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EP-4741397-A1 - FUSED TRICYCLIC COMPOUND, AND PREPARATION METHOD THEREFOR AND USE THEREOF

EP4741397A1EP 4741397 A1EP4741397 A1EP 4741397A1EP-4741397-A1

Abstract

The present invention relates to a fused tricyclic compound, and a preparation method therefor and a use thereof. The compound has a structure shown in a formula (I), has an SARM1 inhibition effect, and can be used for treating neurodegenerative diseases.

Inventors

  • XUN, GUOLIANG
  • WANG, SHAOHUI
  • ZHANG, PEIYU
  • E, Jingwen
  • DU, Lifei
  • PAN, WEI
  • ZHOU, JIANLAI
  • MA, HONGYAN
  • CHEN, JIJUN
  • CAO, BIN
  • CHEN, BIN

Assignees

  • Shenzhen Zhongge Biological Technology Co., Ltd.

Dates

Publication Date
20260513
Application Date
20240705

Claims (20)

  1. A compound represented by Formula (I), or a stereoisomer, tautomer, polymorph, solvate, hydrate, N-oxide, isotope-labeled compound, metabolite, ester, prodrug of the compound, or a pharmaceutically acceptable salt thereof, Wherein, is selected from a single bond, a double bond, and a triple bond; Z is selected from O and S; L 1 is selected from -C 1-3 alkylene-, =CH-, -NH-, and -O-, or L 1 is absent; ring A is selected from phenyl, 5-6 membered heteroaryl, C 4-8 cyclic groups, and 4-8 membered heterocyclyl; preferably, ring A is selected from phenyl, dihydropyranyl, pyridyl, dihydropyridyl, and oxepanyl; ring B is selected from phenyl, 5-6 membered heteroaryl, and 5-6 membered heterocyclyl; ring C is selected from C 6-10 aryl, 5-12 membered heteroaryl, C 3-12 cyclic groups, and 4-10 membered heterocyclyl; ring E is selected from 5-6 membered heteroaryl and phenyl; R 1 is selected from H, -OH, halogen, -NH 2 , -CN, -NO 2 , -COOH, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, -C 1-6 alkylene-OH, -O-C 1-6 haloalkyl, -C 3-7 cycloalkyl, and 3-7 membered heterocycloalkyl; R 2 is selected from H, -OH, halogen, -CN, -NH 2 , -NO 2 , -COOH, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, -C 1-6 alkylene-OH, -O-C 1-6 haloalkyl, -C 1-6 alkylene-C 1-6 alkoxy, -C 3-7 cycloalkyl, and 3-7 membered heterocycloalkyl; R 3 is selected from H, C 1-6 alkyl, and -C(=O)-C 1-6 alkyl, wherein the C 1-6 alkyl and -C(=O)-C 1-6 alkyl are optionally substituted with 1, 2, 3, 4 or 5 substituents selected from halogen, -OH, -NH 2 , -CN, -NO 2 , and -COOH; W is selected from -C(R 5 R 6 )-, -CR 5 =, -C(=CH 2 )-, and -NR 5 -, wherein R 5 is selected from H, -OH, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 haloalkyl, and C 1-6 haloalkoxy; or W and R 3 together with the atoms to which they are attached form a 4-6 membered heterocyclyl, wherein the 4-6 membered heterocyclyl is optionally substituted with 1, 2, 3, 4 or 5 R; or W and ring B together with the atoms to which they are attached form a 6-10 membered heterocyclyl, wherein the 6-10 membered heterocyclyl is optionally substituted with 1, 2, 3, 4 or 5 R; R 4 is selected from halogen, -OH, -CN, -NH 2 , C 1-6 alkyl, C 1-6 alkoxy, C 1-6 haloalkyl, and C 1-6 haloalkoxy; R 6 is selected from H, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 haloalkyl, and C 1-6 haloalkoxy; R 7 is selected from H, halogen, -OH, -NO 2 , -CN, -NH 2 , -COOH, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 haloalkyl, -C 1-6 alkylene-OH, -O-C 1-6 haloalkyl, -C 3-7 cycloalkyl, and 3-7 membered heterocycloalkyl; R is selected from halogen, -OH, -CN, =O, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 haloalkyl, and C 1-6 haloalkoxy; m is selected from 0 and 1; n is selected from 0, 1, 2, 3, 4, and 5; preferably, selected from 0, 1, 2, and 3; r, s, and t are each independently 0, 1, 2, 3, 4, or 5; preferably 0, 1, or 2; more preferably 0 or 1.
  2. The compound, or a stereoisomer, tautomer, polymorph, solvate, hydrate, N-oxide, isotope-labeled compound, metabolite, ester, prodrug of the compound, or a pharmaceutically acceptable salt thereof according to claim 1, wherein, W is selected from -C(R 5 R 6 )-, -CR 5 =, -C(=CH 2 )-, and -NR 5 -, or W and R 3 together with the atoms to which they are attached form a 4-6 membered heterocyclyl, wherein the 4-6 membered heterocyclyl is optionally substituted with 1, 2, 3, 4 or 5 R; preferably, W is selected from -C(R 5 R 6 )- and -C(=CH 2 )-, or W and R 3 together with the atoms to which they are attached form a 4-6 membered heterocyclyl, wherein the 4-6 membered heterocyclyl is optionally substituted with 1, 2, 3, 4 or 5 R; preferably, W is selected from -C(R 5 R 6 )- and -C(=CH 2 )-, or W and R 3 together with the atoms to which they are attached form a 5-6 membered heterocyclyl, wherein the 5-6 membered heterocyclyl is optionally substituted with 1, 2, 3, 4 or 5 R; preferably, W is -C(R 5 R 6 )-, or W and R 3 together with the atoms to which they are attached form a 5-6 membered heterocyclyl, wherein the 5-6 membered heterocyclyl is optionally substituted with 1, 2, 3, 4 or 5 R.
  3. The compound, or a stereoisomer, tautomer, polymorph, solvate, hydrate, N-oxide, isotope-labeled compound, metabolite, ester, prodrug of the compound, or a pharmaceutically acceptable salt thereof according to claim 1 or 2, wherein, m is 1.
  4. The compound, or a stereoisomer, tautomer, polymorph, solvate, hydrate, N-oxide, isotope-labeled compound, metabolite, ester, prodrug of the compound, or a pharmaceutically acceptable salt thereof according to any one of claims 1-3, wherein, R 1 is selected from H, -OH, halogen, -CN, -NH 2 , -NO 2 , -COOH, C 1-4 alkyl, C 1-4 haloalkyl, C 1-4 alkoxy, -C 1-4 alkylene-OH, -O-C 1-4 haloalkyl, -C 3-6 cycloalkyl, and 5-6 membered heterocycloalkyl; preferably, R 1 is selected from H, -OH, F, Cl, Br, I, -NH 2 , -CN, -NO 2 , -COOH, methyl, ethyl, n -propyl, isopropyl, n -butyl, isobutyl, sec- butyl, tert -butyl, halomethyl, haloethyl, halopropyl, halobutyl, methoxy, ethoxy, propoxy, butoxy, halomethoxy, haloethoxy, halopropoxy, halobutoxy, hydroxymethyl, hydroxyethyl, hydroxypropyl, cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl; preferably, R 1 is selected from H, -OH, F, Cl, Br, -NH 2 , -CN, -NO 2 , -COOH, methyl, ethyl, n-propyl, methoxy, ethoxy, monofluoromethyl, difluoromethyl, trifluoromethyl, hydroxymethyl, and hydroxyethyl; preferably, R 1 is selected from F, Cl, Br, and I; preferably, R 1 is selected from -NH 2 , -CN, -NO 2 , and -COOH; preferably, R 1 is selected from methyl, methoxy, monofluoromethyl, difluoromethyl, trifluoromethyl, hydroxymethyl, and hydroxyethyl; preferably, R 1 is selected from H and -OH; preferably, R 1 is H.
  5. The compound, or a stereoisomer, tautomer, polymorph, solvate, hydrate, N-oxide, isotope-labeled compound, metabolite, ester, prodrug of the compound, or a pharmaceutically acceptable salt thereof according to any one of claims 1-4, wherein, R 2 is selected from H, -OH, halogen, -CN, -NH 2 , -NO 2 , -COOH, C 1-4 alkyl, C 1-4 haloalkyl, C 1-4 alkoxy, -C 1-4 alkylene-OH, -O-C 1-4 haloalkyl, -C 1-4 alkylene-C 1-4 alkoxy, -C 3-6 cycloalkyl, and 4-6 membered heterocycloalkyl; preferably, R 2 is selected from H, -OH, F, Cl, Br, I, -CN, -NH 2 , -NO 2 , -COOH, methyl, ethyl, n -propyl, isopropyl, n -butyl, isobutyl, sec -butyl, tert -butyl, halomethyl, haloethyl, halopropyl, halobutyl, methoxy, ethoxy, propoxy, butoxy, hydroxymethyl, hydroxyethyl, hydroxypropyl, halomethoxy, haloethoxy, halopropoxy, halobutoxy, - CH 2 OCH 3 , -(CH 2 ) 2 OCH 3 , -(CH 2 ) 3 OCH 3 , -CH 2 OCH 2 CH 3 , -CH 2 O(CH 2 ) 2 CH 3 , cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl; preferably, R 2 is selected from H, -OH, F, Cl, Br, -NH 2 , -CN, -NO 2 , -COOH, methyl, ethyl, n -propyl, methoxy, ethoxy, monofluoromethyl, difluoromethyl, trifluoromethyl, hydroxymethyl, hydroxyethyl, -CH 2 OCH 3 , - (CH 2 ) 2 OCH 3 , and -CH 2 OCH 2 CH 3 ; preferably, R 2 is selected from H, Cl, -CN, -NH 2 , -CH 3 , and -CH 2 OCH 3 ; preferably, R 2 is selected from H, -NH 2 , -CH 3 , and -CH 2 OCH 3 ; preferably, R 2 is selected from H, -CH 3 , and -CH 2 OCH 3 ; preferably, R 2 is selected from H and -NH 2 ; preferably, R 2 is H.
  6. The compound, or a stereoisomer, tautomer, polymorph, solvate, hydrate, N-oxide, isotope-labeled compound, metabolite, ester, prodrug of the compound, or a pharmaceutically acceptable salt thereof according to any one of claims 1-5, wherein, R 7 is selected from H, halogen, -OH, -NO 2 , -CN, -NH 2 , -COOH, C 1-4 alkyl, C 1-4 alkoxy, C 1-4 haloalkyl, -C 1-4 alkylene-OH, -O-C 1-4 haloalkyl, -C 3-6 cycloalkyl, and 4-6 membered heterocycloalkyl; preferably, R 7 is selected from H, F, Cl, Br, I, -OH, -NO 2 , -CN, -NH 2 , -COOH, methyl, ethyl, n -propyl, isopropyl, n -butyl, isobutyl, sec -butyl, tert -butyl, methoxy, ethoxy, propoxy, butoxy, halomethoxy, haloethoxy, halopropoxy, halobutoxy, hydroxymethyl, hydroxyethyl, hydroxypropyl, halomethoxy, haloethoxy, halopropoxy, halobutoxy, cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl; preferably, R 7 is selected from H, F, Cl, Br, I, -OH, -NO 2 , -CN, -NH 2 , -COOH, methyl, ethyl, methoxy, and ethoxy; preferably, R 7 is selected from H, F, Cl, Br, and -CH 3 ; preferably, R 7 is selected from H, F, Cl, and Br; preferably, R 7 is H.
  7. The compound, or a stereoisomer, tautomer, polymorph, solvate, hydrate, N-oxide, isotope-labeled compound, metabolite, ester, prodrug of the compound, or a pharmaceutically acceptable salt thereof according to any one of claims 1-6, wherein, the structural unit is selected from wherein, is selected from a single bond and a double bond; Z 1 and Z 2 are each independently selected from CH and N; V is selected from C, CH, and N; preferably, V is selected from C and N; T 1 , T 2 , and T 3 are each independently selected from CH 2 , O, S, and NH; preferably, T 1 , T 2 , and T 3 are each independently selected from CH 2 , O, and NH; u is selected from 0, 1, and 2; preferably, u is selected from 0 and 1; preferably, the structural unit is selected from preferably, the structural unit is selected from preferably, the structural unit is selected from more preferably, the structural unit is selected from more preferably, the structural unit is selected from and
  8. The compound, or a stereoisomer, tautomer, polymorph, solvate, hydrate, N-oxide, isotope-labeled compound, metabolite, ester, prodrug of the compound, or a pharmaceutically acceptable salt thereof according to any one of claims 1-7, wherein, ring B is selected from 5-membered nitrogen-containing heteroaryl and 5-membered nitrogen-containing heterocyclic alkenyl; preferably, ring B is selected from pyrrolyl, pyrazolyl, imidazolyl, oxazolyl and dihydrotriazolyl; preferably, ring B is selected from pyrrolyl, pyrazolyl, imidazolyl, and oxazolyl; more preferably, ring B is selected from imidazolyl, pyrazolyl, and oxazolyl.
  9. The compound, or a stereoisomer, tautomer, polymorph, solvate, hydrate, N-oxide, isotope-labeled compound, metabolite, ester, prodrug of the compound, or a pharmaceutically acceptable salt thereof according to any one of claims 1-8, wherein, ring E is 6-membered nitrogen-containing heteroaryl; preferably, ring E is selected from pyridyl and pyridazinyl; more preferably, ring E is pyridyl.
  10. The compound, or a stereoisomer, tautomer, polymorph, solvate, hydrate, N-oxide, isotope-labeled compound, metabolite, ester, prodrug of the compound, or a pharmaceutically acceptable salt thereof according to any one of claims 1-9, wherein, the structural unit is selected from (preferably, ), wherein, Y 1 , and Y 2 are each independently selected from CH and N; preferably, Y 1 is N and Y 2 is CH, or Y 1 is CH and Y 2 is N, or Y 1 is N, and Y 2 is N; preferably, is selected from wherein, is selected from a single bond and a double bond; Z 1 and Z 2 are each independently selected from CH and N; V is selected from C, CH, and N; preferably, V is selected from C and N; T 1 , T 2 , and T 3 are each independently selected from CH 2 , O, and NH; u is selected from 0, 1, and 2; preferably, u is selected from 0 and 1; preferably, is selected from preferably, is selected from preferably, is selected from and
  11. The compound, or a stereoisomer, tautomer, polymorph, solvate, hydrate, N-oxide, isotope-labeled compound, metabolite, ester, prodrug of the compound, or a pharmaceutically acceptable salt thereof according to any one of claims 1-10, wherein, the structural unit is selected from wherein, is selected from a single bond and a double bond; Y 1 and Y 2 are each independently selected from CH and N; V is selected from C, CH, and N; preferably, V is selected from C and N; U 1 and U 2 are each independently selected from O, N, NH, and CH; W 1 and W 3 are selected from CH and N; W 2 is selected from NH and O; ring A is selected from phenyl, 5-6 membered heteroaryl, C 4-8 cyclic groups, and 4-8 membered heterocyclyl; preferably, ring A is selected from phenyl, 6 membered heteroaryl, C 6-7 cyclic groups, and 6-7 membered heterocyclyl; more preferably, ring A is selected from phenyl and 6-7 membered heterocyclyl; preferably, the structural unit is selected from preferably, is selected from wherein, is selected from a single bond and a double bond, and when two are attached to the same atom, one is a single bond, and the other is a double bond; Y 1 and Y 2 are each independently selected from CH and N; Z 1 and Z 2 are each independently selected from CH and N; U 1 and U 2 are each independently selected from O, N, NH, and CH; T 1 , T 2 , and T 3 are each independently selected from CH 2 , O, and NH; W 1 and W 3 are selected from CH and N; W 2 is selected from NH and O; u is selected from 0 and 1; preferably, the structural unit is selected from wherein, in the structural unit preferably, Y 1 is N, and Y 2 is CH, or Y 1 is N, and Y 2 is N; more preferably, Y 1 is N, and Y 2 is CH; preferably, Z 1 is CH, and Z 2 is CH, or Z 1 is N, and Z 2 is CH, or Z 1 is CH, and Z 2 is N; more preferably, Z 1 is CH, and Z 2 is CH; preferably, U 1 is selected from N and CH, U 2 is selected from NH and O, or U 1 is selected from NH and O, U 2 is selected from N and CH; more preferably, U 1 is N, and U 2 is NH, or U 1 is NH, and U 2 is N, or U 1 is N, and U 2 is O; in the structural unit preferably, Y 1 is N, and Y 2 is CH; preferably, T 1 is CH 2 , T 2 is selected from O and NH, and T 3 is CH 2 ; or T 1 is O, and T 1 and T 3 are CH 2 ; preferably, U 1 is N, and U 2 is NH; or U 1 is NH, and U 2 is N; in the structural unit preferably, Y 1 is N, and Y 2 is CH; preferably, T 1 is NH, and T 3 is CH 2 , or T 1 is CH 2 , and T 3 is NH, or T 1 is O, and T 3 is CH 2 , or T 1 is CH 2 , and T 3 is O, or T 1 is CH 2 , and T 3 is CH 2 ; more preferably, T 1 is O, and T 3 is CH 2 ; preferably, U 1 is selected from N and CH, and U 2 is NH, or U 1 is NH, and U 2 is selected from N and CH; more preferably, U 1 is N, and U 2 is NH, or U 1 is NH, and U 2 is N; in the structural unit preferably, Y 1 is N, and Y 2 is CH; preferably, Z 1 is CH, and Z 2 is CH; preferably, W 1 is N, and W 2 is NH; in the structural unit preferably, Y 1 is N, and Y 2 is CH; preferably, Z 1 is CH, and Z 2 is CH; preferably, W 1 is N, and W 3 is CH; in the structural unit preferably, Y 1 is N, and Y 2 is CH; preferably, T 1 is O, and T 2 and T 3 are CH 2 , or T 1 is CH 2 , T 2 is O, and T 3 is CH 2 ; more preferably, T 1 is O, and T 2 and T 3 are CH 2 ; preferably, W 1 is N, and W 2 is NH; in the structural unit preferably, Y 1 is N, and Y 2 is CH; preferably, T 1 is O, and T 3 is CH 2 , or T 1 is CH 2 , and T 3 is O, or T 1 is NH, and T 3 is CH 2 , or T 1 is CH 2 , and T 3 is NH; preferably, W 1 is N, and W 2 is NH; in the structural unit preferably, Y 1 is N, and Y 2 is CH; preferably, Z 1 is CH, and Z 2 is CH; preferably, U 1 is N, and U 2 is NH, or U 1 is NH, and U 2 is N; more preferably, U 1 is N, and U 2 is NH; in the structural unit preferably, Y 1 is N, and Y 2 is CH; preferably, T 1 is selected from CH 2 and O, and T 2 is CH 2 ; preferably, U 1 is N, and U 2 is NH, or U 1 is NH, and U 2 is N; more preferably, U 1 is N, and U 2 is NH; in the structural unit preferably, Y 1 is N, and Y 2 is CH; preferably, T 1 is O, and T 2 and T 3 are CH 2 ; preferably, W 1 is N; more preferably, the structural unit is selected from further preferably, is selected from and further preferably, the structural unit is selected from further preferably, the structural unit is selected from
  12. The compound, or a stereoisomer, tautomer, polymorph, solvate, hydrate, N-oxide, isotope-labeled compound, metabolite, ester, prodrug of the compound, or a pharmaceutically acceptable salt thereof according to any one of claims 1-11, wherein, the structural unit is selected from preferably, the structural unit is selected from preferably, the structural unit is selected from preferably, the structural unit is selected from preferably, the structural unit is
  13. The compound, or a stereoisomer, tautomer, polymorph, solvate, hydrate, N-oxide, isotope-labeled compound, metabolite, ester, prodrug of the compound, or a pharmaceutically acceptable salt thereof according to any one of claims 1-12, wherein, the structural unit is selected from preferably, the structural unit is selected from and preferably, the structural unit is preferably, is
  14. The compound, or a stereoisomer, tautomer, polymorph, solvate, hydrate, N-oxide, isotope-labeled compound, metabolite, ester, prodrug of the compound, or a pharmaceutically acceptable salt thereof according to any one of claims 1-13, wherein, W is selected from -C(R 5 R 6 )-, -C(=CH 2 )-, and -NR 5 -, wherein R 5 , R 6 are defined as claim 1; preferably, R 5 is selected from H, -OH, C 1-4 alkyl, C 1-4 alkoxy, C 1-4 haloalkyl, and C 1-4 haloalkoxy; R 6 is selected from H, C 1-4 alkyl, C 1-4 alkoxy, C 1-4 haloalkyl, and C 1-4 haloalkoxy; preferably, R 5 is selected from H, -OH, methyl, ethyl, n-propyl, n-butyl, methoxy, ethoxy, propoxy, butoxy, halomethyl, haloethyl, halopropyl, halobutyl, halomethoxy, haloethoxy, halopropoxy, and halobutoxy; R 6 is selected from H, methyl, ethyl, n -propyl, n -butyl, methoxy, ethoxy, propoxy, butoxy, halomethyl, haloethyl, halopropyl, halobutyl, halomethoxy, haloethoxy, halopropoxy, and halobutoxy; preferably, R 5 is selected from H, -OH, methyl, methoxy, monofluoromethyl, difluoromethyl, and trifluoromethyl; R 6 is selected from H, methyl, ethyl, methoxy, monofluoromethyl, difluoromethyl, and trifluoromethyl; preferably, R 5 is selected from H and -OH, and R 6 is H; preferably, R 5 is H, and R 6 is H; preferably, W is selected from -CH 2 -, -CH(OH)-, -C(=CH 2 )-, and -NH-; preferably, W is selected from -CH 2 - and -NH-; preferably, W is selected from -CH 2 - and -C(=CH 2 )-; preferably, W is -CH 2 -.
  15. The compound, or a stereoisomer, tautomer, polymorph, solvate, hydrate, N-oxide, isotope-labeled compound, metabolite, ester, prodrug of the compound, or a pharmaceutically acceptable salt thereof according to any one of claims 1-14, wherein, R 3 is selected from H, C 1-4 alkyl, and -C(=O)-C 1-4 alkyl, wherein the C 1-4 alkyl and -C(=O)-C 1-4 alkyl are optionally substituted with 1, 2, 3, 4 or 5 substituents selected from halogen, -OH, -NH 2 , -CN, -NO 2 , and -COOH; preferably, R 3 is selected from H, methyl, ethyl, n -propyl, isopropyl, n -butyl, sec -butyl, tert -butyl, isobutyl, - C(=O)CH 3 , -C(=O)CH 2 CH 3 , -C(=O)(CH 2 ) 2 CH 3 , and -C(=O)(CH 2 ) 3 CH 3 ; preferably, R 3 is selected from H, -CH 3 , and -C(=O)CH 3 ; further preferably, R 3 is H.
  16. The compound, or a stereoisomer, tautomer, polymorph, solvate, hydrate, N-oxide, isotope-labeled compound, metabolite, ester, prodrug of the compound, or a pharmaceutically acceptable salt thereof according to any one of claims 1-15, wherein, the structural unit is selected from wherein "*" indicates a connection to ring B; preferably, the structural unit is selected from and preferably, the structural unit is selected from and preferably, the structural unit preferably, the structural unit is selected from -C(=O)-CH 2 -, -NH-C(=O)-CH 2 -, -N(CH 3 )-C(=O)-CH 2 -, -N(C(=O)CH 3 )-C(=O)-CH 2 -, -N(CH 3 )-C(=O)-CH(OH)-, -NH-C(=O)-C(=CH 2 )-, and -NH-C(=S)-CH 2 -; preferably, the structural unit is -NH-C(=O)-CH 2 -; or, the structural unit wherein "*" indicates a connection to ring B; preferably, the structural unit is selected from *-C(=O)-CH 2 -, *-NH-C(=O)-CH 2 -, *-N(CH 3 )-C(=O)-CH 2 -, *-N(C(=O)CH 3 )-C(=O)-CH 2 -, *-N(CH 3 )-C(=O)-CH(OH)-, *-NH-C(=O)-C(=CH 2 )-, and *-NH-C(=S)-CH 2 -, wherein "*" indicates a connection to ring B; further preferably, the structural unit is *-NH-C(-O)-CH 2 -, wherein "*" indicates a connection ring B.
  17. The compound, or a stereoisomer, tautomer, polymorph, solvate, hydrate, N-oxide, isotope-labeled compound, metabolite, ester, prodrug of the compound, or a pharmaceutically acceptable salt thereof according to any one of claims 1-16, wherein, R is selected from halogen, -OH, -CN, =O, C 1-4 alkyl, C 1-4 alkoxy, C 1-4 haloalkyl, and C 1-4 haloalkoxy; preferably, R is selected from F, Cl, Br, I, -OH, -CN, =O, methyl, ethyl, n -propyl, isopropyl, n -butyl, sec -butyl, isobutyl, tert -butyl, methoxy, ethoxy, propoxy, butoxy, halomethyl, haloethyl, halopropyl, halobutyl, halomethoxy, haloethoxy, halopropoxy, and halobutoxy; preferably, R is selected from F, Cl, Br, I, -OH, -CN, =O, methyl, ethyl, n-propyl, methoxy, ethoxy, monofluoromethyl, difluoromethyl, and trifluoromethyl; preferably, R is selected from F, Cl, Br, -OH, =O, methyl, ethyl, monofluoromethyl, difluoromethyl, and trifluoromethyl; preferably, R is selected from -OH, -CH 3 , and =O.
  18. The compound, or a stereoisomer, tautomer, polymorph, solvate, hydrate, N-oxide, isotope-labeled compound, metabolite, ester, prodrug of the compound, or a pharmaceutically acceptable salt thereof according to any one of claims 1-17, wherein, the structural unit is selected from wherein p is selected from 0, 1, and 2; q is selected from 0, 1, 2, 3, 4, and 5; is selected from a single bond and a double bond; preferably, is selected from preferably, is selected from and preferably, is selected from preferably, the structural unit is selected from further preferably, the structural unit is selected from or, the structural unit is wherein "*" indicates a connection to ring B; preferably, the structural unit is selected from wherein "*" indicates a connection to ring B; preferably, is selected from wherein "*" indicates a connection to ring B; preferably, the structural unit is selected from wherein "*" indicates a connection to ring B; further preferably, the structural unit is selected from wherein "*" indicates a connection to ring B.
  19. The compound, or a stereoisomer, tautomer, polymorph, solvate, hydrate, N-oxide, isotope-labeled compound, metabolite, ester, prodrug of the compound, or a pharmaceutically acceptable salt thereof according to any one of claims 1-18, wherein, W and ring B together with the atoms to which they are attached form a 7-9 membered heterocyclyl; preferably, W and ring B together with the atoms to which they are attached form a 7 membered heterocyclyl; preferably, the 7 membered heterocyclyl is selected from , wherein "*" indicates a fusion with ring B; preferably, the 7 membered heterocyclyl is selected from , wherein "*" indicates a fusion with ring B.
  20. The compound, or a stereoisomer, tautomer, polymorph, solvate, hydrate, N-oxide, isotope-labeled compound, metabolite, ester, prodrug of the compound, or a pharmaceutically acceptable salt thereof according to any one of claims 1-19, wherein, L 1 is absent, or L 1 is selected from -CH 2 -, -CH 2 CH 2 -, =CH-, -NH-, and -O-; preferably, L 1 is -CH 2 -.

Description

Cross-Reference to Related Applications The present application claims the priorities of Chinese Patent Applications 202310834844.5, filed on July 7, 2023, and 202311370973.X, filed on October 20, 2023, the contents of which are hereby incorporated by reference into the application in their entirety and for all purposes. Technical Field The present invention relates to the field of medicine, specifically to a fused tricyclic compound and a preparation method therefor and a use thereof. Background Axon degeneration is closely related to the occurrence and development of neurological diseases. Wallerian degeneration is the main pathway of axon degeneration. Wallerian degeneration, also known as secondary degeneration, refers to a process in which the distal nerve fibers of axons begin to degrade after the axons are broken due to trauma. Two key proteins are involved in this process: nicotinamide adenine dinucleotide (NAD+) synthase NMNAT2 and NAD+ hydrolase SARM1. SARM1 (Sterile alpha and Toll/interleukin-1 receptor motif-containing 1) is the main executive molecule of this neurodegradation process, and the regulation of its activity plays an important role in the treatment of corresponding neurological diseases. In healthy neurons, NMNAT2 is transported along axons, maintaining high levels of NAD+ and low levels of nicotinamide mononucleotide (NMN), and SARM1 is maintained at a low activity level. When neurons are damaged, the transport of NMNAT2 stops along axons, and NMNAT2 rapidly decomposes, causing NMN levels to begin to rise and NAD+ levels to begin to decrease. This period is called the axonal degeneration latency period. Changes in NMN and NAD+ lead to the activation of SARM1, which in turn causes Ca2+ influx, calpain activation, and ATP depletion. With the accumulation of ROS, axonal degeneration begins to occur. At present, it is reported in many literature that knocking out or inhibiting SARM1 has a protective effect in various neurological disease models, such as peripheral neuropathy, traumatic brain injury, amyotrophic lateral sclerosis, Parkinson's disease, glaucoma, etc. The treatment methods for neurological diseases such as Alzheimer's disease, Parkinson's disease, multiple sclerosis, amyotrophic sclerosis, Huntington's disease, etc., are very limited, and there is no effective treatment available. At present, most of the treatment methods are symptomatic treatments to alleviate symptoms, which cannot prevent the development of the disease, let alone cure it. In addition, the incidence of neurodegenerative diseases is increasing as the population ages. Therefore, there is an urgent need to develop more effective drugs to help slow down disease progression, improve patients' quality of life, or even prevent disease development in early stages. Summary of the invention The first aspect of the present invention provides a compound represented by formula (I) or a stereoisomer, tautomer, polymorph, solvate, hydrate, N-oxide, isotope-labeled compound, metabolite, ester, prodrug of the compound, or a pharmaceutically acceptable salt thereof, wherein, is selected from a single bond, a double bond, and a triple bond;Z is selected from O and S;L1 is selected from -C1-3 alkylene-, =CH-, -NH-, and -O-, or L1 is absent;ring A is selected from phenyl, 5-6 membered heteroaryl, C4-8 cyclic groups, and 4-8 membered heterocyclyl; ring B is selected from phenyl, 5-6 membered heteroaryl, and 5-6 membered heterocyclyl;ring C is selected from C6-10 aryl, 5-12 membered heteroaryl, C3-12 cyclic groups, and 4-10 membered heterocyclyl; ring E is selected from 5-6 membered heteroaryl and phenyl;R1 is selected from H, -OH, halogen, -NH2, -CN, -NO2, -COOH, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, C1-6 alkylene-OH, -O-C1-6 haloalkyl, -C3-7 cycloalkyl, and 3-7 membered heterocycloalkyl;R2 is selected from H, -OH, halogen, -CN, -NH2, -NO2, -COOH, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, C1-6 alkylene-OH, -O-C1-6 haloalkyl, -C1-6 alkylene-C1-6 alkoxy, -C3-7 cycloalkyl, and 3-7 membered heterocycloalkyl; R3 is selected from H, C1-6 alkyl, and -C(=O)C1-6 alkyl, wherein the C1-6 alkyl and -C(=O)C1-6 alkyl are optionally substituted with 1, 2, 3, 4 or 5 substituents selected from halogen, -OH, -NH2, -CN, -NO2, and -COOH;W is selected from -C(R5R6)-, -CR5=, -C(=CH2)-, and -NR5-, wherein R5 is selected from H, -OH, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, and C1-6 haloalkoxy; orW and R3 together with the atoms to which they are attached form a 4-6 membered heterocyclyl, wherein the 4-6 membered heterocyclyl is optionally substituted with 1, 2, 3, 4 or 5 R; orW and ring B together with the atoms to which they are attached form a 6-10 membered heterocyclyl, wherein the 6-10 membered heterocyclyl is optionally substituted with 1, 2, 3, 4 or 5 R;R4 is selected from halogen, -OH, -CN, -NH2, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, and C1-6 haloalkoxy;R6 is selected from H, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, and C1-6 haloalkox