Heterocyclic compound, and pharmaceutical composition thereof, intermediate thereof, preparation method therefor and use thereof

Abstract

Disclosed in the present invention are a heterocyclic compound, and a pharmaceutical composition thereof, an intermediate thereof, a preparation method therefor and a use thereof. Specifically provided is a compound represented by formula (A) or a pharmaceutically acceptable salt thereof. The compound of the present invention has one or more of the following effects: (1) having inhibitory activity against Nav1.8; (2) having good solubility; (3) having good analgesic effect; (4) having good pharmacokinetic characteristics; (5) having rapid onset of action; (6) having rapid oral absorption; and (7) satisfying injection administration.

Description

A heterocyclic compound, its pharmaceutical composition, its intermediate, its preparation method and application

[0001] This application claims priority to Chinese patent applications 2025100175911 (filed January 3, 2025), 2025113785624 (filed September 24, 2025), 2025115559026 (filed October 28, 2025), and 2025119434068 (filed December 22, 2025). The full text of the aforementioned Chinese patent applications is incorporated herein by reference. Technical Field

[0002] This invention relates to the pharmaceutical field, specifically to a heterocyclic compound, its pharmaceutical composition, its intermediate, its preparation method, and its application. Background Technology

[0003] Pain is one of the most common clinical symptoms and the most frequent reason for patients to seek medical attention. It can generally be divided into acute and chronic pain, and may be accompanied by actual or potential tissue damage. Intense or persistent pain can cause physiological dysfunction and seriously affect quality of life. Pain can be classified according to its mechanism into nociceptive pain (caused by tissue damage), such as pain caused by mechanical, chemical, or thermal stimuli, and neuropathic pain (caused by nerve damage), which is commonly seen in diabetic neuropathy, postherpetic neuralgia, and post-stroke pain.

[0004] Sodium ion channels (Nav) play a crucial role in pain perception, pain transmission, and the presentation of pain signals to the central nervous system. The Nav family comprises nine subtypes, Nav1.1 to Nav1.9. Nav1.8 has been confirmed to be closely related to pain transmission, playing a key role in pain signal transduction in the peripheral nervous system, a role that has been genetically verified. Nav1.8 is primarily expressed in neurons that transmit pain signals in the dorsal root ganglion (DRG). It is a voltage-gated sodium channel; its opening induces sodium ion influx, causing cell membrane depolarization and leading to the generation of action potentials. Abnormal activity of this channel results in pain generation and transmission. Therefore, inhibiting abnormal sodium ion channel activity is beneficial for pain treatment and relief, and Nav1.8 has become a hot topic in pain management drug research.

[0005] Vertex's Nav1.8 inhibitor VX-548 demonstrated significant efficacy in a phase III clinical trial for treating moderate to severe acute pain, becoming the first non-opioid acute pain medication in twenty years. However, VX-548 cannot be administered intravenously due to poor solubility and has a slow rate of oral absorption (T0). maxDue to its slow onset of action (approximately 6 hours), its use is limited for indications requiring rapid analgesia.

[0006] Other publicly reported Nav1.8 inhibitors, including VX-150, HRS-4800, JMKX-000623, and HBW-004, have entered clinical trials. However, some compounds have been discontinued in the preclinical stage due to problems such as poor solubility, limited efficacy, or slow onset of action. Therefore, developing suitable Nav1.8 inhibitors is of significant value. Summary of the Invention

[0007] This invention provides a compound of formula (A) or a pharmaceutically acceptable salt thereof.

[0008] in,

[0009] R 1 C 1-3 Alkyl, C 1-3 Alkoxy, C 3-6 cycloalkyl, C 1-3 Deuterated alkyl or C 1-3 Halogenated alkyl groups;

[0010] Z is a single bond, O, S, or N(R) Z );

[0011] R Z For H, C 1-3 Alkyl or C 1-3 Deuterated alkyl groups;

[0012] R 2 For H, C 1-3 Alkyl or C 3-6 cycloalkyl, wherein the C 1-3 The alkyl group may optionally be selected independently from one or more deuterium, halogen, hydroxyl, C 1-3 Alkoxy, C 3-6 Substituents of cycloalkyl groups;

[0013] R 3 and R 4 Each can be independently H, deuterium, or halogen;

[0014] R 5 and R 6 Each is independently H, deuterium, and C. 1-3 Alkyl or halogen;

[0015] R 8 and R 9 Each is independently H, deuterium, halogen, C 1-3 Alkyl, C 1-3 Deuterated alkyl or C 1-3 Halogenated alkyl groups;

[0016] X is O, S, or N(R) X );

[0017] R X For H or C 1-3 alkyl;

[0018] Y is CH, C, N, or NH, and T is O or CHR. T Where Y is CH or C, and T is CHR T At that time, R 7 and R T Together with the atoms it is attached to, it forms a 6-membered nitrogen-containing heterocycle, wherein the 6-membered nitrogen-containing heterocycle is optionally... Substitution, and the 6-membered nitrogen-containing heterocycle forms a fused ring with W; when Y is CH or C, and T is O, R 7 H, halogen or C 1-3 Alkyl; when Y is N or NH, T is O, R 7 It does not exist;

[0019] In W, two atoms or groups marked with * are in adjacent positions;

[0020] W represents phenyl, 5-6 membered heteroaryl, 5-6 membered heterocyclic group, C represents... 3-6 Cycloalkyl or dicyclic; each ring in the dicyclic group is independently a benzene ring, a 5-6 membered heteroaromatic ring, a 5-6 membered heterocycle, or a C-ring. 3-6 Monocyclic carbocyclic ring; wherein the phenyl, 5-6 membered heteroaryl, 5-6 membered heterocyclic group, C 3-6 Cycloalkyl and dicycloalkyl groups are optionally separated by one or more R W replace;

[0021] Each R W Each group independently consists of carbamoyl, halogen, oxo, aminosulfonyl, amidine, and C. 1-3 Alkyl, C 3-6 cycloalkyl or The amidoyl group, C 1-3 Alkyl and C 3-6 The cycloalkyl group may optionally be selected by one or more groups, each independently chosen from hydroxyl, amino, C... 1-3 Alkoxy, C 1-3 Alkyl, C 1-3 Alkyl-C(O)-O- and C 1-3 Substituents of alkyl-OC(O)- groups;

[0022] L stands for -(CH2) m -OC(O)-R L1 -(CH2) n -OR L2 Or -(CH2)p -C(O)-OR L3 ;

[0023] m, n, and p are each independently 1, 2, or 3;

[0024] R L1 C 1-6 Alkyl, the C 1-6 Alkyl groups are optionally selected from deuterium, hydroxyl, and -NR. L1-1 R L1-2 , -(OCH2CH2) t OR L1-6 -[OC(O)-(CH2) r ] s -R L1-7 , -OP(=O)(OH)2, -OP(=O)(ONa)2, -OP(=O)(OH)(ONa) and -(NCH3-CO-CH2) u R L1-8 One or more substituents are substituted in the sample;

[0025] t and u are each an independent integer from 1 to 20;

[0026] r can be 0, 1, 2, or 3;

[0027] s is 1, 2, or 3;

[0028] M is an anion;

[0029] R L1-1 R L1-2 R L1-3 R L1-4 R L1-5 R L1-6 and R L1-8 Each is independently H, deuterium, and C. 1-3 Alkyl or C 1-3 Deuterated alkyl groups;

[0030] R L1-7 H, deuterium, C 1-3 Alkyl, C 1-3 Deuterated alkyl or -NR L1-71 R L1-72 ;R L1-71 and R L1-72 Each is independently H, deuterium, and C. 1-3 Alkyl or C 1-3 Deuterated alkyl groups;

[0031] R L2 For H, C 1-3Alkyl group, -P(=O)(OH)2, -P(=O)(ONa)2 or -P(=O)(OH)(ONa);

[0032] R L3 For H or C 1-3 alkyl;

[0033] The number of heteroatoms in each of the 5-6 membered heteroaryl, 5-6 membered heterocyclic group, 5-6 membered heteroaromatic ring, and 5-6 membered heterocyclic ring is independently 1, 2, or 3, and each heteroatom is independently selected from N, O, or S, wherein N is optionally oxidized to N→O, and S is optionally simultaneously oxidized to N→O. replace;

[0034] R is H or C 1-3 alkyl.

[0035] In some embodiments, the compound represented by formula (A) or a pharmaceutically acceptable salt thereof, wherein the compound represented by formula (A) is the compound represented by formula (A-1) below.

[0036] In W, two atoms or groups marked with * are in adjacent positions;

[0037] R 8 and R 9 They are different and each independently consists of H, deuterium, halogen, and C. 1-3 Alkyl, C 1-3 Deuterated alkyl or C 1-3 Halogenated alkyl groups;

[0038] R 1 R 2 R 3 R 4 R 5 R 6 R 7 The definitions of T, X, Y, Z, L and W are as described in any one of the present invention.

[0039] In some embodiments, the compound represented by formula (A) or (A-1) or a pharmaceutically acceptable salt thereof,

[0040] R 1 C 1-3 Alkyl, C 1-3 Alkoxy or C 3-6 cycloalkyl;

[0041] Z is a single bond or O (preferably O);

[0042] R 2 C 1-3 Alkyl, C 1-3 Deuterated alkyl or C 1-3Halogenated alkyl groups;

[0043] R 3 and R 4 Each is independently H or halogen;

[0044] R 5 and R 6 Each independently represents H and C. 1-3 Alkyl or halogen;

[0045] R 8 C 1-3 Alkyl (e.g., methyl) or C 1-3 Deuterated alkyl groups (e.g., -CD3);

[0046] R 9 C 1-3 Halogenated alkyl groups (e.g., -CF3);

[0047] In W, two atoms or groups marked with * are in adjacent positions;

[0048] R 7 The definitions of T, X, Y, L and W are as described in any one of the present invention.

[0049] In some embodiments, in the compound represented by formula (A) or formula (A-1) or a pharmaceutically acceptable salt thereof, M is Q. - R L1-9 COO - 1 / 3 P(=O)(O) - )3 or R L1-10 S(O)2O - Q is a halogen; R L1-9 H, deuterium, C 1-3 Alkyl or C 1-3 Deuterated alkyl; R L1-10 C 1-3 Alkyl, C 1-3 Deuterated alkyl or C 1-3 Halogenated alkyl groups.

[0050] In some embodiments, the compound represented by formula (A) or a pharmaceutically acceptable salt thereof, wherein the compound represented by formula (A) is the compound represented by formula (I) below.

[0051] in,

[0052] R 1 C 1-3 Alkyl, C 1-3 Alkoxy or C 3-6 cycloalkyl;

[0053] R 2 C 1-3Alkyl, C 1-3 Deuterated alkyl or C 1-3 Halogenated alkyl groups;

[0054] R 3 and R 4 Each is independently H or halogen;

[0055] R 5 and R 6 Each independently represents H and C. 1-3 Alkyl or halogen;

[0056] X is O, S, or N(R) X );

[0057] R X For H or C 1-3 alkyl;

[0058] Y is CH, C, N, or NH, and T is O or CHR. T Where Y is CH or C, and T is CHR T At that time, R 7 and R T The methylene group forms a 6-membered nitrogen-containing heterocycle with the atoms it is attached to, wherein the methylene group is optionally... Substitution, and the 6-membered nitrogen-containing heterocycle forms a fused ring with W; when Y is CH or C, and T is O, R 7 H, halogen or C 1-3 Alkyl; when Y is N or NH, T is O, R 7 It does not exist;

[0059] In W, two atoms or groups marked with * are in adjacent positions;

[0060] W is a phenyl, a 5-6-membered heteroaryl, a 5-6-membered heterocyclic, a 5-6-membered heterocyclic phenyl, or a 5-6-membered heterocyclic 5-6-membered heteroaryl, wherein the phenyl, 5-6-membered heteroaryl, 5-6-membered heterocyclic phenyl, and 5-6-membered heterocyclic 5-6-membered heteroaryl are optionally surrounded by one or more R W replace;

[0061] Each R W Each group independently consists of carbamoyl, halogen, oxo, aminosulfonyl, amidine, and C. 1-3 Alkyl or C 3-6 cycloalkyl, wherein the amidine group, C 1-3 Alkyl and C 3-6 The cycloalkyl group may optionally be selected by one or more groups, each independently chosen from hydroxyl, amino, C... 1-3 Alkoxy, C 1-3 Alkyl, C 1-3 Alkyl-C(O)-O- and C 1-3Substituents of alkyl-OC(O)- groups;

[0062] L stands for -(CH2) m -OC(O)-R L1 -(CH2) n -OR L2 Or -(CH2) p -C(O)-OR L3 ;

[0063] m, n, and p are each independently 1, 2, or 3;

[0064] R L1 C 1-3 alkyl;

[0065] R L2 and R L3 Each independently is H or C 1-3 alkyl;

[0066] The number of heteroatoms in the 5-6 membered heteroaryl, 5-6 membered heterocyclic, 5-6 membered heterocyclic phenyl, or 5-6 membered heterocyclic 5-6 membered heteroaryl is 1, 2, or 3, and each heteroatom is independently selected from N, O, or S, wherein N is optionally oxidized to N→O, and S is optionally simultaneously oxidized to N→O. replace;

[0067] R is H or C 1-3 alkyl.

[0068] In this invention, those skilled in the art will understand that R 7 and R T Through methylene (the methylene group is optionally...) When the substituted atom forms a 6-membered nitrogen-containing heterocycle together with the atoms it is attached to, the compound shown in formula (I) is:

[0069] In some implementation schemes, R 1 R Z R 2 R 5 R 6 R 7 R 8 R 9 R X R W R L1 R L1-1 R L1-2 R L1-3 R L1-4 R L1-5 R L1-6 R L1-7 R L1-71 R L1-72 R L1-8 R L1-9 R L1-10 R L2 R L3 In and R, the C 1-3 The alkyl group is methyl, ethyl, n-propyl or isopropyl, preferably methyl, ethyl or isopropyl.

[0070] In some implementation schemes, R 1 R L1-1 R L1-2 R L1-3 R L1-4 R L1-5 R L1-6 R L1-71 R L1-72 R X R L2 In and R, the C 1-3 Alkyl groups are preferably methyl groups.

[0071] In some implementation schemes, R 2 In, the C 1-3 The alkyl group is preferably methyl or ethyl.

[0072] In some implementation schemes, R W In, the C 1-3 The alkyl group is preferably methyl or ethyl.

[0073] In some implementation schemes, R W and R L1 In, the C 1-3 The alkyl group is preferably methyl or isopropyl.

[0074] In some implementation schemes, R L1 In, the C 1-6 The alkyl group is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, neopentyl, sec-pentyl, tert-pentyl, dimethylpropyl, n-hexyl, methylpentyl, dimethylbutyl, ethylbutyl, trimethylpropyl, or 1-ethyl-1-methylpropyl. The C 1-6 Alkyl groups are preferably C 1-3 alkyl.

[0075] In some implementation schemes, R 1 R 2 and R W In, the C 1-3 The alkoxy group is methoxy, ethoxy, n-propoxy, or isopropoxy, preferably methoxy.

[0076] In some implementation schemes, R 1 R 2 W and R W In, the C 3-6 Cycloalkyl group is C 3-6 The monocyclic cycloalkyl group is preferably cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl, more preferably cyclopropyl, cyclopentyl or cyclohexyl.

[0077] In some implementation schemes, R 1 and R W In, the C 3-6 Cycloalkyl group is C 3-6 The monocyclic cycloalkyl group is preferably cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl, and more preferably cyclopropyl.

[0078] In some implementations, in W, the C 3-6 Cycloalkyl group is C 3-6 Monocyclic cycloalkyl, preferably cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl, preferably cyclopentyl or cyclohexyl.

[0079] In some implementation schemes, R 1 R Z R 8 R 9 R L1-1 R L1-2 R L1-3 R L1-4 R L1-5 R L1-6 R L1-7 R L1-71 R L1-72 R L1-8 R L1-9 R L1-10 and R 2 In, the C 1-3 C in deuterated alkyl groups 1-3 The alkyl group is methyl, ethyl, n-propyl, or isopropyl, preferably methyl. The C 1-3 The number of deuterium atoms in the deuterated alkyl group is 1, 2, 3 or more, preferably 3. The C 1-3 The deuterated alkyl group is preferably -CD3.

[0080] In some implementation schemes, R 1 R 2 R 8 R 9 and R L1-10 In, the C 1-3 C in haloalkyl 1-3 The alkyl group is methyl, ethyl, n-propyl, or isopropyl, preferably methyl. The C 1-3The halogen in the haloalkyl group is F, Cl, Br, or I, preferably F. The C 1-3 The number of halogens in the haloalkyl group is one, two, three, or more, preferably two or three. The C 1-3 The alkyl halogroup is preferably -CHF2 or -CF3.

[0081] In some implementation schemes, R 2 R 3 R 4 R 5 R 6 R 7 R 8 R 9 R W In Q, the halogen is F, Cl, Br or I, preferably F or Cl.

[0082] In some implementation schemes, R 3 R 4 R 5 R 6 R 7 and R W In this context, the halogen is F, Cl, Br, or I, preferably F.

[0083] In some embodiments, the halogen in Q is F, Cl, Br, or I, preferably Cl.

[0084] In some embodiments, in W, the number of heteroatoms in the 5-6-membered heteroaryl group is preferably 1 or 2, more preferably 1. The heteroatom in the 5-6-membered heteroaryl group is preferably N, wherein N is optionally oxidized to N→O. The 5-6-membered heteroaryl group is preferably a 6-membered heteroaryl group.

[0085] In some embodiments, in W, the 5-6 heteroaryl group is pyridyl, N-pyridyl oxide, or pyrimidinyl, preferably pyridyl or N-pyridyl oxide.

[0086] In some implementations, in W, the 5-6 member heteroaryl group is Preferred

[0087] In some embodiments, in W, the number of heteroatoms in the 5-6 membered heterocyclic group is preferably one. The heteroatoms in the 5-6 membered heterocyclic group are preferably N or S, wherein S is optionally simultaneously... Replacement. The 5-6 membered heterocyclic group is preferably a 6 membered heterocyclic group.

[0088] In some implementations, in W, the 5-6 membered heterocyclic group is

[0089] In some embodiments, in W, the number of heteroatoms in the 5-6 membered heteroaromatic ring is preferably 1 or 2. The heteroatoms in the 5-6 membered heteroaromatic ring are preferably N. The 5-6 membered heteroaromatic ring is preferably a 5-membered heteroaromatic ring.

[0090] In some embodiments, the 5-6 membered heteroaromatic ring in W is pyrazole or pyrrole.

[0091] In some embodiments, in W, the number of heteroatoms in the 5-6 membered heterocycle is preferably one or two. The heteroatoms in the 5-6 membered heterocycle are preferably N. The 5-6 membered heterocycle is preferably a 5-membered heterocycle or a 6-membered heterocycle.

[0092] In some embodiments, the 5-6 membered heterocycle in W is tetrahydropyrrole, dihydropyridine, or tetrahydropyrimidine (e.g., 1,2,3,4-tetrahydropyrimidine), preferably dihydropyridine (e.g., 1,2-dihydropyridine) or tetrahydropyrrole.

[0093] In some implementations, in W, the C 3-6 The monocyclic carbon ring is cyclopropane, cyclobutane, cyclopentane, or cyclohexane, preferably cyclopentane or cyclohexane.

[0094] In some embodiments, in W, the dicyclic cycloyl group is a 5-6 membered heterocyclic cyclophenyl, a 5-6 membered heterocyclic cyclophenyl, a 5-6 membered heterocyclic cyclophenyl-5-6 membered heteroaryl, a 5-6 membered heterocyclic cyclophenyl-5-6 membered heterocyclic group, or a 5-6 membered heterocyclic cyclophenyl-C 3-6 cycloalkyl, 5-6 membered heteroaryl, 5-6 membered heteroaryl, 5-6 membered heteroaryl, 5-6 membered heteroaryl, 5-6 membered heteroaryl 3-6 cycloalkyl, naphthyl, benzocyclopentaenoyl 5-6 membered heteroaryl, benzocyclopentaenoyl 5-6 membered heterocyclic, benzocyclopentaenoyl C 3-6 cycloalkyl, C 3-6 Monocyclic carbocyclophenyl, C 3-6 Monocyclic carbocyclic 5-6 membered heteroaryl, C 3-6 Monocyclic carbocyclic 5-6 membered heterocyclic groups or C 3-6 Monocyclic carbon ring fused C 3-6 Cycloalkyl, preferably 5-6 membered heterocyclic phenyl or 5-6 membered heterocyclic 5-6 membered heteroaryl.

[0095] In some embodiments, in W, the number of heteroatoms in the 5-6 membered heterocyclic benzophenyl ring is preferably one. The heteroatomancy in the 5-6 membered heterocyclic benzophenyl ring is preferably N. The 5-6 membered heterocyclic benzophenyl ring is preferably a 5-membered heterocyclic benzophenyl ring.

[0096] In some embodiments, in W, the 5-6 membered heterocyclic phenyl group is...

[0097] In some embodiments, in W, the number of heteroatoms in the 5-6 membered heterocyclic 5-6 membered heteroaryl group is preferably 2 or 3. The heteroatoms in the 5-6 membered heterocyclic 5-6 membered heteroaryl group are preferably N. The 5-6 membered heterocyclic 5-6 membered heteroaryl group is preferably a 6 membered heterocyclic 5 membered heteroaryl group.

[0098] In some embodiments, in W, the 5-6 membered heterocyclic 5-6 membered heteroaryl is

[0099] In some embodiments, W contains phenyl, 5-6-membered heteroaryl, 5-6-membered heterocyclic group, C 3-6 Cycloalkyl and dicyclic groups are optionally separated by one or two R groups. W replace.

[0100] In some embodiments, in W, the phenyl, 5-6-membered heteroaryl, 5-6-membered heterocyclic, 5-6-membered heterocyclic phenyl, and 5-6-membered heterocyclic 5-6-membered heteroaryl are optionally replaced by one or two R. W replace.

[0101] In some embodiments, in W, the phenyl group is optionally mixed with two R groups. W The 5-6 aryl group is optionally replaced by one or two R groups. W Replacement, preferably optional, by an R W Replacement. The 5-6 membered heterocyclic group is optionally replaced by an R W Replacement. The bicyclic base is optionally replaced by an R W Substitution. The 5-6 membered heterocyclic phenyl group is optionally replaced by an R W Substitution. The 5-6 membered heterocyclic ring and 5-6 membered heteroaryl group are optionally replaced by an R W replace.

[0102] In some embodiments, in W, the phenyl group is reacted with two R groups. W The 5-6 membered heteroaryl group is replaced by one or two R groups. W Replacement, preferably by an R W The 5-6 membered heterocyclic group is replaced by an R W The bicyclic group is replaced by an R W Substitution. The 5-6 membered heterocyclic phenyl group is replaced by an R W Substitution. The 5-6 membered heterocyclic 5-6 membered heteroaryl group is replaced by an R W replace.

[0103] In some implementation schemes, R W In this context, the amidine group is optionally replaced by a compound selected from hydroxyl, C... 1-3 Alkoxy and C 1-3 Alkyl-OC(O)- substituents. The C 1-The 3 alkyl groups are optionally selected from two independently chosen from hydroxyl and C. 1-3 The alkyl-C(O)-O- group is substituted, preferably optionally substituted with two hydroxyl groups. The C 3-6 The cycloalkyl group may be optionally substituted with an amino group.

[0104] In some implementation schemes, R W In this context, the amidine group is optionally replaced by a compound selected from hydroxyl, C... 1-3 Alkoxy and C 1-3 Alkyl-OC(O)- substituents. The C 1- The 3 alkyl groups are optionally selected from two independently chosen from hydroxyl and C. 1-3 The alkyl-C(O)-O- group is substituted, preferably with two hydroxyl groups. The C 3-6 The cycloalkyl group is replaced by an amino group.

[0105] In some implementations, when W is phenyl, each R W Each can be independently carbamoyl, halogen, aminosulfonyl, or Preferably, it is halogenated or aminosulfonyl.

[0106] In some implementations, when W is phenyl, each R W Each group is independently carbamoyl, halogen, or aminosulfonyl, preferably halogen or aminosulfonyl.

[0107] In some implementations, when W is a 5-6 member heteroaryl group, each R W Each is independently composed of carbamoyl, halogen, amidine, and C. 1-3 Alkyl, C 3-6 cycloalkyl or The amidoyl group, C 1-3 Alkyl and C 3-6 The cycloalkyl group may optionally be selected by one or more groups, each independently chosen from hydroxyl, amino, C 1-3 Alkoxy, C 1-3 Alkyl, C 1-3 Alkyl-C(O)-O- and C 1-3 Alkyl-OC(O)- substituent substitution. In some embodiments, when W is a 5-6 membered heteroaryl group, each R W Each is independently composed of carbamoyl, halogen, amidine, and C. 1-3 Alkyl or C 3-6 cycloalkyl, wherein the amidine group, C 1-3 Alkyl and C 3-6 The cycloalkyl group may optionally be selected by one or more groups, each independently chosen from hydroxyl, amino, C 1-3 Alkoxy, C 1-3 Alkyl, C 1-3 Alkyl-C(O)-O- and C1-3 Substituents of alkyl-OC(O)-.

[0108] In some implementations, when W is a 5-6 member heteroaryl group, each R W Each is preferably independently carbamoyl or C 1-3 alkyl or Wherein C 1-3 Alkyl groups may optionally be selected from one or more hydroxyl groups and C12 groups. 1-3 Substituents of alkyl-C(O)-O-.

[0109] In some implementations, when W is a 5-6 member heteroaryl group, each R W Each is preferably carbamoyl or C. 1-3 Alkyl, wherein the C 1-3 Alkyl groups may optionally be selected from one or more hydroxyl groups and C12 groups. 1-3 Alkyl-C(O)-O- substituents. In some embodiments, when W is a 5-6 membered heterocyclic group, R... W It is an oxygen-based process.

[0110] In some implementations, when W is a bis-cyclic base, R W It is oxygenated.

[0111] In some implementations, when W is a 5-6 membered heterocyclic phenyl group, R W It is oxygenated.

[0112] In some implementations, when W is a 5-6 membered heterocyclic ring and a 5-6 membered heteroaryl group, R W It is oxygenated.

[0113] In some implementation schemes, R 1 C 1-3 alkyl.

[0114] In some implementations, Z is O.

[0115] In some implementation schemes, R 2 C 1-3 Alkyl or C 1-3 Deuterated alkyl groups.

[0116] In some implementation schemes, R 3 and R 4 Each is an independent halogen.

[0117] In some implementation schemes, R 5 and R 6 For H.

[0118] In some implementation schemes, R 8 C1-3 Alkyl or C 1-3 Deuterated alkyl groups.

[0119] In some implementation schemes, R 9 C 1-3 Halogenated alkyl groups.

[0120] In some implementations, X is O, S, N(H), or N(CH3).

[0121] In some implementations, Y is CH or C, and T is O or CHR. T Where Y is CH or C, and T is CHR T At that time, R 7 and R T The methylene group forms a 6-membered nitrogen-containing heterocycle with the atoms it is attached to, wherein the methylene group is optionally... Substitution, and the 6-membered nitrogen-containing heterocycle forms a fused ring with W; when Y is CH or C, and T is O, R 7 H, halogen or C 1-3 alkyl.

[0122] In some implementations, Y is CH or C, T is O, and R is R. 7 H, halogen or C 1-3 alkyl.

[0123] In some embodiments, W is phenyl, 5-6-membered heteroaryl, or dicyclic, preferably phenyl or 5-6-membered heteroaryl.

[0124] In some embodiments, W is phenyl, 5-6-membered heteroaryl, or 5-6-membered heterocyclic phenyl, preferably 5-6-membered heteroaryl.

[0125] In some implementations, Y is CH or C, and T is O, R 7 H, halogen or C 1-3 Alkyl group; W is phenyl, 5-6 membered heteroaryl, or 5-6 membered heterocyclic phenyl.

[0126] In some implementations, Y is C, and T is O, R 7 H represents H; W represents 5-6 heteroaryl groups.

[0127] In some implementations, each R W Each can be independently carbamoyl, halogen, oxo, aminosulfonyl, or C. 1-3 Alkyl, preferably carbamoyl, halogen or C 1-3 Alkyl, wherein the C 1-3 Alkyl groups may optionally be selected from one or more hydroxyl groups and C12 groups. 1-3 Alkyl-C(O)-O- substituents; preferably, the C 1-3The alkyl group may be selected by one or two independently chosen from hydroxyl and C. 1-3 Substituents of alkyl-C(O)-O-.

[0128] In some implementations, each R W Each can be independently carbamoyl, halogen, oxo, aminosulfonyl, or C. 1-3 Alkyl, preferably carbamoyl or C 1-3 Alkyl, wherein the C 1-3 Alkyl groups may optionally be selected from one or more hydroxyl groups and C12 groups. 1-3 Alkyl-C(O)-O- substituents; preferably, the C 1-3 The alkyl group may be selected by one or two independently chosen from hydroxyl and C. 1-3 Substituents of alkyl-C(O)-O-.

[0129] In some implementations, L stands for -(CH2). m -OC(O)-R L1 .

[0130] In some implementations, m is 1 or 2, preferably 1.

[0131] In some implementations, n is 1 or 2.

[0132] In some implementations, p is 1.

[0133] In some implementation schemes, R L1 C 1-3 Alkyl, the C 1-3 Alkyl groups may be selected from hydroxyl, -NR L1-1 R L1-2 , -(OCH2CH2) t OR L1- 6 -[OC(O)-(CH2) r ] s -R L1-7 , -OP(=O)(OH)2, -OP(=O)(ONa)2, -OP(=O)(OH)(ONa) and -(NCH3-CO-CH2) u R L1-8 One or two substituents are substituted.

[0134] In some implementation schemes, R L1 C 1-3 Alkyl, the C 1-3 Alkyl groups may be selected from hydroxyl groups, One or more substituents from -OP(=O)(OH)2, -OP(=O)(ONa)2, and -OP(=O)(OH)(ONa) are substituted. Preferably, R L1 C 1-3 Alkyl, the C 1-3 Alkyl groups may be selected from hydroxyl groups, One or two of the substituents in -OP(=O)(OH)2, -OP(=O)(ONa)2 and -OP(=O)(OH)(ONa) are substituted.

[0135] In some implementation schemes, R L1 C 1-3 Alkyl, the C 1-3 Alkyl groups may be optionally replaced by hydroxyl groups and / or Substituents are used for substitution. Preferably, R L1 C 1-3 Alkyl, the C 1-3 Alkyl groups are replaced by hydroxyl groups, or by hydroxyl groups and... replace.

[0136] In some implementation schemes, R L1 C 1-3 alkyl.

[0137] In some implementations, t is any integer from 1 to 15, preferably any integer from 3 to 11, such as 3, 5 or 11.

[0138] In some implementations, u is any integer from 5 to 15, for example, 10.

[0139] In some implementations, r is 1, 2, or 3, for example, 1.

[0140] In some implementations, s is 1 or 2, for example, 1.

[0141] In some implementations, M is Q - Or R L1-9 COO - .

[0142] In some implementation schemes, R L1-1 and R L1-2 Each independently is H or C 1-3 Alkyl, preferably H or methyl.

[0143] In some implementation schemes, R L1-3 R L1-4 and R L1-5 Each independently is C 1-3 Alkyl (e.g., methyl).

[0144] In some implementation schemes, RL1-6 For H or C 1-3 Alkyl, preferably H or methyl.

[0145] In some implementation schemes, R L1-7 For -NR L1-71 R L1-72 .

[0146] In some implementation schemes, R L1-71 and R L1-72 Each independently is C 1-3 Alkyl (e.g., methyl).

[0147] In some implementation schemes, R L1-8 For H.

[0148] In some implementation schemes, R L1-9 For H or C 1-3 Alkyl group, preferably H.

[0149] In some implementation schemes, R L1-10 C 1-3 Alkyl or C 1-3 Halogenated alkyl groups, preferably C 1-3 alkyl.

[0150] In some implementation schemes, R L2 For H, C 1-3 Alkyl or -P(=O)(OH)2, preferably C 1-3 Alkyl or -P(=O)(OH)2.

[0151] In some implementation schemes, R L2 For H or C 1-3 alkyl.

[0152] In some implementation schemes, R L2 C 1-3 alkyl.

[0153] In some implementation schemes, R L3 For H.

[0154] In some implementations, R is C 1-3 alkyl.

[0155] In some implementation schemes, R 1 It is methyl, methoxy, or cyclopropyl, preferably methyl.

[0156] In some implementation schemes, R 2 It is -CD3, -CH3, -CH2CH3, -CHF2 or -CF3, preferably -CD3 or -CH3.

[0157] In some implementation schemes, R3 and R 4 It is F.

[0158] In some implementation schemes, R 8 It is methyl or deuterated methyl.

[0159] In some implementation schemes, R 9 It is -CF3.

[0160] In some implementation schemes, R X It is H or methyl.

[0161] In some implementations, X is O or S.

[0162] In some implementations, X is O.

[0163] In some implementations, T is O.

[0164] In some implementation schemes, R 7 For H.

[0165] In some implementations, Y is C, T is O, and R is... 7 H represents H; W represents pyridinyl.

[0166] In some implementations, each R W Each independently (For example ), (For example ), (For example ),

[0167] In some implementations, each R W Each independently (For example ),

[0168] In some implementations, each R W Each independently (For example ).

[0169] In some implementations, each R W Each independently (For example ).

[0170] In some implementations, each R W Each independently

[0171] In some implementations, each R W Each independently

[0172] In some implementations, fragments for

[0173] In some implementations, fragments for

[0174] In some implementations, fragments for

[0175] In some implementations, fragments for

[0176] In some implementations, fragments for

[0177] In some implementations, fragments for

[0178] In some implementations, fragments for

[0179] In some implementations, fragments for

[0180] In some implementations, fragments for

[0181] In some implementations, fragments for

[0182] In some implementations, fragments for

[0183] In some implementations, fragments for

[0184] In some implementations, fragments for

[0185] In some implementations, fragments for

[0186] In some implementation schemes, R L1 The following are the possible values: methyl, ethyl, isopropyl, -CH2-N(CH3)2, -(CH2)2-N(CH3)2, -(CH2)3-N(CH3)2, -CH2-NHCH3, -CH2-NH2, -CH2-N + (CH3)3·M、-(CH2)3-N + (CH3)3·M, -CH2-(OCH2CH2)3OH, -CH2-(OCH2CH2)5OH, -(CH2)2-(OCH2CH2)5OH, -(CH2)2-(OCH2CH2)5OCH3, -(CH2)2-(OCH2CH2) 11 OCH3, -CH2-OC(O)-CH2-N(CH3)2, -CH2-OH, -CH2-OP(=O)(OH)2, -CH2-OP(=O)(ONa)2, -CH2-OP(=O)(OH)(ONa), -CH2-(NCH3-CO-CH2) 10 H or -CH2-CH(OH)-CH2-N + (CH3)3·M (e.g.) Preferred );

[0187] in,

[0188] M is an anion, preferably Q. - R L1-9 COO - 1 / 3 P(=O)(O) - )3 or R L1-10 S(O)2O - Q is preferred. - or R L1-9 COO - ;

[0189] The -CH2-N + (CH3)3·M is preferably -CH2-N + (CH3)3·HCOO - -CH2-N + (CH3)3·Cl - -CH2-N +(CH3)3·CH3COO - -CH2-N + (CH3)3·CH3S(O)2O - -CH2-N + (CH3)3·1 / 3P(=O)(O - )3 or -CH2-N + (CH3)3·CF3S(O)2O - ;

[0190] The -(CH2)3-N + (CH3)3·M is preferably -(CH2)3-N + (CH3)3·HCOO - ;

[0191] The -CH2-CH(OH)-CH2-N + (CH3)3·M is preferably -CH2-CH(OH)-CH2-N + (CH3)3·M (e.g.) Preferred ).

[0192] In some implementation schemes, R L1 The following are the possible values: methyl, ethyl, isopropyl, -CH2-N(CH3)2, -(CH2)2-N(CH3)2, -(CH2)3-N(CH3)2, -CH2-NHCH3, -CH2-NH2, -CH2-N + (CH3)3·M, -CH2-(OCH2CH2)3OH, -CH2-(OCH2CH2)5OH, -(CH2)2-(OCH2CH2)5OH, -(CH2)2-(OCH2CH2)5OCH3, -(CH2)2-(OCH2CH2) 11 OCH3, -CH2-OC(O)-CH2-N(CH3)2, -CH2-OH, -CH2-(NCH3-CO-CH2) 10 H or -CH2-CH(OH)-CH2-N + (CH3)3·M (e.g.) Preferred );

[0193] in,

[0194] M is an anion, preferably Q. - R L1-9 COO - 1 / 3 P(=O)(O) - )3 or R L1-10S(O)2O - Q is preferred. - Or R L1-9 COO - ;

[0195] The -CH2-N + (CH3)3·M is preferably -CH2-N + (CH3)3·HCOO - ;

[0196] The -CH2-CH(OH)-CH2-N + (CH3)3·M is preferably -CH2-CH(OH)-CH2-N + (CH3)3·Cl - (For example Preferred ).

[0197] In some implementation schemes, R L1 It can be methyl, -CH2-OH, -CH2-OP(=O)(OH)2, -CH2-OP(=O)(ONa)2, -CH2-OP(=O)(OH)(ONa) or -CH2-CH(OH)-CH2-N + (CH3)3·M (e.g.) Preferred );

[0198] in,

[0199] M is an anion, preferably Q. - R L1-9 COO - 1 / 3 P(=O)(O) - )3 or R L1-10 S(O)2O - Q is preferred. - Or R L1-9 COO - ;

[0200] The -CH2-CH(OH)-CH2-N + (CH3)3·M is preferably -CH2-CH(OH)-CH2-N + (CH3)3·Cl - (For example Preferred ).

[0201] In some implementation schemes, R L1 It is methyl, -CH2-OH or -CH2-CH(OH)-CH2-N+ (CH3)3·Cl - (For example Preferred ).

[0202] In some implementation schemes, R L1 It is methyl, ethyl or isopropyl, preferably methyl or isopropyl, more preferably methyl.

[0203] In some implementation schemes, R L2 It can be H, methyl, -P(=O)(OH)2, -P(=O)(ONa)2 or -P(=O)(OH)(ONa), preferably methyl or -P(=O)(OH)2.

[0204] In some implementation schemes, R L2 It is H or methyl, preferably methyl.

[0205] In some implementations, L is -CH2-OC(O)-CH3, -CH2-C(O)-OH, -CH2-O-CH3, -(CH2)2-OC(O)-CH3, -(CH2)2-O-CH3, -(CH2)2-OC(O)-CH(CH3)2, -(CH2)2-OH, -CH2-OC(O)-CH(CH3)2, -CH2-OC(O)-CH2-CH3, -CH2-OP(=O)(OH)2, -CH2-OC(O)-CH2-N(CH3)2, -CH2-OC(O)-(CH2)2-N(CH3)2, -CH2-OC(O)-(CH2)3-N(CH3)2, -CH2-OC(O)-CH2-NHCH3, -CH2-OC(O)-CH2-NH2, -CH2-OC(O)-CH2-N + (CH3)3·M, -CH2-OC(O)-(CH2)3-N + (CH3)3·M, -CH2-OC(O)-CH2-(OCH2CH2)3OH, -CH2-OC(O)-CH2-(OCH2CH2)5OH, -CH2-OC(O)-(C H2)2-(OCH2CH2)5OH, -CH2-OC(O)-(CH2)2-(OCH2CH2)5OCH3, -CH2-OC(O)-(CH2)2-(OCH2CH2) 11OCH3, -CH2-OC(O)-CH2-OC(O)-CH2-N(CH3)2, -CH2-OC(O)-CH2-OH, -CH2-OC(O)-CH2-OP(=O)(OH)2, -C H2-OC(O)-CH2-OP(=O)(ONa)2, -CH2-OC(O)-CH2-OP(=O)(OH)(ONa), -CH2-OC(O)-CH2-(NCH3-CO-CH2) 10 H or -CH2-OC(O)-CH2-CH(OH)-CH2-N + (CH3)3·M (e.g.) Preferred );

[0206] M is an anion, preferably Q. - R L1-9 COO - 1 / 3 P(=O)(O) - )3 or R L1-10 S(O)2O - Q is preferred. - Or R L1-9 COO - ;

[0207] The -CH2-OC(O)-CH2-N + (CH3)3·M is preferably -CH2-OC(O)-CH2-N + (CH3)3·HCOO - -CH2-OC(O)-CH2-N + (CH3)3·Cl - -CH2-OC(O)-CH2-N + (CH3)3·CH3COO - -CH2-OC(O)-CH2-N + (CH3)3·CH3S(O)2O - -CH2-OC(O)-CH2-N + (CH3)3·1 / 3P(=O)(O - 3、-CH2-OC(O)-CH2-N + (CH3)3·CF3S(O)2O - ;

[0208] The -CH2-OC(O)-(CH2)3-N + (CH3)3·M is preferably -CH2-OC(O)-(CH2)3-N + (CH3)3·HCOO- ;

[0209] The -CH2-OC(O)-CH2-CH(OH)-CH2-N + (CH3)3·M is preferably -CH2-OC(O)-CH2-CH(OH)-CH2-N + (CH3)3·Cl - (For example Preferred ).

[0210] In some implementations, L is -CH2-OC(O)-CH3, -CH2-C(O)-OH, -CH2-O-CH3, -(CH2)2-OC(O)-CH3, -(CH2)2-O-CH3, -(CH2)2-OC(O)-CH(CH3)2, -CH2-OP(=O)(OH)2, -CH2-OC(O)-CH2-N(CH3)2, -CH2-OC(O)-(CH2)2-N(CH3)2, -CH2-OC(O)-(CH2)3-N(CH3)2, -CH2-OC(O)-CH2-NHCH3, -CH2-OC(O)-CH2-NH2, -CH2-OC(O)-CH2-N + (CH3)3·M, -CH2-OC(O)-(CH2)3-N + (CH3)3·M, -CH2-OC(O)-CH2-(OCH2CH2)3OH, -CH2-OC(O)-CH2-(OCH2CH2)5OH, -CH2-OC(O)-(C H2)2-(OCH2CH2)5OH, -CH2-OC(O)-(CH2)2-(OCH2CH2)5OCH3, -CH2-OC(O)-(CH2)2-(OCH2CH2) 11 OCH3, -CH2-OC(O)-CH2-OC(O)-CH2-N(CH3)2, -CH2-OC(O)-CH2-OH, -CH2-OC(O)-CH2-OP(=O)(OH)2, -CH2-OC(O)-CH2-(NCH3-CO-CH2) 10 H or -CH2-OC(O)-CH2-CH(OH)-CH2-N + (CH3)3·M (e.g.) Preferred );

[0211] M is an anion, preferably Q. - R L1-9 COO -1 / 3 P(=O)(O) - )3 or R L1-10 S(O)2O - Q is preferred. - Or R L1-9 COO - ;

[0212] The -CH2-OC(O)-CH2-N + (CH3)3·M is preferably -CH2-OC(O)-CH2-N + (CH3)3·HCOO - ;

[0213] The -CH2-OC(O)-(CH2)3-N + (CH3)3·M is preferably -CH2-OC(O)-(CH2)3-N + (CH3)3·HCOO - ;

[0214] The -CH2-OC(O)-CH2-CH(OH)-CH2-N + (CH3)3·M is preferably -CH2-OC(O)-CH2-CH(OH)-CH2-N + (CH3)3·Cl - (For example Preferred ).

[0215] In some implementations, L is -CH2-OC(O)-CH3, -CH2-OC(O)-CH2-OH, -CH2-OC(O)-CH2-OP(=O)(OH)2, -CH2-OC(O)-CH2-OP(=O)(ONa)2, -CH2-OC(O)-CH2-OP(=O)(OH)(ONa) or -CH2-OC(O)-CH2-CH(OH)-CH2-N + (CH3)3·M (e.g.) Preferred );

[0216] M is an anion, preferably Q. - R L1-9 COO - 1 / 3 P(=O)(O) - )3 or R L1-10 S(O)2O - Q is preferred. - Or R L1-9 COO - ;

[0217] The -CH2-OC(O)-CH2-CH(OH)-CH2-N + (CH3)3·M is preferably -CH2-OC(O)-CH2-CH(OH)-CH2-N + (CH3)3·Cl - (For example Preferred ).

[0218] In some implementations, L is -CH2-OC(O)-CH3, -CH2-OC(O)-CH2-OH, or -CH2-OC(O)-CH2-CH(OH)-CH2-N + (CH3)3·Cl - (For example Preferred ).

[0219] In some implementations, L is -CH2-OC(O)-CH3, -CH2-C(O)-OH, -CH2-O-CH3, -(CH2)2-OC(O)-CH3, -(CH2)2-O-CH3, -(CH2)2-OC(O)-CH(CH3)2, -(CH2)2-OH, -CH2-OC(O)-CH(CH3)2 or -CH2-OC(O)-CH2-CH3.

[0220] In some implementations, L is -CH2-OC(O)-CH3, -CH2-C(O)-OH, -CH2-O-CH3, -(CH2)2-OC(O)-CH3, -(CH2)2-O-CH3 or -(CH2)2-OC(O)-CH(CH3)2.

[0221] In some implementations, L is -CH2-OC(O)-CH3.

[0222] In some implementations, R is methyl.

[0223] In some embodiments, the compound represented by formula (A) or a pharmaceutically acceptable salt thereof, wherein the compound represented by formula (A) is a compound represented by formula (II) below.

[0224] In W, the two atoms or groups marked with * are in adjacent positions; R 1 R 2 R 3 R 4 R 5 R 6 R 7X, Y, T, W, m and R L1 The definition is as described in any one of the present invention.

[0225] In some embodiments, in the compound represented by formula (II), the fragment for R 1 R 2 R 3 R 4 R 5 R 6 X, Y, T, m and R L1 The definitions are as described in any one of the present invention.

[0226] In some embodiments, in the compound represented by formula (II), the fragment for (preferred) ); R 1 R 2 R 3 R 4 R 5 R 6 X, Y, T, m and R L1 The definitions are as described in any one of the present invention.

[0227] In some embodiments, in the compound represented by formula (II),

[0228] Excerpt for (preferred) For example, );

[0229] R 1 C 1-3 Alkyl, C 1-3 Alkoxy or C 3-6 cycloalkyl (preferably C) 1-3 alkyl);

[0230] R 2 C 1-3 Alkyl, C 1-3 Deuterated alkyl or C 1-3 Halogenated alkyl groups (preferably C14) 1-3 Alkyl or C 1-3 (deuterated alkyl);

[0231] R 3 R 4 Each is independently a halogen (preferably F);

[0232] R 5 R6 Each is independently H or deuterium (preferably H);

[0233] X is O or S (preferably O);

[0234] T is O;

[0235] m is 1 or 2 (preferably 1);

[0236] R L1 C 1-3 Alkyl, the C 1-3 Alkyl groups are optionally selected from hydroxyl, -NR L1-1 R L1-2 , -(OCH2CH2) t OR L1-6 -[OC(O)-(CH2) r ] s -R L1-7 , -OP(=O)(OH)2, -OP(=O)(ONa)2, -OP(=O)(OH)(ONa) and -(NCH3-CO-CH2) u R L1-8 One or two substituents are substituted (preferably, the C 1-3 Alkyl groups are optionally selected from hydroxyl groups, One or two of the substituents in -OP(=O)(OH)2, -OP(=O)(ONa)2, and -OP(=O)(OH)(ONa) are substituted; more preferably, the C 1-3 Alkyl groups may be selected from hydroxyl groups and / or Substituents of R; more preferably, R L1 It is -CH2-OH or -CH2-CH(OH)-CH2-N + (CH3)3·Cl - For example, R L1 -CH2-OH, For example, R L1 -CH2-OH or );

[0237] t is any integer from 3 to 11 (preferably 3, 5 or 11);

[0238] u is any integer from 5 to 15 (preferably 10);

[0239] r is 1, 2 or 3 (preferably 1);

[0240] s is 1 or 2 (preferably 1);

[0241] M is an anion (preferably Q). - RL1-9 COO - 1 / 3 P(=O)(O) - )3 or R L1-10 S(O)2O - Q is preferred. - Or R L1-9 COO - (Q is halogen);

[0242] R L1-1 and R L1-2 Each independently is H or C 1-3 alkyl;

[0243] R L1-3 R L1-4 and R L1-5 Each independently is C 1-3 alkyl;

[0244] R L1-6 For H or C 1-3 alkyl;

[0245] R L1-7 For -NR L1-71 R L1-72 ;

[0246] R L1-71 and R L1-72 Each independently is C 1-3 alkyl;

[0247] R L1-8 For H;

[0248] R L1-9 For H or C 1-3 Alkyl group (preferably H);

[0249] R L1-10 C 1-3 Alkyl or C 1-3 Halogenated alkyl groups.

[0250] In some embodiments, in the compound represented by formula (II),

[0251] Excerpt for (preferred) );

[0252] R 1 C 1-3 Alkyl, C 1-3 Alkoxy or C 3-6 cycloalkyl (preferably C) 1-3 alkyl);

[0253] R 2 C1-3 Alkyl, C 1-3 Deuterated alkyl or C 1-3 Halogenated alkyl groups (preferably C14) 1-3 Alkyl or C 1-3 (deuterated alkyl);

[0254] R 3 R 4 Each is independently a halogen (preferably F);

[0255] R 5 R 6 Each is independently H or deuterium (preferably H);

[0256] X is O;

[0257] T is O;

[0258] m is 1 or 2 (preferably 1);

[0259] R L1 C 1-3 Alkyl, the C 1-3 Alkyl groups are optionally selected from hydroxyl, -NR L1-1 R L1-2 , -(OCH2CH2) t OR L1-6 -[OC(O)-(CH2) r ] s -R L1-7 , -OP(=O)(OH)2, -OP(=O)(ONa)2, -OP(=O)(OH)(ONa) and -(NCH3-CO-CH2) u R L1-8 One or two substituents are substituted (preferably, the C 1-3 Alkyl groups are optionally selected from hydroxyl groups, One or two of the substituents in -OP(=O)(OH)2, -OP(=O)(ONa)2, and -OP(=O)(OH)(ONa) are substituted; more preferably, the C 1-3 Alkyl groups may be selected from hydroxyl groups and / or Substituents of R; more preferably, R L1 It is -CH2-OH or -CH2-CH(OH)-CH2-N + (CH3)3·Cl - For example, R L1 -CH2-OH, For example, R L1 -CH2-OH or );

[0260] t is any integer from 3 to 11 (preferably 3, 5 or 11);

[0261] u is any integer from 5 to 15 (preferably 10);

[0262] r is 1, 2 or 3 (preferably 1);

[0263] s is 1 or 2 (preferably 1);

[0264] M is an anion (preferably Q). - R L1-9 COO - 1 / 3 P(=O)(O) - )3 or R L1-10 S(O)2O - Q is preferred. - Or R L1-9 COO - (Q is halogen);

[0265] R L1-1 and R L1-2 Each independently is H or C 1-3 alkyl;

[0266] R L1-3 R L1-4 and R L1-5 Each independently is C 1-3 alkyl;

[0267] R L1-6 For H or C 1-3 alkyl;

[0268] R L1-7 For -NR L1-71 R L1-72 ;

[0269] R L1-71 and R L1-72 Each independently is C 1-3 alkyl;

[0270] R L1-8 For H;

[0271] R L1-9 For H or C 1-3 Alkyl group (preferably H);

[0272] R L1-10 C 1-3 Alkyl or C 1-3 Halogenated alkyl groups.

[0273] In some embodiments, the compound represented by formula (A) or a pharmaceutically acceptable salt thereof, wherein the compound represented by formula (A) is the compound represented by formula (III) below.

[0274] In W, the two atoms or groups marked with * are in adjacent positions; R 1 R 2 R 7 The definitions of X, Y, L and W are as described in any one of the present invention.

[0275] In some embodiments, in the compound represented by formula (III), the fragment for X, R 1 R 2 The definitions of L are as described in any one of the present invention.

[0276] In some embodiments, in the compound represented by formula (III), the fragment for (preferred) ); X, R 1 R 2 The definitions of L are as described in any one of the present invention.

[0277] In some embodiments, in the compound represented by formula (III),

[0278] Excerpt for (preferred) For example, );

[0279] R 1 C 1-3 Alkyl, C 1-3 Alkoxy or C 3-6 cycloalkyl (preferably C) 1-3 alkyl);

[0280] R 2 C 1-3 Alkyl, C 1-3 Deuterated alkyl or C 1-3 Halogenated alkyl groups (preferably C14) 1-3 Alkyl or C 1-3 (deuterated alkyl);

[0281] X is O or S (preferably O);

[0282] The definition of L is as described in any one of the claims of this invention.

[0283] In some embodiments, in the compound represented by formula (III),

[0284] Excerpt for (preferred) );

[0285] R 1 C 1-3 Alkyl, C 1-3 Alkoxy or C 3-6 cycloalkyl (preferably C) 1-3 alkyl);

[0286] R 2 C 1-3 Alkyl, C 1-3 Deuterated alkyl or C 1-3 Halogenated alkyl groups (preferably C14) 1-3 Alkyl or C 1-3 (deuterated alkyl);

[0287] X is O;

[0288] The definition of L is as described in any one of the claims of this invention.

[0289] In some embodiments, the compound represented by formula (A) or a pharmaceutically acceptable salt thereof, wherein the compound represented by formula (A) is the compound represented by formula (IV) below.

[0290] In W, the two atoms or groups marked with * are in adjacent positions; R 1 R 2 R 7 X, Y, W, m and R L1 The definition is as described in any one of the present invention.

[0291] In some embodiments, in the compound represented by formula (IV), the fragment for (preferred) ); X, R 1 R 2 m and R L1 The definition is as described in any one of the present invention.

[0292] In some embodiments, in the compound represented by formula (IV), the fragment for (preferred) ); X, R 1 R 2 m and R L1 The definition is as described in any one of the present invention.

[0293] In some embodiments, in the compound represented by formula (IV),

[0294] Excerpt for (preferred) For example, );

[0295] R 1 C 1-3 Alkyl, C 1-3 Alkoxy or C 3-6 Cycloalkyl, preferably C 1-3 alkyl;

[0296] R 2 C 1-3 Alkyl, C 1-3 Deuterated alkyl or C 1-3 Halogenated alkyl groups, preferably C 1-3 Alkyl or C 1-3 Deuterated alkyl groups;

[0297] X is either O or S, preferably O;

[0298] m is 1 or 2, preferably 1;

[0299] R L1 C 1-3 Alkyl, the C 1-3 Alkyl groups may be selected from hydroxyl, -NR L1-1 R L1-2 , -(OCH2CH2) t OR L1-6 -[OC(O)-(CH2) r ] s -R L1-7 , -OP(=O)(OH)2, -OP(=O)(ONa)2, -OP(=O)(OH)(ONa) and -(NCH3-CO-CH2) u R L1-8 One or two substituents are substituted; preferably, the C 1-3 Alkyl groups may be selected from hydroxyl groups, One or two of the substituents in -OP(=O)(OH)2, -OP(=O)(ONa)2, and -OP(=O)(OH)(ONa) are substituted; more preferably, the C 1-3 Alkyl groups may be selected from hydroxyl groups and / or Substituents; for example, R L1 It is -CH2-OH or -CH2-CH(OH)-CH2-N + (CH3)3·Cl - ;

[0300] t is any integer from 3 to 11 (preferably 3, 5 or 11);

[0301] u is any integer from 5 to 15 (preferably 10);

[0302] r is 1, 2 or 3 (preferably 1);

[0303] s is 1 or 2 (preferably 1);

[0304] M is an anion (preferably Q). - R L1-9 COO - 1 / 3 P(=O)(O) - )3 or R L1-10 S(O)2O - Q is preferred. - Or R L1-9 COO - (Q is halogen);

[0305] R L1-1 and R L1-2 Each independently is H or C 1-3 alkyl;

[0306] R L1-3 R L1-4 and R L1-5 Each independently is C 1-3 alkyl;

[0307] R L1-6 For H or C 1-3 alkyl;

[0308] R L1-7 For -NR L1-71 R L1-72 ;

[0309] R L1-71 and R L1-72 Each independently is C 1-3 alkyl;

[0310] R L1-8 For H;

[0311] R L1-9 For H or C 1-3 Alkyl group (preferably H);

[0312] R L1-10 C 1-3 Alkyl or C 1-3 Halogenated alkyl groups.

[0313] In some embodiments, in the compound represented by formula (IV),

[0314] Excerpt for (preferred) );

[0315] R 1 C 1-3 Alkyl, C 1-3 Alkoxy or C 3-6 Cycloalkyl, preferably C 1-3 alkyl;

[0316] R 2 C 1-3 Alkyl, C 1-3 Deuterated alkyl or C 1-3 Halogenated alkyl groups, preferably C 1-3 Alkyl or C 1-3 Deuterated alkyl groups;

[0317] X is O;

[0318] m is 1 or 2, preferably 1;

[0319] R L1 C 1-3 Alkyl, the C 1-3 Alkyl groups may be selected from hydroxyl, -NR L1-1 R L1-2 , -(OCH2CH2) t OR L1-6 -[OC(O)-(CH2) r ] s -R L1-7 , -OP(=O)(OH)2, -OP(=O)(ONa)2, -OP(=O)(OH)(ONa) and -(NCH3-CO-CH2) u R L1-8 One or two substituents are substituted; preferably, the C 1-3 Alkyl groups are optionally selected from hydroxyl groups, One or two of the substituents in -OP(=O)(OH)2, -OP(=O)(ONa)2, and -OP(=O)(OH)(ONa) are substituted; more preferably, the C 1-3 Alkyl groups may be selected from hydroxyl groups and / or Substituents; for example, R L1 It is -CH2-OH or -CH2-CH(OH)-CH2-N + (CH3)3·Cl - ;

[0320] t is any integer from 3 to 11 (preferably 3, 5 or 11);

[0321] u is any integer from 5 to 15 (preferably 10);

[0322] r is 1, 2 or 3 (preferably 1);

[0323] s is 1 or 2 (preferably 1);

[0324] M is an anion (preferably Q). - R L1-9 COO - 1 / 3 P(=O)(O) - )3 or R L1-10 S(O)2O - Q is preferred. - Or R L1-9 COO - (Q is halogen);

[0325] R L1-1 and R L1-2 Each independently is H or C 1-3 alkyl;

[0326] R L1-3 R L1-4 and R L1-5 Each independently is C 1-3 alkyl;

[0327] R L1-6 For H or C 1-3 alkyl;

[0328] R L1-7 For -NR L1-71 R L1-72 ;

[0329] R L1-71 and R L1-72 Each independently is C 1-3 alkyl;

[0330] R L1-8 For H;

[0331] R L1-9 For H or C 1-3 Alkyl group (preferably H);

[0332] R L1-10 C 1-3 Alkyl or C 1-3 Halogenated alkyl groups.

[0333] In some embodiments, the compound represented by formula (A) or a pharmaceutically acceptable salt thereof, wherein the compound represented by formula (A) is a compound represented by formula (V).

[0334] In W, the two atoms or groups marked with * are in adjacent positions; R 1 R 2R 3 R 4 R 5 R 6 R 7 The definitions of X, Y, T and W are as described in any one of the present invention.

[0335] In some embodiments, in the compound represented by formula (V), the fragment for

[0336] In some embodiments, in the compound represented by formula (V), the fragment for (preferred) ).

[0337] In some embodiments, T is O in the compound represented by formula (V).

[0338] In some embodiments, in the compound represented by formula (V), R 3 and R 4 For F, R 5 and R 6 For H.

[0339] In some embodiments, in the compound represented by formula (V), the fragment for (preferred) For example ); T is O; R 3 and R 4 For F, R 5 and R 6 For H.

[0340] In some embodiments, in the compound represented by formula (V), the fragment for (preferred) ); T is O; R 3 and R 4 For F, R 5 and R 6 For H.

[0341] In some embodiments, the compound represented by formula (A) or a pharmaceutically acceptable salt thereof, wherein the compound represented by formula (A) is a compound represented by formula (VI) below.

[0342] In W, the two atoms or groups marked with * are in adjacent positions; L and R 1 R 2 R 3 R 4 R 5 R 6 The definitions of X, Y, and W are as described in any one of the present invention.

[0343] In some embodiments, W in the compound shown in formula (VI) is a 5-6 membered heteroaryl or a 5-6 membered heterocyclic group.

[0344] In some embodiments, the compound represented by formula (A) or a pharmaceutically acceptable salt thereof is a compound represented by formula (VII).

[0345] In W, the two atoms or groups marked with * are in adjacent positions; R 8 and R 9 They are different and each independently consists of H, deuterium, halogen, and C. 1-3 Alkyl, C 1-3 Deuterated alkyl or C 1-3 Halogenated alkyl; R 1 R 2 R 3 R 4 R 5 R 6 R 7 The definitions of X, Y, and W are as described in any one of the present invention.

[0346] In some embodiments, in the compound represented by formula (VII), the fragment for R 8 and R 9 They are different and each independently consists of H, deuterium, halogen, and C. 1-3 Alkyl, C 1-3 Deuterated alkyl or C 1-3 Haloalkyl (preferably, R) 8 C 1-3 Alkyl (e.g., methyl) or C 1-3 Deuterated alkyl groups (e.g., -CD3); R 9 C 1-3 Halogenated alkyl groups (e.g., -CF3); R 1 R 2 R 3 R 4 R 5 R 6 The definitions of X and X are as described in any one of the present invention.

[0347] In some embodiments, in the compound represented by formula (VII), the fragment for (preferred) ); R 8 and R 9 They are different and each independently consists of H, deuterium, halogen, and C. 1-3 Alkyl, C 1- 3-deuterated alkyl or C 1-3 Haloalkyl (preferably, R) 8 C 1-3 Alkyl (e.g., methyl) or C 1-3 Deuterated alkyl groups (e.g., -CD3); R 9 C 1-3 Halogenated alkyl groups (e.g., -CF3); R 1 R 2 R 3 R 4 R 5 R 6 The definitions of X and X are as described in any one of the present invention.

[0348] In some embodiments, in the compound represented by formula (VII),

[0349] Excerpt for (preferred) For example, );

[0350] R 1 C 1-3 Alkyl, C 1-3 Alkoxy or C 3-6 cycloalkyl (preferably C) 1-3 Alkyl groups (e.g., methyl groups);

[0351] R 2 C 1-3 Alkyl, C 1-3 Deuterated alkyl or C 1-3 Halogenated alkyl groups (preferably C14) 1-3 Alkyl (e.g., methyl) or C 1-3 Deuterated alkyl groups (e.g., deuterated methyl groups);

[0352] R 3 and R 4 Each is an independent halogen (e.g., F);

[0353] R 5 and R 6 Each is independently H or deuterium (preferably H);

[0354] R8 and R 9 They are different and each independently consists of H, deuterium, halogen, and C. 1-3 Alkyl, C 1-3 Deuterated alkyl or C 1-3 Haloalkyl (preferably, R) 8 C 1-3 Alkyl (e.g., methyl) or C 1-3 Deuterated alkyl groups (e.g., -CD3); R 9 C 1-3 Halogenated alkyl groups (e.g., -CF3);

[0355] X can be O or S, preferably O.

[0356] In some embodiments, in the compound represented by formula (VII),

[0357] Excerpt for (preferred) );

[0358] R 1 C 1-3 Alkyl, C 1-3 Alkoxy or C 3-6 cycloalkyl (preferably C) 1-3 Alkyl groups (e.g., methyl groups);

[0359] R 2 C 1-3 Alkyl, C 1-3 Deuterated alkyl or C 1-3 Halogenated alkyl groups (preferably C14) 1-3 Alkyl (e.g., methyl) or C 1-3 Deuterated alkyl groups (e.g., deuterated methyl groups);

[0360] R 3 and R 4 Each is an independent halogen (e.g., F);

[0361] R 5 and R 6 Each is independently H or deuterium (preferably H);

[0362] R 8 and R 9 They are different and each independently consists of H, deuterium, halogen, and C. 1-3 Alkyl, C 1-3 Deuterated alkyl or C 1-3 Haloalkyl (preferably, R) 8 C 1-3 Alkyl (e.g., methyl) or C 1-3 Deuterated alkyl groups (e.g., -CD3); R 9 C1-3 Halogenated alkyl groups (e.g., -CF3);

[0363] X is O.

[0364] In some embodiments, in the compound represented by formula (VII),

[0365] Excerpt for

[0366] R 1 C 1-3 Alkyl groups (e.g., methyl groups);

[0367] R 2 C 1-3 Alkyl (e.g., methyl) or C 1-3 Deuterated alkyl groups (e.g., deuterated methyl groups);

[0368] R 3 and R 4 Each is an independent halogen (e.g., F);

[0369] R 5 and R 6 Each is independently represented by H;

[0370] R 8 C 1-3 Alkyl (e.g., methyl) or C 1-3 Deuterated alkyl groups (e.g., -CD3);

[0371] R 9 C 1-3 Halogenated alkyl groups (e.g., -CF3);

[0372] X can be O or S, preferably O.

[0373] In some embodiments, in the compound represented by formula (VII),

[0374] Excerpt for

[0375] R 1 C 1-3 Alkyl groups (e.g., methyl groups);

[0376] R 2 C 1-3 Alkyl (e.g., methyl) or C 1-3 Deuterated alkyl groups (e.g., deuterated methyl groups);

[0377] R 3 and R 4 Each is an independent halogen (e.g., F);

[0378] R 5 and R 6 Each is independently represented by H;

[0379] R 8 C 1-3 Alkyl (e.g., methyl) or C 1-3 Deuterated alkyl groups (e.g., -CD3);

[0380] R 9 C 1-3 Halogenated alkyl groups (e.g., -CF3);

[0381] X is O.

[0382] In some embodiments, the compound represented by formula (A) or a pharmaceutically acceptable salt thereof, wherein the compound represented by formula (A) is the compound represented by formula (VIII) below.

[0383] In W, the two atoms or groups marked with * are in adjacent positions; R 8 and R 9 They are different and each independently consists of H, deuterium, halogen, and C. 1-3 Alkyl, C 1-3 Deuterated alkyl or C 1-3 Halogenated alkyl; R 1 R 2 R 3 R 4 R 5 R 6 R 7 The definitions of X, Y, M and W are as described in any one of the present invention.

[0384] In some embodiments, the compound represented by formula (A) is a compound represented by formula (VIII-1) or formula (VIII-2).

[0385] In W, the two atoms or groups marked with * are in adjacent positions; R 8 and R 9 They are different and each independently consists of H, deuterium, halogen, and C. 1-3 Alkyl, C 1-3 Deuterated alkyl or C 1-3 Halogenated alkyl; R 1 R 2 R 3 R 4 R 5 R 6 R 7 The definitions of X, Y, M and W are as described in any one of the present invention.

[0386] In some embodiments, in the compounds represented by formulas (VIII), (VIII-1), and (VIII-2), the fragments for R 8 and R 9 They are different and each independently consists of H, deuterium, halogen, and C. 1-3 Alkyl, C 1-3 Deuterated alkyl or C 1-3 Haloalkyl (preferably, R) 8 C 1-3 Alkyl (e.g., methyl) or C 1-3 Deuterated alkyl groups (e.g., -CD3); R 9 C 1-3 Halogenated alkyl groups (e.g., -CF3); R 1 R 2 R 3 R 4 R 5 R 6 The definitions of M and X are as described in any one of the present invention.

[0387] In some embodiments, in the compounds represented by formulas (VIII), (VIII-1), and (VIII-2), the fragments for (preferred) ); R 8 and R 9 They are different and each independently consists of H, deuterium, halogen, and C. 1-3 Alkyl, C 1-3 Deuterated alkyl or C 1-3 Haloalkyl (preferably, R) 8 C 1-3 Alkyl (e.g., methyl) or C 1-3 Deuterated alkyl groups (e.g., -CD3); R 9 C 1-3 Halogenated alkyl groups (e.g., -CF3); R 1 R 2 R 3 R 4 R 5 R 6 The definitions of M and X are as described in any one of the present invention.

[0388] In some embodiments, the compounds represented by formulas (VIII), (VIII-1), and (VIII-2),

[0389] Excerpt for (preferred) For example, );

[0390] R 1 C 1-3 Alkyl, C 1-3 Alkoxy or C 3-6 cycloalkyl (preferably C) 1-3 Alkyl groups (e.g., methyl groups);

[0391] R 2 C 1-3 Alkyl, C 1-3 Deuterated alkyl or C 1-3 Halogenated alkyl groups (preferably C14) 1-3 Alkyl (e.g., methyl) or C 1-3 Deuterated alkyl groups (e.g., deuterated methyl groups);

[0392] R 3 and R 4 Each is an independent halogen (e.g., F);

[0393] R 5 and R 6 Each is independently H or deuterium (preferably H);

[0394] R 8 and R 9 They are different and each independently consists of H, deuterium, halogen, and C. 1-3 Alkyl, C 1-3 Deuterated alkyl or C 1-3 Haloalkyl (preferably, R) 8 C 1-3 Alkyl (e.g., methyl) or C 1-3 Deuterated alkyl groups (e.g., -CD3); R 9 C 1-3 Halogenated alkyl groups (e.g., -CF3);

[0395] X is either O or S, preferably O;

[0396] M is Q - R L1-9 COO - 1 / 3 P(=O)(O) - )3 or R L1-10 S(O)2O - (preferably Q) - Or R L1-9 COO - Q is preferred. - );

[0397] Q is a halogen (e.g., Cl);

[0398] R L1-9 For H or C 1-3 Alkyl group (preferably H);

[0399] R L1-10 C 1-3 Alkyl or C 1-3 Halogenated alkyl groups (e.g., fluoromethyl groups).

[0400] In some embodiments, the compounds represented by formulas (VIII), (VIII-1), and (VIII-2),

[0401] Excerpt for (preferred) );

[0402] R 1 C 1-3 Alkyl, C 1-3 Alkoxy or C 3-6 cycloalkyl (preferably C) 1-3 Alkyl groups (e.g., methyl groups);

[0403] R 2 C 1-3 Alkyl, C 1-3 Deuterated alkyl or C 1-3 Halogenated alkyl groups (preferably C14) 1-3 Alkyl (e.g., methyl) or C 1-3 Deuterated alkyl groups (e.g., deuterated methyl groups);

[0404] R 3 and R 4 Each is an independent halogen (e.g., F);

[0405] R 5 and R 6 Each is independently H or deuterium (preferably H);

[0406] R 8 and R 9 They are different and each independently consists of H, deuterium, halogen, and C. 1-3 Alkyl, C 1-3 Deuterated alkyl or C 1-3 Haloalkyl (preferably, R) 8 C 1-3 Alkyl (e.g., methyl) or C 1-3 Deuterated alkyl groups (e.g., -CD3); R 9 C 1-3 Halogenated alkyl groups (e.g., -CF3);

[0407] X is O;

[0408] M is Q - R L1-9 COO - 1 / 3 P(=O)(O)- )3 or R L1-10 S(O)2O - (preferably Q) - Or R L1-9 COO - Q is preferred. - );

[0409] Q is a halogen (e.g., Cl);

[0410] R L1-9 For H or C 1-3 Alkyl group (preferably H);

[0411] R L1-10 C 1-3 Alkyl or C 1-3 Halogenated alkyl groups (e.g., fluoromethyl groups).

[0412] In some embodiments, the compounds represented by formulas (VIII), (VIII-1), and (VIII-2),

[0413] Excerpt for

[0414] R 1 C 1-3 Alkyl groups (e.g., methyl groups);

[0415] R 2 C 1-3 Alkyl (e.g., methyl) or C 1-3 Deuterated alkyl groups (e.g., deuterated methyl groups);

[0416] R 3 and R 4 Each is an independent halogen (e.g., F);

[0417] R 5 and R 6 Each is independently represented by H;

[0418] R 8 C 1-3 Alkyl or C 1-3 Deuterated alkyl groups (e.g., methyl or -CD3);

[0419] R 9 C 1-3 Halogenated alkyl groups (e.g., -CF3);

[0420] X is either O or S, preferably O;

[0421] M is Q - Or R L1-9 COO - ; Preferably Q- ;

[0422] Q is a halogen (e.g., Cl);

[0423] R L1-9 For H.

[0424] In some embodiments, the compounds represented by formulas (VIII), (VIII-1), and (VIII-2),

[0425] Excerpt for

[0426] R 1 C 1-3 Alkyl groups (e.g., methyl groups);

[0427] R 2 C 1-3 Alkyl (e.g., methyl) or C 1-3 Deuterated alkyl groups (e.g., deuterated methyl groups);

[0428] R 3 and R 4 Each is an independent halogen (e.g., F);

[0429] R 5 and R 6 Each is independently represented by H;

[0430] R 8 C 1-3 Alkyl or C 1-3 Deuterated alkyl groups (e.g., methyl or -CD3);

[0431] R 9 C 1-3 Halogenated alkyl groups (e.g., -CF3);

[0432] X is O;

[0433] M is Q - or R L1-9 COO - ; Preferably Q - ;

[0434] Q is a halogen (e.g., Cl);

[0435] R L1-9 For H.

[0436] In the compounds of the present invention or their pharmaceutically acceptable salts, the compounds are selected from any of the following compounds:

[0437] The compounds of this invention can be prepared by referring to the methods in the examples.

[0438] The present invention also provides a pharmaceutical composition comprising:

[0439] (1) The compound or a pharmaceutically acceptable salt thereof described in any one of the present invention, and

[0440] (2) Pharmaceutically acceptable excipients.

[0441] The present invention also provides the use of any of the compounds of the present invention or a pharmaceutically acceptable salt thereof or any of the pharmaceutical compositions of the present invention in the preparation of Nav1.8 channel inhibitors.

[0442] In some implementations, the Nav1.8 channel inhibitor is an in vitro Nav1.8 channel inhibitor.

[0443] The present invention also provides the use of any compound of the present invention or a pharmaceutically acceptable salt thereof or any pharmaceutical composition of the present invention as a medicine.

[0444] The present invention also provides a compound of any one of the present invention or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition of any one of the present invention, as a medicine.

[0445] In some implementations, the drug is a drug for treating diseases related to the Nav1.8 channel.

[0446] In some implementations, the drug is a pain-relieving drug.

[0447] In some implementations, the disease associated with the Nav1.8 channel is pain.

[0448] In some implementations, the pain is acute pain.

[0449] The present invention also provides the use of any compound of the present invention or a pharmaceutically acceptable salt thereof or any pharmaceutical composition of the present invention in the preparation of a medicament.

[0450] In some implementations, the drug is a drug for treating diseases related to the Nav1.8 channel.

[0451] In some implementations, the drug is a drug for treating pain associated with the Nav1.8 channel.

[0452] In some implementations, the drug is a drug for acute pain associated with the Nav1.8 channel.

[0453] In some implementations, the drug is a pain-relieving drug.

[0454] In some implementations, the disease associated with the Nav1.8 channel is pain.

[0455] In some implementations, the pain is acute pain.

[0456] The present invention also provides a method for treating pain, comprising administering to a patient an effective amount of any of the compounds of the present invention or a pharmaceutically acceptable salt thereof or a pharmaceutical composition of any of the present invention.

[0457] This invention also provides any of the following compounds:

[0458] The present invention also provides a method for preparing the compound shown in formula (III), wherein,

[0459] (i) When fragment for When the compound represented by formula (III) is the same as the compound represented by formula (III-1), its preparation method includes the following steps:

[0460] In a solvent, in the presence of a catalyst, the compound shown in formula (III-1-1) undergoes the reduction reaction shown below to give the compound shown in formula (III-1);

[0461] Among them, R 1 R 2 The definitions of X and L are as described in any one of the present invention;

[0462] (ii) When fragment for When the compound represented by formula (III) is the same as the compound represented by formula (III-2), its preparation method includes the following steps:

[0463] In a solvent, in the presence of an acid, the compound shown in formula (III-2-1) undergoes the deprotection reaction shown below to give the compound shown in formula (III-2);

[0464] Among them, R 1 R 2 The definitions of X and L are as described in any one of the present invention;

[0465] (iii) When the fragment for When the compound represented by formula (III) is the same as the compound represented by formula (III-3), its preparation method includes the following steps:

[0466] In a solvent, in the presence of an oxidizing agent, the compound shown in formula (III-1) undergoes the following oxidation reaction to give the compound shown in formula (III-3);

[0467] Among them, R 1 R 2 The definitions of X and L are as described in any one of the present invention;

[0468] (iv) When fragment for When L is -CH2-OC(O)-CH3, the compound represented by formula (III) is the compound represented by formula (III-4), and its preparation method includes the following steps:

[0469] In a solvent, in the presence of a catalyst, the compound shown in formula (III-4-1) undergoes the reaction shown below to give the compound shown in formula (III-4);

[0470] Among them, R 1 R 2 The definitions of X and X are as described in any one of the present invention.

[0471] In the preparation method of the compound shown in formula (III-1), the reaction conditions for the reduction reaction can be conventional reaction conditions for such reactions in the art. The solvent can be a conventional solvent for such reactions in the art, such as ethanol and water. The catalyst can be a conventional catalyst for such reactions in the art, such as a platinum(II) hydrogenated complex of (dimethylphosphonic acid).

[0472] In the preparation method of the compound shown in formula (III-2), the deprotection reaction conditions can be conventional reaction conditions for such reactions in the art. The solvent can be a conventional solvent for such reactions in the art, such as hexafluoroisopropanol. The acid can be a conventional acid for such reactions in the art, such as trifluoroacetic acid.

[0473] In the preparation method of the compound shown in formula (III-3), the reaction conditions for the oxidation reaction can be conventional reaction conditions for such reactions in the art. The solvent can be a conventional solvent for such reactions in the art, such as dichloromethane. The oxidant can be a conventional oxidant for such reactions in the art, such as m-chloroperoxybenzoic acid.

[0474] In the method for preparing the compound shown in formula (III-4), the reaction conditions can be conventional reaction conditions for such reactions in the art. The solvent can be a conventional solvent for such reactions in the art, such as toluene. The catalyst can be a conventional catalyst for such reactions in the art, such as lead tetraacetate and copper acetate.

[0475] The present invention also provides a method for preparing the compound shown in formula (III-1-1), which includes the following steps:

[0476] In a solvent, in the presence of a catalyst, the compound shown in formula (III-1-2) undergoes the reaction shown below to give the compound shown in formula (III-1-1);

[0477] Where L is -CH2-OC(O)-CH3, R 1 R 2 The definitions of X and X are as described in any one of the present invention.

[0478] In the method for preparing the compound represented by formula (III-1-1), the reaction conditions can be those conventional for such reactions in the art. The solvent can be a conventional solvent for such reactions in the art, such as toluene. The catalyst can be a conventional catalyst for such reactions in the art, such as lead tetraacetate and copper acetate.

[0479] The present invention also provides a method for preparing the compound shown in formula (III-2-1), which includes the following steps:

[0480] In a solvent, in the presence of a catalyst, the compound shown in formula (III-2-2) undergoes the reaction shown below to give the compound shown in formula (III-2-1);

[0481] Where L is -CH2-OC(O)-CH3, R 1 R 2 The definitions of X and X are as described in any one of the present invention.

[0482] In the method for preparing the compound represented by formula (III-2-1), the reaction conditions can be those conventional for such reactions in the art. The solvent can be a conventional solvent for such reactions in the art, such as toluene. The catalyst can be a conventional catalyst for such reactions in the art, such as lead tetraacetate and copper acetate.

[0483] In some embodiments, the method for preparing the compound represented by formula (III-1) further includes the method for preparing the compound represented by formula (III-1-1).

[0484] In some embodiments, the method for preparing the compound represented by formula (III-2) further includes the method for preparing the compound represented by formula (III-2-1).

[0485] The present invention also provides a method for preparing the compound shown in formula (IV), which includes the following steps:

[0486] In a solvent, in the presence of an iodine reagent, a base, and an optional molecular sieve, the compound shown in formula (IV-1) and the compound shown in formula (IV-2) or their salts undergo the substitution reaction shown below to give the compound shown in formula (IV).

[0487] In W, the two *-marked atoms or groups are in adjacent positions; B is Cl or Br (preferably Cl), m, R 1 R 2 R 7 X, Y, W and R L1 The definition is as described in any one of the present invention.

[0488] In the preparation method of the compound shown in formula (IV), the reaction conditions for the substitution reaction can be conventional reaction conditions for such reactions in the art. The solvent can be a conventional solvent for such reactions in the art, such as a nitrile solvent, preferably acetonitrile. The iodination reagent can be a conventional iodination reagent for such reactions in the art, such as NaI or KI, preferably NaI. The base can be a conventional base for such reactions in the art, such as an alkali metal salt of carbonate, preferably sodium carbonate. The molecular sieve can be a conventional molecular sieve for such reactions in the art, such as 4A molecular sieve.

[0489] In some embodiments, the preparation of the compound represented by formula (IV) may further include post-treatment purification. This post-treatment purification may be a conventional post-treatment purification method for such reactions in the art, such as purification by reversed-phase column chromatography.

[0490] Terminology Explanation

[0491] In addition to the foregoing, when used in the specification and claims of this invention, the following terms shall have the following meanings unless otherwise specifically indicated.

[0492] In this invention, the term "pharmaceutically acceptable salt" refers to a salt obtained by reacting a compound with a pharmaceutically acceptable acid or base. When a compound contains a relatively acidic functional group, a base addition salt can be obtained by contacting the compound with a sufficient amount of a pharmaceutically acceptable base in a suitable inert solvent. When a compound contains a relatively basic functional group, an acid addition salt can be obtained by contacting the compound with a sufficient amount of a pharmaceutically acceptable acid in a suitable inert solvent. See Handbook of Pharmaceutical Salts: Properties, Selection, and Use (P. Heinrich Stahl, Camille G. Wermuth, 2011, 2nd Revised Edition).

[0493] The term "pharmaceuticalally acceptable excipients" refers to excipients and additives used in the manufacture and dispensing of pharmaceutical products. These are all substances included in pharmaceutical preparations, excluding the active ingredient. See the Pharmacopoeia of the People's Republic of China (2015 edition), Volume IV, or the Handbook of Pharmaceutical Excipients (Raymond C. Rowe, 2009 Sixth Edition).

[0494] The pharmaceutical compositions of the present invention can be prepared using any method known to those skilled in the art, based on the disclosure.

[0495] The term “treatment” refers to a therapeutic approach or a remission measure. When a specific condition is involved, treatment means: (1) alleviating one or more biological manifestations of the disease or condition; (2) interfering with (a) one or more points in a biological cascade that causes or precipitates the condition or (b) one or more biological manifestations of the condition; (3) improving one or more symptoms, effects, or side effects associated with the condition, or one or more symptoms, effects, or side effects associated with the condition or its treatment; or (4) slowing the progression of the disease or one or more biological manifestations of the condition. “Treatment” can also mean prolonging survival compared to expected survival without treatment.

[0496] Unless otherwise stated, this invention employs traditional methods of mass spectrometry and elemental analysis, and the steps and conditions can be referred to conventional operating procedures and conditions in the field.

[0497] Unless otherwise specified, this invention employs standard nomenclature and standard laboratory procedures and techniques of analytical chemistry, organic synthetic chemistry, and optics. In some cases, standard techniques are used in chemical synthesis and chemical analysis.

[0498] Furthermore, it should be noted that, unless otherwise explicitly stated, the descriptive phrase "...independently (as / selected from)" used in this invention should be interpreted broadly, meaning that the described entities are independent of each other and can independently be the same or different specific functional groups. More specifically, the descriptive phrase "...independently (as / selected from)" can mean either that the specific options expressed by the same symbol in different functional groups do not affect each other, or that the specific options expressed by the same symbol in the same functional group do not affect each other.

[0499] The term "optionally replaced by one or more A's" refers to both cases where the object is not replaced by an A and cases where the object is replaced by one or more A's.

[0500] The term "N is arbitrarily oxidized to N→O" refers to two scenarios: N is not oxidized and N is oxidized to N→O.

[0501] The term "S optional and simultaneously" "Substitution" means that S is not substituted and is simultaneously substituted. Replaces both scenarios.

[0502] The term "replaced by" refers to the substitution 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.

[0503] When a substituent is described using a conventional chemical formula written from left to right, that substituent also includes chemically equivalent substituents obtained when the structural formula is written from right to left. For example, CH2O is equivalent to OCH2. As used herein, Indicates the linking site of a functional group.

[0504] The numerical ranges described in this application specification and claims, when interpreted as "integers," should be understood to include both endpoints of the range and every integer within that range. For example, "any integer from 1 to 20" should be understood as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20; and "integers from 1 to 6" should be understood as including every integer of 1, 2, 3, 4, 5, and 6.

[0505] The term "halogen" refers to fluorine, chlorine, bromine, and iodine.

[0506] The term "amino" represents -NH2.

[0507] The term "cyano" represents -CN.

[0508] Term "C" 1-6 "Alkyl" should be understood as a straight-chain or branched saturated monovalent hydrocarbon group having 1, 2, 3, 4, 5 or 6 carbon atoms.

[0509] Term "C" 1-3 "Alkyl" should be understood to refer to a straight-chain or branched saturated monovalent hydrocarbon group having 1, 2, or 3 carbon atoms. 1-3 Alkyl groups are, for example, methyl, ethyl, n-propyl, isopropyl, or their isomers.

[0510] Term "C" 1-3 "Alkoxy" should be understood as representing a straight-chain or branched saturated monovalent hydrocarbon group with 1, 2, or 3 carbon atoms and an oxygen atom, or represented as C 1-3 Alkyl-O-. C 1-3 Alkyl groups are defined as described in this specification, and oxygen atoms may be attached to C. 1-3 On any carbon atom of the straight or branched alkyl chain. Including but not limited to: methoxy (CH3-O-), ethoxy (C2H5-O-), propoxy (C3H7-O-).

[0511] Term "C" 3-6 "Cycloalkyl" should be understood to mean a cyclic alkyl group having 3 to 6, 3 to 5, or 3 to 4 carbon atoms, which may contain 1 to 2 rings and may be monocyclic, bicyclic, spirocyclic, or bridged. Monocyclic is preferred.

[0512] The term "halogenated alkyl" refers to an alkyl group that has been substituted with one or more halogens. Therefore, "halogenated alkyl" encompasses the definitions of halogens and alkyl groups above. For example, alkyl groups substituted with 1-6 halogens, preferably alkyl groups substituted with 1-3 halogens. The term "C"... 1-3 "Halogenated alkyl" refers to C 1-3 The alkyl group is substituted with one or more halogens, preferably C1 substituted with one, two or three halogens. 1-3 Alkyl groups, such as trifluoromethyl, difluoromethyl, difluoroethyl, and trifluoroethyl.

[0513] The term "deuterated alkyl" refers to an alkyl group in which any one hydrogen atom is replaced by one or more deuterium atoms, and can be an alkyl group substituted with 1 to 6 deuterium atoms, preferably an alkyl group substituted with 1 to 3 deuterium atoms. The term "C" 1-3 "Deuterated alkyl" refers to C 1-3 The alkyl group is substituted with one or more deuterium atoms, preferably C atoms substituted with 1, 2 or 3 deuterium atoms. 1-3 Alkyl groups, such as methyl groups substituted with 1-3 deuterium atoms, ethyl groups substituted with 1-3 deuterium atoms, n-propyl groups substituted with 1-3 deuterium atoms, and isopropyl groups substituted with 1-3 deuterium atoms. The term "deuterated methyl" refers to a methyl group in which any one hydrogen atom is replaced by one or more deuterium atoms, which can be substituted with 1, 2, or 3 deuterium atoms, such as monodeuterated methyl, dideuterated methyl, and trideuterated methyl.

[0514] The term "5-6 membered heteroaryl" or "5-6 membered heteroaryl ring" refers to a monocyclic heteroaryl group or ring having aromaticity and 5-6 ring atoms, containing 1-4 heteroatoms selected from one or more of nitrogen (N), oxygen (O), and sulfur (S), with the remaining ring atoms being carbon (C), wherein N can be oxidized to N→O. The heteroaryl group is linked to the parent molecule via any connectable atoms. Exemplary examples include, but are not limited to: 5-membered heteroaryl groups: furanyl, thiophene, pyrrole, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, imidazolyl, pyrazolyl, 1,2,3-triazolyl, 1,2,4-triazolyl, tetrazolyl; 6-membered heteroaryl groups: pyridinyl, N-oxypyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, 1,3,5-triazinyl.

[0515] The term "5-6 membered heterocyclic group" or "5-6 membered heterocycle" refers to a non-aromatic, saturated or partially unsaturated monocyclic heterocyclic group or ring with 5-6 ring atoms, containing 1-4 heteroatoms selected from one or more of nitrogen (N), oxygen (O), and sulfur (S), with the remaining ring atoms being carbon (C). S may be simultaneously... Substitution. The heterocyclic group is linked to the parent molecule via any connectable atom. Exemplary examples include, but are not limited to: saturated heterocyclic groups / saturated heterocycles (fully saturated): nitrogen-containing heterocyclic butyl, pyrrolyl, imidazolyl, pyrazolyl, piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl (1,4-thiazinyl), tetrahydrofuranyl, tetrahydropyranyl, 1,4-dioxane, oxane-butyl, tetrahydrothiophenyl, tetrahydrothiophenyl; partially unsaturated heterocyclic groups / partially unsaturated heterocycles: dihydrofuranyl (e.g., 2,5-dihydrofuran-3-yl), dihydrothiophenyl (e.g., 2,5-dihydrothiophen-3-yl), dihydropyrrolyl (e.g., ... 2,5-Dihydro-1H-pyrrolo-3-yl), 4H-oxazoline (e.g., 4,5-dihydrooxazo-4-yl), 2,5-dihydrooxazolyl, 4,5-dihydro-1H-imidazolyl, dihydropyranyl (e.g., 3,4-dihydro-2H-pyran-5-yl, 5,6-dihydro-2H-pyran-3-yl), dihydrothiaranyl, 1,2-dihydropyridyl, 1,2-dihydropyrimidinyl, 1,4-dihydropyridyl, 1,2,3,4-tetrahydropyridyl, 2,3-dihydropyridazinyl, 4H-pyranyl (e.g., 4H-pyran-4-yl).

[0516] The term "diacyclic group" refers to an 8- to 12-membered bicyclic system formed by two rings sharing a common side. Each of the two rings is independently selected from: a benzene ring, a 5-6 membered heteroaromatic ring, a 5-6 membered heterocycle, or a C3-6 monocyclic carbon ring (such as cyclopropane, cyclobutane, cyclopentane, or cyclohexane). The dicyclic group is connected to the parent molecule via any connectable atom.

[0517] Based on common knowledge in the field, the above-mentioned preferred conditions / implementations can be combined arbitrarily to obtain various preferred embodiments of the present invention.

[0518] The reagents and raw materials used in this invention are all commercially available.

[0519] The positive and progressive effects of the present invention are that the compounds of the present invention have one or more of the following effects: (1) inhibitory activity against Nav1.8; (2) good solubility; (3) good analgesic effect; (4) good pharmacokinetic characteristics; (5) rapid onset of action; (6) rapid oral absorption; and (7) suitable for injection administration. Attached Figure Description

[0520] Figure 1 shows the analgesic effect of the I-001 mouse incision pain model, where * represents the significant difference between the I-001 10mpk group and the model group (*** indicates extremely significant difference P<0.01; * indicates significant difference P<0.05), and # represents the significant difference between the I-001 5mpk group and the model group (# indicates significant difference P<0.05).

[0521] Figure 2 shows the analgesic effect of the I-002 mouse incision pain model, where * represents the significant difference between the I-002 10mpk group and the model group (*** indicates extremely significant difference P<0.01; * indicates significant difference P<0.05).

[0522] Figure 3 shows the analgesic effect of the I-029 rat incision pain model, where * represents the significant difference between the I-029 30mpk group and the model group (* indicates a significant difference P<0.05).

[0523] Figure 4 shows the analgesic effect of the I-029 mouse incision pain model, where * represents the significant difference between the I-029 3mpk group and the model group (* indicates a significant difference P<0.05). Detailed Implementation

[0524] The present invention is further illustrated below by way of embodiments, but the invention is not limited to the scope of the embodiments described herein. Experimental methods in the following embodiments that do not specify specific conditions were performed according to conventional methods and conditions, or as selected according to the product instructions.

[0525] Specific Implementation

[0526] Example 1: Synthesis method of compound I-001

[0527] Synthesis of intermediates 1-2 in step 1

[0528] Compound 1-1a (8.24 g, 49.14 mmol, 2 eq) and compound 1-1 (3 g, 24.57 mmol, 1 eq) were dissolved in 50 mL of acetonitrile, and triethylamine (7.46 g, 73.71 mmol, 10.26 mL, 3 eq) was added. The reaction mixture was heated under reflux at 90 °C for 2 h. LC-MS monitoring showed complete consumption of the starting materials and formation of the main product. The reaction mixture was filtered, and the filtrate was concentrated under reduced pressure to the residue, which was then subjected to silica gel column chromatography. 40g Purification was performed using a silica gel column (eluting with 0-80% ethyl acetate / petroleum ether, 50 mL / min) to give intermediates 1-2 as white solids (3.62 g, yield: 63.14%). LCMS (ESI): m / z C 12 H 16 N3O2 + Calculated value [M+H] + =234.12, measured value =234.1. 1H NMR (400MHz, CDCl3) δppm 8.28 (d, J = 5.7 Hz, 1H), 6.84 (d, J = 2.3 Hz, 1H), 6.59 (dd, J = 2.5, 5.8 Hz, 1H), 3.85 (d, J = 4.8 Hz, 2H), 1.53 (s, 9H).

[0529] Synthesis of intermediates 1-4 in step 2

[0530] Compounds 1-3 (preparation method according to patent WO2021 / 113627 A1) (1 g, 2.82 mmol, 1 eq) were dissolved in 6 mL of dichloromethane, and DMF (20.63 mg, 282.27 μmol, 21.72 μL, 0.1 eq) was added. Oxaloyl chloride (1.07 g, 8.47 mmol, 741.26 μL, 3 eq) was slowly added dropwise to the above reaction system. The reaction solution was stirred at 25 °C for 5 hours, and then concentrated under reduced pressure to obtain intermediate 1-4, a colorless oily substance (1.05 g, crude product).

[0531] Synthesis of intermediates 1-5 in step 3

[0532] Intermediate 1-2 (375.51 mg, 1.61 mmol, 2 eq) was dissolved in 5 mL of dichloromethane, and diisopropylethylamine (416.10 mg, 3.22 mmol, 4 eq) and intermediate 1-4 (300 mg, 804.91 μmol, 1 eq) were added sequentially. The reaction mixture was stirred at 20 °C for 1 hour. LC-MS monitoring was performed to confirm complete consumption of the starting materials and product formation. The reaction mixture was concentrated under reduced pressure to the residue and subjected to silica gel column chromatography (ISCO Preparative Liquid Chromatography; column model: 24g). Intermediates 1-5 were prepared using a Silica Flash Column; mobile phase gradient: 0–60% ethyl acetate / petroleum ether; flow rate: 40 mL / min, as colorless oils (420 mg, yield: 91.62%). LCMS (ESI): m / z C 27 H 29 F5N3O5 + Calculated value [M+H] + =570.20, measured value =570.2. 1H NMR(400MHz,DMSO-d6)δppm 8.78(d,J=5.3Hz,1H),8.06(s,1H),7.73(d,J=5.0Hz,1H),7.07(q,J=8.9Hz,1H),6.96-6.83(m,1H),5.14(d,J=5.3Hz,1H),4 .60-4.36(m,2H),4.28(t,J=8.5Hz,1H),3.94(s,3H),2.67(t,J=7.5Hz,1H),1.48(s,3H),1.35(s,9H),0.64(d,J=6.0Hz,3H).

[0533] Synthesis of intermediates 1-6 in step 4

[0534] Intermediate 1-5 (400 mg, 702.35 μmol, 1 eq) was dissolved in 5 mL of dichloromethane, and trifluoroacetic acid (15.34 g, 134.54 mmol, 10 mL) was added dropwise to the solution. The reaction mixture was stirred at 40 °C for 1 hour. LC-MS monitoring showed complete consumption of the starting material and formation of the main product. The reaction solution was concentrated under reduced pressure to the residue and subjected to silica gel column chromatography (ISCO Preparative Liquid Chromatography; column model: 12 g). Intermediates 1-6 were prepared using a Silica Flash Column; mobile phase gradient: 0–10% methanol / dichloromethane; flow rate: 30 mL / min, as a white solid (340 mg, yield: 94.29%). LCMS (ESI): m / z C 23 H 21 F5N3O5 + Calculated value [M+H] + =514.14, measured value =514.3. 1 H NMR(400MHz,DMSO-d6)δppm 13.24-12.87(m,1H),8.76(d,J=5.4Hz,1H),8.05(d,J=1.9Hz,1H),7.74(dd,J=2.1,5.5Hz,1H),7.05(q,J=8.8Hz,1H),6.87(d,J=4.6Hz, 1H), 5.24-5.05 (m, 1H), 4.48 (s, 2H), 4.27 (t, J = 8.8Hz, 1H), 3.94 (d, J = 1.9Hz, 3H), 2.71-2.66 (m, 1H), 1.49 (s, 3H), 0.64 (d, J = 6.1Hz, 3H).

[0535] Synthesis of intermediates 1-7 in step 5

[0536] Intermediate 1-6 (300 mg, 584.32 μmol, 1 eq) was dissolved in 40 mL of anhydrous toluene, and lead tetraacetate (388.61 mg, 876.49 μmol, 1.5 eq) and copper acetate (10.61 mg, 58.43 μmol, 0.1 eq) were added sequentially. The reaction system was protected under nitrogen and stirred at 90 °C for 1 hour. LC-MS monitoring showed that the main product was formed, indicating complete consumption of the starting materials. The reaction solution was quenched with 5 mL of saturated sodium sulfite solution, the organic phase was separated, and the solution was washed sequentially with water (10 mL × 2), saturated brine (10 mL), dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure to the residue, which was then subjected to silica gel column chromatography (ISCO Preparative Liquid Chromatography; column model: 24g). Intermediates 1-7 were prepared using a Silica Flash Column; mobile phase gradient: 0–80% ethyl acetate / petroleum ether; flow rate: 40 mL / min, as a colorless oil (160 mg, yield: 51.92%). LCMS (ESI): m / z C 24 H 23 F5N3O5 + Calculated value [M+H] + =528.16, measured value =528.3. 1 H NMR (400MHz, CDCl3) δppm 8.75(d,J=5.3Hz,1H),7.76(d,J=1.5Hz,1H),7.55(dd,J=1.5,5.3Hz,1H) ,6.83(q,J=8.8Hz,1H),6.59(s,1H),5.93(d,J=10.3Hz,1H),5.66(d,J=11 .5Hz,1H),5.22-5.05(m,1H),4.46(t,J=9.2Hz,1H),4.03(d,J=2.3Hz,3H ), 2.75 (t, J = 7.8Hz, 1H), 2.12 (s, 3H), 1.57 (s, 3H), 0.76 (d, J = 6.5Hz, 3H).

[0537] Step 6: Synthesis of Compound I-001

[0538] Intermediate 1-7 (160 mg, 303.35 μmol, 1 eq) was dissolved in 5 mL of ethanol and 0.8 mL of water, and the platinum(II) hydrogenated complex of (dimethylphosphonic acid) (CAS: 173416-05-2) (12.96 mg, 30.34 μmol, 0.1 eq) was added. The reaction system was stirred at 85 °C for 1 hour. LCMS monitoring showed complete consumption of the starting material and formation of the main product. The reaction solution was concentrated under reduced pressure to the residue and subjected to silica gel column chromatography (ISCO Preparative Liquid Chromatography; column model: 12g). Compound I-001 was prepared as a white solid (130 mg, yield: 78.57%) using a silica flash column; mobile phase gradient: 0–100% ethyl acetate / petroleum ether; flow rate: 40 mL / min. LCMS (ESI): m / z C 24 H 25 F5N3O6 + Calculated value [M+H] + =546.17, measured value =546.1. 1 H NMR(400MHz,DMSO-d6)δppm 8.66(d,J=5.3Hz,1H),8.15(s,1H),7.94(d,J=2.0Hz,1H),7.74(d,J=1.3H z,1H),7.59(dd,J=2.0,5.3Hz,1H),7.08(q,J=8.8Hz,1H),6.86(s,1H),5. 82-5.68(m,2H),5.31-5.12(m,1H),4.30(t,J=8.7Hz,1H),3.95(d,J=2.0H z, 3H), 2.80-2.69 (m, 1H), 2.01 (s, 3H), 1.50 (s, 3H), 0.66 (d, J = 6.0Hz, 3H).

[0539] Example 2: Synthesis method of compound I-002

[0540] Synthesis of intermediates 2-4 in step 1

[0541] Referring to the synthesis method in steps 2 to 4 of Example 1, intermediate 2-1 was used as the raw material (LCMS(ESI): m / z C 15 H 13 D3F5O4 + Calculated value [M+H] + =358.12, measured value =358.1. 1 ¹H NMR (400MHz, CDCl₃) δppm 7.01-6.94 (m, 1H), 6.93-6.85 (m, 1H), 4.99 (d, J = 10.8Hz, 1H), 4.13 (d, J = 7.5Hz, 1H), 2.76 (q, J = 7.7Hz, 1H), 1.66 (s, 3H), 0.79 (d, J = 7.0Hz, 3H). Intermediates 2-4 were prepared according to the synthesis method described in patent WO2022 / 256702A1, and were white solids. LCMS (ESI): m / z C 23 H 18 D3F5N3O5 +Calculated value [M+H] + =517.16, measured value =517.2. 1 H NMR(400MHz,DMSO-d6)δppm 13.02(s,1H),8.76(d,J=5.5Hz,1H),8.05(d,J=2.0Hz,1H),7.73(dd,J=2.3,5.3Hz,1H),7.12-6.97(m,1H),6.90-6.79(m ,1H),5.21-5.03(m,1H),4.62-4.36(m,2H),4.27(t,J=8.4Hz,1H),2.74-2.62(m,1H),1.49(s,3H),0.64(d,J=5.6Hz,3H).

[0542] Synthesis of intermediates 2-5 in step 2

[0543] Following the synthesis method in step 5 of Example 1, intermediate 2-5 was prepared from intermediate 2-4 as a raw material; it was a colorless oily substance. LCMS(ESI): m / zC 24 H 20 D3F5N3O5 + Calculated value [M+H] + =531.17, measured value =531.1. 1 H NMR (400MHz, CDCl3) δppm 8.75(d,J=5.4Hz,1H),7.75(d,J=2.0Hz,1H),7.54(dd,J=2.1,5.4Hz,1H),6.86-6.77(m,1H),6.59(s,1H),6.00-5.85(m,1H),5.66(d ,J=11.6Hz,1H),5.11(d,J=3.6Hz,1H),4.46(t,J=9.2Hz,1H),2.75(q,J=7.7Hz,1H),2.12(s,3H),1.57(s,3H),0.76(d,J=5.8Hz,3H).

[0544] Step 3: Synthesis of compound I-002

[0545] Following the synthesis method in step 6 of Example 1, compound I-002, a white solid, was prepared using intermediates 2-5 as raw materials. LCMS(ESI): m / z C 24 H 22 D3F5N3O6 + Calculated value [M+H] + =549.18, measured value =549.2. 1H NMR(400MHz,DMSO-d6)δppm 8.66(d,J=5.2Hz,1H),8.15(s,1H),7.94(d,J=1.7Hz,1H),7.74(s,1H),7.59(dd,J=2.1,5.2Hz,1H),7.08(q,J=8.6Hz,1H),6.86(d,J=6.4Hz,1H ),5.80-5.63(m,2H),5.20(dd,J=1.9,3.8Hz,1H),4.30(t,J=8.5Hz,1H),2.72(t,J=7.6Hz,1H),2.01(s,3H),1.50(s,3H),0.66(d,J=5.6Hz,3H).

[0546] Example 3 Synthesis of Compound I-003

[0547] Synthesis of intermediate 3-2 in step 1

[0548] Intermediate 3-1 (203.24 mg, 1.05 mmol, 1.3 eq) (synthetic method according to patent reference WO2024 / 123815A1) was dissolved in 5 mL of dichloromethane, and diisopropylethylamine (416.10 mg, 3.22 mmol, 560.79 μL, 4 eq) and intermediate 1-4 (0.3 g, 804.91 μmol, 1 eq) were added sequentially. The reaction system was stirred at 20 °C for 1 hour. LC-MS monitoring showed complete consumption of the starting materials and formation of products. The reaction solution was concentrated under reduced pressure to the residue and subjected to silica gel column chromatography (ISCO Preparative Liquid Chromatography; column model: 24 g). Intermediate 3-2 was prepared using a Silica Flash Column; mobile phase gradient: 0–60% ethyl acetate / petroleum ether; flow rate: 40 mL / min, as a white solid (354 mg, yield: 82.91%). LCMS (ESI): m / z C 25 H 28 F5N2O5 + Calculated value [M+H] + =531.19, measured value =531.2. 1¹H NMR (400MHz, DMSO-d⁶) δppm 10.45(s,1H),8.71(d,J=2.3Hz,1H),8.07(d,J=8.7Hz,1H),7.45(d,J=8.6Hz, 1H),7.22-7.12(m,2H),5.12-5.05(m,2H),4.33(dd,J=6.7,8.2Hz,1H),4.25( dd,J=7.7,10.2Hz,1H),3.95(d,J=2.0Hz,3H),3.82(dd,J=6.7,8.2Hz,1H),2. 82-2.72(m,1H),1.61(s,3H),1.42(s,3H),1.39(s,3H),0.73(d,J=6.1Hz,3H).

[0549] Synthesis of intermediate 3-3 in step 2

[0550] Intermediate 3-2 (300 mg, 565.52 μmol, 1 eq) was dissolved in 10 mL of tetrahydrofuran, and sodium hydride (113.10 mg, 2.83 mmol, 5 eq) of 60% purity was added in portions at 0 °C. After stirring the reaction system at 0 °C for 10 min, compound 3-2a (1.30 g, 5.66 mmol, 887.29 μL, 10 eq) and sodium iodide (25.43 mg, 169.66 μmol, 0.3 eq) were added. The system was then protected with nitrogen and stirred at 20 °C for 12 h. The reaction solution was quenched with 10 mL of saturated ammonium chloride solution, and the mixture was extracted with ethyl acetate (5 mL × 3). The organic phases were combined, dried over anhydrous magnesium sulfate, filtered, and the filtrate was concentrated under reduced pressure to the residue, which was then subjected to silica gel column chromatography (ISCO Preparative Liquid Chromatography; column model: 40 g). Intermediate 3-3 was prepared using a Silica Flash Column; mobile phase gradient: 0–60% ethyl acetate / petroleum ether; flow rate: 40 mL / min, as a white solid (340 mg, yield: 88.59%). LCMS (ESI): m / z C 34 H 36 F5N2O7 + Calculated value [M+H] + =679.24, measured value =679.2. 1H NMR (400MHz, CDCl3) δppm 8.54(d,J=2.0Hz,1H),7.81(dd,J=2.1,8.2Hz,1H),7.57(d,J=8.3Hz,1H),7.38-7.29(m,5H),6. 80-6.65(m,1H),6.36(t,J=6.1Hz,1H),5.24(t,J=6.5Hz,1H),5.14(s,2H),4.63(d,J=9.3Hz,1H ),4.56-4.47(m,2H),4.35(t,J=9.2Hz,1H),4.29(d,J=17.3Hz,1H),4.01(d,J=2.3Hz,3H),3.95 (dd,J=6.5,8.5Hz,1H),2.71(q,J=7.8Hz,1H),1.56(s,6H),1.52(s,3H),0.61(d,J=6.0Hz,3H).

[0551] Synthesis of intermediates 3-4 in step 3

[0552] Intermediate 3-3 (40 mg, 58.94 μmol, 1 eq) was dissolved in 5 mL of anhydrous ethanol. Palladium hydroxide on carbon (16.55 mg) was added under a nitrogen atmosphere. The reaction system was evacuated and then purged with hydrogen, repeated three times. The system was then stirred at 25 °C for 4 hours under a hydrogen atmosphere. LCMS monitoring confirmed complete consumption of the starting material. The reaction solution was filtered, and the filtrate was concentrated to obtain intermediate 3-4 as a colorless oil (35 mg, crude product). LCMS (ESI): m / z C 27 H 30 O7N2F5 + Calculated value [M+H] + =589.2, measured value =589.3. 1 H NMR(400MHz,DMSO-d6)δppm 8.52(d,J=2.1Hz,1H),7.83(dd,J=2.3,8.3Hz,1H),7.50(d,J=8.3Hz,1H),7.01(q,J= 8.9Hz,1H),6.56(t,J=6.9Hz,1H),5.14(t,J=6.6Hz,1H),4.74(d,J=8.9Hz,1H),4.34 (s,1H),4.30(s,2H),4.20(t,J=8.7Hz,1H),3.95(d,J=1.7Hz,3H),3.81(d,J=6.9Hz, 1H), 2.69-2.67 (m, 1H), 1.50 (s, 3H), 1.44 (s, 3H), 1.42 (s, 3H), 0.56 (d, J = 6.3Hz, 3H).

[0553] Synthesis of intermediates 3-5 in step 4

[0554] Intermediate 3-4 (35 mg, 59.47 μmol, 1 eq) was dissolved in 4 mL of anhydrous toluene, and lead tetraacetate (39.55 mg, 89.21 μmol, 1.5 eq) and copper acetate (1.08 mg, 5.95 μmol, 0.1 eq) were added sequentially. The reaction system was protected under nitrogen and stirred at 90 °C for 40 min. LC-MS monitoring showed that the main product was formed, indicating complete consumption of the starting materials. The reaction solution was quenched with 5 mL of saturated sodium sulfite solution to separate the organic phase. The organic phase was washed sequentially with water (10 mL × 2), then with saturated brine (10 mL), dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure to the residue. The residue was then subjected to silica gel column chromatography (ISCO Preparative Liquid Chromatography; column model: 4g). Intermediate 3-5 was prepared using a SilicaFlash Column; mobile phase gradient: 0–80% ethyl acetate / petroleum ether; flow rate: 30 mL / min, as a colorless oil (17 mg, yield: 47.44%). LCMS (ESI): m / z C 28 H 32 F5N2O7 + Calculated value [M+H] + =603.22, measured value =603.2.

[0555] Step 5: Synthesis of compound I-003

[0556] Intermediate 3-5 (17 mg, 28.21 μmol, 1 eq) was dissolved in 1 mL of hexafluoroisopropanol, and 0.2 mL of trifluoroacetic acid was added. The reaction system was stirred at 50 °C for 1 hour under nitrogen protection. LCMS monitoring showed that the main product was formed, indicating complete consumption of the starting material. The reaction solution was directly concentrated to the residue, and compound I-003 was prepared by silica gel plate preparation (electrolyte: ethyl acetate / ethanol = 20 / 1; Rf = 0.5) as a white solid (4.32 mg, yield: 27.22%). LCMS (ESI): m / z C 25 H 28 F5N2O7 + Calculated value [M+H] + =563.18, measured value =563.2. 1¹H NMR (400MHz, CDCl₃) δppm 8.49(s,1H),7.71(dd,J=2.1,8.3Hz,1H),7.51(d,J=8.3Hz,1H),7.25(s,1H) ,6.90-6.73(m,1H),6.50-6.25(m,1H),5.60(s,2H),4.91(t,J=4.8Hz,1H),4 .39(s,1H),4.02(d,J=2.4Hz,3H),3.97(dd,J=3.7,11.3Hz,1H),3.81(dd,J= 5.7,11.3Hz,1H),2.70(s,3H),2.07(s,3H),1.55(s,3H),0.76-0.46(m,3H).

[0557] Example 4 Synthesis of Compound I-004

[0558] Following the synthesis method of Example 3, compound I-004, a white solid, was prepared using intermediate 2-2 as a starting material. LCMS (ESI): m / z C 25 H 25 D3F5N2O7 + Calculated value [M+H] + =566.20, measured value =566.2. 1 H NMR (400MHz, CDCl3) δppm 8.59 (s, 1H), 8.45 (s, 1H), 8.11 (dd, J = 1.7, 8.5Hz, 1H), 7.33 (d, J = 8.5Hz, 1H), 7.09 (br t,J=6.6Hz,1H),6.98-6.85(m,1H),5.03(d,J=10.8Hz,1H),4.79(br t,J=4.4Hz,1H),4.11(dd,J=8.5,10.4Hz,1H),3.90(dd,J=3.5,11.3Hz,1H),3.73(dd, J=5.7,11.3Hz,1H),2.79–2.72(m,1H),2.62-2.10(m,2H),1.75-1.50(m,3H),0.80(br d,J=6.1Hz,3H).

[0559] Example 5: Synthesis of Compound I-005

[0560] Compound I-001 (20 mg, 36.67 μmol, 1 eq) was dissolved in 2 mL of dichloromethane, and m-chloroperoxybenzoic acid (119.10 mg, 586.67 μmol, 85% purity, 16 eq) was added. The reaction system was stirred at 25 °C for 20 h under nitrogen protection. TLC monitoring showed the formation of the main product, with a small amount of reactants remaining. The reaction solution was concentrated under reduced pressure to the residue, and then subjected to silica gel column chromatography (ISCO Preparative Liquid Chromatography; column model: 8g). Intermediate I-005 was prepared as a white solid (13.2 mg, yield: 64.11%) using a Silica Flash Column mobile phase gradient (0–90% ethyl acetate / petroleum ether; flow rate: 35 mL / min). LCMS (ESI): m / z C 24 H 25 F5N3O7 + Calculated value [M+H] + =562.16, measured value =562.1. 1 ¹H NMR (400MHz, DMSO-d⁶) δppm 10.19(d,J=3.3Hz,1H),8.45(d,J=7.0Hz,1H),8.32(d,J=3.8Hz,1H),8.09(d ,J=3.1Hz,1H),7.60(dd,J=3.2,7.0Hz,1H),7.07(q,J=8.9Hz,1H),6.92(s,1 H),5.67(s,2H),5.17(d,J=10.6Hz,1H),4.31(t,J=8.7Hz,1H),3.96(d,J=1. 8Hz, 3H), 2.77-2.68 (m, 1H), 2.01 (s, 3H), 1.51 (s, 3H), 0.67 (d, J = 5.8Hz, 3H).

[0561] Example 6 Synthesis of Compound I-006

[0562] Following the synthesis method in step 6 of Example 1, compound I-006, a white solid, was prepared using intermediates 1-6 as raw materials. LCMS(ESI): m / z C 23 H 23 F5N3O6 + Calculated value [M+H] + =532.15, measured value =532.1. 1H NMR(400MHz,DMSO-d6)δppm 13.40-12.53(m,1H),8.70(d,J=5.2Hz,1H),8.20(s,1H),8.01(d,J=1.9Hz,1H),7.78(d,J=1.0Hz,1H),7.63(d,J=3.7Hz,1H),7.11-6.95(m,1 H),6.82-6.55(m,1H),5.19-4.86(m,1H),4.69-4.39(m,2H),4.34(t,J =7.9Hz,1H),4.00(s,3H),2.79-2.73(m,1H),1.57(s,3H),0.67(s,3H).

[0563] Example 7 Synthesis of Compound I-007

[0564] Synthesis of intermediate 7-2 in step 1

[0565] Intermediate 7-1 (671.18 mg, 5.63 mmol, 2 eq) was dissolved in 6 mL of dichloromethane, and diisopropylethylamine (1.46 g, 11.27 mmol, 1.96 mL, 4 eq) was added. Intermediate 1-4 (1.05 g, 2.82 mmol, 1 eq) was added to the above solution. The reaction mixture was stirred at 20 °C for 1 hour. LC-MS monitoring was performed to confirm complete consumption of the starting material and product formation. The reaction mixture was concentrated under reduced pressure to the residue and subjected to silica gel column chromatography (ISCO Preparative Liquid Chromatography; column model: 24 g). Intermediate 7-2 was prepared using a Silica Flash Column; mobile phase gradient: 0–60% ethyl acetate / petroleum ether; flow rate: 40 mL / min, as a white solid (810 mg, yield: 63.14%). LCMS (ESI): m / z C 21 H 19 F5N3O3 + Calculated value [M+H] + =456.13, measured value =456.2. 1H NMR (400MHz, CDCl3) δppm 8.71-8.54(m,2H),8.06(d,J=2.0Hz,1H),7.67(dd,J=2.1,5.6Hz,1H),7.11-7.04(m,1H),6.98-6.90(m,1H),5.05(d,J= 11.2Hz, 1H), 4.11 (dd, J = 8.1, 11.1Hz, 1H), 4.04 (d, J = 2.9Hz, 3H), 2.78 (q, J = 7.7Hz, 1H), 1.71 (s, 3H), 0.85-0.78 (m, 3H).

[0566] Synthesis of intermediate 7-3 in step 2

[0567] Intermediate 7-2 (40 mg, 87.84 μmol, 1 eq) was dissolved in 2 mL of tetrahydrofuran, and cesium carbonate (286.20 mg, 878.39 μmol, 10 eq) and compound 7-2a (109.77 mg, 878.39 μmol, 71.70 μL, 10 eq) were added sequentially. The reaction system was stirred at 50 °C for 24 hours. LC-MS monitoring showed a small amount of reactant remaining and the formation of the main product. The reaction solution was filtered, and the filtrate was concentrated under reduced pressure to obtain the residue, which was dissolved in 4 mL of dichloromethane and washed successively with water (2 mL × 2) and saturated brine (2 mL). The residue was dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure to obtain intermediate 7-3, a colorless oily substance (50 mg, crude product). LC-MS (ESI): m / z C 23 H 23 F5N3O4 + Calculated value [M+H] + =500.16, measured value =500.1.

[0568] Step 3: Synthesis of compound I-007

[0569] Following the synthetic method in step 6 of Example 1, compound I-007 was prepared from intermediate 7-3 as a starting material. It was a white solid (20 mg, yield: 36.79%). LCMS (ESI): m / z C 23 H 25 F5O5N3 + Calculated value [M+H] + =518.16, measured value =518.1. 1H NMR(400MHz,DMSO-d6)δppm 8.65(d,J=5.2Hz,1H),8.15(s,1H),7.93(d,J=1.8Hz,1H),7.73(s,1H),7.57(dd,J=2.0,5.2Hz,1H),7.07(q,J=8.7Hz,1H),6.80(s,1H), 5.21-5.03(m,3H),4.30(t,J=8.7Hz,1H),3.94(d,J=1.8Hz,3H),3.23(s,3H),2.73(q,J=7.5Hz,1H),1.52(s,3H),0.65(d,J=6.1Hz,3H).

[0570] Example 8 Synthesis of Compound I-008

[0571] Synthesis of intermediate 8-2 in step 1

[0572] Intermediate 8-1 (300.00 mg, 2.17 mmol, 1 eq) and intermediate 8-1a (906.66 mg, 6.50 mmol, 3 eq) were dissolved in 3 mL of acetonitrile, and cesium carbonate (2.12 g, 6.50 mmol, 3 eq) was added. The reaction mixture was stirred at 90 °C for 12 hours. LC-MS monitoring showed complete consumption of the starting materials and product formation. The reaction mixture was filtered, and the filtrate was concentrated under reduced pressure to the residue, followed by silica gel column chromatography (ISCO Preparative Liquid Chromatography; column model: 24 g). Intermediate 8-2 was prepared as a white solid (210 mg, yield: 47%) using a Silica Flash Column; mobile phase gradient: 0–100% ethyl acetate / petroleum ether; flow rate: 40 mL / min. LCMS (ESI): m / z C 10 H 12 N3O2 + Calculated value [M+H] + =206.09, measured value =206.1. 1 H NMR (400MHz, CDCl3) δppm 8.26(d,J=5.8Hz,1H), 6.89(d,J=2.3Hz,1H), 6.62(dd,J=2.3,5.8Hz,1H), 4.94(s,1H), 4.32(t,J=5.4Hz,2H), 3.47(q,J=5.4Hz,2H), 2.10(s,3H).

[0573] Synthesis of intermediate 8-3 in step 2

[0574] Intermediate 8-2 (107.37 mg, 523.19 μmol, 1.5 eq) was dissolved in 4 mL of dichloromethane, and diisopropylethylamine (180.31 mg, 1.40 mmol, 4 eq) and intermediate 1-4 (130 mg, 348.79 μmol, 1 eq) were added sequentially. The reaction mixture was stirred at 20 °C for 1 hour. LC-MS monitoring showed complete consumption of the starting material and product formation. The reaction solution was concentrated under reduced pressure to the residue and subjected to silica gel column chromatography (ISCO Preparative Liquid Chromatography; column model: 24g). Intermediate 8-3 was prepared using a Silica Flash Column; mobile phase gradient: 0–60% ethyl acetate / petroleum ether; flow rate: 40 mL / min, as a white solid (61 mg, yield: 32.3%). LCMS (ESI): m / z C 25 H 25 F5N3O5 + Calculated value [M+H] + =542.17, measured value =542.2. 1 H NMR (400MHz, CDCl3) δppm 8.80 (d, J = 5.2Hz, 1H), 7.77 (d, J = 1.8Hz, 1H), 7.59 (dd, J = 2.0, 5.3Hz, 1H), 6.87-6.68 (m, 1H), 6.50 -6.26(m,1H),4.70-4.57(m,1H),4.43(t,J=9.2Hz,1H),4.31-4.18(m,2H),4.11-4.05(m,1H),4.03(d,J=2 .5Hz,3H),4.01-3.93(m,1H),2.74(q,J=8.0Hz,1H),1.92(s,3H),1.60-1.57(m,3H),0.69(d,J=6.1Hz,3H).

[0575] Step 3: Synthesis of compound I-008

[0576] Following the synthesis method in step 6 of Example 1, compound I-008, a white solid, was prepared using intermediate 8-3 as a starting material. LCMS (ESI): m / z C 25 H 27 F5N3O6 + Calculated value [M+H] + =560.18, measured value =560.2. 1¹H NMR (400MHz, CDCl₃) δppm 8.64(d,J=5.1Hz,1H),8.17(d,J=2.0Hz,1H),7.85(d,J=3.1Hz,1H),7.54(dd, J=2.1,5.2Hz,1H),6.80-6.67(m,1H),6.30(d,J=3.2Hz,1H),5.65(d,J=3.1Hz, 1H),4.72-4.56(m,1H),4.39(t,J=9.2Hz,1H),4.28-4.14(m,2H),4.12-3.92( m, 5H), 2.72 (q, J = 7.8Hz, 1H), 1.95 (s, 3H), 1.59 (s, 3H), 0.63 (d, J = 6.0Hz, 3H).

[0577] Example 9: Synthesis of Compound I-009

[0578] Following the synthesis method of Example 8, and replacing the corresponding starting materials, compound I-009 was prepared using intermediate 9-1a as the starting material. It was a white solid (10 mg, yield: 32.21%). LCMS (ESI): m / z C 24 H 27 F5N3O5 + Calculated value [M+H] + =532.19, measured value =532.2. 1 H NMR (400MHz, DMSO-d6) δppm8.65(d,J=5.2Hz,1H),8.14(s,1H),7.92(s,1H),7.72(s,1H),7.56(dd,J=2.1,5.2Hz,1H),7.13-6.95(m,1H),6.83-6.55 (m,1H),4.31-4.22(m,1H),3.94(d,J=1.5Hz,6H),3.47-3.35(m,2H),3.15 (s,3H),2.70(dd,J=7.7,15.4Hz,1H),1.51(s,3H),0.60(d,J=2.9Hz,3H).

[0579] Example 10 Synthesis of Compound I-010

[0580] Following the synthesis method of Example 8, and replacing the corresponding starting materials, compound I-010 was prepared using intermediate 10-1a as the starting material. It is a white solid. LCMS (ESI): m / z C 27 H 31 F5N3O6 + Calculated value [M+H]+ =588.22, measured value =588.2. 1 H NMR (400MHz, CDCl3) δppm 8.64(d,J=5.2Hz,1H),8.15(d,J=2.0Hz,1H),7.85(d,J=3.6Hz,1H),7.55(dd,J=2.1,5.2Hz, 1H),6.80-6.67(m,1H),6.29(s,1H),5.65(d,J=3.1Hz,1H),4.80-4.52(m,1H),4.40(t,J=9.2 Hz,1H),4.26-4.15(m,3H),4.01(d,J=2.5Hz,3H),3.97-3.87(m,1H),2.72(q,J=7.7Hz,1H),2 .40(td,J=7.0,14.0Hz,1H),1.58(s,3H),1.04(dd,J=7.0,9.3Hz,6H),0.62(d,J=6.4Hz,3H).

[0581] Example 11 Synthesis of Compound I-011

[0582] Step 1: Synthesis of Compound 11-2

[0583] Intermediate 11-1 (300.00 mg, 2.02 mmol, 1 eq) and intermediate 11-1a (357 mg, 2.02 mmol, 1 eq, 50% toluene solution) were dissolved in 50 mL of methanol, and sodium cyanoborohydride (254.49 mg, 4.05 mmol, 2 eq) was added. The reaction mixture was stirred at 20 °C for 1 hour. LC-MS monitoring showed complete consumption of the starting materials and product formation. The reaction solution was concentrated under reduced pressure to the residue and subjected to silica gel column chromatography (ISCO Preparative Liquid Chromatography; column model: 20 g). Intermediate 11-2 was prepared by Silica Flash Column (mobile phase gradient: 0–100% ethyl acetate / petroleum ether; flow rate: 35 mL / min), as a colorless oil (200 mg, yield: 44%). LCMS (ESI): m / z C 11 H 13 N2O3 + Calculated value [M+H] + =220.09, measured value =221.0. 1H NMR(400MHz,DMSO-d6)δppm 8.35(s,1H),7.26(d,J=8.2Hz,1H),6.85(dd,J=2.1,8.2Hz,1H),6.72(d,J=2.0 Hz, 1H), 6.29 (t, J = 6.2 Hz, 1H), 4.20 (s, 2H), 3.97 (d, J = 6.4 Hz, 2H), 3.66 (s, 3H).

[0584] Step 2: Synthesis of compound 11-3

[0585] Intermediate 11-2 (200 mg, 908.17 μmol, 1 eq) was dissolved in 30 mL of methanol and 5 mL of water, and sodium hydroxide (54.49 mg, 1.36 mmol, 1.5 eq) was added. The reaction mixture was stirred at 20 °C for 1 hour. LC-MS monitoring showed complete consumption of the starting material and product formation. The reaction mixture was concentrated under reduced pressure to 2 mL, and 1 M dilute hydrochloric acid was added dropwise until the pH reached 3. A precipitate formed, which was filtered, washed with water, and dried under vacuum to obtain intermediate 11-3 as a white solid (150 mg, yield: 80%). 1 H NMR (400MHz, DMSO-d6) δppm 8.34 (s, 1H), 7.25 (d, J = 8.2Hz, 1H), 6.86 (dd, J = 2.3, 8.2Hz, 1H), 6.71 (d, J = 2.1Hz, 1H), 4.19 (s, 2H), 3.85 (s, 2H).

[0586] Step 3: Synthesis of compound 11-4

[0587] Following the synthesis method in step 1 of Example 7, compound 11-4, a white solid, was prepared from intermediate 11-3. LCMS (ESI): m / z C 25 H 21 D3F5N2O6 + Calculated value [M+H] + =546.18, measured value =546.2. 1 H NMR (400MHz, CDCl3) δppm 7.85 (s, 1H), 7.76 (s, 1H), 7.63 (d, J = 7.7Hz, 1H), 7.45 (d, J = 8.0Hz, 1H), 6.71-6.57 (m, 1H), 6.32 -6.21(m,1H),4.61(d,J=9.2Hz,1H),4.45(s,1H),4.43(s,2H),4.28(t,J=8.8Hz,1H),2.74-2.63(m,1H),1.53(s,3H),0.54(d,J=7.2Hz,3H).

[0588] Step 3: Synthesis of compound I-011

[0589] Intermediate 11-4 (30 mg, 55.00 μmol, 1 eq) was dissolved in 3 mL of toluene. Under a nitrogen atmosphere, lead tetraacetate (36.58 mg, 82.50 μmol, 1.5 eq) and copper acetate (998.96 μg, 5.50 μmol, 0.1 eq) were added sequentially. The reaction system was stirred at 90 °C for 40 min. LCMS monitoring showed complete consumption of the starting material and product formation. The reaction solution was concentrated under reduced pressure to the residue, and compound I-011 was prepared by thin-layer silica gel chromatography (ethyl acetate / methanol / petroleum ether = 100 / 5 / 50), yielding a colorless oily compound (9.1 mg, yield: 29.57%). LCMS (ESI): m / z C 26 H 23 D3F5N2O6 + Calculated value [M+H] + =560.19, measured value =560.2. 1 H NMR (400 MHz, CDCl3) δppm 7.71(s,1H),7.54(s,2H),7.19(s,1H),6.72(d,J=6.0Hz,1H),6.29(s,1H),5.65(d,J=16.6Hz,2H),4.5 9(d,J=8.8Hz,1H),4.51(s,2H),4.35(s,1H),2.77-2.64(m,1H),2.04(s,3H),1.58(s,3H),0.60(s,3H).

[0590] Example 12 Synthesis of Compound I-012

[0591] Following the synthesis method of Example 11, and replacing the corresponding starting materials, compound I-012 was prepared using intermediate 12-1 as the starting material. It is a white solid. LCMS (ESI): m / z C 24 H 22 D3F6N2O7S + Calculated value [M+H] + =602.15, measured value =602.2.

[0592] Example 13: Synthesis method of compound I-013

[0593] Synthesis of intermediate 13-2 in step 1

[0594] Intermediate 13-1 (10.0 g, 83.95 mmol, 1.0 eq) was dissolved in 40 mL of acetonitrile, and compound 13-1a (12.16 g, 125.92 mmol, 1.5 eq), cesium carbonate (54.70 g, 167.89 mmol, 2 eq), and sodium iodide (1.26 g, 8.39 mmol, 0.1 eq) were added sequentially. The reaction mixture was stirred at 65 °C for 5 hours. LC-MS monitoring showed that some reactants remained and the main product was formed. The reaction mixture was filtered, and the filtrate was diluted with 20 mL of water and 20 mL of ethyl acetate. The organic phase was separated, and the aqueous phase was extracted with ethyl acetate (10 mL × 3). The combined organic phases were washed with saturated brine (10 mL × 2), dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure to obtain the residue, which was then subjected to silica gel column chromatography. 12g Intermediate 13-2 was purified by silica gel column chromatography (elution buffer: 0-90% ethyl acetate / petroleum ether, 40 mL / min) to a white solid (1.9 g, yield: 12.63%). LCMS (ESI): m / z C8H 10 N3S + Calculated value [M+H] + =180.06, measured value [M+H] + =180.1. 1 HNMR (400MHz, CDCl3) δppm 8.31 (d, J = 5.7Hz, 1H), 6.96 (d, J = 2.1Hz, 1H), 6.71 (dd, J = 2.4, 5.7Hz, 1H), 5.00 (s, 1H), 4.36 (d, J = 6.4Hz, 2H), 2.17 (s, 3H).

[0595] Synthesis of intermediates 1-4 in step 2

[0596] Compounds 1-3 (500 mg, 1.41 mmol, 1 eq) were dissolved in 6 mL of dichloromethane, and DMF (10.32 mg, 141.14 μmol, 0.1 eq) was added. Oxaloyl chloride (537.41 mg, 4.23 mmol, 3 eq) was then slowly added dropwise to the above reaction system. After the addition was complete, the reaction solution was stirred at 25 °C for 5 hours. The reaction solution was then concentrated under reduced pressure to give intermediate 1-4, a colorless oily substance (526 mg, crude product).

[0597] Synthesis of intermediate 13-3 in step 3

[0598] Intermediate 13-2 (240.45 mg, 1.34 mmol, 2 eq) was dissolved in 4 mL of dichloromethane, and diisopropylethylamine (346.75 mg, 2.68 mmol, 4 eq) and intermediate 1-4 (250 mg, 670.76 μmol, 1 eq) were added sequentially. The reaction mixture was stirred at 20 °C for 1 hour. LC-MS monitoring was performed to confirm complete consumption of the starting material and product formation. The reaction mixture was concentrated under reduced pressure to the residue and subjected to silica gel column chromatography (ISCO Preparative Liquid Chromatography; column model: 12g). Intermediate 13-3 was prepared using a Silica Flash Column; mobile phase gradient: 0–60% ethyl acetate / petroleum ether; flow rate: 40 mL / min. It was a colorless oil (210 mg, yield: 60.73%). LCMS (ESI): m / z C 23 H 23 F5N3O3S + Calculated value [M+H] + =516.14, measured value =516.2. 1 H NMR (400MHz, CDCl3) δppm 8.81(d,J=5.2Hz,1H),7.83(d,J=1.8Hz,1H),7.64(dd,J=2.1,5.4Hz,1H),6.87-6.72(m,1H),6.41(s,1H),5.02(d,J=13.9Hz,1H),4.79(d,J=14 .1Hz,1H),4.44(t,J=9.4Hz,1H),4.28-4.26(m,1H),4.03(d,J=2.6Hz,3 H), 2.78-2.70 (m, 1H), 2.12 (s, 3H), 1.59 (s, 3H), 0.69 (d, J = 5.8Hz, 3H).

[0599] Synthesis of intermediate 13-4 in step 4

[0600] Intermediate 13-3 (150 mg, 290.98 μmol, 1 eq) was dissolved in 3 mL of dichloromethane, and thioyl chloride (54.98 mg, 407.38 μmol, 1.4 eq) was added. The reaction mixture was stirred at 25 °C for 1 hour. LCMS monitoring showed complete consumption of the starting material and product formation. The reaction solution was concentrated under reduced pressure to obtain intermediate 13-4, a colorless oil (146 mg, crude product). LCMS (ESI): m / z C 22 H 20 ClF5N3O3 + Calculated value [M+H] + =504.11, measured value [M+H] + =504.1.

[0601] Synthesis of intermediate 13-5 in step 5

[0602] Intermediate 13-4 (146 mg, 289.77 μmol, 1 eq) was dissolved in 6 mL of acetonitrile, and compound 13-4a (143.90 mg, 579.54 μmol, 2 eq), sodium iodide (8.69 mg, 57.95 μmol, 0.2 eq), sodium carbonate (61.42 mg, 579.54 μmol, 2 eq), and 4A molecular sieve (50 mg) were added sequentially. The reaction system was stirred at 40 °C for 1 hour. LCMS was used to monitor complete consumption of the starting material and the formation of products. The reaction solution was filtered, and the filtrate was concentrated under reduced pressure to the residue, which was then subjected to silica gel column chromatography. 4g Intermediate 13-5 was purified by silica gel column chromatography (elution buffer: 0-90% ethyl acetate / n-hexane, 35 mL / min) to a white solid (140 mg, yield: 71.3%). LCMS (ESI): m / z C 30 H 38 F5N3O7P + Calculated value [M+H] + =678.24, measured value [M+H] + =678.2. 1 H NMR (400MHz, CDCl3) δppm 8.73(d,J=5.5Hz,1H),7.89(d,J=2.0Hz,1H),7.68(dd,J=2.1,5.5Hz,1H),6.88-6.74(m,2H),6.06-5.80(m,1H),5.60-5.23(m, 2H),4.58-4.44(m,1H),4.05(d,J=2.4Hz,3H),2.80-2.73(m,1H),1.60(s,3H),1.51(s,9H),1.48(s,9H),0.80(d,J=6.0Hz,3H).

[0603] Synthesis of intermediates 13-6 in step 6

[0604] Intermediate 13-5 (137 mg, 202.19 μmol, 1 eq) was dissolved in 15 mL of ethanol, and then 1 mL of water and Perkins catalyst (CAS: 173416-05-2) (8.64 mg, 20.22 μmol, 0.1 eq) were added sequentially. The reaction system was stirred at 50 °C for 1 hour. LCMS was used to monitor complete consumption of the starting material. The reaction solution was filtered, and the filtrate was concentrated under reduced pressure to the residue, which was then subjected to silica gel column chromatography (…). 4g Intermediate 13-6 was purified by silica gel column chromatography (elution buffer: 0-80% ethyl acetate / n-hexane, 35 mL / min) to a white solid (128 mg, yield: 91.0%). LCMS (ESI): m / z C 30 H 40 F5N3O8P + Calculated value [M+H] + =696.25, measured value [M+H] + =696.2.

[0605] Step 7: Synthesis of compound I-013

[0606] Intermediate 13-6 (70 mg, 100.63 μmol, 1 eq) was dissolved in 2 mL of trifluoroacetic acid, and the mixture was stirred at 25 °C for 10 min. LCMS monitoring showed complete consumption of the starting material and product formation. The reaction solution was concentrated under reduced pressure to the residue and then subjected to reversed-phase column chromatography (column type: 86-Wepure PHS Phenyl; size: 150*30 mm; particle size: 7 μm; mobile phase: [phase A: water (0.075% trifluoroacetic acid) - phase B: acetonitrile]; gradient: 42%-72% B, 15 min) to prepare compound I-013 as a white solid (3 mg, yield: 5.11%). LCMS (ESI): m / z C 22 H 24 F5N3O8P + Calculated value [M+H] + =584.12, measured value [M+H] + =584.2.

[0607] Example 14 Synthesis method of compound I-014

[0608] Synthesis of intermediates 2-3 in step 1

[0609] Following the synthesis method in steps 2 to 3 of Example 13, intermediate 14-1, a white solid, was prepared using intermediate 2-1 as the raw material. LCMS(ESI): m / z C 23 H 20 D3F5N3O3S + Calculated value [M+H] + =519.16, measured value =519.1. 1H NMR(400MHz,DMSO-d6)δppm 8.80(d,J=5.2Hz,1H),8.14(d,J=1.9Hz,1H),7.82(dd,J=2.1,5.4Hz,1H),7.12-6.99(m,1H),6.87(t,J=6.6Hz,1H) ,5.15-4.82(m,3H),4.24(t,J=8.9Hz,1H),2.66(t,J=7.7Hz,1H),1.99(s,3H),1.47(s,3H),0.62(d,J=6.3Hz,3H).

[0610] Synthesis of intermediate 14-2 in step 2

[0611] Intermediate 14-1 (1.8 g, 3.47 mmol, 1 eq) was dissolved in 20 mL of ethanol, and 1 mL of water and Perkins catalyst (CAS: 173416-05-2) (74.15 mg, 173.57 μmol, 0.05 eq) were added. The reaction mixture was stirred at 50 °C for 2 hours. LC-MS monitoring showed complete consumption of the starting material and product formation. The reaction solution was concentrated under reduced pressure to the residue and then subjected to silica gel column chromatography (…). 20g Intermediate 14-2 was purified by silica gel column chromatography (elution buffer: 0-90% ethyl acetate / n-hexane, 35 mL / min) to a white solid (400 mg, yield: 21.48%). LCMS (ESI): m / z C 23 H 22 D3F5N3O4S + Calculated value [M+H] + =537.17, measured value [M+H] + =537.2. 1 H NMR (400MHz, CDCl3) δppm 8.68(d,J=5.2Hz,1H),8.17(d,J=2.0Hz,1H),7.87(d,J=2.9Hz,1H),7.5 8(dd,J=2.1,5.2Hz,1H),6.87-6.68(m,1H),6.35(s,1H),5.76(d,J=2.7H z,1H),5.12(d,J=14.1Hz,1H),4.71(d,J=13.9Hz,1H),4.40(t,J=9.2Hz, 1H), 2.76-2.68 (m, 1H), 2.12 (s, 3H), 1.59 (s, 3H), 0.64 (d, J = 6.1Hz, 3H).

[0612] Synthesis of intermediate 14-3 in step 3

[0613] Intermediate 14-2 (200 mg, 372.76 μmol, 1 eq) was dissolved in 4 mL of dichloromethane, and thioyl chloride (72.88 mg, 539.97 μmol, 1.45 eq) was added. The reaction mixture was stirred at 25 °C for 1 hour. LCMS monitoring showed complete consumption of the starting material and product formation. The reaction solution was concentrated under reduced pressure to obtain intermediate 14-3, a colorless oil (205 mg, crude product). LCMS (ESI): m / z C 22 H 19 D3ClF5N3O4 + Calculated value [M+H] + =525.14, measured value [M+H] + =525.1.

[0614] Synthesis of intermediate 14-4 in step 4

[0615] Intermediate 14-3 (200.0 mg, 381.04 μmol, 1 eq) was dissolved in 10 mL of acetonitrile, and dibenzyl hydrogen phosphate (212.04 mg, 762.08 μmol, 2 eq), sodium carbonate (121.16 mg, 1.14 mmol, 3 eq), sodium iodide (11.42 mg, 76.21 μmol, 0.2 eq), and 4A molecular sieve (50 mg) were added sequentially. The reaction system was stirred at 40 °C for 1 hour. LCMS was used to monitor complete consumption of the starting materials. The reaction solution was filtered, and the filtrate was concentrated under reduced pressure. It was dissolved in 15 mL of ethyl acetate, washed with water (10 mL × 2), washed with saturated brine (10 mL), dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure to obtain the residue, which was then subjected to silica gel column chromatography. 12g Intermediate 14-4 was purified by silica gel column chromatography (elution buffer: 0-90% ethyl acetate / n-hexane, 40 mL / min) to a white solid (180 mg, yield: 61.62%). LCMS (ESI): m / z C 36 H 33 D3F5N3O8P + Calculated value [M+H] + =767.23, measured value [M+H] + =767.2.

[0616] Step 5: Synthesis of compound I-014

[0617] Intermediate 14-4 (50 mg, 65.22 μmol, 1 eq) was dissolved in 5 mL of ethyl acetate. Under a nitrogen atmosphere, 10% palladium on carbon (2 mg) was added. The system was evacuated and then purged three times with hydrogen. The system was stirred at 25 °C for 5 hours under a hydrogen atmosphere (15 pi s). LCMS monitoring showed complete consumption of the starting material and formation of the main product. The system was filtered, and the filtrate was concentrated under reduced pressure to give compound I-014 as a colorless oil (27 mg, crude product). LCMS (ESI): m / z C 22 H 21 D3F5N3O8P + Calculated value [M+H] + =587.14, measured value [M+H] + =587.1.

[0618] Example 15: Synthesis method of compound I-015

[0619] Intermediate 14-3 (100 mg, 190.52 μmol, 1 eq) was dissolved in 20 mL of acetonitrile. Sodium iodide (5.71 mg, 38.10 μmol, 0.2 eq), compound 15-1 (39.29 mg, 381.04 μmol, 2 eq), sodium carbonate (60.58 mg, 571.56 μmol, 3 eq), and 4A molecular sieve (40 mg) were added sequentially. The reaction mixture was stirred at 40 °C for 1 hour. LC-MS monitoring showed complete consumption of the starting materials and product formation. The reaction solution was filtered, and the filtrate was concentrated under reduced pressure to the residue. The residue was then subjected to reversed-phase column chromatography (column type: 40-WePure Biotech XP tC18; size: 150*30mm; particle size: 7μm; mobile phase: [A phase: water (0.225% formic acid) - B phase: acetonitrile]; gradient: 30%-60% B, 7 minutes) to prepare compound I-015 as a colorless oil (47mg, yield: 41.7%). LCMS (ESI): m / z C 26 H 27 D3F5N4O6 + Calculated value [M+H] + =592.23, measured value [M+H] + =592.2. 1H NMR (400MHz, CDCl3) δppm 8.62(d,J=5.2Hz,1H),8.12(d,J=2.0Hz,1H),7.83(d,J=3.2Hz,1H),7.49 (dd,J=2.1,5.2Hz,1H),6.90-6.72(m,1H),6.51(s,1H),6.07-5.82(m,1H) ,5.80-5.64(m,2H),5.14-4.81(m,1H),4.42(t,J=9.1Hz,1H),3.20(s,2H ), 2.73 (t, J = 7.9Hz, 1H), 2.32 (s, 6H), 1.57 (s, 3H), 0.70 (d, J = 6.2Hz, 3H).

[0620] Example 16: Synthesis of Compound I-016

[0621] Following the synthesis method of Example 15, and replacing the corresponding starting materials, compound I-016 was prepared using compound 16-1 as the starting material. It is a colorless oil. LCMS (ESI): m / z C 27 H 29 D3F5N4O6 + Calculated value [M+H] + = 606.24, measured value [M+H] + =606.2. 1 ¹H NMR (400MHz, CDCl₃) δppm 8.64(d,J=5.4Hz,1H),8.14(d,J=1.9Hz,1H),7.84(d,J=3.7Hz,1H),7.53(dd ,J=2.1,5.1Hz,1H),6.94-6.72(m,1H),6.64-6.48(m,1H),5.98-5.82(m,1H) ,5.74-5.59(m,2H),5.13-4.84(m,1H),4.44(t,J=8.9Hz,1H),2.79-2.65(m, 3H), 2.59 (d, J = 6.3Hz, 2H), 2.30 (s, 6H), 1.58 (s, 3H), 0.72 (d, J = 6.1Hz, 3H).

[0622] Example 17: Synthesis of Compound I-017

[0623] Following the synthesis method of Example 15, and replacing the corresponding starting materials, compound I-017 was prepared using compound 17-1 as the starting material. It is a colorless oil. LCMS (ESI): m / z C 28 H 31D3F5N4O6 + Calculated value [M+H] + =620.26, measured value [M+H] + =620.3. 1 H NMR (400MHz, CDCl3) δppm 8.62(d,J=5.1Hz,1H),8.12(d,J=2.0Hz,1H),7.83(d,J=3.9Hz,1H),7.49(dd,J=2.1,5. 2Hz,1H),6.85-6.72(m,1H),6.62-6.44(m,1H),5.94-5.79(m,1H),5.74-5.59(m,2H),5. 08-4.85(m,1H),4.42(t,J=9.1Hz,1H),2.80-2.67(m,1H),2.38(t,J=7.4Hz,2H),2.30( t,J=7.2Hz,2H),2.22(s,6H),1.78(d,J=7.3Hz,2H),1.57(s,3H),0.70(d,J=6.4Hz,3H).

[0624] Example 18: Synthesis of Compound I-018

[0625] Synthesis of intermediate 18-2 in step 1

[0626] Following the synthesis method of Example 15, and replacing the corresponding starting materials, intermediate 18-2 was prepared using compound 18-1 as the starting material. This intermediate was a white solid. LCMS(ESI): m / z C 26 H 25 D3F5N4O8 + The calculated value is [Mt-Bu+H]. + =622.20, measured value [Mt-Bu+H] + =622.2.

[0627] Step 2: Synthesis of compound I-018

[0628] Intermediate 18-2 (129.10 mg, 190.52 μmol, 1 eq) was dissolved in 2 mL of dichloromethane, and 2 mL of trifluoroacetic acid was added dropwise. The reaction system was stirred at 25 °C for 1 hour. LCMS monitoring showed complete consumption of the starting material and formation of the main product. The reaction solution was concentrated under reduced pressure to the residue, and compound I-018 was prepared by reversed-phase column chromatography (column type: 40-WePureBiotech XP tC18; size: 150*30 mm; particle size: 7 μm; mobile phase: [A phase: water (0.225% formic acid) - B phase: acetonitrile]; gradient: 28%-58% B, 7 min), as a white solid (79.8 mg, yield: 67.17%). LCMS (ESI): m / z C 25 H 25 D3F5N4O6 + Calculated value [M+H] + =578.21, measured value [M+H] + =578.2. 1 ¹H NMR (400MHz, CDCl₃) δppm 8.62(d,J=5.2Hz,1H),8.10(d,J=1.8Hz,1H),7.84(d,J=3.9Hz,1H),7.50(dd, J=2.1,5.2Hz,1H),6.87-6.71(m,1H),6.47(d,J=1.3Hz,1H),5.98(d,J=4.1Hz, 1H),5.91-5.69(m,2H),4.97-4.74(m,1H),4.38(t,J=8.9Hz,1H),3.71(d,J=5 .0Hz,1H),2.82-2.67(m,3H),2.62(s,3H),1.55(s,3H),0.67(d,J=5.8Hz,3H).

[0629] Example 19: Synthesis of Compound I-019

[0630] Following the synthesis method of Example 18, and replacing the corresponding starting materials, compound I-019 was prepared using compound 19-1 as the starting material. It is a white solid. LCMS(ESI): m / z C 24 H 23 D3F5N4O6 + Calculated value [M+H] + =564.20, measured value [M+H] + =564.2. 1H NMR (400MHz, CDCl3) δppm 8.55(d,J=4.8Hz,1H),8.12-8.00(m,1H),7.94-7.84(m,1H),7.49(d,J= 5.5Hz,1H),6.75(d,J=8.0Hz,1H),6.60(d,J=2.9Hz,1H),6.47(dd,J=2.3 ,3.5Hz,1H),5.80(d,J=1.8Hz,2H),4.96-4.75(m,1H),4.45-4.29(m,1H ),3.78-3.72(m,1H),2.78-2.68(m,3H),1.57-1.49(m,4H),0.67(s,3H).

[0631] Example 20: Synthesis method of compound I-020

[0632] Following the synthesis method of Example 15, and replacing the corresponding starting materials, a crude compound was synthesized using compound 20-1 as the starting material. The crude compound was further prepared by reversed-phase column chromatography (column type: 40-WePure Biotech XP tC18; size: 150*30mm; particle size: 7μm; mobile phase: [phase A: water (0.225% formic acid) - phase B: acetonitrile]; gradient: 28%-58% B, 7 minutes) to obtain compound I-020, a white solid, which is a formate salt. 1 H NMR (400MHz, CDCl3) δppm 8.73(d,J=5.0Hz,1H),8.13-8.05(m,1H),7.86(d,J=3.2Hz,1H),7.79(d,J =4.1Hz,1H),6.96-6.86(m,1H),6.67-6.55(m,1H),5.97(s,1H),5.87(s,2H ),5.32-5.19(m,1H),5.18-5.06(m,1H),4.95-4.75(m,1H),4.34(t,J=8.8H z,1H),3.54(s,9H),2.74–2.66(m,1H),1.55(s,3H),0.68(d,J=6.1Hz,3H).

[0633] Example 21: Synthesis method of compound I-021

[0634] Following the synthesis method of Example 15, and replacing the corresponding raw materials, a crude compound was synthesized using compound 21-1 as the raw material. The crude compound was further prepared by reversed-phase column chromatography (column type: 40-WePure Biotech XP tC18; size: 150*30mm; particle size: 7μm; mobile phase: [phase A: water (0.225% formic acid) - phase B: acetonitrile]; gradient: 29%-59% B, 7 minutes) to obtain compound I-021, which is a white solid. 1 H NMR(400MHz,D2O)δppm 8.61(d,J=5.2Hz,1H),8.39(s,1H),7.56(s,1H),7.52(dd,J=2.1,5.2Hz,1H),6.65(q ,J=8.9Hz,1H),6.46-6.34(m,1H),5.83(d,J=10.7Hz,1H),5.48(d,J=10.7Hz,1H),5.0 8(d,J=9.3Hz,1H),4.17(t,J=9.4Hz,1H),3.33-3.19(m,2H),3.07(s,9H),2.81-2.65 (m,1H),2.47(t,J=6.6Hz,2H),2.07-1.94(m,2H),1.58(s,3H),0.63(d,J=6.4Hz,3H).

[0635] Example 22 Synthesis method of compound I-022

[0636] Synthesis of intermediate 22-2 in step 1

[0637] Compound 3-1 (0.5 g, 2.57 mmol, 1 eq) was dissolved in 15 mL of acetonitrile, and compound 13-1a (497.24 mg, 5.15 mmol, 2 eq), cesium carbonate (1.68 g, 5.15 mmol, 2 eq), and sodium iodide (38.59 mg, 257.43 μmol, 0.1 eq) were added sequentially. The reaction system was stirred at 65 °C for 5 hours. LCMS monitoring showed that some reactants remained and the main product was formed. The reaction solution was filtered, and the filtrate was diluted with 20 mL of water and 20 mL of ethyl acetate. The organic phase was separated, and the aqueous phase was extracted with ethyl acetate (10 mL × 3). The combined organic phases were washed with saturated brine (10 mL × 2), dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure to obtain the residue, which was then subjected to silica gel column chromatography. 12g Intermediate 22-1 was purified by silica gel column chromatography (elution buffer: 0-90% ethyl acetate / petroleum ether, 40 mL / min) to a white solid (123 mg, yield: 18.79%). LCMS (ESI): m / z C 12H 19 N2O2S + Calculated value [M+H] + =255.12, measured value [M+H] + =255.1. 1 HNMR(400MHz,DMSO-d6)δppm 7.98(d,J=2.6Hz,1H),7.22(d,J=8.5Hz,1H),7.06(dd,J=2.7,8.4Hz,1H),6.77(t,J=7.0Hz,1H),4.96(t,J=6.9Hz,1 H), 4.38 (d, J = 7.2Hz, 2H), 4.24 (dd, J = 6.6, 8.0Hz, 1H), 3.82 (t, J = 7.7Hz, 1H), 2.02 (s, 3H), 1.41 (s, 3H), 1.37 (s, 3H).

[0638] Synthesis of intermediate 22-2 in step 2

[0639] Following the synthesis methods in steps 2 and 3 of Example 13, and replacing the corresponding starting materials, compound 22-2 was prepared using compounds 2-1 and 22-1 as starting materials. It is a white solid. LCMS(ESI): m / z C 27 H 29 D3F5N2O5S + Calculated value [M+H] + =594.21, measured value [M+H] + =594.2. 1 H NMR (400MHz, CDCl3) δppm 8.50(d,J=2.0Hz,1H),7.75(d,J=6.0Hz,1H),7.65(d,J=8.3Hz,1H),6.84-6.71(m, 1H),6.33(d,J=6.8Hz,1H),5.27(t,J=6.8Hz,1H),4.99(d,J=13.8Hz,1H),4.66(d,J =13.8Hz,1H),4.58-4.48(m,2H),4.45-4.31(m,1H),3.99(t,J=7.4Hz,1H),2.79-2 .62(m,1H),2.12(s,3H),1.58(s,3H),1.55(d,J=5.8Hz,6H),0.61(d,J=6.5Hz,3H).

[0640] Synthesis of intermediate 22-4 in step 3

[0641] Following the synthesis methods of Step 4 in Example 13 and Example 17, and replacing the corresponding starting materials, compound 22-4 was prepared from compound 22-2 as the starting material. It is a white solid. LCMS(ESI): m / z C 32 H 38 D3F5N3O7 + Calculated value [M+H] + =677.30, measured value [M+H] + =677.3.

[0642] Step 4: Synthesis of compound I-022

[0643] Intermediate 22-4 (20 mg, 29.56 μmol, 1 eq) was dissolved in 7 mL of hexafluoroisopropanol, and trifluoroacetic acid (674.01 mg, 5.91 mmol, 439.09 μL, 200 eq) was added dropwise. The reaction mixture was stirred at 50 °C for 30 min. LC-MS monitoring showed complete consumption of the starting material and formation of the product. The reaction mixture was concentrated under reduced pressure to the residue and then subjected to reversed-phase column chromatography (column type: 40-WePure Biotech XP tC18; size: 150*30 mm; particle size: 7 μm; mobile phase: [phase A: water (0.225% formic acid) - phase B: acetonitrile]; gradient: 28%-58% B, 7 min) to prepare compound I-022 as a white solid. 1 H NMR (400MHz, CDCl3) δppm 8.48(s,1H),7.69(d,J=4.2Hz,1H),7.62-7.49(m,1H),6.85-6.72(m,1H),6.39(d,J =3.5Hz,1H),5.79-5.60(m,2H),4.91(s,1H),4.64-4.52(m,1H),4.39(d,J=5.7Hz,1 H),4.08-3.93(m,1H),3.93-3.77(m,1H),2.77(d,J=6.0Hz,2H),2.70(s,1H),2.60( s, 6H), 2.42 (d, J = 1.0Hz, 2H), 1.91 (d, J = 2.1Hz, 2H), 1.56 (s, 3H), 0.69-0.56 (m, 3H).

[0644] Example 23: Synthesis method of compound I-023

[0645] Following the synthesis method of Example 15, and replacing the corresponding starting materials, a crude compound was synthesized using compound 23-1 as the starting material. This crude compound was further prepared by reversed-phase column chromatography (column type: 40-WePure Biotech XP tC18; size: 150*30mm; particle size: 7μm; mobile phase: [A phase: water (0.225% formic acid) - B phase: acetonitrile]; gradient: 45%-75% B, 7 minutes) to obtain compound I-023, which was a light yellow oily substance. LCMS (ESI): m / z C 30 H 34 D3F5N3O 10 + Calculated value [M+H] + =697.26, measured value [M+H] + =697.5. 1 H NMR (400MHz, CDCl3) δppm 8.65(d,J=5.2Hz,1H),8.13(d,J=1.7Hz,1H),7.86(d,J=2.9Hz,1H),7.52 (dd,J=2.0,5.1Hz,1H),6.87-6.74(m,1H),6.51(d,J=2.6Hz,1H),5.98-5 .71(m,3H),5.03-4.82(m,1H),4.42(t,J=9.1Hz,1H),4.20(s,2H),3.79- 3.59(m,13H),2.74(t,J=7.9Hz,1H),1.58(s,3H),0.71(d,J=5.6Hz,3H).

[0646] Example 24: Synthesis of Compound I-024

[0647] Following the synthesis method of Example 15, and replacing the corresponding starting materials, a crude compound was synthesized using compound 24-1 as the starting material. This crude compound was further prepared by reversed-phase column chromatography (column type: 40-WePure Biotech XP tC18; size: 150*30mm; particle size: 7μm; mobile phase: [A phase: water (0.225% formic acid) - B phase: acetonitrile]; gradient: 43%-73% B, 7 minutes) to obtain compound I-024, which was a light yellow oily substance. LCMS (ESI): m / z C 34 H 42 D3F5N3O 12 + Calculated value [M+H] + =785.31, measured value [M+H] + =785.3. 1H NMR (400MHz, CDCl3) δppm 8.58(d,J=5.2Hz,1H),8.02(d,J=1.8Hz,1H),7.80(d,J=2.0Hz,1H),7.48(dd,J=2.1,5.2Hz,1H),6.88-6.80(m,1H),6.76(s,1H),6.58(d ,J=2.0Hz,1H),5.21-5.07(m,2H),4.97-4.81(m,1H),4.34(s,1H),3.58-3.46(m,21H),1.92(s,3H),1.53(s,3H),0.63(d,J=5.6Hz,3H).

[0648] Example 25: Synthesis method of compound I-025

[0649] Following the synthesis method of Example 15, and replacing the corresponding starting materials, a crude compound was synthesized using compound 25-1 as the starting material. This crude compound was further prepared by reversed-phase column chromatography (column type: 57-Phenomenex Gemini NX C18; size: 150*30mm; particle size: 5μm; mobile phase: [A phase: water (0.225% formic acid) - B phase: acetonitrile]; gradient: 42%-72% B, 8 minutes) to obtain compound I-025, which was a light yellow oily substance. LCMS (ESI): m / z C 35 H 44 D3F5N3O 12 + Calculated value [M+H] + =799.33, measured value [M+H] + =799.3. 1 H NMR (400MHz, CDCl3) δppm 8.63(d,J=5.4Hz,1H),8.13(d,J=1.7Hz,1H),7.87(d,J=2.6Hz,1H),7.50(dd,J=2.1 ,5.3Hz,1H),6.93-6.73(m,1H),6.63-6.45(m,1H),6.02-5.78(m,2H),5.68(d,J=11 .0Hz,1H),5.09-4.86(m,1H),4.42(t,J=8.9Hz,1H),3.76-3.60(m,19H),3.57(s,4H ), 2.73 (t, J = 7.9Hz, 1H), 2.61 (t, J = 6.2Hz, 2H), 1.57 (s, 3H), 0.70 (d, J = 5.6Hz, 3H).

[0650] Example 26: Synthesis of Compound I-026

[0651] Following the synthesis method of Example 15, and replacing the corresponding starting materials, a crude compound was synthesized using compound 26-1 as the starting material. This crude compound was further prepared by reversed-phase column chromatography (column type: 40-WePure Biotech XP tC18; size: 150*30mm; particle size: 7μm; mobile phase: [A phase: water (0.225% formic acid) - B phase: acetonitrile]; gradient: 50%-80% B, 7 minutes) to obtain compound I-026, which was a light yellow oily substance. LCMS (ESI): m / z C 36 H 46 D3F5N3O 12 + Calculated value [M+H] + = 813.34, measured value [M+H] + =813.3. 1 H NMR (400MHz, CDCl3) δppm 8.65(d,J=5.1Hz,1H),8.17(s,1H),7.90(d,J=1.4Hz,1H),7.52(d,J=3.7Hz,1H),6.90- 6.72(m,1H),6.65-6.47(m,1H),5.93(dd,J=5.0,6.0Hz,1H),5.84-5.74(m,1H),5.69(d ,J=10.8Hz,1H),5.16-4.88(m,1H),4.42(t,J=9.1Hz,1H),3.73-3.55(m,22H),3.43-3. 35(m,3H),2.81-2.69(m,1H),2.62(t,J=6.2Hz,2H),1.57(s,3H),0.71(d,J=6.4Hz,3H).

[0652] Example 27: Synthesis method of compound I-027

[0653] Following the synthesis method of Example 15, and replacing the corresponding starting materials, a crude compound was synthesized using compound 27-1 as the starting material. This crude compound was further prepared by reversed-phase column chromatography (column type: 40-WePure Biotech XP tC18; size: 150*30mm; particle size: 7μm; mobile phase: [A phase: water (0.225% formic acid) - B phase: acetonitrile]; gradient: 50%-80% B, 7 minutes) to obtain compound I-027, which was a light yellow oily substance. LCMS (ESI): m / z C 48 H 70 D3F5N3O 18 + Calculated value [M+H]+ =1077.50, measured value [1 / 2M+H] + =539.3. 1 H NMR (400MHz, CDCl3) δppm 8.67(d,J=5.4Hz,1H),8.20(s,1H),7.93(s,1H),7.62-7.46(m,1H),6.88-6.74(m,1H) ,6.56(s,1H),5.94(s,2H),5.70(d,J=11.1Hz,1H),5.16-4.93(m,1H),4.42(t,J=9.1H z,1H),3.71(t,J=6.2Hz,2H),3.67-3.63(m,34H),3.60(s,4H),3.58-3.54(m,6H),3.3 8(s,3H),2.81-2.70(m,1H),2.61(t,J=6.2Hz,2H),1.56(s,3H),0.71(d,J=6.2Hz,3H).

[0654] Example 28: Synthesis of Compound I-028

[0655] Following the synthesis method of Example 15, but replacing the corresponding starting materials, compound 28-1 (preparation method reference: European Journal of Medicinal Chemistry, 2022, vol. 238, art. no. 114515) was synthesized. 1 Using ¹H NMR (400MHz, CD₃OD) δppm 4.86(s, 2H), 4.29(s, 2H), 3.01(s, 6H) as the starting material, a crude compound was synthesized and further purified by reversed-phase column chromatography (column type: 40-WePure Biotech XP tC18; size: 150*30mm; particle size: 7μm; mobile phase: [A phase: water (0.225% formic acid) - B phase: acetonitrile]; gradient: 30%-60% B, 7 min) to obtain compound I-028, a white solid. LCMS (ESI): m / z C 28 H 29 D3F5N4O8 + Calculated value [M+H] + =650.23, measured value [M+H] + =650.2. 1H NMR(400MHz,CDCI3)δppm 8.65(d,J=5.1Hz,1H),8.13(s,1H),7.84(d,J=3.8Hz,1H),7.55-7.44(m,1 H),6.90-6.75(m,1H),6.60-6.43(m,1H),6.12-5.84(m,1H),5.78-5.62(m, 2H),5.06-4.79(m,1H),4.67(d,J=3.0Hz,2H),4.43(t,J=9.4Hz,1H),3.31( s,2H),2.79-2.67(m,1H),2.39(s,6H),1.58(s,3H),0.71(d,J=7.5Hz,3H).

[0656] Example 29: Synthesis method of compound I-029

[0657] Referring to the synthesis method of Example 15, and replacing the corresponding starting materials, using compound 29-1 as the starting material, a crude compound was synthesized and further subjected to silica gel column chromatography (…). 20g Compound I-029 was prepared as a white solid by silica gel column chromatography (eluting with 0-100% ethyl acetate / petroleum ether, 50 mL / min). LCMS (ESI): m / z C 24 H 22 D3F5N3O7 + Calculated value [M+H] + =565.18, measured value [M+H] + =565.2. 1 H NMR(400MHz,DMSO-d6)δppm 8.66(d,J=5.2Hz,1H),8.15(s,1H),7.94(d,J=2.0Hz,1H),7.73(d,J=1.8 Hz,1H),7.59(dd,J=2.1,5.2Hz,1H),7.16-7.00(m,1H),6.83(s,1H),5.79 (s,2H),5.41(t,J=6.5Hz,1H),5.24-5.08(m,1H),4.34-4.23(m,1H),4.0 0(d,J=6.6Hz,2H),2.78-2.66(m,1H),1.50(s,3H),0.65(d,J=6.0Hz,3H).

[0658] Example 30: Synthesis method of compound I-030

[0659] Synthesis of intermediate 30-2 in step 1

[0660] Referring to the synthesis method of Example 15, the corresponding raw materials were replaced with compound 30-1 (preparation method refers to patent WO2020 / 77217A1). 1 Compound 30-2 was prepared from raw materials using ¹H NMR (400MHz, CDCl₃) δppm 4.26 (d, J = 8.1Hz, 2H), 1.40 (s, 18H). It was a white solid. 1 ¹H NMR (400MHz, CDCl₃) δppm 8.42(d,J=5.2Hz,1H),7.90(d,J=1.9Hz,1H),7.62(d,J=3.9Hz,1H),7.28(dd,J= 2.1,5.2Hz,1H),6.69-6.53(m,1H),6.31(d,J=4.8Hz,1H),5.88-5.66(m,1H),5. 58-5.47(m,2H),4.90-4.60(m,1H),4.30(d,J=8.9Hz,2H),4.20(t,J=9.0Hz,1H) ,2.54-2.47(m,1H),1.35(s,3H),1.26(d,J=1.8Hz,18H),0.48(d,J=6.6Hz,3H).

[0661] Step 2: Synthesis of compound I-030

[0662] Intermediate 30-2 (80 mg, 105.73 μmol, 1 eq) was dissolved in 3 mL of dichloromethane, and trifluoroacetic acid (3.9 mL) was slowly added dropwise. After the addition was complete, the reaction mixture was stirred at 30 °C for 1 hour. LCMS monitoring showed complete consumption of the starting material and formation of the product. The reaction mixture was concentrated under reduced pressure to obtain the residue, which was then subjected to reversed-phase column chromatography (C18 column, mobile phase: acetonitrile / water, 0-50%). The resulting fraction was extracted with ethyl acetate (30 mL × 4). The organic phases were combined, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure to give compound I-030 as a white solid (42 mg, yield: 61.64%). LCMS (ESI): m / z C 24 H 23 D3F5N3O 10 P + Calculated value [M+H] + =645.15, measured value [M+H] + =645.1. 1H NMR(400MHz,D2O)δppm 8.62(d,J=5.5Hz,1H),7.65(d,J=1.8Hz,1H),7.56(dd,J=2.1,5.2Hz,1H),6.81-6.58(m,1H),6.46(d,J=5.4Hz,1H),5.89(d,J=10.7 Hz,1H),5.65(d,J=10.6Hz,1H),5.15(d,J=8.8Hz,1H),4.50-4.40(m,3H),2.77(t,J=8.2Hz,1H),1.60(s,3H),0.66(d,J=5.8Hz,3H).

[0663] Example 31: Synthesis method of compound I-031

[0664] Following the synthesis method of Example 15, and replacing the corresponding starting materials, a crude compound was synthesized using compound 31-1 as the starting material. This crude compound was further prepared by reversed-phase column chromatography (column type: 40-WePure Biotech XP tC18; size: 150*30mm; particle size: 7μm; mobile phase: [A phase: water (0.225% formic acid) - B phase: acetonitrile]; gradient: 40%-70% B, 7 minutes) to obtain compound I-031, a light yellow solid. LCMS (ESI): m / z C 54 H 72 D3F5N 13 O 16 + Calculated value [M+H] + =1259.56, measured value [1 / 2M+H] + =630.4. 1 H NMR (400MHz, CDCl3) δppm 8.64(d,J=5.0Hz,1H),8.08(s,1H),7.85(d,J=2.3Hz,1H),7.57-7.44(m,1H),6.89-6.74(m,1H),6.62-6.39(m,1H),6.14-5.79(m,2H ),5.79-5.63(m,1H),4.40(t,J=9.4Hz,1H),4.33-3.88(m,22H),3.12-2.86(m,32H),2.72(t,J=7.6Hz,1H),1.56(s,3H),0.69(s,3H).

[0665] Example 32: Synthesis method of compound I-032

[0666] Following the synthesis method of Example 15, and replacing the corresponding starting materials, compound 32-1 (CAS: 541-15-1) was used as the starting material to synthesize a crude compound. This crude compound was further prepared by reversed-phase column chromatography (column type: Ultimate XB-C18; size: 250*50mm; particle size: 10μm; mobile phase: [A phase: water (0.25% hydrochloric acid) - B phase: acetonitrile]; gradient: 35%-75% B, flow rate 65mL / min) to obtain compound I-032, a white solid. LCMS (ESI): m / z C 29 H 33 D3F5N4O7 + Calculated value [M] + =650.27, measured value [M] + =650.2. 1 H NMR(400MHz,DMSO-d6)δppm 8.68(d,J=5.2Hz,1H),8.17(d,J=1.8Hz,1H),7.97(d,J=2.0Hz,1H),7.76(s,1H),7.62(dd ,J=2.1,5.2Hz,1H),7.06(q,J=8.9Hz,1H),6.88-6.75(m,1H),5.87-5.65(m,3H),5.25-5.0 6(m,1H),4.39(d,J=6.2Hz,1H),4.29(t,J=8.8Hz,1H),3.34-3.33(m,2H),3.11(s,9H),2. 76-2.67(m,1H),2.59-2.53(m,1H),2.48-2.43(m,1H),1.51(s,3H),0.65(d,J=5.6Hz,3H).

[0667] Biological Test Example 1: Patch-clamp assay to study the inhibitory activity of compounds on Nav1.8 channels

[0668] 1. Experimental objective:

[0669] The inhibitory activity of the test compound on the Nav1.8 channel was evaluated using a CHO cell line that stably expresses the human Nav1.8 channel.

[0670] 2. Test methods:

[0671] Cell culture: Cells were cultured in Ham's F-12 nutrient mixture containing 10% fetal bovine serum and 10 μg / mL Blasticidin S, 200 μg / mL Hygromycin B, 0.8 mg / mL G418, and 100 μg / mL Zeocin at 37°C and 5% carbon dioxide.

[0672] Cell passage: Remove the old culture medium and wash once with PBS, then add 1 mL of 0.25% Trypsin-EDTA solution and incubate at 37°C for approximately 1.5 min. When the cells detach from the bottom of the dish, add approximately 5 mL of preheated (37°C) complete culture medium. Gently pipette the cell suspension to separate aggregated cells. Transfer the cell suspension to sterile centrifuge tubes and centrifuge at 1000 rpm for 5 min to collect the cells. For expansion or maintenance culture, seed the cells in 6 cm cell culture dishes at a density of 2.5 × 10⁶ cells per dish. 5 100 cells (final volume: 5 mL). To maintain the electrophysiological activity of the cells, the cell density should not exceed 80%.

[0673] Compound administration and patch-clamp assay: Cells were separated using 0.25% Trypsin-EDTA prior to the assay, and 6.5 × 10⁶ cells were administered. 3 The cells were seeded onto coverslips and cultured in 24-well plates (final volume: 500 μL). After induction with tetracycline for 24-72 hours, the cells were tested.

[0674] Once the current amplitude stabilized in the control extracellular solution, drug administration began. After each drug concentration reached equilibrium (approximately 5 minutes), the next concentration was measured. The control extracellular solution and the working solution of the test compound were sequentially flowed from low to high concentration through the recording bath using gravity perfusion, thus acting on the cells. Simultaneously, a peristaltic pump was used for fluid replacement during recording. All electrophysiological experiments were performed at room temperature.

[0675] All experiments were conducted in the presence of 100 nM TTX in the extracellular fluid to block endogenous TTX-S (tetrodotoxin-sensitive) Na+ in cells. + Electric current.

[0676] Extracellular fluid: 140 mM NaCl, 3.5 mM KCl, 1 mM MgCl2·6H2O, 2 mM CaCl2·2H2O, 10 mM D-Glucose, 10 mM HEPES, 1.25 mM NaH2PO4·2H2O; pH adjusted to 7.4 with NaOH.

[0677] Intracellular fluid: 50 mM CsCl, 10 mM NaCl, 10 mM HEPES, 60 mM CsF, 20 mM EGTA, CsOH adjusted to pH 7.2.

[0678] The voltage stimulation protocol for whole-cell patch-clamp recording of Nav1.8 channel currents is as follows: After whole-cell sealing, the cell voltage is clamped at -120 mV. First, the voltage is stepped from -110 mV to -20 mV in 10 mV increments and held for 5 s. Then, a 0 mV depolarization pulse is applied to measure the peak value of the inward current to obtain the half-inactivation voltage (Vhalf). The conditional voltage is then adjusted to Vhalf and held for 5 s. Next, the voltage is restored to -120 mV and held for 20 ms to allow the unbound and inactivated channels to recover. A depolarization pulse (TP2) to 0 mV is then applied for 50 ms to detect the sodium current in the half-inactivated state. Finally, the clamp voltage is restored to -120 mV, and data acquisition is repeated at 20 s intervals.

[0679] 3. Data Analysis:

[0680] The test data were acquired by the EPC 10 amplifier (HEKA) and stored in the PatchMaster (HEKA) software.

[0681] First, the peak sodium current (Peak current compound) and the peak current (Peak current control) after treatment at a specific drug concentration (10 nM) were normalized. Then, the inhibition rate corresponding to the drug concentration in the semi-activated state was calculated.

[0682] 4. Experimental Results:

[0683] The experimental results are shown in Table 1, where A: inhibition rate ≥ 50%, B: 50% > inhibition rate ≥ 10%, C: inhibition rate < 10%; VX-548 is a Nav1.8 inhibitor from Vertex, and VX-548-D3 is Cmpd 26 in patent WO2021113627A1, with the structure shown below.

[0684] Table 1: Inhibition rate of compounds against Nav1.8 at 10 nM concentration (manual patch-clamp)

[0685] The compounds of this invention have Nav1.8 inhibitory activity and have potential therapeutic effects on pain.

[0686] Biological Test Example 2: Compound Solubility Study

[0687] 1. Solubility study of the compound in artificial gastric juice, artificial intestinal juice, and 0.5% CMC.

[0688] 1.1 Experimental Objective:

[0689] Evaluate the solubility of the test compound in the solvent.

[0690] 1.2 Test Methods:

[0691] Solvent configuration:

[0692] Artificial gastric juice: Take 16.4 mL of dilute hydrochloric acid, add about 800 mL of water and 10 g of pepsin, shake well, and then dilute with water to 1000 mL.

[0693] Artificial intestinal fluid: Dissolve 6.8g of potassium dihydrogen phosphate in 500mL of water, adjust the pH to 6.8 with 0.1mol / L sodium hydroxide solution, and dissolve 10g of pancreatic enzyme in an appropriate amount of water. Mix the two solutions and dilute with water to 1000mL to obtain the final product.

[0694] 0.5% CMC: Weigh 0.5g of dried CMC-Na and dissolve it in 100mL of 0.9% physiological saline (0.9g NaCl dissolved in 100mL dd H2O) to prepare a clear solution. Under stirring and heating (50-65℃), slowly add CMC-Na to 0.9% Saline (physiological saline) to help accelerate dissolution.

[0695] 1.3 Experimental Procedure:

[0696] Accurately weigh an appropriate amount of the analyte and prepare a 10 mg / mL stock solution using DMSO as the solvent, which will serve as the reference solution. Dissolve 1-2 mg of the analyte sample in 100-200 μL of the corresponding solvent (theoretical concentration 10 mg / mL), mix vigorously (undispersible lumpy solids require ultrasonic dispersion), shake in a constant temperature shaker at 37°C for 4 hours, centrifuge at 10000 rpm for 10 min, and use the supernatant as the sample solution for liquid chromatography analysis.

[0697] 1.4 Test Results:

[0698] The experimental results are shown in Table 2-1, where solubility (mg / mL) = peak area of ​​sample / peak area of ​​reference × concentration of reference solution (mg / mL) × dilution factor of sample solution.

[0699] Table 2-1: Solubility of compounds in different solvents

[0700] The compounds of this invention exhibit significantly improved solubility in at least one solvent. I-001 shows a much higher solubility in 0.5% CMC and artificial intestinal fluid compared to VX-548.

[0701] 2. Solubility study of the compound in water for injection and physiological saline

[0702] 2.1 Experimental Objective:

[0703] Evaluate the solubility of the test compound in water for injection or physiological saline.

[0704] 2.2 Test Methods:

[0705] Accurately weigh an appropriate amount of the analyte and prepare a 1 mg / mL stock solution using 50% acetonitrile as the solvent, as a reference solution. Accurately weigh 3 mg of the analyte using a balance and add it to 10 mL of water for injection or physiological saline to prepare a theoretical concentration of 0.3 mg / mL. After homogenization by sonication, place the solution in a 37°C constant temperature shaker and shake for 1 hour. Filter with a water membrane (0.45 μM), discarding approximately 8 mL. Collect the filtrate and transfer it to a liquid chromatography-mass spectrometry (LC-GC) solution for analysis.

[0706] 2.3 Experimental Results:

[0707] The experimental results are shown in Table 2-2, where solubility (mg / mL) = peak area of ​​sample / peak area of ​​reference × concentration of reference solution (mg / mL) × dilution factor of sample solution.

[0708] Table 2-2: Solubility of compounds in different solvents

[0709] I-032 is extremely soluble in water for injection, with a solubility >400 mg / mL; however, the actual concentration was not determined by HPLC. The compounds of this invention exhibit significantly improved solubility in water for injection or physiological saline, meeting the requirements for injection administration.

[0710] Biological Test Example 3: In vivo analgesic effect of compound administered via gavage to mice

[0711] 1. Experimental objective:

[0712] A plantar incision pain model was established using male C57 BL / 6J mice. The analgesic effect of the test compound was evaluated by measuring changes in the animals' pain threshold.

[0713] 2. Test methods:

[0714] Experimental animal species, strain, age, and sex: C57BL / 6J mice, 7-8 weeks old, male.

[0715] Animals were acclimatized for 7 days after purchase, with free access to food. Before testing, animals underwent a 3-day acclimatization period, during which they were placed on a metal pain assessment frame for 40-60 minutes, allowing researchers to have acclimatization contact with them to reduce stress on the animals. After the acclimatization period, the baseline values ​​of all animals were measured.

[0716] A plantar incision pain model was established. The day after modeling, experimental animals were grouped (n=6) and administered the drug. The solvent (vehicle) was Solutol Hs15: 0.5% CMC Saline (10:90 v / v). Animals were fasted for 12 hours before administration. The mechanical pain threshold of all animals was measured using Von-Frey fibers before administration and at 1 hour, 2 hours, and 4 hours after administration. Statistical analysis was performed using two-way ANOVA and multiple comparisons.

[0717] The experimental groups are shown in Tables 3 and 4 below.

[0718] Table 3: Grouping and Dosage

[0719] Table 4: Grouping and Dosage

[0720] 3. Experimental Results:

[0721] The experimental results are shown in Figure 1 and Figure 2.

[0722] The compounds of this invention have good analgesic effects. At the same dose (10 mpk) for 1 hour, I-001 has better analgesic effects than VX-548, and I-002 has better analgesic effects than VX-548-D3; I-001 at 5 mpk has similar effects to VX-548 at 10 mpk; and I-002 at 5 mpk has similar effects to VX-548-D3 at 10 mpk.

[0723] Biological Test Example 4: Pharmacokinetic Study of Compounds in Mice

[0724] 1. Experimental objective:

[0725] Evaluate the pharmacokinetic characteristics of the test compound in mice.

[0726] 2. Experimental animals:

[0727] C57BL / 6J mice, male, 6-7 weeks old, were purchased from Vital River Laboratory Animal Technology Co., Ltd.

[0728] 3. Test methods:

[0729] C57BL / 6J mice, 6 mice per group, blood was collected alternately, and the test compound was administered intravenously at 1 mg / kg or by gavage at 5 mg / kg, depending on body weight. The solvent was 10% (v / v) DMSO + 10% (v / v) Solutol HS15 + 80% 0.9% sodium chloride solution, administration volume 10 mL / kg.

[0730] Approximately 50 μL of whole blood was collected from the fundus venous plexus at 0.25, 0.5, 1, 2, 4, 6, and 8 hours after drug administration and placed into EDTA-K2 anticoagulant tubes. Within half an hour, the plasma was centrifuged (6000 rpm, 8 minutes, 4°C) and stored at -80°C for later use.

[0731] The concentration of the target compound in plasma samples was analyzed by HPLC-MS / MS and pharmacokinetic parameters were calculated.

[0732] 4. Experimental Results:

[0733] The compounds of this invention are rapidly absorbed orally and exhibit good pharmacokinetic characteristics.

[0734] Biological Test Example 5: Study on the analgesic effect of compound administered by gavage to rats

[0735] 1. Experimental objective:

[0736] A plantar incision pain model was established using male SD rats. The analgesic effect of the test compound was evaluated by measuring changes in the animals' pain threshold.

[0737] 2. Experimental animals:

[0738] Species, strain, age, and sex of experimental animals: SD rats, 6-7 weeks old (190-220g), male, purchased from Shanghai Slack Laboratory Animal Co., Ltd.

[0739] 3. Test methods:

[0740] Animals were acclimatized for 7 days after purchase, with free access to food. Before the test, they underwent a 3-day acclimatization period, during which they were placed on a metal pain assessment frame for 40-60 minutes. The testers had acclimatization contact with the animals to reduce the stress response of the test animals to the testers. After the acclimatization period, the baseline values ​​of all animals were tested.

[0741] A plantar incision pain model was established. The day after modeling, experimental animals were grouped and administered 30 mg / kg of the drug (n=6, model group administered the drug via vehicle): 10% (v / v) DMA + 10% (v / v) DMA. Solutol HS15 + 80% 0.9% sodium chloride, administration volume: 10 mL / kg. Animals were fasted for 12 hours prior to administration. Mechanical pain thresholds in all animals were measured using Von-Frey fibers before and 1 hour after administration. Statistical analysis was performed using one-way ANOVA with intergroup comparison tests.

[0742] 4. Experimental Results:

[0743] The experimental results are shown in Figure 3.

[0744] The compounds of this invention exhibit good analgesic effects and rapid onset of action after oral administration. Compared with the model group, I-029 showed significant efficacy 1 hour after oral administration, while the same dose of VX-548 or VX-548-D3 showed no significant efficacy.

[0745] Biological Test Example 6: Pharmacokinetic Study of Compound Administered by Gavage to Rats

[0746] 1. Experimental objective:

[0747] To evaluate the pharmacokinetic characteristics of the test compound administered to rats via gavage.

[0748] 2. Experimental animals:

[0749] Male SD rats, 190-220g, were purchased from Shanghai Jihui Experimental Animal Breeding Co., Ltd.

[0750] 3. Test methods:

[0751] Administration: SD rats, 3 rats per group, were administered the test compound by gavage at a concentration of 0.5% CMC at a concentration of 0.5 mg / mL and a volume of 10 mL / kg.

[0752] Blood samples were collected at 0.25, 0.5, 1, 2, 4.0, 6.0, 8.0 and 24 hours after drug administration.

[0753] Plasma collection and processing: At the above-set time points, 200 μL of blood was collected via the jugular vein or a suitable site, placed in an EDTA-K2 test tube, centrifuged at 3500 rpm for 10 min, the plasma was separated, and stored frozen at -20℃.

[0754] The concentration of the target compound in plasma samples was analyzed by HPLC-MS / MS and pharmacokinetic parameters were calculated.

[0755] 4. Experimental Results:

[0756] The compound of this invention is rapidly absorbed, allowing for a faster analgesic effect. (I-029's T) maxThe time is 1 hour, which is significantly better than VX-548(T). max (3h), VX-548-D3 (T) max (4h), and has a higher C max value.

[0757] Biological Test Example 7: Tissue Distribution Study of Compound After Gavage Administration in Rats

[0758] 1. Experimental objective:

[0759] To evaluate the tissue distribution characteristics of the test compound after oral administration to rats.

[0760] 2. Experimental animals:

[0761] Male SD rats, 190-220g, were purchased from Shanghai Shengchang Biotechnology Co., Ltd.

[0762] 3. Test methods:

[0763] SD rats, 3 rats per group, were administered the test compound by gavage according to their body weight. The solvent was Solutol Hs15:20% Hp-β-CD = 6:94 (v:v), the administration volume was 10 mL / kg, and the administration dose was 5 mg / kg.

[0764] Sample collection and processing:

[0765] plasma:

[0766] Animals were anesthetized and euthanized at set time points (0.5h, 4h, 8h), and venous blood was collected. 1 mL of whole blood was placed in an EDTA-K2 test tube, centrifuged at 11000 rpm for 5 min, and plasma was separated. 500 μL of plasma was quantitatively extracted and frozen in a -80℃ freezer.

[0767] DRG organization:

[0768] Tissue samples from the two largest pairs of nerve ganglia (DRGs) near the spinal cord on the back of rats were collected. The contents and residual blood were washed away with ice-cold saline, blotted dry with filter paper, and homogenized with 50% methanol-water (v / v) at a ratio of 1:30. All samples were collected and stored frozen at -80°C. The final volume should not be less than 200 μL.

[0769] HPLC-MS / MS was used to analyze the concentration of the target compound in plasma and tissue samples and to calculate pharmacokinetic parameters.

[0770] 4. Experimental Results:

[0771] The high plasma and DRG tissue exposure levels of the compound of this invention suggest that the clinical dosage of the drug may be lower.

[0772] Biological Test Example 8: Study on the analgesic effect of compound administered via IV injection in mice

[0773] 1. Experimental objective:

[0774] A plantar incision pain model was established using male C57 BL / 6J mice. The analgesic effect of the test compound was evaluated by measuring changes in the animals' pain threshold.

[0775] 2. Experimental animals:

[0776] Experimental animal species, strain, age, and sex: C57BL / 6J mice, 7-8 weeks old, male.

[0777] 3. Test methods:

[0778] Animals were acclimatized for 7 days after purchase, with free access to food. Before the test, they underwent a 3-day acclimatization period, during which they were placed on a metal pain assessment frame for 40-60 minutes. The testers had acclimatization contact with the animals to reduce the stress response of the test animals to the testers. After the acclimatization period, the baseline values ​​of all animals were tested.

[0779] A plantar incision pain model was established. The day after modeling, experimental animals were grouped and administered medication (n=7 per group). The intravenous solvent was 0.9% sodium chloride solution, with the model group receiving the same solvent. Animals were fasted for 12 hours before administration. Mechanical pain thresholds in all animals were measured using Von-Frey fibers before and 1 hour after administration. Statistical analysis was performed using one-way ANOVA with intergroup comparison tests.

[0780] 4. Experimental Results:

[0781] The results are shown in Figure 4.

[0782] The compound of this invention has a good analgesic effect after intravenous injection and a rapid onset of action. Compared with the model group, I-029 showed significant efficacy after intravenous administration of 3 mpk for 1 hour, which is superior to oral administration of VX-548-D3 at 10 mpk. However, the solubility of VX-548-D3 in physiological saline does not support injection administration.

[0783] Biological Test Example 9: Pharmacokinetic Study of Compound Intravenous Injection in Monkeys

[0784] 1. Experimental objective:

[0785] To evaluate the pharmacokinetic characteristics of the test compound administered intravenously to rhesus monkeys.

[0786] 2. Experimental animals:

[0787] Rhesus monkeys, 4.5-6 kg, female, sourced from the New Drug Evaluation Center of Shandong Academy of Pharmaceutical Sciences.

[0788] 3. Test methods:

[0789] Administration: Two rhesus monkeys per group were administered the test compound intravenously at a dose of 1 mg / kg according to their body weight. The solvent was 10% (v / v) DMSO + 10% (v / v) DMSO. Solutol HS15 + 80% 0.9% sodium chloride solution, administration concentration 0.2 mg / mL, administration volume 5 mL / kg.

[0790] Blood samples were collected at 0.083, 0.25, 0.5, 1, 2, 4.0, 8.0, 24 and 48 h after drug administration.

[0791] Plasma collection and processing: Whole blood samples were collected in blood collection tubes containing sodium heparin and NaF, centrifuged at 3500 rpm for 10 min, plasma was separated, and stored frozen at -20℃.

[0792] The concentration of the target compound in plasma samples was analyzed by HPLC-MS / MS and pharmacokinetic parameters were calculated.

[0793] 3. Experimental Results:

[0794] The compounds I-001, I-002, I-029, and I-032 of this invention, when administered intravenously, exhibit good exposure to the target compound, meeting the requirements for injection administration.

Claims

1. A compound of formula (A) or a pharmaceutically acceptable salt thereof, in, R 1 C 1-3 Alkyl, C 1-3 Alkoxy, C 3-6 cycloalkyl, C 1-3 Deuterated alkyl or C 1-3 Halogenated alkyl groups; Z is a single bond, O, S, or N(R) Z ); R Z For H, C 1-3 Alkyl or C 1-3 Deuterated alkyl groups; R 2 For H, C 1-3 Alkyl or C 3-6 cycloalkyl, wherein the C 1-3 The alkyl group may optionally be selected independently from one or more deuterium, halogen, hydroxyl, C 1-3 Alkoxy, C 3-6 Substituents of cycloalkyl groups; R 3 and R 4 Each can be independently H, deuterium, or halogen; R 5 and R 6 Each is independently H, deuterium, and C. 1-3 Alkyl or halogen; R 8 and R 9 Each is independently H, deuterium, halogen, C 1-3 Alkyl, C 1-3 Deuterated alkyl or C 1-3 Halogenated alkyl groups; X is O, S, or N(R) X ); R X For H or C 1-3 alkyl; Y is CH, C, N, or NH, and T is O or CHR. T Where Y is CH or C, and T is CHR T At that time, R 7 and R T Together with the atoms it is attached to, it forms a 6-membered nitrogen-containing heterocycle, wherein the 6-membered nitrogen-containing heterocycle is optionally... Substitution, and the 6-membered nitrogen-containing heterocycle forms a fused ring with W; when Y is CH or C, and T is O, R 7 H, halogen or C 1-3 Alkyl; when Y is N or NH, T is O, R 7 It does not exist; In W, two atoms or groups marked with * are in adjacent positions; W represents phenyl, 5-6 membered heteroaryl, 5-6 membered heterocyclic group, C represents... 3-6 Cycloalkyl or dicyclic; each ring in the dicyclic group is independently a benzene ring, a 5-6 membered heteroaromatic ring, a 5-6 membered heterocycle, or a C-ring. 3-6 Monocyclic carbocyclic ring; wherein the phenyl, 5-6 membered heteroaryl, 5-6 membered heterocyclic group, C 3-6 Cycloalkyl and dicycloalkyl groups are optionally separated by one or more R W replace; Each R W Each group independently consists of carbamoyl, halogen, oxo, aminosulfonyl, amidine, and C. 1-3 Alkyl, C 3-6 cycloalkyl or The amidoyl group, C 1-3 Alkyl and C 3-6 The cycloalkyl group may optionally be selected by one or more groups, each independently chosen from hydroxyl, amino, C... 1-3 Alkoxy, C 1-3 Alkyl, C 1-3 Alkyl-C(O)-O- and C 1-3 Substituents of alkyl-OC(O)- groups; L stands for -(CH2) m -OC(O)-R L1 -(CH2) n -OR L2 Or -(CH2) p -C(O)-OR L3 ; m, n, and p are each independently 1, 2, or 3; R L1 C 1-6 Alkyl, the C 1-6 Alkyl groups are optionally selected from deuterium, hydroxyl, and -NR. L1-1 R L1-2 , -(OCH2CH2) t OR L1-6 -[OC(O)-(CH2) r ] s -R L1-7 , -OP(=O)(OH)2, -OP(=O)(ONa)2, -OP(=O)(OH)(ONa) and -(NCH3-CO-CH2) u R L1-8 One or more substituents are substituted in the sample; t and u are each an independent integer from 1 to 20; r can be 0, 1, 2, or 3; s is 1, 2, or 3; M is an anion; R L1-1 R L1-2 R L1-3 R L1-4 R L1-5 R L1-6 and R L1-8 Each is independently H, deuterium, and C. 1-3 Alkyl or C 1-3 Deuterated alkyl groups; R L1-7 H, deuterium, C 1-3 Alkyl, C 1-3 Deuterated alkyl or -NR L1-71 R L1-72 ;R L1-71 and R L1-72 Each is independently H, deuterium, and C. 1-3 Alkyl or C 1-3 Deuterated alkyl groups; R L2 For H, C 1-3 Alkyl group, -P(=O)(OH)2, -P(=O)(ONa)2 or -P(=O)(OH)(ONa); R L3 For H or C 1-3 alkyl; The number of heteroatoms in each of the 5-6 membered heteroaryl, 5-6 membered heterocyclic group, 5-6 membered heteroaromatic ring, and 5-6 membered heterocyclic ring is independently 1, 2, or 3, and each heteroatom is independently selected from N, O, or S, wherein N is optionally oxidized to N→O, and S is optionally simultaneously oxidized to N→O. replace; R is H or C 1-3 alkyl.

2. The compound of claim 1 or a pharmaceutically acceptable salt thereof, characterized in that, The compound satisfies one or more of the following conditions: (1) The compound is the compound shown in formula (A-1) below. Among them, R 8 and R 9 They are different and each independently consists of H, deuterium, halogen, and C. 1-3 Alkyl, C 1-3 Deuterated alkyl or C 1-3 Halogenated alkyl groups; (2) M is Q - R L1-9 COO - 1 / 3 P(=O)(O) - )3 or R L1-10 S(O)2O - Q is a halogen; R L1-9 H, deuterium, C 1-3 Alkyl or C 1-3 Deuterated alkyl; R L1-10 C 1-3 Alkyl, C 1-3 Deuterated alkyl or C 1-3 Halogenated alkyl groups.

3. The compound of claim 1 or 2, or a pharmaceutically acceptable salt thereof, characterized in that, R 1 C 1-3 Alkyl, C 1-3 Alkoxy or C 3-6 cycloalkyl; Z is a single bond or O (preferably O); R 2 C 1-3 Alkyl, C 1-3 Deuterated alkyl or C 1-3 Halogenated alkyl groups; R 3 and R 4 Each is independently H or halogen; R 5 and R 6 Each independently represents H and C. 1-3 Alkyl or halogen; R 8 C 1-3 Alkyl (e.g., methyl) or C 1-3 Deuterated alkyl groups (e.g., -CD3); R 9 C 1-3 Halogenated alkyl groups (e.g., -CF3); In W, two atoms or groups marked with * are in adjacent positions; R 7 The definitions of T, X, Y, L and W are as described in claim 1 or 2.

4. The compound of claim 1 or a pharmaceutically acceptable salt thereof, characterized in that, The compound is a compound of the following formula (I). in, R 1 C 1-3 Alkyl, C 1-3 Alkoxy or C 3-6 cycloalkyl; R 2 C 1-3 Alkyl, C 1-3 Deuterated alkyl or C 1-3 Halogenated alkyl groups; R 3 and R 4 Each is independently H or halogen; R 5 and R 6 Each independently represents H and C. 1-3 Alkyl or halogen; X is O, S, or N(R) X ); R X For H or C 1-3 alkyl; Y is CH, C, N, or NH, and T is O or CHR. T Where Y is CH or C, and T is CHR T At that time, R 7 and R T The methylene group forms a 6-membered nitrogen-containing heterocycle with the atoms it is attached to, wherein the methylene group is optionally... Substitution, and the 6-membered nitrogen-containing heterocycle forms a fused ring with W; when Y is CH or C, and T is O, R 7 H, halogen or C 1-3 Alkyl; when Y is N or NH, T is O, R 7 It does not exist; In W, two atoms or groups marked with * are in adjacent positions; W is a phenyl, a 5-6-membered heteroaryl, a 5-6-membered heterocyclic, a 5-6-membered heterocyclic phenyl, or a 5-6-membered heterocyclic 5-6-membered heteroaryl, wherein the phenyl, 5-6-membered heteroaryl, 5-6-membered heterocyclic phenyl, and 5-6-membered heterocyclic 5-6-membered heteroaryl are optionally surrounded by one or more R W replace; Each R W Each group independently consists of carbamoyl, halogen, oxo, aminosulfonyl, amidine, and C. 1-3 Alkyl or C 3-6 cycloalkyl, wherein the amidine group, C 1- 3-alkyl and C 3-6 The cycloalkyl group may optionally be selected by one or more groups, each independently chosen from hydroxyl, amino, C... 1-3 Alkoxy, C 1-3 Alkyl, C 1-3 Alkyl-C(O)-O- and C 1-3 Substituents of alkyl-OC(O)- groups; L stands for -(CH2) m -OC(O)-R L1 -(CH2) n -OR L2 Or -(CH2) p -C(O)-OR L3 ; m, n, and p are each independently 1, 2, or 3; R L1 C 1-3 alkyl; R L2 and R L3 Each independently is H or C 1-3 alkyl; The number of heteroatoms in the 5-6 membered heteroaryl, 5-6 membered heterocyclic, 5-6 membered heterocyclic phenyl, or 5-6 membered heterocyclic 5-6 membered heteroaryl is 1, 2, or 3, and each heteroatom is independently selected from N, O, or S, wherein N is optionally oxidized to N→O, and S is optionally simultaneously oxidized to N→O. replace; R is H or C 1-3 alkyl.

5. The compound or a pharmaceutically acceptable salt thereof as described in any one of claims 1-4, characterized in that, It meets one or more of the following conditions: (1)R 1 R Z R 2 R 5 R 6 R X R 7 R 8 R 9 R W R L1 R L1-1 R L1-2 R L1-3 R L1-4 R L1-5 R L1-6 R L1-7 R L1-71 R L1-72 R L1-8 R L1-9 R L1-10 R L2 R L3 In R, the C 1-3 The alkyl group is methyl, ethyl, n-propyl or isopropyl, preferably methyl, ethyl or isopropyl; (2)R L1 In, the C 1-6 The alkyl group is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, neopentyl, sec-pentyl, tert-pentyl, dimethylpropyl, n-hexyl, methylpentyl, dimethylbutyl, ethylbutyl, trimethylpropyl, or 1-ethyl-1-methylpropyl, preferably C10. 1-3 alkyl; (3)R 1 R 2 and R W In, the C 1-3 The alkoxy group is methoxy, ethoxy, n-propoxy, or isopropoxy, preferably methoxy; (4)R 1 R 2 W and R W In, the C 3-6 Cycloalkyl group is C 3-6 Monocyclic cycloalkyl, preferably cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl, more preferably cyclopropyl, cyclopentyl or cyclohexyl; (5)R 1 R Z R 8 R 9 R L1-1 R L1-2 R L1-3 R L1-4 R L1-5 R L1-6 R L1-7 R L1-71 R L1-72 R L1-8 R L1-9 R L1-10 and R 2 In, the C 1-3 C in deuterated alkyl groups 1-3 The alkyl group is methyl, ethyl, n-propyl, or isopropyl, preferably methyl; (6)R 1 R Z R 8 R 9 R L1-1 R L1-2 R L1-3 R L1-4 R L1-5 R L1-6 R L1-7 R L1-71 R L1-72 R L1-8 R L1-9 R L1-10 and R 2 In, the C 1-3 The number of deuterium atoms in the deuterated alkyl group is 1, 2, 3 or more, preferably 3; (7)R 1 R 2 R 8 R 9 and R L1-10 In, the C 1-3 C in haloalkyl 1-3 The alkyl group is methyl, ethyl, n-propyl, or isopropyl, preferably methyl; (8)R 1 R 2 R 8 R 9 and R L1-10 In, the C 1-3 The halogen in the haloalkyl group is F, Cl, Br or I, preferably F; (9)R 1 R 2 R 8 R 9 and R L1-10 In, the C 1-3 The number of halogens in the haloalkyl group is 1, 2, 3 or more, preferably 2 or 3; (10)R 2 R 3 R 4 R 5 R 6 R 7 R 8 R 9 R W In Q, the halogen is F, Cl, Br or I, preferably F or Cl; (11) In W, the number of heteroatoms in the 5-6 membered heteroaryl group is 1 or 2, preferably 1; (12)W, the heteroatom in the 5-6 membered heteroaryl group is N, wherein N is optionally oxidized to N→O; (13)W, the 5-6 membered heteroaryl is a 6 membered heteroaryl; (14) In W, the number of heteroatoms in the 5-6 membered heterocyclic group is 1; (15) In W, the heteroatom in the 5-6 membered heterocyclic group is N or S, wherein S is optionally simultaneously... replace; (16)W, ​​the 5-6 member heterocyclic group is a 6 member heterocyclic group; (17)W, the number of heteroatoms in the 5-6 membered heteroaromatic ring is 1 or 2; (18) In W, the heteroatom in the 5-6 membered heteroaromatic ring is N; (19)W, the 5-6 member heteroaryl ring is a 5 member heteroaryl ring; In (20)W, the number of heteroatoms in the 5-6 membered heterocycle is 1 or 2; (21) In W, the heteroatom in the 5-6 membered heterocycle is N; (22)W, the 5-6 member heterocycle is a 5-membered heterocycle or a 6-membered heterocycle; (23)W, the C 3-6 The monocyclic carbocyclic ring is cyclopropane, cyclobutane, cyclopentane or cyclohexane, preferably cyclopentane or cyclohexane; (24)W, wherein the dicyclic cycloyl group is a 5-6 membered heterocyclic cyclophenyl, a 5-6 membered heterocyclic cyclophenyl, a 5-6 membered heterocyclic cyclophenyl-5-6 membered heteroaryl, a 5-6 membered heterocyclic cyclophenyl-5-6 membered heterocyclic group, or a 5-6 membered heterocyclic cyclophenyl-C 3-6 cycloalkyl, 5-6 membered heteroaryl, 5-6 membered heteroaryl, 5-6 membered heteroaryl, 5-6 membered heteroaryl, 5-6 membered heteroaryl 3-6 cycloalkyl, naphthyl, benzocyclopentaenoyl 5-6 membered heteroaryl, benzocyclopentaenoyl 5-6 membered heterocyclic, benzocyclopentaenoyl C 3-6 cycloalkyl, C 3-6 Monocyclic carbocyclophenyl, C 3-6 Monocyclic carbocyclic 5-6 membered heteroaryl, C 3-6 Monocyclic carbocyclic 5-6 membered heterocyclic groups or C 3-6 Monocyclic carbon ring fused C 3-6 Cycloalkyl, preferably 5-6 membered heterocyclic phenyl or 5-6 membered heterocyclic 5-6 membered heteroaryl; (25)W, the number of heteroatoms in the 5-6 membered heterocyclic phenyl group is 1; (26)W, the heteroatom in the 5-6 membered heterocyclic phenyl group is N; (27)W, the 5-6 membered heterocyclic benzophenyl is a 5-membered heterocyclic benzophenyl; (28)W, the number of heteroatoms in the 5-6 membered heterocyclic 5-6 membered heteroaryl group is 2 or 3; (29)W, the heteroatom in the 5-6 membered heterocyclic 5-6 membered heteroaryl group is N; In (30)W, the 5-6 membered heterocyclic 5-6 membered heteroaryl is a 6 membered heterocyclic 5 membered heteroaryl; (31)W, wherein the phenyl, 5-6-membered heteroaryl, 5-6-membered heterocyclic group, C 3-6 Cycloalkyl and dicyclic groups are optionally separated by one or two R groups. W replace; (32)R W In this context, the amidine group is optionally replaced by a compound selected from hydroxyl, C... 1-3 Alkoxy and C 1-3 Substituents of alkyl-OC(O)- groups; (33)R W In, the C 1-3 The alkyl group may be optionally selected from two independently chosen hydroxyl and C. 1-3 The alkyl-C(O)-O- substituents are preferably substituted with two hydroxyl groups, more preferably with two hydroxyl groups; (34)R W In, the C 3-6 The cycloalkyl group may be optionally substituted with one amino group, preferably with one amino group.

6. The compound or a pharmaceutically acceptable salt thereof as described in any one of claims 1-5, characterized in that, It meets one or more of the following conditions: (1)R 1 R L1-1 R L1-2 R L1-3 R L1-4 R L1-5 R L1-6 R L1-71 R L1-72 R X R L2 In R, the C 1-3 The alkyl group is methyl; (2)R 2 In, the C 1-3 The alkyl group is methyl or ethyl; (3)R W In, the C 1-3 The alkyl group is methyl or ethyl; (4)R 1 and R W In, the C 3-6 The cycloalkyl group is cyclopropyl; (5) In W, the C 3-6 The cycloalkyl group is cyclopentyl or cyclohexyl; (6)R 1 R Z R 8 R 9 R L1-1 R L1-2 R L1-3 R L1-4 R L1-5 R L1-6 R L1-7 R L1-71 R L1-72 R L1-8 R L1-9 R L1-10 and R 2 In, the C 1-3 The deuterated alkyl group is -CD3; (7)R 1 R 2 R 8 R 9 and R L1-10 In, the C 1-3 The alkyl halide is -CHF2 or -CF3; (8)R 3 R 4 R 5 R 6 R 7 and R W In this context, the halogen is F; (9) In Q, the halogen is Cl; In (10)W, the 5-6 member heteroaryl group is pyridyl, N-pyridyl oxide, or pyrimidinyl, preferably pyridyl or N-pyridyl oxide; more preferably, the 5-6 member heteroaryl group is Preferred (11)W, the 5-6 member heterocyclic group is (12)W, the 5-6 membered heteroaryl ring is pyrazole or pyrrole; (13)W, wherein the 5-6 membered heterocycle is tetrahydropyrrole, dihydropyridine or tetrahydropyrimidine (e.g. 1,2,3,4-tetrahydropyrimidine), preferably dihydropyridine (e.g. 1,2-dihydropyridine) or tetrahydropyrrole; (14)W, the 5-6 membered heterocyclic phenyl group is In (15)W, the 5-6 membered heterocyclic 5-6 membered heteroaryl is (16)W, ​​the phenyl group is optionally coated with two R groups. W Replacement, preferably by two R W replace; (17)W, the 5-6 heteroaryl group is optionally coated with one or two R groups. W Replacement, preferably optional, by an R W Substitution; preferably, the 5-6 membered heteroaryl group is replaced by one or two R groups. W Replacement, preferably by an R W replace; In (18)W, the 5-6 member heterocyclic group is optionally replaced by an R W Replacement, preferably by an R W replace; In (19)W, the biparacyclic base is arbitrarily assigned to an R. W Replacement, preferably by an R W replace; In (20)W, the 5-6 membered heterocyclic phenyl group is optionally surrounded by an R W Replacement, preferably by an R W replace; (21)W, the 5-6 membered heterocyclic 5-6 membered heteroaryl group is optionally replaced by an R W Replacement, preferably by an R W replace; (22) When W is phenyl, each R W Each can be independently carbamoyl, halogen, aminosulfonyl, or Preferably, it is halogenated or aminosulfonyl; (23) When W is a 5-6 member heteroaryl group, each R W Each is independently composed of carbamoyl, halogen, amidine, and C. 1-3 Alkyl, C 3-6 cycloalkyl or The amidoyl group, C 1-3 Alkyl and C 3-6 The cycloalkyl group may optionally be selected by one or more groups, each independently chosen from hydroxyl, amino, C... 1-3 Alkoxy, C 1-3 Alkyl, C 1-3 Alkyl-C(O)-O- and C 1-3 Alkyl-OC(O)- substituents; preferably, each R W Each is independently carbamoyl, C 1-3 alkyl or Wherein C 1-3 Alkyl groups may optionally be selected from one or more hydroxyl groups and C12 groups. 1-3 Alkyl-C(O)-O- substituents; (24) When W is a 5-6 member heterocyclic group, R W For oxygenation; (25) When W is a bis-ring base, R W For oxygenation; (26) When W is a 5-6 membered heterocyclic phenyl group, R W For oxygenation; (27) When W is a 5-6 membered heterocyclic compound and a 5-6 membered heteroaryl compound, R W It is an oxygen-based process.

7. The compound or a pharmaceutically acceptable salt thereof as described in any one of claims 1-3, characterized in that, It meets one or more of the following conditions: (1)R 1 C 1-3 alkyl; (2) Z is O; (3)R 2 C 1-3 Alkyl or C 1-3 Deuterated alkyl groups; (4)R 3 and R 4 Each is an independent halogen; (5)R 5 and R 6 For H; (6)R 8 C 1-3 Alkyl or C 1-3 Deuterated alkyl groups; (7)R 9 C 1-3 Halogenated alkyl groups; (8) X is O, S, N(H) or N(CH3); (9) Y is CH or C, and T is O or CHR. T Where Y is CH or C, and T is CHR T At that time, R 7 and R T The methylene group forms a 6-membered nitrogen-containing heterocycle with the atoms it is attached to, wherein the methylene group is optionally... Substitution, and the 6-membered nitrogen-containing heterocycle forms a fused ring with W; when Y is CH or C, and T is O, R 7 H, halogen or C 1-3 Alkyl; preferably, Y is CH or C, T is O, and R is... 7 H, halogen or C 1-3 alkyl; (10)W is phenyl, 5-6-membered heteroaryl or dicyclic, preferably phenyl, 5-6-membered heteroaryl or 5-6-membered heterocyclic phenyl, more preferably phenyl or 5-6-membered heteroaryl, for example 5-6-membered heteroaryl; (11) Each R W Each can be independently carbamoyl, halogen, oxo, aminosulfonyl, or C. 1-3 Alkyl, wherein the C 1-3 Alkyl groups may optionally be selected from one or more hydroxyl groups and C12 groups. 1-3 Alkyl-C(O)-O- substituents, wherein C 1-3 The alkyl group is preferably selected by one or two independently chosen from hydroxyl and C. 1-3 Alkyl-C(O)-O- substituents; preferably carbamoyl, halogen or C 1-3 Alkyl, wherein the C 1-3 Alkyl groups may optionally be selected from one or more hydroxyl groups and C12 groups. 1-3 Alkyl-C(O)-O- substituents, wherein C 1-3 The alkyl group is preferably selected by one or two independently chosen from hydroxyl and C. 1- Substituents of 3 alkyl-C(O)-O- are preferred; more preferably carbamoyl or C 1-3 Alkyl, wherein the C 1-3 Alkyl groups may optionally be selected from one or more hydroxyl groups and C12 groups. 1-3 Alkyl-C(O)-O- substituents, wherein C 1-3 The alkyl group is preferably selected by one or two independently chosen from hydroxyl and C. 1-3 Alkyl-C(O)-O- substituents; (12) m is 1 or 2, preferably 1; (13) n is 1 or 2; (14) p is 1; (15)R L1 C 1-3 Alkyl, the C 1-3 Alkyl groups may be selected from hydroxyl, -NR L1-1 R L1-2 , -(OCH2CH2) t OR L1-6 -[OC(O)-(CH2) r ] s -R L1-7 , -OP(=O)(OH)2, -OP(=O)(ONa)2, -OP(=O)(OH)(ONa) and -(NCH3-CO-CH2) u R L1-8 One or both substituents are substituted; or, R L1 C 1-3 Alkyl, the C 1-3 Alkyl groups are optionally selected from hydroxyl groups, One or more substituents from -OP(=O)(OH)2, -OP(=O)(ONa)2, and -OP(=O)(OH)(ONa) are substituted; or, R L1 C 1-3 Alkyl, the C 1-3 Alkyl groups may be selected from hydroxyl groups, One or both of the substituents in -OP(=O)(OH)2, -OP(=O)(ONa)2 and -OP(=O)(OH)(ONa) are substituted; or, R L1 C 1-3 Alkyl, the C 1-3 Alkyl groups may be optionally replaced by hydroxyl groups and / or Substituents; or R L1 C 1-3 Alkyl, the C 1-3 Alkyl groups are replaced by hydroxyl groups, or by hydroxyl groups and... replace; (16) t is any integer from 1 to 15, preferably any integer from 3 to 11, for example, 3, 5 or 11; (17) u is any integer from 5 to 15, for example, 10; (18) r is 1, 2 or 3, for example, 1; (19) s is 1 or 2, for example, 1; (20) M is Q - or R L1-9 COO - ; (21)R L1-1 and R L1-2 Each independently is H or C 1-3 Alkyl groups, preferably H- or methyl groups; (22)R L1-3 R L1-4 and R L1-5 Each independently is C 1-3 Alkyl groups, such as methyl groups; (23)R L1-6 For H or C 1-3 Alkyl groups, preferably H- or methyl groups; (24)R L1-7 For -NR L1-71 R L1-72 ;R L1-71 and R L1-72 Each is independently preferred to be C 1-3 Alkyl groups, such as methyl groups; (25)R L1-8 For H; (26)R L1-9 For H or C 1-3 Alkyl group, preferably H; (27)R L1-10 C 1-3 Alkyl or C 1-3 Halogenated alkyl groups, preferably C 1-3 alkyl; (28)R L2 For H, C 1-3 Alkyl or -P(=O)(OH)2, preferably C 1-3 Alkyl groups or -P(=O)(OH)2, for example, C 1-3 alkyl; (29)R L3 For H; (30)L is -(CH2) m -OC(O)-R L1 ; (31) R is C 1-3 alkyl.

8. The compound or a pharmaceutically acceptable salt thereof as described in any one of claims 1-7, characterized in that, It meets one or more of the following conditions: (1)R 1 It is methyl, methoxy, or cyclopropyl, preferably methyl; (2)R 2 It is -CD3, -CH3, -CH2CH3, -CHF2 or -CF3, preferably -CD3 or -CH3; (3)R 3 and R 4 For F; (4)R 8 It is -CH3 or -CD3; (5)R 9 -CF3; (6)R X It is H or methyl; (7) X is O or S; preferably, X is O; (8) T is 0; (9)R 7 For H; (10) Each R W Each independently (For example )、 (For example )、 (For example )、 Preferably, each R W Each independently (For example )、 More preferably, each R W Each independently (For example Further preferably, each R W Each independently (For example For example, each R W Each independently (11) fragment for Preferably, fragments for Preferably, fragments for More preferably, fragments for More preferably, fragments for More preferably, fragments for (12) fragment for Preferably, fragments for Preferably, fragments for More preferably, fragments for More preferably, fragments for More preferably, fragments for (13)R L1 The following are the possible values: methyl, ethyl, isopropyl, -CH2-N(CH3)2, -(CH2)2-N(CH3)2, -(CH2)3-N(CH3)2, -CH2-NHCH3, -CH2-NH2, -CH2-N + (CH3)3·M、-(CH2)3-N + (CH3)3·M, -CH2-(OCH2CH2)3OH, -CH2-(OCH2CH2)5OH, -(CH2)2-(OCH2CH2)5OH, -(CH2)2-(OCH2CH2)5OCH3, -(CH2)2-(OCH2CH2) 11 OCH3, -CH2-OC(O)-CH2-N(CH3)2, -CH2-OH, -CH2-OP(=O)(OH)2, -CH2-OP(=O)(ONa)2, -CH2-OP(=O)(OH)(ONa), -CH2-(NCH3-CO-CH2) 10 H or -CH2-CH(OH)-CH2-N + (CH3)3·M (e.g.) Preferred Preferably, methyl, ethyl, isopropyl, -CH2-N(CH3)2, -(CH2)2-N(CH3)2, -(CH2)3-N(CH3)2, -CH2-NHCH3, -CH2-NH2, -CH2-N + (CH3)3·M, -CH2-(OCH2CH2)3OH, -CH2-(OCH2CH2)5OH, -(CH2)2-(OCH2CH2)5OH, -(CH2)2-(OCH2CH2)5OCH3, -(CH2)2-(OCH2CH2) 11 OCH3, -CH2-OC(O)-CH2-N(CH3)2, -CH2-OH, -CH2-OP(=O)(OH)2, -CH2-OP(=O)(ONa)2, -CH2-OP(=O)(OH)(ONa), -CH2-(NCH3-CO-CH2) 10 H or -CH2-CH(OH)-CH2-N + (CH3)3·M (e.g.) Preferred More preferably, it is methyl, -CH2-OH, -CH2-OP(=O)(OH)2, -CH2-OP(=O)(ONa)2, -CH2-OP(=O)(OH)(ONa) or -CH2-CH(OH)-CH2-N + (CH3)3·M (e.g.) Preferred )； (14)R L2 It can be H, methyl, -P(=O)(OH)2, -P(=O)(ONa)2 or -P(=O)(OH)(ONa), preferably methyl or -P(=O)(OH)2; (15)L is -CH2-O-C(O)-CH3, -CH2-C(O)-OH, -CH2-O-CH3, -(CH2)2-O-C(O)-CH3, -(CH2)2-O-CH3, -(CH2)2-O-C(O)-CH(CH3)2, -(CH2)2-OH, -CH2-O-C(O)-CH(CH3)2, -CH2-O-C(O)-CH2-CH3, -CH2-OP(=O)(OH)2, -CH2-O-C(O)-CH2-N(CH3)2, -CH2-O-C(O)-(CH2)2-N(CH3)2, -CH2-O-C(O)-(CH2)3-N(CH3)2, -CH2-O-C(O)-CH2-NHCH3, -CH2-O-C(O)-CH2-NH2, -CH2-O-C(O)-CH2-N + (CH3)3·M, -CH2-O-C(O)-(CH2)3-N + (CH3)3·M, -CH2-O-C(O)-CH2-(OCH2CH2)3OH, -CH2-O-C(O)-CH2-(OCH2CH2)5OH, -CH2-O-C(O)-(CH2)2-(OCH2CH2)5OH, -CH2-O-C(O)-(CH2)2-(OCH2CH2)5OCH3, -CH2-O-C(O)-(CH2)2-(OCH2CH2) 11 OCH3, -CH2-O-C(O)-CH2-O-C(O)-CH2-N(CH3)2, -CH2-O-C(O)-CH2-OH, -CH2-O-C(O)-CH2-OP(=O)(OH)2, -CH2-O-C(O)-CH2-OP(=O)(ONa)2, -CH2-O-C(O)-CH2-OP(=O)(OH)(ONa), -CH2-O-C(O)-CH2-(NCH3-CO-CH2) 10 H or -CH2-O-C(O)-CH2-CH(OH)-CH2-N + (CH3)3·M (for example Preferred ); Preferably, L is -CH2-O-C(O)-CH3, -CH2-C(O)-OH, -CH2-O-CH3, -(CH2)2-O-C(O)-CH3, -(CH2)2-O-CH3, -(CH2)2-O-C(O)-CH(CH3)2, -CH2-OP(=O)(OH)2, -CH2-O-C(O)-CH2-N(CH3)2, -CH2-O-C(O)-(CH2)2-N(CH3)2, -CH2-O-C(O)-(CH2)3-N(CH3)2, -CH2-O-C(O)-CH2-NHCH3, -CH2-O-C(O)-CH2-NH2, -CH2-O-C(O)-CH2-N + (CH3)3·M, -CH2-O-C(O)-(CH2)3-N + (CH3)3·M, -CH2-O-C(O)-CH2-(OCH2CH2)3OH, -CH2-O-C(O)-CH2-(OCH2CH2)5OH, -CH2-O-C(O)-(CH2)2-(OCH2CH2)5OH, -CH2-O-C(O)-(CH2)2-(OCH2CH2)5OCH3, -CH2-O-C(O)-(CH2)2-(OCH2CH2) 11 OCH3, -CH2-O-C(O)-CH2-O-C(O)-CH2-N(CH3)2, -CH2-O-C(O)-CH2-OH, -CH2-O-C(O)-CH2-OP(=O)(OH)2, -CH2-O-C(O)-CH2-OP(=O)(ONa)2, -CH2-O-C(O)-CH2-OP(=O)(OH)(ONa), -CH2-O-C(O)-CH2-(NCH3-CO-CH2) 10 H or -CH2-O-C(O)-CH2-CH(OH)-CH(OH)-CH2-N + (CH3)3·M (for example Preferred More preferably, L is -CH2-OC(O)-CH3, -CH2-OC(O)-CH2-OH, -CH2-OC(O)-CH2-OP(=O)(OH)2, -CH2-OC(O)-CH2-OP(=O)(ONa)2, -CH2-OC(O)-CH2-OP(=O)(OH)(ONa) or -CH2-OC(O)-CH2-CH(OH)-CH2-N + (CH3)3·M (e.g.) Preferred Further preferably, L is -CH2-OC(O)-CH3, -CH2-OC(O)-CH2-OH, or -CH2-OC(O)-CH2-CH(OH)-CH2-N. + (CH3)3·Cl - (For example Preferred )； (16) R is methyl.

9. The compound or a pharmaceutically acceptable salt thereof as claimed in any one of claims 1-8, characterized in that, It meets one of the following conditions: (1) Y is CH or C, and T is O, R 7 H, halogen or C 1-3 Alkyl group; W is phenyl, 5-6 membered heteroaryl, or 5-6 membered heterocyclic phenyl group; (2) Y is C, and T is O, R 7 H is a 5-6 membered heteroaryl group, W is a 5-6 membered heteroaryl group; preferably, Y is C, T is O, and R is R. 7 H is 0, and W is pyridinyl.

10. The compound or a pharmaceutically acceptable salt thereof as claimed in any one of claims 1-9, characterized in that, The compound is a compound of formula (II), a compound of formula (III), a compound of formula (IV), a compound of formula (V), a compound of formula (VI), a compound of formula (VII), or a compound of formula (VIII) (e.g., a compound of formula (VIII-1) or formula (VIII-2)). (For example ); In W, two atoms or groups marked with * are in adjacent positions; R 1 R 2 R 3 R 4 R 5 R 6 R 7 X, Y, T, W, L, m, R L1 The definition of M is as described in any one of claims 1-9; wherein, in the compounds represented by formula (VII) and formula (VIII) (e.g., the compounds represented by formula (VIII-1) and formula (VIII-2), R 8 and R 9 They are different and each independently consists of H, deuterium, halogen, and C. 1-3 Alkyl, C 1-3 Deuterated alkyl or C 1-3 Halogenated alkyl groups; Preferably, in the compound represented by formula (II), the fragment for (preferred) For example, )； Preferably, in the compound represented by formula (III), the fragment for (preferred) For example, )； Preferably, in the compound represented by formula (IV), the fragment for (preferred) )； Preferably, the compound represented by formula (V) satisfies one or more of the following conditions: (1) Fragment for (preferred) For example )； (2) T is 0; (3)R 3 and R 4 For F; (4)R 5 and R 6 For H; Preferably, in the compound shown in formula (VI), W is a 5-6 membered heteroaryl or a 5-6 membered heterocyclic group; Preferably, in the compounds shown in formula (VII) and formula (VIII) (e.g., compounds shown in formula (VIII-1) and formula (VIII-2), the fragment for (preferred) For example, )。 11. The compound of claim 10 or a pharmaceutically acceptable salt thereof, characterized in that, (1) In the compound shown in formula (II), Excerpt for (preferred) )； R 1 C 1-3 Alkyl, C 1-3 Alkoxy or C 3-6 cycloalkyl (preferably C) 1-3 alkyl); R 2 C 1-3 Alkyl, C 1-3 Deuterated alkyl or C 1-3 Halogenated alkyl groups (preferably C14) 1-3 Alkyl or C 1-3 (deuterated alkyl); R 3 R 4 Each is independently a halogen (preferably F); R 5 R 6 Each is independently H or deuterium (preferably H); X is O; T is O; m is 1 or 2 (preferably 1); R L1 C 1-3 Alkyl, the C 1-3 Alkyl groups may be selected from hydroxyl, -NR L1-1 R L1-2 , -(OCH2CH2) t OR L1-6 -[OC(O)-(CH2) r ] s -R L1-7 , -OP(=O)(OH)2, -OP(=O)(ONa)2, -OP(=O)(OH)(ONa) and -(NCH3-CO-CH2) u R L1-8 One or two substituents are substituted (preferably, the C 1-3 Alkyl groups are optionally selected from hydroxyl groups, One or two of the substituents in -OP(=O)(OH)2, -OP(=O)(ONa)2, and -OP(=O)(OH)(ONa) are substituted; more preferably, the C 1-3 Alkyl groups may be selected from hydroxyl groups and / or Substituents of R; more preferably, R L1 It is -CH2-OH or -CH2-CH(OH)-CH2-N + (CH3)3·Cl - For example, R L1 -CH2-OH, For example, R L1 -CH2-OH or )； t is any integer from 3 to 11 (preferably 3, 5 or 11); u is any integer from 5 to 15 (preferably 10); r is 1, 2 or 3 (preferably 1); s is 1 or 2 (preferably 1); M is an anion (preferably Q). - R L1-9 COO - 1 / 3 P(=O)(O) - )3 or R L1-10 S(O)2O - Q is preferred. - Or R L1-9 COO - Where Q is a halogen, and R L1-9 For H or C 1-3 Alkyl, R L1-10 C 1-3 Alkyl or C 1-3 (halogenated alkyl); R L1-1 and R L1-2 Each independently is H or C 1-3 alkyl; R L1-3 R L1-4 and R L1-5 Each independently is C 1-3 alkyl; R L1-6 For H or C 1-3 alkyl; R L1-7 For -NR L1-71 R L1-72 ; R L1-71 and R L1-72 Each independently is C 1-3 alkyl; R L1-8 For H; (2) In the compound shown in formula (III), Excerpt for (preferred) )； R 1 C 1-3 Alkyl, C 1-3 Alkoxy or C 3-6 cycloalkyl (preferably C) 1-3 alkyl); R 2 C 1-3 Alkyl, C 1-3 Deuterated alkyl or C 1-3 Halogenated alkyl groups (preferably C14) 1-3 Alkyl or C 1-3 (deuterated alkyl); X is O; The definition of L is as described in any one of claims 1-10; (3) In the compound shown in formula (IV), Excerpt for (preferred) )； R 1 C 1-3 Alkyl, C 1-3 Alkoxy or C 3-6 Cycloalkyl, preferably C 1-3 alkyl; R 2 C 1-3 Alkyl, C 1-3 Deuterated alkyl or C 1-3 Halogenated alkyl groups, preferably C 1-3 Alkyl or C 1-3 Deuterated alkyl groups; X is O; m is 1 or 2, preferably 1; R L1 C 1-3 Alkyl, the C 1-3 Alkyl groups may be selected from hydroxyl, -NR L1-1 R L1-2 , -(OCH2CH2) t OR L1-6 -[OC(O)-(CH2) r ] s -R L1-7 , -OP(=O)(OH)2, -OP(=O)(ONa)2, -OP(=O)(OH)(ONa) and -(NCH3-CO-CH2) u R L1-8 One or two substituents are substituted; preferably, the C 1-3 Alkyl groups are optionally selected from hydroxyl groups, One or two of the substituents in -OP(=O)(OH)2, -OP(=O)(ONa)2, and -OP(=O)(OH)(ONa) are substituted; more preferably, the C 1-3 Alkyl groups may be selected from hydroxyl groups and / or Substituents; for example, R L1 It is -CH2-OH or -CH2-CH(OH)-CH2-N + (CH3)3·Cl - ; t is any integer from 3 to 11 (preferably 3, 5 or 11); u is any integer from 5 to 15 (preferably 10); r is 1, 2 or 3 (preferably 1); s is 1 or 2 (preferably 1); M is an anion (preferably Q). - R L1-9 COO - 1 / 3 P(=O)(O) - )3 or R L1-10 S(O)2O - Q is preferred. - Or R L1-9 COO - Where Q is a halogen, and R L1-9 For H or C 1-3 Alkyl, R L1-10 C 1-3 Alkyl or C 1-3 (Halogenated alkyl); R L1-1 and R L1-2 Each independently is H or C 1-3 alkyl; R L1-3 R L1-4 and R L1-5 Each independently is C 1-3 alkyl; R L1-6 For H or C 1-3 alkyl; R L1-7 For -NR L1-71 R L1-72 ; R L1-71 and R L1-72 Each independently is C 1-3 alkyl; R L1-8 For H; (4) In the compound shown in formula (VII), Excerpt for (preferred) )； R 1 C 1-3 Alkyl, C 1-3 Alkoxy or C 3-6 cycloalkyl (preferably C) 1-3 Alkyl groups (e.g., methyl groups); R 2 C 1-3 Alkyl, C 1-3 Deuterated alkyl or C 1-3 Halogenated alkyl groups (preferably C14) 1-3 Alkyl (e.g., methyl) or C 1-3 Deuterated alkyl groups (e.g., deuterated methyl groups); R 3 and R 4 Each is an independent halogen (e.g., F); R 5 and R 6 Each is independently H or deuterium (preferably H); R 8 and R 9 They are different and each independently consists of H, deuterium, halogen, and C. 1-3 Alkyl, C 1-3 Deuterated alkyl or C 1-3 Haloalkyl (preferably, R) 8 C 1-3 Alkyl (e.g., methyl) or C 1-3 Deuterated alkyl groups (e.g., -CD3); R 9 C 1-3 Halogenated alkyl groups (e.g., -CF3); X is O; (5) Among the compounds shown in formula (VIII), formula (VIII-1) and formula (VIII-2), Excerpt for (preferred) )； R 1 C 1-3 Alkyl, C 1-3 Alkoxy or C 3-6 cycloalkyl (preferably C) 1-3 Alkyl groups (e.g., methyl groups); R 2 C 1-3 Alkyl, C 1-3 Deuterated alkyl or C 1-3 Halogenated alkyl groups (preferably C14) 1-3 Alkyl (e.g., methyl) or C 1-3 Deuterated alkyl groups (e.g., deuterated methyl groups); R 3 and R 4 Each is an independent halogen (e.g., F); R 5 and R 6 Each is independently H or deuterium (preferably H); R 8 and R 9 They are different and each independently consists of H, deuterium, halogen, and C. 1-3 Alkyl, C 1-3 Deuterated alkyl or C 1-3 Haloalkyl (preferably, R) 8 C 1-3 Alkyl (e.g., methyl) or C 1-3 Deuterated alkyl groups (e.g., -CD3); R 9 C 1-3 Halogenated alkyl groups (e.g., -CF3); X is O; M is Q - R L1-9 COO - 1 / 3 P(=O)(O) - )3 or R L1-10 S(O)2O - (preferably Q) - Or R L1-9 COO - Q is preferred. - ); Q is a halogen (e.g., Cl); R L1-9 For H or C 1-3 Alkyl group (preferably H); R L1-10 C 1-3 Alkyl or C 1-3 Halogenated alkyl groups (e.g., fluoromethyl groups); (6) In the compound shown in formula (VII), Excerpt for R 1 C 1-3 Alkyl groups (e.g., methyl groups); R 2 C 1-3 Alkyl (e.g., methyl) or C 1-3 Deuterated alkyl groups (e.g., deuterated methyl groups); R 3 and R 4 Each is an independent halogen (e.g., F); R 5 and R 6 Each is independently represented by H; R 8 C 1-3 Alkyl (e.g., methyl) or C 1-3 Deuterated alkyl groups (e.g., -CD3); R 9 C 1-3 Halogenated alkyl groups (e.g., -CF3); X is O; Or (7) the compounds shown in formula (VIII), formula (VIII-1) and formula (VIII-2), Excerpt for R 1 C 1-3 Alkyl groups (e.g., methyl groups); R 2 C 1-3 Alkyl (e.g., methyl) or C 1-3 Deuterated alkyl groups (e.g., deuterated methyl groups); R 3 and R 4 Each is an independent halogen (e.g., F); R 5 and R 6 Each is independently represented by H; R 8 C 1-3 Alkyl or C 1-3 Deuterated alkyl groups (e.g., methyl or -CD3); R 9 C 1-3 Halogenated alkyl groups (e.g., -CF3); X is O; M is Q - Or R L1-9 COO - ; Preferably Q - ; Q is a halogen (e.g., Cl); R L1-9 For H.

12. A compound or a pharmaceutically acceptable salt thereof, characterized in that, The compound is selected from any of the following compounds:

13. A pharmaceutical composition comprising: (1) The compound or a pharmaceutically acceptable salt thereof as described in any one of claims 1-12, and (2) Pharmaceutically acceptable excipients.

14. The use of the compound of any one of claims 1-12 or a pharmaceutically acceptable salt thereof, or the pharmaceutical composition of claim 13, in the preparation of a medicament or a Nav1.8 channel inhibitor; Preferably, the Nav1.8 channel inhibitor is an in vitro Nav1.8 channel inhibitor; Preferably, the drug is a drug for treating diseases related to the Nav1.8 channel, wherein the disease related to the Nav1.8 channel is preferably pain, and the pain is preferably acute pain; Preferably, the drug is a pain treatment drug, and the pain is preferably acute pain.

15. A method for preparing the compound of formula (III) or the compound of formula (IV) as described in any one of claims 10-11, characterized in that, (i) When fragment for When the compound represented by formula (III) is the same as the compound represented by formula (III-1), its preparation method includes the following steps: In a solvent, in the presence of a catalyst, the compound shown in formula (III-1-1) undergoes the reduction reaction shown below to give the compound shown in formula (III-1); Among them, R 1 R 2 The definitions of X and L are as described in any one of claims 10-11; (ii) When fragment for When the compound represented by formula (III) is the same as the compound represented by formula (III-2), its preparation method includes the following steps: In a solvent, in the presence of an acid, the compound shown in formula (III-2-1) undergoes the deprotection reaction shown below to give the compound shown in formula (III-2); Among them, R 1 R 2 The definitions of X and L are as described in any one of claims 10-11; (iii) When the fragment for When the compound represented by formula (III) is the same as the compound represented by formula (III-3), its preparation method includes the following steps: In a solvent, in the presence of an oxidizing agent, the compound shown in formula (III-1) undergoes the following oxidation reaction to give the compound shown in formula (III-3); Among them, R 1 R 2 The definitions of X and L are as described in any one of claims 10-11; (iv) When fragment for When L is -CH2-OC(O)-CH3, the compound represented by formula (III) is the compound represented by formula (III-4), and its preparation method includes the following steps: In a solvent, in the presence of a catalyst, the compound shown in formula (III-4-1) undergoes the reaction shown below to give the compound shown in formula (III-4); Among them, R 1 R 2 The definition of X is as described in any one of claims 10-11; (v) The method for preparing the compound represented by formula (IV) includes the following steps: In a solvent, in the presence of an iodine reagent, a base, and an optional molecular sieve, the compound shown in formula (IV-1) and the compound shown in formula (IV-2) or their salts undergo the substitution reaction shown below to give the compound shown in formula (IV). In W, the two *-marked atoms or groups are in adjacent positions; B is Cl or Br (preferably Cl), m, R 1 R 2 R 7 X, Y, W and R L1 The definition is as described in any one of claims 10-11; Preferably, the method for preparing the compound represented by formula (III-1) further includes a method for preparing the compound represented by formula (III-1-1), wherein the method for preparing the compound represented by formula (III-1-1) includes the following steps: In a solvent, in the presence of a catalyst, the compound shown in formula (III-1-2) undergoes the reaction shown below to give the compound shown in formula (III-1-1); Where L is -CH2-OC(O)-CH3, R 1 R 2 The definition of X is as described in any one of claims 10-11; Preferably, the method for preparing the compound represented by formula (III-2) further includes the method for preparing the compound represented by formula (III-2-1), wherein the method for preparing the compound represented by formula (III-2-1) includes the following steps: In a solvent, in the presence of a catalyst, the compound shown in formula (III-2-2) undergoes the reaction shown below to give the compound shown in formula (III-2-1); Where L is -CH2-OC(O)-CH3, R 1 R 2 The definition of X is as described in any one of claims 10-11.

16. A compound, characterized in that, The compound is selected from any of the following compounds:

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