GLP-1R receptor agonist compound and use thereof

1. A compound represented by the following formula (I) or a pharmaceutically acceptable salt thereof,

wherein,

A is phenyl or 5- to 6-membered heteroaryl containing one or two heteroatoms selected from O and N;

R 1 is —H, halogen, —CN, —OH, deuterium, —C 1-6 alkyl, —C 1-6 alkoxy, —C 2-6 alkenyl, —C 2-6 alkynyl, —C 6-10 aryl or —C 5-10 heteroaryl containing one or two heteroatoms selected from O and N; the —C 1-6 alkyl, —C 1-6 alkoxy, —C 2-6 alkenyl or —C 2-6 alkynyl is substituted by 0-3 F;

subscript m is an integer of 0, 1, 2 or 3;

R 2 , R 3 are each independently —H, deuterium, or C 1-6 alkyl; or R 2 , R 3 together with the carbon atom to which they are attached form a 3- to 6-membered cycloalkyl or heterocycloalkyl containing one or two heteroatoms selected from O and N;

L is —O—, —S—, —NR 11 — or —C(R 11 R 12 )—; the R 11 , R 12 are hydrogen or —C 1-6 alkyl;

R 4 is halogen, —CN, —OH, deuterium, —C 1-6 alkyl, —C 1-6 alkoxy, —C 2-6 alkenyl or —C 2-6 alkynyl;

the —C 1-6 alkyl, —C 1-6 alkoxy, —C 2-6 alkenyl or —C 2-6 alkynyl is substituted by 0-3 F;

subscript n is an integer of 0, 1 or 2;

B is

R 5 is —H, halogen, —CN, —OH, deuterium, —C 1-6 alkyl, —C 1-6 alkoxy, —C 2-6 alkenyl or —C 2-6 alkynyl; the —C 1-6 alkyl, —C 1-6 alkoxy, —C 2-6 alkenyl or —C 2-6 alkynyl is substituted by 0-3 F;

subscript o is an integer of 0, 1 or 2;

R 6 , R 7 are each independently —H, deuterium, or —C 1-6 alkyl; or R 6 , R 7 together with the carbon atom to which they are attached form a 3- to 6-membered cycloalkyl or a 3- to 6-membered heterocycloalkyl containing one or two heteroatoms selected from O and N; or R 6 , B ring together with the carbon atom to which they are attached form a 3- to 6-membered cycloalkyl or a 3- to 6-membered heterocycloalkyl containing one or two heteroatoms selected from O and N;

R 8 is —C 1-3 alkyl, -methylene-C 3-6 cycloalkyl or -methylene-C 4-6 heterocycloalkyl containing one or two heteroatoms selected from O and N; wherein, the —C 1-3 alkyl, -methylene-C 3-6 cycloalkyl or -methylene-C 4-6 heterocycloalkyl containing one or two heteroatoms selected from O and N is unsubstituted or substituted by one or more substituents selected from halogen, —CN, —OH, deuterium, —C 1-6 alkyl, —C 1-6 alkoxy, —C 2-6 alkenyl, —C 2-6 alkynyl and 5- to 6-membered heteroaryl containing one or two heteroatoms selected from O and N;

Z is N or CR 13 ;

R 9 is hydrogen, halogen, —CN, —OH, deuterium, —C 1-6 alkyl, —C 1-6 alkoxy, —C 2-6 alkenyl or —C 2-6 alkynyl; the —C 1-6 alkyl, —C 1-6 alkoxy, —C 2-6 alkenyl or —C 2-6 alkynyl is substituted by 0-3 F;

subscript p is an integer of 0, 1 or 2;

R 10 is —COOH or an isostere of carboxyl;

R 13 is hydrogen, halogen, —CN, —OH, deuterium, —C 1-6 alkyl, —C 1-6 alkoxy, —C 2-6 alkenyl or —C 2-6 alkynyl; the —C 1-6 alkyl, —C 1-6 alkoxy, —C 2-6 alkenyl or —C 2-6 alkynyl is substituted by 0-3 F;

the halogen is selected from F, Cl and Br.

2. The compound or the pharmaceutically acceptable salt thereof according to claim 1 , wherein, the compound or the pharmaceutically acceptable salt thereof has a structure represented by the following formula (II):

wherein,

A is phenyl or pyridyl;

R 1 is halogen, —CN, —OH, deuterium, —C 1-6 alkyl, —C 1-6 alkoxy, —C 2-6 alkenyl, or —C 2-6 alkynyl; the —C 1-6 alkyl, —C 1-6 alkoxy, —C 2-6 alkenyl or —C 2-6 alkynyl is substituted by 0-3 F;

subscript m is an integer of 0, 1 or 2;

R 2 , R 3 are each independently —H, deuterium, or C 1-6 alkyl;

R 4 is halogen, —CN, —OH, deuterium, —C 1-6 alkyl or —C 1-6 alkoxy;

subscript n is an integer of 0 or 1;

B is

R 5 is halogen, —OH, —C 1-6 alkyl or —C 1-6 alkoxy;

subscript o is an integer of 0, 1 or 2;

R 6 , R 7 are each independently —H, deuterium, or C 1-6 alkyl; or R 6 , R 7 together with the carbon atom to which they are attached form a 3- to 6-membered cycloalkyl or a 3- to 6-membered heterocycloalkyl containing one or two heteroatoms selected from O and N;

R 8 is —C 1-3 alkyl, -methylene-C 3-6 cycloalkyl or -methylene-C 4-6 heterocycloalkyl containing one or two heteroatoms selected from O and N; wherein, the —C 1-3 alkyl, -methylene-C 3-6 cycloalkyl or -methylene-C 4-6 heterocycloalkyl containing one or two heteroatoms selected from O and N is unsubstituted or substituted by one or more substituents selected from halogen, —CN, —OH, deuterium, —C 1-6 alkyl, —C 1-6 alkoxy, —C 2-6 alkenyl, —C 2-6 alkynyl and 5- to 6-membered heteroaryl containing one or two heteroatoms selected from O and N;

Z is N or CR 13 ;

R 13 is hydrogen, halogen, —CN, —OH, deuterium, —C 1-6 alkyl or —C 1-6 alkoxy.

3. The compound or the pharmaceutically acceptable salt thereof according to claim 1 , wherein, the compound or the pharmaceutically acceptable salt thereof has a structure represented by the following formula (III):

wherein,

R 1 is halogen, —CN, —OH, deuterium, —C 1-6 alkyl, —C 1-6 alkoxy, —C 2-6 alkenyl, or —C 2-6 alkynyl; the —C 1-6 alkyl, —C 1-6 alkoxy, —C 2-6 alkenyl or —C 2-6 alkynyl is substituted by 0-3 F;

subscript m is an integer of 1 or 2;

A is phenyl, or pyridyl;

R 4 is halogen, —OH, deuterium, —C 1-6 alkyl or —C 1-6 alkoxy;

subscript n is an integer of 0 or 1;

B is

R 5 is halogen, —OH, —C 1-6 alkyl or —C 1-6 alkoxy;

subscript o is an integer of 0, 1 or 2;

R 8 is —C 1-3 alkyl, -methylene-C 3-6 cycloalkyl or -methylene-C 4-6 heterocycloalkyl.

4. The compound or the pharmaceutically acceptable salt thereof according to claim 1 , wherein, the compound or the pharmaceutically acceptable salt thereof has a structure represented by the following formula (IV):

wherein,

R 1 is halogen, —CN, —OH, deuterium, —C 1-6 alkyl, —C 1-6 alkoxy, —C 2-6 alkenyl, or —C 2-6 alkynyl; the —C 1-6 alkyl, —C 1-6 alkoxy, —C 2-6 alkenyl or —C 2-6 alkynyl is substituted by 0-3 F;

subscript m is an integer of 1 or 2;

A is phenyl, or pyridyl;

R 4 is halogen, —OH, deuterium, —C 1-6 alkyl or —C 1-6 alkoxy;

subscript n is an integer of 0 or 1;

B is

R 5 is —C 1-6 alkyl;

subscript o is an integer of 0 or 1.

5. The compound or the pharmaceutically acceptable salt thereof according to claim 4 , wherein, in the structure of the compound represented by formula (IV) or the pharmaceutically acceptable salt thereof, R 1 is —F, —Cl, —Br, —CN, —C 1-6 alkyl, —C 1-6 alkoxy, —C 2-6 alkenyl or —C 2-6 alkynyl;

subscript m is 2;

A is phenyl;

R 4 is —F, or —Cl;

B is

6. The compound or the pharmaceutically acceptable salt thereof according to claim 4 , wherein, subscript o is 0.

7. The compound or the pharmaceutically acceptable salt thereof according to claim 1 , wherein the compound is selected from one of the following compounds:

8. A pharmaceutical composition, comprising a therapeutically effective amount of the compound or the pharmaceutically acceptable salt thereof according to claim 1 as an active ingredient, and a pharmaceutically acceptable excipient.

9. A method for treating metabolism-related diseases by activating a GLP-1R receptor in a subject in need thereof, comprising: administering the compound or the pharmaceutically acceptable salt thereof according to claim 1 to the subject.

10. The method according to claim 9 , wherein the metabolism-related diseases are selected from glucose intolerance, hyperglycemia, dyslipidemia, type 1 diabetes (T1D), type 2 diabetes (T2D), hypertriglyceridemia, syndrome X, insulin resistance, impaired glucose tolerance (IGT), diabetic dyslipidemia, hyperlipidemia, arteriosclerosis, atherosclerosis, hypertension, obesity, non-alcoholic fatty liver, non-alcoholic steatohepatitis, hepatic fibrosis, cirrhosis, and lethargy.

11. A method for treating metabolism-related diseases by activating a GLP-1R receptor in a subject in need thereof, comprising: administering the compound or the pharmaceutically acceptable salt thereof according to claim 7 to the subject.

12. The method according to claim 11 , wherein the metabolism-related diseases are selected from glucose intolerance, hyperglycemia, dyslipidemia, type 1 diabetes (T1D), type 2 diabetes (T2D), hypertriglyceridemia, syndrome X, insulin resistance, impaired glucose tolerance (IGT), diabetic dyslipidemia, hyperlipidemia, arteriosclerosis, atherosclerosis, hypertension, obesity, non-alcoholic fatty liver, non-alcoholic steatohepatitis, hepatic fibrosis, cirrhosis, and lethargy.

13. A method for activating a GLP-1R receptor in a subject in need thereof, comprising: administering the compound or the pharmaceutically acceptable salt thereof according to claim 1 to the subject.

14. A method for activating a GLP-1R receptor in a subject in need thereof, comprising: administering the compound or the pharmaceutically acceptable salt thereof according to claim 7 to the subject.