GLP-1R Agonist and Therapeutic Method Thereof

1 - 25 . (canceled)

26 . A compound of Formula (I), a stereoisomer, a pharmaceutically acceptable salt, or a deuterated compound thereof:

wherein,

X is selected from the group consisting of N and —CR a ; wherein R a is selected from the group consisting of hydrogen, halogen, and C 1-6 alkyl;

wherein Y is —C(═O)—;

wherein each of Z 3 , Z 4 , Z 5 , Z 6 , Z 7 , Z 8 , Z 9 , Z 10 , Z 11 , Z 12 and Z 13 is independently selected from the group consisting of N and C;

wherein Q 1 is selected from the group consisting of C 6-10 aryl and 5- to 10-membered heteroaryl, wherein C 6-10 aryl or 5- to 10-membered heteroaryl is optionally substituted by one to five substituents independently selected from the group consisting of halogen, C 1-6 alkyl, C 1-6 haloalkyl and C 1-6 alkoxy;

wherein Q 2 is selected from the group consisting of 3- to 12-membered heterocyclic, and 5- to 10-membered heteroaryl, wherein 3- to 12-membered heterocyclic, and 5- to 10-membered heteroaryl are optionally substituted by 1-3 substituents independently selected from the group consisting of halogen, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, and —NR Qa R Qb , or wherein two C 1-6 alkyl groups optionally together with the carbon atoms to which they are attached form C 3-8 carbocyclic ring; wherein R Qa and R Qb are independently selected from the group consisting of hydrogen, C 1-6 alkyl, C 1-6 haloalkyl and (C 1-6 alkyl) carbonyl;

wherein each of R 1 , R 2 , R 3 , R 1 ′, R 2 ′ and R 3 ′ is independently selected from the group consisting of hydrogen, halogen, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, cycloalkyl and heterocycloalkyl; wherein C 1-6 alkyl, cycloalkyl or heterocycloalkyl is optionally substituted by one or more substituents independently selected from the group consisting of halogen, C 1-6 alkoxy and hydroxyl; or

wherein R 2 and R 3 together with the carbon atom to which they are attached form 4- to 8-membered heterocycloalkyl;

each of R 4 , R 5 and R 6 is independently selected from the group consisting of hydrogen, halogen and C 1-6 alkyl;

each of R 7 and R 8 is independently selected from the group consisting of hydrogen and C 1-6 alkyl, wherein C 1-6 alkyl is optionally substituted with one or more substituents independently selected from the group consisting of halogen and C 3-15 cycloalkyl;

or R 7 and R 8 together with the carbon atom to which they are attached form C 3-15 carbocyclic ring, wherein C 3-15 carbocyclic ring is optionally substituted by one to three C 1-6 alkyl, wherein C 1-6 alkyl is optionally substituted by one or more substituents independently selected from the group consisting of halogen, hydroxyl, —NR 7a R 7b , C 1-6 alkoxy and 3- to 12-membered heterocyclic, and R 7a and R 7b are independently selected from the group consisting of hydrogen, C 1-6 alkyl and (C 1-6 alkyl) carbonyl; and any two C 1-6 alkyl optionally together with the carbon atom to which they are attached form C 3-15 carbocyclic ring;

n1 is 0, 1, 2 or 3;

n2 is 0, 1, 2, 3, 4 or 5;

n3 is 0 or 1;

R 9 is selected from the group consisting of:

—CO 2 R 9f and —C(═O)—NR 9g R 9h ; and each of R 9a , R 9b , R 9c , R 9d and R 9g is independently selected from the group consisting of hydrogen, C 1-6 alkyl and (C 1-6 alkyl) carbonyl, wherein C 1-6 alkyl is optionally substituted with one or more substituents independently selected from the group consisting of halogen and C 1-6 alkoxy;

R 9e is selected from the group consisting of hydrogen and C 1-6 alkyl optionally substituted by one or more halogen;

R 9f is selected from the group consisting of hydrogen and C 1-6 alkyl;

R 9h is selected from the group consisting of hydrogen, C 1-6 alkyl, (C 1-6 alkyl) carbonyl, cyano and —S(═O) n9 —R 9i ; n9 is 0, 1 or 2;

R 9i is C 1-6 alkyl;

Z 1 is selected from the group consisting of:

wherein R za is selected from the group consisting of hydrogen, C 1-6 alkyl and (C 1-6 alkyl) carbonyl, and each of R zb and R zc is independently selected from the group consisting of hydrogen and C 1-6 alkyl;

n4 is 1, 2 or 3;

each of n5 and n6 is independently an integer selected from 0 to 10;

Z 2 is 5- to 10-membered heteroaryl; and Z 2 is substituted with one halogen and one of C 3 -C 15 cycloalkyl and C 1 -C 6 alkyl-C 3 -C 15 cycloalkyl; wherein the cycloalkyl or alkyl is optionally substituted by one or more substituents independently selected from the group consisting of halogen, oxo, C 1-6 alkyl, C 1-6 alkoxy and (C 1-6 alkyl) carbonyl, wherein each of alkyl and alkoxy is optionally substituted with halogen.

27 . The compound, the stereoisomer, the pharmaceutically acceptable salt, or the deuterated compound thereof of claim 26 , wherein Z 2 is indazolyl.

28 . The compound, the stereoisomer, the pharmaceutically acceptable salt, or the deuterated compound thereof of claim 27 , wherein the indazolyl is substituted with one halogen and one of C 3 -C 15 cycloalkyl and C 1 -C 6 alkyl-C 3 -C 15 cycloalkyl.

29 . The compound, the stereoisomer, the pharmaceutically acceptable salt, or the deuterated compound thereof of claim 28 , wherein Q 1 is C 6-10 aryl, and C 6-10 aryl is optionally substituted with one to five substituents selected from the group consisting of halogen, C 1-6 alkyl, C 1-6 haloalkyl and C 1-6 alkoxy.

30 . The compound, the stereoisomer, the pharmaceutically acceptable salt, or the deuterated compound thereof of claim 26 , wherein the compound is selected from the group consisting of

31 . The compound, the stereoisomer, the pharmaceutically acceptable salt, or the deuterated compound thereof of claim 26 , wherein the compound has a structure of Formula (II),

wherein ring A is selected from the group consisting of cyclopropyl, cyclobutyl, and cyclopentyl;

t is 0 or 1; and

R qm and R qn are each independently selected from the group consisting of hydrogen and C 1-6 alkyl.

32 . The compound, the stereoisomer, the pharmaceutically acceptable salt, or the deuterated compound thereof of claim 26 , wherein the compound is selected from the group consisting of

33 . A compound, a stereoisomer, a pharmaceutically acceptable salt, or a deuterated compound thereof of Formula (III),

wherein

X is —CR a ; R a is H;

Y is —C(═O)—;

Z 3 , Z 4 , Z 5 , Z 6 , Z 8 , Z 9 , Z 10 , Z 12 and Z 13 are C;

Z 7 and Z 11 are N;

Q 1 is C 6-10 aryl, wherein C 6-10 aryl is optionally substituted with one to five substituents independently selected from the group consisting of halogen and C 1-6 alkyl;

Q 2 is 3- to 12-membered heterocyclic, wherein 3- to 12-membered heterocyclic is optionally substituted with 1-3 substituents independently selected from the group consisting of halogen and C 1-6 alkyl, or wherein two C 1-6 alkyl groups optionally together with the carbon atoms to which they are attached form C 3-8 carbocyclic ring;

wherein each of R 1 , R 2 , R 1 ′, and R 2 ′ is independently selected from the group consisting of hydrogen and C 1-6 alkyl;

R 3 and R 3 ′ are independently selected from the group consisting of hydrogen and C 1-6 alkyl;

R 4 , R 5 and R 6 are H;

each of R 7 and R 8 is independently selected from the group consisting of hydrogen and C 1-6 alkyl; or R 7 and R 8 together with the carbon atom to which they are attached form C 3-15 carbocyclic ring, wherein C 3-15 carbocyclic ring is optionally substituted by one to three C 1-6 alkyl;

n1 is 0 or 1;

n2 is 0 or 1;

n3 is 1;

R 9 is

and R 9a is H;

Z 1 is

Z 2 is 5- to 10-membered heteroaryl, and Z 2 is substituted with one halogen and one of C 3 -C 15 cycloalkyl and C 1 -C 6 alkyl-C 3 -C 15 cycloalkyl; wherein the cycloalkyl or alkyl is optionally substituted with one or more substituents independently selected from the group consisting of halogen, oxo, C 1-6 alkyl, C 1-6 alkoxy and (C 1-6 alkyl) carbonyl, wherein each of alkyl and alkoxy is optionally substituted with halogen.

34 . The compound, the stereoisomer, the pharmaceutically acceptable salt, or the deuterated compound thereof of claim 33 , wherein Q 1 is

and R n1 and R n3 are each independently selected from the group consisting of H, methyl, and ethyl; and R n2 is halogen.

35 . The compound, the stereoisomer, the pharmaceutically acceptable salt, or the deuterated compound thereof of claim 33 , wherein Q 2 is

wherein R qm and R qn are each independently selected from the group consisting of H, methyl, and ethyl; or R qm and R qn together with the carbon atom to which they are attached form C 3-6 cycloalkyl; p is 0, 1, or 2.

36 . The compound, the stereoisomer, the pharmaceutically acceptable salt, or the deuterated compound thereof of claim 33 , wherein Z 2 is

wherein R z1 is halogen;

m1 is 1;

R z2 is selected from the group consisting of C 3-8 cycloalkyl and C 1-6 alkyl-C 3-8 cycloalkyl; and R z2 is optionally substituted with one or more substituents selected from the group consisting of halogen, C 1-6 alkyl, and C 1-6 alkoxy.

37 . The compound, the stereoisomer, the pharmaceutically acceptable salt, or the deuterated compound thereof of claim 33 , wherein Z 2 is

R z1 is selected from the group consisting of F, Cl, and Br;

R z2 is selected from the group consisting of

38 . The compound, the stereoisomer, the pharmaceutically acceptable salt, or the deuterated compound thereof of claim 33 , wherein Z 2 is selected from the group consisting of

and Z 2 is substituted with one halogen.

39 . The compound, the stereoisomer, the pharmaceutically acceptable salt, or the deuterated compound thereof of claim 33 , wherein Z 2 is selected from the group consisting of

40 . A compound, a stereoisomer, a pharmaceutically acceptable salt, or a deuterated compound thereof of Formula (IV),

wherein:

each of X, Z 4 and Z 6 is independently selected from the group consisting of N and CH;

R z1 is selected from the group consisting of halogen, C 1-3 alkyl, and C 3-8 cycloalkyl;

R z2 is selected from the group consisting of C 3-8 cycloalkyl and C 1-6 alkyl-C 3-8 cycloalkyl; and R z2 is optionally substituted with substituents independently selected from the group consisting of halogen, —OH, C 1-6 alkyl, and C 1-6 alkoxy; and

m1 is 0, 1, 2 or 3.

41 . The compound, the stereoisomer, the pharmaceutically acceptable salt, or the deuterated compound thereof of claim 40 , wherein

R m is selected from the group consisting of H, C 1-6 alkyl, C 1-6 haloalkyl, and C 1-6 alkoxy;

R n is selected from the group consisting of halogen, C 1-6 alkyl, C 1-6 haloalkyl, and C 1-6 alkoxy;

m is 0, 1, 2, or 3; and

R 3 is selected from the group consisting of H, halogen, C 1-6 alkyl, C 1-6 alkoxy and C 1-6 haloalkoxy.

42 . The compound, the stereoisomer, the pharmaceutically acceptable salt, or the deuterated compound thereof of claim 40 , wherein

R z1 is selected from the group consisting of F, Cl, Br, methyl, ethyl, n-Propyl, isopropyl and cyclopropyl;

m is 0, 1, 2, or 3;

R z2 is selected from the group consisting of

R m is independently selected from the group consisting of halogen, —CH 3 , —CH 2 CH 3 and —OCH 3 ;

R n is selected from the group consisting of methyl, ethyl, F and Cl; and

R 3 is methyl.

43 . The compound, the stereoisomer, the pharmaceutically acceptable salt, or the deuterated compound thereof of claim 40 , wherein Q 2 is

wherein R qm and R qn are each independently selected from the group consisting of H, methyl, and ethyl;

or R qm and R qn together with the carbon atom to which they are attached form a C 3-6 cycloalkyl; and p is 0, 1, or 2.

44 . The compound, the stereoisomer, the pharmaceutically acceptable salt, or the deuterated compound thereof of claim 40 , wherein Q 2 is selected from the group consisting of

45 . A compound, a stereoisomer, a pharmaceutically acceptable salt, or a deuterated compound thereof of Formula (V)

wherein:

each of X, Z 4 and Z 6 is independently selected from the group consisting of N and CH;

Q 2 is selected from the group consisting of

R n is selected from the group consisting of halogen, C 1-6 alkyl, C 1-6 haloalkyl and C 1-6 alkoxy;

m is 0, 1, 2 or 3;

R z2 is selected from the group consisting of C 3-8 cycloalkyl and C 1-6 alkyl-C 3-8 cycloalkyl; and R z2 is optionally substituted with substituents independently selected from the group consisting of halogen, hydroxyl, C 1-6 alkyl and C 1-6 alkoxy.

46 . The compound, the stereoisomer, the pharmaceutically acceptable salt, or the deuterated compound thereof of claim 45 , wherein R z2 is selected from the group consisting of

R n is selected from the group consisting of methyl, ethyl, F, and Cl.

47 . The compound, the stereoisomer, the pharmaceutically acceptable salt, or the deuterated compound thereof of claim 45 , wherein the compound has a structure of Formula (VI),

wherein:

each of X, Z 4 and Z 6 is independently selected from the group consisting of N and CH;

R z2 is selected from the group consisting of C 3-8 cycloalkyl and C 1-6 alkyl-C 3-8 cycloalkyl; and R z2 is optionally substituted with substituents independently selected from the group consisting of halogen, hydroxyl, C 1-6 alkyl and C 1-6 alkoxy;

Q 2 is selected from the group consisting of

48 . The compound, the stereoisomer, the pharmaceutically acceptable salt, or the deuterated compound thereof of claim 47 ,

wherein R z2 is selected from the group consisting of

49 . The compound, the stereoisomer, the pharmaceutically acceptable salt, or the deuterated compound thereof of claim 45 , wherein the compound has a structure of Formula (VII),

R z2 is selected from the group consisting of C 3-8 cycloalkyl and C 1-6 alkyl-C 3-8 cycloalkyl; and R z2 is optionally substituted with substituents independently selected from the group consisting of halogen, hydroxyl, C 1-6 alkyl and C 1-6 alkoxy; and

Q 2 is selected from the group consisting of

50 . The compound, the stereoisomer, the pharmaceutically acceptable salt, or the deuterated compound thereof of claim 49 , wherein R z2 is selected from the group consisting of

51 . A compound, a stereoisomer, a pharmaceutically acceptable salt, or a deuterated compound thereof of Formula (VIII),

wherein each of X, Z 4 and Z 6 is independently selected from the group consisting of N and CH;

R m is selected from the group consisting of H, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy and C 1-6 haloalkoxy;

R n1 and R n3 are each independently selected from the group consisting of hydrogen, halogen, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, and C 1-6 haloalkoxy; R n2 is halogen;

R 3 is selected from the group consisting of hydrogen, halogen, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy and C 1-6 haloalkoxy;

R z1 is selected from the group consisting of hydrogen, halogen, C 1-3 alkyl and C 3-8 cycloalkyl;

R z2 is selected from the group consisting of

and

R qm and R qn are each independently selected from the group consisting of H, methyl, and ethyl, or R qm and R qn together with the carbon atom to which they are attached form a C 3-6 cycloalkyl.

52 . The compound, the stereoisomer, the pharmaceutically acceptable salt, or the deuterated compound thereof of claim 51 , wherein,

R m is independently selected from the group consisting of halogen, —CH 3 , —CH 2 CH 3 and —OCH 3

R n1 and R n3 are each independently selected from the group consisting of hydrogen, methyl, and ethyl;

R n2 is F;

R 3 is methyl; and

R z1 is selected from the group consisting of hydrogen, F, Cl, methyl, ethyl, n-propyl, isopropyl, and cyclopropyl.

53 . A compound, a stereoisomer, a pharmaceutically acceptable salt, or a deuterated compound thereof of Formula (IX),

wherein each of X, Z 4 and Z 6 is independently selected from the group consisting of N and CH;

Z 2 is selected from the group consisting of

R n is selected from the group consisting of halogen, C 1-6 alkyl, C 1-6 haloalkyl and C 1-6 alkoxy; and

m is 0, 1, 2 or 3.

54 . The compound the stereoisomer, the pharmaceutically acceptable salt or the deuterated compound thereof of claim 53 , wherein

R m is selected from the group consisting of H, C 1-6 alkyl, C 1-6 haloalkyl, and C 1-6 alkoxy;

R 3 is selected from the group consisting of H, halogen, C 1-6 alkyl, C 1-6 alkoxy and C 1-6 haloalkoxy; and

R 10 and R 11 is independently selected from the group consisting of H, F, Cl, methyl, ethyl, n-propyl, isopropyl, and cyclopropyl.

55 . The compound, the stereoisomer, the pharmaceutically acceptable salt, or the deuterated compound thereof of claim 53 , wherein R m is independently selected from the group consisting of halogen, —CH 3 , —CH 2 CH 3 and —OCH 3 ; and R n is independently selected from the group consisting of —CH 3 , —CH 2 CH 3 , F, and Cl; R 3 is —CH 3 .

56 . The compound, the stereoisomer, the pharmaceutically acceptable salt, or the deuterated compound thereof of claim 53 , wherein Z 2 is selected from the group consisting of

57 . The compound, the stereoisomer, the pharmaceutically acceptable salt, or the deuterated compound thereof of claim 53 , wherein Q 2 is

wherein R qm and R qn are each independently selected from the group consisting of H, methyl, and ethyl; or R qm and R qn together with the carbon atom to which they are attached form a C 3-6 Cycloalkyl; p is 0, 1, or 2.

58 . The compound, the stereoisomer, the pharmaceutically acceptable salt, or the deuterated compound thereof of claim 53 , wherein Q 2 is selected from the group consisting of

59 . The compound, the stereoisomer, the pharmaceutically acceptable salt, or the deuterated compound thereof of claim 53 , wherein the compound is selected from the group consisting of

60 . A compound of Formula (X), a stereoisomer, a pharmaceutically acceptable salt, or a deuterated compound thereof,

wherein:

each of X, Z 4 and Z 6 is independently selected from the group consisting of N and CH;

m is 0, 1, 2 or 3;

R p is selected from the group consisting of —CH 2 —P(═O)R zm R zn and —P(═O)OR zm OR zn ;

R q is selected from the group consisting of halogen, —NH—C 1-6 alkyl, —C 1-6 alkyl, —O—C 1-6 alkyl, 3- to 12-membered heterocyclic, C 3 -C 15 cycloalkyl and C 1 -C 6 alkyl-C 3 -C 15 cycloalkyl;

wherein each of R zm and R zn is independently selected from the group consisting of hydrogen, C 1-6 alkyl and C 6-10 aryl; or R zm and R zn together with the phosphorous atom to which they are attached form 5- to 8-membered heterocycloalkyl, wherein the heterocycloalkyl is optionally substituted with one to three C 1-6 alkyl.

61 . The compound, the stereoisomer, the pharmaceutically acceptable salt, or the deuterated compound thereof of claim 60 , wherein R p is selected from the group consisting of

R m is selected from the group consisting of H, C 1-6 alkyl, C 1-6 haloalkyl, and C 1-6 alkoxy;

R n is selected from the group consisting of halogen, C 1-6 alkyl, C 1-6 haloalkyl, and C 1-6 alkoxy;

m is 0, 1, 2, and 3; and

R 3 is selected from the group consisting of H, halogen, C 1-6 alkyl, C 1-6 alkoxy and C 1-6 haloalkoxy.

62 . The compound, the stereoisomer, the pharmaceutically acceptable salt, or the deuterated compound thereof of claim 60 , wherein R m is selected from the group consisting of H, methyl, ethyl and methoxy; R n is selected from the group consisting of methyl, ethyl, F and Cl; and R 3 is methyl.

63 . The compound, the stereoisomer, the pharmaceutically acceptable salt, or the deuterated compound thereof of claim 60 , wherein Q 2 is

wherein R qm and R qn are each independently selected from the group consisting of H, methyl, and ethyl; or R qm and R qn together with the carbon atom to which they are attached form C 3-6 cycloalkyl; and p is 0, 1, or 2.

64 . The compound, the stereoisomer, the pharmaceutically acceptable salt, or the deuterated compound thereof of claim 60 , wherein Q 2 is selected from the group consisting of

65 . The compound, the stereoisomer, the pharmaceutically acceptable salt, or the deuterated compound thereof of claim 60 , wherein the compound is selected from the group consisting of

66 . A compound of Formula (XI), a stereoisomer, a pharmaceutically acceptable salt, or a deuterated compound thereof:

wherein:

Q 1 is C 6-10 aryl, and the C 6-10 aryl is optionally substituted with one to five substituents selected from the group consisting of halogen, C 1-6 alkyl, C 1-6 haloalkyl and C 1-6 alkoxy;

Q 2 is selected from the group consisting of 3- to 12-membered heterocyclic, and 5- to 10-membered heteroaryl, wherein 3- to 12-membered heterocyclic, and 5- to 10-membered heteroaryl are optionally substituted by 1-3 substituents independently selected from the group consisting of halogen, C 1-6 alkyl, C 1-6 haloalkyl, and C 1-6 alkoxy, wherein two C 1-6 alkyl groups optionally together with the carbon atoms to which they are attached form a C 3-8 carbocyclic ring;

X 1 , X 2 , and X 3 are independently selected from the group consisting of N and C;

X 4 , and X 5 are independently selected from the group consisting of N and C;

R m is selected from the group consisting of H, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy and C 1-6 haloalkoxy; and

R z2 is selected from the group consisting of C 3-8 cycloalkyl and C 1-6 alkyl-C 3-8 cycloalkyl.

67 . The compound, the stereoisomer, the pharmaceutically acceptable salt, or the deuterated compound thereof of claim 66 , wherein

Q 1 is

and R n1 and R n3 are each independently selected from the group consisting of H, methyl, and ethyl; R 2 is halogen;

Q 2 is selected from the group consisting of

and

R z2 is selected from the group consisting of

68 . The compound, the stereoisomer, the pharmaceutically acceptable salt, or the deuterated compound thereof of claim 66 , wherein the compound is selected from the group consisting of

69 . A compound, a stereoisomer, a pharmaceutically acceptable salt, or a deuterated compound thereof, wherein the compound is selected from the group consisting of:

70 . A pharmaceutical composition, comprising the compound, the stereoisomer, the pharmaceutically acceptable salt, or the deuterated compound thereof of claim 26 , and a pharmaceutically acceptable excipient.

71 . A method for treating a GLP-1R-mediated disease or condition, comprising administering to a subject in need thereof a therapeutically effective amount of the compound, the stereoisomer, the pharmaceutically acceptable salt, or the deuterated compound thereof of claim 26 .

72 . The method of claim 71 , wherein the GLP-1R-mediated disease or condition is selected from the group consisting of T1D (type 1 diabetes), T2DM (type 2 diabetes mellitus), pre-diabetes, idiopathic T1D (idiopathic type 1 diabetes), LADA (latent autoimmune diabetes in adults), EOD (early onset diabetes), YOAD (young onset adult diabetes), MODY (maturity onset diabetes of the young), malnutrition-related diabetes, gestational diabetes, hyperglycemia, insulin resistance, hepatic insulin resistance, impaired glucose tolerance, diabetic neuropathy, diabetic nephropathy, kidney disease, diabetic retinopathy, adipocyte dysfunction, visceral adipose deposition, sleep apnea, obesity, overweight, eating disorders, weight gain from use of other agents, excessive sugar craving, dyslipidemia, hyperinsulinemia, NAFLD, NASH, fibrosis, cirrhosis, hepatocellular carcinoma, cardiovascular disease, atherosclerosis, coronary artery disease, peripheral vascular disease, hypertension, endothelial dysfunction, impaired vascular compliance, congestive heart failure, myocardial infarction, stroke, hemorrhagic stroke, ischemic stroke, traumatic brain injury, pulmonary hypertension, restenosis after angioplasty, intermittent claudication, post-prandial lipemia, metabolic acidosis, ketosis, arthritis, osteoporosis, parkinson's disease, left ventricular hypertrophy, peripheral arterial disease, macular degeneration, cataract, glomerulosclerosis, chronic renal failure, metabolic syndrome, syndrome X, premenstrual syndrome, angina pectoris, thrombosis, atherosclerosis, transient ischemic attacks, vascular restenosis, impaired glucose metabolism, conditions of impaired fasting plasma glucose, hyperuricemia, gout, erectile dysfunction, skin and connective tissue disorders, psoriasis, foot ulcerations, ulcerative colitis, hyper apo B lipoproteinemia, alzheimer's disease, schizophrenia, impaired cognition, inflammatory bowel disease, short bowel syndrome, crohn's disease, colitis, irritable bowel syndrome, polycystic ovary syndrome, substance addiction, chronic kidney disease, atherosclerotic cardiovascular disease, heart failure, heart failure with reduced ejection fraction, heart failure with preserved ejection fraction and obstructive sleep apnea.

73 . A method for weight management, chronic weight management or diabetes prevention, comprising administering to a subject in need thereof an effective amount of the compound, the stereoisomer, the pharmaceutically acceptable salt, or the deuterated compound thereof of claim 26 .