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EP-4737454-A1 - GLP-1 RECEPTOR AGONIST, AND PREPARATION METHOD THEREFOR AND USE THEREOF

EP4737454A1EP 4737454 A1EP4737454 A1EP 4737454A1EP-4737454-A1

Abstract

Disclosed in the present invention are a GLP-1 receptor agonist, and a preparation method therefor and a use thereof. Specifically, disclosed are a compound represented by formula (I), and a use thereof in preparation of a drug for treating or preventing GLP-1 receptor-mediated diseases.

Inventors

  • FENG, Jianbo
  • YAO, Yuanshan
  • CHEN, JIAYU

Assignees

  • Wayne Biotechnology Co., Ltd.

Dates

Publication Date
20260506
Application Date
20240627

Claims (20)

  1. A compound of formula (I), a stereoisomer, a tautomer, or a pharmaceutically acceptable salt thereof, wherein, ring A is selected from a group consisting of a 3-12 membered heterocyclyl, C 6-10 aryl, and 5-10 membered heteroaryl; R 1 is selected from a group consisting of cyano, halogen, C 1-10 alkyl, C 3-12 cycloalkyl, 3-12 membered heterocyclyl, halogenated C 1-10 alkyl, halogenated C 3-12 cycloalkyl, halogenated 3-12 membered heterocyclyl, halogenated C 1-10 alkoxy, halogenated C 1-10 alkylthio, C 1-6 alkyl-substituted C 3-12 cycloalkyl, and C 1-6 alkyl-substituted 3-12 membered heterocyclyl; R 2 is selected from a group consisting of hydrogen, cyano, C 1-10 alkyl, halogenated C 1-10 alkyl, C 1-10 alkoxy, halogenated C 1-10 alkoxy, and -NR 12 R 13 ; R 3 is selected from a group consisting of C 3-12 cycloalkyl, 3-12 membered heterocyclyl, C 6-10 aryl, and 5-10 membered heteroaryl, wherein above groups are optionally further substituted with one or more substituents selected from a group consisting of halogen, cyano, nitro, azido, C 1-10 alkyl, halogenated C 1-10 alkyl, C 2-10 alkenyl, C 2-10 alkynyl, C 3-12 cycloalkyl, 3-12 membered heterocyclyl, C 6-10 aryl, 5-10 membered heteroaryl, =O, -SF 5 , -S(O) r R 9 , -O-R 10 , -C(O)OR 10 , - C(O)R 11 , -O-C(O)R 11 , -NR 12 R 13 , -C(=NR 12 )R 11 , -N(R 12 )-C(=NR 13 )R 11 , -C(O)NR 12 R 13 , and - N(R 12 )-C(O)R 11 ; R 4 and R 5 are each independently selected from a group consisting of hydrogen, halogen, hydroxyl, C 1-10 alkyl, halogenated C 1-10 alkyl, C 1-10 alkoxy, and halogenated C 1-10 alkoxy, or R 4 and R 5 together with a carbon atom to which they are directly attached form a C 3-12 cycloalkyl, wherein said C 3-12 cycloalkyl is optionally further substituted with one or more substituents selected from a group consisting of hydrogen, halogen, amino, hydroxyl, C 1-10 alkyl, halogenated C 1-10 alkyl, C 1-10 alkoxy, and halogenated C 1-10 alkoxy; R 6 is 5-10 membered heteroaryl; R 7 is 3-12 membered heterocyclyl or 5-10 membered heteroaryl, wherein above groups are optionally substituted with one or more substituents selected from a group consisting of halogen, hydroxyl, cyano, nitro, C 1-10 alkyl, halogenated C 1-10 alkyl, C 1-10 alkoxy, halogenated C 1-10 alkoxy, and -NR 12 R 13 , or any two substituents on the same carbon atom of said 3-12 membered heterocyclyl together with a carbon atom to which they are attached form a C 3-6 cycloalkyl, wherein said C 3-6 cycloalkyl is optionally further substituted with one or more substituents selected from a group consisting of halogen, cyano, C 1-6 alkyl, halogenated C 1-6 alkyl, and C 1-6 alkoxy; R 8 is selected from a group consisting of hydrogen, cyano, C 3-12 cycloalkyl, 3-12 membered heterocyclyl, C 1-10 alkyl, halogenated C 1-10 alkyl, C 1-10 alkoxy, halogenated C 1-10 alkoxy, and - NR 12 R 13 ; each R 9 is independently selected from a group consisting of hydrogen, deuterium, hydroxyl, C 1-10 alkyl, C 2-10 alkenyl, C 3-12 cycloalkyl, 3-12 membered heterocyclyl, C 6-10 aryl, 5-10 membered heteroaryl, and -NR 12 R 13 , wherein above groups are independently optionally further substituted with one or more substituents selected from a group consisting of deuterium, halogen, hydroxyl, oxo, C 1-10 alkyl, C 1-10 alkoxy, C 3-12 cycloalkyl, C 3-12 cycloalkoxy, 3-12 membered heterocyclyl, 3-12 membered heterocycloxy, C 6-10 aryl, C 6-10 aryloxy, 5-10 membered heteroaryl, 5-10 membered heteroaryloxy, and -NR 12 R 13 ; each R 10 is independently selected from a group consisting of hydrogen, deuterium, C 1-10 alkyl, C 2-10 alkenyl, C 3-12 cycloalkyl, 3-12 membered heterocyclyl, C 6-10 aryl, and 5-10 membered heteroaryl, wherein above groups are independently optionally further substituted with one or more substituents selected from a group consisting of deuterium, halogen, hydroxyl, oxo, cyano, C 1-10 alkyl, C 1-10 alkoxy, C 3-12 cycloalkyl, C 3-12 cycloalkoxy, 3-12 membered heterocyclyl, 3-12 membered heterocycloxy, C 6-10 aryl, C 6-10 aryloxy, 5-10 membered heteroaryl, 5-10 membered heteroaryloxy, and -NR 12 R 13 ; each R 11 is selected from a group consisting of hydrogen, deuterium, hydroxyl, C 1-10 alkyl, C 1-10 alkoxy, C 2-10 alkenyl, C 2-10 alkynyl, C 3-12 cycloalkyl, C 3-12 cycloalkoxy, 3-12 membered heterocyclyl, 3-12 membered heterocycloxy, C 6-10 aryl, C 6-10 aryloxy, 5-10 membered heteroaryl, 5-10 membered heteroaryloxy, and -NR 12 R 13 , wherein above groups are independently optionally further substituted with one or more substituents selected from a group consisting of deuterium, halogen, hydroxyl, cyano, C 1-10 alkyl, halogenated C 1-10 alkyl, C 1-10 alkoxy, C 3-12 cycloalkyl, C 3-12 cycloalkoxy, 3-12 membered heterocyclyl, 3-12 membered heterocycloxy, C 6-10 aryl, C 6-10 aryloxy, 5-10 membered heteroaryl, 5-10 membered heteroaryloxy, and -NR 12 R 13 ; each R 12 and each R 13 are independently selected from a group consisting of hydrogen, deuterium, hydroxyl, C 1-10 alkyl, C 2-10 alkenyl, C 2-10 alkynyl, C 3-12 cycloalkyl, 3-12 membered heterocyclyl, C 6-10 aryl, 5-10 membered heteroaryl, sulfinyl, sulfonyl, methanesulfonyl, isopropylsulfonyl, cyclopropylsulfonyl, p-toluenesulfonyl, aminosulfonyl, dimethylaminosulfonyl, amino, mono-C 1-10 alkylamino, di-C 1-10 alkylamino, and C 1-10 alkanoyl, wherein above groups are independently optionally further substituted with one or more substituents selected from a group consisting of deuterium, halogen, hydroxyl, C 1-10 alkyl, C 2-10 alkenyl, C 2-10 alkynyl, halogenated C 1-10 alkyl, deuterium-substituted C 1-10 alkyl, C 1-10 alkoxy, C 3-12 cycloalkyl, C 3-12 cycloalkoxy, 3-12 membered heterocyclyl, 3-12 membered heterocycloxy, C 6-10 aryl, C 6-10 aryloxy, 5-10 membered heteroaryl, 5-10 membered heteroaryloxy, amino, mono-C 1-10 alkylamino, di-C 1-10 alkylamino, and C 1-10 alkanoyl; or R 12 and R 13 together with a nitrogen atom to which they are directly attached form a 4-10 membered heterocyclyl or 4-10 membered heteroaryl, wherein said 4-10 membered heterocyclyl or 4-10 membered heteroaryl is optionally further substituted with one or more substituents selected from a group consisting of deuterium, halogen, hydroxyl, C 1-10 alkyl, C 2-10 alkenyl, C 2-10 alkynyl, halogenated C 1-10 alkyl, deuterium-substituted C 1-10 alkyl, C 1-10 alkoxy, C 3-12 cycloalkyl, C 3-12 cycloalkoxy, 3-12 membered heterocyclyl, 3-12 membered heterocycloxy, C 6-10 aryl, C 6-10 aryloxy, 5-10 membered heteroaryl, 5-10 membered heteroaryloxy, amino, mono-C 1-10 alkylamino, di-C 1-10 alkylamino, and C 1-10 alkanoyl; with the proviso that when A is selected from a group consisting of C 6-10 aryl and 5-10 membered heteroaryl, n is not equal to 0, at least one R 1 is selected from a group consisting of cyano, C 3-12 cycloalkyl, 3-12 membered heterocyclyl, halogenated C 3-12 cycloalkyl, halogenated 3-12 membered heterocyclyl, halogenated C 1-10 alkoxy, C 1-6 alkyl-substituted C 3-12 cycloalkyl, and C 1-6 alkyl-substituted 3-12 membered heterocyclyl, or when A is selected from a group consisting of C 6-10 aryl and 5-10 membered heteroaryl, n is not equal to 0, and R 1 is only selected from halogen and/or C 1-10 alkyl and/or halogenated C 1-10 alkyl, and R 3 is selected from a group consisting of C 6-8 aryl and 5-6 membered heteroaryl, R 3 is substituted with at least one substituent selected from a group consisting of cyano, -NR 12 R 13 , - C(O)NR 12 R 13 , and -N(R 12 )-C(O)R 11 , wherein in said -NR 12 R 13 and -C(O)NR 12 R 13 , R 12 or R 13 is selected from a group consisting of C 3-12 cycloalkyl, wherein in said -N(R 12 )-C(O)R 11 , R 11 or R 12 is C 3-12 cycloalkyl, wherein said C 3-12 cycloalkyl is independently optionally further substituted with one or more substituents selected from a group consisting of deuterium, halogen, hydroxyl, cyano, C 1-10 alkyl, halogenated C 1-10 alkyl, and C 1-10 alkoxy; each r is independently 0, 1, or 2; n is 0, 1, 2, 3, or 4.
  2. The compound of claim 1, stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein ring A is selected from a group consisting of 3-6 membered heterocyclyl, C 6-8 aryl, and 5-8 membered heteroaryl; R 1 is selected from a group consisting of cyano, halogen, C 1-6 alkyl, C 3-6 cycloalkyl, 3-6 membered heterocyclyl, halogenated C 1-6 alkyl, halogenated C 3-6 cycloalkyl, halogenated 3-6 membered heterocyclyl, halogenated C 1-6 alkoxy, halogenated C 1-6 alkylthio, C 1-6 alkyl-substituted C 3-6 cycloalkyl, and C 1-6 alkyl-substituted 3-6 membered heterocyclyl; R 2 is selected from a group consisting of hydrogen, C 1-6 alkyl, halogenated C 1-6 alkyl, C 1-6 alkoxy, and halogenated C 1-6 alkoxy; R 3 is selected from a group consisting of 5-10 membered heteroaryl and C 6-10 aryl, wherein above groups are optionally further substituted with one or more substituents selected from a group consisting of halogen, cyano, nitro, hydroxyl, C 1-6 alkyl, halogenated C 1-6 alkyl, C 3-6 cycloalkyl, C 1-6 alkoxy, halogenated C 1-6 alkoxy, -S(O) r R 9 , -C(O)NR 12 R 13 , -N(R 12 )-C(O)R 11 , and -NR 12 R 13 ; R 4 and R 5 together with a carbon atom to which they are directly attached form a C 3-6 cycloalkyl, wherein said C 3-6 cycloalkyl is optionally further substituted with one or more substituents selected from a group consisting of hydrogen, halogen, amino, hydroxyl, C 1-6 alkyl, and halogenated C 1-6 alkyl; R 6 is 5-6 membered heteroaryl; R 7 is 3-6 membered heterocyclyl, wherein said 3-6 membered heterocyclyl is optionally substituted with one or more substituents selected from a group consisting of halogen, hydroxyl, cyano, nitro, C 1-6 alkyl, and halogenated C 1-6 alkyl, or any two substituents on the same carbon atom of said 3-6 membered heterocyclyl together with a carbon atom to which they are attached form a C 3-6 cycloalkyl, wherein said C 3-6 cycloalkyl is optionally further substituted with one or more substituents selected from a group consisting of halogen, cyano, C 1-6 alkyl, halogenated C 1-6 alkyl, and C 1-6 alkoxy; R 8 is selected from a group consisting of hydrogen, cyano, C 3-6 cycloalkyl, 3-6 membered heterocyclyl, C 1-6 alkyl, halogenated C 1-6 alkyl, C 1-6 alkoxy, halogenated C 1-6 alkoxy, and -NR 12 R 13 R 11 , R 12 , and R 13 are each independently selected from a group consisting of hydrogen, deuterium, C 1-6 alkyl, and C 3-6 cycloalkyl, wherein said C 3-6 cycloalkyl is optionally further substituted with one or more substituents selected from a group consisting of halogen, halogenated C 1-6 alkyl, and C 1-6 alkyl; with the proviso that when A is selected from a group consisting of C 6-8 aryl and 5-8 membered heteroaryl, n is not equal to 0, at least one R 1 is selected from a group consisting of cyano, C 3-6 cycloalkyl, 3-6 membered heterocyclyl, halogenated C 3-6 cycloalkyl, halogenated 3-6 membered heterocyclyl, halogenated C 1-6 alkoxy, C 1-6 alkyl-substituted C 3-6 cycloalkyl, and C 1-6 alkyl-substituted 3-6 membered heterocyclyl; or when A is selected from a group consisting of C 6-8 aryl and 5-8 membered heteroaryl, n is not equal to 0, and R 1 is only selected from halogen and/or C 1-6 alkyl and/or halogenated C 1-6 alkyl, and R 3 is selected from a group consisting of C 6-8 aryl and 5-6 membered heteroaryl, R 3 is substituted with at least one substituent selected from a group consisting of cyano, -NR 12 R 13 , - C(O)NR 12 R 13 , and -N(R 12 )-C(O)R 11 , wherein in said -NR 12 R 13 and -C(O)NR 12 R 13 , R 12 or R 13 is C 3-12 cycloalkyl, wherein in said -N(R 12 )-C(O)R 11 , R 11 or R 12 is C 3-6 cycloalkyl, wherein said C 3-6 cycloalkyl is independently optionally further substituted with one or more substituents selected from a group consisting of deuterium, halogen, halogenated C 1-6 alkyl, and C 1-6 alkyl.
  3. The compound of any one of claims 1-2, stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein ring A is selected from a group consisting of phenyl, pyridinyl, and pyrimidinyl; R 2 is selected from a group consisting of methyl, ethyl, and isopropyl; R 4 and R 5 together with a carbon atom to which they are directly attached form a cyclopropyl or cyclobutyl, wherein said cyclopropyl or cyclobutyl is optionally further substituted with one or more substituents selected from a group consisting of methyl, ethyl, and isopropyl; R 6 is
  4. The compound of any one of claims 1-3, stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein the compound has the following formula: wherein R 3 is selected from a group consisting of 5-10 membered heteroaryl and C 6-10 aryl, wherein above groups are optionally further substituted with one or more substituents selected from a group consisting of halogen, cyano, nitro, hydroxyl, C 1-6 alkyl, halogenated C 1-6 alkyl, C 3-6 cycloalkyl, C 1-6 alkoxy, halogenated C 1-6 alkoxy, -S(O) r R 9 , -C(O)NR 12 R 13 , -N(R 12 )-C(O)R 11 , and -NR 12 R 13 ; R 11 , R 12 , and R 13 are each independently selected from a group consisting of hydrogen, deuterium, C 1-6 alkyl, and C 3-6 cycloalkyl, wherein said C 3-6 cycloalkyl is optionally further substituted with one or more substituents selected from a group consisting of halogen, halogenated C 1-6 alkyl, and C 1-6 alkyl; n is 1, 2, 3, or 4; R 1 , R 7 , and R 8 are as defined in any one of claims 1-3.
  5. The compound of any one of claims 1-4, stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein R 3 is selected from phenyl, pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, or the following groups: wherein above groups are optionally further substituted with one or more substituents selected from a group consisting of cyano, nitro, hydroxyl, halogen, C 1-6 alkyl, halogenated C 1-6 alkyl, C 3-6 cycloalkyl, C 1-6 alkoxy, halogenated C 1-6 alkoxy, -C(O)NR 12 R 13 , -N(R 12 )-C(O)R 11 , and -NR 12 R 13 ; R 11 , R 12 , and R 13 are as defined in any one of claims 1-4.
  6. The compound of any one of claims 1-5, stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein the compound has the following formula: wherein n is 1, 2, 3, or 4; m is 0, 1, 2, 3, 4, 5, or 6; R 14 is selected from a group consisting of hydrogen, cyano, hydroxyl, nitro, halogen, C 1-6 alkyl, halogenated C 1-6 alkyl, C 3-6 cycloalkyl, C 1-6 alkoxy, halogenated C 1-6 alkoxy, -C(O)NR 12 R 13 , -N(R 12 )-C(O)R 11 , and -NR 12 R 13 ; R 11 , R 12 , and R 13 are each independently selected from a group consisting of hydrogen, deuterium, C 1-6 alkyl, and C 3-6 cycloalkyl, wherein said C 3-6 cycloalkyl is optionally further substituted with one or more substituents selected from a group consisting of halogen, halogenated C 1-6 alkyl, and C 1-6 alkyl; R 1 , R 7 , and R 8 are as defined in any one of claims 1-5.
  7. The compound of any one of claims 1-6, stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein \R 7 is 5-6 membered heterocyclyl, wherein said 5-6 membered heterocyclyl is optionally substituted with one or more substituents selected from a group consisting of halogen, hydroxyl, cyano, nitro, C 1-6 alkyl, and halogenated C 1-6 alkyl, or any two substituents on the same carbon atom of said 5-6 membered heterocyclyl together with a carbon atom to which they are attached form a C 3-6 cycloalkyl, wherein said C 3-6 cycloalkyl is optionally further substituted with one or more substituents selected from a group consisting of halogen, cyano, C 1-6 alkyl, halogenated C 1-6 alkyl, and C 1-6 alkoxy.
  8. The compound of any one of claims 1-7, stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein R 7 is tetrahydropyranyl, wherein said tetrahydropyranyl is optionally substituted with one or more substituents selected from a group consisting of methyl, ethyl, isopropyl, fluoromethyl, difluoromethyl, and trifluoromethyl, or any two substituents on the same carbon atom of said tetrahydropyranyl together with a carbon atom to which they are attached form a cyclopropyl, cyclobutyl, or cyclopentyl, wherein the formed ring is optionally further substituted with one or more substituents selected from a group consisting of fluoro, chloro, bromo, cyano, methyl, ethyl, isopropyl, fluoromethyl, difluoromethyl, trifluoromethyl, methoxy, and ethoxy.
  9. The compound of claim 6, stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein R 14 is selected from a group consisting of hydrogen, cyano, nitro, hydroxyl, fluoro, chloro, bromo, methyl, ethyl, propyl, isopropyl, fluoromethyl, difluoromethyl, trifluoromethyl, methoxy, ethoxy, isopropoxy, fluoromethoxy, difluoromethoxy, trifluoromethoxy, fluoroethoxy, difluoroethoxy, trifluoroethoxy, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, -C(O)NR 12 R 13 , -N(R 12 )-C(O)R 11 , and -NR 12 R 13 ; R 11 , R 12 , and R 13 are each independently selected from a group consisting of hydrogen, deuterium, methyl, ethyl, propyl, cyclopropyl, cyclobutyl, cyclopentyl, and bicyclo[1.1.1]pentanyl, wherein above groups are optionally substituted with one or more substituents selected from a group consisting of fluoro, chloro, bromo, fluoromethyl, difluoromethyl, trifluoromethyl, methyl, ethyl, propyl, and isopropyl; or R 14 is selected from a group consisting of the following groups:
  10. The compound of any one of claims 1-9, stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein the compound is selected from: wherein R 14 is selected from a group consisting of hydrogen, cyano, hydroxyl, nitro, halogen, C 1-6 alkyl, halogenated C 1-6 alkyl, C 3-6 cycloalkyl, C 1-6 alkoxy, halogenated C 1-6 alkoxy, - C(O)NR 12 R 13 , -N(R 12 )-C(O)R 11 , and -NR 12 R 13 ; m is 1, 2, 3, or 4; n is 1, 2, 3, or 4; R 1 and R 8 are as defined in any one of claims 1-9.
  11. The compound of any one of claims 1-10, stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein R 1 is selected from a group consisting of cyano, halogen, C 1-6 alkyl, halogenated C 1-6 alkyl, C 3-6 cycloalkyl, 3-6 membered heterocyclyl, halogenated C 3-6 cycloalkyl, halogenated 3-6 membered heterocyclyl, halogenated C 1-6 alkoxy, halogenated C 1-6 alkylthio, C 1-6 alkyl-substituted C 3-6 cycloalkyl, and C 1-6 alkyl-substituted 3-6 membered heterocyclyl; R 8 is selected from a group consisting of hydrogen, cyano, C 3-6 cycloalkyl, 3-6 membered heterocyclyl, C 1-6 alkyl, halogenated C 1-6 alkyl, halogenated C 1-6 alkoxy, and -NR 12 R 13 .
  12. The compound of any one of claims 1-11, stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein R 1 is selected from a group consisting of cyano, fluoro, chloro, bromo, methyl, ethyl, isopropyl, fluoromethyl, difluoromethyl, trifluoromethyl, fluoromethoxy, difluoromethoxy, trifluoromethoxy, and trifluoromethylthio, or is selected from a group consisting of the following groups: R 8 is selected from a group consisting of hydrogen, cyano, amino, cyclopropyl, cyclobutyl, cyclopentyl, methyl, ethyl, isopropyl, fluoromethyl, difluoromethyl, trifluoromethyl, fluoromethoxy, difluoromethoxy, trifluoromethoxy, trifluoromethylthio, azetidinyl, and methylamino.
  13. The compound of any one of claims 1-12, stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein the compound is selected from: wherein R 14 is selected from a group consisting of hydrogen, cyano, hydroxyl, nitro, halogen, C 1-6 alkyl, halogenated C 1-6 alkyl, C 3-6 cycloalkyl, C 1-6 alkoxy, halogenated C 1-6 alkoxy, - C(O)NR 12 R 13 , -N(R 12 )-C(O)R 11 , and -NR 12 R 13 ; m is 1, 2, 3, or 4.
  14. The compound of any one of claims 10-13, stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein R 14 is selected from a group consisting of hydrogen, cyano, nitro, hydroxyl, fluoro, chloro, bromo, methyl, ethyl, propyl, isopropyl, fluoromethyl, difluoromethyl, trifluoromethyl, methoxy, ethoxy, isopropoxy, fluoromethoxy, difluoromethoxy, trifluoromethoxy, fluoroethoxy, difluoroethoxy, trifluoroethoxy, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, - C(0)NR 12 R 13 , -N(R 12 )-C(O)R 11 , and -NR 12 R 13 , wherein R 11 , R 12 , and R 13 are each independently selected from a group consisting of hydrogen, deuterium, methyl, ethyl, propyl, cyclopropyl, cyclobutyl, cyclopentyl, and bicyclo[1.1.1]pentanyl, wherein above groups are optionally substituted with one or more substituents selected from a group consisting of fluoro, chloro, bromo, fluoromethyl, difluoromethyl, trifluoromethyl, methyl, ethyl, propyl, and isopropyl; preferably, R 14 is selected from a group consisting of hydrogen, cyano, fluoro, chloro, bromo, C 1-6 alkyl, halogenated C 1-6 alkyl, and halogenated C 1-6 alkoxy; more preferably, R 14 is selected from a group consisting of hydrogen, cyano, fluoro, chloro, methyl, ethyl, propyl, trifluoromethyl, and trifluoromethoxy.
  15. The compound of any one of claims 1-14, stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein the compound is selected from a group consisting of the following compounds:
  16. The compound of any one of claims 1-15, stereoisomer, tautomer, or a pharmaceutically acceptable salt thereof, wherein the compound is selected from a group consisting of the following compounds:
  17. A method of preparing the compound of any one of claims 1-16, stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, comprising: wherein R 16 is H; R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , and n are as defined in any one of claims 1-16.
  18. A pharmaceutical composition comprising the compound of any one of claims 1-16, stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.
  19. Use of the compound of any one of claims 1-16, stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, or the pharmaceutical composition of claim 18 in the preparation of a medicament for treating and/or preventing a disease mediated by a GLP-1 receptor agonist.
  20. Use of the compound of any one of claims 1-16, stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, or the pharmaceutical composition of claim 18 in the preparation of a medicament for preventing and/or treating diabetes, hyperglycemia, insulin resistance, glucose intolerance, diabetic nephropathy, diabetic neuropathy, diabetic retinopathy, adipocyte dysfunction, obesity, dyslipidemia, and hyperinsulinemia.

Description

TECHNICAL FIELD The present invention relates to the pharmaceutical field, specifically to a GLP-1 receptor agonist compound and preparation method thereof, as well as use of thr compound in the preparation of a medicament for treating or preventing GLP-1 receptor mediated disease. BACKGROUND Obesity is a prevalent chronic disease in modern society and is associated with many medical problems, including hypertension, hypercholesterolemia, and coronary heart disease. Currently, the only treatment that eliminates obesity with high efficacy is weight reduction surgery, but this treatment is expensive and carries high risks. Pharmacological interventions are generally less effective and associated with side effects. Therefore, there is a clear need for more effective pharmacological interventions with fewer side effects and convenient administration. Glucagon-like peptide-1 (GLP-1) is an incretin secreted by intestinal epithelial L cells that exerts physiological effects by binding to its receptor. The GLP-1 receptor (GLP-1R) belongs to the G protein-coupled receptor subfamily, and when GLP-1 binds to the GLP-1 receptor, it triggers a series of biological effects. Studies have shown that GLP-1 promotes insulin secretion in a glucose-dependent manner, meaning that when blood glucose concentration rises in the human body, GLP-1 stimulates islet cells, increases insulin secretion, and lowers blood glucose. GLP-1 receptor agonists are a new type of hypoglycemic drug that can effectively control blood glucose levels without causing hypoglycemia, and can effectively reduce weight by increasing satiety, delaying gastric emptying, suppressing appetite, slowing intestinal movement to delay food absorption, and reducing fat accumulation, thereby achieving weight loss. Peptide-based GLP-1 receptor agonist drugs such as liraglutide, exenatide, and semaglutide have been applied to obese type II diabetic patients as well as patients with simple obesity or overweight, all showing significant weight reduction effects, but are often accompanied by gastrointestinal adverse reactions such as nausea and vomiting. At the same time, injectable peptide products have poor patient compliance, while oral peptide drugs have low bioavailability, strict medication regimens, high prices, and still relatively high rates of gastrointestinal reactions. Therefore, it is necessary to develop a new compound with good biological properties, good compliance, and safety. SUMMARY OF THE INVENTION The purpose of the present invention is to provide a new GLP-1 receptor agonist and preparation method therefor, pharmaceutical compositions containing it, and use thereof in medicaments, particularly for the preparation of a medicament for treating or preventing GLP-1 receptor mediated disease, with the potential to be developed into a new generation of GLP-1 receptor agonist. Specifically, the present invention provides the following technical solutions. One aspect of the present invention provides a compound of formula (I), a stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein, ring A is selected from a group consisting of 3-12 membered heterocyclyl, C6-10 aryl, and 5-10 membered heteroaryl;R1 is selected from a group consisting of cyano, halogen, C1-10 alkyl, C3-12 cycloalkyl, 3-12 membered heterocyclyl, halogenated C1-10 alkyl, halogenated C3-12 cycloalkyl, halogenated 3-12 membered heterocyclyl, halogenated C1-10 alkoxy, halogenated C1-10 alkylthio, C1-6 alkyl-substituted C3-12 cycloalkyl, and C1-6 alkyl-substituted 3-12 membered heterocyclyl;R2 is selected from a group consisting of hydrogen, cyano, C1-10 alkyl, halogenated C1-10 alkyl, C1-10 alkoxy, halogenated C1-10 alkoxy, and -NR12R13;R3 is selected from a group consisting of C3-12 cycloalkyl, 3-12 membered heterocyclyl, C6-10 aryl, and 5-10 membered heteroaryl, above groups are optionally further substituted with one or more substituents selected from a group consisting of halogen, cyano, nitro, azido, C1-10 alkyl, halogenated C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, C3-12 cycloalkyl, 3-12 membered heterocyclyl, C6-10 aryl, 5-10 membered heteroaryl, =O, -SF5, -S(O)rR9, -O-R10, -C(O)OR10, -C(O)R11, -O-C(O)R11, -NR12R13, -C(=NR12)R11, -N(R12)-C(=NR13)R11, -C(O)NR12R13, and -N(R12)-C(O)R11;R4 and R5 are each independently selected from a group consisting of hydrogen, halogen, hydroxyl, C1-10 alkyl, halogenated C1-10 alkyl, C1-10 alkoxy, and halogenated C1-10 alkoxy, or R4 and R5, together with a carbon atom to which they are directly attached, form a C3-12 cycloalkyl, wherein said C3-12 cycloalkyl is optionally further substituted with one or more substituents selected from a group consisting of hydrogen, halogen, amino, hydroxyl, C1-10 alkyl, halogenated C1-10 alkyl, C1-10 alkoxy, and halogenated C1-10 alkoxy;R6 is 5-10 membered heteroaryl;R7 is selected from 3-12 membered heterocyclyl, or 5-10 membered heteroaryl, wherein above groups are optionally substituted with one