-4 alkyl), -N (C1-4 alkyl)2; preferably, each R d Each is independently selected from hydrogen or halogen; preferably, each R d Each is independently selected from hydrogen, deuterium, F, Cl, Br, cyano, hydroxyl, mercapto, oxo, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, methoxy, ethoxy, fluoromethyl, fluoroethyl, fluoromethoxy, fluoroethoxy, methylthio, ethylthio, methylamino, ethylamino, and dimethylamino.

[0119] d is 0, 1, 2 or 3; preferably, d is 0, 1 or 2; more preferably, d is 0 or 1; even more preferably, d is 0;

[0120] R c-1 R c-2 R c-3 R c-4 R c-5 R c-6 R c-7Each of the following groups is independently hydrogen, deuterium, halogen, cyano, hydroxyl, amino, mercapto, oxo, C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkylthio, -NH(C1-6 alkyl), -N(C1-6 alkyl)2, C3-6 cycloalkyl, C3-6 cycloalkoxy, 4-7 membered heterocyclic, C6-10 aryl, 5-10 membered heteroaryl; wherein the C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, and C2-6 alkynyl groups are... The C1-6 alkylthioyl, -NH(C1-6 alkyl), -N(C1-6 alkyl)2, C3-6 cycloalkyl, C3-6 cycloalkoxy, 4-7 heterocyclic, C6-10 aryl, and 5-10 heteroaryl groups are optionally substituted by one or more substituents selected from deuterium, halogen, cyano, hydroxyl, amino, oxo, C1-6 alkyl, C1-6 alkoxy, C3-6 cycloalkyl, 4-7 heterocyclic, C6-10 aryl, and 5-10 heteroaryl groups; preferably, R c-1 R c-2 R c-3 R c-4 R c-5 R c-6 R c-7 Each of the following groups is independently substituted with hydrogen, deuterium, halogen, cyano, hydroxyl, amino, mercapto, oxo, C1-4 alkyl, C1-4 alkoxy, C2-4 alkenyl, C1-4 alkylthio, -NH(C1-4 alkyl), -N(C1-4 alkyl)2, C3-6 cycloalkyl, C3-6 cycloalkoxy, or 4-7 heterocyclic groups; wherein the C1-4 alkyl, C1-4 alkoxy, C2-4 alkenyl, C1-4 alkylthio, -NH(C1-4 alkyl), -N(C1-4 alkyl)2, C3-6 cycloalkyl, C3-6 cycloalkoxy, or 4-7 heterocyclic groups are optionally substituted with one or more substituents selected from deuterium, halogen, hydroxyl, amino, oxo, C1-4 alkyl, C1-4 alkoxy, C3-6 cycloalkyl, 4-7 heterocyclic groups, phenyl, or 5-6 heteroaryl; preferably, R c-1 It can be hydrogen, halogen, cyano, C1-4 alkyl, C1-4 alkoxy, C2-4 alkenyl, C1-4 alkylthio, C1-4 haloalkyl, C1-4 haloalkoxy, C3-6 cycloalkyl, or C3-6 cycloalkoxy; R c-2 For hydrogen, halogen; R c-3 For hydrogen, halogen; R c-4 For hydrogen, halogen; R c-5 It is a C1-4 alkyl, C1-4 deuterated alkyl, C1-4 haloalkyl, C3-6 cycloalkyl, C1-4 alkylene, or 4-7 membered heterocyclic group; R c-6 For hydrogen, halogens (e.g., F); R c-7 It is hydrogen; preferably, R c-7 For hydrogen, R c-6 It is hydrogen or halogen (e.g., F); Rc-5 It is a C1-6 alkyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, C3-6 cycloalkyl-C1-3 alkylene-, or 4-7 membered heterocyclic alkyl; preferably, R c-7 For hydrogen, R c-6 It is hydrogen or halogen (e.g., F); R c-5 It is a C1-4 alkyl, C1-4 deuterated alkyl, or C1-4 haloalkyl.

[0121] In some embodiments, the present invention provides compounds of formula (I) as described above, wherein the compounds have the structure shown in formula (X):

[0122] Wherein, G1, G2, G3, and G4 are each independently selected from CH or N; preferably, one of G1, G2, G3, and G4 is selected from N, and the rest are selected from CH; preferably, G1, G2, G3, and G4 are all selected from CH.

[0123] R a9 Selected from C1-6 alkyl or C1-6 haloalkyl;

[0124] R a Selected from hydrogen, hydroxyl, or C1-6 alkyl; preferably, R a Selected from hydrogen or C1-4 alkyl;

[0125] a1 is selected from 0, 1, or 2; preferably a1 is selected from 0 or 1; more preferably a1 is 0;

[0126] X0 is selected from CH or N; preferably, X0 is CH;

[0127] R b Selected from hydrogen, halogen, or C1-6 alkyl; preferably, R b Selected from hydrogen, halogens, or C1-4 alkyl groups;

[0128] b is selected from 0 or 1; preferably b is 0.

[0129] R 1 R 2 Each is independently selected from hydrogen, halogen, or C1-6 alkyl; preferably, R 1 R 2 All are hydrogen, or R 1 R 2 One is hydrogen, and the other is halogen or C1-4 alkyl; more preferably, R 1 R 2 All are hydrogen;

[0130] Each R d Each is independently selected from hydrogen, halogen, C1-6 alkyl, or C1-6 haloalkyl; preferably, each R dEach is independently selected from hydrogen or halogens (e.g., F);

[0131] d is selected from 0, 1 or 2, preferably d is selected from 0 or 1; more preferably d is 0;

[0132] R c-7 For hydrogen, R c-6 It is hydrogen or halogen (e.g., F); R c-5 It is a C1-6 alkyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, C3-6 cycloalkyl-C1-3 alkylene-, or 4-7 membered heterocyclic alkyl; preferably, R c-7 For hydrogen, R c-6 It is hydrogen or halogen (e.g., F); R c-5 It is a C1-4 alkyl, C1-4 deuterated alkyl, or C1-4 haloalkyl.

[0133] In some embodiments, the present invention provides a compound of formula (I), or a stereoisomer, tautomer, diastereomer, racemate, cis-trans isomer, isotopically labeled compound (preferably deuterated), N-oxide, metabolite, ester, prodrug, crystal form, hydrate, solvate, or pharmaceutically acceptable salt thereof, wherein the compound is selected from:

[0134] In some embodiments, the present invention provides a compound of formula (I), or a stereoisomer, tautomer, diastereomer, racemic compound, cis-trans isomer, isotopically labeled compound (preferably deuterated), N-oxide, metabolite, ester, prodrug, crystal form, hydrate, solvate or pharmaceutically acceptable salt thereof, for inhibiting CYP11A1.

[0135] In another aspect, the present invention provides a pharmaceutical composition comprising a compound of formula (I) above or its stereoisomers, tautomers, diastereomers, racemic compounds, cis-trans isomers, isotopically labeled compounds (preferably deuterated compounds), N-oxides, metabolites, esters, prodrugs, crystal forms, hydrates, solvates or pharmaceutically acceptable salts and pharmaceutically acceptable carriers.

[0136] Preferably, the pharmaceutical composition comprises a compound of formula (I) and at least one additional active ingredient selected from the following list: - glucocorticoids; - mineralocorticoids; - nonsteroidal androgen receptor antagonists; - steroid synthesis inhibitors; - chemotherapeutic agents; - antiestrogens; - epigenetic regulators; - mTOR inhibitors (e.g., everolimus); - AKT inhibitors (e.g., AZ5363); - radiopharmaceuticals (e.g., Alpharadin); - GnRH / LHRH analogs (e.g., leuprorelin); - PI3K inhibitors; and - CDK4 / 6 inhibitors.

[0137] In another aspect, the present invention provides a compound of formula (I), or its stereoisomers, tautomers, diastereomers, racemates, cis-trans isomers, isotopically labeled compounds (preferably deuterated), N-oxides, metabolites, esters, prodrugs, crystal forms, hydrates, solvates, or pharmaceutically acceptable salts or pharmaceutical compositions thereof, for the treatment of steroid receptor-dependent conditions and diseases, said method comprising administering to an individual in need a therapeutically effective amount of a compound of formula (I) above, or its stereoisomers, tautomers, diastereomers, racemates, cis-trans isomers, isotopically labeled compounds (preferably deuterated), N-oxides, metabolites, esters, prodrugs, crystal forms, hydrates, solvates, or pharmaceutically acceptable salts or pharmaceutical compositions thereof; wherein the steroid receptor-dependent disease is preferably cancer; the cancer is preferably prostate cancer; the prostate cancer is preferably castration-resistant prostate cancer (CRPC);

[0138] The application of a therapeutically effective amount of a compound of formula (I) is preferred, and glucocorticoids and / or mineralocorticoids are also preferably applied, and one or more anticancer drugs are optionally applied.

[0139] The treatment involves administering a therapeutically effective amount of a compound of formula (I) with one or more anticancer drugs, preferably selected from: - nonsteroidal androgen receptor antagonists; - steroid synthesis inhibitors; - chemotherapeutic agents; - antiestrogenic drugs; - epigenetic regulators; - mTOR inhibitors (e.g., everolimus); - AKT inhibitors (e.g., AZ5363); - radiopharmaceuticals (e.g., alpharadin); - GnRH / LHRH analogs (e.g., leuprorelin); - PI3K inhibitors; and - CDK4 / 6 inhibitors. Detailed Implementation

[0140] definition

[0141] Unless otherwise defined below, all technical and scientific terms used herein are intended to have the same meaning as those commonly understood by those skilled in the art. References to technology used herein are intended to refer to technology commonly understood in the art, including variations of technology or substitutions of equivalent technology that would be apparent to those skilled in the art. While it is believed that the following terms are well understood by those skilled in the art, the following definitions are set forth to better explain the present invention.

[0142] The terms “comprising,” “including,” “having,” “containing,” or “involving,” and their other variations herein, are inclusive or open-ended and do not exclude other unlisted elements or method steps (i.e., these terms also cover the terms “consistently made up of” and “comprises of”).

[0143] The terms "substitution" or "substituted" refer to the replacement of one or more hydrogen atoms on a specific atom by a substituent, provided that the valence state of the specific atom is normal and the substituted compound is stable. When the substituent is an oxo group (i.e., =O) or a thio group (i.e., =S), it means that two hydrogen atoms are replaced, and the oxo and / or thio group will not occur on the aromatic group.

[0144] The terms "optional" or "optionally" mean that the event or condition described below may or may not occur, including both the occurrence and non-occurrence of the event or condition. For example, "optionally substituted 3-7-membered heterocycles with one or more substituents selected from deuterium" means that the 3-7-membered heterocyclic group can be unsubstituted, monosubstituted, polysubstituted, or fully substituted. Those skilled in the art will understand that for any group containing one or more substituents, no substitution or substitution pattern that is spatially impossible and / or synthetically unsynthetic is introduced.

[0145] As used herein, the term "one or more" means one or more substituents under reasonable conditions, such as two, three, four, five, or ten. Wherein, when a group is substituted by "one or more" substituents, it means that one or more hydrogen atoms in that group are substituted by one or more substituents from the indicated group, for example, by 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, etc., provided that the normal valence of the specified atom is not exceeded and the substitution forms a stable compound. Combinations of substituents and / or variables are permitted only if such combinations form a stable compound.

[0146] If a substituent is described as being “independently selected” from a group, then each substituent is selected independently of the others. Therefore, each substituent may be the same as or different from another (other) substituent.

[0147] Unless otherwise indicated, as used herein, the point of attachment of a substituent may be from any suitable position of the substituent.

[0148] When a substituent is shown to be a bond that passes through the ring and connects two atoms (“floating bond”), such a substituent may be bonded to any cyclic atom in the substituted ring, unless otherwise stated. In cases where a substituted hydrogen atom is shown to be carried by a substituted ring member, the substituted hydrogen atom is substantially substituted (i.e., not present) when the floating bond is bonded to that substituted ring member.

[0149] As used herein, the term "alkyl" refers to a straight-chain or branched monovalent saturated aliphatic hydrocarbon, which can be considered as a group obtained by losing one hydrogen atom from an alkane. In some embodiments, the alkyl group has 1 to 12, for example, 1 to 6 (e.g., 1, 2, 3, 4, 5, or 6) carbon atoms. For example, as used herein, the term "C1-6 alkyl" refers to a straight-chain or branched group with 1 to 6 carbon atoms, including "C2-6 alkyl", "C2-5 alkyl", "C1-4 alkyl", "C1-3 alkyl", and "C1-2 alkyl". Examples of "C1-6 alkyl" include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, and n-hexyl. The term "C1-4 alkyl" refers to an alkyl group having 1 to 4 carbon atoms (i.e., methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, or tert-butyl).

[0150] As used herein, the term "alkylene" refers to a straight-chain or branched divalent saturated aliphatic hydrocarbon obtained by further losing one hydrogen atom from the "alkyl" described above. In some embodiments, the alkylene has 1 to 12 carbon atoms, preferably 1, 2, 3, 4, 5 or 6 carbon atoms, such as methylene, ethylene, propylene or butylene.

[0151] Those skilled in the art will readily understand that, in cases where an alkyl group is part of a substituent and is attached to another group on each side thereon, if the term "alkyl" is still used, then the term "alkyl" actually refers to the corresponding alkylene group. For example, "C1-C6 alkyl" in "hydroxyC1-C6 alkyl-" actually means "C1-C6 alkylene group".

[0152] As used herein, the term "alkoxy" refers to an -O-alkyl group, wherein the alkyl group is as defined above. The term "C1-6 alkoxy" refers to a linear or branched alkoxy group having 1 to 6 carbon atoms (e.g., methoxy, ethoxy, n-propoxy, isopropoxy, tert-butoxy, n-pentoxy, or n-hexoxy). The term "C1-4 alkoxy" refers to a linear or branched alkoxy group having 1 to 4 carbon atoms (e.g., methoxy, ethoxy, n-propoxy, isopropoxy, tert-butoxy).

[0153] As used herein, the term "alkathio" refers to -S-alkyl, wherein the alkyl group is as defined above. The term "C1-6 alkathio" refers to a linear or branched alkathio group having 1 to 6 carbon atoms (e.g., methylthio, ethylthio, n-propylthio, isopropylthio, tert-butylthio, n-pentylthio, or n-hexylthio).

[0154] As used herein, the term "alkenyl" refers to a straight-chain or branched monovalent aliphatic hydrocarbon group containing one or more double bonds. In some embodiments, the alkenyl group has 2-6 carbon atoms ("C2-6 alkenyl"), for example 2 to 4 carbon atoms ("C2-4 alkenyl"), or 2 to 3 carbon atoms ("C2-3 alkenyl"). Examples of said alkenyl groups include, for example, -CH=CH2, -CH2CH=CH2, -C(CH3)=CH2, -CH2-CH=CH-CH3, 2-pentenyl, 3-pentenyl, 4-pentenyl, 2-hexenyl, 3-hexenyl, 4-hexenyl, 5-hexenyl, 2-methyl-2-propenyl, and 4-methyl-3-pentenyl. When the compounds of the present invention contain an alkenyl group, the compounds may exist in pure E (isolateral) form, pure Z (isolateral) form, or any mixture thereof. The term "alkenyl" refers to the corresponding divalent group, including, for example, "C2-6 alkenyl", "C2-4 alkenyl" and "C2-3 alkenyl", and specific examples include, but are not limited to: -CH=CH-, -CH2CH=CH-, -C(CH3)=CH-, butenyl, pentenyl, hexenyl, cyclopentenyl, cyclohexenyl, etc.

[0155] As used herein, the term "alkynyl" refers to a straight-chain or branched monovalent aliphatic hydrocarbon group containing one or more triple bonds. In some embodiments, the alkynyl group has 2, 3, 4, 5, or 6 carbon atoms ("C2-6 alkynyl"), such as 2 to 4 carbon atoms ("C2-4 alkynyl"), or 2 to 3 carbon atoms ("C2-3 alkynyl"), such as ethynyl, 2-propynyl, 2-butynyl, 1,3-butydinyl, etc. The term "ynynyl" refers to the corresponding divalent group, including, for example, "C2-6 ynynyl," "C2-4 ynynyl," and "C2-3 ynynyl." Examples include, but are not limited to, those mentioned above. wait.

[0156] As used herein, the terms “cycloalkyl,” “hydrocarbon,” and “cycloalkylene group” refer to a saturated (i.e., “cycloalkyl” and “cycloalkylene”) or partially unsaturated (i.e., having one or more double bonds (i.e., “cycloalkenyl” and “cycloalkylene”) and / or triple bonds within the ring) monocyclic or polycyclic (e.g., bicyclic) hydrocarbon ring having, for example, 3 to 10 (suitably 3 to 8, more preferably 3 to 7, 3 to 6, 4 to 6, or 5 to 6) cyclic carbon atoms. The cycloalkyl group may be… It is a fused ring, spiro ring, bridged ring, or combination thereof, including but not limited to ()cyclopropyl (ring), ()cyclobutyl (ring), ()cyclopentyl (ring), ()cyclohexyl (ring), ()cycloheptyl (ring), ()cyclooctyl (ring), ()cyclononyl (ring), ()cyclobutenyl (ring), ()cyclopentenyl (ring), ()cyclohexenyl (ring), ()cycloheptenyl (ring), ()cyclooctenyl (ring), ()cyclononenyl (ring), etc. In some embodiments, the cyclic hydrocarbon group includes aryl-fused cyclic hydrocarbon groups, provided that the entire ring system is non-aromatic.

[0157] As used herein, the terms "cycloalkyl" and "cycloalkylene" refer to saturated monocyclic or polycyclic (such as bicyclic) hydrocarbon rings (e.g., monocyclic, such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, cyclononyl), or bicyclic, such as... The cycloalkyl and cycloalkylene groups can be fused rings, spiro rings, bridged rings, or combinations thereof (such as bicyclo[1.1.1]pentyl, bicyclo[2.2.1]heptyl, bicyclo[3.2.1]octyl, or bicyclo[5.2.0]nonyl, decahydronaphthyl, etc.). The cycloalkyl and cycloalkylene groups have 3 to 10 carbon atoms, suitably 3 to 8, for example 3 to 7, 3 to 6, 4 to 6, or 5 to 6 carbon atoms. For example, the term "C3-6 cycloalkyl" refers to a saturated monocyclic or polycyclic (such as bicyclic) hydrocarbon ring (e.g., cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl) with 3 to 6 cyclic carbon atoms.

[0158] As used herein, the terms "cycloalkenyl" and "cycloalkyleneide" refer to a monocyclic or polycyclic (such as bicyclic) hydrocarbon ring having one or more double bonds within the ring (e.g., monocyclic, such as cyclopropenyl, cyclobutenyl, cyclopentenyl, cyclopentadienyl, cyclohexenyl, cyclohexadienyl, cycloheptenyl, cyclooctenyl, cyclononenyl, or bicyclic). The "cycloalkenyl" and "cycloalkyleneide" can be fused rings, spirocyclic, bridged rings, or combinations thereof. The cycloalkenyl and "cycloalkyleneide" have 3 to 10 carbon atoms, suitably 3 to 8, for example 3 to 7, 3 to 6, 4 to 6, or 5 to 6.

[0159] As used herein, the terms “heterocyclic,” “heterocyclic,” and “heterocyclic-insoluble” refer to a saturated (i.e., “heterocyclic alkyl” and “heterocyclic alkyl-insoluble”) or partially unsaturated (e.g., having one or more double bonds within a ring (i.e., “heterocyclic alkenyl,” “heterocyclic alkenyl,” or “benzo[heterocyclic alkyl]” and “benzo[heterocyclic alkyl-insoluble”)) monovalent or divalent monocyclic or polycyclic (e.g., bicyclic) cyclic structure having 2, 3, 4, 5, 6, 7, 8, 9, or 10 carbon atoms and one or more (e.g., 1, 2, 3, 4, or 5) heteroatom-containing groups selected from N, O, S, S(O), S(O)2, and NR', wherein R' is a hydrogen atom, a C1-6 alkyl, or a C1-6 haloalkyl. In some embodiments, the heteroatom of the heterocyclic group is selected from nitrogen, oxygen, or sulfur. In some embodiments, the heteroatom of the heterocyclic group is nitrogen. In some embodiments, the number of heteroatoms in the heterocyclic group is selected from 1 or 2. In some embodiments, the number of heteroatoms in the heterocyclic group is 1. The heterocyclic group can be connected to the rest of the molecule via any one of the carbon atoms or a nitrogen atom (if present). The heterocyclic group can be a fused ring, a spiro ring, a bridged ring, or a combination thereof (e.g., Heterocyclic groups include aryl or heteroaryl fused heterocyclic groups, provided that the entire ring system is non-aromatic (e.g., Specifically, 3-10 membered heterocyclic groups are groups having 3-10 (e.g., 3-8, 3-7, 3-6, 4-6, or 5-6) carbon atoms and heteroatoms in the ring. Heterocyclic groups include nitrogen-containing heterocyclic groups, oxygen-containing heterocyclic groups, and sulfur-containing heterocyclic groups. Examples that can be listed include, but are not limited to, ethylene oxide, aziridinyl, azetidinyl, oxetanyl, tetrahydrofuranyl, tetrahydrothiophenyl, dioxolinyl, pyrrolyl, pyrrolidone, oxazolyl, thiazolyl, pyrazolyl, imidazolyl, pyrazolyl, pyrrolinyl, tetrahydropyranyl, piperidinyl, hexahydropyrimidinyl, triazineyl, morpholinyl, dithianyl, thiomorpholinyl, piperazine, trithianyl, azetidinyl, dihydropyrrolyl, dihydroimidazolyl, and azetidinyl.

[0160] As used herein, the term "aryl" refers to an all-carbon monocyclic or fused-ring polycyclic aromatic group having a conjugated π-electron system. For example, as used herein, the term "C6-14 aryl" means an aromatic group containing 6 to 14 (e.g., 6 to 12) carbon atoms, and "C6-10 aryl" means an aromatic group containing 6 to 10 carbon atoms, such as phenyl or naphthyl.

[0161] As used herein, the term "heteroaryl" refers to a monocyclic or polycyclic (e.g., bicyclic or tricyclic) aromatic ring system having 5 to 14 ring atoms, such as 5, 6, 7, 8, 9, 10, 11, 12, 13, or 14 ring atoms, particularly having 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, or 13 carbon atoms and 1, 2, 3, 4, or 5 identical or different heteroatoms independently selected from N, O, and S. Heteroaryl groups can be benzofused. Examples of heteroaryl groups include, but are not limited to: pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, thiazolyl, thiopheneyl, oxazolyl, furanyl, pyrroloyl, pyrazolyl, triazolyl, tetrazolyl, isoxazolyl, isothiazolyl, imidazoleyl, triazinyl, oxadiazolyl, thiadiazolyl, benzothiazolyl, benzoisothiazolyl, imidazole-pyridinyl, quinolinyl, indolyl, pyrrolopyridazinyl, benzo[] Furanyl, benzothiophenyl, indazole, benzoxazolyl, benzoisoxazolyl, quinazolinyl, pyrrolopyridyl, pyrazolopyrimidinyl, imidazopyridazinyl, pyrazolopyridyl, triazolopyridyl, isoquinolinyl, tetrahydroisoquinolinyl, benzoimidazoyl, cyclolinyl, indoleyl, phthalazinyl, isoindolyl, pteridinyl, purineyl, quinoxalinyl, naphthidyl, or furanolopyridyl.

[0162] As used herein, the term "ring" includes any of the cycloalkyl, cycloalkenyl, heterocyclic, aryl, and heteroaryl groups described above. For example, "3-7 membered ring," "5-7 membered ring," "3-8 membered ring," and "5-10 membered ring" refer to cycloalkyl, cycloalkenyl, heterocyclic, aryl, or heteroaryl groups with 3-7 (3, 4, 5, 6, or 7), 5-7 (5, 6, or 7), 3-8 (3, 4, 5, 6, 7, or 8), or 5-10 (5, 6, 7, 8, 9, or 10) ring atoms.

[0163] As used herein, the term “halogenated” or “halogenated” is defined as including F, Cl, Br, or I.

[0164] As used herein, the term "haloalkyl" refers to an alkyl group substituted with one or more (such as 1, 2, 3, 4, 5, or 6) identical or different halogen atoms, as defined herein. The terms "C1-6 haloalkyl," "C1-4 haloalkyl," and "C1-3 haloalkyl" refer to haloalkyl groups having 1 to 6 carbon atoms, 1 to 4 carbon atoms, and 1 to 3 carbon atoms, respectively, such as -CF3, -C2F5, -CHF2, -CH2F, -CH2CF3, -CH2Cl, or -CH2CH2CF3, etc. In particular, "haloalkyl" does not limit the number of halogen substitutions; it can be one or more. For example, "fluoromethyl" or "fluoromethoxy" refers to a methyl or methoxy group substituted with 1, 2, or 3 fluorine atoms, and "fluoroethyl" or "fluoroethoxy" refers to an ethyl or ethoxy group substituted with 1, 2, 3, 4, or 5 fluorine atoms.

[0165] This invention also includes all pharmaceutically acceptable isotopically labeled compounds that are identical to the compounds of this invention, except that one or more atoms are replaced by atoms having the same atomic number but with an atomic mass or mass number different from the dominant atomic mass or mass number in nature. Examples of isotopes suitable for inclusion in the compounds of this invention include (but are not limited to) isotopes of hydrogen (e.g., deuterium (D, ...). 2 H), tritium (T), 3 H); carbon isotopes (e.g., ... 11 C 13 C and 14 C); isotopes of chlorine (e.g.) 36 Cl); isotopes of fluorine (e.g., Cl); 18 F); isotopes of iodine (e.g., F); 123 I and 125 I); isotopes of nitrogen (e.g. 13 N and 15 N); oxygen isotopes (e.g. 15 O、 17 O and 18 O); isotopes of phosphorus (e.g., O); phosphorus isotopes ... 32 P); and isotopes of sulfur (e.g. 35 S). Certain isotope-labeled compounds of the present invention (e.g., those doped with radioactive isotopes) can be used in drug and / or substrate tissue distribution studies (e.g., analysis). Radioactive isotope tritium (i.e. 3 H) and carbon-14 (i.e. 14 C) It is particularly suitable for this purpose due to its ease of incorporation and detection. Using positron-emitting isotopes (e.g.) 11 C 18 F, 15 O and 13Substitution of N) can be used in positron emission tomography (PET) studies to examine substrate acceptor occupancy. The isotopically labeled compounds of the present invention can be prepared by methods similar to those described in the accompanying routes and / or examples and preparations, by using a suitable isotopically labeled reagent instead of the previously used unlabeled reagent. Pharmaceutically acceptable solvates of the present invention include those in which the crystallization solvent can be isotopically substituted, for example, D2O, acetone-d6, or DMSO-d6. In some embodiments, the isotopically labeled compounds of the present invention are deuterated.

[0166] As used in this article, the term "oxygenation" refers to...

[0167] The term "stereoisomer" refers to isomers formed due to at least one asymmetric center, having the same chemical composition but different spatial arrangements of atoms or groups. In compounds having one or more (e.g., 1, 2, 3, or 4) asymmetric centers, racemic mixtures, single enantiomers, diastereomer mixtures, and individual diastereomers can occur. Specific individual molecules can also exist as geometric isomers (cis / trans). Similarly, the compounds of the present invention can exist as mixtures of two or more structurally different forms in rapid equilibrium (commonly referred to as tautomers). Representative examples of tautomers include keto-enol tautomers, phenol-keto tautomers, nitroso-oxime tautomers, imine-enamine tautomers, etc. It should be understood that the scope of this application covers all such isomers or mixtures thereof in any proportion (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%).

[0168] A diastereomer is a stereoisomer that has two or more chiral centers and whose molecules are not mirror images of each other. Diastereomers have different physical properties, such as melting point, boiling point, spectral properties, and reactivity. Mixtures of diastereomers can be separated by high-resolution analytical methods such as electrophoresis and chromatography.

[0169] "Enantiomers" refer to two stereoisomers of a compound that are non-overlapping mirror images of each other.

[0170] The term "chirality" refers to molecules that have mirror pairs that are not overlapping, while the term "chirality" refers to molecules that can overlap on their mirror pairs.

[0171] The compounds of the present invention can be prepared in racemic form, or a single enantiomer can be prepared by enantioselective synthesis or by resolution.

[0172] As used herein, the terms “cis-trans isomers” or “geometric isomers” arise from the fact that the single bonds of double or cyclic carbon atoms cannot rotate freely. The compounds presented herein include all cis, trans, syn, anti, engegen (E), and zusammen (Z) isomers and their corresponding mixtures.

[0173] Solid lines (—) and solid wedges may be used in this article. Or virtual wedge The chemical bonds of the compounds of the present invention are depicted. Solid lines are used to depict bonds to asymmetric carbon atoms to indicate that all possible stereoisomers (e.g., specific enantiomers, racemic mixtures, etc.) are included at that carbon atom. Solid or imaginary wedges are used to depict bonds to asymmetric carbon atoms to indicate the presence of the indicated stereoisomers. When present in racemic mixtures, solid and imaginary wedges are used to define relative stereochemistry, not absolute stereochemistry. Unless otherwise specified, the compounds of the present invention are intended to exist as stereoisomers (including cis and trans isomers, optical isomers (e.g., R and S enantiomers), diastereomers, geometric isomers, rotational isomers, conformational isomers, trans-blocking isomers, and mixtures thereof). The compounds of the present invention may exhibit more than one type of isomerism and may consist of mixtures thereof (e.g., racemic mixtures and diastereomer pairs).

[0174] It should also be understood that certain compounds of the present invention may exist in their free form for therapeutic purposes, or, where appropriate, in their pharmaceutically acceptable derivative forms. In the present invention, pharmaceutically acceptable derivatives include, but are not limited to, pharmaceutically acceptable salts, esters, solvates, metabolites, or prodrugs, which, upon administration to a patient in need, can directly or indirectly provide the compounds of the present invention or their metabolites or residues. Therefore, when referring to "compounds of the present invention" herein, it is also intended to cover the various derivative forms of the compounds described above.

[0175] The term "pharmaceutically acceptable" means that a substance or composition must be chemically and / or toxicologically compatible with other components constituting the formulation and / or the mammals treated with it.

[0176] Pharmaceutically acceptable salts of the compounds of the present invention include their acid addition salts and base addition salts.

[0177] Suitable acid addition salts are formed from acids that form pharmaceutically acceptable salts. Examples include aspartate, benzoate, bicarbonate / carbonate, bisulfate / sulfate, fumarate, glucohepanoate, glucuronate, hexafluorophosphate, hydrobromide / bromide, hydroiodate / iodide, maleate, malonate, methyl sulfate, naphthylcarbamate, nicotinate, nitrate, orotate, oxalate, palmitate, and other similar salts.

[0178] Suitable base addition salts are formed from bases that form pharmaceutically acceptable salts. Examples include aluminum salts, arginine salts, choline salts, diethylamine salts, lysine salts, magnesium salts, meglumine salts, potassium salts, and other similar salts.

[0179] For a review of suitable salts, see Stahl and Wermuth's "Handbook of Pharmaceutical Salts: Properties, Selection, and Use" (Wiley-VCH, 2002). Methods for preparing pharmaceutically acceptable salts for the compounds of the present invention are known to those skilled in the art.

[0180] As used herein, the term "ester" means an ester derived from the various general formula compounds of this application, including physiologically hydrolyzable esters (the compounds of the present invention that can be hydrolyzed under physiological conditions to release free acids or alcohols). The compounds of the present invention may themselves also be esters.

[0181] This invention covers all possible crystalline forms or polymorphs of the compounds of this invention, which may be a single polymorph or a mixture of more than one polymorph in any proportion.

[0182] The compounds of the present invention can exist as solvates (preferably hydrates), wherein the compounds of the present invention contain a polar solvent, particularly, for example, water, methanol, or ethanol, as a structural element of the lattice of the compound. The amount of the polar solvent, particularly water, can be stoichiometric or non-stoichiometric.

[0183] Those skilled in the art will understand that not all nitrogen-containing heterocycles can form N-oxides because nitrogen requires available lone pairs of electrons to be oxidized into oxides; those skilled in the art will identify nitrogen-containing heterocycles that can form N-oxides. Those skilled in the art will also recognize that tertiary amines can form N-oxides. Synthetic methods for preparing N-oxides of heterocycles and tertiary amines are well known to those skilled in the art, including the oxidation of heterocycles and tertiary amines with peroxy acids such as peracetic acid and m-chloroperoxybenzoic acid (MCPBA), hydrogen peroxide, alkyl peroxides such as tert-butyl peroxide, sodium perborate, and dioxiranes such as dimethyldioxirane. These methods for preparing N-oxides have been extensively described and reviewed in the literature, see, for example: T.L. Gilchrist, Comprehensive Organic Synthesis, vol. 7, pp. 748-750; A.R. Katritzky and A.J. Boulton, Eds., Academic Press; and G.W. H. Heeseman and E.S. G. Wierstiuk, Advances in Heterocyclic Chemistry, vol. 22, pp. 390-392, A.R. Katritzky and A.J. Boulton, Eds., Academic Press.

[0184] The scope of this invention also includes metabolites of the compounds of this invention, i.e., substances formed in the body when the compounds of this invention are administered. Such products can be generated, for example, by oxidation, reduction, hydrolysis, amidation, deamidation, esterification, defatting, enzymatic hydrolysis, etc., of the administered compound. Therefore, this invention includes metabolites of the compounds of this invention, including compounds obtained by methods that expose the compounds of this invention to mammals for a time sufficient to produce their metabolites.

[0185] This invention further includes, within its scope, prodrugs of the compounds of the invention, which are certain derivatives of the compounds of the invention that may themselves have little or no pharmacological activity, which, when administered to or onto the body, can be converted, for example, by hydrolysis and cleavage into the compounds of the invention having the desired activity. Typically, such prodrugs are functional group derivatives of the compounds that readily convert in vivo into the compounds with the desired therapeutic activity. Further information regarding the use of prodrugs can be found in “Pro-drugs as Novel Delivery Systems,” Vol. 14, ACS Symposium Series (T. Higuchi and V. Stella) and “Bioreversible Carriers in Drug Design,” Pergamon Press, 1987 (EB Roche, editor, American Pharmaceutical Association). The prodrugs of the invention can be prepared, for example, by replacing suitable functional groups present in the compounds of the invention with certain portions known to those skilled in the art as “pro-moiety” (e.g., as described in “Design of Prodrugs,” H. Bundgaard (Elsevier, 1985)).

[0186] This invention also covers compounds of the invention containing protecting groups. In any process of preparing the compounds of the invention, protection of sensitive or reactive groups on any relevant molecule may be necessary and / or desired, thereby forming a form of chemical protection for the compounds of the invention. This can be achieved by conventional protecting groups, for example, those described in *Protective Groups in Organic Chemistry*, ed. J.F.W. McOmie, Plenum Press, 1973; and T.W. Greene & P. ​​G.W. Uts, *Protective Groups in Organic Synthesis*, John Wiley & Sons, 1991, which are incorporated herein by reference. Protecting groups can be removed at appropriate subsequent stages using methods known in the art.

[0187] As used herein, the term “about” means within ±10% of the stated value, preferably within ±5%, and more preferably within ±2%.

[0188] Example

[0189] The embodiments of the present invention will be described in detail below with reference to examples. However, those skilled in the art will understand that the following examples are for illustrative purposes only and should not be considered as limiting the scope of the invention. Unless otherwise specified in the examples, conventional conditions or conditions recommended by the manufacturer are followed. Reagents or instruments whose manufacturers are not specified are all commercially available conventional products.

[0190] NMR was performed using a Bruker Avance III 400 NMR spectrometer, with chemical shifts (δ) expressed in terms of 10⁻⁶. -6 (ppm) is given as the unit. Solvents include deuterated methanol (CD3OD), deuterated chloroform (CDCl3), or hexadeuterated dimethyl sulfoxide (DMSO-d6), etc., and the internal standard is tetramethylsilane (TMS).

[0191] MS measurements were performed using an Agilent (ESI) mass spectrometer (Agilent 1260, Agilent 6125B).

[0192] High-performance liquid chromatography (HPLC) determination conditions: SUIMADZU HPLC (LC-2030Plus), Waters Sunfire C18 column (3.5μm, 4.6×100mm), UV detection bands of 220 and 254nm, elution conditions of 5-95% acetonitrile (containing 0.05%-0.1% v / v formic acid or trifluoroacetic acid or ammonium bicarbonate), flow rate of 1.8mL / min.

[0193] Reverse-phase purification was performed using the Biotage Isolera rapid purification system.

[0194] Thin-layer chromatography separation and purification were performed using thin-layer chromatography silica gel plates (Meck aluminum plates (20cm x 20cm x 1mm) or Yantai GF 254).

[0195] The microwave reaction was performed using a Biotage Initiator+ (400W, RT~300℃) microwave reactor.

[0196] TLC or LCMS are commonly used for reaction monitoring. Commonly used developing solvent systems include dichloromethane / methanol, n-hexane / ethyl acetate, and petroleum ether / ethyl acetate. The volume ratio of the solvent is adjusted according to the polarity of the compound or by adding triethylamine, etc.

[0197] The silica gel used in column chromatography is generally 100-200 mesh. Commonly used eluent systems include dichloromethane / methanol and petroleum ether / ethyl acetate. The volume ratio of the solvent is adjusted according to the polarity of the compound, and a small amount of triethylamine can also be added for adjustment.

[0198] The reagents and solvents used in this invention were purchased from Aldrich Chemical Company, Amex, Bailingwei Technology, Shanghai Bid Pharmaceutical Technology Co., Ltd., Yaoshi Technology, and Shanghai Titan Technology Co., Ltd.

[0199] Synthesis Examples

[0200] Example 1 Synthesis of Compound 1

[0201] Step 1: At 25°C, concentrated sulfuric acid (0.50 mL) was added to a methanol (30 mL) solution of compound 1-1 (4.40 g, 20.09 mmol). The temperature was raised to 80°C, and the mixture was stirred for 12 hours. The reaction was monitored by LCMS until completion. The temperature was then lowered to 25°C. The reaction solution was concentrated under reduced pressure, neutralized with saturated sodium bicarbonate solution (50 mL), and extracted with ethyl acetate (50 mL × 3). The organic phases were combined, washed with saturated brine (50 mL), dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure to obtain compound 1-2. LCMS: m / z 234.2 [M+H] + .

[0202] Step 2: At 25°C, hydrogen peroxide (5.30 g, 33 wt%) was added to a solution of compounds 1-2 (4.00 g, 17.16 mmol) and trifluoroacetic anhydride (10.80 g, 51.42 mmol) in dichloromethane (60 mL). The mixture was stirred for 18 hours, and the reaction was monitored by LCMS until completion. The reaction solution was quenched with saturated sodium bicarbonate solution (50 mL) and then quenched with saturated sodium sulfite solution (50 mL). The mixture was extracted with dichloromethane (100 mL × 3), and the organic phases were combined. The mixture was washed with saturated brine (100 mL), dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 3:1) to obtain compounds 1-3. LCMS: m / z 249.9 [M+H] + .

[0203] Step 3: At 0°C, trifluoroacetic anhydride (5.06 g, 24.09 mmol) was added to a solution of compounds 1-3 (3.00 g, 12.04 mmol) in N,N-dimethylformamide (50 mL). The mixture was heated to 50°C and stirred for 1 hour. The reaction was monitored by LCMS until completion. The reaction solution was quenched with water (100 mL), extracted with ethyl acetate (100 mL × 3), and the organic phases were combined. The mixture was washed with saturated sodium bicarbonate solution (100 mL), then with saturated brine (100 mL), dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by solvent slurrying (petroleum ether:ethyl acetate = 8:1) to obtain compounds 1-4. LCMS: m / z 249.8 [M+H] + .

[0204] Step 4: At 25°C, potassium carbonate (1.66 g, 12.02 mmol) was added to a solution of compounds 1-4 (1.50 g, 6.02 mmol) and iodomethane (2.56 g, 18.02 mmol) in N,N-dimethylformamide (10 mL). The reaction mixture was stirred at 25°C for 3 hours, and the reaction was monitored by LCMS until completion. The reaction mixture was quenched with water (50 mL), extracted with ethyl acetate (50 mL × 3), and the organic phases were combined. The mixture was washed with saturated brine (50 mL), dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (petroleum ether:ethyl acetate = 1:1.5) to obtain compounds 1-5. LCMS: m / z 263.9 [M+H] + .

[0205] Step 5: At 25°C, compounds 1-5 (1.00 g, 3.79 mmol) were dissolved in tetrahydrofuran (10 mL), followed by the addition of lithium chloride (1.61 g, 37.87 mmol) and sodium borohydride (1.43 g, 37.87 mmol), and the mixture was stirred for 12 hours. The reaction was monitored by LCMS until completion. The reaction was quenched with water (20 mL), extracted with ethyl acetate (20 mL × 3), and the combined organic phases were washed with saturated brine (50 mL), dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure to obtain compounds 1-6. LCMS: m / z 237.8 [M+H] + .

[0206] Step 6: At 25°C, compounds 1-6 (350 mg, 1.48 mmol) were dissolved in dichloromethane (5 mL), followed by the sequential addition of triethylamine (0.41 mL, 2.97 mmol) and methanesulfonic anhydride (387 mg, 2.22 mmol), and the mixture was stirred for 2 hours. The reaction was monitored by LCMS until completion. The reaction was quenched with water (10 mL), and the mixture was extracted with dichloromethane (10 mL × 2). The combined organic phases were washed with saturated brine (20 mL), dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure to obtain compounds 1-7. LCMS: m / z 314.8 [M + H] + .

[0207] Step 7: At 25°C, potassium carbonate (389 mg, 2.82 mmol) was added to a solution of compounds 1-7 (590 mg, crude) and 1-8 (432 mg, 2.82 mmol) in N,N-dimethylformamide (10 mL). The mixture was heated to 50°C and stirred for 2 hours. The reaction was monitored by LCMS until completion. Water (10 mL) was added to quench the reaction. The mixture was extracted with ethyl acetate (10 mL × 3). The combined organic phases were washed with saturated brine (40 mL), dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated. The residue was purified by silica gel column chromatography (petroleum ether:ethyl acetate = 1:1) to obtain compounds 1-9. LCMS: m / z 337.0 [M+H] + .

[0208] Step 8: Dissolve compound 1-10 (200 mg, 0.61 mmol) in tetrahydrofuran (10 mL), purge with nitrogen three times, cool to -78 °C, and slowly add n-butyllithium-tetrahydrofuran solution (0.88 mL, 1.42 mmol, 1.6 M). Stir for 30 minutes, then add compound 1-11 (112 mg, 0.61 mmol) and stir for 2 hours. The reaction was monitored by LCMS until completion. The reaction solution was quenched with water (2 mL), filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 3:1) to obtain compound 1-12. LCMS: m / z 378.2 [M+H] + .

[0209] Step 9: Compounds 1-12 (100 mg, 0.27 mmol), compounds 1-9 (178 mg, 0.53 mmol), potassium carbonate (109 mg, 0.80 mmol), and tetrakis(triphenylphosphine)palladium (55 mg, 0.05 mmol) were dissolved in 1,4-dioxane (5 mL) and water (1 mL). Nitrogen gas was purged three times, the mixture was heated to 100 °C, and stirred for 3 hours. The reaction was monitored by LCMS until completion. The reaction mixture was extracted with water (20 mL) and ethyl acetate (20 mL × 3). The organic phases were combined, washed with saturated brine (20 mL), and dried over anhydrous sodium sulfate. The mixture was filtered, the filtrate was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 1:1) to give compounds 1-13. LCMS: m / z 508.3 [M+H] + .

[0210] Step 10: At 25°C, add 3 mL of dioxane hydrochloride solution (4 M) to compound 1-13 (75 mg, 0.15 mmol) and stir for 20 minutes. The reaction was monitored by LCMS until completion. The reaction solution was concentrated under reduced pressure to obtain compound 1-14 hydrochloride. LCMS: m / z 408.2 [M+H] + .

[0211] Step 11: At 25°C, methanesulfonic anhydride (19 mg, 0.11 mmol) was added to a solution of compound 1-14 hydrochloride (45 mg, crude product) and triethylamine (0.23 mL, 0.22 mmol) in dichloromethane (3 mL), and the mixture was stirred at 25°C for 20 minutes. The reaction was monitored by LCMS until completion. The reaction solution was quenched with water (5 mL), extracted with ethyl acetate (5 mL × 3), the organic phases were combined, washed with saturated brine (10 mL), and dried over anhydrous sodium sulfate. The mixture was filtered, the filtrate was concentrated under reduced pressure, and the residue was purified by preparative high-performance liquid chromatography (ammonia bicarbonate conditions) to obtain compound 1. LCMS: m / z 486.2 [M+H] + ; 1 H NMR (400MHz, CDCl3) δ: 8.54 (s, 1H), 7.91 (s, 1H), 7.57 (d, J = 9.6Hz, 1H), 7.25-7.20 (m, 4H), 4.29 (s, 1H), 4.14-4. 00(m,6H),3.95-3.87(m,2H),3.83(s,3H),3.02-2.94(m,2H),2.85(s,3H),2.34-2.24(m,3H),2.24-2.18(m,1H).

[0212] Following the synthesis method described in Example 1, the following compounds were synthesized.

[0213] Example 18 Synthesis of Compound 36

[0214] Step 1: Compound 36-1 (209 mg, 1 mmol) and palladium on carbon (105 mg, 0.1 mmol, 10%) were dissolved in isopropanol (5 mL) and stirred for 2 hours at 25 °C under a hydrogen atmosphere. The reaction mixture was filtered, and the filtrate was concentrated under reduced pressure to obtain compound 36-2. LCMS: m / z 211.9 [M+H] + .

[0215] Step 2: At 25°C, compound 36-2 (315 mg, 1.5 mmol) was dissolved in dichloromethane (5 mL), followed by the addition of triethylamine (0.4 mL, 3 mmol) and methanesulfonic anhydride (390 mg, 2.2 mmol), and the mixture was stirred for 2 hours. The reaction was monitored by LCMS until completion. The reaction was quenched with water (10 mL), extracted with dichloromethane (10 mL × 2), and the combined organic phases were washed with saturated brine (20 mL). The mixture was dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure to obtain compound 36-3. LCMS: m / z 289.9 [M + H] + .

[0216] Step 3: At 25°C, potassium carbonate (345 mg, 2.5 mmol) was added to a solution of compound 36-3 (530 mg, crude) and compound 1-8 (382 mg, 2.5 mmol) in N,N-dimethylformamide (10 mL). The temperature was raised to 50°C and stirred for 2 hours. The reaction was monitored by LCMS until completion. Water (10 mL) was added to quench the reaction, followed by extraction with ethyl acetate (10 mL × 3). The combined organic phases were washed with saturated brine (40 mL), dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated. The residue was purified by silica gel column chromatography (petroleum ether:ethyl acetate = 1:1) to obtain compound 36-4. LCMS: m / z 313.0 [M+H] + .

[0217] Step 4: Compounds 1-12 (113 mg, 0.3 mmol), 36-4 (160 mg, 0.5 mmol), potassium carbonate (110 mg, 0.80 mmol), and tetra(triphenylphosphine)palladium (55 mg, 0.05 mmol) were dissolved in 1,4-dioxane (5 mL) and water (1 mL). Nitrogen gas was purged three times, the mixture was heated to 100 °C, and stirred for 3 hours. The reaction was monitored by LCMS until completion. The reaction mixture was extracted with water (20 mL) and ethyl acetate (20 mL × 3). The organic phases were combined, washed with saturated brine (20 mL), and dried over anhydrous sodium sulfate. The mixture was filtered, the filtrate was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 1:1) to give compound 36-5. LCMS: m / z 484.2 [M+H] + .

[0218] Step 5: At 25°C, add 3 mL of hydrochloric acid-dioxane solution (4 M) to compound 36-5 (97 mg, 0.2 mmol) and stir for 20 minutes. The reaction was monitored by LCMS until completion. The reaction solution was concentrated under reduced pressure to obtain compound 36-6 hydrochloride. LCMS: m / z 384.2 [M+H] + .

[0219] Step 6: At 25°C, methanesulfonic anhydride (22 mg, 0.13 mmol) was added to a solution of compound 36-6 hydrochloride (50 mg, crude product) and triethylamine (0.3 mL, 0.28 mmol) in dichloromethane (3 mL), and the mixture was stirred at 25°C for 20 minutes. The reaction was monitored by LCMS until completion. The reaction solution was quenched with water (5 mL), extracted with ethyl acetate (5 mL × 3), and the organic phases were combined. The mixture was then washed with saturated brine (10 mL) and dried over anhydrous sodium sulfate. The mixture was filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by preparative high-performance liquid chromatography (ammonia bicarbonate conditions) to obtain compound 36. LCMS: m / z 462.2 [M+H]+ ;

[0220] Referring to the synthesis method of Example 18, the following compounds were synthesized by replacing the starting materials.

[0221] Biological test examples

[0222] Test Example 1: Inhibition of Pregnenolone Biosynthesis in NCI-H295R Cells (ELISA Method)

[0223] 1. Test Purpose

[0224] This experiment examined the inhibitory effect of the compound on cellular enolone biosynthesis, based on IC50. 50 The size of the compound disclosed in this invention was evaluated to assess its inhibitory effect on the CYP11A1 target.

[0225] II. Experimental Methods

[0226] NCI-H295R cells (Mingzhou Biotechnology, MZ-2138) were cultured in NCI-H295R complete medium (Mingzhou Biotechnology, MCM-0399).

[0227] NCI-H295R cells were seeded at a density of 5000 cells / well in a new 384-well cell culture plate (Greiner, 781091), with 45 μL of cell suspension per well. For the preparation of the test compound, 5 μL of a 10-fold concentration of the compound was added to each well, bringing the final concentration to a maximum of 10 μM. The compound was then diluted 3-fold, with 10 consecutive dilutions, resulting in a final DMSO concentration of 0.1%. The cells were centrifuged at 1000 rpm for 1 minute at room temperature and incubated at 37°C in a 5% CO2 cell culture incubator for 3 days.

[0228] Pregnenolone levels in cell culture supernatants were detected using the Pregnenolone ELISA kit (Abnova, KA1912). The reagents were brought to room temperature for 1 hour before the assay. The cell supernatant was removed from the 384-well plate and diluted 5-fold with the Assay Buffer provided in the kit. The competing molecule working solution and washing buffer were prepared according to the instructions. 50 μL of the cell supernatant dilution was added to each well of a 96-well plate provided with the ELISA kit, and 100 μL of the competing molecule working solution was added to each well. The plate was incubated at room temperature for 1.5 hours. The liquid was discarded, and each well was washed three times with 300 μL of washing buffer and dried. 150 μL of substrate chromogenic solution was added to each well, and the plate was incubated at room temperature for 10–15 minutes. 50 μL of stop solution was added to each well, and the plate was incubated at room temperature for 10–15 minutes. The absorbance at 450 nm was read using an Envision HTS Multilabel Reader.

[0229] III. Data Analysis

[0230] Wells containing 1 μM ODM-208 were defined as 100% inhibition (positive control), and wells containing a final concentration of 0.1% DMSO were defined as 0% inhibition (negative control). The inhibition rate was calculated as (test sample value - average negative control value) / (average positive control value - average negative control value) * 100%. The IC50 values ​​of the compounds were calculated using a four-parameter fitting technique with GraphPad Prism, and the results are shown in the table below.

[0231] The structure of ODM-208 is as follows

[0232] Tests showed that the compounds of this invention can effectively inhibit the conversion of cholesterol to pregnenolone in NCI-H295R cells, and some compounds have an IC50 assay. 50 <100 nM, for example, compound 1.

[0233] Test Example 2: PK Study

[0234] Test steps

[0235] 1. Laboratory animals

[0236] Six male / female ICR mice were randomly divided into two groups: one receiving oral administration and the other receiving intravenous administration, with three mice in each group. The mice were fasted for 10-14 hours prior to administration, but had free access to water.

[0237] 2. Preparation of drug formulations

[0238] Weigh the test compound according to the dosage and prepare an appropriate concentration of the drug preparation with solvent (% DMSO + 10% Solutol + 85% physiological saline) (administered intravenously and orally to mice at a volume of 5 mL / kg and 10 mL / kg, respectively). The intravenous injection is a clear solution, and the oral preparation is a clear solution or a homogeneous suspension.

[0239] 3. Animal drug administration and blood sample collection

[0240] Animals were administered the drug via intravenous injection and oral gavage. Blood samples were collected at 0.033, 0.083, 0.25, 0.5, 1, 2, 4, 8, and 24 hours after intravenous administration, and at the same time after oral administration. Whole blood was centrifuged at 6800g for 6 minutes at 4°C, and the supernatant plasma was collected and stored at -80°C for analysis.

[0241] 4. Plasma sample testing

[0242] Dilute the DMSO stock solution of the analyte with methanol or acetonitrile to prepare a series of working solutions, add them to the blank plasma matrix, and prepare a standard curve and quality control samples. Take an appropriate volume of plasma sample and add an appropriate amount of methanol or acetonitrile containing internal standard according to the response to precipitate proteins. Centrifuge all samples at 4°C, 18000g for 10 min, and take an appropriate amount of supernatant for LC-MS / MS analysis.

[0243] 5. Parameter Calculation

[0244] Based on the test concentration, a blood drug concentration-time curve was plotted. Using WinNonlin software, pharmacokinetic parameters were calculated according to a non-compartmental model, including: half-life (T1 / 2), area under the curve (AUC0-t), clearance (CL), steady-state volume of distribution (Vss), and bioavailability (F).

[0245] Tests have shown that the compounds disclosed herein have good pharmacokinetic parameters, and the pharmacokinetic (PK) of some compounds is significantly better than that of *Gynostemma pentaphyllum*.

[0246] For example, at an oral dose of 5 mpk, the Cmax of *Codonopsis pilosula* was 807 (ng / ml), the AUC was 1309 (ng / ml*h), and the bioavailability F was 59%. The Cmax of compound 1 of the present invention was 1632 (ng / ml), the AUC was 3444 (ng / ml*h), and the bioavailability F was 98%.

[0247] Test Example 3: Compound Stability Experiment

[0248] Objective: To test the chemical stability of the compounds of this invention.

[0249] Experimental Procedure: 1 mg of each analyte was weighed and processed as shown in Table 1. The purity of the compounds was tested before and after processing to determine their stability under different conditions. Compound purity was analyzed using reversed-phase high-performance liquid chromatography (HPLC). Measurement Conditions: SUIMADZU HPLC (LC-2030Plus), Waters Sunfire C18 column (3.5 μm, 4.6 × 100 mm), UV detection bands of 220 and 254 nm, elution conditions of 5-95% acetonitrile (containing 0.05%-0.1% v / v formic acid or trifluoroacetic acid or ammonium bicarbonate), flow rate of 1.8 mL / min.

[0250] Tests have shown that at least some of the compounds of this invention exhibit good stability.

[0251] Test Example 4: In vivo pharmacodynamic study of the test product in a VCaP-resistant castration-resistant prostate cancer subcutaneous xenograft model

[0252] Experimental objective: To evaluate the pharmacological and pharmacodynamic effects of the compounds of this invention in a VCaP-resistant subcutaneous prostate cancer xenograft model.

[0253] Experimental materials: Male SCID-Beige mice, 6-8 weeks old or 18-22g, were provided by Vital River Laboratory Animal Technology Co., Ltd.

[0254] Experimental Methods: All experimental animals were housed in a specific pathogen-free (SPF) barrier facility. Experiments began after 3 days of acclimatization. VCaP tumor cells were cultured in DMEM complete medium (supplemented with 10% fetal bovine serum and 1% penicillin & streptomycin) at 37°C in air containing 5% CO2. Tumor cells were routinely passaged 2-3 times per week. Cells in the exponential growth phase were collected and counted for tumor cell seeding. 10 x 10⁶ VCaP tumor cells were resuspended in 0.1 ml of... The solution was mixed with 0.1 ml of matrigel in PBS and injected subcutaneously into the right side of each mouse to induce tumor formation. When the average tumor volume of the tumor-bearing mice reached approximately 200 mm³, castration was performed. One week after castration, the tumor volume of all mice was measured, and suitable tumor-bearing mice were randomly assigned to the following groups: blank control group, prednisone (0.6 mg / kg, QD), and abiraterone (33.73 mg / kg, QD) + prednisone (0.6 mg / kg, QD). The study included three groups: ODM-208 (30 mg / kg, BID) + prednisone (0.6 mg / kg, QD), and the compound of this invention (30 mg / kg, BID) + prednisone (0.6 mg / kg, QD). The blank control group was orally administered solvent (0.5% MC + 0.5% Tween 80 and 0.5% CMCNa), while other groups were orally administered the corresponding compound. The treatment lasted for 32 days. During the experiment, the tumor volume and animal weight of each group were monitored twice a week.

[0255] Tests have shown that at least some of the compounds of this invention exhibit good tumor proliferation inhibitory activity in a VCaP castration-resistant prostate cancer subcutaneous xenograft model.

[0256] Test Example 5: Detection of testosterone, progesterone, and adrenaline concentrations in mouse tumors and adrenal glands using LC-MS

[0257] Experimental materials:

[0258] tissue sample homogenate:

[0259] Mouse tumors were homogenized using PBS at a ratio of 1:5 (tumor weight (g): PBS volume (mL), w / v).

[0260] Mouse adrenal glands were homogenized using PBS at a ratio of 1:10 (adrenal gland weight (g): PBS volume (mL), w / v).

[0261] Standards: Testosterone (LGC, C17322500), progesterone (MCE, HY-N0437) and adrenaline (MCE, HY-B1618).

[0262] Experimental method: Testosterone, progesterone and adrenaline are all endogenous substances, and these markers are also present in the blank matrix. Therefore, PBS was used as an alternative matrix to prepare the standard curve.

[0263] Testosterone: Testosterone concentrations in mouse tumors and adrenal glands were detected using a multiple reaction detection (MRM) method. Mass spectrometry: AB Sciex Triple Quad 6500+; Liquid chromatography: Shimadzu 40A; Column: Waters XBridge BEH C18 2.5µm 2.1*50mm; Testosterone ion pair: 289.4 / 97.2. Methanol was used as the precipitant for both tumor and adrenal tissue samples, and tolbutamide was used as an internal standard for sample pretreatment. The linear range was 50–50,000 pg / mL.

[0264] Progesterone and adrenaline: The concentrations of testosterone and adrenaline in mouse tumors and adrenal glands were detected using a multiple reaction detection (MRM) method. Mass spectrometry: AB Sciex Triple Quad 6500+; Liquid chromatography: Shimadzu 40A; Column: Waters XSelect HSS T3 2.5um 2.1*50mm; Progesterone ion pair: 315.4 / 97.2; Adrenaline ion pair: 347.4 / 121.3. For tumor tissue, acetonitrile was used as the precipitant, and propranolol / diclofenac was used as the internal standard for sample pretreatment. The linear range was: progesterone 0.05-10 ng / mL, adrenaline 0.10-20 ng / mL. For adrenal tissue, methanol was used as the precipitant, and propranolol / diclofenac was used as the internal standard for sample pretreatment. The linear range was: progesterone 5-2500 ng / mL, adrenaline 5-2500 ng / mL.

[0265] Conclusion: Tests showed that some of the compounds of this invention significantly inhibited the secretion of testosterone, progesterone, and adrenaline in mouse tumors and adrenal glands in a VCaP castration-resistant prostate cancer subcutaneous xenograft model.

[0266] Test Example 6: hERG Test

[0267] I. Experimental Methods:

[0268] The cells used in this experiment were HEK293 cell lines (#60187, provided by BPS, with P3-P23 cells used as substitutes for the experimental research) transfected with hERG cDNA and stably expressing the hERG channel. Cell culture was conducted in a medium containing the following components: MEM medium, 10% (v / v) inactivated fetal bovine serum, 1 mM sodium pyruvate, 500 μg / ml genimycin, 0.1 mM non-essential amino acids, and 100 U / ml penicillin / streptomycin. HEK293 hERG cells were grown in culture dishes containing the above medium and cultured at 37°C in a 5% CO2 incubator, passaged approximately three times per week, maintaining cell confluence between 40% and 80%. 24 to 48 hours before electrophysiological experiments, HEK293 hERG cells were transferred to slides pretreated with 0.05 mg / ml PDL and placed in 48-well plates at a density of 1 × 10⁴ cells, and grown under the same medium and conditions. The density of HEK293 hERG cells on each circular slide needs to be such that the vast majority of cells are independent and singular. The extracellular fluid composition (mM) used in the hERG assay is as follows: 145 NaCl, 4 KCl, 2 CaCl2, 1 MgCl2, 10 glucose, and 10 HEPES (pH adjusted to 7.40 using NaOH). The intracellular fluid composition (mM) is as follows: 130 KCl, 2 MgCl2, 5 EGTA, 10 HEPES, and 5 Na2ATP (pH adjusted to 7.25 using KOH). To obtain the IC50 of the compound, tests were performed at the following concentrations (30, 10, 3, 1, 0.3, and 0.1 μM) (the test concentration can be adjusted appropriately if the compound has a strong effect). Before the assay, stock solutions were first serially diluted with DMSO to 10, 3, 1, 0.3, and 0.1 mM, and then diluted with extracellular fluid to the final μM test concentration. The final concentration of DMSO in each compound solution ranged from 0.1% to 0.3%. All compound solutions were subjected to standard sonication and thorough shaking for 5 to 10 minutes to ensure complete dissolution of the compounds, and all test solutions were mixed by rotation for at least 10 minutes.

[0269] Electrophysiological experiments were performed using a manual patch-clamp system (HEKA EPC-10 signal amplifier and digital conversion system, HEKA Electronics, Germany) to record whole-cell currents. The specific testing method is described below: A circular slide with CHO hERG cells grown on its surface was placed in an electrophysiological recording chamber under an inverted microscope. The recording chamber was continuously perfused with extracellular fluid (approximately 1 ml per minute). The experiment employed standard whole-cell patch-clamp current recording techniques. Unless otherwise specified, experiments were conducted at normal room temperature (~25°C). Cells were clamped at -80 mV. The cell clamping voltage was depolarized to +30 mV to activate hERG potassium channels, and after 5 seconds, it was clamped again to -50 mV to eliminate inactivation and generate a tail current. The peak value of the tail current was used as the magnitude of the hERG current. After the hERG potassium current recorded in the above steps stabilized under continuous extracellular fluid perfusion in the recording chamber, the drug to be tested could be continuously perfused until the inhibitory effect of the drug on the hERG current reached a stable state. Generally, the overlap of the three most recent consecutive current recording lines is used as the standard for judging whether a stable state has been reached.

[0270] II. Data Analysis

[0271] The dose-response curves of the test compounds were plotted with the %hERG inhibition rate on the vertical axis and the concentration of the test compounds on the horizontal axis, and the IC50 was calculated.

[0272] Tests showed that the compounds of this invention had no significant inhibitory effect on hERG; for example, the IC50 of compound 1 was greater than 10 μM.

[0273] While some exemplary embodiments of this application have been described and illustrated, this application is not limited to the disclosed embodiments. Rather, those skilled in the art will recognize that modifications and changes may be made to the described embodiments without departing from the spirit and scope of this application as described in the appended claims.

Claims

1. A compound of formula (I), or a stereoisomer, tautomer, diastereomer, racemate, cis-trans isomer, isotopically labeled compound (preferably deuterated), N-oxide, metabolite, ester, prodrug, crystal form, hydrate, solvate, or pharmaceutically acceptable salt thereof: in: Ring A is a 4-12 membered heterocyclic group; wherein the heteroatoms in the 4-12 membered heterocyclic group are selected from N, O and S, and the number of heteroatoms is 1, 2, 3 or 4; Each R a Each can be independently represented by hydrogen, deuterium, halogen, cyano, nitro, hydroxyl, amino, mercapto, oxo, or -C(O)-R. a1 、-(CR a2 R a3 ) p -C(=O)-OR a4 -C(=O)-NR a5 R a6 -C(=NR) a7 )-(R a8 -S(O)2-R a9 -S(O)2-NR a10 R a11 -NR a12 S(O)2-R a13 -P(=O)-R a14 R a15 The C1-6 alkyl, C2-6 alkenyl, C1-6 alkoxy, C1-6 alkylthio, -NH(C1-6 alkyl), -N(C1-6 alkyl)2, C3-10 cycloalkyl, 3-10 heterocyclic group may be substituted with one or more substituents selected from deuterium, halogen, cyano, hydroxyl, amino, oxo, C1-6 alkyl, C2-6 alkenyl, C1-6 alkoxy, C1-6 alkylthio, -NH(C1-6 alkyl), -N(C1-6 alkyl)2, C3-6 cycloalkyl, 3-10 heterocyclic group, C6-10 aryl, 5-10 heteroaryl group; R a1 R a2 R a3 R a4 R a5 R a6 R a7 R a8 R a9 R a10 R a11 R a12 R a13 R a14 R a15 Each is independently hydrogen, C1-6 alkyl, C2-6 alkenyl, C2-6 ynyl, C3-10 cyclic hydrocarbon, 3-10 heterocyclic, C6-10 aryl, 5-10 heteroaryl, or R a5 and R a6 and the N atoms and R atoms connected to them a10 and R a11 The N atoms attached to them form 4-7 membered heterocyclic groups, namely C1-6 alkyl, C2-6 alkenyl, C2-6 ynyl, C3-10 cyclic hydrocarbon, 3-10 membered heterocyclic group, C6-10 aryl, 5-10 membered heteroaryl, or R a5 and R a6 and the N atoms and R atoms connected to them a10 and R a11 The N atoms connected to them form 4-7 membered heterocyclic groups, which may be optionally substituted by one or more substituents selected from deuterium, halogen, cyano, hydroxyl, amino, oxo, C1-6 alkyl, C1-6 alkoxy, -NH(C1-6 alkyl), -N(C1-6 alkyl)2; Ring B is a 5-6 membered heteroaryl group; Each R b Each of these can be independently hydrogen, deuterium, halogen, cyano, hydroxyl, amino, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, -NH(C1-6 alkyl), -N(C1-6 alkyl)2; The ring C is C6-10 aryl, 5-10 heteroaryl, or 5-12 heterocyclic. Each R c Each can be independently represented by hydrogen, deuterium, halogen, cyano, nitro, hydroxyl, amino, mercapto, oxo, or -C(O)NR. c1 R c2 -C(O)R c3 -S(O)2R c4 C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkylthio, -NH (C1-6 alkyl), -N (C1-6 alkyl)2, C3-10 cycloalkyl, C3-10 cycloalkyloxy, 3-10 heterocyclic, C6-10 aryl, 5-10 heteroaryl, or two adjacent R groups c Together with the ring atoms they are attached to, they form a 5-6 membered ring; the C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkylthio, -NH(C1-6 alkyl), -N(C1-6 alkyl)2, C3-10 cycloalkyl, C3-10 cycloalkyloxy, 3-10 heterocyclic, C6-10 aryl, 5-10 heteroaryl, or two adjacent R groups c Together with the ring atoms they are attached to, they form a 5-6 membered ring which may be optionally substituted by one or more substituents selected from deuterium, halogen, cyano, hydroxyl, amino, oxo, C1-6 alkyl, C1-6 alkoxy, C3-6 cycloalkyl, 3-10 heterocyclic, C6-10 aryl, and 5-10 heteroaryl. R c1 R c2 R c3 R c4 Each is independently selected from hydrogen, C1-6 alkyl, C1-6 alkoxy, C3-10 cycloalkyl, or R c1 R c2 Together with the N atoms attached to them, they form 4-7 membered heterocyclic groups; the C1-6 alkyl, C1-6 alkoxy, C3-10 cycloalkyl, or R c1 R c2 Together with the N atoms attached to them, they form 4-7 membered heterocyclic groups, which may be optionally replaced by one or more groups selected from deuterium, halogen, hydroxyl, amino, oxo, C1-6 alkyl, C1-6 alkoxy, and C3-10 cycloalkyl. R 1 R 2 Each is independently selected from hydrogen, deuterium, halogen, C1-6 alkyl, C1-6 haloalkyl, C1-6 deuteralkyl, C1-6 alkoxy, C1-6 haloalkoxy, or R 1 R 2 Together with the carbon atoms they are attached to, they form 3-10 membered rings; Ring D is a 9-10 membered heterocyclic group or a 9-10 membered heteroaryl group; Each R d Each is independently selected from hydrogen, deuterium, halogen, cyano, nitro, hydroxyl, mercapto, oxo, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C1-6 alkylthio, -NH(C1-6 alkyl), -N(C1-6 alkyl)2, hydroxyC1-6 alkyl, -C(O)(C1-6 alkyl), -C(O)O(C1-6 alkyl), -S(O)(C1-6 alkyl), -S(O)2(C1-6 alkyl), C3-10 cycloalkyl, 3-10 heterocyclic, C6-10 aryl, 5-10 heteroaryl; a can be 0, 1, 2, 3, 4, 5, or 6; p is 0, 1, 2, 3 or 4; b can be 0, 1, 2, or 3; c can be 0, 1, 2, 3, 4, 5, or 6; d can be 0, 1, 2, 3 or 4.

2. The compound of formula (I) according to claim 1, or its stereoisomers, tautomers, diastereomers, racemic derivatives, cis-trans isomers, isotopically labeled compounds (preferably deuterated), N-oxides, metabolites, esters, prodrugs, crystal forms, hydrates, solvates, or pharmaceutically acceptable salts, wherein, Each R a Each can be independently represented by hydrogen, deuterium, halogen, cyano, hydroxyl, amino, mercapto, oxo, or -C(O)-R. a1 、-(CR a2 R a3 ) p -C(=O)-OR a4 -C(=O)-NR a5 R a6 -C(=NR) a7 )-(R a8 -S(O)2-R a9 -S(O)2-NR a10 R a11 -NR a12 S(O)2-R a13 -P(=O)-R a14 R a15 C1-4 alkyl, C2-4 alkenyl, C1-4 alkoxy, C1-4 alkylthio, -NH(C1-4 alkyl), -N(C1-4 alkyl)2, C3-6 cycloalkyl, C5-10 cycloalkenyl, 3-10 membered heterocyclic groups; wherein the C1-4 alkyl, C2-4 alkenyl, C1-4 alkoxy, C1-4 alkylthio, -NH(C1-4 alkyl), -N(C1-4 alkyl)2, C3-6 cycloalkyl, C The 5-10 cycloalkenyl or 3-10 heterocyclic group is optionally substituted by one or more substituents selected from deuterium, halogen, cyano, hydroxyl, amino, oxo, C1-4 alkyl, C2-4 alkenyl, C1-4 alkoxy, C1-4 alkylthio, -NH(C1-4 alkyl), -N(C1-4 alkyl)2, C3-6 cycloalkyl, 3-10 heterocyclic, C6-10 aryl, and 5-10 heteroaryl; provided that at least one R a Selected from oxo groups, -C(O)-R a1 、-(CR a2 R a3 ) p -C(=O)-OR a4 -C(=O)-NR a5 R a6 -C(=NR) a7 )-(R a8 -S(O)2-R a9 -S(O)2-NR a10 R a11 -NR a12 S(O)2-R a13 -P(=O)-R a14 R a15 ; R a1 R a2 R a3 R a4 R a5 R a6 R a7 R a8 R a9 R a10 R a11 R a12 R a13 R a14 R a15 Each of the following is independently hydrogen, C1-4 alkyl, C2-4 alkenyl, C2-4 ynyl, C3-6 cycloalkyl, C5-10 cycloalkenyl, 3-10 heterocyclic, C6-10 aryl, 5-10 heteroaryl, or R a5 and R a6 and the N atoms and R atoms connected to them a10 and R a11 The N atoms attached to them form 4-7 membered saturated or partially saturated heterocyclic groups, namely C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, C3-6 cycloalkyl, C5-10 cycloalkenyl, 3-10 membered heterocyclic groups, C6-10 aryl, 5-10 membered heteroaryl, or R a5 and R a6 and the N atoms and R atoms connected to them a10 and R a11 The N atoms connected to them form 4-7 member saturated or partially saturated heterocyclic groups, which may be optionally substituted by one or more substituents selected from deuterium, halogen, cyano, hydroxyl, amino, oxo, C1-4 alkyl, C1-4 alkoxy, -NH (C1-4 alkyl), -N (C1-4 alkyl)2; Preferably, each R a Each of these groups can be independently represented as hydrogen, deuterium, F, Cl, Br, cyano, hydroxyl, amino, mercapto, oxo, or -C(O)-R. a1 -C(=O)-OR a4 -C(=O)-NR a5 R a6 -C(=NR) a7 )-(R a8 -S(O)2-R a9 -S(O)2-NR a10 R a11 -NR a12 S(O)2-R a13 -P(=O)-R a14 R a15 C1-4 alkyl, C1-4 alkoxy, C1-4 alkylthio, -NH(C1-4 alkyl), -N(C1-4 alkyl)2, C3-6 cycloalkyl, 4-7 membered heterocyclic group; wherein the C1-4 alkyl, C1-4 alkoxy, C1-4 alkylthio, -NH(C1-4 alkyl), -N(C1-4 alkyl)2, C3-6 cycloalkyl, 4-7 membered heterocyclic group is optionally substituted by one or more substituents selected from deuterium, halogen, cyano, hydroxyl, amino, oxo, C1-4 alkyl, C1-4 alkoxy, C1-4 alkylthio, -NH(C1-4 alkyl), -N(C1-4 alkyl)2; provided that at least one R a Selected from oxo groups, -C(O)-R a1 -C(=O)-OR a4 -C(=O)-NR a5 R a6 -C(=NR) a7 )-(R a8 -S(O)2-R a9 -S(O)2-NR a10 R a11 -NR a12 S(O)2-R a13 -P(=O)-R a14 R a15 ; R a1 R a4 R a5 R a6 R a7 R a8 R a9 R a10 R a11 R a12 R a13 R a14 R a15 Each of the following is independently hydrogen, C1-4 alkyl, C2-4 alkenyl, C3-6 cycloalkyl, 4-7 heterocyclic, phenyl, 5-6 heteroaryl, or R a5 and R a6 and the N atoms and R atoms connected to them a10 and R a11 The N atoms attached to them form 4-6 membered saturated or partially saturated heterocyclic groups, namely C1-4 alkyl, C2-4 alkenyl, C3-6 cycloalkyl, 4-7 membered heterocyclic group, phenyl, 5-6 membered heteroaryl, or R a5 and R a6 and the N atoms and R atoms connected to them a10 and R a11 The N atoms connected to them form 4-6 member saturated or partially saturated heterocyclic groups, which may be optionally substituted by one or more substituents selected from deuterium, halogen, cyano, hydroxyl, amino, oxo, C1-4 alkyl, C1-4 alkoxy, -NH (C1-4 alkyl), -N (C1-4 alkyl)2; Preferably, R a Each of these groups is independently hydrogen, deuterium, F, Cl, Br, cyano, hydroxyl, amino, oxo, -C(O)-(C1-4 alkyl), -C(O)-(C1-4 haloalkyl), -C(O)-(C1-4 alkyl)-CN, -C(O)-(C3-6 cycloalkyl), -C(=O)-OC1-4 alkyl, -C(=O)-OC3-6 cycloalkyl, -S(O)2-(C1-C4 alkyl), -S(O)2-(C1-C4 haloalkyl), -S(O)2-(C2-C4 alkenyl), -S(O)2-(C3-6 cycloalkyl), -S(O)2-phenyl-C1-4 alkyl. -S(O)2-5-6 heteroaryl, -C(=O)-NH(C1-4 alkyl), -C(=NH)(C1-4 alkyl), -P(=O)(C1-C4 alkyl)2, -NHS(O)2-(C1-C4 alkyl), C1-4 alkyl, C1-4 alkoxy, -NH(C1-4 alkyl), -N(C1-4 alkyl)2; wherein the C1-4 alkyl, C1-4 alkoxy, -NH(C1-4 alkyl), -N(C1-4 alkyl)2 is optionally substituted by one or more substituents selected from deuterium, halogen, cyano, hydroxyl, amino, oxo, C1-4 alkyl; provided that at least one R a Selected from -C(O)-(C1-4 alkyl), -C(O)-(C1-4 haloalkyl), -C(O)-(C1-4 alkyl)-CN, -C(O)-(C3-6 cycloalkyl), -C(=O)-OC1-4 alkyl, -C(=O)-OC3-6 cycloalkyl, -S(O)2-(C1-C4 alkyl), -S(O)2-(C1-C4 haloalkyl), -S(O)2-(C2-C4 alkenyl), -S(O)2-(C3-6 cycloalkyl), -S(O)2-phenyl-C1-4 alkyl, -S(O)2-5-6 heteroaryl, -C(=O)-NH(C1-4 alkyl), -C(=NH)(C1-4 alkyl), -P(=O)(C1-C4 alkyl)2, -NHS(O)2-(C1-C4 alkyl); Preferably, R a Selected from -C(O)-R a1 or -S(O)2-R a9 Preferably, R a Selected from -S(O)2-R a9 ; Preferably, R a1 Selected from C1-6 alkyl, C1-6 haloalkyl, cyanoC1-6 alkyl, or C3-6 cycloalkyl; preferably, R a1 Selected from C1-6 alkyl or cyanoC1-6 alkyl-; Preferably, R a9 Selected from C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C3-6 cycloalkyl, phenyl, 5-6 heteroaryl; wherein the phenyl and 5-6 heteroaryl groups are optionally substituted with one or more halogens or C1-6 alkyl groups; preferably, R a9 Selected from C1-6 alkyl groups; preferably, R a Selected from Preferably, R a Selected from 3. The compound of formula (I) according to any one of claims 1-2, or its stereoisomers, tautomers, diastereomers, racemic derivatives, cis-trans isomers, isotopically labeled compounds (preferably deuterated), N-oxides, metabolites, esters, prodrugs, crystal forms, hydrates, solvates, or pharmaceutically acceptable salts, in, Ring A is a 4-12 membered heterocyclic group; wherein the heteroatoms in the 4-12 membered heterocyclic group are selected from N, O and S, and the number of heteroatoms is 1, 2, 3 or 4, wherein at least one heteroatom is N; Preferably, ring A is a 4-7 member monocyclic heterocyclic group, a 7-12 member bridged ring heterocyclic group, a 6-12 member fused bicyclic heterocyclic group, or a 7-12 member spirocyclic heterocyclic group; wherein the heteroatoms in the 4-7 member monocyclic heterocyclic group, the 7-12 member bridged ring heterocyclic group, the 6-12 member fused bicyclic heterocyclic group, or the 7-12 member spirocyclic heterocyclic group are selected from N, O, and S, and the number of heteroatoms is 1, 2, or 3, wherein at least one heteroatom is N; Preferably, ring A is Preferably, ring A is selected from 4. The compound of formula (I) according to any one of claims 1-3, or its stereoisomers, tautomers, diastereomers, racemic derivatives, cis-trans isomers, isotopically labeled compounds (preferably deuterated), N-oxides, metabolites, esters, prodrugs, crystal forms, hydrates, solvates, or pharmaceutically acceptable salts, in, Selected from a1 is 0, 1, 2, 3, 4 or 5; Preferably, Selected from a1 is 0, 1, 2, 3 or 4; a2 is 0, 1 or 2; a3 is 0, 1 or 2; Preferably, Selected from a1 is 0, 1, 2, 3, or 4; preferably, a1 is 0, 1, or 2; more preferably, a1 is 0; a2 is 0, 1, or 2; a3 is 0, 1, or 2; preferably, a2 is 0 and a3 is 0; wherein, each R a Each of the following is independently substituted with hydrogen, deuterium, halogen, cyano, hydroxyl, amino, mercapto, oxo, C1-6 alkyl, C2-6 alkenyl, C1-6 alkoxy, C1-6 alkylthio, -NH(C1-6 alkyl), or -N(C1-6 alkyl)2; wherein the C1-6 alkyl, C2-6 alkenyl, C1-6 alkoxy, C1-6 alkylthio, -NH(C1-6 alkyl), or -N(C1-6 alkyl)2 is optionally substituted with one or more substituents selected from deuterium, halogen, cyano, hydroxyl, amino, oxo, C1-6 alkyl, C2-6 alkenyl, C1-6 alkoxy, C1-6 alkylthio, -NH(C1-6 alkyl), or -N(C1-6 alkyl)2; Preferably, each R a Each of the following is independently hydrogen, F, Cl, Br, cyano, hydroxyl, amino, oxo, C1-4 alkyl, C1-4 alkoxy, -NH(C1-4 alkyl), -N(C1-4 alkyl)2; wherein the C1-4 alkyl, C1-4 alkoxy, -NH(C1-4 alkyl), -N(C1-4 alkyl)2 is optionally substituted by one or more substituents selected from deuterium, halogen, cyano, hydroxyl, amino, oxo, C1-4 alkyl, C1-4 alkoxy, -NH(C1-4 alkyl), -N(C1-4 alkyl)2; Preferably, each R a Each of these can be independently represented as hydrogen, F, Cl, Br, cyano, ethyl cyano, hydroxyl, amino, oxo, methyl, ethyl, methoxy, ethoxy, fluoromethyl, fluoroethyl, fluoromethoxy, fluoroethoxy, methylamino, and dimethylamino. Preferably, Selected from Preferably, Selected from Preferably, Selected from Preferably, Selected from Preferably, Selected from Preferably, Selected from More preferably, Selected from 5. The compound of formula (I) according to any one of claims 1-4, or its stereoisomers, tautomers, diastereomers, racemic derivatives, cis-trans isomers, isotopically labeled compounds (preferably deuterated), N-oxides, metabolites, esters, prodrugs, crystal forms, hydrates, solvates, or pharmaceutically acceptable salts, in, Ring B is a 5-membered heteroaryl group; Preferably, ring B is Preferably, ring B is Preferably, ring B is The key marked with "#" is connected to ring A, and the key marked with "$" is connected to ring C.

6. The compound of formula (I) according to any one of claims 1-5, or its stereoisomers, tautomers, diastereomers, racemic derivatives, cis-trans isomers, isotopically labeled compounds (preferably deuterated), N-oxides, metabolites, esters, prodrugs, crystal forms, hydrates, solvates, or pharmaceutically acceptable salts, wherein, Each R b Each of these can be independently hydrogen, deuterium, halogen, cyano, hydroxyl, amino, C1-4 alkyl, C1-4 alkoxy, C1-4 haloalkyl, C1-4 haloalkoxy, -NH(C1-4 alkyl), -N(C1-4 alkyl)2; Preferably, R b Each of these can be independently represented as hydrogen, deuterium, F, Cl, Br, cyano, hydroxyl, amino, methyl, ethyl, methoxy, ethoxy, fluoromethyl, fluoroethyl, fluoromethoxy, fluoroethoxy, methylamino, ethylamino, and dimethylamino. b is 0, 1, or 2; preferably, b is 0 or 1; more preferably, b is 0.

7. The compound of formula (I) according to any one of claims 1-6, or its stereoisomers, tautomers, diastereomers, racemic derivatives, cis-trans isomers, isotopically labeled compounds (preferably deuterated), N-oxides, metabolites, esters, prodrugs, crystal forms, hydrates, solvates, or pharmaceutically acceptable salts, wherein, The ring C is C6-10 aryl, 5-10 heteroaryl, or 5-10 heterocyclic; the heteroatoms in the 5-10 heteroaryl and 5-10 heterocyclic groups are selected from N, O, and S, and the number of heteroatoms is 1, 2, 3, or 4. Preferably, ring C is Preferably, ring C is Preferably, ring C is 8. The compound of formula (I) according to any one of claims 1-7, or its stereoisomers, tautomers, diastereomers, racemic derivatives, cis-trans isomers, isotopically labeled compounds (preferably deuterated), N-oxides, metabolites, esters, prodrugs, crystal forms, hydrates, solvates, or pharmaceutically acceptable salts, in, R c Each can be independently represented by hydrogen, deuterium, halogen, cyano, nitro, hydroxyl, amino, mercapto, oxo, or -C(O)NR. c1 R c2 -C(O)R c3 -S(O)2R c4 C1-4 alkyl, C1-4 alkoxy, C2-4 alkenyl, C2-4 alkynyl, C1-4 alkylthio, -NH(C1-4 alkyl), -N(C1-4 alkyl)2, C3-6 cycloalkyl, C5-10 cycloalkenyl, C3-6 cycloalkoxy, 4-7 membered heterocyclic, C6-10 aryl, 5-10 membered heteroaryl, or two adjacent R groups. c Together with the ring atoms they are attached to, they form a 5-6 membered carbon ring or heterocycle; the C1-4 alkyl, C1-4 alkoxy, C2-4 alkenyl, C2-4 alkynyl, C1-4 alkylthio, -NH(C1-4 alkyl), -N(C1-4 alkyl)2, C3-6 cycloalkyl, C5-10 cycloalkenyl, C3-6 cycloalkoxy, 4-7 membered heterocyclic, C6-10 aryl, 5-10 membered heteroaryl, or two adjacent R groups. c Together with the ring atoms attached to them, they form a 5-6 membered carbon ring or heterocycle, which may be optionally substituted by one or more substituents selected from deuterium, halogen, cyano, hydroxyl, amino, oxo, C1-4 alkyl, C1-4 alkoxy, C3-6 cycloalkyl, 4-7 membered heterocyclic, C6-10 aryl, and 5-10 membered heteroaryl. R c1 R c2 R c3 R c4 Each is independently selected from hydrogen, C1-4 alkyl, C1-4 alkoxy, C3-6 cycloalkyl, or R c1 R c2 Together with the N atoms attached to them, they form 4-7 membered heterocyclic groups; the C1-4 alkyl, C1-4 alkoxy, C3-6 cycloalkyl, or R c1 R c2 Together with the N atoms attached to them, they form 4-7 membered heterocyclic groups, which may be optionally replaced by one or more groups selected from deuterium, halogen, hydroxyl, amino, oxo, C1-4 alkyl, C1-4 alkoxy, and C3-6 cycloalkyl. Preferably, R c Each of these groups is independently hydrogen, deuterium, halogen, cyano, hydroxyl, amino, mercapto, oxo, C1-4 alkyl, C1-4 alkoxy, C2-4 alkenyl, C1-4 alkylthio, -NH(C1-4 alkyl), -N(C1-4 alkyl)2, C3-6 cycloalkyl, C3-6 cycloalkoxy, 4-7 membered heterocyclic, C1-4 haloalkyl, C1-4 haloalkoxy, C1-4 deuterated alkyl, C3-6 cycloalkyl, C1-4 alkylene-; Preferably, R c Each of these can be independently halogen, C1-6 alkyl, C1-6 haloalkyl, C1-6 deuterated alkyl, C3-6 cycloalkyl, 4-7 heterocyclic alkyl, C3-6 cycloalkyl, C1-4 alkyl-; Preferably, R c Each is independently a halogen, a C1-4 alkyl, a C1-4 haloalkyl, or a C1-4 deuterated alkyl; Preferably, R c Each of these groups can be independently hydrogen, F, Cl, Br, cyano, hydroxyl, oxo, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, cyclopropyl, oxetane, azirone, cyclopropylmethylene, methoxy, trifluoromethoxy, difluoromethoxy, monofluoromethoxy, ethoxy, isopropoxy, cyclopropoxy, vinyl, propenyl, methylthio, fluoromethyl (e.g., monofluoromethyl, difluoromethyl, trifluoromethyl), fluoroethyl (e.g., -CH2CF3, -CH2CHF2), deuterated methyl (e.g., -CDH2, -CD2H, -CD3).

9. The compound of formula (I) according to any one of claims 1-8, or its stereoisomers, tautomers, diastereomers, racemic derivatives, cis-trans isomers, isotopically labeled compounds (preferably deuterated), N-oxides, metabolites, esters, prodrugs, crystal forms, hydrates, solvates, or pharmaceutically acceptable salts, in, Selected from Where c is 0, 1, 2, 3, or 4; c2 is 0, 1, or 2; c3 is 0, 1, or 2; and the key marked "1" connects to ring B, and the key marked "2" connects to... Preferably, Selected from Where c is 0, 1, 2, 3, or 4; c1 is 0, 1, 2, or 3; preferably c1 is 1 or 2; wherein the key marked "1" is connected to ring B, and the key marked "2" is connected to... Preferably, Selected from Wherein, c is 0, 1, 2, 3, or 4; preferably, c is 0, 1, 2, or 3; c1 is 0, 1, 2, or 3; preferably, c1 is 1 or 2; wherein the key marked "1" is connected to ring B, and the key marked "2" is connected to... Preferably, Selected from Where c1 is 0, 1, 2, or 3; preferably c1 is 1 or 2; wherein the key marked "1" is connected to ring B, and the key marked "2" is connected to... Preferably, Selected from Preferred More The key marked "1" connects to ring B, and the key marked "2" connects to...

10. The compound of formula (I) according to any one of claims 1-9, or its stereoisomers, tautomers, diastereomers, racemic derivatives, cis-trans isomers, isotopically labeled compounds (preferably deuterated), N-oxides, metabolites, esters, prodrugs, crystal forms, hydrates, solvates, or pharmaceutically acceptable salts, in, R 1 R 2 Each is independently selected from hydrogen, deuterium, halogen, C1-4 alkyl, C1-4 haloalkyl, C1-4 deuteralkyl, C1-4 alkoxy, C1-4 haloalkoxy, or R 1 R 2 Together with the carbon atoms they are attached to, they form 3-7 membered carbon rings or heterocycles; Preferably, R 1 R 2 Each is independently selected from hydrogen, deuterium, F, Cl, Br, methyl, ethyl, methoxy, ethoxy, or R. 1 R 2 Together with the carbon atoms they are attached to, they form cyclopropyl, cyclobutyl, oxocyclobutyl, and azircyclobutyl groups; Preferably, R 1 R 2 All are hydrogen, or R 1 R 2 One is hydrogen, and the other is deuterium, F, Cl, Br, methyl, ethyl, methoxy, or ethoxy. More preferably, R 1 R 2 Both are hydrogen.

11. The compound of formula (I) according to any one of claims 1-10, or its stereoisomers, tautomers, diastereomers, racemic derivatives, cis-trans isomers, isotopically labeled compounds (preferably deuterated), N-oxides, metabolites, esters, prodrugs, crystal forms, hydrates, solvates, or pharmaceutically acceptable salts, in, Ring D is a 5-6 member nitrogen-containing heterocyclic benzobenzene, a 5-6 member nitrogen-containing heterocyclic benzo6 member nitrogen-containing heteroaryl, a 5-6 member nitrogen-containing heteroaryl benzobenzene, or a 5-6 member nitrogen-containing heteroaryl benzo6 member nitrogen-containing heteroaryl; Preferably, ring D is Wherein, G1, G2, G3, and G4 are each independently selected from CH or N; G5 is selected from CH2, NH, O, or S; preferably, G1, G2, G3, and G4 are each independently selected from CH, or one of G1, G2, G3, and G4 is selected from N, and the rest are selected from CH; G5 is selected from CH2, NH, or O. Preferably, ring D is Wherein, G1, G2, G3, and G4 are each independently selected from CH or N; G5 is selected from CH2, NH, O, or S; preferably, G1, G2, G3, and G4 are each independently selected from CH, or one of G1, G2, G3, and G4 is selected from N, and the rest are selected from CH; G5 is selected from CH2, NH, or O. Preferably, ring D is More preferably, ring D is More preferably, ring D is 12. The compound of formula (I) according to any one of claims 1-11, or its stereoisomers, tautomers, diastereomers, racemic derivatives, cis-trans isomers, isotopically labeled compounds (preferably deuterated), N-oxides, metabolites, esters, prodrugs, crystal forms, hydrates, solvates, or pharmaceutically acceptable salts, in, R d Each is independently selected from hydrogen, deuterium, halogen, cyano, nitro, hydroxyl, mercapto, oxo, C1-4 alkyl, C1-4 alkoxy, C1-4 haloalkyl, C1-4 haloalkoxy, C1-4 alkylthio, -NH(C1-4 alkyl), -N(C1-4 alkyl)2, hydroxyC1-4 alkyl, -C(O)(C1-4 alkyl), -C(O)O(C1-4 alkyl), -S(O)(C1-4 alkyl), -S(O)2(C1-4 alkyl), C3-6 cycloalkyl, 4-7 membered heterocyclic, C6-10 aryl, 5-10 membered heteroaryl; Preferably, R d Each is independently selected from hydrogen, deuterium, F, Cl, Br, cyano, nitro, hydroxyl, mercapto, oxo, methyl, ethyl, propyl, butyl, methoxy, ethoxy, propoxy, fluoromethyl, fluoroethyl, fluoromethoxy, fluoroethoxy, methylthio, ethylthio, methylamino, ethylamino, dimethylamino, hydroxymethyl, hydroxyethyl, -C(O)CH3, -C(O)OCH3, -S(O)CH3, -S(O)2CH3, cyclopropyl, cyclobutyl, oxetanebutyl, azirone, phenyl, pyridinyl, pyrroleyl, pyrimidinyl, and pyrazinyl.

13. The compound of formula (I) according to any one of claims 1-12, or its stereoisomers, tautomers, diastereomers, racemic derivatives, cis-trans isomers, isotopically labeled compounds (preferably deuterated), N-oxides, metabolites, esters, prodrugs, crystal forms, hydrates, solvates, or pharmaceutically acceptable salts, in, a can be 0, 1, 2 or 3, preferably a is 1; b is 0, 1, or 2; preferably, b is 0 or 1. c is 0, 1, 2, 3 or 4, preferably c is 0, 1, 2 or 3; d is 0, 1, 2 or 3, preferably d is 0, 1 or 2, more preferably d is 0.

14. The compound of formula (I) according to any one of claims 1-13, or its stereoisomers, tautomers, diastereomers, racemic derivatives, cis-trans isomers, isotopically labeled compounds (preferably deuterated), N-oxides, metabolites, esters, prodrugs, crystal forms, hydrates, solvates, or pharmaceutically acceptable salts, wherein the compound has the structure shown in formula (I-1):

15. The compound according to claim 14, or its stereoisomers, tautomers, diastereomers, racemic derivatives, cis-trans isomers, isotopically labeled compounds (preferably deuterated), N-oxides, metabolites, esters, prodrugs, crystal forms, hydrates, solvates, or pharmaceutically acceptable salts, wherein the compound is shown in any one of formulas (I-1-1), (I-1-2), or (I-1-3):

16. The compound according to claim 15, or its stereoisomers, tautomers, diastereomers, racemic derivatives, cis-trans isomers, isotopically labeled compounds (preferably deuterated), N-oxides, metabolites, esters, prodrugs, crystal forms, hydrates, solvates, or pharmaceutically acceptable salts, wherein the compound is shown in any one of the structures of formula (I-1-1'), (I-1-2'), or (I-1-3'): in, Z1, Z2, Z3, and Z4 are each independently selected from CH or N; preferably, one or two of Z1, Z2, Z3, and Z4 are N, and the rest are CH. c can be 0, 1, 2, 3 or 4, with c preferably being 0, 1, 2 or 3; c1 can be 0, 1, 2 or 3, with c1 preferably being 1 or 2.

17. The compound of formula (I-1-1') according to claim 16, or its stereoisomers, tautomers, diastereomers, racemic derivatives, cis-trans isomers, isotopically labeled compounds (preferably deuterated), N-oxides, metabolites, esters, prodrugs, crystal forms, hydrates, solvates, or pharmaceutically acceptable salts, wherein the compound is as shown in any of the structures of formulas (I-1-A), (I-1-B), (I-1-C), (I-1-D), (I-1-E), (I-1-F), (I-1-G), and (I-1-H):

18. The compound of formula (I) according to any one of claims 1-13, or its stereoisomers, tautomers, diastereomers, racemic derivatives, cis-trans isomers, isotopically labeled compounds (preferably deuterated), N-oxides, metabolites, esters, prodrugs, crystal forms, hydrates, solvates, or pharmaceutically acceptable salts, wherein the compound has the structure shown in formula (I-2): in, This indicates a 5-membered heteroaryl group, where Y1 and Y3 are independently C and N, and Y2, Y4, and Y5 are independently N, NH, O, S, or CH; the group connected to Y1, Y2, Y3, Y4, and Y5... Each can independently represent a single or double bond; two bonds connected to one atom They are not all double bonds at the same time; when Y2, Y4, and Y5 are O, S, or NH, the bonds they are connected to... It is a single key.

19. The compound according to claim 18, or its stereoisomers, tautomers, diastereomers, racemic derivatives, cis-trans isomers, isotopically labeled compounds (preferably deuterated), N-oxides, metabolites, esters, prodrugs, crystal forms, hydrates, solvates, or pharmaceutically acceptable salts, wherein the compound has the structure shown in formula (I-2'):

20. The compound according to claim 19, or its stereoisomers, tautomers, diastereomers, racemic derivatives, cis-trans isomers, isotopically labeled compounds (preferably deuterated), N-oxides, metabolites, esters, prodrugs, crystal forms, hydrates, solvates, or pharmaceutically acceptable salts, wherein the compound is shown in any one of the structures of formula (I-2'-1), (I-2'-2), or (I-2'-3): in, Z1, Z2, Z3, and Z4 are each independently selected from CH or N; preferably, one or two of Z1, Z2, Z3, and Z4 are N, and the rest are CH. c can be 0, 1, 2, 3 or 4, with c preferably being 0, 1, 2 or 3; c1 can be 0, 1, 2 or 3, with c1 preferably being 1 or 2.

21. The compound according to claim 20, or its stereoisomers, tautomers, diastereomers, racemic derivatives, cis-trans isomers, isotopically labeled compounds (preferably deuterated), N-oxides, metabolites, esters, prodrugs, crystal forms, hydrates, solvates, or pharmaceutically acceptable salts, wherein the compound is shown in any of formulas (I-3) and (I-4):

22. The compound according to claim 21, or its stereoisomers, tautomers, diastereomers, racemic derivatives, cis-trans isomers, isotopically labeled compounds (preferably deuterated), N-oxides, metabolites, esters, prodrugs, crystal forms, hydrates, solvates, or pharmaceutically acceptable salts, wherein the compound is as shown in any one of formulas (I-3-1), (I-3-2), (I-4-1), and (I-4-2):

23. The compound according to claim 22, or its stereoisomers, tautomers, diastereomers, racemic derivatives, cis-trans isomers, isotopically labeled compounds (preferably deuterated), N-oxides, metabolites, esters, prodrugs, crystal forms, hydrates, solvates, or pharmaceutically acceptable salts, wherein the compound is shown in any of the structures of formulas (I-3') and (I-4'): in, R a9 The compounds are C1-6 alkyl, C2-6 alkenyl, C2-6 ynyl, C3-10 cycloalkyl, 3-10 heterocyclic, C6-10 aryl, or 5-10 heteroaryl; wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 ynyl, C3-10 cycloalkyl, 3-10 heterocyclic, C6-10 aryl, or 5-10 heteroaryl are optionally substituted by one or more substituents selected from deuterium, halogen, cyano, hydroxyl, amino, oxo, C1-6 alkyl, C1-6 alkoxy, -NH(C1-6 alkyl), or -N(C1-6 alkyl)2. Preferably, R a9 The compounds are C1-4 alkyl, C2-4 alkenyl, C3-6 cycloalkyl, 4-7 heterocyclic, C6-10 aryl, or 5-10 heteroaryl; the C1-4 alkyl, C2-4 alkenyl, C3-6 cycloalkyl, 4-7 heterocyclic, C6-10 aryl, or 5-10 heteroaryl are optionally substituted by one or more substituents selected from deuterium, halogen, cyano, hydroxyl, amino, oxo, C1-4 alkyl, C1-4 alkoxy, -NH(C1-4 alkyl), or -N(C1-4 alkyl)2. Preferably, R a9 The C1-4 alkyl, C2-4 alkenyl, C3-6 cycloalkyl, 4-6 heterocyclic, phenyl, and 5-6 heteroaryl groups are selected; the C1-4 alkyl, C2-4 alkenyl, C3-6 cycloalkyl, 4-6 heterocyclic, phenyl, and 5-6 heteroaryl groups are optionally substituted by one or more substituents selected from deuterium, halogen, cyano, hydroxyl, amino, oxo, C1-4 alkyl, C1-4 alkoxy, -NH(C1-4 alkyl), and -N(C1-4 alkyl)2. Preferably, R a9 It is a C1-6 alkyl or a C1-6 haloalkyl; Preferably, R a9 The compounds are methyl, ethyl, trifluoromethyl, difluoromethyl, cyclopropyl, cyclobutane, oxetane, azirone, phenyl, methylphenylene, thienyl, and pyridyl. Each R a Each of the following is independently substituted with hydrogen, deuterium, halogen, cyano, hydroxyl, amino, mercapto, oxo, C1-6 alkyl, C2-6 alkenyl, C1-6 alkoxy, C1-6 alkylthio, -NH(C1-6 alkyl), or -N(C1-6 alkyl)2; wherein the C1-6 alkyl, C2-6 alkenyl, C1-6 alkoxy, C1-6 alkylthio, -NH(C1-6 alkyl), or -N(C1-6 alkyl)2 is optionally substituted with one or more substituents selected from deuterium, halogen, cyano, hydroxyl, amino, oxo, C1-6 alkyl, C2-6 alkenyl, C1-6 alkoxy, C1-6 alkylthio, -NH(C1-6 alkyl), or -N(C1-6 alkyl)2; Preferably, each R a Each of the following is independently hydrogen, F, Cl, Br, cyano, hydroxyl, amino, oxo, C1-4 alkyl, C1-4 alkoxy, -NH(C1-4 alkyl), -N(C1-4 alkyl)2; wherein the C1-4 alkyl, C1-4 alkoxy, -NH(C1-4 alkyl), -N(C1-4 alkyl)2 is optionally substituted by one or more substituents selected from deuterium, halogen, cyano, hydroxyl, amino, oxo, C1-4 alkyl, C1-4 alkoxy, -NH(C1-4 alkyl), -N(C1-4 alkyl)2; Preferably, each R a Each is independently hydrogen or C1-4 alkyl; Preferably, each R a Each of these groups can be independently identified as hydrogen, F, Cl, Br, cyano, hydroxyl, amino, oxo, methyl, ethyl, methoxy, ethoxy, fluoromethyl, fluoroethyl, fluoromethoxy, fluoroethoxy, methylamino, and dimethylamino. a1 is 0, 1, or 2; preferably, a1 is 0 or 1; more preferably, a1 is 0; Ring A is a 4-7 member saturated or partially saturated monocyclic heterocyclic group or a 7-12 member bicyclic heterocyclic group; the 7-12 member bicyclic heterocyclic group is a fused ring, a spiro ring, or a bridged ring; the heteroatoms in the 4-7 member saturated or partially saturated monocyclic heterocyclic group or the 7-12 member bicyclic heterocyclic group are selected from N, O, and S, and the number of heteroatoms is 1, 2, or 3; Preferably, ring A is a 5-7 member saturated monocyclic heterocyclic group, an 8-11 member fused bicyclic heterocyclic group, or a 9-11 member spirocyclic heterocyclic group; the heteroatoms in the 5-7 member saturated monocyclic heterocyclic group, the 8-11 member fused bicyclic heterocyclic group, or the 9-11 member spirocyclic heterocyclic group are selected from N, O, and S, and the number of heteroatoms is 1, 2, or 3, wherein at least one heteroatom is N; Preferably, ring A is The key marked with "a" is connected to Keys marked with "b" are connected to Each R b Each of these can be independently hydrogen, deuterium, halogen, cyano, hydroxyl, amino, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, -NH(C1-6 alkyl), -N(C1-6 alkyl)2; Preferably, each R b Each of these can be independently hydrogen, deuterium, halogen, cyano, hydroxyl, amino, C1-4 alkyl, C1-4 alkoxy, C1-4 haloalkyl, C1-4 haloalkoxy, -NH(C1-4 alkyl), -N(C1-4 alkyl)2; Preferably, each R b Each of these can be independently represented as hydrogen, deuterium, F, Cl, Br, cyano, hydroxyl, amino, methyl, ethyl, methoxy, ethoxy, fluoromethyl, fluoroethyl, fluoromethoxy, fluoroethoxy, methylamino, ethylamino, and dimethylamino. b is 0, 1, or 2; preferably, b is 0 or 1; more preferably, b is 0; This indicates a 5-membered heteroaryl group, where Y1 and Y3 are independently C and N, and Y2, Y4, and Y5 are independently N, NH, O, S, or CH; the group connected to Y1, Y2, Y3, Y4, and Y5... Each can independently represent a single or double bond; two bonds connected to one atom They are not all double bonds at the same time; when Y2, Y4, and Y5 are O, S, or NH, the bonds they are connected to... It is a single bond; preferably, one of Y1 and Y3 is selected from N and the other is selected from C, one of Y2, Y4 and Y5 is selected from N and the other two are selected from CH; more preferably, Y1 and Y5 are selected from N, Y3 is selected from C, and Y2 and Y4 are selected from CH. R 1 R 2 Each is independently selected from hydrogen, deuterium, halogen, C1-6 alkyl, C1-6 haloalkyl, C1-6 deuteralkyl, C1-6 alkoxy, C1-6 haloalkoxy, or R 1 R 2 Together with the carbon atoms they are attached to, they form 3-7 membered rings; Preferably, R 1 R 2 Each is independently selected from hydrogen, deuterium, halogen, C1-4 alkyl, C1-4 haloalkyl, C1-4 deuteralkyl, C1-4 alkoxy, C1-4 haloalkoxy, or R 1 R 2 Together with the carbon atoms they are attached to, they form 3-7 membered carbon rings or heterocycles; Preferably, R 1 R 2 Each is independently selected from hydrogen, deuterium, F, Cl, Br, methyl, ethyl, methoxy, ethoxy, fluoromethyl, fluoromethoxy, deuterated methyl, deuterated methoxy, or R. 1 R 2 Together with the carbon atoms they are attached to, they form cyclopropyl, cyclobutyl, oxocyclobutyl, and azircyclobutyl groups; Preferably, R 1 R 2 All are hydrogen, or R 1 R 2 One is hydrogen, and the other is deuterium, F, Cl, Br, methyl, ethyl, methoxy, ethoxy, trifluoromethyl, difluoromethyl, -CD3, -OCD3; Preferably, R 1 R 2 All are hydrogen; Each R d Each is independently selected from hydrogen, deuterium, halogen, cyano, hydroxyl, mercapto, oxo, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C1-6 alkylthio, -NH(C1-6 alkyl), -N(C1-6 alkyl)2; Preferably, each R d Each is independently selected from hydrogen, deuterium, halogen, cyano, hydroxyl, mercapto, oxo, C1-4 alkyl, C1-4 alkoxy, C1-4 haloalkyl, C1-4 haloalkoxy, C1-4 alkylthio, -NH(C1-4 alkyl), -N(C1-4 alkyl)2; Preferably, each R d Each is independently selected from hydrogen or halogen; Preferably, each R d Each is independently selected from hydrogen, deuterium, F, Cl, Br, cyano, hydroxyl, mercapto, oxo, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, methoxy, ethoxy, fluoromethyl, fluoroethyl, fluoromethoxy, fluoroethoxy, methylthio, ethylthio, methylamino, ethylamino, and dimethylamino. d is 0, 1, 2 or 3; preferably, d is 0 or 1; more preferably, d is 0; R c-1 R c-2 R c-3 R c-4 R c-5 R c-6 R c-7 Each of these groups is independently hydrogen, deuterium, halogen, cyano, hydroxyl, amino, mercapto, oxo, C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkylthio, -NH(C1-6 alkyl), -N(C1-6 alkyl)2, C3-6 cycloalkyl, C3-6 cycloalkoxy, 4-7 membered heterocyclic, C6-10 aryl, 5-10 membered heteroaryl; wherein the C1-6 alkyl, C1-6 alkoxy, C2-6 alkenyl, C2- The 6-alkynyl, C1-6 alkylthio, -NH(C1-6 alkyl), -N(C1-6 alkyl)2, C3-6 cycloalkyl, C3-6 cycloalkoxy, 4-7 heterocyclic, C6-10 aryl, and 5-10 heteroaryl groups are optionally substituted by one or more substituents selected from deuterium, halogen, cyano, hydroxyl, amino, oxo, C1-6 alkyl, C1-6 alkoxy, C3-6 cycloalkyl, 4-7 heterocyclic, C6-10 aryl, and 5-10 heteroaryl groups; Preferably, R c-1 R c-2 R c-3 R c-4 R c-5 R c-6 R c-7 Each of the following groups is independently substituted with hydrogen, deuterium, halogen, cyano, hydroxyl, amino, mercapto, oxo, C1-4 alkyl, C1-4 alkoxy, C2-4 alkenyl, C1-4 alkylthio, -NH(C1-4 alkyl), -N(C1-4 alkyl)2, C3-6 cycloalkyl, C3-6 cycloalkoxy, 4-7 heterocyclic group; wherein the C1-4 alkyl, C1-4 alkoxy, C2-4 alkenyl, C1-4 alkylthio, -NH(C1-4 alkyl), -N(C1-4 alkyl)2, C3-6 cycloalkyl, C3-6 cycloalkoxy, 4-7 heterocyclic group is optionally substituted with one or more substituents selected from deuterium, halogen, hydroxyl, amino, oxo, C1-4 alkyl, C1-4 alkoxy, C3-6 cycloalkyl, 4-7 heterocyclic group, phenyl, 5-6 heteroaryl. Preferably, R c-1 It can be hydrogen, halogen, cyano, C1-4 alkyl, C1-4 alkoxy, C2-4 alkenyl, C1-4 alkylthio, C1-4 haloalkyl, C1-4 haloalkoxy, C3-6 cycloalkyl, or C3-6 cycloalkoxy; R c-2 For hydrogen, halogen; R c-3 For hydrogen, halogen; R c-4 For hydrogen, halogen; R c-5 It is a C1-4 alkyl, C1-4 deuterated alkyl, C1-4 haloalkyl, C3-6 cycloalkyl, C1-4 alkylene-, or 4-7 membered heterocyclic group; R c-6 For hydrogen, halogens (e.g., F); R c-7 It is hydrogen; Preferably, R c-7 For hydrogen, R c-6 It is hydrogen or halogen (e.g., F); R c-5 It is a C1-6 alkyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, C3-6 cycloalkyl-C1-3 alkylene-, or 4-7 membered heterocyclic alkyl; Preferably, R c-7 For hydrogen, R c-6 It is hydrogen or halogen (e.g., F); R c-5 It is a C1-4 alkyl, C1-4 deuterated alkyl, or C1-4 haloalkyl.

24. The compound according to any one of claims 1-23, or its stereoisomers, tautomers, diastereomers, racemic derivatives, cis-trans isomers, isotopically labeled compounds (preferably deuterated), N-oxides, metabolites, esters, prodrugs, crystal forms, hydrates, solvates, or pharmaceutically acceptable salts, wherein the compound has the structure shown in formula (X): in, G1, G2, G3, and G4 are each independently selected from CH or N; preferably, one of G1, G2, G3, and G4 is selected from N, and the rest are selected from CH; preferably, G1, G2, G3, and G4 are all selected from CH. R a9 Selected from C1-6 alkyl or C1-6 haloalkyl; R a Selected from hydrogen, hydroxyl, or C1-6 alkyl; preferably, R a Selected from hydrogen or C1-4 alkyl; a1 is selected from 0, 1, or 2; preferably a1 is selected from 0 or 1; more preferably a1 is 0; X0 is selected from CH or N; preferably, X0 is CH; R b Selected from hydrogen, halogen, or C1-6 alkyl; preferably, R b Selected from hydrogen, halogens, or C1-4 alkyl groups; b is selected from 0 or 1; preferably b is 0. R 1 R 2 Each is independently selected from hydrogen, halogen, or C1-6 alkyl; preferably, R 1 R 2 All are hydrogen, or R 1 R 2 One is hydrogen, and the other is halogen or C1-4 alkyl; more preferably, R 1 R 2 All are hydrogen; Each R d Each is independently selected from hydrogen, halogen, C1-6 alkyl, or C1-6 haloalkyl; preferably, each R d Each is independently selected from hydrogen or halogens (e.g., F); d is selected from 0, 1 or 2, preferably d is selected from 0 or 1; more preferably d is 0; R c-7 For hydrogen, R c-6 It is hydrogen or halogen (e.g., F); R c-5 It is a C1-6 alkyl, C1-6 deuterated alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, C3-6 cycloalkyl-C1-3 alkylene-, or 4-7 membered heterocyclic alkyl; preferably, R c-7 For hydrogen, R c-6 It is hydrogen or halogen (e.g., F); R c-5 It is a C1-4 alkyl, C1-4 deuterated alkyl, or C1-4 haloalkyl.

25. The compound according to any one of claims 1-24, or its stereoisomers, tautomers, diastereomers, racemic derivatives, cis-trans isomers, isotopically labeled compounds (preferably deuterated), N-oxides, metabolites, esters, prodrugs, crystal forms, hydrates, solvates, or pharmaceutically acceptable salts, selected from:

26. A compound of formula (I) as described in any one of claims 1-25, or a stereoisomer, tautomer, diastereomer, racemic compound, cis-trans isomer, isotopically labeled compound (preferably deuterated), N-oxide, metabolite, ester, prodrug, crystal form, hydrate, solvate or pharmaceutically acceptable salt thereof, for the purpose of inhibiting CYP11A1.

27. A pharmaceutical composition comprising a compound of formula (I) as claimed in any one of claims 1-26, or a stereoisomer, tautomer, diastereomer, racemic compound, cis-trans isomer, isotopically labeled compound (preferably deuterated), N-oxide, metabolite, ester, prodrug, crystal form, hydrate, solvate or pharmaceutically acceptable salt, and a pharmaceutically acceptable carrier; Preferably, the pharmaceutical composition comprises a compound of formula (I) and at least one additional active ingredient selected from: - Glucocorticoids; -Mineralocorticoids; -Nonsteroidal androgen receptor antagonists; - Steroid synthesis inhibitors; - Chemotherapy agents; - Anti-estrogens; - Epigenetic regulators; -mTOR inhibitors (e.g., everolimus); -AKT inhibitors (e.g., AZ5363); - Radiopharmaceuticals (e.g., Alpharadin); -GnRH / LHRH analogues (such as leuprolide); -PI3K inhibitors; and -CDK4 / 6 inhibitors.

28. A compound of formula (I) as claimed in any one of claims 1-26, or a stereoisomer, tautomer, diastereomer, racemate, cis-trans isomer, isotopically labeled compound (preferably deuterated), N-oxide, metabolite, ester, prodrug, crystal form, hydrate, solvate or pharmaceutically acceptable salt thereof, or a pharmaceutical composition of claim 27, for the treatment of steroid receptor-dependent disorders and diseases, the method comprising administering to an individual in need a therapeutically effective amount of a compound of formula (I) or a stereoisomer, tautomer, diastereomer, racemate, cis-trans isomer, isotopically labeled compound (preferably deuterated), N-oxide, metabolite, ester, prodrug, crystal form, hydrate, solvate or pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof; wherein the steroid receptor-dependent disorder is preferably cancer; the cancer is preferably prostate cancer; the prostate cancer is preferably castration-resistant prostate cancer (CRPC); in, Administer a therapeutically effective amount of a compound of formula (I), preferably also administering glucocorticoids and / or mineralocorticoids, and optionally administering one or more anticancer drugs; In this embodiment, a therapeutically effective amount of a compound of formula (I) is administered with one or more anticancer drugs, wherein the anticancer drugs are preferably selected from: -Nonsteroid androgen receptor antagonists; - Steroid synthesis inhibitors; - Chemotherapy agents; -Anti-estrogens; - Epigenetic regulators; -mTOR inhibitors (e.g., everolimus); -AKT inhibitors (e.g., AZ5363); - Radiopharmaceuticals (e.g., alpharadin); -GnRH / LHRH analogues (e.g., leuprolide); -PI3K inhibitors; and -CDK4 / 6 inhibitors.

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