[0001] This application claims priority to Indian Provisional Application Number

201611012425, filed on April 8, 2016, which is hereby incorporated by reference in its entireties.

Field of Invention

[0002] The present invention relates to novel GPR119 agonists that are useful in the treatment and prevention of metabolic disorders, including diabetes mellitus (type I and type II), and related disorders, pharmaceutical compositions containing such compounds and methods of preparation thereof.

Background of the Invention

[0003] Diabetes is a life-style related disease derived from multiple causative factors. It is characterized by elevated levels of plasma glucose (hyperglycemia) in the fasting state or after administration of glucose during an oral glucose tolerance test. There are two generally recognized forms of diabetes: type 1 and type 2 diabetes mellitus. In type 1 diabetes, or insulin-dependent diabetes mellitus (IDDM), patients produce little or no insulin, the hormone which regulates glucose utilization. In type 2 diabetes, or noninsulin-dependent diabetes mellitus (T2DM), insulin is still produced in the body, and patients demonstrate resistance to the effects of insulin in stimulating glucose and lipid metabolism in the main insulin-sensitive tissues, namely, muscle, liver and adipose tissue. These patients often have normal levels of insulin, and may have hyperinsulinemia (elevated plasma insulin levels), as they compensate for the reduced effectiveness of insulin by secreting increased amounts of insulin.

[0004] The treatment of T2DM generally begins with weight loss, healthy diet and exercise program. Although these factors are important especially to resolve the increased risk of cardiovascular disorders related to diabetes mellitus, they are not generally effective for control of diabetes mellitus itself. There are many drugs useful for the treatment of diabetes mellitus, including insulin, metformin, sulfonylureas, acarbose, thiazolidinediones, GLP-1 analogue and DPP IV inhibitors. There are, however deficiencies associated with currently available treatment, including hypoglycemic episodes, weight gain, loss in responsiveness to therapy over time, gastrointestinal problems, and edema.

[0005] Although number of receptor classes exist in humans, the most abundant and therapeutically relevant is G protein-coupled receptor (GPCR) class, it is estimated that approximately 4% of the protein-coding genome encodes GPCRs. GPCRs are also known as seven-transmembrane domain receptors as they share a common structural motif, having seven sequences of between 22 to 24 hydrophobic amino acids that form seven alpha helices, each of which spans the membrane. Further, there has been renewed focus on pancreatic islet-based insulin secretion that is controlled by glucose-dependent insulin secretion (GDIS). GPR119 is a cell-surface GPCR that is highly expressed in human (and rodent) islets as well as in insulin-secreting cell lines. Activation of GPR119 stimulate intracellular cAMP leading to glucose dependent GLP-1 and insulin secretion (T.Soga et al Biochem. Biophys. Res. Commun. 2005,326). Synthetic GPR119 agonists augment the release of insulin from isolated static mouse islets only under conditions of elevated glucose, and improve glucose tolerance in diabetic mice and diet-induced obese (DIO) C57/B6 mice without causing hypoglycemia.

[0006] There still remains a need for alternative novel synthetic compounds which acts as

GPR119 agonists and are useful in the treatment and prevention of metabolic disorders, including diabetes mellitus (type I and type II), obesity and related disorders.

Summary of the Invention

[0007] In one aspect, the present invention provides novel compounds of formula (I):

Formula (I)

[0008] wherein,

[0009] Xi, X2, X3 and X4isN, O, S or CH;

[0010] Y is selected from H, OH, halogen, Ci-6 alkyl, Ci-6alkoxy, -(CH)n, amino, -CO, - CONH, -NH(Alkyl), -N(Alkyl)2, -NH-aralkyl, -OCH(CH3);

[0011] n is 0, 1, 2 or 3;

[0012] ^ is independently either a single bond or a double bond, provided that adjacent double bonds (=C=) are not allowed;



[0014] R3 is selected from H, OH, halogen, C1-6 alkyl, Ci-6alkoxy, - , amino, -CO, - CONH, -NH(Alkyl), -N(Alkyl)2, -NH-aralkyl, -CF3, -OCH(CH3), ~

and salts, hydrates and stereoisomers thereof.

[0015] In an embodiment, the invention provides compounds having the formula (II):

(II).

[0016] Preferably, the compounds of this embodiment of the invention have active GLP- 1 secretion greater than -lfold with respect to vehicle.

[0017] Preferably, the compounds of this embodiment of the invention have significant glucose reduction at both 3mpk and lOmpk in glucose tolerance test.

[0018] Preferably, the compounds of this embodiment of the invention show increase in insulin secretion at an EC50 of less than Ι μΜ in an in-vitro model of pancreatic beta cells.

[0019] In one variant, there are provided the compounds wherein Rl is

[0020] In another variant, there are provided the compound of claim 2, wherein Rl is

[0021] In another variant, there are provided the compounds wherein Rl is

[0022] In another variant, there are provided the compounds wherein Rl is

[0023] All individual combination of substituents are separately contemplated.

[0024] In another variant, preferably Y is hydrogen.

[0025] Individual compounds disclosed and claimed herein are individually contemplated, including pharmaceutically acceptable salts, hydrates and stereoisomers.

[0026] In another aspect of the invention, there is provided a method of treating diabetes comprising administering compounds of the invention to a patient in need thereof.

Detailed description of the Invention

[0027] A. Compounds of the present invention

Accordingly, the present invention provides novel compound of Formula I:

Formula (I)

[0028] wherein,

[0029] Xi, X2, X3 and X4 is N, O, S or CH;

[0030] Y is selected from H, OH, halogen, Ci-6 alkyl,
-(CH)n, amino, -CO, - CONH, - H(Alkyl), -N(Alkyl)2, - H-aralkyl, -OCH(CH3);

[0031] n is 0, 1, 2 or 3;

i'

[0032] is independently either a single bond or a double bond, provided that adjacent double bonds (=C=) are not allowed;

Ri is selected from

[0033] R2 is selected from

[0034] R3 is selected from H, OH, halogen, Ci-6 alkyl, Ct-6alkoxy, -(CH)n, amino, -CO, -

CONH, -NH(Alkyl), -N(Alkyl)2, -NH-aralkyl, -CF3,-OCH(CH3), ^H" ^0^;

and salts, hydrates and stereoisomers thereof.

[0035] The term "alkyl" refers to a linear or branched saturated monovalent hydrocarbon, wherein the alkylene may optionally be substituted as described herein. The term "alkyl" also encompasses both linear and branched alkyl, unless otherwise specified. In certain embodiments, the alkyl is a linear saturated monovalent hydrocarbon that has the specified number of carbon atoms, or branched saturated monovalent hydrocarbon of specified number of carbon atoms. As used herein, linear CI- C6 and branched C3- C6 alkyl groups are also referred as "lower alkyl. "Examples of alkyl groups include, but are not limited to, methyl, ethyl, propyl (including allisomeric forms), ^-propyl, isopropyl, butyl (including all isomeric forms), «-butyl, isobutyl, sec-butyl,t-buty\, pentyl (including all isomeric forms), and hexyl (including all isomeric forms). For example, CI - C6 alkyl refers to a linear saturated monovalent hydrocarbon of 1 to 6 carbon atoms or a branched saturated monovalent hydrocarbon of 3 to 6 carbon atoms.

[0036] The term "alkoxy" refers to the group R'O— wherein R' is alkyl. The term "lower alkoxy" refers to alkoxy groups having from 1 to 3 carbon atoms; examples include methoxy, ethoxy, isopropoxy, and the like.

[0037] The term "aralkyl" or "aryl-alkyl" refers to a monovalent alkyl group substituted with aryl. In certain embodiments, the alkyl and aryl moieties are optionally substituted as described herein.

[0038] The term "halogen", "halide" or "halo" refers to fluorine, chlorine, bromine, and iodine.

[0039] The use of terms "a" and "an" and "the" and similar references in the context of describing the invention (especially in the context of the following claims) are to be construed to cover both the singular and the plural, unless otherwise indicated herein or clearly contraindicated by context.

[0040] The term "salt(s)", as employed herein, denotes acidic and/or basic salts formed with inorganic and/or organic acids and bases. Zwitterions (internal or inner salts) are included within the term "salt(s)" as used herein (and may be formed, for example, where the R substituents comprise a basic moiety such as an amino group). Also included herein are quaternary ammonium salts such as alkyl ammonium salts. Pharmaceutically acceptable (i.e., non-toxic, physiologically acceptable) salts are preferred.

[0041] The term "hydrate" as used herein designates a crystalline molecular compound in which water molecules are incorporated into the crystal lattice. Generally speaking, a hydrate thus designates a crystalline form of a molecular compound, whereby the only further molecules incorporated into the crystal lattice are water molecules.

[0042] The term "stereoisomer's" refers to at least two compounds having the same molecular formula and connectivity of atoms, but having a different arrangement of atoms in a three-dimensional space. In view of the present disclosure, a stereoisomer can be, for example, an enantiomer, a diastereomer, or a meso compound.

[0043] The term "GPRl 19" as used herein refers to the G protein-coupled receptor that in humans is encoded by the GPRl 19 gene.

[0044] The present invention provides compound represented by formula (I) that act as

GPRl 19 agonist and is used in the treatment of metabolic disorders, preferably type I and type II diabetes mellitus, obesity and related disorders.

[0045] The compounds of the present invention may be illustrated but not limited to the examples as provided at Table 1.

Table 1: Illustrative compounds of present invention

carboxylate Λ

1038 3-isopropyl-5-(4-(((7-methyl-5-(4- (methylsulfonyl)phenyl)thiazolo[5 ,4-b]pyridin-2- yl)oxy)methyl)piperidin- 1 -yl)- 1,2,4-oxadiazole

1039 3-isopropyl-5-(4-(l-((6-methyl-5- (4- (methylsulfonyl)phenyl)thiazolo[5 ,4-b]pyridin-2- yl)oxy)ethyl)piperidin- 1 -yl)- 1 ,2,4- Λ oxadiazole

1040 5-(4-(cyclopropyl((5-(4- (methylsulfonyl)phenyl)thiazolo[5

,4-b]pyridin-2- yl)oxy)methyl)piperidin- 1 -yl)-3 - isopropyl-l,2,4-oxadiazole

1041 3-isopropyl-5-(4-(2-((5-(4- (methylsulfonyl)phenyl)thiazolo[5 ,4-b]pyridin-2-yl)oxy)ethylidene) piperidin- 1 -yl)- 1 ,2,4-oxadiazole

1042 3-isopropyl-5-(4-(2-((5-(4- (methylsulfonyl)phenyl)thiazolo[5

,4-b]pyridin-2- yl)oxy)ethyl)piperidin- 1 -yl)- 1 ,2,4- oxadiazole Λ

1043 3-isopropyl-5-(4-(2-((5-(4- (methylsulfonyl)phenyl)thiazolo[5 ,4-b]pyridin-2-yl)oxy)propyl) piperidin- 1 -yl)- 1 ,2,4-oxadiazole

1044 3-isopropyl-5- (4- (2 - ((5- (4- N

(methylsulfonyl)phenyl)thiazolo[5 ,4-b]pyridin-2-yl)oxy)

propylidene) piperi din- 1-yl) - 1,2,4- oxadiazole

1045 (S)-4-(2-(l -( 1 -(3 -isopropyl- 1 ,2,4- oxadiazol-5-yl)piperidin-4- yl)ethoxy)thiazolo[5,4-b]pyridin- 5-yl)-N,N-dimethylbenzamide

1046 3 -fluoro-4-(2-( 1 -( 1 -(3 -i sopropyl- l,2,4-oxadiazol-5-yl)piperidin-4- yl)ethoxy)thiazolo[5,4-b]pyridin- 5-yl)-N,N-dimethylbenzamide

claim:

A compound of the formula

wherein,

Xi, X2, X3 and X4 are each independently N, O, S or CH;

Y is selected from H, OH, halogen, Ci-6 alkyl,
-(CH)n, amino, -CO, -CONH, -NH(Alkyl), -N(Alkyl)2, -NH-aralkyl, -OCH(CH3);

, 1, 2 or 3;

is independently either a single bond or a double bond, provided that adjacent double bonds (=C=) are not allowed;

Ri is selected from

R3 is selected from H, OH, halogen, C,_6 alkyl, Ci_6alko -(CH)n, amino, -CO, -CO H, - NH(Alkyl), -N(Alkyl)2, -NH-aralkyl, -CF3, -OCH(CH3),

and pharmaceutically acceptable salts, hydrates and stereoisomers thereof.

The compound of claim 1 having the formula II):

(II).

The compound of claim 2 having active GLP-1 secretion greater than -lfold with respect to vehicle.

The compound of claim 2 having significant dose dependent glucose reduction at both 3mpk and lOmpk in oral glucose tolerance test in rat model.

The compound of claim 2 having significant dose dependent glucose reduction at both 3mpk and lOmpk in oral glucose tolerance test in mice model.

The compound of claim 2 showing increase in insulin secretion at an EC50 of less than Ι μΜ in an in-vitro model of pancreatic beta cells.

The compound of claim 2 wherein Rl is

The compound of claim 2, wherein Rl is

The compound of claim 2, wherein Rl is

10. The compound of claim 2, wherein Y is hydrogen.

11. A compound of claim 1 having the structure:

carboxylate

amine 1018 i sopropyl 4-((5-(4-(dimethyl

carb amoy l)pheny l)thi azol o

[5,4-b]pyridin-2-

yl)(methyl)amino)

piped dine- 1 -carboxylate

1019 i sopropyl (5-(4-(methyl

sulfonyl)phenyl)thiazolo[5,

4-b]pyridin-2-yl) carbonate %X 0

The compound of claim 1 having the structure:

1039 3-isopropyl-5-(4-(l-((6- methyl-5-(4- ¾ XJ °'N

(m ethyl sulfonyl)phenyl)thi Λ

azolo[5,4-b]pyridin-2- yl)oxy)ethyl)piperidin- 1 - yl)- 1 ,2,4-oxadiazole

13. The compound of claim 1 having the structure:

yl)-l,2,4-oxadiazole 1049 N-cyclopropyl-4-(2-( 1 -(1 -(3 - isopropyl- 1 ,2,4-oxadiazol- 5-yl)piperidin-4- yl)ethoxy)thiazolo [5,4- b]pyridin-5-yl)benzamide

1050 4_(2-( 1 -( 1 -(3 -isopropyl- 1 ,2,4- oxadiazol-5-yl)piperidin-4- yl)ethoxy)thiazolo[5,4- b]pyridin-5-yl)-N-(2- methoxyethyl) benzamide

1051 (4-(2-(l -( 1 -(3 -isopropyl- 1 ,2,4- oxadiazol-5-yl)piperidin-4- yl)ethoxy)thiazolo[5,4- b]pyridin-5- yl)phenyl)(morpholino) methanone

1052 N-cyclopropyl-4-(2-( 1 -(1 -(3 - isopropyl- 1 ,2,4-oxadiazol- 5-yl)piperidin-4- yl)ethoxy)thiazolo [5,4- b ] py ri din- 5 -y l)-N-methy 1 benzamide

1053 5-(4-(methylsulfonyl)phenyl)- 2-(l-(l-(5- propylpyrimidin-2-yl) piperidine-4- yl)ethoxy)thiazolo [5,4- b]pyridine

oxadiazole

14. The compound of claim 1 having the structure:

isopropyl- 1 ,2,4-oxadiazole

measure

oxadiazole

15. The compound of claim 1 having the structure:

1090 (R)-5-(4- (methyl sulfonyl)phenyl)-2- * 0 ( 1 -( 1 -(5 -propylpyrimidin- 2-yl)piperidin-4- yl)ethoxy)thiazolo [5,4- b]pyridine

1091 3 -i sopropy 1-5 - (4-(((5 - (6- (methylsulfonyl)pyridin-3- yl)thiazolo[5,4-b]pyridin- o 2-yl)oxy)methyl)piperidin- 1 -yl)- 1 ,2,4-oxadiazole

1092 (S)-3-isopropyl-5-(4-(l-((5- (pyridin-4-yl)thiazolo[5,4- b]pyridin-2-yl)oxy)ethyl) piperidin- 1 -yl)- 1 ,2,4- oxadiazole

1093 (S)-5-(4-(l-((5-(2- fluoropyridin-4- yl)thiazolo[5,4-b]pyridin- F

2-yl)oxy)ethyl)piperidin- 1 - yl)-3 -isopropyl- 1 ,2,4- oxadiazole

1094 3-isopropyl-5-(4-(2,2,2- trifluoro-l-((5-(4- (m ethyl sulfonyl)phenyl) 0 thiazolo[5,4-b]pyridin-2- yl)oxy)ethyl)piperidin- 1 - yl)- 1 ,2,4-oxadiazole

thiazolo [5,4-b]pyridine The compound of claim 1 having the structure

oxadiazole The compound of claim 1 having the structure:

oxadiazole

yl)thiazolo[5,4-b]pyridine N-(5-(2-(l -( 1 -(3 -isopropyl- 1 ,2,4- oxadiazol-5-yl)piperidin-4- yl)ethoxy)thiazolo[5,4- b]pyridin-5-yl)pyrimidin-2-yl)- N-methy 1 acetami de

The compound of claim 1 having the structure:

azolo[5,4-b]pyridine

yl)thiazolo[5,4-b]pyridine

yl)thiazolo[5,4-b]pyridine

azolo[5,4-b]pyridine

19. The compound of claim 1, which is

3-isopropyl-5-(l-(5-(4-(methylsulfonyl)phenoxy)thiazolo[5,4-b]pyridin-2-yl)piperidin-4-yl)- 1,2,4-oxadiazole:

3-isopropyl-5-(4-(((5-(4-(methylsulfonyl)phenoxy)thiazolo[5,4-b]pyridin-2- yl)oxy)methyl)piperidin- 1 -yl)- 1 ,2,4-oxadiazole;

3-isopropyl-5-(l-(2-(4-(methylsulfonyl)phenyl)thiazolo[5,4-b]pyridin-5-yl)piperidin-4-yl)- 1,2,4-oxadiazole;

3-isopropyl-5-(l-(5-(4-(methylsulfonyl)phenyl)thiazolo[5,4-b]pyridin-2-yl)piperidin-4-yl)- 1,2,4-oxadiazole;

3-isopropyl-5-(4-((5-(4-(methylsulfonyl)phenoxy)thiazolo[5,4-b]pyridin-2-yl)oxy)piperidin-1 -yl)- 1 ,2,4-oxadiazole;

3-isopropyl-5-(4-(((5-(4-(methylsulfonyl)phenyl)thiazolo[5,4-b]pyridin-2-yl)oxy)methyl)piperidin- 1 -yl)- 1 ,2,4-oxadiazole;

3-isopropyl-5-(4-((5-(4-(methylsulfonyl)phenyl)thiazolo[5,4-b]pyridin-2-yl)oxy)piperidin-l-yl)-l,2,4-oxadiazole;

2-(4-(5-ethylpyrimidin-2-yl)piperazin-l-yl)-5-(4-(methylsulfonyl)phenyl)thiazolo[5,4-b]pyridine;

5-((l-benzylpiperidin-4-yl)methoxy)-2-(4-(methylsulfonyl)phenyl)thiazolo[5,4-b]pyridine;

2-(4-(5-ethylpyrimidin-2-yl)piperazin-l-yl)-5-(4-(methylsulfonyl)phenoxy)thiazolo[5,4-b]pyridine;

isopropyl 4-(5-(4-(methyl sulfonyl)phenyl)thiazolo[5,4-b]pyridin-2-yl)-5,6-dihydropyridine-1 (2H)-carboxylate;

isopropyl4-(5-(4-(methylsulfonyl)phenyl)thiazolo[5,4-b]pyridin-2-yl) piperazine-1-carboxylate;

isopropyl-4-(5-(4-(methylsulfonyl)phenyl)thiazolo[5,4-b]pyridin-2-yl) piped dine- 1-carboxylate;

1- (5-ethylpyrimidin-2-yl)-N-(5-(4-(methylsulfonyl)phenyl)thiazolo[5,4-b]pyridin-2-yl)piperidine-4-carboxamide;

2- (4-(5-(4-(methylsulfonyl)phenyl)thiazolo[5,4-b]pyridin-2-yl)-5,6-dihydropyridin-l(2H)-yl)ethanol;

isopropyl-4-(methyl(5-(4-(methylsulfonyl)phenyl)thiazolo[5,4-b]pyridin-2-yl)amino )piperidine- 1 -carboxylate;

N-(l-(5-ethylpyrimidin-2-yl)piperidin-4-yl)-N-methyl-5-(4-(methylsulfonyl)phenyl) thiazolo[5,4-b]pyridin-2-amine;

isopropyl 4-((5-(4-(dimethyl carbamoyl)phenyl)thiazolo[5,4-b]pyridin-2-yl)(methyl)amino)piperidine- 1 -carboxylate;

isopropyl (5-(4-(methyl sulfonyl)phenyl)thiazolo[5,4-b]pyridin-2-yl) carbonate;

3- isopropyl-5-(4-(l-((5-(4-(methylsulfonyl)phenyl)thiazolo[5,4-b]pyridin-2-yl)oxy)ethyl)piperidin- 1 -yl)- 1 ,2,4-oxadiazole;

3- isopropyl-5-(l-(5-(4-(methylsulfonyl)phenyl)thiazolo[5,4-b]pyridin-2-yl)pyrrolidin-3-yl)- 1,2,4-oxadiazole;

4- (2-(4-(3-isopropyl-l,2,4-oxadiazol-5-yl)piperidin-l-yl)thiazolo[5,4-b]pyridin-5-yl)-N,N- dimethylbenzamide;

N-(l-(3-isopropyl-l,2,4-oxadiazol-5-yl)piperidin-4-yl)-N-methyl-5-(4- (methylsulfonyl)phenyl)thiazolo[5,4-b]pyridin-2-amine;

4- (2-(4-(3-isopropyl-l,2,4-oxadiazol-5-yl)piperidin-l-yl)thiazolo[5,4-b]pyridin-5-yl)-N-(2- methoxyethyl)benzamide;

N-(3-fluoro-4-(methylsulfonyl)phenyl)-2-(4-(3-isopropyl-l,2,4-oxadiazol-5-yl)piperidin-l- yl)thiazolo[5,4-b]pyridin-5-amine.

20. The compound of claim 1, which is

5- (4-(methylsulfonyl)phenyl)-2-(l-tosyl-l,2,3,6-tetrahydropyridin-4-yl)thiazolo[5,4- b]pyridine;

N,N-dimethyl-4-(5-(4-(methylsulfonyl)phenyl)thiazolo[5,4-b]pyridin-2-yl)-5,6- dihydropyridine- 1 (2H)-carboxamide;

N,N-dimethyl-4-(5-(4-(methylsulfonyl)phenyl)thiazolo[5,4-b]pyridin-2-yl)piperidine-l- carboxamide;

(4-(2-(4-(3-isopropyl-l,2,4-oxadiazol-5-yl)piperidin-l-yl)thiazolo[5,4-b]pyridin-5- yl)phenyl)(morpholino)methanone;

N,N-diisopropyl-4-(5-(4-(methylsulfonyl)phenyl)thiazolo[5,4-b]pyridin-2-yl)-5,6- dihydropyridine- 1 (2H)-carboxamide;

(S)-3-isopropyl-5-(4-(l-((5-(4-(methylsulfonyl)phenyl)thiazolo[5,4-b]pyridin-2- yl)oxy)ethyl)piperidin- 1 -yl)- 1 ,2,4-oxadiazole;

(R)-3-isopropyl-5-(4-(l-((5-(4-(methylsulfonyl)phenyl)thiazolo[5,4-b]pyridin-2- yl)oxy)ethyl)piperidin- 1 -yl)- 1 ,2,4-oxadiazole;

3-cyclopropyl-5-(4-((5-(4-(methylsulfonyl)phenyl)thiazolo[5,4-b]pyridin-2-yl)oxy)piperidin- 1 -yl)- 1 ,2,4-oxadiazole;

isopropyl 4-(2-((5-(4-(methyl sulfonyl)phenyl)thiazolo[5,4-b]pyridin-2-yl)oxy)ethyl)-5,6- dihydropyridine- 1 (2H)-carboxylate;

3-isopropyl-5-(4-(2-((5-(4-(methyl sulfonyl)phenyl)thiazolo[5,4-b]pyridin-2-yl)oxy)ethyl)- 5,6-dihydropyridin- 1 (2H)-yl)- 1 ,2,4-oxadiazole;

3-isopropyl-5-(4-(2-methoxy-l-((5-(4-(methylsulfonyl); phenyl)thiazolo[5,4-b]pyridin-2- yl)oxy)ethyl)piperidin- 1 -yl)- 1 ,2,4-oxadiazole

3-isopropyl-5-(4-(l-((7-methyl-5-(4-(methylsulfonyl)phenyl)thiazolo[5,4-b]pyridin-2- yl)oxy)ethyl)piperidin- 1 -yl)- 1 ,2,4-oxadiazole;

3-isopropyl-5-(4-(((7-methyl-5-(4-(methylsulfonyl)phenyl)thiazolo[5,4-b]pyridin-2- yl)oxy)methyl)piperidin- 1 -yl)- 1 ,2,4-oxadiazole;

3-isopropyl-5-(4-(l-((6-methyl-5-(4-(methylsulfonyl)phenyl)thiazolo[5,4-b]pyridin-2- yl)oxy)ethyl)piperidin- 1 -yl)- 1 ,2,4-oxadiazole;

5-(4-(cyclopropyl((5-(4-(methylsulfonyl)phenyl)thiazolo[5,4-b]pyridin-2- yl)oxy)methyl)piperidin-l-yl)-3-isopropyl-l,2,4-oxadiazole;

3-isopropyl-5-(4-(2-((5-(4-(methylsulfonyl)phenyl)thiazolo[5,4-b]pyridin-2- yl)oxy)ethylidene) piperidin- 1 -yl)- 1 ,2,4-oxadiazole;

3-isopropyl-5-(4-(2-((5-(4-(methylsulfonyl)phenyl)thiazolo[5,4-b]pyridin-2- yl)oxy)ethyl)piperidin- 1 -yl)- 1 ,2,4-oxadiazole.

21. The compound of claim 1, which is

3-isopropyl-5-(4-(2-((5-(4-(methylsulfonyl)phenyl)thiazolo[5,4-b]pyridin-2-yl)oxy)propyl) piperidin- 1 -yl)- 1 ,2,4-oxadiazole;

3-isopropyl-5-(4-(2-((5-(4-(methylsulfonyl)phenyl)thiazolo[5,4-b]pyridin-2- yl)oxy)propylidene) piperidin- 1 -yl)- 1 ,2,4-oxadiazole;

(S)-4-(2-(l-(l-(3-isopropyl-l,2,4-oxadiazol-5-yl)piperidin-4-yl)ethoxy)thiazolo[5,4- b]pyridin-5-yl)-N,N-dimethylbenzamide;

3-fluoro-4-(2-(l-(l-(3-isopropyl-l,2,4-oxadiazol-5-yl)piperidin-4-yl)ethoxy)thiazolo[5,4- b]pyridin-5-yl)-N,N-dimethylbenzamide;

2- fluoro-4-(2-(l-(l-(3-isopropyl-l,2,4-oxadiazol-5-yl)piperidin-4-yl)ethoxy)thiazolo[5,4- b]pyridin-5-yl)-N,N-dimethylbenzamide;

3- cyclopropyl-5-(4-(l-((5-(4-(methylsulfonyl)phenyl)thiazolo[5,4-b]pyridin-2- yl)oxy)ethyl)piperidin- 1 -yl)- 1 ,2,4-oxadiazole;

N-cyclopropyl-4-(2-(l-(l-(3-isopropyl-l,2,4-oxadiazol-5-yl)piperidin-4-yl)ethoxy)thiazolo [5,4-b]pyridin-5-yl)benzamide;

4- (2-(l-(l-(3-isopropyl-l,2,4-oxadiazol-5-yl)piperidin-4-yl)ethoxy)thiazolo[5,4-b]pyridin-5-yl)-N-(2-methoxyethyl)benzamide;

(4-(2-(l-(l-(3-isopropyl-l,2,4-oxadiazol-5-yl)piperidin-4-yl) ethoxy)thiazolo[5,4-b]pyridin- 5- yl)phenyl)(mo holino)methanone;

N-cyclopropyl-4-(2-(l-(l-(3-isopropyl-l,2,4-oxadiazol-5-yl)piperidin-4-yl)ethoxy)thiazolo [5,4-b]pyridin-5-yl)-N-methylbenzamide;

5 -(4-(methyl sulfonyl)phenyl)-2-( 1 -( 1 -(5 -propylpyrimidin-2-yl) piped dine-4-yl)ethoxy)thiazolo [5,4-b]pyridine;

3-isopropyl-5-(4-(l-((5-(pyridin-3-yl)thiazolo[5,4-b]pyridin-2-yl)oxy) ethyl)piperidin-l-yl)-1,2,4-oxadiazole;

2- (l-(l-(5-ethylpyrimidin-2-yl)piperidin-4-yl)ethoxy)-5-(4-(methylsulfonyl)phenyl)thiazolo[5,4-b]pyridine;

isopropyl-4-(l-((5-(4-(methylsulfonyl)phenyl)thiazolo[5,4-b]pyridin-2-yl)oxy)ethyl)piperidine-l-carboxylate;

3- isopropyl-5-(4-(l-((5-(4-((methylsulfonyl)methyl)phenyl)thiazolo[5,4-b]pyridin-2-yl)oxy)ethyl)piperidin- 1 -yl)- 1 ,2,4-oxadiazole;

5-isopropyl-3-(4-(l-((5-(4-(methylsulfonyl)phenyl)thiazolo[5,4-b]pyridin-2-yl)oxy)ethyl)piperidin- 1 -yl)- 1 ,2,4-oxadiazole;

3-isopropyl-5-(4-(l-((5-(4-(methylsulfonyl)phenyl)thiazolo[5,4-b]pyridin-2-yl)oxy)ethyl)phenyl)-l,2,4-oxadiazole;

5-(3-fluoro-4-((5-(4-(methylsulfonyl)phenyl)thiazolo[5,4-b]pyridin-2-yl)oxy)piperidin-l-yl)- 3- isopropyl-l,2,4-oxadiazole;

4- (2-(l-(l-(3-isopropyl-l,2,4-oxadiazol-5-yl)piperidin-4-yl)ethoxy)thiazolo[5,4-b]pyridin-5-yl)-N-methylbenzenesulfonamide;

5- (4-(l-((5-(4-(ethylsulfonyl)phenyl)thiazolo[5,4-b]pyridin-2-yl)oxy)ethyl)piperidin-l-yl)-3-isopropyl-l,2,4-oxadiazole;

5-(4-(l-((5-(4-(cyclopropylsulfonyl)phenyl)thiazolo[5,4-b]pyridin-2-yl)oxy)ethyl)piperidin-1 -yl)-3 -isopropyl- 1 ,2,4-oxadiazole;

5-(4-(l-((5-(4-(cyclopropylsulfinyl)phenyl)thiazolo[5,4-b]pyridin-2-yl)oxy)ethyl)piperidin-l-yl)-3-isopropyl-l,2,4-oxadiazole;

4-(2-(l-(l-(3-isopropyl-l,2,4-oxadiazol-5-yl)piperidin-4-yl)ethoxy)thiazolo[5,4-b]pyridin-5-yl)benzonitrile;

4-(2-(l-(l-(3-isopropyl-l,2,4-oxadiazol-5-yl)piperidin-4-yl)ethoxy)thiazolo[5,4-b]pyridin-5-yl)-N-(2-methoxyethyl)benzene sulfonamide;

3-isopropyl-5-(4-(l-((5-(4-((2-methoxyethyl)sulfonyl)phenyl)thiazolo[5,4-b]pyridin-2-yl)oxy)ethyl) piped din- 1 -yl)- 1 ,2,4-oxadiazole;

3-isopropyl-5-(4-(l-((5-(4-((2-methoxyethyl)sulfinyl)phenyl)thiazolo[5,4-b]pyridin-2-yl)oxy)ethyl) piped din- 1 -yl)- 1 ,2,4-oxadiazole;

3- isopropyl-5-(4-(l-((5-(6-(methylsulfonyl)pyridin-3-yl)thiazolo[5,4-b]pyridin-2-yl)oxy)ethyl)piperidin- 1 -yl)- 1 ,2,4-oxadiazole;

(R)-3-isopropyl-5-(4-(l-((5-(pyridin-4-yl)thiazolo[5,4-b]pyridin-2-yl)oxy)ethyl)piperidin-l-yl)-l,2,4-oxadiazole;

(R)-4-(2-(l-(l-(3-isopropyl-l,2,4-oxadiazol-5-yl)piperidin-4-yl)ethoxy)thiazolo[5,4-b]pyridin-5-yl)- 1 -methylpyridin- 1 -ium;

N,N-dimethyl-4-(2-(l-(l-(5-propylpyrimidin-2-yl)piperidin-4-yl)ethoxy)imidazo[2,l-b][l,3,4] thiadiazol-6-yl)benzamide;

4- (2-(4-(3-isopropyl-l,2,4-oxadiazol-5-yl)piperidin-l-yl)thiazolo[5,4-b]pyridin-5-yl)-N-methylbenzenesulfonamide;

4-(2-(4-(3-isopropyl-l,2,4-oxadiazol-5-yl)piperidin-l-yl)thiazolo[5,4-b]pyridin-5-yl)-N-(2-methoxyethyl) benzenesulfonamide;

N-(4-(2-(l-(l-(3-isopropyl-l,2,4-oxadiazol-5-yl)piperidin-4-yl)ethoxy)thiazolo[5,4-b]pyridin-5-yl)phenyl)methanesulfonamide;

2- (l-(l-(l-methyl-lH-tetrazol-5-yl)piperidin-4-yl)ethoxy)-5-(4-(methylsulfonyl)phenyl)thiazolo[5,4-b]pyridine;

(S)-5-(4-(l-((5-(3-fluoropyridin-4-yl)thiazolo[5,4-b]pyridin-2-yl)oxy)ethyl)piperidin-l-yl)-3-isopropyl-l,2,4-oxadiazole;

3- isopropyl-5-(l-(5-(pyridin-4-yl)thiazolo[5,4-b]pyridin-2-yl)piperidin-4-yl)-l,2,4-oxadiazole;

3-isopropyl-5-(l-(5-(4-((2-methoxyethyl)sulfonyl)phenyl)thiazolo[5,4-b]pyridin-2- yl)piperidin-4-yl)- 1 ,2,4-oxadiazole;

5-(4-(l-((5-(4-(lH-tetrazol-l-yl)phenyl)thiazolo[5,4-b]pyridin-2-yl)oxy)ethyl)piperidin-l- yl)-3-isopropyl-l,2,4-oxadiazole;

3-isopropyl-5-(l-(5-(6-(methylsulfonyl)pyridin-3-yl)thiazolo[5,4-b]pyridin-2-yl)piperidin-4- yl)-l,2,4-oxadiazole;

5-(4-(l-((5-(2-fluoropyridin-4-yl)thiazolo[5,4-b]pyridin-2-yl)oxy)ethyl)piperidin-l-yl)-3- isopropyl-l,2,4-oxadiazole.

22. The compound of claim 1, which is

(S)-3-isopropyl-5-(4-(l-((5-(6-(methylsulfonyl)pyridin-3-yl)thiazolo[5,4-b]pyridin-2- yl)oxy)ethyl)piperidin- 1 -yl)- 1 ,2,4-oxadiazole;

3-isopropyl-5-(4-(((5-(pyridin-4-yl)thiazolo[5,4-b]pyridin-2-yl)oxy)methyl)piperidin-l-yl)- 1,2,4-oxadiazole;

5-(4-(((5-(3-fluoropyridin-4-yl)thiazolo[5,4-b]pyridin-2-yl)oxy)methyl)piperidin-l-yl)-3- isopropyl-l,2,4-oxadiazole;

5-(4-(((5-(4-(lH-tetrazol-l-yl)phenyl)thiazolo[5,4-b]pyridin-2-yl)oxy)methyl)piperidin-l- yl)-3-isopropyl-l,2,4-oxadiazole;

5-(4-(((5-(2-fluoropyridin-4-yl)thiazolo[5,4-b]pyridin-2-yl)oxy)methyl)piperidin-l-yl)-3- isopropyl-l,2,4-oxadiazole;

2- (l-(l-(5-ethylpyridin-2-yl)piperidine-4-yl)ethoxy)-5-(4- (methylsulfonyl)phenyl)thiazolo[5,4-b]pyridine;

5-(4-(methylsulfonyl)phenyl)-2-(l-(l-(5-vinylpyridin-2-yl)piperidin-4- yl)ethoxy)thiazolo[5,4-b]pyridine;

(S)-5-(4-(methylsulfonyl)phenyl)-2-(l-(l-(5-propylpyrimidin-2-yl)piperidin-4- yl)ethoxy)thiazolo [5,4-b]pyridine;

(R)-5-(4-(methylsulfonyl)phenyl)-2-(l-(l-(5-propylpyrimidin-2-yl)piperidin-4- yl)ethoxy)thiazolo [5,4-b]pyridine;

3- isopropyl-5-(4-(((5-(6-(methylsulfonyl)pyridin-3-yl)thiazolo[5,4-b]pyridin-2- yl)oxy)methyl)piperidin- 1 -yl)- 1 ,2,4-oxadiazole;

(S)-3 sopropyl-5-(4-(l-((5-(pyridin-4-yl)thiazolo[5,4-b]pyridin-2-yl)oxy)ethyl)piperidin-l-yl)-l,2,4-oxadiazole;

(S)-5-(4-(l-((5-(2-fluoropyridin-4-yl)thiazolo[5,4-b]pyridin-2-yl)oxy)ethyl)piperidin-l-yl)-3-isopropyl-l,2,4-oxadiazole;

3- isopropyl-5-(4-(2,2,2-trifluoro-l-((5-(4-(methylsulfonyl)phenyl) thiazolo[5,4-b]pyridin-2-yl)oxy)ethyl)piperidin- 1 -yl)- 1 ,2,4-oxadiazole;

(S)-5-(4-(l-((5-(4-(cyclopropylsulfonyl)phenyl)thiazolo[5,4-b]pyridin-2-yl)oxy)ethyl)piperidin-l-yl)-3-isopropyl-l,2,4-oxadiazole;

(S)-5-(4-(l-((5-(3-fluoropyridin-4-yl)thiazolo[5,4-b]pyridin-2-yl)oxy)ethyl)piperidin-l-yl)-3-isopropyl-l,2,4-oxadiazole;

2- isopropyl-5-(4-(l-((5-(4-(methylsulfonyl)phenyl)thiazolo[5,4-b]pyridin-2-yl)oxy)ethyl)piperidin- 1 -yl)- 1 ,3 ,4-oxadiazole;

4- (2-(l-(l-(3-isopropyl-l,2,4-oxadiazol-5-yl)piperidin-4-yl) ethoxy)thiazolo[5,4-b]pyridin-5-yl)pyridine 1 -oxide;

(S)-5-(6-(methylsulfonyl)pyridin-3-yl)-2-(l-(l-(5-propylpyrimidin-2-yl)piperidin-4-yl)ethoxy)thiazolo [5,4-b]pyridine;

5- (4-(l-((5-(3-fluoro-4-(methylsulfonyl)phenyl)thiazolo[5,4-b]pyridin-2-yl)oxy)ethyl)piperidin-l-yl)-3-isopropyl-l,2,4-oxadiazole;

(S)-5-(2-fluoropyridin-4-yl)-2-(l-(l-(5-propylpyrimidin-2-yl)piperidin-4-yl)ethoxy)thiazolo[5,4-b]pyridine;

3- isopropyl-5-(4-(2,2,2-trifluoro-l-((5-(6-(methylsulfonyl)pyridin-3-yl)thiazolo[5,4-b]pyridin-2-yl)oxy) ethyl)piperidin- 1 -yl)- 1 ,2,4-oxadiazole;

3-isopropyl-5-(4-(2,2,2-trifluoro-l-((5-(2-fluoropyridin-4-yl)thiazolo [5,4-b]pyridin-2-yl)oxy)ethyl) piped din- 1 -yl)- 1 ,2,4-oxadiazole;

(S)-2-(l-(l-(5-ethylpyrimidin-2-yl)piperidin-4-yl)ethoxy)-5-(2-fluoropyridin-4-yl)thiazolo[5,4-b]pyridine;

3-isopropyl-5-(4-(l-((5-(4-(methylsulfonyl)phenyl)thiazolo[5,4-b]pyridin-2-yl)oxy)ethyl) cyclohexyl)- 1 ,2,4-oxadiazole;

(S)-2-(l-(l-(5-ethylpyrimidin-2-yl)piperidin-4-yl)ethoxy)-5-(6-(methylsulfonyl)pyridin-3-yl) thiazolo[5,4-b]pyridine;

2- (l-(l-(3-isopropyl-l,2,4-thiadiazol-5-yl)piperidin-4-yl)ethoxy)-5-(4-(methyl sulfonyl)phenyl)thiazolo[5,4-b]pyridine;

3- isopropyl-5-(4-(l-((6-(4-(methyl sulfonyl)phenyl)thiazolo[4,5-b] pyrazin-2- yl)oxy)ethyl)piperidin- 1 -yl)- 1 ,2,4-oxadiazole;

2-(l-(l-(cyclopropylsulfonyl)piperidin-4-yl)ethoxy)-5-(4-(methyl

sulfonyl)phenyl)thiazolo[5,4-b] pyridine;

6-(4-(methylsulfonyl)phenyl)-2-(l-(l-(5-propylpyrimidin-2-yl)piperidin-4- yl)ethoxy)thiazolo[4,5-b]pyrazine;

5-(4-(l-((5-(2-fluoro-4-(methylsulfonyl)phenyl)thiazolo[5,4-b]pyridin-2- yl)oxy)ethyl)piperidin-l-yl)-3-isopropyl-l,2,4-oxadiazole;

5-(3-fluoro-4-(l-((5-(4-(methylsulfonyl)phenyl)thiazolo[5,4-b]pyridin-2- yl)oxy)ethyl)piperidin-l-yl)-3-isopropyl-l,2,4-oxadiazole.

23. The compound of claim 1, which is

2-(l-(l-(5-isopropylpyrimidin-2-yl)piperidin-4-yl)ethoxy)-5-(4- (methylsulfonyl)phenyl)thiazolo[5,4-b]pyridine;

(S)-3-isopropyl-5-(4-(l-((6-(6-(methylsulfonyl)pyridin-3-yl)thiazolo[4,5-b]pyrazin-2-yl)oxy) ethyl)piperidin- 1 -yl)- 1 ,2,4-oxadiazole;

5-(4-(methylsulfonyl)phenyl)-2-(l-(l-(propylsulfonyl)piperidin-4-yl)ethoxy)thiazolo[5,4- b]pyridine;

5-(4-(l-((5-(2-chloropyrimidin-5-yl)thiazolo[5,4-b]pyridin-2-yl) oxy)ethyl)piperidin-l-yl)-3- isopropyl-l,2,4-oxadiazole;

1- methylcyclopropyl4-(l-((5-(4-(methylsulfonyl)phenyl)thiazolo[5,4-b]pyridin-2- yl)oxy)ethyl) piperidine- 1 -carboxylate;

5-(4-(methylsulfonyl)phenyl)-2-(l-(l-(5-(prop-l-en-2-yl)pyrimidin-2-yl)piperidin-4- yl)ethoxy)thiazolo [5,4-b]pyridine;

(S)-5-(4-(l-((5-(2-chloropyrimidin-5-yl)thiazolo[5,4-b]pyridin-2-yl)oxy)ethyl)piperidin-l- yl)-3-isopropyl-l,2,4-oxadiazole;

2- (l-(l-(5-chloropyrimidin-2-yl)piperidin-4-yl)ethoxy)-5-(4- (methylsulfonyl)phenyl)thiazolo[5,4-b]pyridine;

3-isopropyl-5-(4-(l-((5-(thiazol-5-yl)thiazolo[5,4-b]pyridin-2-yl)oxy)ethyl)piperidin-l-yl)-1,2,4-oxadiazole;

3-isopropyl-5-(4-(l-((5-(isoxazol-4-yl)thiazolo[5,4-b]pyridin-2-yl)oxy)ethyl)piperidin-l-yl)-1,2,4-oxadiazole;

3-isopropyl-5-(4-(l-((5-(2-methylpyridin-4-yl)thiazolo[5,4-b]pyridin-2-yl)oxy)ethyl)piperidin- 1 -yl)- 1 ,2,4-oxadiazole;

3-isopropyl-5-(4-(l-((5-(isothiazol-4-yl)thiazolo[5,4-b]pyridin-2-yl)oxy)ethyl)piperidin-l-yl)- 1,2,4-oxadiazole;

3- isopropyl-5-(4-(l-((5-(3-methylisothiazol-4-yl)thiazolo[5,4-b]pyridin-2-yl)oxy)ethyl)piperidin- 1 -yl)- 1 ,2,4-oxadiazole;

4- (2-(l-(l-(3-isopropyl-l,2,4-oxadiazol-5-yl)piperidin-4-yl)ethoxy)thiazolo[5,4-b]pyridin-5-yl)pyridin-2(lH)-one;

4- (2-(l-(l-(3-isopropyl-l,2,4-oxadiazol-5-yl)piperidin-4-yl)ethoxy)thiazolo[5,4-b]pyridin-5-yl)- 1 -methylpyridin-2( 1 H)-one;

5- ((3R,4S)-3-fluoro-4-(((5-(4-(methylsulfonyl)phenyl)thiazolo[5,4-b]pyridin-2-yl)oxy)methyl)piperi din- l-yl)-3-isopropyl- 1,2,4-oxadiazole;

5-((3S,4S)-3-fluoro-4-(((5-(4-(methylsulfonyl)phenyl)thiazolo[5,4-b]pyridin-2-yl)oxy)methyl) piperidin-l-yl)-3-isopropyl-l,2,4-oxadiazole;

3-isopropyl-5-(4-(l-(5-(4-(methyl sulfonyl)phenyl)thiazolo[5,4-b]pyridin-2-yl)ethoxy)piperidin- 1 -yl)- 1 ,2,4-oxadiazole;

5-(4-(l-((5-(4-(methylsulfonyl)phenyl)thiazolo[5,4-b]pyridin-2-yl)oxy)ethyl)piperidin-l-yl)-3 -(trifluoromethyl)- 1 ,2,4-oxadiazole;

5-(4-(l-((5-(2-chloropyridin-4-yl)thiazolo[5,4-b]pyridin-2-yl)oxy)ethyl)piperidin-l-yl)-3-isopropyl-l,2,4-oxadiazole;

3-isopropyl-5-(4-(l-((5-(2-(methylsulfonyl)pyrimidin-5-yl)thiazolo[5,4-b]pyridin-2-yl)oxy)ethyl)piperidin- 1 -yl)- 1 ,2,4-oxadiazole;

3-isopropyl-5-(4-(l-((5-(pyridazin-4-yl)thiazolo[5,4-b]pyridin-2-yl)oxy)ethyl)piperidin-l-yl)- 1,2,4-oxadiazole;

3-isopropyl-5-(4-(l-((5-(pyridazin-4-yl)thiazolo[5,4-b]pyridin-2- yl)oxy)ethyl)piperidin-l-yl)- 1,2,4-oxadiazole;

2-((S)-l-(l-(5-ethylpyrimidin-2-yl)piperidin-4-yl)ethoxy)-5-(2-chloropyrimidin-5- yl)thiazolo[5,4-b]pyridine;

2-((S)-l-(l-(5-chloropyrimidin-2-yl)piperidin-4-yl)ethoxy)-5-(6- (methylsulfonyl)pyridin-3- yl)thiazolo[5,4-b]pyridine;

2-(l-(l-(5-cyclopropylpyrimidin-2-yl)piperidin-4-yl)ethoxy)-5-(6-(methylsulfonyl)pyridin-3- yl)thiazolo[5,4-b]pyridine;

2-((S)-l-(l-(3-isopropyl-l,2,4-oxadiazol-5-yl)piperidin-4-yl)ethoxy)-5-(2- (methylsulfinyl)pyrimidin-5-yl)thiazolo[5,4-b]pyridine;

N-(5-(2-(l-(l-(3-isopropyl-l,2,4-oxadiazol-5-yl)piperidin-4-yl)ethoxy)thiazolo[5,4- b]pyridin-5-yl)pyrimidin-2-yl)-N-methylacetamide;

2-((R)-l-(l-(3-isopropyl-l,2,4-oxadiazol-5-yl)pyrrolidin-3-yl)ethoxy)-5-(6- (methylsulfonyl)pyridin-3-yl)thiazolo[5,4-b]pyridine;

2-((S)- 1 -(1 -(3 -isopropyl- 1 ,2,4-oxadiazol-5-yl)pyrrolidin-3 -yl)ethoxy)-5-(6- (methylsulfonyl)pyridin-3-yl)thiazolo[5,4-b]pyridine;

2-(l-(l-(3-isopropyl-l,2,4-oxadiazol-5-yl)piperidin-4-yl)ethoxy)-5-(6-chloropyridin-3- yl)thiazolo[5,4-b]pyridine.

24. The compound of claim 1, which is

2-((S)-l-(l-(3-isopropyl-l,2,4-oxadiazol-5-yl)piperidin-4-yl)ethoxy)-5-(2-chloropyridin-4- yl)thiazolo[5,4-b]pyridine;

1- (5-(2-(l-(l-(3-isopropyl-l,2,4-oxadiazol-5-yl)piperidin-4-yl)ethoxy)thiazolo[5,4-b]pyridin- 5-yl)pyridin-2-yl)imidazolidin-2-one;

2- ((S)-l-(l-(3-(trifluoromethyl)-l,2,4-oxadiazol-5-yl)piperidin-4-yl)ethoxy)-5-(6- (methylsulfonyl)pyridin-3-yl)thiazolo[5,4-b]pyridine;

1- (5-(2-(l-(l-(3-isopropyl-l,2,4-oxadiazol-5-yl)piperidin-4-yl)ethoxy)thiazolo[5,4-b]pyridin- 5-yl)pyridin-2-yl)pyrrolidin-2-one;

2- (l-(l-(3-isopropyl-l,2,4-oxadiazol-5-yl)piperidin-4-yl)ethoxy)-5-(6- (trifluoromethyl)pyridin-3-yl)thiazolo[5,4-b]pyridine;

2-(l-(l-(5-chloropyrazin-2-yl)piperidin-4-yl)ethoxy)-5-(4- (methylsulfonyl)phenyl)thiazolo[5,4-b]pyridine;

2-(l-(l-(5-ethylpyrimidin-2-yl)piperidin-4-yl)ethoxy)-5-(pyridin-4-yl)thiazolo[5,4-b]pyridine;

2-(l-(l-(5-propylpyrimidin-2-yl)piperidin-4-yl)ethoxy)-5-(pyridin-4-yl)thiazolo[5,4-b]pyridine;

2-(l-(l-(5-chloropyrazin-2-yl)piperidin-4-yl)ethoxy)-5-(6-(methylsulfonyl)pyridin-3-yl)thiazolo[5,4-b]pyridine;

2-((S)-l-(l-(3-isopropyl-l,2,4-oxadiazol-5-yl)piperidin-4-yl)ethoxy)-5-(6-(trifluoromethyl)pyridin-3-yl)thiazolo[5,4-b]pyridine;

2-((S)-l-(l-(5-propylpyrimidin-2-yl)piperidin-4-yl)ethoxy)-5-(pyridin-4-yl)thiazolo[5,4-b]pyridine;

2-((S)-l-(l-(5-ethylpyrimidin-2-yl)piperidin-4-yl)ethoxy)-5-(6-(trifluoromethyl)pyridin-3-yl)thiazolo[5,4-b]pyridine;

2-((S)-l-(l-(3-isopropyl-l,2,4-oxadiazol-5-yl)piperidin-4-yl)ethoxy)-5-(3-fluoro-4-(methylsulfonyl)phenyl)thiazolo[5,4-b]pyridine;

2-(l-(l-(3-ethyl-l,2,4-oxadiazol-5-yl)piperidin-4-yl)ethoxy)-5-(6-(methylsulfonyl)pyridin-3-yl)thiazolo[5,4-b]pyridine;

2-(l-(l-(5-methylpyrimidin-2-yl)piperidin-4-yl)ethoxy)-5-(6-(methylsulfonyl)pyridin-3-yl)thiazolo[5,4-b]pyridine;

2-(l-(l-(3-isopropyl-l,2,4-oxadiazol-5-yl)piperidin-4-yl)ethoxy)-5-(5- (methylsulfonyl)pyrazin-2-yl)thiazolo[5,4-b]pyridine;

2-(l-(l-(5-(trifluoromethyl)pyrimidin-2-yl)piperidin-4-yl)ethoxy)-5-(6- (methylsulfonyl)pyridin-3-yl)thiazolo[5,4-b]pyridine;

2-((S)- 1 -(1 -(3 -ethyl- 1 ,2,4-oxadiazol-5-yl)piperidin-4-yl)ethoxy)-5-(6- (methylsulfonyl)pyridin-3-yl)thiazolo[5,4-b]pyridine;

2-(l-(l-(3-isopropyl-l,2,4-oxadiazol-5-yl)piperidin-4-yl)ethoxy)-5-(5- (methylsulfonyl)pyridin-2-yl)thiazolo[5,4-b]pyridine;

2-(l-(l-(3-isopropyl-l,2,4-oxadiazol-5-yl)piperidin-4-yl)ethoxy)-5-(6- (methylsulfonyl)pyridin-3-yl)thiazolo[5,4-d]pyrimidine;

2-(l-(l-(5-(methoxymethyl)pyrimidin-2-yl)piperidin-4-yl)ethoxy)-5-(6- (methylsulfonyl)pyridin-3-yl)thiazolo[5,4-b]pyridine;

2-((R)-l-(l-(3-isopropyl-l,2,4-oxadiazol-5-yl)piperidin-4-yl)ethoxy)-5-(6- (cyclopropylsulfonyl)pyridin-3-yl)thiazolo[5,4-b]pyridine;

2-((R)- 1 -(1 -(5-(methoxymethyl)pyrimidin-2-yl)piperidin-4-yl)ethoxy)-5-(6- (methylsulfonyl)pyridin-3-yl)thiazolo[5,4-b]pyridine;

2-((S)-l-(l-(5-(trifluoromethyl)pyrimidin-2-yl)piperidin-4-yl)ethoxy)-5-(6- (methylsulfonyl)pyridin-3-yl)thiazolo[5,4-b]pyridine;

2-((S)-l-(l-(3-isopropyl-l,2,4-oxadiazol-5-yl)piperidin-4-yl)ethoxy)-5-(2-fluoro-6- (methylsulfonyl)pyridin-3-yl)thiazolo[5,4-b]pyridine;

2-((R)-l-(l-(3-isopropyl-l,2,4-oxadiazol-5-yl)piperidin-4-yl)ethoxy)-5-(2-methyl-6- (methylsulfonyl)pyridin-3-yl)thiazolo[5,4-b]pyridine;

2-((R)-l-(l-(3-isopropyl-l,2,4-oxadiazol-5-yl)piperidin-4-yl)ethoxy)-5-(2-methyl-4- (methylsulfonyl)phenyl)thiazolo[5,4-b]pyridine.

25. A method of treating diseases and conditions mediated through GPR119 comprising administering the compound of claim 1 to a patient in need thereof.

26. A method of treatment diseases and conditions mediated through GPR119 comprising administering the compound of claim 2 to a patient in need thereof.

27. The method of claim 25, wherein said disease is metabolic disorder.

28. The method of claim 26, wherein said disease is metabolic disorder.

29. The method of claim 25, wherein said disease is diabetes.

30. The method of claim 26, wherein said disease is diabetes.

31. The method of claim 29, wherein said disease is Type II diabetes.

32. The method of claim 30, wherein said disease is Type II diabetes.