A novel glp-1 receptor agonist and uses thereof

Abstract

The present application relates to a novel GLP-1 receptor agonist, which is a compound of Formula (I) or a pharmaceutically acceptable salt thereof, and methods of treating or preventing GLP-1 receptor mediated diseases or disorders or modulating GLP-1 receptor. Formula (I).

Description

Technical Field

[0001] This invention relates to a novel GLP-1 receptor agonist and its application in the treatment or prevention of GLP. 1. Receptor-mediated diseases or disorders or regulation of GLP 1. Application of receptors. Background Technology

[0002] Diabetes is a chronic metabolic disease characterized primarily by abnormally high blood sugar levels. It is generally classified into type 1 diabetes, type 2 diabetes, and gestational diabetes. Type 1 diabetes is often caused by autoimmune damage to pancreatic beta cells, leading to insufficient insulin secretion, while type 2 diabetes is closely related to insulin resistance and impaired pancreatic beta cell function. Long-term hyperglycemia can lead to serious complications such as cardiovascular disease, kidney disease, and retinopathy; therefore, blood sugar control is the core goal of diabetes management.

[0003] Glucagon-like peptide-1 (GLP-1) is an incretin hormone secreted by intestinal L cells and plays a crucial role in glycemic regulation. GLP-1 lowers blood glucose through multiple mechanisms, including stimulating insulin secretion, inhibiting glucagon release, delaying gastric emptying, and increasing satiety. Furthermore, GLP-1 also protects pancreatic β-cells, improves insulin sensitivity, and has potential cardiovascular protective effects. GLP-1-based therapies, such as GLP-1 receptor agonists (e.g., semaglutide), have become an important treatment option for type 2 diabetes, effectively controlling blood glucose, reducing weight, and lowering cardiovascular risk, providing a more comprehensive management plan for diabetic patients.

[0004] Smegglutide is a novel GLP-1 receptor agonist widely used in the treatment of type 2 diabetes and the management of obesity. It works by mimicking the action of GLP-1, enhancing insulin secretion, inhibiting glucagon release, delaying gastric emptying, and increasing satiety, thereby effectively lowering blood glucose levels and helping to control weight. Compared to traditional hypoglycemic agents, smegglutide has a long-lasting effect, requiring only once-weekly injections, significantly improving patient adherence. Furthermore, studies have shown that smegglutide performs well in reducing cardiovascular risk, decreasing the incidence of major cardiovascular events and providing more comprehensive health benefits for diabetic patients. In recent years, smegglutide has also been approved for long-term weight management in obese or overweight adults, further expanding its clinical applications. Despite its excellent performance in treating type 2 diabetes and obesity, its administration method still presents some inconvenience.

[0005] Currently, semaglutide is primarily administered via subcutaneous injection. Although its long-acting nature allows for once-weekly injections, the procedure may cause psychological distress or discomfort for some patients, especially those with needle phobia or limited self-injection skills. Furthermore, pre-injection preparation and strict adherence to storage conditions (such as refrigeration) increase the complexity of its use. While oral formulations of semaglutide have been approved, its absorption is affected by food intake and timing, requiring patients to take it under specific conditions, which may limit their daily lives. Overall, there is still room for improvement in the convenience of semaglutide's administration method to meet the needs of more patients.

[0006] LY3502970 is an oral small-molecule GLP-1 receptor agonist developed by Eli Lilly for the treatment of type 2 diabetes and obesity. As a novel oral GLP-1 receptor agonist, LY3502970 exhibits significant blood glucose-lowering and weight-loss effects. Its oral administration method enhances the patient experience and holds promise for playing an important role in the future treatment of diabetes and obesity.

[0007]

[0008] Currently, small molecule GLP 1-receptor agonists have become a hot topic in drug development in recent years due to their potential for high oral bioavailability. Summary of the Invention

[0009] This invention provides compounds of formula (I) or pharmaceutically acceptable salts thereof.

[0010] Formula (I) in, Selected from or .

[0011] R3 is selected from (CR) C R C ) 0-2 -cyclic hydrocarbon group, (CR C R C ) 0-2 -Aryl, (CR C R C ) 0-2 - Heterocyclic group or (CR) C R C ) 0-2- Heteroaryl, wherein the cyclic hydrocarbon group is a spirocyclic hydrocarbon group, a bridged cyclic hydrocarbon group, or a monocyclic hydrocarbon group, and the aryl, heterocyclic, or heteroaryl group is a spirocyclic, bridged ring, fused ring, or monocyclic ring; the cyclic hydrocarbon group, aryl, heterocyclic, or heteroaryl group is optionally substituted by one or more substituents independently selected from: C1-C6 alkyl, C1-C6 haloalkyl, C3-C 10 Cycloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, OH, halogen, NH2, oxo, NH-(C1-C6 alkyl), N(C1-C6 alkyl)2, CN, NO2, phenyl or heteroaryl; or when the carbon atom on the cycloalkyl, aryl, heteroaryl or heterocyclic ring is replaced by two C1-C6 alkyl groups, the two C1-C6 alkyl groups can form a C3-C group together with the carbon atom to which they are attached. 10 Cyclic hydrocarbon groups; each R C It is independently H, C1-C3 alkyl, or C1-C3 haloalkyl; or two R C Together with the carbon atoms to which they are attached, they form C3-C 10 Cyclic hydrocarbon group; the C3-C 10 The cyclic hydrocarbon group is optionally substituted by one or more substituents independently selected from the following: C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, OH or halogen.

[0012] A is selected from E is selected from O or S, and F is independently selected from NR. d , O, S or -C(R) e )2-, the R d R e Each is independently selected from H, C1-C6 alkyl, C3-C6 cycloalkyl, and C3-C6 heterocyclic groups, wherein the C1-C6 alkyl, C3-C6 cycloalkyl, and C3-C6 heterocyclic groups are optionally substituted by one or more substituents independently selected from the following: C1-C6 alkyl, C3-C6 cycloalkyl, halogen, methanesulfonyl, ethanesulfonyl, propanesulfonyl, cyclopropanesulfonyl, 3- to 6-membered heterocyclic groups, or 5- to 6-membered heteroaryl groups, wherein the 3- to 6-membered heterocyclic groups and 5- to 6-membered heteroaryl groups are optionally substituted by one or more substituents independently selected from the following Substituents: deuterium, halogen, cyano, amino, methanesulfonyl, ethanesulfonyl, propanesulfonyl, cyclopropanesulfonyl, C1-C6 alkyl, C1-C6 alkoxy, C3-C6 cycloalkyl, C3-C6 epoxyalkyl, wherein the C1-C6 alkyl, C3-C6 cycloalkyl, and C3-C6 epoxyalkyl are optionally substituted by one or more substituents independently selected from the following: halogen, C1-C6 alkyl, C3-C6 cycloalkyl, C1-C6 alkoxy, C1-C6 haloalkyl, where n is an integer from 0 to 10.

[0013] B is selected from C3-C10 The aryl, heterocyclic, or heteroaryl group comprises one or two 5- or 6-membered rings and 1 to 3 heteroatoms selected from N, O, and S, or comprises one or two 5- or 6-membered rings and 1 to 3 heteroatoms selected from N, O, and S, wherein the aryl, heterocyclic, or heteroaryl group is a spirocyclic, bridged ring, fused ring, or monocyclic ring; wherein the aryl, heterocyclic, or heteroaryl group is optionally substituted by one or more substituents independently selected from: C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C3-C6 ... 12 Cycloalkyl groups, C1-C6 alkyl groups, C3-C6 alkyl groups 12 Cyclic hydrocarbon group, OH, halogen, NH2, NH-(C1-C6 alkyl), N(C1-C6 alkyl)2, NH-S(=O)2R a CN, NO2, P(=O)R a R b S(=O)2R a Oxygenation, thiolation, , or The cyclic hydrocarbon group is a spirocyclic hydrocarbon group, a bridged cyclic hydrocarbon group, or a monocyclic hydrocarbon group, wherein R a R b Each is independently selected from halogens, C1-C6 alkyl groups, and C3-C4 alkyl groups. 10 Cyclic hydrocarbon group, phenyl group.

[0014] Z is selected from CH or N.

[0015] C is selected from CH2 or C=O.

[0016] It is selected from aryl, heterocyclic or heteroaryl, wherein the aryl, heterocyclic or heteroaryl is a spirocyclic, bridged ring, fused ring or monocyclic.

[0017] L is selected from C3-C 10 A cyclic hydrocarbon group, carbonyl group, phenylene group, or heteroaryl group comprising one or two 5- or 6-membered rings and 1-3 heteroatoms selected from N, O, and S, wherein the cyclic hydrocarbon group, phenylene group, or heteroaryl group is optionally substituted by one or more substituents independently selected from: C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, or halogen; or wherein when the phenylene group is substituted by two substituents attached to adjacent carbon atoms in the phenylene ring, the two substituents together with the carbon atoms to which they are attached can form a 5- or 6-membered ring, the 5- or 6-membered ring optionally comprising 1-3 heteroatoms selected from N, O, and S.

[0018] R4 and R5 are each independently selected from H, D, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, OH, or halogen, or R4 and R5 together with the carbon atom to which they are attached form a C3-C... 10 Cyclic hydrocarbon group, the C3-C 10 The cyclic hydrocarbon group is optionally substituted by one or more substituents independently selected from the following: C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, OH or halogen.

[0019] T is selected from C(O)OH, (CH2)NHS(O)2-R y C(O)NHS(O)2R y A heterocyclic group comprising one or two 5- or 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S, or a heteroaryl group comprising one 5- or 6-membered ring and 1 to 4 heteroatoms selected from N, O, and S, wherein the heterocyclic group or heteroaryl group is optionally substituted with C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, OH, halogen, or oxo.

[0020] R1 is independently selected from H, deuterium, halogen, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 alkylamine, C3-C 10 Cycloalkyl, phenyl, wherein C1-C6 alkyl, C1-C6 alkoxy, C1-C6 alkylamine, C3-C 10 The cyclic hydrocarbon group and phenyl group are optionally substituted by one or more substituents independently selected from the following: C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, OH, halogen, NH2, NH-(C1-C6 alkyl), N(C1-C6 alkyl)2, CN or NO2.

[0021] Alternatively, the two R1 atoms together with the atoms they are attached to form a C3-C. 10 Cyclic hydrocarbon group or C3-C 12 A heterocyclic group containing one, two, or three heteroatoms independently selected from oxygen, sulfur, nitrogen, and phosphorus, wherein the C3-C 10 Cyclic hydrocarbon group or C3-C 12 The heterocyclic group is optionally substituted by one or more substituents independently selected from the following: C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, OH or halogen.

[0022] R2 is independently selected from H, halogen, and -OR. y -SR y -NR y R z , C1-C6 alkyl, C3-C 10 Cycloalkyl, C1-C6 alkoxy, phenyl, vinyl, ethynyl, cyano, 3- to 12-membered heterocyclic, or 5- to 12-membered heteroaryl, wherein the alkyl, cycloalkyl, alkoxy, phenyl, vinyl, ethynyl, heterocyclic, or heteroaryl group is optionally represented by one or more independent R groups. x replace.

[0023] R x Selected independently from halogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, OH, halogen, NH2, oxo, thio, NH-(C1-C6 alkyl), N(C1-C6 alkyl)2, CN, NO2, -C1-C6 alkyl C1-C6 alkyl, C3-C 10 Cyclic hydrocarbon group or -C1-C6 alkyl-C3-C 10 Cyclic hydrocarbon group.

[0024] R y or R z Each is independently selected from H, deuterium, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxy-substituted alkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, OH, halogen, C2-C6 alkenyl, C2-C6 alkynyl, C3-C 10 Cyclic hydrocarbon group, -C1-C6 alkyl, -C3-C 10 Cyclic hydrocarbon group.

[0025] p, s, or q are each independently selected from integers from 0 to 5.

[0026] In some embodiments of the present invention, the above-mentioned Selected from .

[0027] In some embodiments of the present invention, the above-mentioned Selected from , , , , , , , , , , or .

[0028] In some embodiments of the present invention, the above-mentioned Selected from or .

[0029] In some embodiments of the present invention, R2 is independently selected from H, halogens, and -OR. y -SR y -NR y R z , C1-C6 alkyl, C3-C 10 Cycloalkyl, C1-C6 alkoxy, phenyl, 3- to 12-membered heterocyclic, or 5- to 12-membered heteroaryl, wherein the alkyl, cycloalkyl, alkoxy, heterocyclic, or heteroaryl group is optionally surrounded by one or more independent R groups. x Replace, R x Selected alone from halogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, OH, halogen, NH2, oxo, CN, NO2, or -C1-C6 alkyl C1-C6 alkyl, R y and R z Each is independently selected from H, deuterium, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxy-substituted alkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, OH, halogen, C2-C6 alkenyl, C2-C6 alkynyl, C3-C 10 Cyclic hydrocarbon group, -C1-C6 alkyl, -C3-C 10 Cyclic hydrocarbon group.

[0030] In some embodiments of the present invention, R3 is selected from (CR C R C ) 0-2 -C3-C6 cyclic hydrocarbon group, (CR C R C ) 0-2 -Phenyl, containing two 5- or 6-membered rings (CR C R C ) 0-2 -aryl, comprising one or two 5- or 6-membered rings and 1-3 heteroatoms selected from N, O, and S (CR C R C ) 0-2 - Heteroaryl or containing one or two 3- to 6-membered rings and 1-3 heteroatoms selected from N, O, and S (CR C R C ) 0-2 - Heterocyclic group, wherein the cyclic hydrocarbon group, phenyl group, aryl group, heteroaryl group or heterocyclic group is optionally substituted by one or more substituents independently selected from: C1-C6 alkyl group, C1-C6 haloalkyl group, C3-C6 alkyl group, C4-C6 alkyl group, C5-C6 alkyl group, C6 ... 10Cycloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, OH, halogen, NH2, NH-(C1-C6 alkyl), N(C1-C6 alkyl)2, CN, NO2, C3-C6 cycloalkyl, phenyl, or heteroaryl; or when the carbon atom on the cycloalkyl, phenyl, aryl, heteroaryl, or heterocyclic ring is replaced by two C1-C6 alkyl groups, the two C1-C6 alkyl groups together with the carbon atoms to which they are attached form a C3-C... 10 Cyclic hydrocarbon groups; each R C It is independently H, C1-C3 alkyl, or C1-C3 haloalkyl; or two R C Together with the carbon atoms to which they are attached, they form C3-C 10 Cyclic hydrocarbon group; the C3-C 10 The cyclic hydrocarbon group is optionally substituted by one or more substituents independently selected from the following: C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, OH or halogen.

[0031] In some embodiments of the present invention, R3 is selected from (CR C R C ) 0-2 -C3-C6 cyclic hydrocarbon group, (CR C R C ) 0-2 -Phenyl, containing two 5- or 6-membered rings (CR C R C ) 0-2 -aryl or containing one or two 5- or 6-membered rings and 1-3 heteroatoms selected from N, O, and S (CR C R C ) 0-2 - Heteroaryl, wherein the cycloalkyl, phenyl, aryl, or heteroaryl group is optionally substituted by one or more substituents independently selected from: C1-C6 alkyl, C1-C6 haloalkyl, C3-C 10 Cyclic hydrocarbon group, C1-C6 alkoxy group, C1-C6 haloalkoxy group, OH, halogen, NH2, NH-(C1-C6 alkyl), N(C1-C6 alkyl)2, CN, NO2 or C3-C6 cyclic hydrocarbon group, each R C Independently, it is H, a C1-C3 alkyl, or a C1-C3 haloalkyl; or when a carbon atom on a cycloalkyl, phenyl, aryl, or heteroaryl ring is replaced by two C1-C6 alkyl groups, the two C1-C6 alkyl groups together with the carbon atoms to which they are attached form a C3-C... 10 Cyclic hydrocarbon group; or two R groups C Together with the carbon atoms to which they are attached, they form C3-C 10 Cyclic hydrocarbon group; the C3-C 10The cyclic hydrocarbon group is optionally substituted by one or more substituents independently selected from the following: C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, OH or halogen.

[0032] In some embodiments of the present invention, A is selected from... E is selected from O or S, and F is independently selected from NR. d , O, S or -C(R) e )2-, the R d R e Each of the groups is independently selected from H, C1-C6 alkyl, C3-C6 cycloalkyl, and C3-C6 heterocyclic groups, wherein the C1-C6 alkyl, C3-C6 cycloalkyl, and C3-C6 heterocyclic groups are optionally substituted by one or more substituents independently selected from the following: C1-C6 alkyl, C3-C6 cycloalkyl, halogen, methanesulfonyl, ethanesulfonyl, propanesulfonyl, cyclopropanesulfonyl, 3- to 6-membered heterocyclic groups, or 5- to 6-membered heteroaryl groups, wherein the 3- to 6-membered heterocyclic groups or 5- to 6-membered heteroaryl groups comprise 1 to 3 heteroatoms optionally selected from N, O, and S.

[0033] In some embodiments of the present invention, the B mentioned above is selected from a heterocyclic group comprising one or two 5- or 6-membered rings and 1 to 3 heteroatoms selected from N, O, and S, or a heteroaryl group comprising one or two 5- or 6-membered rings and 1 to 3 heteroatoms selected from N, O, and S, wherein the heterocyclic group or the heteroaryl group is optionally substituted by one or more substituents independently selected from: C1-C6 alkoxy-substituted C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C3-C 12 Cyclic hydrocarbon group, OH, halogen, NH2, NH-(C1-C6 alkyl), N(C1-C6 alkyl)2, CN or NO2.

[0034] In some embodiments of the present invention, A is selected from... , where R dIndependently selected from H, C1-C3 alkyl; the C1-C3 alkyl group is optionally substituted by one or more substituents independently selected from the following: C1-C6 alkyl, C3-C6 cycloalkyl, halogen, methanesulfonyl, ethanesulfonyl, propanesulfonyl, cyclopropanesulfonyl, 3- to 6-membered heterocyclic group or 5- to 6-membered heteroaryl group, wherein the 3- to 6-membered heterocyclic group or 5- to 6-membered heteroaryl group is optionally substituted by one or more substituents independently selected from the following: halogen, methanesulfonyl, ethanesulfonyl, propanesulfonyl C1-C6 alkyl, C1-C6 alkoxy, C3-C6 cycloalkyl, C3-C6 epoxyalkyl, wherein the C1-C6 alkyl, C3-C6 cycloalkyl, C3-C6 epoxyalkyl are optionally substituted by one or more substituents independently selected from the following: halogen, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, wherein the 3- to 6-membered heterocyclic group and the 5- to 6-membered heteroaryl group contain 1 to 3 heteroatoms optionally selected from N, O and S, where n is 0 or 1.

[0035] In some embodiments of the present invention, A is selected from... , where R d Independently selected from H, C1-C3 alkyl; the C1-C3 alkyl group is optionally substituted by one or more substituents independently selected from the following: C1-C6 alkyl, C3-C6 cycloalkyl, halogen, methanesulfonyl, ethanesulfonyl, propanesulfonyl, cyclopropanesulfonyl, 3- to 6-membered heterocyclic group or 5- to 6-membered heteroaryl group, wherein the 3- to 6-membered heterocyclic group or 5- to 6-membered heteroaryl group is optionally substituted by one or more substituents independently selected from the following: halogen, methanesulfonyl, ethanesulfonyl, propanesulfonyl C1-C6 alkyl, C1-C6 alkoxy, C3-C6 cycloalkyl, C3-C6 epoxyalkyl, wherein the C1-C6 alkyl, C3-C6 cycloalkyl, C3-C6 epoxyalkyl are optionally substituted by one or more substituents independently selected from the following: halogen, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, wherein the 3- to 6-membered heterocyclic group and the 5- to 6-membered heteroaryl group contain 1 to 3 heteroatoms optionally selected from N, O and S, where n is 0 or 1.

[0036] In some embodiments of the present invention, the above-mentioned R d R e Each is independently selected from H, , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , or .

[0037] In some embodiments of the present invention, A is selected from... , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , or .

[0038] In some embodiments of the present invention, n is 0.

[0039] In some embodiments of the present invention, n is 1.

[0040] In some embodiments of the present invention, B is selected from... , , , , , , , , , , , , , , , , , , , , , or .

[0041] In some embodiments of the present invention, Z is selected from N.

[0042] In some embodiments of the present invention, the C mentioned above is selected from C=O.

[0043] In some embodiments of the present invention, R2 is independently selected from halogens, C1-C6 alkyl groups, C3-C6 alkyl groups, and C4-C6 alkyl groups. 10Cycloalkyl, C1-C6 alkoxy, phenyl, vinyl, ethynyl, cyano, heterocyclic group comprising one or two 3- to 6-membered rings and 1-3 heteroatoms selected from N, O, and S, or heteroaryl group comprising one or two 5- or 6-membered rings and 1-3 heteroatoms selected from N, O, and S, wherein the alkyl, cycloalkyl, alkoxy, phenyl, vinyl, ethynyl, heterocyclic, or heteroaryl group is optionally substituted by one or more substituents independently selected from: halogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, OH, halogen, NH2, oxo, NH-(C1-C6 alkyl), N(C1-C6 alkyl)2, CN or NO2, -C1-C6 alkyl C1-C6 alkyl groups.

[0044] In some embodiments of the present invention, R2 is selected from C3-C 10 Cyclic hydrocarbon group, the C3-C 10 The cyclic hydrocarbon group is optionally substituted by one or more substituents independently selected from the following: C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, OH, halogen, NH2, NH-(C1-C6 alkyl), N(C1-C6 alkyl)2, CN or NO2, wherein the cyclic hydrocarbon group is a spirocyclic hydrocarbon group, a bridged cyclic hydrocarbon group or a monocyclic hydrocarbon group.

[0045] In some embodiments of the present invention, R2 is selected from vinyl or ethynyl groups, wherein the vinyl or ethynyl group is optionally substituted by one or more substituents independently selected from the following: , or .

[0046] In some embodiments of the present invention, R2 is selected from tetrahydropyranyl, which is optionally substituted by one or more substituents independently selected from the following: C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, OH, halogen, NH2, NH-(C1-C6 alkyl), N(C1-C6 alkyl)2, CN and NO2.

[0047] In some embodiments of the present invention, L is selected from... R4 and R5 are each independently H, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, OH, or halogen; or R4 and R5 together with the carbon atoms to which they are attached form a C3-C group. 10 Cyclic hydrocarbon group, the C3-C 10The cyclic hydrocarbon group is optionally substituted by one or more substituents independently selected from the following: C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, OH or halogen.

[0048] In some embodiments of the present invention, the T mentioned above is selected from a heteroaryl group comprising a 5- or 6-membered ring and 1 to 4 heteroatoms selected from N, O, and S, wherein the heteroaryl group is optionally substituted with C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, OH, halogen, or oxo.

[0049] In some embodiments of the present invention, R1 is selected from H, halogen, C1-C6 alkyl, and C1-C6 haloalkyl.

[0050] In some embodiments of the present invention, the two R1 atoms together with the atoms they are attached to form a C3-C6 cyclic hydrocarbon group or a C3-C6 heterocyclic group, wherein the heterocyclic group contains one, two, or three heteroatoms independently selected from oxygen, sulfur, and nitrogen, and the C3-C... 10 Cyclic hydrocarbon group or C3-C 12 The heterocyclic group is optionally substituted by one or more substituents independently selected from the following: C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, OH or halogen.

[0051] In some embodiments of the present invention, R3 is selected from... , , , , , , , , , , , , , , , , , , , , or .

[0052] In some embodiments of the present invention, R2 is selected from... , , , , or .

[0053] In some embodiments of the present invention, L is selected from... , , , , , , , , , , , , , , , , , , or .

[0054] In some embodiments of the present invention, the T mentioned above is selected from oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, oxadiazolyl, thiazolyl, oxadiazolone, thiazolyl or tetrazolyl, wherein each is optionally substituted by C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, OH, halogen or oxo.

[0055] In some embodiments of the present invention, T is... .

[0056] In some embodiments of the present invention, T is C(O)OH.

[0057] In some embodiments of the present invention, T is... .

[0058] In some embodiments of the present invention, the above-mentioned for .

[0059] In some embodiments of the present invention, p is selected from 0, 1, or 2.

[0060] In some embodiments of the present invention, q is selected from 0, 1, or 2.

[0061] In some embodiments of the present invention, s is selected from 0, 1 or 2.

[0062] In some embodiments of the present invention, the above-mentioned compound has the formula (I-1):

[0063] A, B, L, T, R2, and R3 are defined as described above.

[0064] This invention provides compounds of the following formula or pharmaceutically acceptable salts thereof.

[0065]

[0066] In some embodiments of the present invention, the above-mentioned compound or a pharmaceutically acceptable salt thereof is selected from,

[0067]

[0068] In some embodiments of the present invention, the present invention provides a pharmaceutical composition comprising the above-described compound or a pharmaceutically acceptable salt thereof as an active ingredient.

[0069] This invention provides a treatment or prevention of GLP. 1. Receptor-mediated diseases or disorders or regulation of GLP A method for treating a receptor includes administering a therapeutically effective amount of the above-described compound or a pharmaceutically acceptable salt thereof or the above-described pharmaceutical composition to a subject who has the corresponding need.

[0070] The present invention provides a method for treating non-insulin-dependent diabetes mellitus (type 2 diabetes), hyperglycemia, impaired glucose tolerance, insulin-dependent diabetes mellitus (type 1 diabetes), diabetic complications, obesity, hypertension, hyperlipidemia, arteriosclerosis, coronary heart disease, cerebral infarction, non-alcoholic steatohepatitis, Parkinson's disease, or dementia, the method comprising administering to a subject requiring the treatment a therapeutically effective amount of the above-described compound or a pharmaceutically acceptable salt thereof or the above-described pharmaceutical composition.

[0071] The present invention provides a method for treating non-insulin-dependent diabetes mellitus (type 2 diabetes) or obesity, the method comprising administering to a subject requiring the treatment a therapeutically effective amount of the above-described compound or a pharmaceutically acceptable salt thereof or the above-described pharmaceutical composition.

[0072] Technical effect The compounds of this invention have a good agonistic effect on GLP-1 receptors.

[0073] Definitions and Explanations Unless otherwise stated, the following terms and phrases as used herein are intended to have the following meanings. A particular term or phrase should not be considered uncertain or unclear unless specifically defined, but should be understood in its ordinary sense. When a trade name appears herein, it is intended to refer to the corresponding product or its active ingredient.

[0074] The term “pharmaceutically acceptable” as used herein refers to compounds, materials, compositions, and / or dosage forms that, within the bounds of reliable medical judgment, are suitable for use in contact with human and animal tissues without excessive toxicity, irritation, allergic reactions, or other problems or complications, in proportion to a reasonable benefit / risk ratio.

[0075] The term "pharmaceutically acceptable salt" refers to a salt of the compounds of this invention, prepared by reacting a compound having specific substituents discovered in this invention with a relatively non-toxic acid or base. When the compounds of this invention contain relatively acidic functional groups, base addition salts can be obtained by contacting a neutral form of such compound with a sufficient amount of base in a pure solution or a suitable inert solvent. Pharmaceutically acceptable base addition salts include sodium, potassium, calcium, ammonium, organic amine, or magnesium salts or similar salts. When the compounds of this invention contain relatively basic functional groups, acid addition salts can be obtained by contacting a neutral form of such compound with a sufficient amount of acid in a pure solution or a suitable inert solvent.

[0076] The pharmaceutically acceptable salts of the present invention can be synthesized from parent compounds containing acid radicals or bases by conventional chemical methods. Generally, such salts are prepared by reacting these compounds in free acid or base form with a stoichiometric amount of a suitable base or acid in water or an organic solvent or a mixture thereof.

[0077] "Pharmaceutical composition" means containing one or more of the compounds described in this application, their isomers or pharmaceutically acceptable salts thereof, and other components such as physiologically / pharmaceutically acceptable carriers and excipients. The purpose of a pharmaceutical composition is to facilitate administration to a living organism, thereby promoting the absorption of the active ingredient and the exertion of its biological activity.

[0078] The term "therapeutic effective amount" refers to an amount of a compound, when administered, sufficient to stop or slow the progression of one or more symptoms or conditions of a disease to a certain extent. The term "therapeutic effective amount" also refers to an amount of a compound sufficient to detect a biological or pharmaceutical response (e.g., protein, enzyme, RNA, or DNA) in a biomolecule, cell, tissue, system, animal, or human. This response is desired by researchers, veterinarians, physicians, or clinicians.

[0079] The compounds, their isomers, or pharmaceutically acceptable salts described in this application refer to solvent-added or crystalline forms, particularly solvates or polymorphs. Solvates contain a stoichiometric or non-stoichiometric solvent and are selectively formed during crystallization of the compound with a pharmaceutically acceptable solvent, such as water, ethanol, etc. For example, a hydrate is formed when the solvent is water, or an ethanolide is formed when the solvent is ethanol. Solvates of compounds of general formula (1) are readily prepared or formed according to the methods described herein. For example, hydrates of compounds of general formula (1) are readily prepared by recrystallization from a mixture of water and an organic solvent, the organic solvent being, but not limited to, tetrahydrofuran, acetone, ethanol, or methanol. Furthermore, the compounds mentioned herein can exist in both non-solventized and solvated forms. In summary, for the purposes of the compounds and methods provided herein, the solvated form is considered equivalent to the non-solventized form.

[0080] Unless otherwise stated, the term "isomer" is intended to include geometric isomers, cis-trans isomers, stereo isomers, enantiomers, optical isomers, diastereomers and tautomers.

[0081] The compounds of this invention can exist in specific geometric or stereoisomeric forms. This invention envisions all such compounds, including cis and trans isomers, (-)- and (+)- enantiomers, ( R )-and( S - Enantiomers, diastereomers, ( D )-Isomer, ( L (Isomers, racemic mixtures thereof, and other mixtures, such as mixtures enriched with enantiomers or diastereomers, are all within the scope of this invention. Additional asymmetric carbon atoms may be present in substituents such as alkyl groups. All such isomers and mixtures thereof are included within the scope of this invention.)

[0082] Unless otherwise stated, the terms "enantiomer" or "optical isomer" refer to stereoisomers that are mirror images of each other.

[0083] Unless otherwise stated, the terms "cis-trans isomers" or "geometric isomers" arise because the single bonds of double bonds or cyclic carbon atoms cannot rotate freely.

[0084] Unless otherwise stated, the term "diastereomer" refers to a stereoisomer of a molecule having two or more chiral centers and being in a non-mirror relationship with each other.

[0085] Unless otherwise stated, "(+)" indicates right-handed rotation, "(-)" indicates left-handed rotation, and "(±)" indicates racemic rotation.

[0086] Unless otherwise specified, use wedge-shaped solid line keys ( ) and wedge-shaped dashed key ( ) represents the absolute configuration of a solid center, using a straight solid line key ( ) and straight dashed key ( The relative configuration of the center of a solid is represented by a wavy line ( ). ) indicates a wedge-shaped solid line key ( ) or wedge-shaped dashed key ( ), or use wavy lines ( ) indicates a straight solid line key ( ) or straight dashed key ( ).

[0087] Unless otherwise stated, the terms "rich in one isomer," "isomer enrichment," "rich in one enantiomer," or "enantiomer enrichment" mean that the content of one isomer or enantiomer is less than 100%, and the content of the isomer or enantiomer is greater than or equal to 60%, or greater than or equal to 70%, or greater than or equal to 80%, or greater than or equal to 90%, or greater than or equal to 95%, or greater than or equal to 96%, or greater than or equal to 97%, or greater than or equal to 98%, or greater than or equal to 99%, or greater than or equal to 99.5%, or greater than or equal to 99.6%, or greater than or equal to 99.7%, or greater than or equal to 99.8%, or greater than or equal to 99.9%.

[0088] Unless otherwise stated, the terms "isomer excess" or "enantiomer excess" refer to the difference between the relative percentages of two isomers or two enantiomers. For example, if one isomer or enantiomer is 90% and the other isomer or enantiomer is 10%, then the isomer or enantiomer excess (ee value) is 80%.

[0089] Optically active materials can be prepared through chiral synthesis, chiral reagents, or other conventional techniques. R )-and( S )-Isomers and D and L Isomers. To obtain an enantiomer of a compound of the present invention, it can be prepared by asymmetric synthesis or by derivatization with a chiral auxiliary, wherein the resulting diastereomeric mixture is separated and the auxiliary group is cleaved to provide a pure desired enantiomer. Alternatively, when the molecule contains a basic functional group (such as an amino group) or an acidic functional group (such as a carboxyl group), a salt of the diastereomeric isomer is formed with a suitable optically active acid or base, and then the diastereomeric isomer is resolved by conventional methods known in the art, and the pure enantiomer is recovered. Furthermore, the separation of enantiomers and diastereomeric isomers is typically accomplished by using chromatography employing a chiral stationary phase and optionally combined with chemical derivatization (e.g., from amines to carbamates).

[0090] The compounds of this invention may contain atomic isotopes in non-natural proportions on one or more atoms constituting the compound. For example, the compounds may be labeled with radioactive isotopes, such as tritium ( 3 H), Iodine-125 ( 125 I) or C-14 14 C). For example, deuterium can be used to replace hydrogen to form deuterated drugs. The bond between deuterium and carbon is stronger than that between ordinary hydrogen and carbon. Compared with undeuterated drugs, deuterated drugs have advantages such as reduced toxicity, increased drug stability, enhanced efficacy, and prolonged drug biological half-life. All isotopic variations of the compounds of this invention, regardless of radioactivity, are included within the scope of this invention.

[0091] The terms “optional” or “optionally” refer to events or conditions that may occur but are not required to occur as described below, and the description includes both cases where said events or conditions occur and cases where said events or conditions do not occur.

[0092] The terms "substituted" or "substituted" refer to the substitution of one or more hydrogen atoms on a particular atom by a substituent, which can include deuterium and hydrogen variants, provided the valence state of the particular atom is normal and the resulting compound is stable. When the substituent is oxygen (i.e., =O) or sulfur (i.e., =S), it means that two hydrogen atoms are substituted. Oxygen substitution or sulfur substitution does not occur on aromatic groups. The term "optionally substituted" means that it may or may not be substituted. Unless otherwise specified, the type and number of substituents can be arbitrary on a chemically feasible basis.

[0093] When any variable (e.g., R) appears more than once in the composition or structure of a compound, its definition is independent in each case. Thus, for example, if a group is substituted by 0-2 Rs, the group can optionally be substituted by at most two Rs, and the Rs in each case have independent options. Furthermore, combinations of substituents and / or their variants are only permitted if such combinations produce a stable compound.

[0094] When the number of a linking group is 0, such as -(CRR)0-, it indicates that the linking group is a single bond.

[0095] When the number of a substituent is 0, it means that the substituent does not exist. For example, -A-(R)0 means that the structure is actually -A.

[0096] When a substituent is vacant, it means that the substituent does not exist. For example, if X is vacant in AX, it means that the structure is actually A.

[0097] When one of the variables is selected as a single bond, it means that the two groups it connects to are directly connected. For example, when L in ALZ represents a single bond, it means that the structure is actually AZ.

[0098] When a substituent can be cross-bonded to two or more atoms on a ring, this substituent can bond with any atom on that ring, for example, structural units. or This indicates that the substituent R can be substituted at any position on the cyclohexyl or cyclohexadiene. When the listed substituents do not specify which atom they are attached to the substituted group, such substituents can be bonded to any of their atoms. For example, a pyridyl group as a substituent can be attached to the substituted group through any carbon atom on the pyridine ring.

[0099] When the listed linking groups do not specify their linking direction, the linking direction is arbitrary, for example, The linker group L is -MW-. In this case, -MW- can connect ring A and ring B in the same direction as the reading order from left to right to form a ring. Alternatively, rings A and B can be connected in the opposite direction to the left-to-right reading order to form a ring. The combination of the linking group, substituents, and / or their variants is permitted only if such a combination produces a stable compound.

[0100] Unless otherwise specified, when a group has one or more connectable sites, any one or more sites of that group can be connected to other groups by chemical bonds. When the chemical bond connection is non-directional and the connectable site contains H atoms, the number of H atoms at that site will decrease accordingly with the number of chemical bonds connected, resulting in a group with a corresponding valence. The chemical bonds connecting the site to other groups can be straight solid line bonds (…). Straight dashed key ( ), or wavy lines ( () indicates that the oxygen atom in the group is bonded to another group. For example, a straight solid line bond in -OCH3 indicates that the oxygen atom in the group is bonded to another group. The straight dashed bond in the diagram indicates that the group is connected to other groups through both ends of the nitrogen atom in the group; The wavy lines in the diagram indicate that the phenyl group is connected to other groups through the carbon atoms at positions 1 and 2.

[0101] Unless otherwise specified, the number of atoms in a ring is usually defined as the elemental number of the ring. For example, a “5-7 elemental ring” refers to a “ring” with 5-7 atoms arranged around it.

[0102] Unless otherwise specified, C n-n+m Or C n-C n+m This includes any specific case with n to n+m carbons, such as C 1-12 Including C1, C2, C3, C4, C5, C6, C7, C8, C9, C 10 C 11 and C 12 It also includes any range from n to n+m, such as C 1-12 Including C 1-3 C 1-6 C 1-9 C 3-6 C 3-9 C 3-12 C 6-9 C 6-12 and C 9-12 Similarly, n-membered to n+m-membered rings represent the number of atoms in the ring from n to n+m. For example, 3-12-membered rings include 3-membered, 4-membered, 5-membered, 6-membered, 7-membered, 8-membered, 9-membered, 10-membered, 11-membered, and 12-membered rings, and also any range from n to n+m. For example, 3-12-membered rings include 3-6-membered, 3-9-membered, 5-6-membered, 5-7-membered, 6-7-membered, 6-8-membered, and 6-10-membered rings, etc.

[0103] Unless otherwise specified, the term "C1-C6 alkyl" is used to denote a straight-chain or branched saturated hydrocarbon group consisting of 1 to 6 carbon atoms. The C1-C6 alkyl group includes C... 1-6 C 1-5 C 1-4 C 1-3 C 1-2 C 2-6 C 2-4 C6, C5, C4, and C3 alkyl groups, etc.; they can be monovalent (e.g., methyl), divalent (e.g., methylene), or polyvalent (e.g., methine). 1-8 Examples of alkyl groups include, but are not limited to, methyl (Me), ethyl (Et), and propyl (including...). n -propyl and isopropyl), butyl (including n -Butyl, Isobutyl s -Butyl and t -Butyl), pentyl (including n -pentyl, isopentyl and neopentyl), hexyl, heptyl, octyl, etc.

[0104] Unless otherwise specified, the term "C" 1-4 "alkyl" is used to denote a straight-chain or branched saturated hydrocarbon group consisting of 1 to 4 carbon atoms. The C 1-4 Alkyl groups include C 1-2 C 1-3 and C 2-3Alkyl groups, etc.; they can be monovalent (e.g., methyl), divalent (e.g., methylene), or polyvalent (e.g., methine). C 1-4 Examples of alkyl groups include, but are not limited to, methyl (Me), ethyl (Et), and propyl (including...). n -propyl and isopropyl), butyl (including n -Butyl, Isobutyl s -Butyl and t (-Butyl) etc.

[0105] Unless otherwise specified, the term "C" 1-3 "alkyl" is used to denote a straight-chain or branched saturated hydrocarbon group consisting of 1 to 3 carbon atoms. The C 1-3 Alkyl groups include C 1-2 and C 2-3 Alkyl groups, etc.; they can be monovalent (e.g., methyl), divalent (e.g., methylene), or polyvalent (e.g., methine). C 1-3 Examples of alkyl groups include, but are not limited to, methyl (Me), ethyl (Et), and propyl (including...). n -propyl and isopropyl, etc.

[0106] Unless otherwise specified, "C3-C6 cycloalkyl" refers to a saturated cyclic hydrocarbon group consisting of 3 to 6 carbon atoms, including monocyclic, bicyclic, and tricyclic systems, of which bicyclic and tricyclic systems include spirocyclic, fused, and bridged rings. 3-6 Examples of cycloalkyl groups include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, etc.

[0107] Unless otherwise specified, "C3-C 10 "Cyclic hydrocarbon group" refers to a saturated or unsaturated cyclic hydrocarbon group consisting of 3 to 10 carbon atoms, including monocyclic, bicyclic, and tricyclic systems, wherein bicyclic and tricyclic systems include spirocyclic, fused, and bridged rings. The C3-C 10 Cyclic hydrocarbon groups include C 3-8 C 3-6 C 3-5 C 4-10 C 4-8 C 4-6 C 4-5 C 5-8 Or C 5-6 etc.; it can be monovalent, divalent, or polyvalent. C 3-10 Examples of cycloalkyl groups include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclohexenyl, cycloheptyl, norbornelalkyl, [2.2.2]bicyclooctane, [4.4.0]bicyclodecane, spiro[2.4]cyclohexane, etc.

[0108] Unless otherwise specified, "C3-C6 cyclic hydrocarbon group" refers to a saturated or unsaturated cyclic hydrocarbon group consisting of 3 to 6 carbon atoms, including monocyclic, bicyclic, and tricyclic systems, wherein bicyclic and tricyclic systems include spirocyclic, fused, and bridged rings. The C3-C6 cyclic hydrocarbon group includes C 3-6 C 3-5 C 4-6 C 4-5 Or C 5-6 etc.; it can be monovalent, divalent, or polyvalent. C 3-6 Examples of cycloalkyl groups include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclohexenyl, etc.

[0109] Unless otherwise specified, the term "3-10 membered heterocyclic alkyl" on its own or in combination with other terms refers to a saturated cyclic group consisting of 3 to 10 ring atoms, wherein 1, 2, 3, or 4 of the ring atoms are heteroatoms independently selected from O, S, N, P, and Se, and the remainder are carbon atoms, wherein the nitrogen atom is optionally quaternized, and the nitrogen, sulfur, and phosphorus heteroatoms may optionally be oxidized (i.e., NO, S(O)). p and P(O) p (where p is 1 or 2). It includes monocyclic, bicyclic, and tricyclic systems, with bicyclic and tricyclic systems including spirocyclic, fused, and bridged rings. Furthermore, regarding the "3-10 membered heterocyclic alkyl," the heteroatom can occupy the connection position between the heterocyclic alkyl group and the rest of the molecule. The 3-10 membered heterocyclic alkyl groups include 3-9, 3-8, 3-6, 5-9, 5, 6, 7, 8, and 9 membered heterocyclic alkyl groups, etc. Examples of 3-10 membered heterocyclic alkyl groups include, but are not limited to, azirrobutyl, oxacyclobutyl, thiocyclobutyl, pyrrolidinyl, pyrazolyl, imidazoalkyl, tetrahydrothiopheneyl (including tetrahydrothiophene-2-yl and tetrahydrothiophene-3-yl, etc.), tetrahydrofuranyl (including tetrahydrofuran-2-yl, etc.), tetrahydropyranyl, piperidinyl (including 1-piperidinyl, 2-piperidinyl and 3-piperidinyl, etc.), piperazinyl (including 1-piperidinyl and 2-piperidinyl, etc.), morpholinyl (including 3-morpholinyl and 4-morpholinyl, etc.), dioxane, dithiaalkyl, isoxazolyl, isothiazolyl, 1,2-oxazinyl, 1,2-thiaazinyl, hexahydropyridazinyl, homopiperidinyl, homopiperidinyl, or dioxaneheptyl, etc.

[0110] Unless otherwise specified, the term "5-membered heterocyclic alkyl" on its own or in combination with other terms refers to a saturated cyclic group consisting of 5 ring atoms, wherein 1, 2, or 3 of the ring atoms are heteroatoms independently selected from O, S, N, P, and Se, and the remainder are carbon atoms, wherein the nitrogen atom is optionally quaternized, and the nitrogen, sulfur, and phosphorus heteroatoms may optionally be oxidized (i.e., NO, S(O)). p and P(O) p(where p is 1 or 2). Examples of 5-membered heterocyclic alkyl groups include, but are not limited to, pyrrolidinyl, pyrazolyl, imidazoalkyl, tetrahydrothiophenyl (including tetrahydrothiophen-2-yl and tetrahydrothiophen-3-yl, etc.), tetrahydrofuranyl (including tetrahydrofuran-2-yl, etc.), tetrahydropyranyl, etc.

[0111] Unless otherwise specified, the term "aryl" refers to a fused or non-fused group or ring system having at least one aromatic ring, either monocyclic or polycyclic (e.g., bicyclic, tricyclic or more rings, wherein at least one is aromatic and the additional rings may be cyclic hydrocarbon groups or aromatic rings). Aryl groups include, but are not limited to, phenyl, naphthyl, 1,2,3,4-tetrahydronaphthyl, indenyl, indanyl, azulel, benzocyclopropyl, benzocyclobutyl, benzocyclopentyl, benzocyclohexyl, benzocyclohexenyl, benzocyclopentenyl, and similar groups.

[0112] Unless otherwise specified, the term "epoxyalkyl" refers to a group formed by the loss of any one hydrogen atom from an epoxy molecule.

[0113] Unless otherwise specified, the term "heteroaryl" refers to a fused or non-fused group or ring system having at least one aromatic ring, having five to twelve ring atoms (one of which is selected from S, O, and N; zero, one, two, or three of which are other heteroatoms independently selected from S, O, and N; and the remaining ring atoms are carbon) of monocyclic or polycyclic (e.g., bicyclic, tricyclic, or more rings). Heteroaryl includes, but is not limited to, pyridinyl, pyrazinyl, pyrimidinyl, pyrroleyl, pyrazolyl, imidazolyl, thiazolyl, oxazolyl, isoxazolyl, thiadiazolyl, oxadiazolyl, thiophene, furanyl, quinolinyl, isoquinolinyl, benzimidazolyl, benzoxazolyl, quinoxolinyl, oxadiazolone, and similar groups.

[0114] Unless otherwise specified, the term “heterocyclic group” or “heterocyclic hydrocarbon group” refers to a saturated or unsaturated non-aromatic 3-, 4-, 5-, 6-, 7-, or 8-membered monocyclic ring system, a 7-, 8-, 9-, 10-, 11-, or 12-membered bicyclic ring system (fused ring, bridged ring, or spirocyclic ring), or an 11-, 12-, 13-, or 14-membered tricyclic ring system (fused ring, bridged ring, or spirocyclic ring), wherein (i) each ring contains one to three heteroatoms independently selected from oxygen, sulfur, and nitrogen, (ii) each 5-membered ring has 0 to 1 double bonds, and each 6-membered ring has 0 to 2 double bonds, (iii) the nitrogen heteroatom and sulfur heteroatom may optionally be oxidized, and (iv) the nitrogen heteroatom may optionally be quaternized. Representative heterocyclic hydrocarbon groups include, but are not limited to, [1,3]dioxacyclopentyl, pyrrolidinyl, pyrazolyl, pyrazolinyl, imidazolinyl, imidazolinyl, imidazoketyl, piperidinyl, piperazinyl, 2-pyridinone, oxazolyl, isoxazolyl, morpholinyl, tetrahydropyranyl, thiazolinyl, isothiazolyl, tetrahydrofuranyl, dioxacyclohexyl, oxetanyl, azetidinyl, thietanyl, oxiranyl, aziridinyl, thiiranyl, 2-oxa-5-azabicyclo[2.2.1]heptyl, 2,5-diazabicyclo[2.2.1]heptyl, 2-oxa-6-azaspiro[3.3]heptyl, 2,6-diazabicyclo[2.2.1]heptyl, and 2,6-diazabicyclo[2.2.1]heptyl. Zazzi[3.3]heptyl, 1,4-dioxa-8-azaspiro[4.5]decyl, 2-azaspiro[3.3]hept-5-amine, 1-azaspiro[3.3]hept-5-amine, 1-oxa-6-azaspiro[3.3]hept-3-amine, 2-azaspiro[3.3]hept-6-amine, 1-azaspiro[3.3]hept-6-amine, 6-azaspiro[3.4]oct-2-amine, 5-azaspiro[3.4]octyl -2-amine, 6-azaspiro[3.4]oct-1-amine, 5-azaspiro[3.4]oct-1-amine, 5-oxa-2-azaspiro[3.4]oct-7-amine, 7-amino-5-thia-2-azaspiro[3.4]octane 5,5-dioxide, 5-oxa-2-azaspiro[3.4]oct-8-amine, 8-amino-5-thia-2-azaspiro[3.4]octane 5,5-dioxide and similar groups.

[0115] According to this application, any one of the rings described herein—aryl, substituted aryl, heteroaryl, and substituted heteroaryl—can be any aromatic group. The aromatic group can be substituted or unsubstituted.

[0116] According to this application, the aryl, heteroaryl, heterocyclic, and heterocyclic groups described herein can be spirocyclic, bridged rings, fused rings, or monocyclic. The ring formed by two rings can be a spirocyclic, bridged ring, fused ring, or monocyclic. The two 5-membered or 6-membered rings can be two 5-membered rings, two 6-membered rings, or a ring composed of one 5-membered ring and one 6-membered ring. This includes, but is not limited to, spiro[2.2]pentane, spiro[5.4]decane, bicyclo[4.3.0]nonane, bicyclo[2.2.1]heptane, bicyclo[3.2.1]octane, and similar groups.

[0117] The compounds of the present invention can be prepared by a variety of synthetic methods known to those skilled in the art, including the specific embodiments listed below, embodiments formed by combining them with other chemical synthetic methods, and equivalent substitutions known to those skilled in the art. Preferred embodiments include, but are not limited to, the embodiments of the present invention.

[0118] The structures of the compounds of this invention can be confirmed using conventional methods well known to those skilled in the art. If this invention relates to the absolute configuration of a compound, the absolute configuration can be confirmed using conventional techniques in the art. For example, single-crystal X-ray diffraction (SXRD) can be used. Diffraction intensity data of the grown single crystal is collected using a Bruker D8 venture diffractometer with Cu-Kα radiation as the light source and φ / ω scanning mode. After collecting the relevant data, the crystal structure can be further analyzed using the direct method (Shelxs 97) to confirm the absolute configuration.

[0119] The solvent used in this invention is commercially available.

[0120] This invention uses the following abbreviations: MeCN or ACN represents acetonitrile; Boc represents tert-butyloxycarbonyl; Bn represents benzyl; DCM represents dichloromethane; DMSO represents dimethyl sulfoxide; ℃ represents degrees Celsius; hr represents hours; LiBH4 represents lithium borohydride; THF represents tetrahydrofuran; Ts represents p-toluenesulfonyl; Ac represents acetyl; Me represents methyl; Et represents ethyl; N2 represents nitrogen; PE represents petroleum ether; EA represents ethyl acetate; DIPEA represents N,N-diisopropylethylamine; K2CO3 represents potassium carbonate; CuI represents cuprous iodide; TBAF represents tetrabutylammonium fluoride; CuBr represents cuprous bromide; DMF represents N,N-dimethylformamide; HC l represents hydrochloric acid; MeOH represents methanol; TEA or Et3N represents triethylamine; DMAP represents 4-dimethylaminopyridine; EDCI represents 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride; MeI represents iodomethane; Pd2(dba)3 represents tris[dibenzylacetone]dipalladium; Pd(dppf)Cl2 represents [1,1'-bis(diphenylphosphine)ferrocene]palladium dichloride; Xantphos represents 4,5-bisdiphenylphosphine-9,9-dimethyloxanthracene; HATU represents 2-(7-azobenzotriazole)-N,N,N',N'-tetramethylurea hexafluorophosphate; Pd(PPh3)2Cl2 represents Bis(triphenylphosphine)palladium(II) dichloride; TBAF represents tetrabutylammonium fluoride; NaH represents sodium hydride; LiOH represents lithium hydroxide; DMPU represents N,N-dimethylpropenylurea; KHMDS represents potassium bis(trimethylsilyl)amino; DBU represents 1,8-diazacyclo[5,4,0]undecene-7; CDI represents N,N'-carbonyldiimidazole; t-BuOK represents potassium tert-butoxide; DCE represents dichloroethane; Triphosgene represents triphosgene; NaBH3CN represents sodium cyanoborohydride; HCl represents hydrochloric acid; Toluene or Tol represents toluene; Dioxane represents dioxane; AcO H represents acetic acid; TFA represents trifluoroacetic acid; NaBH4 represents sodium borohydride; Cu(OTf)2 represents copper trifluoromethanesulfonate; n-BuLi represents n-butyllithium; MsCl represents methanesulfonyl chloride; NaI represents sodium iodide; DMA represents N,N-dimethylacetamide; Py represents pyridine; DMEDA represents N,N'-dimethylethylenediamine; LAH represents lithium aluminum hydride; HBPin represents pinacol borane; [Ir(cod)OMe]2 represents methoxy(cyclooctadiene)iridium(I) dimer; dtbpy represents 4,4-di-tert-butylbipyridine; rt represents room temperature; Solutol represents polyethylene glycol-15-hydroxystearate.

[0121] Compounds are named according to conventional naming principles in the art or using ChemDraw® software; commercially available compounds are named according to the supplier catalog. Detailed Implementation

[0122] The present invention will be described in detail below with reference to embodiments, but this does not imply any adverse limitation on the invention. The present invention has been described in detail, and specific embodiments thereof have been disclosed. It will be apparent to those skilled in the art that various changes and modifications can be made to the specific embodiments of the present invention without departing from the spirit and scope thereof.

[0123] Example 1

[0124] Synthetic route

[0125] Note: The synthesis of intermediate compound 9 is based on Example 9 of PCT / CN2024 / 137939. Step 1: Synthesis of Compound 88-3 In a 50 mL double-necked flask, compound 88-1 (0.5 g, 8.76 mmol), compound 88-2 (1.82 g, 10.51 mmol), and acetonitrile (25 mL) were added. The mixture was substituted with N2 three times. Then, diethylamine (3.2 g, 43.79 mmol) was added dropwise at 0 °C. The mixture was stirred at 0 °C for 30 min and then moved to room temperature for 2 h. The reaction solution was used directly as the raw material for the next step.

[0126] Step 2: Synthesis of Compound 88 Compound 9 (100 mg, 111.4 μmol), sodium ascorbate (119 mg, 601 μmol), and copper sulfate (38 mg, 240 μmol) were added to a 50 mL flask, followed by acetonitrile (5 mL) and water (1 mL) solution. Finally, compound 88-3 (100 mg, 1.19 mmol) was added. After the addition was complete, the mixture was transferred to an oil bath at 70 °C and reacted for 2 h. EA and saturated NH4Cl solution were added, and the organic phase was washed three times with saturated NH4Cl solution. The mixture was dried over anhydrous sodium sulfate, filtered, and purified by column chromatography (DCM / MeOH (V / V) = 10 / 1) to give 45 mg of a white solid, yield 41.2%. MS: (ESI, pos.ion) m / z: 980.4520 [M+H] + .

[0127] Example 2:

[0128] Compound 2 was synthesized according to the method described in Example 10 of PCT / CN2024 / 137939. It was a white solid, and MS (ESI, pos.ion) m / z: 997.4169 [M+H]+ .

[0129] Example 3:

[0130] Synthetic route

[0131] Step 1: Synthesis of compound 3-2 Compound 3-1 (5.0 g, 13.35 mmol) was added to a clean flask, followed by THF (50 mL), 3-trimethylsilylpropynaldehyde (1.68 g, 13.35 mmol), and tris(2,2,2-trifluoroethyl) borate (4.93 g, 16.02 mmol). The mixture was heated to 70 °C and stirred for 1 h until the reaction was complete. The mixture was then concentrated and purified by column chromatography (PE / EA(V / V) = 4 / 1) to give 5.38 g of a yellow solid compound 3-2, with a yield of 83.6%.

[0132] Step 2: Synthesis of compound 3-3 Compound 3-2 (5.38 g, 11.15 mmol) was added to a clean flask, purged three times with nitrogen, dissolved in THF (70 mL), cooled to -78 °C, and a THF solution containing lithium methyl (20.9 mL, 1.6 mol / L in THF) was added dropwise over 30 min. After the addition was complete, the mixture was stirred at -78 °C for 1 h. The mixture was slowly heated to room temperature, and the reaction was quenched by adding H2O (50 mL). The mixture was extracted with EA (100 mL × 3), the organic phases were combined, washed with saturated brine, dried over anhydrous sodium sulfate, concentrated, and purified by column chromatography (PE / EA(V / V) = 4 / 1) to give a yellow solid compound 3-3, 2.54 g, yield 53.4%.

[0133] Step 3: Synthesis of compounds 3-4 Compound 3-3 (500 mg, 1.17 mmol), sodium ascorbate (161 mg, 813 μmol), and copper sulfate (37 mg, 234 μmol) were added to a clean flask, followed by acetonitrile (5 mL) and water (1 mL) solution. Finally, compound 88-3 (976 mg, 11.7 mmol) was added. After the addition was complete, the mixture was transferred to an oil bath at 70 °C and reacted for 2 h. EA and saturated NH4Cl solution were added, and the organic phase was washed three times with saturated NH4Cl solution. The mixture was dried over anhydrous sodium sulfate, filtered, and purified by column chromatography (PE / EA(V / V) = 3 / 2) to give a pale yellow solid compound 3-4, 455 mg, in 76.2% yield.

[0134] Step 4: Synthesis of Compound 3 The synthesis of compound 3 was performed according to Example 9 of PCT / CN2024 / 137939. The crude product 3 obtained by silica gel column chromatography was purified by HPLC to obtain optically pure compounds 3-A and 3-B.

[0135] 3-A, white solid, MS (ESI, pos.ion) m / z: 1020.4834 [M+H] + . 1 H NMR (600 MHz, DMSO, 120℃) δ= 11.48 (s, 1H), 8.05 (s, 2H), 7.58–7.22 (m, 6H), 7.11 (s, 2H), 6.86 (s, 1H), 5.74 (s, 1H), 5.37 (dd, J = 12.3, 7.8 Hz, 1H), 4.48 (s, 1H), 3.81–3.74 (m, 3H), 3.66 (s, 1H), 3.48 (d, J = 34.6 Hz, 1H), 3.11–2.94 (m, 3H), 2.27 (s, 6H), 1.88–1.55 (m, 10H), 1.44–1.28 (m, 6H), 1.23 (s, 6H), 1.16 (d, J = 5.8 Hz, 4H), 1.05 (s, 4H). Retention time: 11.240 min.

[0136] 3-B, white solid, MS (ESI, pos.ion) m / z: 1020.4834 [M+H] + Retention time: 11.487 min.

[0137] Example 4:

[0138] Synthesis route:

[0139] Compound 4 was synthesized according to the steps in Example 3, and optically pure compounds 4-A and 4-B were obtained by HPLC resolution and purification.

[0140] 4-A, white solid, MS (ESI, pos.ion) m / z: 1036.4803 [M+H] + Retention time: 10.926 min.

[0141] 4-B, white solid, MS (ESI, pos.ion) m / z: 1036.4803 [M+H] + Retention time: 11.186 min.

[0142] Example 5

[0143] Synthesis route:

[0144] Step 1: Synthesis of Compound 5-1 Compound 3-1 (4.0 g, 10.68 mmol) was added to a clean flask, followed by THF (50 mL), cyclopropaneformaldehyde (1.12 g, 16.02 mmol), and tris(2,2,2-trifluoroethyl) borate (4.93 g, 16.02 mmol). The mixture was heated to 70 °C and stirred for 1 h until the reaction was complete. The solution was concentrated and purified by column chromatography (PE / EA(V / V) = 4 / 1) to give a yellow solid, compound 5-1, 2.6 g, yield 57.1%. MS: (ESI, pos.ion) m / z: 427.2622 [M+H] + .

[0145] Step 2: Synthesis of Compound 5-2 Compound 5-1 (2.6 g, 6.10 mmol) was added to a clean flask. Under nitrogen protection, THF (25 mL) was added, and the mixture was cooled to -78 °C. A THF solution of trimethylsilylacetylene (24.38 mL, 1 mol / L in THF) was added dropwise. After the addition was complete, the mixture was slowly heated to room temperature and stirred overnight. The reaction was quenched by adding saturated ammonium chloride solution (50 mL), extracted with EA (100 mL × 3), concentrated, and purified by column chromatography (PE / EA(V / V) = 9 / 1) to give 1.8 g of a yellow foamy solid, compound 5-2, in 56.2% yield. MS: (ESI, pos.ion) m / z: 525.3142 [M+H] + .

[0146] Step 3: Synthesis of compound 5-3 Compound 5-2 (1.8 g, 3.43 mmol) and THF (10 mL) were added to a clean flask. TBAF in THF solution (6.86 mL, 1 mol / L in THF) was added, and the mixture was stirred at room temperature for 1 h. The reaction solution was concentrated and subjected to silica gel column chromatography to obtain a yellow foamy solid 5-3, 1.3 g, with a yield of 83.7%.

[0147] Step 4: Synthesis of Compound 5 Compound 5 was synthesized following the steps in Example 3, and optically pure compounds 5-A and 5-B were obtained by HPLC separation and purification.

[0148] 5-A, white solid, MS (ESI, pos.ion) m / z: 1046.5021 [M+H] + Retention time: 12.126 min.

[0149] 5-B, white solid, MS (ESI, pos.ion) m / z: 1046.5021 [M+H] + . 1 H NMR (600 MHz, DMSO, 120℃) δ 11.50 (s, 1H), 8.01 (d, J = 29.4 Hz, 2H), 7.52 – 7.47 (m, 2H), 7.40 (d, J = 8.4 Hz, 1H), 7.36 – 7.19 (m, 3H), 6.98 (s, 2H), 6.83 (s, 1H), 5.86(s, 1H), 4.79 (s, 1H), 4.53 (s, 1H), 3.75 (dd, J = 14.5, 7.0 Hz, 3H), 3.65 (s,1H), 3.50 (s, 1H), 3.17 – 2.98 (m, 3H), 2.82 – 2.71 (m, 2H), 2.23 (s, 6H), 1.75 (dd, J = 24.0, 11.3 Hz, 7H), 1.67 – 1.52 (m, 3H), 1.30 (s, 4H), 1.26 –1.20 (m, 6H), 1.15 (d, J = 6.7 Hz, 4H), 1.04 (d, J = 6.1 Hz, 2H), 0.94 (s, 2H), 0.43 (s, 1H), 0.02 (dd, J = 55.1, 30.1 Hz, 1H). Retention time: 11.713 min.

[0150] The synthesis methods in the following embodiments are the same as those in Example 1.

[0151] Table 1

[0152] Example 25

[0153] Synthesis route:

[0154] Note: Intermediate 5-3 was synthesized according to the method in Example 5. Step 1: Synthesis of Compound 25-1 Compound 5-3 (0.8 g, 1.77 mmol), BTC (triphosgene) (0.39 g, 1.33 mmol), and toluene (20 mL) were added to a clean 50 mL two-necked flask. Then, TEA (0.27 g, 2.65 mmol) was slowly added dropwise. After the addition was complete, the mixture was stirred overnight at 110 °C. Post-treatment: The solvent was concentrated, followed by column chromatography purification (PE / EA(V / V) = 3 / 1) to give a pale yellow, fluffy solid, compound 25-1, 0.18 g, yield 19.8%. MS: (ESI, pos.ion) m / z: 515.2262 [M+H] + .

[0155] Step 2: Synthesis of Compound 25-3 Compound 25-1 (0.18 g, 0.35 mmol), compound 25-2 (0.06 g, 0.31 mmol), NaHCO3 (0.09 g, 1.05 mmol), and toluene (5 mL) were added to a clean 50 mL single-necked flask and stirred overnight at 110 °C. Post-treatment: The solvent was concentrated and purified by column chromatography (PE / EA(V / V) = 2 / 1) to give a pale yellow, fluffy solid, compound 25-3, 0.076 g, yield 32.4%. MS: (ESI, pos.ion) m / z: 670.3393 [M+H] + .

[0156] Step 3: Synthesis of compound 25-4 HCl-Dioxane (4M, 10 mL) and compound 25-3 (76 mg, 0.11 mmol) were added to a clean 50 mL single-necked flask and stirred at room temperature for 1 h. Post-treatment: The solvent was concentrated to give a yellow viscous compound 25-4, 64.6 mg, in 100% yield.

[0157] Step 4: Synthesis of compound 25-5 In a clean 50 mL single-necked flask, 10 mL of DMF was added, followed by compounds 3-8 (55 mg, 0.13 mmol), HATU (64 mg, 0.16 mmol), and DIPEA (45 mg, 0.34 mmol). The mixture was stirred at 0 °C for 30 min, and then compound 25-4 (64 mg, 0.11 mmol) was added. The mixture was stirred overnight at room temperature. Post-treatment: EA and purified water were added. The mixture was extracted three times with EA, washed three times with saturated brine, dried over anhydrous sodium sulfate, filtered, and purified by solvent column chromatography (PE / EA (V / V) = 1-100%) to give a pale yellow solid, compound 25-5, 100 mg, yield 94.4%. MS: (ESI, pos.ion) m / z: 963.4486 [M+H] + .

[0158] Step 5: Synthesis of Compound 25 In a clean 250 mL flask, compound 5-8 (0.514 g, 0.54 mmol), 3-oxacyclobutane azide (0.2 g, 2.02 mmol), sodium ascorbate (0.2 g, 1.0 mmol), CuSO4 (0.06 g, 0.4 mmol), 20 mL acetonitrile, and 4 mL purified water were added. The mixture was stirred at 70 °C for 120 min. Post-treatment: An appropriate amount of EA was added, and the mixture was washed three times with saturated NH4Cl solution. The organic phase was dried over anhydrous sodium sulfate, filtered, and purified by solvent column chromatography (PE / EA(V / V) = 1 / 1) to give a pale yellow, foamy solid, compound 25 (single chiral pure product), 380 mg, yield 66.2%. MS: (ESI, pos.ion) m / z: 1062.4969 [M+H] + .

[0159] 1 H NMR (600 MHz, DMSO, 120℃) δ 11.48 (s, 1H), 8.03 (d, J = 20.9 Hz,2H), 7.66–7.46 (m, 3H), 7.41 (d, J = 8.5 Hz, 1H), 7.31 (s, 1H), 7.23 (d, J = 8.1Hz, 1H), 7.02 (s, 2H), 6.87 (s, 1H), 5.86 (s, 1H), 5.52 (s, 1H), 4.96 (d, J =6.3 Hz, 2H), 4.82 (s, 1H), 4.67 (d, J= 29.2 Hz, 2H), 4.60–4.44 (m, 1H), 3.76(dd, J = 14.4, 6.9 Hz, 3H), 3.53 (s, 1H), 3.11–3.00 (m, 2H), 2.85–2.82 (m, 2H), 2.21 (s, 6H), 1.76 (dd, J = 24.4, 15.8 Hz, 7H), 1.67–1.52 (m, 3H), 1.31 (s,3H), 1.23 (d, J = 9.2 Hz, 6H), 1.16 (d, J = 6.5 Hz, 4H), 0.43 (s, 2H), 0.14–-0.14(m, 2H).

[0160] Example 26: GLP 1. Receptor activity test h GLP 1. Activity determination is as follows: 1) Prepare the Assay buffer (1XHBSS+20mM HEPES+0.1%BSA+500μMIBMX) in advance according to the table below, dispense it, and store it at -20℃ for later use.

[0161] Table 2: Preparation of Stock Solution Reagents

[0162] 2) CHO-K1 GLP-1R cells were cultured in a CO2 incubator at 37°C using complete culture medium until the cell density reached 70-80% confluence, at which point the cell suspension was collected. Experimental wells and blank control wells were also provided.

[0163] 3) Compound preparation: First, prepare a 400X working solution concentration using DMSO. Dilute the natural peptide 3-fold and the test compound 5-fold. Apply 10 spots, either in replicates or single wells. Then, dilute the compound 100-fold using Assy buffer to prepare a 4X working solution concentration (the working concentration should be 4 times the final concentration). The final DMSO concentration is 0.25%.

[0164] 4) CHO-K1 GLP-1R cells were seeded at a density of approximately 2000 cells / well in 7.5 μL of serum-containing complete medium into 384-well microplates with an opaque white bottom. An equal volume of complete medium was added to each well of the blank control.

[0165] 5) Add 2.5 μL / well of the serially diluted test compound or quality control STD (cAMP) from step 2 to a 384 microplate, centrifuge at 200g for 30s, and incubate at 37℃ for 30min. Add an equal volume of Assaybuffer to each blank control well.

[0166] 6) Remove the 384-well plate after incubation. Add 5 μL of Uligh-anti-cAMP (1 / 5 times) to each well, then add 5 μL of Eu-Camp tracer (1 / 5 times) to each well. Cover the plate, centrifuge at 200g for 30s, and incubate at 25℃ for 60min.

[0167] 7) Data were read using an Enhance 2014 multi-functional microplate reader. The detection conditions were: excitation light: 340nm, emission light: 665nm and 620nm. Data reading: Ratio = 665nm / 620nm 1000.

[0168] 8) Data Analysis: The EC50 was calculated using the "log(agonist) vs. response -- Variable slope" model in GraphPad Prism 8.0. % Activity = (VC - Detection Data) / (VC - PC) 100%; PC: 10 nM GLP-1 (7-37) corresponding well data average; VC: 0.25% DMSO corresponding well data average.

[0169] 9) Use GraphPad Prism 8.0 to process experimental data.

[0170] As shown in Table 3 below, the compounds exhibit effective h GLP 1. Agonistaltic activity (“A” means >0 nM and ≤1 nM; “B” means >1 nM and ≤10 nM; “C” means >10 nM).

[0171] Table 3: h of the compounds in this application GLP 1 activity

[0172] Conclusion: Through in vivo / in vitro GLP 1. Receptor activity assays showed that the compounds of the present invention have activity against GLP-1 receptors. 1 receptor has a good agonistic effect.

[0173] Example 27: Pharmacokinetic Evaluation in C57 Mice Test Methods: The pharmacokinetic characteristics of the compounds in C57 mice after a single intravenous injection or single oral administration were tested using a standard protocol. All candidate compounds were prepared into a clear solution using a solvent system of 5% DMSO + 10% Solutol + 85% Saline. A single intravenous injection (IV, n=3) of 1 mg / kg and a single oral administration (PO, n=3) of 5 mg / kg were administered. Whole blood was collected from the animals at 5 min, 15 min, 30 min, 1 h, 2 h, 4 h, 6 h, 8 h, and 24 h after administration. Plasma was separated, and pharmacokinetic parameters were calculated using Phoenix WinNonlin 8.2.0 based on the blood drug concentration data at different time points. The parameters AUC0-t, AUC0-∞, MRT0-∞, Cmax, Tmax, and Tt were provided. 1 / 2 Parameters such as F, and their mean and standard deviation.

[0174] Table 4: Pharmacokinetic parameters of C57 mice

[0175] Conclusion: The compounds of this invention significantly increased plasma exposure compared to orforglipron. Compound 5-B of Example 5 exhibited slower elimination rate, longer half-life, and better pharmacokinetic properties.

[0176] The above embodiments are preferred embodiments of the present invention, but the embodiments of the present invention are not limited to the above embodiments. Any changes, modifications, substitutions, combinations, or simplifications made without departing from the spirit and principle of the present invention shall be considered equivalent substitutions and shall be included within the protection scope of the present invention.

Claims

1. The compound represented by formula (I) or a pharmaceutically acceptable salt thereof, Formula (I) in, Selected from or ; R3 is selected from (CR) C R C ) 0-2 -cyclic hydrocarbon group, (CR C R C ) 0-2 -Aryl, (CR C R C ) 0-2 - Heterocyclic group or (CR) C R C ) 0-2 - Heteroaryl, wherein the cyclic hydrocarbon group is selected from spirocyclic hydrocarbon groups, bridged cyclic hydrocarbon groups, or monocyclic hydrocarbon groups, and the aryl, heterocyclic, or heteroaryl group is spirocyclic, bridged ring, fused ring, or monocyclic; the cyclic hydrocarbon group, aryl, heterocyclic, or heteroaryl group is optionally substituted by one or more substituents independently selected from: C1-C6 alkyl, C1-C6 haloalkyl, C3-C 10 Cycloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, OH, halogen, NH2, oxo, NH-(C1-C6 alkyl), N(C1-C6 alkyl)2, CN, NO2, phenyl or heteroaryl; or when the carbon atom on the cycloalkyl, aryl, heteroaryl or heterocyclic ring is replaced by two C1-C6 alkyl groups, the two C1-C6 alkyl groups can form a C3-C group together with the carbon atom to which they are attached. 10 Cyclic hydrocarbon groups; each R C It is independently H, C1-C3 alkyl, or C1-C3 haloalkyl; or two R C Together with the carbon atoms to which they are attached, they form C3-C 10 Cyclic hydrocarbon group; the C3-C 10 The cyclic hydrocarbon group is optionally substituted by one or more substituents independently selected from the following: C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, OH or halogen; A is selected from Where E is selected from O or S, and F is independently selected from NR. d , O, S or -C(R) e )2-, the R d R e Each is independently selected from H, C1-C6 alkyl, C3-C6 cycloalkyl, and C3-C6 heterocyclic groups, wherein the C1-C6 alkyl, C3-C6 cycloalkyl, and C3-C6 heterocyclic groups are optionally substituted by one or more substituents independently selected from the following: C1-C6 alkyl, C3-C6 cycloalkyl, halogen, methanesulfonyl, ethanesulfonyl, propanesulfonyl, cyclopropanesulfonyl, 3- to 6-membered heterocyclic groups, or 5- to 6-membered heteroaryl groups; wherein the 3- to 6-membered heterocyclic groups and 5- to 6-membered heteroaryl groups are optionally substituted by one or more substituents independently selected from the following The substituents are: deuterium, halogen, cyano, amino, methanesulfonyl, ethanesulfonyl, propanesulfonyl, cyclopropanesulfonyl, C1-C6 alkyl, C1-C6 alkoxy, C3-C6 cycloalkyl, C3-C6 epoxyalkyl; wherein the C1-C6 alkyl, C3-C6 cycloalkyl, and C3-C6 epoxyalkyl are optionally substituted by one or more substituents independently selected from: halogen, C1-C6 alkyl, C3-C6 cycloalkyl, C1-C6 alkoxy, C1-C6 haloalkyl; n is an integer from 0 to 10; B is selected from C3-C 10 Cycloalkyl, aryl, heterocyclic group comprising one or two 5- or 6-membered rings and 1-3 heteroatoms selected from N, O, and S, or heteroaryl group comprising one or two 5- or 6-membered rings and 1-3 heteroatoms selected from N, O, and S; wherein the aryl, heterocyclic, or heteroaryl group is a spirocyclic, bridged ring, fused ring, or monocyclic ring; wherein the cycloalkyl, aryl, heterocyclic, or heteroaryl group is optionally substituted by one or more substituents independently selected from: C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C3-C 12 Cycloalkyl groups, C1-C6 alkyl groups, C3-C6 alkyl groups 12 Cyclic hydrocarbon group, OH, halogen, NH2, NH-(C1-C6 alkyl), N(C1-C6 alkyl)2, NH-S(=O)2R a CN, NO2, P(=O)R a R b S(=O)2R a Oxygenation, thiolation, , or Wherein, the cyclic hydrocarbon group is a spirocyclic hydrocarbon group, a bridged cyclic hydrocarbon group, or a monocyclic hydrocarbon group, and the R a R b Each is independently selected from halogens, C1-C6 alkyl groups, and C3-C4 alkyl groups. 10 Cyclic hydrocarbon group, phenyl group; Z is selected from CH or N; C is selected from CH2 or C=O; It is selected from aryl, heterocyclic or heteroaryl, wherein the aryl, heterocyclic or heteroaryl is a spirocyclic, bridged ring, fused ring or monocyclic; L is selected from C3-C 10 The alkylene group, carbonyl group, phenylene group, or heteroaryl group comprising one or two 5- or 6-membered rings and 1-3 heteroatoms selected from N, O, and S, wherein the alkylene group, phenylene group, or heteroaryl group is optionally substituted by one or more substituents independently selected from: C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, or halogen; or, when the phenylene group is substituted by two substituents attached to adjacent carbon atoms in the phenylene ring, the two substituents may form a 5- or 6-membered ring together with the carbon atoms to which they are attached, the 5- or 6-membered ring optionally comprising 1-3 heteroatoms selected from N, O, and S; R4 and R5 are each independently selected from H, D, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, OH, or halogen, or R4 and R5 together with the carbon atom to which they are attached form a C3-C... 10 Cyclic hydrocarbon group, the C3-C 10 The cyclic hydrocarbon group is optionally substituted by one or more substituents independently selected from the following: C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, OH or halogen; T is selected from C(O)OH, (CH2)NHS(O)2-R y C(O)NHS(O)2R y A heterocyclic group comprising one or two 5- or 6-membered rings and 1 to 4 heteroatoms selected from N, O, and S, or a heteroaryl group comprising one 5- or 6-membered ring and 1 to 4 heteroatoms selected from N, O, and S, wherein the heterocyclic group or heteroaryl group is optionally substituted with C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, OH, halogen, or oxo. R1 is independently selected from H, deuterium, halogen, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 alkylamine, C3-C 10 Cyclic hydrocarbon groups, phenyl groups, wherein C1-C6 alkyl, C1-C6 alkoxy, C1-C6 alkylamine, C3-C 10 The cycloalkyl group and phenyl group are optionally substituted by one or more substituents independently selected from the following: C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, OH, halogen, NH2, NH-(C1-C6 alkyl), N(C1-C6 alkyl)2, CN or NO2; Alternatively, the two R1 atoms together with the atoms they are attached to form a C3-C. 10 Cyclic hydrocarbon group or C3-C 12 A heterocyclic group containing one, two, or three heteroatoms independently selected from O, S, N, and P, wherein the C3-C 10 Cyclic hydrocarbon group or C3-C 12 The heterocyclic group is optionally substituted by one or more substituents independently selected from the following: C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, OH or halogen; R2 is independently selected from H, halogen, and -OR. y -SR y -NR y R z , C1-C6 alkyl, C3-C 10 Cycloalkyl, C1-C6 alkoxy, phenyl, vinyl, ethynyl, cyano, 3- to 12-membered heterocyclic, or 5- to 12-membered heteroaryl, wherein the alkyl, cycloalkyl, alkoxy, phenyl, vinyl, ethynyl, heterocyclic, or heteroaryl group is optionally separated by one or more independent R groups. x replace; R x Selected independently from halogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, OH, halogen, NH2, oxo, thio, NH-(C1-C6 alkyl), N(C1-C6 alkyl)2, CN, NO2, -C1-C6 alkyl C1-C6 alkyl, C3-C 10 Cyclic hydrocarbon group or -C1-C6 alkyl-C3-C 10 Cyclic hydrocarbon group; R y Or R z Each is independently selected from H, deuterium, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxy-substituted alkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, OH, halogen, C2-C6 alkenyl, C2-C6 alkynyl, C3-C 10 Cyclic hydrocarbon group, -C1-C6 alkyl, -C3-C 10 Cyclic hydrocarbon group; p, s, and q are each independently selected from integers from 0 to 5.

2. The compound of formula (I) according to claim 1, or a pharmaceutically acceptable salt thereof, characterized in that, Selected from .

3. The compound of formula (I) according to claim 1, or a pharmaceutically acceptable salt thereof, characterized in that, Selected from , , , , , , , , , , or .

4. The compound of formula (I) according to claim 1, or a pharmaceutically acceptable salt thereof, characterized in that, Selected from or .

5. The compound of formula (I) according to claim 3, or a pharmaceutically acceptable salt thereof, characterized in that, The R2 is independently selected from H, halogen, and -OR. y -SR y -NR y R z , C1-C6 alkyl, C3-C 10 Cycloalkyl, C1-C6 alkoxy, phenyl, 3- to 12-membered heterocyclic, or 5- to 12-membered heteroaryl, wherein the alkyl, cycloalkyl, alkoxy, heterocyclic, or heteroaryl group is optionally separated by one or more independent R groups. x Replace, R x Selected alone from halogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, OH, halogen, NH2, oxo, CN, NO2, or -C1-C6 alkyl C1-C6 alkyl, R y and R z Each is independently selected from H, deuterium, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxy-substituted alkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, OH, halogen, C2-C6 alkenyl, C2-C6 alkynyl, C3-C 10 Cyclic hydrocarbon group, -C1-C6 alkyl, -C3-C 10 Cyclic hydrocarbon group.

6. The compound of formula (I) according to claim 1, or a pharmaceutically acceptable salt thereof, characterized in that, The R3 is selected from (CR) C R C ) 0-2 -C3-C6 cyclic hydrocarbon group, (CR C R C ) 0-2 -Phenyl, containing two 5- or 6-membered rings (CR C R C ) 0-2 -aryl, comprising one or two 5- or 6-membered rings and 1-3 heteroatoms selected from N, O, and S (CR C R C ) 0-2 - Heteroaryl or containing one or two 3- to 6-membered rings and 1-3 heteroatoms selected from N, O, and S (CR C R C ) 0-2 - Heterocyclic group, wherein the cyclic hydrocarbon group, phenyl group, aryl group, heteroaryl group, or heterocyclic group is optionally substituted by one or more substituents independently selected from: C1-C6 alkyl group, C1-C6 haloalkyl group, C3-C6 alkyl group, C4-C6 alkyl group, C5-C6 alkyl group, C6 ... 10 Cycloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, OH, halogen, NH2, NH-(C1-C6 alkyl), N(C1-C6 alkyl)2, CN, NO2, C3-C6 cycloalkyl, phenyl, or heteroaryl; or, when the carbon atom on the cycloalkyl, phenyl, aryl, heteroaryl, or heterocyclic ring is replaced by two C1-C6 alkyl groups, the two C1-C6 alkyl groups together with the carbon atoms to which they are attached form a C3-C... 10 Cyclic hydrocarbon groups; each R C It is independently H, C1-C3 alkyl, or C1-C3 haloalkyl; or two R C Together with the carbon atoms to which they are attached, they form C3-C 10 Cyclic hydrocarbon group; the C3-C 10 The cyclic hydrocarbon group is optionally substituted by one or more substituents independently selected from the following: C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, OH or halogen.

7. The compound of formula (I) according to claim 6, or a pharmaceutically acceptable salt thereof, characterized in that, The R3 is selected from (CR) C R C ) 0-2 -C3-C6 cyclic hydrocarbon group, (CR C R C ) 0-2 -Phenyl, containing two 5- or 6-membered rings (CR C R C ) 0-2 -aryl or containing one or two 5- or 6-membered rings and 1-3 heteroatoms selected from N, O, and S (CR C R C ) 0-2 - Heteroaryl, wherein the cycloalkyl, phenyl, aryl, or heteroaryl group is optionally substituted by one or more substituents independently selected from: C1-C6 alkyl, C1-C6 haloalkyl, C3-C 10 Cyclic hydrocarbon group, C1-C6 alkoxy group, C1-C6 haloalkoxy group, OH, halogen, NH2, NH-(C1-C6 alkyl), N(C1-C6 alkyl)2, CN, NO2 or C3-C6 cyclic hydrocarbon group, each R C Independently, it is H, a C1-C3 alkyl, or a C1-C3 haloalkyl; or when a carbon atom on a cycloalkyl, phenyl, aryl, or heteroaryl ring is replaced by two C1-C6 alkyl groups, the two C1-C6 alkyl groups together with the carbon atoms to which they are attached form a C3-C... 10 Cyclic hydrocarbon group; or two R groups C Together with the carbon atoms to which they are attached, they form C3-C 10 Cyclic hydrocarbon group; the C3-C 10 The cyclic hydrocarbon group is optionally substituted by one or more substituents independently selected from the following: C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, OH or halogen.

8. The compound of formula (I) according to claim 1, or a pharmaceutically acceptable salt thereof, characterized in that, The A is selected from Where E is selected from O or S, and F is independently selected from NR. d , O, S or -C(R) e )2-, the R d R e Each of the following groups is independently selected from H, C1-C6 alkyl, C3-C6 cycloalkyl, and C3-C6 heterocyclic groups, wherein the C1-C6 alkyl, C3-C6 cycloalkyl, and C3-C6 heterocyclic groups are optionally substituted by one or more substituents independently selected from the following: C1-C6 alkyl, C3-C6 cycloalkyl, halogen, methanesulfonyl, ethanesulfonyl, propanesulfonyl, cyclopropanesulfonyl, 3- to 6-membered heterocyclic groups, or 5- to 6-membered heteroaryl groups, wherein the 3- to 6-membered heterocyclic groups or 5- to 6-membered heteroaryl groups contain 1 to 3 heteroatoms selected from N, O, and S.

9. The compound of formula (I) according to claim 1, or a pharmaceutically acceptable salt thereof, characterized in that, The B is selected from a heterocyclic group comprising one or two 5- or 6-membered rings and 1 to 3 heteroatoms selected from N, O, and S, or a heteroaryl group comprising one or two 5- or 6-membered rings and 1 to 3 heteroatoms selected from N, O, and S, wherein the heterocyclic group or the heteroaryl group is optionally substituted by one or more substituents independently selected from: C1-C6 alkoxy-substituted C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C3-C 12 Cyclic hydrocarbon group, OH, halogen, NH2, NH-(C1-C6 alkyl), N(C1-C6 alkyl)2, CN or NO2.

10. The compound of formula (I) according to claim 1, or a pharmaceutically acceptable salt thereof, characterized in that, The A is selected from , where R d Independently selected from H, C1-C3 alkyl; said C1-C3 alkyl is optionally substituted by one or more substituents independently selected from: C1-C6 alkyl, C3-C6 cycloalkyl, halogen, methanesulfonyl, ethanesulfonyl, propanesulfonyl, cyclopropanesulfonyl, 3 to 6-membered heterocyclic or 5 to 6-membered heteroaryl, said 3 to 6-membered heterocyclic or 5 to 6-membered heteroaryl is optionally substituted by one or more substituents independently selected from: halogen, methanesulfonyl, ethanesulfonyl, propanesulfonyl, ... C1-C6 alkyl, C1-C6 alkoxy, C3-C6 cycloalkyl, C3-C6 epoxyalkyl, wherein the C1-C6 alkyl, C3-C6 cycloalkyl, C3-C6 epoxyalkyl are optionally substituted by one or more substituents independently selected from: halogen, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, wherein the 3 to 6 membered heterocyclic group and the 5 to 6 membered heteroaryl group contain 1 to 3 heteroatoms optionally selected from N, O and S, where n is 0 or 1.

11. The compound of formula (I) according to claim 1, or a pharmaceutically acceptable salt thereof, characterized in that, The A is selected from , where R d Independently selected from H, C1-C3 alkyl; said C1-C3 alkyl is optionally substituted by one or more substituents independently selected from: C1-C6 alkyl, C3-C6 cycloalkyl, halogen, methanesulfonyl, ethanesulfonyl, propanesulfonyl, cyclopropanesulfonyl, 3 to 6-membered heterocyclic or 5 to 6-membered heteroaryl, said 3 to 6-membered heterocyclic or 5 to 6-membered heteroaryl is optionally substituted by one or more substituents independently selected from: halogen, methanesulfonyl, ethanesulfonyl, propanesulfonyl, ... C1-C6 alkyl, C1-C6 alkoxy, C3-C6 cycloalkyl, C3-C6 epoxyalkyl, wherein the C1-C6 alkyl, C3-C6 cycloalkyl, C3-C6 epoxyalkyl are optionally substituted by one or more substituents independently selected from: halogen, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, wherein the 3- to 6-membered heterocyclic group and the 5- to 6-membered heteroaryl group contain 1 to 3 heteroatoms selected from N, O and S, and n is 0 or 1.

12. The compound of formula (I) according to claim 1, or a pharmaceutically acceptable salt thereof, characterized in that, R d R e Each is independently selected from H, , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , or .

13. The compound of formula (I) according to claim 1, or a pharmaceutically acceptable salt thereof, characterized in that, The A is selected from , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , or .

14. The compound of formula (I) according to claim 1, or a pharmaceutically acceptable salt thereof, characterized in that, n is 0.

15. The compound of formula (I) according to claim 1, or a pharmaceutically acceptable salt thereof, characterized in that, n is 1.

16. The compound of formula (I) according to claim 1, or a pharmaceutically acceptable salt thereof, characterized in that, The B is selected from , , , , , , , , , , , , , , , , , , , , , or .

17. The compound of formula (I) according to claim 1, or a pharmaceutically acceptable salt thereof, characterized in that, Z is selected from N.

18. The compound of formula (I) according to claim 1, or a pharmaceutically acceptable salt thereof, characterized in that, The C is selected from C=O.

19. The compound of formula (I) according to claim 1, or a pharmaceutically acceptable salt thereof, characterized in that, The R2 is independently selected from halogens, C1-C6 alkyl groups, and C3-C4 alkyl groups. 10 Cycloalkyl, C1-C6 alkoxy, phenyl, vinyl, ethynyl, cyano, heterocyclic group comprising one or two 3- to 6-membered rings and 1-3 heteroatoms selected from N, O, and S, or heteroaryl group comprising one or two 5- or 6-membered rings and 1-3 heteroatoms selected from N, O, and S, wherein the alkyl, cycloalkyl, alkoxy, phenyl, vinyl, ethynyl, heterocyclic, or heteroaryl group is optionally substituted by one or more substituents independently selected from: halogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, OH, halogen, NH2, oxo, NH-(C1-C6 alkyl), N(C1-C6 alkyl)2, CN or NO2, -C1-C6 alkyl C1-C6 alkyl groups.

20. The compound of formula (I) according to claim 1, or a pharmaceutically acceptable salt thereof, characterized in that, R2 is selected from C3-C. 10 Cyclic hydrocarbon group, the C3-C 10 The cyclic hydrocarbon group is optionally substituted by one or more substituents independently selected from the following: C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, OH, halogen, NH2, NH-(C1-C6 alkyl), N(C1-C6 alkyl)2, CN or NO2, wherein the cyclic hydrocarbon group is a spirocyclic hydrocarbon group, a bridged cyclic hydrocarbon group or a monocyclic hydrocarbon group.

21. The compound of formula (I) according to claim 1, or a pharmaceutically acceptable salt thereof, characterized in that, The R2 is selected from vinyl or ethynyl groups, which are optionally substituted by one or more substituents independently selected from the following: , or .

22. The compound of formula (I) according to claim 1, or a pharmaceutically acceptable salt thereof, characterized in that, The R2 is selected from tetrahydropyranyl and optionally substituted by one or more substituents independently selected from the following: C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, OH, halogen, NH2, NH-(C1-C6 alkyl), N(C1-C6 alkyl)2, CN and NO2.

23. The compound of formula (I) according to claim 1, or a pharmaceutically acceptable salt thereof, characterized in that, The L is selected from R4 and R5 are each independently selected from H, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, OH, or halogen; or R4 and R5 together with the carbon atom to which they are attached form a C3-C 10 Cyclic hydrocarbon group, the C3-C 10 The cyclic hydrocarbon group is optionally substituted by one or more substituents independently selected from the following: C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, OH or halogen.

24. The compound of formula (I) according to claim 1, or a pharmaceutically acceptable salt thereof, characterized in that, The T is selected from a heteroaryl group comprising a 5- or 6-membered ring and 1 to 4 heteroatoms selected from N, O, and S, wherein the heteroaryl group is optionally substituted with C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, OH, halogen, or oxo.

25. The compound of formula (I) according to claim 1, or a pharmaceutically acceptable salt thereof, characterized in that, R1 is selected from H, halogens, C1-C6 alkyl groups, and C1-C6 haloalkyl groups.

26. The compound of formula (I) according to claim 1, or a pharmaceutically acceptable salt thereof, characterized in that, The two R1 atoms, together with the atoms they are attached to, form a C3-C6 cyclic hydrocarbon group or a C3-C6 heterocyclic group, wherein the heterocyclic group contains one, two, or three heteroatoms independently selected from O, S, and N, and the C3-C... 10 Cyclic hydrocarbon group or C3-C 12 The heterocyclic group is optionally substituted by one or more substituents independently selected from the following: C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, OH or halogen.

27. The compound of formula (I) according to claim 1, or a pharmaceutically acceptable salt thereof, characterized in that, R3 is selected from , , , , , , , , , , , , , , , , , , , , or .

28. The compound of formula (I) according to claim 1, or a pharmaceutically acceptable salt thereof, characterized in that, R2 is selected from , , , , or .

29. The compound of formula (II) according to claim 1, or a pharmaceutically acceptable salt thereof, characterized in that, The L is selected from , , , , , , , , , , , , , , , , , , or .

30. The compound of formula (I) according to claim 1, or a pharmaceutically acceptable salt thereof, characterized in that, The T is selected from oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, oxadiazolyl, thiazolyl, oxadiazolone, thiazolyl or tetrazolyl, each of which is optionally substituted by C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, OH, halogen or oxo.

31. The compound of formula (I) according to claim 30, or a pharmaceutically acceptable salt thereof, characterized in that, The T is .

32. The compound of formula (I) according to claim 1, or a pharmaceutically acceptable salt thereof, characterized in that, The T is C(O)OH.

33. The compound of formula (I) according to claim 1, or a pharmaceutically acceptable salt thereof, characterized in that, The T is .

34. The compound of formula (I) according to claim 1, or a pharmaceutically acceptable salt thereof, characterized in that... The for .

35. The compound of formula (I) according to claim 1, characterized in that... p is selected from 0, 1 or 2.

36. The compound of formula (I) according to claim 1, characterized in that... The q is selected from 0, 1 or 2.

37. The compound of formula (I) according to claim 1, characterized in that... The s is selected from 0, 1 or 2.

38. The compound of formula (I) according to claim 1, or a pharmaceutically acceptable salt thereof, characterized in that, The compound has the formula (I-1): Wherein, A, B, L, T, R2 and R3 are as defined in claim 1.

39. A compound of the following formula or a pharmaceutically acceptable salt thereof, 。 40. The compound of claim 39 or a pharmaceutically acceptable salt thereof, wherein the compound is selected from, 。 41. A pharmaceutical composition comprising, as an active ingredient, a compound according to any one of claims 1-40 or a pharmaceutically acceptable salt thereof.

42. Use of the compound of any one of claims 1-40 or a pharmaceutically acceptable salt thereof or the pharmaceutical composition of claim 41 in the preparation of a medicament for treating or preventing GLP-1 receptor-mediated diseases or disorders or for modulating GLP-1 receptors.

43. Use of the compound of any one of claims 1-40 or a pharmaceutically acceptable salt thereof or the pharmaceutical composition of claim 41 in the preparation of a medicament for treating non-insulin-dependent type 2 diabetes, hyperglycemia, impaired glucose tolerance, insulin-dependent type 1 diabetes, diabetic complications, obesity, hypertension, hyperlipidemia, arteriosclerosis, coronary heart disease, cerebral infarction, non-alcoholic steatohepatitis, Parkinson's disease, or dementia.

44. Use of a compound of any one of claims 1-40 or a pharmaceutically acceptable salt thereof or a pharmaceutical composition of claim 41 in the preparation of a medicament for treating non-insulin-dependent type 2 diabetes or obesity.

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