LXR modulators with a bicyclic core moiety for the treatment of dyslipidemia

Abstract

The present disclosure relates to novel compounds that are liver X receptor (LXR) modulators, and pharmaceutical compositions containing the same. The disclosure further relates to the use of the compounds in the prevention and / or treatment of diseases associated with LXR modulation, such as dyslipidemia. The disclosure further relates to the use of the compounds in the prevention and / or treatment of metabolic disorders associated with impaired lipid homeostasis. In some variations, the method is directed to treating dyslipidemia. In other variations, the method is directed to metabolic disorders, such as those associated with impaired lipid homeostasis. In some variations, the method of treatment is achieved by administering a compound of Formula (I) or a pharmaceutically acceptable salt thereof.

Description

[Technical Field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims the benefit of U.S. Provisional Application No. 63 / 382,217, filed November 3, 2022, the contents of which are incorporated herein by reference in their entirety.

[0002] The present disclosure relates to novel compounds that are liver X receptor (LXR) modulators, and pharmaceutical compositions containing the same. The present disclosure further relates to the use of the compounds in the prevention and / or treatment of diseases associated with LXR modulation, such as dyslipidemia. The present disclosure further relates to the use of the compounds in the prevention and / or treatment of metabolic disorders associated with impaired lipid homeostasis. [Background technology]

[0003] The liver X receptors, LXRα (NR1H3) and LXRβ (NR1H2), are members of the nuclear receptor protein superfamily. Both receptors form heterodimeric complexes with retinoid X receptors (RXRα, β, or γ) and bind to LXR-responsive elements (e.g., DR4 elements) located in the promoter regions of LXR-responsive genes. Both receptors are transcription factors physiologically regulated by the binding of ligands such as oxysterols or intermediates in the cholesterol biosynthetic pathway, such as desmosterol. In the absence of ligand, the LXR-RXR heterodimer remains bound to the DR4 element in complex with a corepressor such as NCOR1, leading to the repression of the corresponding target genes. Upon binding of an agonist ligand, either endogenous, such as the aforementioned oxysterols or steroid intermediates, or synthetic pharmacological ligands, the conformation of the heterodimeric complex changes, leading to the release of corepressor proteins and the recruitment of coactivator proteins, such as NCOA1 (SRC1), resulting in the transcriptional stimulation of their respective target genes. While LXRβ is expressed in most tissues, LXRα is more selectively expressed in liver, intestinal, and adipose tissue cells and macrophages. The relative expression of LXRα and LXRβ at the mRNA or protein level can vary between different tissues of the same species or between different species within a given tissue. LXR-regulated reverse cholesterol transport, i.e., the transfer of peripheral cholesterol bound to tissues to HDL and from there to bile and feces, is mediated by the transcriptional regulation of target genes such as ABCA1 and ABCG1 in macrophages and ABCG5 and ABCG8 in the liver and intestine. This explains the antiatherogenic effect of LXR agonists in the diet-induced LDLR-KO mouse model. However, LXR also regulates the transcription of genes involved in adipogenesis (e.g., Srebp1c, Scd1, Fasn), which contributes to the hepatic steatosis observed after long-term treatment with LXR agonists. Summary of the Invention

[0004] The present disclosure relates to a method of treating a metabolic disorder associated with dyslipidemia or impaired lipid homeostasis, or a method of treating such a metabolic disorder in a subject in need thereof, the method comprising administering to a subject a compound of formula (I): [ka] and administering to a subject in need of treatment an effective amount of a compound represented by the formula: glycine conjugate, tauro conjugate, enantiomer, diastereomer, tautomer, N-oxide, solvate, prodrug, and pharmaceutically acceptable salt thereof, wherein rings A, B, C, D, and residues L and R 1 is described herein.

[0005] In some variations, the methods are directed to treating dyslipidemia. In other variations, the methods are directed to metabolic disorders, such as those associated with impaired lipid homeostasis. In some variations, the methods of treatment are achieved by administering a compound of Formula (I) or a pharmaceutically acceptable salt thereof.

[0006] The compounds of the present disclosure exhibit favorable liver / blood ratios after oral administration, allowing them to avoid disruption of anti-atherosclerotic reverse cholesterol transport mediated by LXR in peripheral macrophages. The incorporation of an acidic moiety (or its biological equivalent) can improve additional parameters, such as microsomal stability, solubility, and lipophilicity.

[0007] That is, the present disclosure further relates to a pharmaceutical composition comprising a compound of formula (I) and at least one pharmaceutically acceptable carrier or excipient.

[0008] Thus, the present disclosure relates to the prevention and / or treatment of dyslipidemia, including the prevention of clinical sequalae associated with dyslipidemia. The present disclosure relates to the prevention and / or treatment of metabolic disorders associated with impaired lipid homeostasis. [Brief explanation of the drawings]

[0009] [Figure 1] FIG. 1 shows a representative dose-response curve of relative fluorescence intensity normalized to dimethyl sulfoxide (DMSO) control in Upcyte hepatocytes treated with a dose range of Compound 21 / 3. [Figure 2] Figure 2A shows representative images of lipid accumulation and gene expression in normal human-derived hepatic organoids (HLOs) and steatotic human-derived hepatic organoids (sHLOs), as assessed by fluorescent BODIPY™ staining. Figure 2B shows a dose-dependent reduction in lipid accumulation in sHLOs treated with Compound 21 / 3 for 3 days. Figure 2C shows a dose-dependent reduction in DNL gene expression in GCKR wild-type (CC) and GCKR mutant (TT)-derived sHLOs treated with Compound 21 / 3 for 3 days. Data for Figure 2A are taken from (Ouchi, Togo et al., 2019). Data are shown as mean ± SD, n = 4 wells per treatment. [Figure 3] Figure 3A shows plasma exposure in mice administered 1 mg / kg of Compound 21 / 3 or Compound Precursor 6 / 3 by oral gavage. Figure 3B shows liver exposure in mice administered 1 mg / kg of Compound 21 / 3 or Compound Precursor 6 / 3 by oral gavage. Figure 3C shows hepatic gene expression of LXR target genes 24 hours after a single oral administration of Compound 21 / 3 or Compound Precursor 6 / 3. Data are shown as mean ± SD. N = 3-8 wells per treatment. [Figure 4-1]Figure 4A shows hepatic target engagement, assessed by expression of genes involved in de novo lipogenesis (DNL), Figure 4B shows hepatic triglyceride (TG) content, and Figure 4C shows plasma TG levels, in diet-induced obese (DIO) mice, high-fat diet (HFD)-fed Zucker diabetic fatty (ZDF) rats, and HFD-fed Sprague-Dawley (SD) rats treated with Compound 21 / 3 once daily by oral gavage for 14 to 21 days, respectively. Data are presented as mean ± SD. N = 5 to 8 animals per group. Unless otherwise indicated, *, p ≤ 0.05, **, p ≤ 0.01, ***, p ≤ 0.001, ****, p ≤ 0.0001, and #, p ≤ 0.05 for pioglitazone versus vehicle. Kruskal-Wallis (nonparametric one-way ANOVA) test with Dunn's multiple comparison test (Figure 4A, Figure 4B), and repeated measures two-way ANOVA with Dunnett's multiple comparison test (Figure 4C). [Figure 4-2]Figure 4D shows ileal Srebp1c expression in diet-induced obese (DIO) mice, high-fat diet (HFD)-fed Zucker diabetic fatty (ZDF) rats, and HFD-fed Sprague-Dawley (SD) rats treated with compound 21 / 3 once daily by oral gavage for 14 to 21 days, respectively. Figure 4E shows intestinal lipid absorption, as measured by the appearance of 3H-triolein in the plasma of DIO mice treated with vehicle or compound precursor 6 / 3 (5 mg / kg by oral gavage). Figure 4F shows the hepatic expression (left) and plasma levels (right) of angiopoietin-line 3 (Angptl3) in HFD-fed ZDF rats treated with vehicle or compound 21 / 3 (15 mg / kg, once daily by oral gavage). Figure 4G shows the hepatic gene expression of enzymes involved in blood TG clearance and / or hepatic TG secretion in HFD-fed ZDF rats treated with vehicle or compound precursor 6 / 3 (5 mg / kg, once daily by oral gavage). Data are shown as mean ± SD. N = 5–8 animals per group. Unless otherwise indicated, *, p ≤ 0.05, **, p ≤ 0.01, ***, p ≤ 0.001, ****, p ≤ 0.0001, and #, p ≤ 0.05 for pioglitazone versus vehicle. Kruskal-Wallis (nonparametric one-way ANOVA) test with Dunn's multiple comparison test (Figure 4D), two-way ANOVA with Sidak's multiple comparison test (Figure 4E), and Mann-Whitney test (Figure 4F-G). [Figure 5-1]Figure 5A shows plasma total cholesterol (TC) levels, Figure 5B shows liver total cholesterol (TC) levels, and Figure 5C shows plasma alanine aminotransferase (ALT) levels in diet-induced obese (DIO) mice, high-fat diet (HFD)-fed Zucker diabetic fatty (ZDF) rats, and HFD-fed Sprague-Dawley (SD) rats treated with Compound 21 / 3 once daily by oral gavage for 14 to 21 days, as shown in the figures herein. Data are presented as mean ± SD. N = 5 to 8 animals per group. Unless otherwise indicated, *, p < 0.05, **, p < 0.01, ***, p < 0.001, ****, p < 0.0001, and #, p < 0.05 for pioglitazone versus vehicle. Two-way ANOVA for repeated measures with Dunnett's multiple comparison test (Figure 5A, Figure 5C), Kruskal-Wallis (nonparametric one-way ANOVA) test with Dunnett's multiple comparison test (Figure 5B). [Figure 5-2] Figure 5D shows plasma aspartate aminotransferase (AST) levels in diet-induced obese (DIO) mice, high-fat diet (HFD)-fed Zucker diabetic fatty (ZDF) rats, and HFD-fed Sprague-Dawley (SD) rats treated with Compound 21 / 3 once daily by oral gavage for 14 to 21 days, as shown in the figures herein. Figure 5E shows liver, ileum, and buffy coat expression of genes involved in cholesterol synthesis, metabolism, and excretory transport in DIO mice in response to Compound 21 / 3. Data are shown as mean ± SD. N = 5 to 8 animals per group. Unless otherwise indicated, *, p ≤ 0.05, **, p ≤ 0.01, ***, p ≤ 0.001, ****, p ≤ 0.0001, and #, p ≤ 0.05 for pioglitazone versus vehicle. Two-way ANOVA for repeated measures with Dunnett's multiple comparison test (Figure 5D), Kruskal-Wallis (nonparametric one-way ANOVA) test with Dunn's multiple comparison test (Figure 5E). [Figure 6]Figure 6A shows hepatic triglyceride (TG) and total cholesterol contents, and Figure 6B shows hepatic expression of genes involved in lipid synthesis and metabolism in humanized liver chimeric PXB mice treated with compound 21 / 3 (1 mg / kg, once daily by oral gavage) for 8 days. Data are shown as mean ± SD. N = 4-5 animals per group. *, p ≤ 0.05, **, p ≤ 0.01, ***, p ≤ 0.001, ****, p ≤ 0.0001. Mann-Whitney test. [Figure 7-1] Figure 7A shows the time course of glucose infusion rate (GIR) over the duration of the clamp. Figure 7B shows steady-state GIR and hepatic glucose production (HGP) during the first (8 mU / kg / min) and second (18 mU / kg / min) phases of insulin infusion. Figure 7C shows tissue glucose uptake measured at the end of the two-phase hyperinsulinemic-euglycemic clamp. Data are presented as mean ± SD. N = 5–11 animals per group. Unless otherwise indicated, *, p ≤ 0.05, **, p ≤ 0.01, ***, p ≤ 0.001, ****, p ≤ 0.0001, and #, p ≤ 0.05 for pioglitazone versus vehicle. Two-way ANOVA with repeated measures and Dunnett's multiple comparison test (Figure 7A), two-way ANOVA with Dunnett's multiple comparison test (Figure 7B, Figure 7C). EDL = extensor digitorum longus, GIR = glucose infusion rate, HGP = hepatic glucose production, iWAT = inguinal white adipose tissue. [Figure 7-2]Figure 7D shows an oral glucose tolerance test performed after 4 weeks of treatment in HFD-fed ZDF rats treated with vehicle or Compound 21 / 3 (15 mg / kg) once daily by oral gavage for 5 weeks. Figure 7E shows immunostaining of pancreatic sections with insulin (red, β cells), glucagon (green, α cells), and 4',6-diamidino-2-phenylindole (DAPI) (blue, nuclei) from HFD-fed ZDF rats treated with vehicle or Compound 21 / 3 (15 mg / kg) once daily by oral gavage for 5 weeks. Data are shown as mean ± SD. N = 5-11 animals per group. Unless otherwise indicated, *, p ≤ 0.05, **, p ≤ 0.01, ***, p ≤ 0.001, ****, p ≤ 0.0001 vs. vehicle; #, p ≤ 0.05 for pioglitazone vs. vehicle. Two-way ANOVA with repeated measures (Figure 7D) with Dunnett's multiple comparison test. EDL = extensor digitorum longus, GIR = glucose infusion rate, HGP = hepatic glucose production, iWAT = inguinal white adipose tissue. [Figure 8] Figure 8A shows representative images of liver sections stained with hematoxylin and eosin (H&E) or picrosil thread (PSR), respectively, from 12-week CDHFD / sodium nitrate-treated rats administered vehicle or compound precursor 6 / 3 (5 mg / kg) once daily by oral gavage for 6 weeks. Figure 8B shows liver hydroxyproline, Figure 8C shows liver collagen, Figure 8D shows liver triglyceride (TG) content, and Figure 8E shows liver gene expression at terminal time from 12-week CDHFD / sodium nitrate-treated rats administered vehicle or compound precursor 6 / 3 (5 mg / kg) once daily by oral gavage for 6 weeks. Data are shown as mean ± SD. N = 7–8 animals per group. *, p ≤ 0.05, **, p ≤ 0.01, ***, p ≤ 0.001, ****, p ≤ 0.0001. The Mann-Whitney test. [Figure 9] FIG. 9 shows the study scheme for the single ascending dose (SAD) cohorts in healthy volunteers in Parts A and C of the overall study design of the Phase 1 study. [Figure 10] Figure 10 shows the study scheme for the multiple ascending dose (MAD) cohorts in Parts B and C of the overall study design of the Phase 1 study. [Figure 11] FIG. 11 shows the plasma concentration-time profiles on day 1 of the SAD study. [Figure 12] FIG. 12 shows the plasma concentration-time profiles on day 14 of the MAD study. [Figure 13-1] Figures 13A-13D show the relative change in serum lipid parameters pre-dose during the MAD phase of the study. Figure 13A shows the relative change (%) in triglycerides from day 1 to day 14 during the MAD phase of the study. Figure 13B shows the relative change (%) in total cholesterol from day 1 to day 14 during the MAD phase of the study. Figure 13C shows the relative change (%) in HDL-C from day 1 to day 14 during the MAD phase of the study. Figure 13D shows the relative change (%) in the TG / HDL-C ratio from day 1 to day 14 during the MAD phase of the study. [Figure 13-2] Figures 13E-13H show the relative change in serum lipid parameters pre-dose during the MAD phase of the study. Figure 13E shows the relative change (%) in LDL-C from days 1 to 14 during the MAD phase of the study. Figure 13F shows the relative change (%) in LDL particles from days 1 to 14 during the MAD phase of the study. Figure 13G shows the relative change (%) in small LDL particles from days 1 to 14 during the MAD phase of the study. Figure 13H shows the relative change (%) in apoB (ApoB) from days 1 to 14 during the MAD phase of the study. [Figure 14] Figure 14A shows apoC3 (ApoC3) levels in response to compound 21 / 3 or placebo treatment from days 1 to 14. Figure 14B shows ANGPTL3 levels in response to compound 21 / 3 or placebo treatment from days 1 to 14. Figure 14C shows reverse cholesterol transport (RCT) gene levels in peripheral blood mononuclear cells (PBMCs) in response to compound 21 / 3 and placebo treatment from days 1 to 14. DETAILED DESCRIPTION OF THE INVENTION

[0010] The present disclosure provides methods for treating or preventing various LXR-mediated diseases, comprising administering to a subject a compound of formula (I): [ka] Methods are provided for treating or preventing various LXR-mediated diseases by administering glycine conjugates, taurine conjugates, enantiomers, diastereomers, tautomers, N-oxides, solvates, prodrugs, and pharmaceutically acceptable salts thereof. [ka] is a fused 5- to 6-membered ring forming a 6-membered aryl or a 5- to 6-membered heteroaryl containing 1 to 3 heteroatoms independently selected from N, O, and S, the ring being unsubstituted or substituted with halogen, CN, SF, NO, C 1~6 -Alkyl, oxo, C 0~6 -Alkylene-OR 11 , C 0~6 -Alkylene-(3- to 6-membered cycloalkyl), C 0~6 -alkylene-(3- to 6-membered heterocycloalkyl), C 0~6 -Alkylene-S(O) n R 11 , C 0~6 -Alkylene-NR 11 S(O)2R 11 , C 0~6 -Alkylene-S(O)NR 11 R 12 , C 0~6 -Alkylene-NR 11 S(O)NR 11 R 12 , C 0~6 -Alkylene-CO2R 11 , O.C. 1~6 -Alkylene-CO2R 11 , C 0~6 -Alkylene-O-COR 11 , C 0~6 -Alkylene-CONR 11 R 12 , C0~6 -Alkylene-NR 11 -COR 11 , C 0~6 -Alkylene-NR 11 -CONR 11 R 12 , C 0~6 -Alkylene-O-CONR 11 R 12 , C 0~6 -Alkylene-NR 11 -CO2R 11 , and C 0~6 -Alkylene-NR 11 R 12 and is substituted with 1 to 4 substituents independently selected from the group consisting of: wherein alkyl, alkylene, cycloalkyl, and heterocycloalkyl are unsubstituted or substituted with halogen, CN, oxo, hydroxy, COH, CO-C 1~4 -Alkyl, CONHCH2CO2H, CONH(CH2)2SO3H, C 1~4 -Alkyl, Halo-C 1~4 -Alkyl, OC 1~4 -Alkyl and O-Halo-C 1~4 -substituted with 1 to 6 substituents independently selected from alkyl; wherein two adjacent substituents on the aryl or heteroaryl moiety may form a 5-8 membered partially unsaturated ring which may contain 1-3 heteroatoms independently selected from O, S or N; The newly formed ring may be unsubstituted or may contain halogen, CN, C 1~4 -Alkyl, Halo-C 1~4 -Alkyl, 3- to 6-membered cycloalkyl, halo-(3- to 6-membered cycloalkyl), 3- to 6-membered heterocycloalkyl, halo-(3- to 6-membered heterocycloalkyl), OH, oxo, CO2H, CO2-C 1~4 -Alkyl, CONHCH2CO2H, CONH(CH2)2SO3H, OC 1~4 -Alkyl and O-Halo-C 1~4 -substituted with 1 to 3 substituents independently selected from alkyl; [ka] is selected from the group consisting of 3- to 10-membered cycloalkyl, 3- to 10-membered heterocycloalkyl containing 1-3 heteroatoms independently selected from N, O, and S, 6- to 14-membered aryl, and 5- to 14-membered heteroaryl containing 1-4 heteroatoms independently selected from N, O, and S; wherein cycloalkyl, heterocycloalkyl, aryl and heteroaryl are unsubstituted or substituted with halogen, CN, SF, NO, oxo, C 1~4 -Alkyl, C 0~6 -Alkylene-OR 21 , C 0~6 -Alkylene-(3- to 6-membered cycloalkyl), C 0~6 -alkylene-(3- to 6-membered heterocycloalkyl), C 0~6 -Alkylene-S(O) n R 21 , C 0~6 -Alkylene-NR 21 S(O)2R 21 , C 0~6 -Alkylene-S(O)NR 21 R 22 , C 0~6 -Alkylene-NR 21 S(O)NR 21 R 22 , C 0~6 -Alkylene-CO2R 21 , O.C. 1~6 -Alkylene-CO2R 21 , C 0~6 -Alkylene-O-COR 21 , C 0~6 -Alkylene-CONR 21 R 22 , C 0~6 -Alkylene-NR 21 -COR 21 , C 0~6 -Alkylene-NR 21 -CONR 21 R 22 , C 0~6 -Alkylene-O-CONR 21 R 22 , C 0~6 -Alkylene-NR 21 -CO2R21 and C 0~6 -Alkylene-NR 21 R 22 and is substituted with 1 to 6 substituents independently selected from the group consisting of: wherein alkyl, alkylene, cycloalkyl and heterocycloalkyl are unsubstituted or substituted with halogen, CN, oxo, hydroxy, COH, CO-C 1~4 -Alkyl, CONHCH2CO2H, CONH(CH2)2SO3H, C 1~4 -Alkyl, Halo-C 1~4 -Alkyl, OC 1~4 -Alkyl and O-Halo-C 1~4 -substituted with 1 to 6 substituents independently selected from alkyl; wherein two adjacent substituents on the aryl or heteroaryl moiety may form a 5-8 membered partially unsaturated ring which may contain 1-3 heteroatoms independently selected from O, S or N; This further ring may be unsubstituted or may be substituted with halogen, CN, oxo, OH, CO2H, CO2-C 1~4 -Alkyl, CONHCH2CO2H, CONH(CH2)2SO3H, C 1~4 -Alkyl, Halo-C 1~4 -Alkyl, OC 1~4 -Alkyl and O-Halo-C 1~4 -substituted with 1 to 4 substituents independently selected from alkyl; wherein two adjacent substituents on the cycloalkyl or heterocycloalkyl moiety may form a 5- to 6-membered unsaturated ring which may contain 1 to 3 heteroatoms independently selected from O, S, or N; This further ring may be unsubstituted or may be substituted with halogen, CN, oxo, OH, CO2H, CO2-C 1~4 -Alkyl, CONHCH2CO2H, CONH(CH2)2SO3H, C 1~4 -Alkyl, Halo-C 1~4 -Alkyl, OC 1~4 -Alkyl and O-Halo-C 1~4 -substituted with 1 to 4 substituents independently selected from alkyl; [ka] is selected from the group consisting of 6- or 10-membered aryl and 5- to 10-membered heteroaryl containing 1-3 heteroatoms independently selected from N, O, and S; wherein cycloalkyl, heterocycloalkyl, aryl and heteroaryl are unsubstituted or substituted with halogen, CN, SF, NO, oxo, C 1~4 -Alkyl, C 0~6 -Alkylene-OR 31 , C 0~6 -Alkylene-(3- to 6-membered cycloalkyl), C 0~6 -alkylene-(3- to 6-membered heterocycloalkyl), C 0~6 -alkylene-(6-membered aryl), C 0~6 -alkylene-(5-6 membered heteroaryl), C 0~6 -Alkylene-S(O) n R 31 , C 0~6 -Alkylene-NR 31 S(O)2R 31 , C 0~6 -Alkylene-S(O)NR 31 R 32 , C 0~6 -Alkylene-NR 31 S(O)NR 31 R 32 , C 0~6 -Alkylene-CO2R 31 , O.C. 1~6 -Alkylene-CO2R 31 , C 0~6 -Alkylene-O-COR 31 , C 0~6 -Alkylene-CONR 31 R 32 , C 0~6 -Alkylene-NR 31 -COR 31 , C 0~6 -Alkylene-NR 31 -CONR 31 R 32 , C 0~6 -Alkylene-O-CONR 31 R 32 , C0~6 -Alkylene-NR 31 -CO2R 31 and C 0~6 -Alkylene-NR 31 R 32 and is substituted with 1 to 4 substituents independently selected from the group consisting of: wherein alkyl, alkylene, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are unsubstituted or substituted with halogen, CN, oxo, hydroxy, COH, CO-C 1~4 -Alkyl, CONHCH2CO2H, CONH(CH2)2SO3H, C 1~4 -Alkyl, Halo-C 1~4 -Alkyl, OC 1~4 -Alkyl and O-Halo-C 1~4 -substituted with 1 to 6 substituents independently selected from alkyl; wherein two adjacent substituents on the aryl or heteroaryl moiety may form a 5-8 membered partially unsaturated ring which may contain 1-3 heteroatoms independently selected from O, S or N; This further ring may be unsubstituted or may be substituted with halogen, CN, oxo, OH, CO2H, CO2-C 1~4 -Alkyl, CONHCH2CO2H, CONH(CH2)2SO3H, C 1~4 -Alkyl, Halo-C 1~4 -Alkyl, OC 1~4 -Alkyl and O-Halo-C 1~4 -substituted with 1 to 4 substituents independently selected from alkyl; [ka] is selected from the group consisting of 3- to 10-membered cycloalkyl, 3- to 10-membered heterocycloalkyl containing 1-3 heteroatoms independently selected from N, O, and S, 6- to 14-membered aryl, and 5- to 14-membered heteroaryl containing 1-4 heteroatoms independently selected from N, O, and S; wherein cycloalkyl, heterocycloalkyl, aryl and heteroaryl are unsubstituted or substituted with halogen, CN, SF, NO, oxo, C1~4 -Alkyl, C 0~6 -Alkylene-OR 21 , C 0~6 -Alkylene-(3- to 6-membered cycloalkyl), C 0~6 -alkylene-(3- to 6-membered heterocycloalkyl), C 0~6 -Alkylene-S(O) n R 21 , C 0~6 -Alkylene-NR 21 S(O)2R 21 , C 0~6 -Alkylene-S(O)NR 21 R 22 , C 0~6 -Alkylene-NR 21 S(O)NR 21 R 22 , C 0~6 -Alkylene-CR 41 (=N-OR 41 ), C 0~6 -Alkylene-CO2R 21 , O.C. 1~6 -Alkylene-CO2R 21 , C 0~6 -Alkylene-O-COR 21 , C 0~6 -Alkylene-CONR 21 R 22 , C 0~6 -Alkylene-NR 21 -COR 21 , C 0~6 -Alkylene-NR 21 -CONR 21 R 22 , C 0~6 -Alkylene-O-CONR 21 R 22 , C 0~6 -Alkylene-NR 21 -CO2R 21 and C 0~6 -Alkylene-NR 21 R 22 and is substituted with 1 to 6 substituents independently selected from the group consisting of: wherein alkyl, alkylene, cycloalkyl and heterocycloalkyl are unsubstituted or substituted with halogen, CN, oxo, hydroxy, COH, CO-C1~4 -Alkyl, CONHCH2CO2H, CONH(CH2)2SO3H, CO-OC 1~4 -Alkyl, C 1~4 -Alkyl, Halo-C 1~4 -Alkyl, OC 1~4 -Alkyl and O-Halo-C 1~4 -substituted with 1 to 6 substituents independently selected from alkyl; wherein two adjacent substituents on the aryl or heteroaryl moiety may form a 5-8 membered partially unsaturated ring which may contain 1-3 heteroatoms independently selected from O, S or N; This further ring may be unsubstituted or may be substituted with halogen, CN, oxo, OH, CO2H, CO2-C 1~4 -Alkyl, CONHCH2CO2H, CONH(CH2)2SO3H, C 1~4 -Alkyl, Halo-C 1~4 -Alkyl, OC 1~4 -Alkyl and O-Halo-C 1~4 -substituted with 1 to 4 substituents independently selected from alkyl; wherein two adjacent substituents on the cycloalkyl or heterocycloalkyl moiety may form a 5- to 6-membered unsaturated ring which may contain 1 to 3 heteroatoms independently selected from O, S, or N; This further ring may be unsubstituted or may be substituted with halogen, CN, oxo, OH, CO2H, CO2-C 1~4 -Alkyl, CONHCH2CO2H, CONH(CH2)2SO3H, C 1~4 -Alkyl, Halo-C 1~4 -Alkyl, OC 1~4 -Alkyl and O-Halo-C 1~4 -substituted with 1 to 4 substituents independently selected from alkyl; During the ceremony, [ka] teeth, [ka] or a further ring fused in a 1,2-orientation, L is a bond, C 1~6 -Alkylene, C 2~6 -Alkenylene, C 2~6 - selected from the group consisting of alkynylene, 3- to 10-membered cycloalkylene, 3- to 10-membered heterocycloalkylene containing 1-4 heteroatoms independently selected from N, O and S, 6- or 10-membered arylene, and 5- to 10-membered heteroarylene containing 1-4 heteroatoms independently selected from N, O and S; wherein alkylene, alkenylene, alkynylene, cycloalkylene, heterocycloalkylene, arylene and heteroarylene are unsubstituted or substituted with halogen, CN, SF, NO, oxo, C 1~4 -Alkyl, C 0~6 -Alkylene-OR 41 , C 0~6 -Alkylene-(3- to 6-membered cycloalkyl), C 0~6 -alkylene-(3- to 6-membered heterocycloalkyl), C 0~6 -Alkylene-S(O) n R 41 , C 0~6 -Alkylene-NR 41 S(O)2R 41 , C 0~6 -Alkylene-S(O)NR 41 R 42 , C 0~6 -Alkylene-NR 41 S(O)NR 41 R 42 , C 0~6 -Alkylene-CO2R 41 , O.C. 1~6 -Alkylene-CO2R 41 , C 0~6 -Alkylene-O-COR 41 , C 0~6 -Alkylene-CONR 41 R 42 , C 0~6 -Alkylene-NR 41 -COR 41 , C 0~6 -Alkylene-NR41 -CONR 41 R 42 , C 0~6 -Alkylene-O-CONR 41 R 42 , C 0~6 -Alkylene-NR 41 -CO2R 41 and C 0~6 -Alkylene-NR 41 R 42 and is substituted with 1 to 6 substituents independently selected from the group consisting of: wherein alkyl, alkylene, cycloalkyl and heterocycloalkyl are unsubstituted or substituted with halogen, CN, oxo, hydroxy, COH, CO-C 1~4 -Alkyl, CONHCH2CO2H, CONH(CH2)2SO3H, C 1~4 -Alkyl, Halo-C 1~4 -Alkyl, OC 1~4 -Alkyl and O-Halo-C 1~4 -substituted with 1 to 6 substituents independently selected from alkyl; wherein two adjacent substituents on the arylene moiety and the heteroarylene moiety may form a 5- to 8-membered partially unsaturated ring which may contain 1 to 3 heteroatoms independently selected from O, S, or N; This further ring may be unsubstituted or may be substituted with halogen, CN, oxo, OH, CO2H, CO2-C 1~4 -Alkyl, C 1~4 -Alkyl, Halo-C 1~4 -Alkyl, OC 1~4 -Alkyl and O-Halo-C 1~4 -substituted with 1 to 4 substituents independently selected from alkyl; R 1 H, halogen, CN, SF5, NO2, oxo, C 1~4 -Alkyl, C 0~6 -Alkylene-OR 41 , Y.C. 0~6 -Alkylene-(3-6 membered cycloalkyl), YC 0~6 -Alkylene-(3-6 membered heterocycloalkyl), YC 0~6-alkylene-(6-membered aryl), YC 0~6 -alkylene-(5-6 membered heteroaryl), C 0~6 -Alkylene-S(=O)(-R 41 )=NR 75 , XC 1~6 -Alkylene-S(=O)(-R 41 )=NR 75 , C 0~6 -Alkylene-S(O) n R 41 , XC 1~6 -Alkylene-S(O) n R 41 , C 0~6 -Alkylene-S(=NR 71 )R 41 , XC 1~6 -Alkylene-S(=NR 71 )R 41 , C 0~6 -Alkylene-S(O)(=NR 71 )R 41 , XC 1~6 -Alkylene-S(O)(=NR 71 )R 41 , C 0~6 -Alkylene-S(=NR 71 )2R 41 , XC 1~6 -Alkylene-S(=NR 71 )2R 41 , C 0~6 -Alkylene-NR 41 S(O)2R 41 , XC 1~6 -Alkylene-NR 41 S(O)2R 41 , C 0~6 -Alkylene-S(O)NR 41 R 42 , XC 1~6 -Alkylene-S(O)NR 41 R 42 , C 0~6 -Alkylene-NR 41 S(O)NR 41 R 42 , XC 1~6 -Alkylene-NR 41 S(O)NR 41 R 42, C 0~6 -Alkylene-SO3R 41 , XC 1~6 -Alkylene-SO3R 41 , C 0~6 -Alkylene-CO2R 41 , XC 1~6 -Alkylene-CO2R 41 , C 0~6 -Alkylene-O-COR 41 , XC 1~6 -Alkylene-O-COR 41 , C 0~6 -Alkylene-CONR 41 R 42 , XC 1~6 -Alkylene-CONR 41 R 42 , C 0~6 -Alkylene-CONR 41 OR 41 , XC 1~6 -Alkylene-CONR 41 OR 41 , C 0~6 -Alkylene-CONR 41 SO2R 41 , XC 1~6 -Alkylene-CONR 41 SO2R 41 , C 0~6 -Alkylene-NR 41 -COR 41 , XC 1~6 -C 0~6 -Alkylene-NR 41 -COR 41 , C 0~6 -Alkylene-NR 41 -CONR 41 R 42 , XC 1~6 -Alkylene-NR 41 -CONR 41 R 42 , C 0~6 -Alkylene-O-CONR 41 R 42 , XC 1~6 -Alkylene-O-CONR 41 R 42 , C 0~6 -Alkylene-NR 41 -CO2R41 , XC 1~6 -Alkylene-NR 41 -CO2R 41 , C 0~6 -Alkylene-NR 41 R 42 , XC 1~6 -Alkylene-NR 41 R 42 is selected from the group consisting of wherein alkyl, alkylene, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are unsubstituted or substituted with halogen, CN, oxo, hydroxy, COH, CO-C 1~4 -Alkyl, CONHCH2CO2H, CONH(CH2)2SO3H, C 1~4 -Alkyl, Halo-C 1~4 -Alkyl, OC 1~4 -Alkyl and O-Halo-C 1~4 -substituted with 1 to 6 substituents independently selected from alkyl; wherein two adjacent substituents on the aryl and heteroaryl moieties may form a 5-8 membered partially unsaturated ring which may contain 1-3 heteroatoms independently selected from O, S or N; This further ring may be unsubstituted or may be substituted with halogen, CN, oxo, OH, CO2H, CO2-C 1~4 -Alkyl, CONHCH2CO2H, CONH(CH2)2SO3H, C 1~4 -Alkyl, Halo-C 1~4 -Alkyl, OC 1~4 -Alkyl and O-Halo-C 1~4 -substituted with 1 to 4 substituents independently selected from alkyl; R 11 , R 12 , R 21 , R 22 , R 31 , R 32 , R 41 , R 42 , R 51 are independently H and C 1~4 -alkyl, wherein alkyl is unsubstituted or is substituted with halogen, CN, C1~4 -Alkyl, Halo-C 1~4 -Alkyl, 3- to 6-membered cycloalkyl, halo-(3- to 6-membered cycloalkyl), 3- to 6-membered heterocycloalkyl, halo-(3- to 6-membered heterocycloalkyl), OH, oxo, CO2H, CO2-C 1~4 -Alkyl, CONHCH2CO2H, CONH(CH2)2SO3H, SO3H, OC 1~4 -Alkyl and O-Halo-C 1~4 -substituted with 1 to 3 substituents independently selected from alkyl; or R 11 and R 12 , R 21 and R 22 , R 31 and R 32 , R 41 and R 42 each, when taken together with the nitrogen to which they are attached, completes a 3- to 6-membered ring containing carbon atoms and optionally containing 1 or 2 heteroatoms independently selected from O, S or N; The newly formed ring may be unsubstituted or may contain halogen, CN, C 1~4 -Alkyl, Halo-C 1~4 -Alkyl, 3- to 6-membered cycloalkyl, halo-(3- to 6-membered cycloalkyl), 3- to 6-membered heterocycloalkyl, halo-(3- to 6-membered heterocycloalkyl), OH, oxo, CO2H, CO2-C 1~4 -Alkyl, CONHCH2CO2H, CONH(CH2)2SO3H, SO3H, OC 1~4 -Alkyl and O-Halo-C 1~4 -substituted with 1 to 3 substituents independently selected from alkyl; R 71 are independently H, CN, NO2, C 1~4 -Alkyl, and C(O)-OC 1~4 -alkyl, wherein alkyl is unsubstituted or is selected from halogen, CN, C 1~4 -Alkyl, Halo-C 1~4-Alkyl, 3- to 6-membered cycloalkyl, halo-(3- to 6-membered cycloalkyl), 3- to 6-membered heterocycloalkyl, halo-(3- to 6-membered heterocycloalkyl), OH, oxo, CO2H, CO2-C 1~4 -Alkyl, CONHCH2CO2H, CONH(CH2)2SO3H, SO3H, OC 1~4 -Alkyl and O-Halo-C 1~4 -substituted with 1 to 3 substituents independently selected from alkyl; R 75 are independently, C 1~4 selected from alkyl, 3- to 6-membered cycloalkyl, 3- to 6-membered heterocycloalkyl, 6-membered aryl, and 5- to 6-membered heteroaryl; wherein alkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl are unsubstituted or substituted with 1 to 3 substituents independently selected from halogen, CN, Me, Et, CHF, CF, OH, oxo, COH, CONHCHCOH, CONH(CH)SOH, SOH, OMe, OEt, OCHF, and OCF; X is independently O, NR 51 , S(O) n , S(=NR 71 ), S(O)(=NR 71 ) and S(=NR 71 )2 is selected, Y is independently a bond, O, or NR 51 , S(O) n , S(=NR 71 ), S(O)(=NR 71 ) and S(=NR 71 )2 is selected, n is independently selected from 0 to 2; however, [ka] The structure is excluded.

[0011] In certain embodiments, in combination with any of the above or below embodiments: [ka] is a fused 5- to 6-membered ring forming a 6-membered aryl or a 5- to 6-membered heteroaryl containing 1 to 3 heteroatoms independently selected from N, O, and S, the ring being unsubstituted or substituted with halogen, CN, SF, NO, C 1~6 -Alkyl, oxo, C 0~6 -Alkylene-OR 11 , C 0~6 -Alkylene-(3- to 6-membered cycloalkyl), C 0~6 -alkylene-(3- to 6-membered heterocycloalkyl), C 0~6 -Alkylene-S(O) n R 11 , C 0~6 -Alkylene-NR 11 S(O)2R 11 , C 0~6 -Alkylene-S(O)NR 11 R 12 , C 0~6 -Alkylene-NR 11 S(O)NR 11 R 12 , C 0~6 -Alkylene-CO2R 11 , O.C. 1~6 -Alkylene-CO2R 11 , C 0~6 -Alkylene-O-COR 11 , C 0~6 -Alkylene-CONR 11 R 12 , C 0~6 -Alkylene-NR 11 -COR 11 , C 0~6 -Alkylene-NR 11 -CONR 11 R 12 , C 0~6 -Alkylene-O-CONR 11 R 12 , C 0~6 -Alkylene-NR 11 -CO2R 11 , and C 0~6 -Alkylene-NR 11 R 12 and is substituted with 1 to 4 substituents independently selected from the group consisting of: wherein alkyl, alkylene, cycloalkyl, and heterocycloalkyl are unsubstituted or substituted with halogen, CN, oxo, hydroxy, COH, CO-C 1~4 -Alkyl, CONHCH2CO2H, CONH(CH2)2SO3H, C 1~4 -Alkyl, Halo-C 1~4 -Alkyl, OC 1~4 -Alkyl and O-Halo-C 1~4 -substituted with 1 to 6 substituents independently selected from alkyl; wherein two adjacent substituents on the aryl or heteroaryl moiety may form a 5-8 membered partially unsaturated ring which may contain 1-3 heteroatoms independently selected from O, S or N; The newly formed ring may be unsubstituted or may contain halogen, CN, C 1~4 -Alkyl, Halo-C 1~4 -Alkyl, 3- to 6-membered cycloalkyl, halo-(3- to 6-membered cycloalkyl), 3- to 6-membered heterocycloalkyl, halo-(3- to 6-membered heterocycloalkyl), OH, oxo, CO2H, CO2-C 1~4 -Alkyl, CONHCH2CO2H, CONH(CH2)2SO3H, OC 1~4 -Alkyl and O-Halo-C 1~4 -substituted with 1 to 3 substituents independently selected from alkyl;

[0012] In certain embodiments, in combination with any of the above or below embodiments: [ka] are fused phenyl, thiophenyl, thiazolyl, pyridyl, pyrimidinyl, pyridazinyl and pyrazinyl, the rings being unsubstituted or substituted with halogen, CN, SF, NO, C 1~6 -Alkyl, oxo, C 0~6 -Alkylene-OR 11 , C 0~6 -Alkylene-(3- to 6-membered cycloalkyl), C 0~6 -alkylene-(3- to 6-membered heterocycloalkyl), C 0~6-Alkylene-S(O) n R 11 , C 0~6 -Alkylene-NR 11 S(O)2R 11 , C 0~6 -Alkylene-S(O)NR 11 R 12 , C 0~6 -Alkylene-NR 11 S(O)NR 11 R 12 , C 0~6 -Alkylene-CO2R 11 , O.C. 1~6 -Alkylene-CO2R 11 , C 0~6 -Alkylene-O-COR 11 , C 0~6 -Alkylene-CONR 11 R 12 , C 0~6 -Alkylene-NR 11 -COR 11 , C 0~6 -Alkylene-NR 11 -CONR 11 R 12 , C 0~6 -Alkylene-O-CONR 11 R 12 , C 0~6 -Alkylene-NR 11 -CO2R 11 , and C 0~6 -Alkylene-NR 11 R 12 and is substituted with 1 to 4 substituents independently selected from the group consisting of: wherein alkyl, alkylene, cycloalkyl and heterocycloalkyl are unsubstituted or substituted with halogen, CN, oxo, hydroxy, COH, CO-C 1~4 -Alkyl, CONHCH2CO2H, CONH(CH2)2SO3H, C 1~4 -Alkyl, Halo-C 1~4 -Alkyl, OC 1~4 -Alkyl, and O-Halo-C 1~4 -substituted with 1 to 6 substituents independently selected from alkyl;

[0013] In certain embodiments, in combination with any of the above or below embodiments: [ka] teeth, [ka] is selected from During the ceremony, [ka] is unsubstituted or is F, Cl, Br, CN, OH, oxo, C 1~4 -Alkyl, Halo-C 1~4 -Alkyl, OC 1~4 -Alkyl, O-Halo-C 1~4 -Alkyl, NH2, NHC 1~4 -Alkyl, N(C 1~4 -Alkyl)2, SO2-C 1~4 -Alkyl, and SO2-Halo-C 1~4 -substituted with 1 to 3 substituents independently selected from the group consisting of alkyl;

[0014] In certain embodiments, in combination with any of the above or below embodiments: [ka] teeth, [ka] and During the ceremony, [ka] is unsubstituted or substituted with 1 to 3 substituents independently selected from the group consisting of F, Cl, Br, CN, Me, Et, CF3, CHF2, OH, OMe, OCF3, and OCHF3.

[0015] In certain embodiments, in combination with any of the above or below embodiments: [ka] is selected from the group consisting of 3- to 10-membered cycloalkyl, 3- to 10-membered heterocycloalkyl containing 1-3 heteroatoms independently selected from N, O, and S, 6- to 14-membered aryl, and 5- to 14-membered heteroaryl containing 1-4 heteroatoms independently selected from N, O, and S; wherein cycloalkyl, heterocycloalkyl, aryl and heteroaryl are unsubstituted or substituted with halogen, CN, SF, NO, oxo, C 1~4 -Alkyl, C 0~6 -Alkylene-OR 21 , C 0~6 -Alkylene-(3- to 6-membered cycloalkyl), C 0~6 -alkylene-(3- to 6-membered heterocycloalkyl), C 0~6 -Alkylene-S(O) n R 21 , C 0~6 -Alkylene-NR 21 S(O)2R 21 , C 0~6 -Alkylene-S(O)NR 21 R 22 , C 0~6 -Alkylene-NR 21 S(O)NR 21 R 22 , C 0~6 -Alkylene-CO2R 21 , O.C. 1~6 -Alkylene-CO2R 21 , C 0~6 -Alkylene-O-COR 21 , C 0~6 -Alkylene-CONR 21 R 22 , C 0~6 -Alkylene-NR 21 -COR 21 , C 0~6 -Alkylene-NR 21 -CONR 21 R 22 , C 0~6 -Alkylene-O-CONR 21 R 22 , C 0~6-Alkylene-NR 21 -CO2R 21 and C 0~6 -Alkylene-NR 21 R 22 and is substituted with 1 to 6 substituents independently selected from the group consisting of: wherein alkyl, alkylene, cycloalkyl and heterocycloalkyl are unsubstituted or substituted with halogen, CN, oxo, hydroxy, COH, CO-C 1~4 -Alkyl, CONHCH2CO2H, CONH(CH2)2SO3H, C 1~4 -Alkyl, Halo-C 1~4 -Alkyl, OC 1~4 -Alkyl and O-Halo-C 1~4 -substituted with 1 to 6 substituents independently selected from alkyl; wherein two adjacent substituents on the aryl or heteroaryl moiety may form a 5-8 membered partially unsaturated ring which may contain 1-3 heteroatoms independently selected from O, S or N; This further ring may be unsubstituted or may be substituted with halogen, CN, oxo, OH, CO2H, CO2-C 1~4 -Alkyl, CONHCH2CO2H, CONH(CH2)2SO3H, C 1~4 -Alkyl, Halo-C 1~4 -Alkyl, OC 1~4 -Alkyl and O-Halo-C 1~4 -substituted with 1 to 4 substituents independently selected from alkyl; wherein two adjacent substituents on the cycloalkyl or heterocycloalkyl moiety may form a 5- to 6-membered unsaturated ring which may contain 1 to 3 heteroatoms independently selected from O, S, or N; This further ring may be unsubstituted or may be substituted with halogen, CN, oxo, OH, CO2H, CO2-C 1~4 -Alkyl, CONHCH2CO2H, CONH(CH2)2SO3H, C 1~4 -Alkyl, Halo-C 1~4 -Alkyl, OC 1~4 -Alkyl and O-Halo-C 1~4-substituted with 1 to 4 substituents independently selected from alkyl;

[0016] In certain embodiments, in combination with any of the above or below embodiments: [ka] is selected from the group consisting of phenyl, pyridyl, and thiophenyl; In the formula, phenyl, pyridyl and thiophenyl are substituted with halogen, CN, SF5, NO2, oxo, C 1~4 -Alkyl, C 0~6 -Alkylene-OR 21 , C 0~6 -Alkylene-(3- to 6-membered cycloalkyl), C 0~6 -alkylene-(3- to 6-membered heterocycloalkyl), C 0~6 -Alkylene-S(O) n R 21 , C 0~6 -Alkylene-NR 21 S(O)2R 21 , C 0~6 -Alkylene-S(O)NR 21 R 22 , C 0~6 -Alkylene-NR 21 S(O)NR 21 R 22 , C 0~6 -Alkylene-CO2R 21 , O.C. 1~6 -Alkylene-CO2R 21 , C 0~6 -Alkylene-O-COR 21 , C 0~6 -Alkylene-CONR 21 R 22 , C 0~6 -Alkylene-NR 21 -COR 21 , C 0~6 -Alkylene-NR 21 -CONR 21 R 22 , C 0~6 -Alkylene-O-CONR 21 R 22 , C 0~6-Alkylene-NR 21 -CO2R 21 and C 0~6 -Alkylene-NR 21 R 22 and is substituted with 1 to 4 substituents independently selected from the group consisting of: wherein alkyl, alkylene, cycloalkyl and heterocycloalkyl are unsubstituted or substituted with halogen, CN, oxo, hydroxy, COH, CO-C 1~4 -Alkyl, CONHCH2CO2H, CONH(CH2)2SO3H, C 1~4 -Alkyl, Halo-C 1~4 -Alkyl, OC 1~4 -Alkyl and O-Halo-C 1~4 -substituted with 1 to 6 substituents independently selected from alkyl; wherein two adjacent substituents on the phenyl and pyridyl moieties may form a 5-8 membered partially unsaturated ring which may contain 1-3 heteroatoms independently selected from O, S or N; This further ring may be unsubstituted or may be substituted with halogen, CN, oxo, OH, CO2H, CO2-C 1~4 -Alkyl, CONHCH2CO2H, CONH(CH2)2SO3H, C 1~4 -Alkyl, Halo-C 1~4 -Alkyl, OC 1~4 -Alkyl and O-Halo-C 1~4 -substituted with 1 to 4 substituents independently selected from alkyl;

[0017] In certain embodiments, in combination with any of the above or below embodiments: [ka] is phenyl, naphthyl, pyridyl, pyrimidinyl, thiophenyl, thiazolyl, cyclopentyl, cyclohexyl, bicyclo[1.1.1]pentyl, bicyclo[2.2.2]octyl, bicyclo[2.2.1]heptyl, pentacyclo[4.2.0.0 2,5 .0 3,8 .0 4,7octyl, and piperidinyl; wherein the ring is unsubstituted or substituted with F, Cl, Br, CN, OH, oxo, C 1~4 -Alkyl, Halo-C 1~4 -Alkyl, OC 1~4 -Alkyl, O-Halo-C 1~4 -Alkyl, C 1~4 -Alkyl-OH, and halo-C 1~4 -alkyl-OH, and two adjacent substituents on a phenyl ring may be taken together to form a -(CH2)3-, -(CH2)4-, -OCF2O-, and -OCHO- group.

[0018] In certain embodiments, in combination with any of the above or below embodiments: [ka] is selected from the group consisting of phenyl and pyridyl; wherein the phenyl and pyridyl are substituted with 1 to 2 substituents independently selected from the group consisting of F, Cl, CN, CF3, CH2F, and CHF2.

[0019] In certain embodiments, in combination with any of the above or below embodiments: [ka] is 4-difluoromethylphenyl.

[0020] In certain embodiments, in combination with any of the above or below embodiments: [ka] is selected from the group consisting of 6- or 10-membered aryl and 5- to 10-membered heteroaryl containing 1-3 heteroatoms independently selected from N, O, and S; wherein cycloalkyl, heterocycloalkyl, aryl and heteroaryl are unsubstituted or substituted with halogen, CN, SF, NO, oxo, C 1~4 -Alkyl, C 0~6 -Alkylene-OR 31 , C 0~6 -Alkylene-(3- to 6-membered cycloalkyl), C 0~6 -alkylene-(3- to 6-membered heterocycloalkyl), C 0~6 -alkylene-(6-membered aryl), C 0~6 -alkylene-(5-6 membered heteroaryl), C 0~6 -Alkylene-S(O) n R 31 , C 0~6 -Alkylene-NR 31 S(O)2R 31 , C 0~6 -Alkylene-S(O)NR 31 R 32 , C 0~6 -Alkylene-NR 31 S(O)NR 31 R 32 , C 0~6 -Alkylene-CO2R 31 , O.C. 1~6 -Alkylene-CO2R 31 , C 0~6 -Alkylene-O-COR 31 , C 0~6 -Alkylene-CONR 31 R 32 , C 0~6 -Alkylene-NR 31 -COR 31 , C 0~6 -Alkylene-NR 31 -CONR 31 R 32 , C 0~6 -Alkylene-O-CONR 31 R 32 , C 0~6 -Alkylene-NR 31 -CO2R 31 and C 0~6 -Alkylene-NR 31 R 32 and is substituted with 1 to 4 substituents independently selected from the group consisting of: wherein alkyl, alkylene, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are unsubstituted or substituted with halogen, CN, oxo, hydroxy, COH, CO-C 1~4 -Alkyl, CONHCH2CO2H, CONH(CH2)2SO3H, C 1~4 -Alkyl, Halo-C 1~4 -Alkyl, OC 1~4 -Alkyl and O-Halo-C 1~4 -substituted with 1 to 6 substituents independently selected from alkyl; wherein two adjacent substituents on the aryl or heteroaryl moiety may form a 5-8 membered partially unsaturated ring which may contain 1-3 heteroatoms independently selected from O, S or N; This further ring may be unsubstituted or may be substituted with halogen, CN, oxo, OH, CO2H, CO2-C 1~4 -Alkyl, CONHCH2CO2H, CONH(CH2)2SO3H, C 1~4 -Alkyl, Halo-C 1~4 -Alkyl, OC 1~4 -Alkyl and O-Halo-C 1~4 -substituted with 1 to 4 substituents independently selected from alkyl;

[0021] In certain embodiments, in combination with any of the above or below embodiments: [ka] is selected from the group consisting of phenyl, pyridyl, and thiophenyl; wherein phenyl, pyridyl and thiophenyl are unsubstituted or substituted with halogen, CN, SF5, NO2, oxo, C 1~4 -Alkyl, C 0~6 -Alkylene-OR 31 , C 0~6 -Alkylene-(3- to 6-membered cycloalkyl), C 0~6 -alkylene-(3- to 6-membered heterocycloalkyl), C 0~6 -alkylene-(6-membered aryl), C 0~6-alkylene-(5-6 membered heteroaryl), C 0~6 -Alkylene-S(O) n R 31 , C 0~6 -Alkylene-NR 31 S(O)2R 31 , C 0~6 -Alkylene-S(O)NR 31 R 32 , C 0~6 -Alkylene-NR 31 S(O)NR 31 R 32 , C 0~6 -Alkylene-CO2R 31 , O.C. 1~6 -Alkylene-CO2R 31 , C 0~6 -Alkylene-O-COR 31 , C 0~6 -Alkylene-CONR 31 R 32 , C 0~6 -Alkylene-NR 31 -COR 31 , C 0~6 -Alkylene-NR 31 -CONR 31 R 32 , C 0~6 -Alkylene-O-CONR 31 R 32 , C 0~6 -Alkylene-NR 31 -CO2R 31 and C 0~6 -Alkylene-NR 31 R 32 and is substituted with 1 to 4 substituents independently selected from the group consisting of: wherein alkyl, alkylene, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are unsubstituted or substituted with halogen, CN, oxo, hydroxy, COH, CO-C 1~4 -Alkyl, CONHCH2CO2H, CONH(CH2)2SO3H, C 1~4 -Alkyl, Halo-C 1~4 -Alkyl, OC 1~4 -Alkyl and O-Halo-C 1~4-substituted with 1 to 6 substituents independently selected from alkyl; In the formula, residue -LR 1 teeth, [ka] and L is not a bond.

[0022] In certain embodiments, in combination with any of the above or below embodiments: [ka] is selected from phenyl, pyridyl and thiophenyl, wherein phenyl, pyridyl and thiophenyl are unsubstituted or selected from F, Cl, CN, OH, oxo, C 1~4 -Alkyl, Halo-C 1~4 -Alkyl, OC 1~4 -Alkyl and O-Halo-C 1~4 -alkyl; and the residue -LR 1 teeth, [ka] and L is not a bond.

[0023] In certain embodiments, in combination with any of the above or below embodiments: [ka] is phenyl, which is unsubstituted or substituted with F, Cl and Me, and the residues -LR 1 teeth, [ka] and L is not a bond.

[0024] In certain embodiments, in combination with any of the above or below embodiments: L is a bond, C 1~6 -Alkylene, C 2~6 -Alkenylene, C 2~6 - selected from the group consisting of alkynylene, 3- to 10-membered cycloalkylene, 3- to 10-membered heterocycloalkylene containing 1-4 heteroatoms independently selected from N, O and S, 6- or 10-membered arylene, and 5- to 10-membered heteroarylene containing 1-4 heteroatoms independently selected from N, O and S; wherein alkylene, alkenylene, alkynylene, cycloalkylene, heterocycloalkylene, arylene and heteroarylene are unsubstituted or substituted with halogen, CN, SF, NO, oxo, C 1~4 -Alkyl, C 0~6 -Alkylene-OR 41 , C 0~6 -Alkylene-(3- to 6-membered cycloalkyl), C 0~6 -alkylene-(3- to 6-membered heterocycloalkyl), C 0~6 -Alkylene-S(O) n R 41 , C 0~6 -Alkylene-NR 41 S(O)2R 41 , C 0~6 -Alkylene-S(O)NR 41 R 42 , C 0~6 -Alkylene-NR 41 S(O)NR 41 R 42 , C 0~6 -Alkylene-CO2R 41 , O.C. 1~6 -Alkylene-CO2R 41 , C 0~6 -Alkylene-O-COR 41 , C 0~6 -Alkylene-CONR 41 R 42 , C 0~6 -Alkylene-NR 41 -COR 41 , C 0~6 -Alkylene-NR 41 -CONR41 R 42 , C 0~6 -Alkylene-O-CONR 41 R 42 , C 0~6 -Alkylene-NR 41 -CO2R 41 and C 0~6 -Alkylene-NR 41 R 42 and is substituted with 1 to 6 substituents independently selected from the group consisting of: wherein alkyl, alkylene, cycloalkyl and heterocycloalkyl are unsubstituted or substituted with halogen, CN, oxo, hydroxy, COH, CO-C 1~4 -Alkyl, CONHCH2CO2H, CONH(CH2)2SO3H, C 1~4 -Alkyl, Halo-C 1~4 -Alkyl, OC 1~4 -Alkyl and O-Halo-C 1~4 -substituted with 1 to 6 substituents independently selected from alkyl; wherein two adjacent substituents on the arylene moiety and the heteroarylene moiety may form a 5- to 8-membered partially unsaturated ring which may contain 1 to 3 heteroatoms independently selected from O, S, or N; This further ring may be unsubstituted or may be substituted with halogen, CN, oxo, OH, CO2H, CO2-C 1~4 -Alkyl, C 1~4 -Alkyl, Halo-C 1~4 -Alkyl, OC 1~4 -Alkyl and O-Halo-C 1~4 -substituted with 1 to 4 substituents independently selected from alkyl;

[0025] In certain embodiments, in combination with any of the above or below embodiments: L is selected from the group consisting of 3- to 10-membered cycloalkylene, 3- to 10-membered heterocycloalkylene containing 1-4 heteroatoms independently selected from N, O, and S, 6-membered arylene, and 5- to 6-membered heteroarylene containing 1-2 heteroatoms independently selected from N, O, and S; wherein cycloalkylene, heterocycloalkylene, arylene and heteroarylene are unsubstituted or substituted with halogen, CN, SF, NO, oxo, C 1~4 -Alkyl, C 0~6 -Alkylene-OR 41 , C 0~6 -Alkylene-(3- to 6-membered cycloalkyl), C 0~6 -alkylene-(3- to 6-membered heterocycloalkyl), C 0~6 -Alkylene-S(O) n R 41 , C 0~6 -Alkylene-NR 41 S(O)2R 41 , C 0~6 -Alkylene-S(O)NR 41 R 42 , C 0~6 -Alkylene-NR 41 S(O)NR 41 R 42 , C 0~6 -Alkylene-CO2R 41 , O.C. 1~6 -Alkylene-CO2R 41 , C 0~6 -Alkylene-O-COR 41 , C 0~6 -Alkylene-CONR 41 R 42 , C 0~6 -Alkylene-NR 41 -COR 41 , C 0~6 -Alkylene-NR 41 -CONR 41 R 42 , C 0~6 -Alkylene-O-CONR 41 R 42 , C 0~6 -Alkylene-NR 41 -CO2R 41 and C 0~6 -Alkylene-NR 41 R 42 and is substituted with 1 to 6 substituents independently selected from the group consisting of: wherein alkyl, alkylene, cycloalkyl and heterocycloalkyl are unsubstituted or substituted with halogen, CN, oxo, hydroxy, COH, CO-C 1~4 -Alkyl, CONHCH2CO2H, CONH(CH2)2SO3H, C 1~4 -Alkyl, Halo-C 1~4 -Alkyl, OC 1~4 -Alkyl and O-Halo-C 1~4 -substituted with 1 to 6 substituents independently selected from alkyl; wherein two adjacent substituents on the arylene moiety and the heteroarylene moiety may form a 5- to 8-membered partially unsaturated ring which may contain 1 to 3 heteroatoms independently selected from O, S, or N; This further ring may be unsubstituted or may be substituted with halogen, CN, oxo, OH, CO2H, CO2-C 1~4 -Alkyl, C 1~4 -Alkyl, Halo-C 1~4 -Alkyl, OC 1~4 -Alkyl and O-Halo-C 1~4 -substituted with 1 to 4 substituents independently selected from alkyl;

[0026] In certain embodiments, in combination with any of the above or below embodiments: -LR 1 teeth, [ka] is selected from wherein the ring is unsubstituted or is selected from the group consisting of F, Cl, Br, CN, OH, oxo, C 1~4 -Alkyl, Halo-C 1~4 -Alkyl, OC 1~4 -Alkyl, O-Halo-C 1~4 -Alkyl, C 1~4 -Alkyl-OH, Halo-C 1~4 -Alkyl-OH, SO2-C 1~4 -Alkyl and SO2-Halo-C 1~4-alkyl, and two adjacent substituents on a phenyl ring may be taken together to form a -(CH2)3-, -(CH2)4-, -OCF2O-, and -OCHO group.

[0027] In certain embodiments, in combination with any of the above or below embodiments, -LR 1 teeth, [ka] is selected from wherein phenyl is unsubstituted or substituted with 1 to 4 substituents independently selected from the group consisting of F, Cl, CN, OH, Me, and OMe.

[0028] In certain embodiments, in combination with any of the above or below embodiments, -LR 1 teeth, [ka] Optionally, selected from glycine and taurine conjugates thereof.

[0029] In certain embodiments, in combination with any of the above or below embodiments: R 1 H, halogen, CN, SF5, NO2, oxo, C 1~4 -Alkyl, C 0~6 -Alkylene-OR 41 , Y.C. 0~6 -Alkylene-(3-6 membered cycloalkyl), YC 0~6 -Alkylene-(3-6 membered heterocycloalkyl), YC 0~6 -alkylene-(6-membered aryl), YC 0~6 -alkylene-(5-6 membered heteroaryl), C 0~6 -Alkylene-S(=O)(-R 41 )=NR 75 , XC 1~6 -Alkylene-S(=O)(-R 41 )=NR 75 , C0~6 -Alkylene-S(O) n R 41 , XC 1~6 -Alkylene-S(O) n R 41 , C 0~6 -Alkylene-S(=NR 71 )R 41 , XC 1~6 -Alkylene-S(=NR 71 )R 41 , C 0~6 -Alkylene-S(O)(=NR 71 )R 41 , XC 1~6 -Alkylene-S(O)(=NR 71 )R 41 , C 0~6 -Alkylene-S(=NR 71 )2R 41 , XC 1~6 -Alkylene-S(=NR 71 )2R 41 , C 0~6 -Alkylene-NR 41 S(O)2R 41 , XC 1~6 -Alkylene-NR 41 S(O)2R 41 , C 0~6 -Alkylene-S(O)NR 41 R 42 , XC 1~6 -Alkylene-S(O)NR 41 R 42 , C 0~6 -Alkylene-NR 41 S(O)NR 41 R 42 , XC 1~6 -Alkylene-NR 41 S(O)NR 41 R 42 , C 0~6 -Alkylene-SO3R 41 , XC 1~6 -Alkylene-SO3R 41 , C 0~6 -Alkylene-CO2R 41 , XC 1~6 -Alkylene-CO2R 41 , C 0~6-Alkylene-O-COR 41 , XC 1~6 -Alkylene-O-COR 41 , C 0~6 -Alkylene-CONR 41 R 42 , XC 1~6 -Alkylene-CONR 41 R 42 , C 0~6 -Alkylene-CONR 41 OR 41 , XC 1~6 -Alkylene-CONR 41 OR 41 , C 0~6 -Alkylene-CONR 41 SO2R 41 , XC 1~6 -Alkylene-CONR 41 SO2R 41 , C 0~6 -Alkylene-NR 41 -COR 41 , XC 1~6 -C 0~6 -Alkylene-NR 41 -COR 41 , C 0~6 -Alkylene-NR 41 -CONR 41 R 42 , XC 1~6 -Alkylene-NR 41 -CONR 41 R 42 , C 0~6 -Alkylene-O-CONR 41 R 42 , XC 1~6 -Alkylene-O-CONR 41 R 42 , C 0~6 -Alkylene-NR 41 -CO2R 41 , XC 1~6 -Alkylene-NR 41 -CO2R 41 , C 0~6 -Alkylene-NR 41 R 42 , XC 1~6 -Alkylene-NR 41 R 42is selected from the group consisting of wherein alkyl, alkylene, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are unsubstituted or substituted with halogen, CN, oxo, hydroxy, COH, CO-C 1~4 -Alkyl, CONHCH2CO2H, CONH(CH2)2SO3H, C 1~4 -Alkyl, Halo-C 1~4 -Alkyl, OC 1~4 -Alkyl and O-Halo-C 1~4 -substituted with 1 to 6 substituents independently selected from alkyl; wherein two adjacent substituents on the aryl and heteroaryl moieties may form a 5-8 membered partially unsaturated ring which may contain 1-3 heteroatoms independently selected from O, S or N; This further ring may be unsubstituted or may be substituted with halogen, CN, oxo, OH, CO2H, CO2-C 1~4 -Alkyl, CONHCH2CO2H, CONH(CH2)2SO3H, C 1~4 -Alkyl, Halo-C 1~4 -Alkyl, OC 1~4 -Alkyl and O-Halo-C 1~4 -substituted with 1 to 4 substituents independently selected from alkyl;

[0030] In certain embodiments, in combination with any of the above or below embodiments: R 1 is selected from CO2H, tetrazole, CH2CO2H, OCH2CO2H, SO2CH2CO2H, CHMeCO2H, CMe2CO2H, C(OH)MeCO2H, CONHSO2Me, and CONH(OH), and optionally glycine and taurine conjugates thereof.

[0031] In certain embodiments, in combination with any of the above or below embodiments: R 1 is selected from COH and C(OH)MeCOH, and optionally their glycine and taurine conjugates.

[0032] In certain embodiments, in combination with any of the above or below embodiments: [ka] is selected from the group consisting of 3- to 10-membered cycloalkyl, 3- to 10-membered heterocycloalkyl containing 1-3 heteroatoms independently selected from N, O, and S, 6- to 14-membered aryl, and 5- to 14-membered heteroaryl containing 1-4 heteroatoms independently selected from N, O, and S; wherein cycloalkyl, heterocycloalkyl, aryl and heteroaryl are unsubstituted or substituted with halogen, CN, SF, NO, oxo, C 1~4 -Alkyl, C 0~6 -Alkylene-OR 21 , C 0~6 -Alkylene-(3- to 6-membered cycloalkyl), C 0~6 -alkylene-(3- to 6-membered heterocycloalkyl), C 0~6 -Alkylene-S(O) n R 21 , C 0~6 -Alkylene-NR 21 S(O)2R 21 , C 0~6 -Alkylene-S(O)NR 21 R 22 , C 0~6 -Alkylene-NR 21 S(O)NR 21 R 22 , C 0~6 -Alkylene-CR 41 (=N-OR 41 ), C 0~6 -Alkylene-CO2R 21 , O.C. 1~6 -Alkylene-CO2R 21 , C 0~6 -Alkylene-O-COR 21 , C 0~6 -Alkylene-CONR 21 R 22 , C 0~6 -Alkylene-NR 21 -COR 21 , C0~6 -Alkylene-NR 21 -CONR 21 R 22 , C 0~6 -Alkylene-O-CONR 21 R 22 , C 0~6 -Alkylene-NR 21 -CO2R 21 and C 0~6 -Alkylene-NR 21 R 22 and is substituted with 1 to 6 substituents independently selected from the group consisting of: wherein alkyl, alkylene, cycloalkyl and heterocycloalkyl are unsubstituted or substituted with halogen, CN, oxo, hydroxy, COH, CO-C 1~4 -Alkyl, CONHCH2CO2H, CONH(CH2)2SO3H, CO-OC 1~4 -Alkyl, C 1~4 -Alkyl, Halo-C 1~4 -Alkyl, OC 1~4 -Alkyl and O-Halo-C 1~4 -substituted with 1 to 6 substituents independently selected from alkyl; wherein two adjacent substituents on the aryl or heteroaryl moiety may form a 5-8 membered partially unsaturated ring which may contain 1-3 heteroatoms independently selected from O, S or N; This further ring may be unsubstituted or may be substituted with halogen, CN, oxo, OH, CO2H, CO2-C 1~4 -Alkyl, CONHCH2CO2H, CONH(CH2)2SO3H, C 1~4 -Alkyl, Halo-C 1~4 -Alkyl, OC 1~4 -Alkyl and O-Halo-C 1~4 -substituted with 1 to 4 substituents independently selected from alkyl; wherein two adjacent substituents on the cycloalkyl or heterocycloalkyl moiety may form a 5- to 6-membered unsaturated ring which may contain 1 to 3 heteroatoms independently selected from O, S, or N; This further ring may be unsubstituted or may be substituted with halogen, CN, oxo, OH, CO2H, CO2-C 1~4 -Alkyl, CONHCH2CO2H, CONH(CH2)2SO3H, C 1~4 -Alkyl, Halo-C 1~4 -Alkyl, OC 1~4 -Alkyl and O-Halo-C 1~4 -substituted with 1 to 4 substituents independently selected from alkyl; [ka] teeth, [ka] or has a further ring fused thereto in a 1,2-orientation.

[0033] In certain embodiments, in combination with any of the above or below embodiments: [ka] is selected from the group consisting of 6- or 10-membered aryl and 5- to 10-membered heteroaryl containing 1-4 heteroatoms independently selected from N, O, and S; wherein aryl and heteroaryl are unsubstituted or substituted with halogen, CN, SF, NO, oxo, C 1~4 -Alkyl, C 0~6 -Alkylene-OR 21 , C 0~6 -Alkylene-(3- to 6-membered cycloalkyl), C 0~6 -alkylene-(3- to 6-membered heterocycloalkyl), C 0~6 -Alkylene-S(O) n R 21 , C 0~6 -Alkylene-NR 21 S(O)2R 21 , C 0~6 -Alkylene-S(O)NR 21 R 22 , C 0~6 -Alkylene-NR21 S(O)NR 21 R 22 , C 0~6 -Alkylene-CR 41 (=N-OR 41 ), C 0~6 -Alkylene-CO2R 21 , O.C. 1~6 -Alkylene-CO2R 21 , C 0~6 -Alkylene-O-COR 21 , C 0~6 -Alkylene-CONR 21 R 22 , C 0~6 -Alkylene-NR 21 -COR 21 , C 0~6 -Alkylene-NR 21 -CONR 21 R 22 , C 0~6 -Alkylene-O-CONR 21 R 22 , C 0~6 -Alkylene-NR 21 -CO2R 21 and C 0~6 -Alkylene-NR 21 R 22 and is substituted with 1 to 6 substituents independently selected from the group consisting of: wherein alkyl, alkylene, cycloalkyl and heterocycloalkyl are unsubstituted or substituted with halogen, CN, oxo, hydroxy, COH, CO-C 1~4 -Alkyl, CONHCH2CO2H, CONH(CH2)2SO3H, CO-OC 1~4 -Alkyl, C 1~4 -Alkyl, Halo-C 1~4 -Alkyl, OC 1~4 -Alkyl and O-Halo-C 1~4 -substituted with 1 to 6 substituents independently selected from alkyl; wherein two adjacent substituents on the aryl or heteroaryl moiety may form a 5-8 membered partially unsaturated ring which may contain 1-3 heteroatoms independently selected from O, S or N; This further ring may be unsubstituted or may be substituted with halogen, CN, oxo, OH, CO2H, CO2-C 1~4 -Alkyl, CONHCH2CO2H, CONH(CH2)2SO3H, C 1~4 -Alkyl, Halo-C 1~4 -Alkyl, OC 1~4 -Alkyl and O-Halo-C 1~4 -substituted with 1 to 4 substituents independently selected from alkyl; [ka] teeth, [ka] or has a further ring fused thereto in a 1,2-orientation.

[0034] In certain embodiments, in combination with any of the above or below embodiments: [ka] teeth, [ka] is selected from the group consisting of R 2 are Me, F, Cl, CN, Me, CHO, CHF2, CF3, SO2Me, [ka] is selected from During the ceremony, [ka] is not further substituted or is further substituted with 1 to 2 substituents selected from the group consisting of F, Cl, CN, Me, OMe, CHO, CHF2 and CF3.

[0035] In certain embodiments, in combination with any of the above or below embodiments: [ka] teeth, [ka] is selected from the group consisting of:

[0036] In certain embodiments, in combination with any of the above or below embodiments: Formula (I) contains a substituent selected from the group consisting of CO2H, tetrazole, CONHSO2Me, and CONH(OH), and optionally glycine and taurine conjugates thereof.

[0037] In certain embodiments, in combination with any of the above or below embodiments: Formula (I) contains a carboxylic acid moiety and, optionally, its glycine and taurine conjugates.

[0038] In certain embodiments, LR 1 teeth, [ka] wherein the ring is unsubstituted or substituted with F, Cl, Br, CN, OH, oxo, C 1~4 -Alkyl, Halo-C 1~4 -Alkyl, OC 1~4 -Alkyl, O-Halo-C 1~4 -Alkyl, C 1~4 -Alkyl-OH, Halo-C 1~4 -Alkyl-OH, SO2-C 1~4 -Alkyl and SO2-Halo-C 1~4 -alkyl, wherein two adjacent substituents on the phenyl ring may be joined to form a -(CH2)3-, -(CH2)4-, -OCF2O-, and -OCHO- group.

[0039] In certain embodiments, R 1 is C0~6 -Alkylene-CO2R 41 Or C 0~6 -Alkylene-CONR 41 R 42 or its glycine or taurine conjugates.

[0040] In certain embodiments, R 1 is COOH or its glycine or taurine conjugates.

[0041] In certain embodiments, R 1 is C 0~6 -Alkylene-CONR 41 R 42 is.

[0042] In certain embodiments, R 41 and R 42 are independently H and C 1~4 alkyl, C 1~4 The alkyl is unsubstituted or substituted with CO2H.

[0043] In certain embodiments, -CLR 1 teeth, [ka] or its glycine or taurine conjugates.

[0044] In certain embodiments, LR 1 teeth, [ka] or its glycine or taurine conjugates. In certain embodiments, LR 1 teeth, [ka] is.

[0045] In certain embodiments, the compound is a glycine conjugate.

[0046] In certain embodiments, the compound is [ka] or a pharmaceutically acceptable salt thereof. In certain embodiments, the compound is [ka] is.

[0047] In certain embodiments, the compound is [ka] or a glycine conjugate thereof, or a pharmaceutically acceptable salt thereof. In certain embodiments, the compound is [ka] or a pharmaceutically acceptable salt thereof. In certain embodiments, the compound is [ka] is.

[0048] The present disclosure also provides compounds of the present disclosure for use as pharmaceuticals.

[0049] Also provided are compounds of the present disclosure for use in the prevention and / or treatment of diseases treatable with LXR modulators. LXR regulates SREBP1c and other genes involved in de novo lipogenesis, such as ACC, FASN, and SCD. The apoC3 (apoC3) and ANGPTL3 / 4 / 8 genes regulated by LXR are involved in triglyceride clearance. LXR also regulates genes involved in cholesterol metabolism, including IDOL, PCSK9, and CETP.

[0050] Also provided are compounds of the present disclosure for use in treating an LXR-mediated disease selected from non-alcoholic fatty liver disease, non-alcoholic steatohepatitis, hepatitis, liver fibrosis, obesity, insulin resistance, type II diabetes, familial hypercholesterolemia, hypercholesterolemia in nephrotic syndrome, metabolic syndrome, cardiac steatosis, cancer, viral myocarditis, hepatitis C virus infection or complications thereof, and undesirable side effects of long-term glucocorticoid treatment in diseases such as rheumatoid arthritis, inflammatory bowel disease, and asthma.

[0051] In certain embodiments, the disease is selected from non-alcoholic fatty liver disease, non-alcoholic steatohepatitis, hepatitis, liver fibrosis, obesity, insulin resistance, type II diabetes, familial hypercholesterolemia, hypercholesterolemia in nephrotic syndrome, metabolic syndrome, or cardiac steatosis.

[0052] In certain embodiments, the disease is cancer.

[0053] In certain embodiments, the disease is selected from viral myocarditis, hepatitis C virus infection, or a complication thereof.

[0054] The present disclosure also relates to methods for preventing and / or treating dyslipidemia.The present disclosure relates to methods for preventing and / or treating metabolic disorders associated with impaired lipid homeostasis.

[0055] Also provided are compounds of the present disclosure for use in treating dyslipidemia, which in certain embodiments includes conditions characterized by alterations in triglycerides, cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein (HDL), other lipids, or lipoproteins.

[0056] Dyslipidemia can be of any of the following types: Fredrickson's phenotype I, Fredrickson's phenotype II, Fredrickson's phenotype III, Fredrickson's phenotype IV, and Fredrickson's phenotype V.

[0057] In certain embodiments, the dyslipidemia is hypertriglyceridemia. In certain embodiments, the dyslipidemia is severe hypertriglyceridemia.

[0058] In certain embodiments, the dyslipidemia is selected from hypertriglyceridemia (HTG), severe hypertriglyceridemia (SHTG), familial hypercholesterolemia, heterozygous familial hypercholesterolemia (HeFH), and homozygous familial hypercholesterolemia (HoFH).

[0059] In certain embodiments, the dyslipidemia is selected from familial chylomicronemia syndrome and mixed disorder chylomicronemia. In certain embodiments, the dyslipidemia is hypercholesterolemia. In certain embodiments, the dyslipidemia is familial combined hyperlipidemia (e.g., elevated LDL and VLDL). In certain embodiments, the dyslipidemia is familial dysbetalipoproteinemia (e.g., elevated VLDL and chylomicrons). In certain embodiments, the dyslipidemia is hypertrigylceridemia (e.g., elevated VLDL, and possibly elevated cholesterol). In certain embodiments, the dyslipidemia is mixed dyslipidemia (e.g., elevated chylomicrons and VLDL, TG >99% percentile).

[0060] In certain embodiments, dyslipidemia is selected from severe hypertriglyceridemia (SHTG) or hypertriglyceridemia (HTG).In certain embodiments, the compound is used to treat SHTG, characterized by serum triglyceride levels greater than 1000 mg / dL.In certain embodiments, the compound is used to reduce triglyceride levels and reduce the risk of pancreatitis.In certain embodiments, the method reduces the risk of pancreatitis in subjects.

[0061] In certain embodiments, the compound is for use in lowering triglyceride levels to reduce cardiovascular risk, hi certain embodiments, the method reduces cardiovascular risk in a subject.

[0062] Also provided are compounds of the present disclosure for use in treating a clinical sequelae of dyslipidemia selected from hypertriglyceridemia (HTG), severe hypertriglyceridemia (SHTG), familial hypercholesterolemia, heterozygous familial hypercholesterolemia, homozygous familial hypercholesterolemia, familial chylomicronemia syndrome, mixed disorder chylomicronemia, hypercholesterolemia, familial combined hyperlipidemia, familial dysbetalipoproteinemia, and mixed dyslipidemia.

[0063] Also provided are compounds of the present disclosure for use in treating metabolic disorders associated with disorders of lipid homeostasis, such as disorders in de novo lipogenesis.

[0064] Also provided are compounds of the present disclosure for use in treating metabolic disorders associated with impaired lipid homeostasis.

[0065] Also provided are compounds of the present disclosure for use in treating non-alcoholic fatty liver disease (NAFLD) or non-alcoholic steatohepatitis (NASH) in a subject with a glucokinase regulatory protein (GCKR) phenotype. In certain embodiments, de novo lipogenesis is enhanced in the subject. In certain embodiments, treatment reduces lipogenic gene expression in the subject and / or lipid accumulation in the subject. In certain embodiments, a method comprises treating a metabolic disorder associated with impaired de novo lipogenesis. In certain embodiments, a method comprises treating non-alcoholic fatty liver disease (NAFLD) or non-alcoholic steatohepatitis (NASH) in a subject in need of treatment, wherein the subject has a glucokinase regulatory protein (GCKR) phenotype. In certain embodiments, de novo lipogenesis is enhanced in the subject.

[0066] The present disclosure further relates to a method for preventing and / or treating an LXR-mediated disease, the method comprising administering to a subject in need of treatment an effective amount of a compound of the present disclosure.

[0067] More specifically, the present disclosure relates to methods for preventing and / or treating diseases selected from non-alcoholic fatty liver disease, non-alcoholic steatohepatitis, hepatitis, liver fibrosis, obesity, insulin resistance, type II diabetes, familial hypercholesterolemia, hypercholesterolemia in nephrotic syndrome, metabolic syndrome, cardiac steatosis, cancer, viral myocarditis, hepatitis C virus infection or complications thereof, and undesirable side effects of long-term glucocorticoid treatment in diseases such as rheumatoid arthritis, inflammatory bowel disease, and asthma.

[0068] The present disclosure also relates to methods for preventing and / or treating diseases such as alcoholic liver disease or alcoholic hepatitis. In certain embodiments, alcoholic liver disease or alcoholic hepatitis is also associated with increased de novo lipogenesis (DNL) / steatosis. Types of alcoholic liver disease include fatty liver, alcoholic hepatitis, and alcoholic cirrhosis. Blood lipids can be associated with alcoholic liver disease. Alcohol consumption can lead to high triglycerides and cholesterol in the liver. Also, when the body breaks down alcohol, high triglyceride levels can occur in the blood.

[0069] Furthermore, the present disclosure also relates to the use of a compound according to the present disclosure in the preparation of a medicament for the prevention and / or treatment of an LXR-mediated disease.

[0070] More specifically, the present disclosure relates to the use of a compound according to the present disclosure in the preparation of a medicament for the prevention and / or treatment of an LXR-mediated disease, wherein the disease is selected from non-alcoholic fatty liver disease, non-alcoholic steatohepatitis, hepatitis, liver fibrosis, obesity, insulin resistance, type II diabetes, familial hypercholesterolemia, hypercholesterolemia in nephrotic syndrome, metabolic syndrome, cardiac steatosis, cancer, viral myocarditis, hepatitis C virus infection or complications thereof, and undesirable side effects of long-term glucocorticoid treatment in diseases such as rheumatoid arthritis, inflammatory bowel disease, and asthma.

[0071] The present disclosure also relates to the use of a compound according to the present disclosure in the preparation of a medicament for the prevention and / or treatment of an LXR-mediated disease.

[0072] The present disclosure also relates to the use of a compound according to the present disclosure in the preparation of a medicament for preventing and / or treating dyslipidemia.The present disclosure also relates to the use of a compound according to the present disclosure in the preparation of a medicament for preventing and / or treating a metabolic disorder associated with impaired lipid homeostasis.In certain embodiments, the expression of lipogenic genes in a subject and / or lipid accumulation in a subject is reduced.

[0073] Also provided are pharmaceutical compositions comprising a compound of the present disclosure and a pharmaceutically acceptable carrier or excipient.

[0074] In the context of this disclosure, "C 1~6 "C -alkyl" means a saturated alkyl chain having from 1 to 6 carbon atoms, which may be straight or branched. Examples include methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, tert-butyl, n-pentyl, isopentyl, n-hexyl, and isohexyl. Similarly, "C 1~4 "-Alkyl" means a saturated alkyl chain having 1 to 4 carbon atoms which may be straight or branched. Examples include methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, and tert-butyl.

[0075] "Haro-C 1~4 The term "-alkyl" means that one or more hydrogen atoms in the alkyl chain have been replaced by a halogen. Examples include CH2F, CHF2, and CF3.

[0076] "C 0~6 "C-alkylene" means that each group is divalent and connects the attached residue to the rest of the molecule. Furthermore, in the context of this disclosure, "C0-alkylene" is meant to represent a bond, while C1-alkylene means a methylene linker, C2-alkylene means an ethylene linker or a methyl-substituted methylene linker, etc. 0~6 Preferably, -alkylene represents a bond, a methylene, an ethylene group, or a propylene group.

[0077] Similarly, "C 2~6 -alkenylene" and "C 2~6 "-Alkynylene" means a divalent alkenyl or alkynyl group connecting two portions of a molecule.

[0078] A 3- to 10-membered cycloalkyl group means a saturated or partially unsaturated monocyclic, bicyclic, spirocyclic, or polycyclic ring system containing 3 to 10 carbon atoms. Examples include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclohexenyl, bicyclo[2.2.2]octyl, bicyclo[3.2.1]octanyl, spiro[3.3]heptyl, bicyclo[2.2.1]heptyl, adamantyl, and penta-cyclo[4.2.0.0]octanyl. 2,5 .0 3,8 .0 4,7 octyl. Consequently, a 3- to 6-membered cycloalkyl group means a saturated or partially unsaturated monocyclic, bicyclic or spirocyclic ring system containing 3 to 6 carbon atoms, while a 5- to 8-membered cycloalkyl group means a saturated or partially unsaturated monocyclic, bicyclic or spirocyclic ring system containing 5 to 8 carbon atoms.

[0079] A 3- to 10-membered heterocycloalkyl group refers to a saturated or partially unsaturated 3- to 10-membered carbon monocyclic, bicyclic, spirocyclic, or polycyclic ring in which 1, 2, 3, or 4 carbon atoms are replaced with 1, 2, 3, or 4 heteroatoms, independently selected from N, O, S, SO, and SO. Examples include epoxydyl, oxetanyl, pyrrolidinyl, tetrahydrofuranyl, piperidinyl, piperazinyl, tetrahydropyranyl, 1,4-dioxanyl, morpholinyl, 4-quinuclidinyl, 1,4-dihydropyridinyl, and 6-azabicyclo[3.2.1]octanyl. A heterocycloalkyl group can be connected to the rest of the molecule through a carbon, nitrogen (e.g., in morpholine or piperidine), or sulfur atom. An example of an S-linked heterocycloalkyl is cyclic sulfonimidamide. [ka]

[0080] A 5- to 14-membered monocyclic, bicyclic, or tricyclic heteroaromatic ring system (also referred to herein as heteroaryl) refers to an aromatic ring system containing up to six heteroatoms independently selected from N, O, S, SO, and SO. Examples of monocyclic heteroaromatic rings include pyrrolyl, imidazolyl, furanyl, thiophenyl (thienyl), pyridinyl, pyrimidinyl, pyrazinyl, pyrazolyl, oxazolyl, isoxazolyl, triazolyl, oxadiazolyl, and thiadiazolyl. This also refers to bicyclic ring systems in which heteroatoms may be present in one or both rings, including bridgehead atoms. Examples include quinolinyl, isoquinolinyl, quinoxalinyl, benzimidazolyl, benzisoxazolyl, benzofuranyl, benzoxazolyl, indolyl, indolizinyl 1,5-naphthyridinyl, 1,7-naphthyridinyl, and pyrazolo[1,5-a]pyrimidinyl. Examples of tricyclic heteroaromatic rings include acridinyl, benzo[b][1,5]naphthyridinyl, and pyrido[3,2-b][1,5]naphthyridinyl.

[0081] The nitrogen or sulfur atom of the heteroaryl system can also be optionally oxidized to the corresponding N-oxide, S-oxide or S,S-dioxide.

[0082] Unless otherwise specified, heteroaryl systems may be bonded via a carbon or nitrogen atom. Examples of N-bonded heterocycles include: [ka] There is.

[0083] A 6-14 membered monocyclic, bicyclic or tricyclic aromatic ring system (also referred to herein as aryl) means an aromatic carbocyclic ring such as phenyl, naphthyl, anthracenyl or phenanthrenyl.

[0084] The term "N-oxide" refers to a compound in which the nitrogen in a heteroaromatic system (preferably pyridinyl) is oxidized. Such compounds can be obtained in a known manner by reacting a compound of the present disclosure (such as a pyridinyl group) with HO or a peracid in an inert solvent.

[0085] The halogen is selected from fluorine, chlorine, bromine, and iodine, more preferably fluorine or chlorine, most preferably fluorine.

[0086] Any formula or structure given herein is also intended to represent unlabeled forms of the compound as well as isotopically labeled forms. Isotopically labeled compounds have the structure shown in the formula given herein except that one or more atoms are replaced with an atom having a selected atomic mass or mass number. Examples of isotopes that may be incorporated into the compounds of the present disclosure include: 2 H (deuterium, D), 3 H (tritium), 11 C. 13 C. 14 C. 15 N, 18 F, 31 P, 32 P, 35 S, 36 Cl, and 125 Included are isotopes of hydrogen, carbon, nitrogen, oxygen, phosphorus, fluorine, and chlorine, such as, but not limited to, I. Various isotopically labeled compounds of the present disclosure, e.g. 3 H, 13 C, and 14These are compounds incorporating a radioactive isotope, such as C. Such isotopically labeled compounds may be useful for detection or imaging techniques, such as positron emission tomography (PET) or single-photon emission computed tomography (SPECT), including metabolic studies, reaction kinetic studies, drug or substrate tissue distribution assays, or radioactive treatment of patients. For example, isotopically labeled compounds of the present disclosure and prodrugs thereof can generally be prepared by carrying out the procedures disclosed in the schemes or examples and preparations described below by substituting readily available isotopically labeled reagents for non-isotopically labeled reagents.

[0087] The present disclosure also includes "deuterated analogs" of compounds of Formula (I) in which one to n hydrogens bonded to a carbon atom have been replaced with deuterium, where n is the number of hydrogens in the molecule. Such compounds may exhibit increased resistance to metabolism and thus may be useful for increasing the half-life of any compound of Formula (I) when administered to a mammal, e.g., a human. See, e.g., Foster in Trends Pharmacol. Sci. 1984:5;524. Such compounds are synthesized by means well known in the art, for example, by employing starting materials in which one or more hydrogens have been replaced with deuterium.

[0088] Therapeutic compounds of the present disclosure that are labeled or substituted with deuterium may have improved DMPK (drug metabolism and pharmacokinetic) properties related to distribution, metabolism, and excretion (ADME). Substitution with heavier isotopes, such as deuterium, may confer certain therapeutic advantages resulting from greater metabolic stability, such as increased in vivo half-life, reduced dose requirements, and / or improved therapeutic index. 18 F-labeled compounds may be useful for PET or SPECT studies.

[0089] The concentration of such heavier isotopes, particularly deuterium, can be determined by isotopic enrichment factor.In the compounds of the present disclosure, any atom that is not specifically designated as a specific isotope is meant to represent any stable isotope of that atom.Unless otherwise stated, when a position is specifically designated as "H" or "hydrogen", it is understood that this position has hydrogen with its natural abundance isotopic composition.Therefore, in the compounds of the present disclosure, any atom that is specifically designated as deuterium (D) is meant to represent deuterium.

[0090] Furthermore, the compounds of the present disclosure are partially subject to tautomerism. For example, when a heteroaromatic group containing a nitrogen atom in the ring is substituted with a hydroxy group on the carbon atom adjacent to the nitrogen atom, the following tautomerism may occur: [ka]

[0091] The cycloalkyl or heterocycloalkyl group can be attached to a linear or spiro ring, for example, when cyclohexane is replaced with the heterocycloalkyl group oxetane, the following structure is possible: [ka]

[0092] The term "1,3-oriented" means that there is at least one possible substituent on the ring and that there are three atoms between the two substituents attached to the ring system, for example: [ka]

[0093] The term "1,2-oriented" (ortho) means that there is one possible substituent on the ring and there are two atoms between the two substituents attached to the ring system, for example: [ka] Alternatively, the residue R may be incorporated into a further fused ring, for example: [ka]

[0094] It will be understood by those skilled in the art that if a list of alternative substituents includes members that cannot be used to replace a particular group because of their valence requirements or for other reasons, the list is intended to be read to include only those members of the list that are suitable to replace that particular group.

[0095] The compounds of the present disclosure may be in the form of prodrug compounds. A "prodrug compound" refers to a derivative that is converted into a compound of the present disclosure by reaction with enzymes, gastric acid, or the like under physiological conditions in vivo, for example, by oxidation, reduction, hydrolysis, or the like, each of which is enzymatic. Examples of prodrugs include compounds in which an amino group in a compound of the present disclosure is acylated, alkylated, or phosphorylated to form, for example, eicosanoylamino, alanylamino, or pivaloyloxymethylamino; a hydroxyl group is acylated, alkylated, phosphorylated, or converted to boric acid to form, for example, acetyloxy, palmitoyloxy, pivaloyloxy, succinyloxy, fumaryloxy, or alanyloxy; or a carboxyl group is esterified or amidated. These compounds can be produced from the compounds of the present disclosure according to well-known methods. Other examples of prodrugs include compounds in which a carboxylic acid salt in a compound of the present disclosure is converted to, for example, an alkyl ester, an aryl ester, an arylalkylene ester, an amino ester, a choline ester, an acyloxyalkyl ester, a 1-((alkoxycarbonyl)oxy)-2-alkyl ester, or a linolenoyl ester (referred to herein as "ester prodrugs"). Exemplary structures for carboxylic acid prodrugs include the following: [ka]

[0096] Ester-based prodrugs can also be formed when a carboxylic acid forms a lactone with a hydroxy group within the molecule. An illustrative example is: [ka]

[0097] The term "-CO2H or its ester" means that carboxylic acids and alkyl esters such as the following are intended: [ka]

[0098] The term "glycine or taurine conjugate thereof" means that a carboxylic acid moiety in the molecule is linked to glycine or taurine, respectively, to form the following conjugate (and potentially a prodrug, solvate, or pharmaceutically acceptable salt thereof): [ka]

[0099] Metabolites of the compounds of the present disclosure are also within the scope of the present disclosure.

[0100] When tautomerism, e.g., keto-enol tautomerism, of a compound of the present disclosure or a prodrug thereof may occur, the individual forms, e.g., keto and enol forms, as well as mixtures thereof in any ratio, are each within the scope of the present disclosure. The same applies to stereoisomers, e.g., enantiomers, cis / trans isomers, atopy isomers, conformational isomers, etc.

[0101] If necessary, isomers can be separated by methods known in the art, for example, by liquid chromatography. The same applies to enantiomers, for example, by using chiral stationary phases. Furthermore, enantiomers can be isolated by converting them into diastereomers, i.e., by coupling with enantiomerically pure auxiliary compounds, followed by separation of the resulting diastereomers, and cleavage of the auxiliary residue. Alternatively, any enantiomer of the compounds of the present disclosure can be obtained from stereoselective synthesis using optically pure starting materials. Another method for obtaining pure enantiomers from racemic mixtures is to use enantioselective crystallization using chiral counterions.

[0102] The compounds of the present disclosure may be in the form of pharmaceutically acceptable salts or solvates. The term "pharmaceutically acceptable salts" refers to salts prepared from pharmaceutically acceptable non-toxic bases or acids, including inorganic and organic bases or acids. When compounds of the present disclosure contain one or more acidic or basic groups, the present disclosure also includes their corresponding pharmaceutically or toxicologically acceptable salts, particularly their pharmaceutically acceptable salts. Thus, compounds of the present disclosure containing acidic groups may exist on these groups and be used in accordance with the present disclosure as, for example, alkali metal salts, alkaline earth metal salts, or ammonium salts. More precise examples of such salts include sodium salts, potassium salts, calcium salts, magnesium salts, or salts with ammonia, or organic amines such as ethylamine, ethanolamine, triethanolamine, or amino acids. Compounds of the present disclosure containing one or more basic groups, i.e., protonatable groups, may exist in the form of their addition salts with inorganic or organic acids and be used in accordance with the present disclosure. Examples of suitable acids include hydrogen chloride, hydrogen bromide, phosphoric acid, sulfuric acid, nitric acid, methanesulfonic acid, p-toluenesulfonic acid, naphthalenedisulfonic acid, oxalic acid, acetic acid, tartaric acid, lactic acid, salicylic acid, benzoic acid, formic acid, propionic acid, pivalic acid, diethylacetic acid, malonic acid, succinic acid, pimelic acid, fumaric acid, maleic acid, malic acid, sulfamic acid, phenylpropionic acid, gluconic acid, ascorbic acid, isonicotinic acid, citric acid, adipic acid, and other acids known to those skilled in the art. When the compounds of the present disclosure contain both acidic and basic groups in the molecule, the present disclosure also includes internal salts, i.e., betaines (zwitterions), in addition to the above-mentioned salt forms. The respective salts can be obtained by conventional methods known to those skilled in the art, for example, by contacting them with organic or inorganic acids or bases in a solvent or dispersant, or by anion or cation exchange with other salts. The present disclosure also includes all salts of the compounds of the present disclosure that are not directly suitable for use in pharmaceuticals due to their poor physiological compatibility, but which can be used, for example, as intermediates in chemical reactions or for the preparation of pharmaceutically acceptable salts.

[0103] Additionally, the compounds of the present disclosure may exist in the form of solvates, such as those that include water as a solvate, or pharmaceutically acceptable solvates such as alcohols, particularly ethanol.

[0104] Additionally, the present disclosure provides pharmaceutical compositions comprising, as an active ingredient, at least one compound of the present disclosure, or a prodrug compound thereof, or a pharmaceutically acceptable salt or solvate thereof, in association with a pharmaceutically acceptable carrier.

[0105] "Pharmaceutical composition" refers to one or more active ingredients and one or more inactive ingredients that constitute a carrier, as well as any product that results directly or indirectly from the combination, complexation, or aggregation of any two or more of the ingredients, or from the dissociation of one or more of the ingredients, or from any other type of reaction or interaction of one or more of the ingredients. Thus, pharmaceutical compositions of the present disclosure encompass any composition made by mixing at least one compound of the present disclosure with a pharmaceutically acceptable carrier.

[0106] The pharmaceutical compositions of the present disclosure may additionally contain one or more other compounds as active ingredients, such as prodrug compounds or other nuclear receptor modulators.

[0107] The compositions are suitable for oral, rectal, topical, parenteral (including subcutaneous, intramuscular, and intravenous), ocular (ocular), pulmonary (nasal or oral inhalation), or intranasal administration, although the most suitable route in any given case will depend on the nature and severity of the condition being treated and the nature of the active ingredient. They may be conveniently presented in unit dosage form and prepared by any of the methods well known in the art of pharmacy.

[0108] The compounds of the present disclosure act as LXR modulators.

[0109] Ligands for nuclear receptors, including LXR ligands, can act as either agonists, antagonists, or inverse agonists. Agonists, in this context, refer to small molecule ligands that bind to the receptor and stimulate transcriptional activity of the receptor, as determined, for example, by an increase in mRNA or protein transcribed under the control of an LXR response element. Transcriptional activity can also be determined in biochemical or cellular in vitro assays that monitor agonist, antagonist, or inverse agonist activity using only the ligand-binding domain of LXRα or LXRβ, potentially in conjunction with a global DNA-binding sequence such as the Gal4 domain, and interactions with cofactors (i.e., corepressors or coactivators).

[0110] By this definition, an agonist stimulates LXR-driven or LXR-Gal4-driven transcriptional activity, whereas an antagonist is defined as a small molecule that binds to LXR and thereby inhibits transcriptional activation that would otherwise occur via endogenous LXR ligands.

[0111] Inverse agonists differ from antagonists in that they not only bind to LXRs and inhibit their transcriptional activity, but also actively block LXR-driven transcription even in the absence of endogenous agonists. Although it is difficult to distinguish between antagonist and inverse agonist activity of LXRs in vivo, given the constant presence of some endogenous LXR agonist, biochemical or cellular reporter assays can more clearly distinguish the two activities. At the molecular level, inverse agonists should not allow the recruitment of coactivator proteins or their active parts, but should instead lead to the active recruitment of corepressor proteins, which are their active parts. In this context, an LXR antagonist is defined as an LXR ligand that does not lead to the recruitment of coactivators or corepressors, but acts only by displacing LXR agonists. Therefore, the use of assays such as the Gal4-mammalian two-hybrid assay is essential to distinguish between LXR compounds that recruit coactivators or corepressors (Kremoser et al., Drug Discov. Today 2007;12:860; Gronemeyer et al., Nat. Rev. Drug Discov. 2004;3:950).

[0112] Because the distinction between LXR agonists, LXR antagonists, and LXR inverse agonists is unclear and fluid, the term "LXR modulator" is designed to encompass all compounds that are not pure LXR agonists but that exhibit some degree of corepressor recruitment in conjunction with a reduction in LXR transcriptional activity.Therefore, it should be noted that LXR modulators encompass LXR antagonists and LXR inverse agonists, and even weak LXR agonists can act as LXR antagonists if they prevent the full transcriptional activation of full agonists.

[0113] The compounds are useful for the prevention and / or treatment of LXR-mediated diseases. Some of these diseases are disorders related to steatosis, i.e., tissue fat accumulation. These diseases include the full range of non-alcoholic fatty liver disease, including non-alcoholic steatohepatitis, hepatitis, and liver fibrosis, as well as insulin resistance, metabolic syndrome, and cardiac steatosis. LXR modulator-based pharmaceuticals may also be useful for treating hepatitis C virus infection or its complications, and for preventing the undesirable side effects of long-term glucocorticoid treatment in diseases such as rheumatoid arthritis, inflammatory bowel disease, and asthma.

[0114] A distinct group of applications for LXR modulators may lie in the treatment of cancer. LXR antagonists or inverse agonists may be useful in countering the so-called Warburg effect, which is associated with the transition from normal differentiated cells to cancer cells (see Liberti et al., Trends Biochem. Sci. 2016;41:211; Ward & Thompson, Cancer Cell 2012;21:297-308). Furthermore, LXRs are known to regulate various components of the innate and adaptive immune systems. Oxysterols, known as endogenous LXR agonists, have been identified as mediators of LXR-dependent immunosuppressive effects present in the tumor microenvironment (Traversari et al., Eur. J. Immunol. 2014;44:1896). Therefore, it is reasonable to hypothesize that LXR antagonists or inverse agonists may be able to stimulate the immune system and antigen-presenting cells, particularly to elicit antitumor immune responses. This latter effect of LXR antagonists or inverse agonists can be used in the treatment of late stage cancers in general, and in particular for cancerous solid tumor types that show very high signs of an inadequate immune response and Warburg metabolism.

[0115] More specifically, the anticancer activity of the LXR inverse agonist SR9243 has been shown to be mediated by disrupting the Warburg effect and lipogenesis in various tumor cells in vitro and in SW620 colon tumor cells in athymic mice in vivo (see Flaveny et al. Cancer Cell. 2015;28:42; Steffensen, Cancer Cell 2015;28:3).

[0116] Therefore, LXR modulators (preferably LXR inverse agonists) may be useful in the treatment of Warburg-dependent cancers.

[0117] LXR modulators (preferably LXR inverse agonists) can counteract the diabetogenic effects of glucocorticoids without impairing their anti-inflammatory effects and may therefore be used to prevent the undesirable side effects of long-term glucocorticoid treatment in diseases such as rheumatoid arthritis, inflammatory bowel disease, and asthma (Patel et al. Endocrinology 2017:158:1034).

[0118] LXR modulators (preferably LXR inverse agonists) may be useful in treating hepatitis C virus-mediated hepatic steatosis (see Garcia-Mediavilla et al. Lab. Invest. 2012;92:1191).

[0119] LXR modulators (preferably LXR inverse agonists) may be useful in the treatment of viral myocarditis (see Papageorgiou et al. Cardiovasc. Res. 2015;107:78).

[0120] LXR modulators (preferably LXR inverse agonists) may be useful in treating insulin resistance (see Zheng et al. PLoS One 2014;9:e101269).

[0121] LXR modulators (preferably LXR inverse agonists) may be useful in the treatment of familial hypercholesterolemia (see Zhou et al. J. Biol. Chem. 2008;283:2129).

[0122] LXR modulators (preferably LXR inverse agonists) may be useful for treating hypercholesterolemia in nephrotic syndrome (see Liu & Vazizi in Nephrol. Dial. Transplant. 2014;29:538).

[0123] The present disclosure relates to a method for treating dyslipidemia in a subject in need of treatment, comprising administering an effective amount of a compound of the present disclosure to the subject in need of treatment. The claimed compounds are effective in lowering the amount of lipids, such as triglycerides, in a patient. Elevated triglyceride levels in a patient are an unhealthy or risky condition in themselves and are involved in many disorders. High triglycerides can contribute to arterial hardening or thickening of arterial walls (atheriosclerosis), which can increase the risk of stroke, heart attack, and heart disease. Very high triglycerides can also cause acute pancreatic inflammation (pancreatitis).

[0124] Disorders of lipid metabolism, or dyslipidemia, include a variety of conditions characterized by abnormal concentrations of one or more lipids (i.e., cholesterol and triglycerides) and / or apolipoproteins (i.e., apolipoproteins A, B, C, and E) and / or lipoproteins (i.e., macromolecular complexes formed by lipids and apolipoproteins that allow lipids to circulate in the blood, such as LDL, VLDL, and IDL). The term "dyslipidemia" refers to disorders of lipoprotein metabolism, including lipoprotein overproduction or deficiency. Dyslipidemia may be manifested by elevated blood levels of total cholesterol, low-density lipoprotein (LDL) cholesterol, and / or triglycerides, and / or reduced blood levels of high-density lipoprotein (HDL) cholesterol.

[0125] In certain embodiments, dyslipidemia is characterized by abnormal levels of one or more lipids and / or apolipoproteins. In certain embodiments, dyslipidemia is characterized by elevated levels of total cholesterol, LDL cholesterol, triglycerides (TG), or any combination of the foregoing. In certain embodiments, dyslipidemia is characterized by reduced levels of HDL cholesterol.

[0126] In the context of the present disclosure, dyslipidemia includes severe hypertriglyceridemia (SHTG), familial hypercholesterolemia, and Fredrickson phenotype hyperlipoproteinemia. Familial hypercholesterolemia includes, for example, heterozygous familial hypercholesterolemia (HeFH) and homozygous familial hypercholesterolemia (HoFH). Fredrickson phenotype hyperlipoproteinemia includes, for example, Fredrickson phenotype I, Fredrickson phenotype II, Fredrickson phenotype IIb, Fredrickson phenotype III, Fredrickson phenotype IV, and Fredrickson phenotype V. Fredrickson phenotype I includes familial chylomicronemia syndrome and mixed disorder chylomicronemia syndrome. Fredrickson phenotype II includes hypercholesterolemia. Fredrickson phenotype IIb includes familial combined hyperlipidemia, characterized by various conditions including elevated LDL and / or VLDL concentrations. Fredrickson phenotype III includes familial dysbetalipoproteinemia characterized by a variety of conditions including elevated VLDL and / or chylomicron concentrations. Fredrickson phenotype IV includes hypertriglyceridemia (HTG) characterized by a variety of conditions including elevated VLDL and / or cholesterol concentrations. Fredrickson phenotype V includes mixed dyslipidemia characterized by a variety of conditions including elevated chylomicrons and / or VLDL concentrations as well as triglyceride (TG) concentrations >99%.

[0127] The present disclosure relates to a method for treating hypertriglyceridemia in a subject in need thereof, comprising administering to the subject in need thereof an effective amount of a compound of the present disclosure. The term "hypertriglyceridemia" refers to high (exceeding) blood (-emia) levels of triglycerides. Elevated triglyceride levels are associated with atherosclerosis and predispose to cardiovascular disease (e.g., contribute to increased cardiovascular risk), even in the absence of hypercholesterolemia (high cholesterol levels). Generally, serum triglyceride levels in the range of 150-199 mg / dL (1.70-2.25 mmol / L) are considered borderline-high, serum triglyceride levels in the range of 200-499 mg / dL (2.26-5.64 mmol / L) are considered high, and serum triglyceride levels in the range of 500 mg / dL (5.65 mmol / L) or higher are considered very high. In certain aspects, these general guidelines may be adjusted based on evolving clinical guidelines for clinicians. In certain embodiments, hypertriglyceridemia is severe hypertriglyceridemia, which is a triglyceride level of 500 mg / dL or higher.

[0128] The present disclosure relates to a method of treating a metabolic disorder associated with impaired lipid homeostasis in a subject in need thereof, the method comprising administering to the subject in need thereof an effective amount of a compound of the present disclosure.

[0129] Glucokinase regulatory protein (GCKR) is a genetic variant that can interfere with glucose and lipid homeostasis by regulating glucose storage / processing and by providing substrates for de novo lipogenesis through inhibition of glucokinase. GCKR may contribute to the development and severity of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH).

[0130] Combination therapy In certain embodiments, the method comprises administering at least one or more second drugs.In further embodiments, the one or more second drugs are therapeutic drugs.In certain embodiments, the composition can further comprise a pharmaceutically active antihyperlipidemic drug or a nutritional supplement that can also affect lipid content.For example, suitable drugs include statins, fish oil, FGF21 agonists, THRβ agonists and PCSK9 inhibitors.

[0131] Administration The present disclosure relates to the administration of a pharmaceutical composition comprising a compound of formula (I), its glycine conjugate, taurine conjugate, enantiomer, diastereomer, tautomer, N-oxide, solvate, prodrug, and pharmaceutically acceptable salt to a subject in need thereof. Reference to a compound of formula (I) herein may include its glycine conjugate, taurine conjugate, enantiomer, diastereomer, tautomer, N-oxide, solvate, prodrug, or pharmaceutically acceptable salt.

[0132] The present disclosure provides for the administration of pharmaceutical compositions at low doses with efficacy. The pharmacokinetic profile of the compounds of the present disclosure provides transient exposure and lower sustained exposure of metabolites.

[0133] The present disclosure provides a method of treating a disorder in a subject in need thereof, comprising daily administration of 0.1 to 25 mg of the compound of formula (I), its glycine conjugates, taurine conjugates, enantiomers, diastereomers, tautomers, N-oxides, solvates, prodrugs, and pharmaceutically acceptable salts.

[0134] In certain embodiments, the compound is compound 21 / 3 or precursor 6 / 3. In certain embodiments, the compound is compound 21 / 3. In certain embodiments, the compound is compound precursor 6 / 3.

[0135] In some embodiments, the pharmaceutical composition contains about 0.1 mg to about 25 mg of the compound of Formula (I), its glycine conjugates, taurine conjugates, enantiomers, diastereomers, tautomers, N-oxides, solvates, prodrugs, and pharmaceutically acceptable salts per dose. In some embodiments, the pharmaceutical composition contains about 0.1 mg to about 20 mg of the compound of Formula (I), its glycine conjugates, taurine conjugates, enantiomers, diastereomers, tautomers, N-oxides, solvates, prodrugs, and pharmaceutically acceptable salts per dose. In some embodiments, the pharmaceutical composition contains about 0.5 mg to about 25 mg of the compound of Formula (I), its glycine conjugates, taurine conjugates, enantiomers, diastereomers, tautomers, N-oxides, solvates, prodrugs, and pharmaceutically acceptable salts per dose. In some embodiments, the pharmaceutical composition contains from about 0.5 mg to about 20 mg of the compound of Formula (I), its glycine conjugates, taurine conjugates, enantiomers, diastereomers, tautomers, N-oxides, solvates, prodrugs, and pharmaceutically acceptable salts per dose.

[0136] In certain embodiments, the pharmaceutical composition comprises: a) a compound of formula (I), its glycine conjugates, taurine conjugates, enantiomers, diastereomers, tautomers, N-oxides, solvates, prodrugs, and pharmaceutically acceptable salts in an amount of 0.1 to 0.5 mg; b) a compound of formula (I), its glycine conjugates, taurine conjugates, enantiomers, diastereomers, tautomers, N-oxides, solvates, prodrugs, and pharmaceutically acceptable salts in an amount of 0.5 to 1 mg; and c) a compound of formula (I), its glycine conjugates, taurine conjugates, enantiomers, diastereomers, tautomers, N-oxides, solvates, prodrugs, and pharmaceutically acceptable salts in an amount of 1 to 5 mg. d) the compounds of formula (I), their glycine conjugates, taurine conjugates, enantiomers, diastereomers, tautomers, N-oxides, solvates, prodrugs and pharmaceutically acceptable salts in an amount of 5 to 10 mg; e) the compounds of formula (I), their glycine conjugates, taurine conjugates, enantiomers, diastereomers, tautomers, N-oxides, solvates, prodrugs and pharmaceutically acceptable salts in an amount of 10 to 20 mg; or f) the compounds of formula (I), their glycine conjugates, taurine conjugates, enantiomers, diastereomers, tautomers, N-oxides, solvates, prodrugs and pharmaceutically acceptable salts in an amount of 20 to 25 mg.

[0137] In certain embodiments, the pharmaceutical composition is administered in the following amounts: a) 5-15 mg of the compound of Formula (I), its glycine conjugates, taurine conjugates, enantiomers, diastereomers, tautomers, N-oxides, solvates, prodrugs, and pharmaceutically acceptable salts; b) 5-10 mg of the compound of Formula (I), its glycine conjugates, taurine conjugates, enantiomers, diastereomers, tautomers, N-oxides, solvates, prodrugs, and pharmaceutically acceptable salts; or c) 10-15 mg of the compound of Formula (I), its glycine conjugates, taurine conjugates, enantiomers, diastereomers, tautomers, N-oxides, solvates, prodrugs, and pharmaceutically acceptable salts.

[0138] In certain embodiments, the pharmaceutical composition is administered in an amount of 0.5, 2, 6, 12, or 20 mg of the compound of formula (I), its glycine conjugate, taurine conjugate, enantiomer, diastereomer, tautomer, N-oxide, solvate, prodrug, and pharmaceutically acceptable salt. In certain embodiments, the compound is compound 21 / 3 or precursor 6 / 3. In certain embodiments, the compound is compound 21 / 3. In certain embodiments, the compound is compound precursor 6 / 3.

[0139] Exemplary Embodiments Embodiment I-1. 1. A method for treating a metabolic disorder associated with dyslipidemia or impaired lipid homeostasis in a subject in need thereof, comprising administering to a subject a compound of formula (I): [ka] administering to a subject in need of treatment an effective amount of a compound represented by its glycine conjugate, taurine conjugate, enantiomer, diastereomer, tautomer, N-oxide, solvate, prodrug, and pharmaceutically acceptable salt; During the ceremony, [ka] is a fused 5- to 6-membered ring forming a 6-membered aryl or a 5- to 6-membered heteroaryl containing 1 to 3 heteroatoms independently selected from N, O, and S, the ring being unsubstituted or substituted with halogen, CN, SF, NO, C 1~6 -Alkyl, oxo, C 0~6 -Alkylene-OR 11 , C 0~6 -Alkylene-(3- to 6-membered cycloalkyl), C 0~6 -alkylene-(3- to 6-membered heterocycloalkyl), C 0~6 -Alkylene-S(O) n R 11 , C 0~6 -Alkylene-NR 11 S(O)2R 11 , C 0~6 -Alkylene-S(O)NR11 R 12 , C 0~6 -Alkylene-NR 11 S(O)NR 11 R 12 , C 0~6 -Alkylene-CO2R 11 , O.C. 1~6 -Alkylene-CO2R 11 , C 0~6 -Alkylene-O-COR 11 , C 0~6 -Alkylene-CONR 11 R 12 , C 0~6 -Alkylene-NR 11 -COR 11 , C 0~6 -Alkylene-NR 11 -CONR 11 R 12 , C 0~6 -Alkylene-O-CONR 11 R 12 , C 0~6 -Alkylene-NR 11 -CO2R 11 and C 0~6 -Alkylene-NR 11 R 12 and is substituted with 1 to 4 substituents independently selected from the group consisting of: wherein alkyl, alkylene, cycloalkyl, and heterocycloalkyl are unsubstituted or substituted with halogen, CN, oxo, hydroxy, COH, CO-C 1~4 -Alkyl, CONHCH2CO2H, CONH(CH2)2SO3H, C 1~4 -Alkyl, Halo-C 1~4 -Alkyl, OC 1~4 -Alkyl and O-Halo-C 1~4 -substituted with 1 to 6 substituents independently selected from alkyl; wherein two adjacent substituents on the aryl or heteroaryl moiety may form a 5-8 membered partially unsaturated ring which may contain 1-3 heteroatoms independently selected from O, S or N; The newly formed ring may be unsubstituted or may contain halogen, CN, C 1~4-Alkyl, Halo-C 1~4 -Alkyl, 3- to 6-membered cycloalkyl, halo-(3- to 6-membered cycloalkyl), 3- to 6-membered heterocycloalkyl, halo-(3- to 6-membered heterocycloalkyl), OH, oxo, CO2H, CO2-C 1~4 -Alkyl, CONHCH2CO2H, CONH(CH2)2SO3H, OC 1~4 -Alkyl and O-Halo-C 1~4 -substituted with 1 to 3 substituents independently selected from alkyl; [ka] is selected from the group consisting of 3- to 10-membered cycloalkyl, 3- to 10-membered heterocycloalkyl containing 1-3 heteroatoms independently selected from N, O, and S, 6- to 14-membered aryl, and 5- to 14-membered heteroaryl containing 1-4 heteroatoms independently selected from N, O, and S; wherein cycloalkyl, heterocycloalkyl, aryl and heteroaryl are unsubstituted or substituted with halogen, CN, SF, NO, oxo, C 1~4 -Alkyl, C 0~6 -Alkylene-OR 21 , C 0~6 -Alkylene-(3- to 6-membered cycloalkyl), C 0~6 -alkylene-(3- to 6-membered heterocycloalkyl), C 0~6 -Alkylene-S(O) n R 21 , C 0~6 -Alkylene-NR 21 S(O)2R 21 , C 0~6 -Alkylene-S(O)NR 21 R 22 , C 0~6 -Alkylene-NR 21 S(O)NR 21 R 22 , C 0~6 -Alkylene-CO2R 21 , O.C. 1~6 -Alkylene-CO2R 21 , C 0~6 -Alkylene-O-COR 21 , C0~6 -Alkylene-CONR 21 R 22 , C 0~6 -Alkylene-NR 21 -COR 21 , C 0~6 -Alkylene-NR 21 -CONR 21 R 22 , C 0~6 -Alkylene-O-CONR 21 R 22 , C 0~6 -Alkylene-NR 21 -CO2R 21 and C 0~6 -Alkylene-NR 21 R 22 and is substituted with 1 to 6 substituents independently selected from the group consisting of: wherein alkyl, alkylene, cycloalkyl and heterocycloalkyl are unsubstituted or substituted with halogen, CN, oxo, hydroxy, COH, CO-C 1~4 -Alkyl, CONHCH2CO2H, CONH(CH2)2SO3H, C 1~4 -Alkyl, Halo-C 1~4 -Alkyl, OC 1~4 -Alkyl and O-Halo-C 1~4 -substituted with 1 to 6 substituents independently selected from alkyl; wherein two adjacent substituents on the aryl or heteroaryl moiety may form a 5-8 membered partially unsaturated ring which may contain 1-3 heteroatoms independently selected from O, S or N; This further ring may be unsubstituted or may be substituted with halogen, CN, oxo, OH, CO2H, CO2-C 1~4 -Alkyl, CONHCH2CO2H, CONH(CH2)2SO3H, C 1~4 -Alkyl, Halo-C 1~4 -Alkyl, OC 1~4 -Alkyl and O-Halo-C 1~4 -substituted with 1 to 4 substituents independently selected from alkyl; wherein two adjacent substituents on the cycloalkyl or heterocycloalkyl moiety may form a 5- to 6-membered unsaturated ring which may contain 1 to 3 heteroatoms independently selected from O, S, or N; This further ring may be unsubstituted or may be substituted with halogen, CN, oxo, OH, CO2H, CO2-C 1~4 -Alkyl, CONHCH2CO2H, CONH(CH2)2SO3H, C 1~4 -Alkyl, Halo-C 1~4 -Alkyl, OC 1~4 -Alkyl and O-Halo-C 1~4 -substituted with 1 to 4 substituents independently selected from alkyl; [ka] is selected from the group consisting of 6- or 10-membered aryl and 5- to 10-membered heteroaryl containing 1-3 heteroatoms independently selected from N, O, and S; wherein cycloalkyl, heterocycloalkyl, aryl and heteroaryl are unsubstituted or substituted with halogen, CN, SF, NO, oxo, C 1~4 -Alkyl, C 0~6 -Alkylene-OR 31 , C 0~6 -Alkylene-(3- to 6-membered cycloalkyl), C 0~6 -alkylene-(3- to 6-membered heterocycloalkyl), C 0~6 -alkylene-(6-membered aryl), C 0~6 -alkylene-(5-6 membered heteroaryl), C 0~6 -Alkylene-S(O) n R 31 , C 0~6 -Alkylene-NR 31 S(O)2R 31 , C 0~6 -Alkylene-S(O)NR 31 R 32 , C 0~6 -Alkylene-NR 31 S(O)NR 31 R 32 , C 0~6 -Alkylene-CO2R31 , O.C. 1~6 -Alkylene-CO2R 31 , C 0~6 -Alkylene-O-COR 31 , C 0~6 -Alkylene-CONR 31 R 32 , C 0~6 -Alkylene-NR 31 -COR 31 , C 0~6 -Alkylene-NR 31 -CONR 31 R 32 , C 0~6 -Alkylene-O-CONR 31 R 32 , C 0~6 -Alkylene-NR 31 -CO2R 31 and C 0~6 -Alkylene-NR 31 R 32 and is substituted with 1 to 4 substituents independently selected from the group consisting of: wherein alkyl, alkylene, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are unsubstituted or substituted with halogen, CN, oxo, hydroxy, COH, CO-C 1~4 -Alkyl, CONHCH2CO2H, CONH(CH2)2SO3H, C 1~4 -Alkyl, Halo-C 1~4 -Alkyl, OC 1~4 -Alkyl and O-Halo-C 1~4 -substituted with 1 to 6 substituents independently selected from alkyl; wherein two adjacent substituents on the aryl or heteroaryl moiety may form a 5-8 membered partially unsaturated ring which may contain 1-3 heteroatoms independently selected from O, S or N; This further ring may be unsubstituted or may be substituted with halogen, CN, oxo, OH, CO2H, CO2-C 1~4 -Alkyl, CONHCH2CO2H, CONH(CH2)2SO3H, C 1~4 -Alkyl, Halo-C 1~4 -Alkyl, OC 1~4-Alkyl and O-Halo-C 1~4 -substituted with 1 to 4 substituents independently selected from alkyl; [ka] is selected from the group consisting of 3- to 10-membered cycloalkyl, 3- to 10-membered heterocycloalkyl containing 1-3 heteroatoms independently selected from N, O, and S, 6- to 14-membered aryl, and 5- to 14-membered heteroaryl containing 1-4 heteroatoms independently selected from N, O, and S; wherein cycloalkyl, heterocycloalkyl, aryl and heteroaryl are unsubstituted or substituted with halogen, CN, SF, NO, oxo, C 1~4 -Alkyl, C 0~6 -Alkylene-OR 21 , C 0~6 -Alkylene-(3- to 6-membered cycloalkyl), C 0~6 -alkylene-(3- to 6-membered heterocycloalkyl), C 0~6 -Alkylene-S(O) n R 21 , C 0~6 -Alkylene-NR 21 S(O)2R 21 , C 0~6 -Alkylene-S(O)NR 21 R 22 , C 0~6 -Alkylene-NR 21 S(O)NR 21 R 22 , C 0~6 -Alkylene-CR 41 (=N-OR 41 ), C 0~6 -Alkylene-CO2R 21 , O.C. 1~6 -Alkylene-CO2R 21 , C 0~6 -Alkylene-O-COR 21 , C 0~6 -Alkylene-CONR 21 R 22 , C 0~6 -Alkylene-NR 21 -COR 21 , C 0~6-Alkylene-NR 21 -CONR 21 R 22 , C 0~6 -Alkylene-O-CONR 21 R 22 , C 0~6 -Alkylene-NR 21 -CO2R 21 and C 0~6 -Alkylene-NR 21 R 22 and is substituted with 1 to 6 substituents independently selected from the group consisting of: wherein alkyl, alkylene, cycloalkyl and heterocycloalkyl are unsubstituted or substituted with halogen, CN, oxo, hydroxy, COH, CO-C 1~4 -Alkyl, CONHCH2CO2H, CONH(CH2)2SO3H, CO-OC 1~4 -Alkyl, C 1~4 -Alkyl, Halo-C 1~4 -Alkyl, OC 1~4 -Alkyl and O-Halo-C 1~4 -substituted with 1 to 6 substituents independently selected from alkyl; wherein two adjacent substituents on the aryl or heteroaryl moiety may form a 5-8 membered partially unsaturated ring which may contain 1-3 heteroatoms independently selected from O, S or N; This further ring may be unsubstituted or may be substituted with halogen, CN, oxo, OH, CO2H, CO2-C 1~4 -Alkyl, CONHCH2CO2H, CONH(CH2)2SO3H, C 1~4 -Alkyl, Halo-C 1~4 -Alkyl, OC 1~4 -Alkyl and O-Halo-C 1~4 -substituted with 1 to 4 substituents independently selected from alkyl; wherein two adjacent substituents on the cycloalkyl or heterocycloalkyl moiety may form a 5- to 6-membered unsaturated ring which may contain 1 to 3 heteroatoms independently selected from O, S, or N; This further ring may be unsubstituted or may be substituted with halogen, CN, oxo, OH, CO2H, CO2-C 1~4 -Alkyl, CONHCH2CO2H, CONH(CH2)2SO3H, C 1~4 -Alkyl, Halo-C 1~4 -Alkyl, OC 1~4 -Alkyl and O-Halo-C 1~4 -substituted with 1 to 4 substituents independently selected from alkyl; During the ceremony, [ka] teeth, [ka] or a further ring fused in a 1,2-orientation, L is a bond, C 1~6 -Alkylene, C 2~6 -Alkenylene, C 2~6 - selected from the group consisting of alkynylene, 3- to 10-membered cycloalkylene, 3- to 10-membered heterocycloalkylene containing 1-4 heteroatoms independently selected from N, O and S, 6- or 10-membered arylene, and 5- to 10-membered heteroarylene containing 1-4 heteroatoms independently selected from N, O and S; wherein alkylene, alkenylene, alkynylene, cycloalkylene, heterocycloalkylene, arylene and heteroarylene are unsubstituted or substituted with halogen, CN, SF, NO, oxo, C 1~4 -Alkyl, C 0~6 -Alkylene-OR 41 , C 0~6 -Alkylene-(3- to 6-membered cycloalkyl), C 0~6 -alkylene-(3- to 6-membered heterocycloalkyl), C 0~6 -Alkylene-S(O) n R 41 , C 0~6 -Alkylene-NR 41 S(O)2R 41 , C 0~6-Alkylene-S(O)NR 41 R 42 , C 0~6 -Alkylene-NR 41 S(O)NR 41 R 42 , C 0~6 -Alkylene-CO2R 41 , O.C. 1~6 -Alkylene-CO2R 41 , C 0~6 -Alkylene-O-COR 41 , C 0~6 -Alkylene-CONR 41 R 42 , C 0~6 -Alkylene-NR 41 -COR 41 , C 0~6 -Alkylene-NR 41 -CONR 41 R 42 , C 0~6 -Alkylene-O-CONR 41 R 42 , C 0~6 -Alkylene-NR 41 -CO2R 41 and C 0~6 -Alkylene-NR 41 R 42 and is substituted with 1 to 6 substituents independently selected from the group consisting of: wherein alkyl, alkylene, cycloalkyl and heterocycloalkyl are unsubstituted or substituted with halogen, CN, oxo, hydroxy, COH, CO-C 1~4 -Alkyl, CONHCH2CO2H, CONH(CH2)2SO3H, C 1~4 -Alkyl, Halo-C 1~4 -Alkyl, OC 1~4 -Alkyl and O-Halo-C 1~4 -substituted with 1 to 6 substituents independently selected from alkyl; wherein two adjacent substituents on the arylene moiety and the heteroarylene moiety may form a 5- to 8-membered partially unsaturated ring which may contain 1 to 3 heteroatoms independently selected from O, S, or N; This further ring may be unsubstituted or may be substituted with halogen, CN, oxo, OH, CO2H, CO2-C 1~4 -Alkyl, C 1~4 -Alkyl, Halo-C 1~4 -Alkyl, OC 1~4 -Alkyl and O-Halo-C 1~4 -substituted with 1 to 4 substituents independently selected from alkyl; R 1 H, halogen, CN, SF5, NO2, oxo, C 1~4 -Alkyl, C 0~6 -Alkylene-OR 41 , Y.C. 0~6 -Alkylene-(3-6 membered cycloalkyl), YC 0~6 -Alkylene-(3-6 membered heterocycloalkyl), YC 0~6 -alkylene-(6-membered aryl), YC 0~6 -alkylene-(5-6 membered heteroaryl), C 0~6 -Alkylene-S(=O)(-R 41 )=NR 75 , XC 1~6 -Alkylene-S(=O)(-R 41 )=NR 75 , C 0~6 -Alkylene-S(O) n R 41 , XC 1~6 -Alkylene-S(O) n R 41 , C 0~6 -Alkylene-S(=NR 71 )R 41 , XC 1~6 -Alkylene-S(=NR 71 )R 41 , C 0~6 -Alkylene-S(O)(=NR 71 )R 41 , XC 1~6 -Alkylene-S(O)(=NR 71 )R 41 , C 0~6 -Alkylene-S(=NR 71 )2R 41 , XC 1~6 -Alkylene-S(=NR 71 )2R41 , C 0~6 -Alkylene-NR 41 S(O)2R 41 , XC 1~6 -Alkylene-NR 41 S(O)2R 41 , C 0~6 -Alkylene-S(O)NR 41 R 42 , XC 1~6 -Alkylene-S(O)NR 41 R 42 , C 0~6 -Alkylene-NR 41 S(O)NR 41 R 42 , XC 1~6 -Alkylene-NR 41 S(O)NR 41 R 42 , C 0~6 -Alkylene-SO3R 41 , XC 1~6 -Alkylene-SO3R 41 , C 0~6 -Alkylene-CO2R 41 , XC 1~6 -Alkylene-CO2R 41 , C 0~6 -Alkylene-O-COR 41 , XC 1~6 -Alkylene-O-COR 41 , C 0~6 -Alkylene-CONR 41 R 42 , XC 1~6 -Alkylene-CONR 41 R 42 , C 0~6 -Alkylene-CONR 41 OR 41 , XC 1~6 -Alkylene-CONR 41 OR 41 , C 0~6 -Alkylene-CONR 41 SO2R 41 , XC 1~6 -Alkylene-CONR 41 SO2R 41 , C 0~6 -Alkylene-NR 41 -COR41 , XC 1~6 -C 0~6 -Alkylene-NR 41 -COR 41 , C 0~6 -Alkylene-NR 41 -CONR 41 R 42 , XC 1~6 -Alkylene-NR 41 -CONR 41 R 42 , C 0~6 -Alkylene-O-CONR 41 R 42 , XC 1~6 -Alkylene-O-CONR 41 R 42 , C 0~6 -Alkylene-NR 41 -CO2R 41 , XC 1~6 -Alkylene-NR 41 -CO2R 41 , C 0~6 -Alkylene-NR 41 R 42 , XC 1~6 -Alkylene-NR 41 R 42 is selected from the group consisting of wherein alkyl, alkylene, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are unsubstituted or substituted with halogen, CN, oxo, hydroxy, COH, CO-C 1~4 -Alkyl, CONHCH2CO2H, CONH(CH2)2SO3H, C 1~4 -Alkyl, Halo-C 1~4 -Alkyl, OC 1~4 -Alkyl and O-Halo-C 1~4 -substituted with 1 to 6 substituents independently selected from alkyl; wherein two adjacent substituents on the aryl and heteroaryl moieties may form a 5-8 membered partially unsaturated ring which may contain 1-3 heteroatoms independently selected from O, S or N; This further ring may be unsubstituted or may be substituted with halogen, CN, oxo, OH, CO2H, CO2-C 1~4-Alkyl, CONHCH2CO2H, CONH(CH2)2SO3H, C 1~4 -Alkyl, Halo-C 1~4 -Alkyl, OC 1~4 -Alkyl and O-Halo-C 1~4 -substituted with 1 to 4 substituents independently selected from alkyl; R 11 , R 12 , R 21 , R 22 , R 31 , R 32 , R 41 , R 42 , R 51 are independently H and C 1~4 -alkyl, wherein alkyl is unsubstituted or is selected from halogen, CN, C 1~4 -Alkyl, Halo-C 1~4 -Alkyl, 3- to 6-membered cycloalkyl, halo-(3- to 6-membered cycloalkyl), 3- to 6-membered heterocycloalkyl, halo-(3- to 6-membered heterocycloalkyl), OH, oxo, CO2H, CO2-C 1~4 -Alkyl, CONHCH2CO2H, CONH(CH2)2SO3H, SO3H, OC 1~4 -Alkyl and O-Halo-C 1~4 -substituted with 1 to 3 substituents independently selected from alkyl; or R 11 and R 12 , R 21 and R 22 , R 31 and R 32 , R 41 and R 42 each, when taken together with the nitrogen to which they are attached, completes a 3- to 6-membered ring containing carbon atoms and optionally containing 1 or 2 heteroatoms independently selected from O, S or N; The newly formed ring may be unsubstituted or may contain halogen, CN, C 1~4 -Alkyl, Halo-C 1~4-Alkyl, 3- to 6-membered cycloalkyl, halo-(3- to 6-membered cycloalkyl), 3- to 6-membered heterocycloalkyl, halo-(3- to 6-membered heterocycloalkyl), OH, oxo, CO2H, CO2-C 1~4 -Alkyl, CONHCH2CO2H, CONH(CH2)2SO3H, SO3H, OC 1~4 -Alkyl and O-Halo-C 1~4 -substituted with 1 to 3 substituents independently selected from alkyl; R 71 are independently H, CN, NO2, C 1~4 -Alkyl, and C(O)-OC 1~4 -alkyl, wherein alkyl is unsubstituted or is selected from halogen, CN, C 1~4 -Alkyl, Halo-C 1~4 -Alkyl, 3- to 6-membered cycloalkyl, halo-(3- to 6-membered cycloalkyl), 3- to 6-membered heterocycloalkyl, halo-(3- to 6-membered heterocycloalkyl), OH, oxo, CO2H, CO2-C 1~4 -Alkyl, CONHCH2CO2H, CONH(CH2)2SO3H, SO3H, OC 1~4 -Alkyl and O-Halo-C 1~4 -substituted with 1 to 3 substituents independently selected from alkyl; R 75 are independently, C 1~4 selected from alkyl, 3- to 6-membered cycloalkyl, 3- to 6-membered heterocycloalkyl, 6-membered aryl, and 5- to 6-membered heteroaryl; wherein alkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl are unsubstituted or substituted with 1 to 3 substituents independently selected from halogen, CN, Me, Et, CHF, CF, OH, oxo, COH, CONHCHCOH, CONH(CH)SOH, SOH, OMe, OEt, OCHF, and OCF; X is independently O, NR 51 , S(O) n , S(=NR 71 ), S(O)(=NR 71 ) and S(=NR 71)2 is selected, Y is independently a bond, O, or NR 51 , S(O) n , S(=NR 71 ), S(O)(=NR 71 ) and S(=NR 71 )2 is selected, n is independently selected from 0 to 2; however, [ka] The structure of the method is excluded.

[0140] Embodiment I-2. [ka] teeth, [ka] is selected from During the ceremony, [ka] is unsubstituted or is F, Cl, Br, CN, OH, oxo, C 1~4 -Alkyl, Halo-C 1~4 -Alkyl, OC 1~4 -Alkyl, O-Halo-C 1~4 -Alkyl, NH2, NHC 1~4 -Alkyl, N(C 1~4 -Alkyl)2, SO2-C 1~4 -Alkyl, and SO2-Halo-C 1~4 The method of embodiment I-1, wherein the aryl group is substituted with 1 to 3 substituents independently selected from the group consisting of -alkyl.

[0141] Embodiment I-3. [ka] is phenyl, naphthyl, pyridyl, pyrimidinyl, thiophenyl, thiazolyl, cyclopentyl, cyclohexyl, bicyclo[1.1.1]pentyl, bicyclo[2.2.2]octyl, bicyclo[2.2.1]heptyl, pentacyclo[4.2.0.0 2,5 .0 3,8 .0 4,7 octyl, and piperidinyl; wherein the ring is unsubstituted or substituted with F, Cl, Br, CN, OH, oxo, C 1~4 -Alkyl, Halo-C 1~4 -Alkyl, OC 1~4 -Alkyl, O-Halo-C 1~4 -Alkyl, C 1~4 -Alkyl-OH, and halo-C 1~4 The method of embodiment I-1 or I-2, wherein the phenyl ring is substituted with 1 to 3 substituents independently selected from the group consisting of -alkyl-OH, and two adjacent substituents on the phenyl ring may be taken together to form a -(CH2)3-, -(CH2)4-, -OCF2O-, and -OCHO- group.

[0142] Embodiment I-4. [ka] is selected from phenyl, pyridyl, and thiophenyl, wherein phenyl, pyridyl, and thiophenyl are unsubstituted or selected from F, Cl, CN, OH, oxo, C 1~4 -Alkyl, Halo-C 1~4 -Alkyl, OC 1~4 -Alkyl, and O-Halo-C 1~4 -alkyl; and the residue -LR 1 teeth, [ka] and L is not a bond.

[0143] Embodiment I-5. -LR 1 teeth, [ka] is selected from wherein the ring is unsubstituted or is selected from the group consisting of F, Cl, Br, CN, OH, oxo, C 1~4 -Alkyl, Halo-C 1~4 -Alkyl, OC 1~4 -Alkyl, O-Halo-C 1~4 -Alkyl, C 1~4 -Alkyl-OH, Halo-C 1~4 -Alkyl-OH, SO2-C 1~4 -Alkyl and SO2-Halo-C 1~4 The method of any one of embodiments I-1 to I-4, wherein the phenyl ring is further substituted with 1 to 4 substituents independently selected from the group consisting of -alkyl, and two adjacent substituents on the phenyl ring may be taken together to form a -(CH2)3-, -(CH2)4-, -OCF2O-, and -OCHO group.

[0144] Embodiment I-6. R 1 The method of any one of embodiments I-1 to I-5, wherein is selected from CO2H, tetrazole, CH2CO2H, OCH2CO2H, SO2CH2CO2H, CHMeCO2H, CMe2CO2H, C(OH)MeCO2H, CONHSO2Me, and CONH(OH), and optionally their glycine and taurine conjugates.

[0145] Embodiment I-7. -LR 1 teeth, [ka] The method of any one of embodiments I-1 to I-6, wherein the compound is selected from the group consisting of methyl methyl ketone, ...

[0146] Embodiment I-8. [ka] teeth, [ka] is selected from the group consisting of R 2 are Me, F, Cl, CN, Me, CHO, CHF2, CF3, SO2Me, [ka] is selected from During the ceremony, [ka] The method of any one of embodiments I-1 to I-7, wherein is optionally further substituted with 1 to 2 substituents selected from the group consisting of F, Cl, CN, Me, OMe, CHO, CHF2, and CF3.

[0147] Embodiment I-9. [ka] teeth, [ka] The method according to any one of embodiments I-1 to I-8, selected from the group consisting of:

[0148] Embodiment I-10. The method of any one of embodiments I-1 to I-9, wherein formula (I) contains a substituent selected from the group consisting of CO2H, tetrazole, CONHSO2Me, and CONH(OH), and optionally glycine and taurine conjugates thereof.

[0149] Embodiment I-11. LR 1 teeth, [ka] wherein the ring is unsubstituted or substituted with F, Cl, Br, CN, OH, oxo, C1~4 -Alkyl, Halo-C 1~4 -Alkyl, OC 1~4 -Alkyl, O-Halo-C 1~4 -Alkyl, C 1~4 -Alkyl-OH, Halo-C 1~4 -Alkyl-OH, SO2-C 1~4 -Alkyl and SO2-Halo-C 1~4 The method of any one of embodiments I-1 to I-10, wherein the phenyl ring is further substituted with 1 to 4 substituents independently selected from the group consisting of -alkyl, wherein two adjacent substituents on the phenyl ring may be taken together to form a -(CH2)3-, -(CH2)4-, -OCF2O-, and -OCHO- group.

[0150] Embodiment I-12. R 1 is C 0~6 -Alkylene-CO2R 41 Or C 0~6 -Alkylene-CONR 41 R 42 or a glycine or taurine conjugate thereof.

[0151] Embodiment I-13. R 1 The method of any one of embodiments I-1 to I-12, wherein is COOH, or a glycine or taurine conjugate thereof.

[0152] Embodiment I-14. R 1 is C 0~6 -Alkylene-CONR 41 R 42 The method of any one of embodiments I-1 to I-12, wherein

[0153] Embodiment I-15. R 41 and R 42 are independently H and C 1~4 alkyl, C 1~4The method of embodiment I-14, wherein the alkyl is unsubstituted or substituted with CO2H.

[0154] Embodiment I-16. LR 1 teeth, [ka] or a glycine or taurine conjugate thereof.

[0155] Embodiment I-17. The method of any one of embodiments I-1 to I-16, wherein the compound is a glycine conjugate.

[0156] Embodiment I-18. The method of any one of embodiments I-1 to I-17, wherein the compound is: [ka]

[0157] Embodiment I-19. The compound is [ka] or a glycine conjugate thereof.

[0158] Embodiment I-20. [ka] [ka] or its glycine or taurine conjugate, and The method of any one of embodiments I-1 to I-17, wherein the compound is selected from an enantiomer, diastereomer, tautomer, N-oxide, solvate, prodrug, and pharmaceutically acceptable salt thereof.

[0159] Embodiment I-21. The method according to any one of embodiments I-1 to I-20, wherein the method is for treating dyslipidemia.

[0160] Embodiment I-22. The method of any one of embodiments I-1 to I-21, wherein the dyslipidemia is hypertriglyceridemia (HTG), severe hypertriglyceridemia (SHTG), familial hypercholesterolemia, heterozygous familial hypercholesterolemia, homozygous familial hypercholesterolemia, familial chylomicronemia syndrome, mixed disorder chylomicronemia, hypercholesterolemia, familial combined hyperlipidemia, familial dysbetalipoproteinemia, and mixed dyslipidemia.

[0161] Embodiment I-23. The method of any one of embodiments I-1 to I-21, wherein the dyslipidemia is severe hypertriglyceridemia (SHTG).

[0162] Embodiment I-24. The method of any one of embodiments I-1 to I-23, wherein the dyslipidemia is characterized by abnormal levels of one or more lipids and / or apolipoproteins.

[0163] Embodiment I-25. The method of any one of embodiments I-1 to I-24, wherein the dyslipidemia is characterized by elevated levels of total cholesterol, LDL cholesterol, triglycerides (TG), or any combination of the foregoing.

[0164] Embodiment I-26. The method of any one of embodiments I-1 to I-25, wherein the dyslipidemia is characterized by a reduced level of HDL cholesterol.

[0165] Embodiment I-27. The method of any one of embodiments I-1 to I-26, wherein the method reduces the risk of pancreatitis in the subject.

[0166] Embodiment I-28. The method according to any one of embodiments I-1 to I-20, wherein the method is for treating a metabolic disorder associated with impaired lipid homeostasis.

[0167] Embodiment I-29. The method of any one of embodiments I-1 to I-20 and I-28, wherein the method comprises treating a metabolic disorder associated with a defect in de novo lipogenesis.

[0168] Embodiment I-30. The method of any one of embodiments I-1 to I-20 and I-28 to I-29, wherein the method comprises treating nonalcoholic fatty liver disease (NAFLD) or nonalcoholic steatohepatitis (NASH) in a subject in need thereof, wherein the subject has a glucokinase regulatory protein (GCKR) phenotype.

[0169] Embodiment I-31. The method of embodiment I-30, wherein de novo lipogenesis is enhanced in the subject.

[0170] Embodiment I-33. The method of embodiment I-30 or I-31, wherein expression of lipogenic genes in the subject and / or lipid accumulation in the subject is reduced.

[0171] Embodiment II-1. 1. A method for treating a metabolic disorder associated with dyslipidemia or impaired lipid homeostasis in a subject in need thereof, comprising administering to a subject a compound of formula (I): [ka] administering to a subject in need of treatment an effective amount of a compound represented by its glycine conjugate, taurine conjugate, enantiomer, diastereomer, tautomer, N-oxide, solvate, prodrug, and pharmaceutically acceptable salt; During the ceremony, [ka] is a fused 5- to 6-membered ring forming a 6-membered aryl or a 5- to 6-membered heteroaryl containing 1 to 3 heteroatoms independently selected from N, O, and S, the ring being unsubstituted or substituted with halogen, CN, SF, NO, C 1~6 -Alkyl, oxo, C 0~6 -Alkylene-OR 11 , C 0~6 -Alkylene-(3- to 6-membered cycloalkyl), C 0~6 -alkylene-(3- to 6-membered heterocycloalkyl), C 0~6 -Alkylene-S(O) n R 11 , C 0~6 -Alkylene-NR 11 S(O)2R 11 , C 0~6 -Alkylene-S(O)NR 11 R 12 , C 0~6 -Alkylene-NR 11 S(O)NR 11 R 12 , C 0~6 -Alkylene-CO2R 11 , O.C. 1~6 -Alkylene-CO2R 11 , C 0~6 -Alkylene-O-COR 11 , C 0~6 -Alkylene-CONR 11 R 12 , C 0~6 -Alkylene-NR 11 -COR 11 , C 0~6 -Alkylene-NR 11 -CONR 11 R 12 , C 0~6 -Alkylene-O-CONR11 R 12 , C 0~6 -Alkylene-NR 11 -CO2R 11 and C 0~6 -Alkylene-NR 11 R 12 and is substituted with 1 to 4 substituents independently selected from the group consisting of: wherein alkyl, alkylene, cycloalkyl, and heterocycloalkyl are unsubstituted or substituted with halogen, CN, oxo, hydroxy, COH, CO-C 1~4 -Alkyl, CONHCH2CO2H, CONH(CH2)2SO3H, C 1~4 -Alkyl, Halo-C 1~4 -Alkyl, OC 1~4 -Alkyl and O-Halo-C 1~4 -substituted with 1 to 6 substituents independently selected from alkyl; wherein two adjacent substituents on the aryl or heteroaryl moiety may form a 5-8 membered partially unsaturated ring which may contain 1-3 heteroatoms independently selected from O, S or N; The newly formed ring may be unsubstituted or may contain halogen, CN, C 1~4 -Alkyl, Halo-C 1~4 -Alkyl, 3- to 6-membered cycloalkyl, halo-(3- to 6-membered cycloalkyl), 3- to 6-membered heterocycloalkyl, halo-(3- to 6-membered heterocycloalkyl), OH, oxo, CO2H, CO2-C 1~4 -Alkyl, CONHCH2CO2H, CONH(CH2)2SO3H, OC 1~4 -Alkyl and O-Halo-C 1~4 -substituted with 1 to 3 substituents independently selected from alkyl; [ka] is selected from the group consisting of 3- to 10-membered cycloalkyl, 3- to 10-membered heterocycloalkyl containing 1-3 heteroatoms independently selected from N, O, and S, 6- to 14-membered aryl, and 5- to 14-membered heteroaryl containing 1-4 heteroatoms independently selected from N, O, and S; wherein cycloalkyl, heterocycloalkyl, aryl and heteroaryl are unsubstituted or substituted with halogen, CN, SF, NO, oxo, C 1~4 -Alkyl, C 0~6 -Alkylene-OR 21 , C 0~6 -Alkylene-(3- to 6-membered cycloalkyl), C 0~6 -alkylene-(3- to 6-membered heterocycloalkyl), C 0~6 -Alkylene-S(O) n R 21 , C 0~6 -Alkylene-NR 21 S(O)2R 21 , C 0~6 -Alkylene-S(O)NR 21 R 22 , C 0~6 -Alkylene-NR 21 S(O)NR 21 R 22 , C 0~6 -Alkylene-CO2R 21 , O.C. 1~6 -Alkylene-CO2R 21 , C 0~6 -Alkylene-O-COR 21 , C 0~6 -Alkylene-CONR 21 R 22 , C 0~6 -Alkylene-NR 21 -COR 21 , C 0~6 -Alkylene-NR 21 -CONR 21 R 22 , C 0~6 -Alkylene-O-CONR 21 R 22 , C 0~6 -Alkylene-NR 21 -CO2R 21 and C 0~6 -Alkylene-NR 21 R 22 and is substituted with 1 to 6 substituents independently selected from the group consisting of: wherein alkyl, alkylene, cycloalkyl and heterocycloalkyl are unsubstituted or substituted with halogen, CN, oxo, hydroxy, COH, CO-C 1~4 -Alkyl, CONHCH2CO2H, CONH(CH2)2SO3H, C 1~4 -Alkyl, Halo-C 1~4 -Alkyl, OC 1~4 -Alkyl and O-Halo-C 1~4 -substituted with 1 to 6 substituents independently selected from alkyl; wherein two adjacent substituents on the aryl or heteroaryl moiety may form a 5-8 membered partially unsaturated ring which may contain 1-3 heteroatoms independently selected from O, S or N; This further ring may be unsubstituted or may be substituted with halogen, CN, oxo, OH, CO2H, CO2-C 1~4 -Alkyl, CONHCH2CO2H, CONH(CH2)2SO3H, C 1~4 -Alkyl, Halo-C 1~4 -Alkyl, OC 1~4 -Alkyl and O-Halo-C 1~4 -substituted with 1 to 4 substituents independently selected from alkyl; wherein two adjacent substituents on the cycloalkyl or heterocycloalkyl moiety may form a 5- to 6-membered unsaturated ring which may contain 1 to 3 heteroatoms independently selected from O, S, or N; This further ring may be unsubstituted or may be substituted with halogen, CN, oxo, OH, CO2H, CO2-C 1~4 -Alkyl, CONHCH2CO2H, CONH(CH2)2SO3H, C 1~4 -Alkyl, Halo-C 1~4 -Alkyl, OC 1~4 -Alkyl and O-Halo-C 1~4 -substituted with 1 to 4 substituents independently selected from alkyl; [ka] is selected from the group consisting of 6- or 10-membered aryl and 5- to 10-membered heteroaryl containing 1-3 heteroatoms independently selected from N, O, and S; wherein cycloalkyl, heterocycloalkyl, aryl and heteroaryl are unsubstituted or substituted with halogen, CN, SF, NO, oxo, C 1~4 -Alkyl, C 0~6 -Alkylene-OR 31 , C 0~6 -Alkylene-(3- to 6-membered cycloalkyl), C 0~6 -alkylene-(3- to 6-membered heterocycloalkyl), C 0~6 -alkylene-(6-membered aryl), C 0~6 -alkylene-(5-6 membered heteroaryl), C 0~6 -Alkylene-S(O) n R 31 , C 0~6 -Alkylene-NR 31 S(O)2R 31 , C 0~6 -Alkylene-S(O)NR 31 R 32 , C 0~6 -Alkylene-NR 31 S(O)NR 31 R 32 , C 0~6 -Alkylene-CO2R 31 , O.C. 1~6 -Alkylene-CO2R 31 , C 0~6 -Alkylene-O-COR 31 , C 0~6 -Alkylene-CONR 31 R 32 , C 0~6 -Alkylene-NR 31 -COR 31 , C 0~6 -Alkylene-NR 31 -CONR 31 R 32 , C 0~6 -Alkylene-O-CONR 31 R 32 , C 0~6 -Alkylene-NR 31 -CO2R 31 and C0~6 -Alkylene-NR 31 R 32 and is substituted with 1 to 4 substituents independently selected from the group consisting of: wherein alkyl, alkylene, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are unsubstituted or substituted with halogen, CN, oxo, hydroxy, COH, CO-C 1~4 -Alkyl, CONHCH2CO2H, CONH(CH2)2SO3H, C 1~4 -Alkyl, Halo-C 1~4 -Alkyl, OC 1~4 -Alkyl and O-Halo-C 1~4 -substituted with 1 to 6 substituents independently selected from alkyl; wherein two adjacent substituents on the aryl or heteroaryl moiety may form a 5-8 membered partially unsaturated ring which may contain 1-3 heteroatoms independently selected from O, S or N; This further ring may be unsubstituted or may be substituted with halogen, CN, oxo, OH, CO2H, CO2-C 1~4 -Alkyl, CONHCH2CO2H, CONH(CH2)2SO3H, C 1~4 -Alkyl, Halo-C 1~4 -Alkyl, OC 1~4 -Alkyl and O-Halo-C 1~4 -substituted with 1 to 4 substituents independently selected from alkyl; [ka] is selected from the group consisting of 3- to 10-membered cycloalkyl, 3- to 10-membered heterocycloalkyl containing 1-3 heteroatoms independently selected from N, O, and S, 6- to 14-membered aryl, and 5- to 14-membered heteroaryl containing 1-4 heteroatoms independently selected from N, O, and S; wherein cycloalkyl, heterocycloalkyl, aryl and heteroaryl are unsubstituted or substituted with halogen, CN, SF, NO, oxo, C 1~4 -Alkyl, C 0~6 -Alkylene-OR 21 , C0~6 -Alkylene-(3- to 6-membered cycloalkyl), C 0~6 -alkylene-(3- to 6-membered heterocycloalkyl), C 0~6 -Alkylene-S(O) n R 21 , C 0~6 -Alkylene-NR 21 S(O)2R 21 , C 0~6 -Alkylene-S(O)NR 21 R 22 , C 0~6 -Alkylene-NR 21 S(O)NR 21 R 22 , C 0~6 -Alkylene-CR 41 (=N-OR 41 ), C 0~6 -Alkylene-CO2R 21 , O.C. 1~6 -Alkylene-CO2R 21 , C 0~6 -Alkylene-O-COR 21 , C 0~6 -Alkylene-CONR 21 R 22 , C 0~6 -Alkylene-NR 21 -COR 21 , C 0~6 -Alkylene-NR 21 -CONR 21 R 22 , C 0~6 -Alkylene-O-CONR 21 R 22 , C 0~6 -Alkylene-NR 21 -CO2R 21 and C 0~6 -Alkylene-NR 21 R 22 and is substituted with 1 to 6 substituents independently selected from the group consisting of wherein alkyl, alkylene, cycloalkyl and heterocycloalkyl are unsubstituted or substituted with halogen, CN, oxo, hydroxy, COH, CO-C 1~4 -Alkyl, CONHCH2CO2H, CONH(CH2)2SO3H, CO-OC 1~4-Alkyl, C 1~4 -Alkyl, Halo-C 1~4 -Alkyl, OC 1~4 -Alkyl and O-Halo-C 1~4 -substituted with 1 to 6 substituents independently selected from alkyl; wherein two adjacent substituents on the aryl or heteroaryl moiety may form a 5-8 membered partially unsaturated ring which may contain 1-3 heteroatoms independently selected from O, S or N; This further ring may be unsubstituted or may be substituted with halogen, CN, oxo, OH, CO2H, CO2-C 1~4 -Alkyl, CONHCH2CO2H, CONH(CH2)2SO3H, C 1~4 -Alkyl, Halo-C 1~4 -Alkyl, OC 1~4 -Alkyl and O-Halo-C 1~4 -substituted with 1 to 4 substituents independently selected from alkyl; wherein two adjacent substituents on the cycloalkyl or heterocycloalkyl moiety may form a 5- to 6-membered unsaturated ring which may contain 1 to 3 heteroatoms independently selected from O, S, or N; This further ring may be unsubstituted or may be substituted with halogen, CN, oxo, OH, CO2H, CO2-C 1~4 -Alkyl, CONHCH2CO2H, CONH(CH2)2SO3H, C 1~4 -Alkyl, Halo-C 1~4 -Alkyl, OC 1~4 -Alkyl and O-Halo-C 1~4 -substituted with 1 to 4 substituents independently selected from alkyl; During the ceremony, [ka] teeth, [ka] or a further ring fused in a 1,2-orientation, L is a bond, C1~6 -Alkylene, C 2~6 -Alkenylene, C 2~6 - selected from the group consisting of alkynylene, 3- to 10-membered cycloalkylene, 3- to 10-membered heterocycloalkylene containing 1-4 heteroatoms independently selected from N, O and S, 6- or 10-membered arylene, and 5- to 10-membered heteroarylene containing 1-4 heteroatoms independently selected from N, O and S; wherein alkylene, alkenylene, alkynylene, cycloalkylene, heterocycloalkylene, arylene and heteroarylene are unsubstituted or substituted with halogen, CN, SF, NO, oxo, C 1~4 -Alkyl, C 0~6 -Alkylene-OR 41 , C 0~6 -Alkylene-(3- to 6-membered cycloalkyl), C 0~6 -alkylene-(3- to 6-membered heterocycloalkyl), C 0~6 -Alkylene-S(O) n R 41 , C 0~6 -Alkylene-NR 41 S(O)2R 41 , C 0~6 -Alkylene-S(O)NR 41 R 42 , C 0~6 -Alkylene-NR 41 S(O)NR 41 R 42 , C 0~6 -Alkylene-CO2R 41 , O.C. 1~6 -Alkylene-CO2R 41 , C 0~6 -Alkylene-O-COR 41 , C 0~6 -Alkylene-CONR 41 R 42 , C 0~6 -Alkylene-NR 41 -COR 41 , C 0~6 -Alkylene-NR 41 -CONR 41 R 42 , C 0~6 -Alkylene-O-CONR41 R 42 , C 0~6 -Alkylene-NR 41 -CO2R 41 and C 0~6 -Alkylene-NR 41 R 42 and is substituted with 1 to 6 substituents independently selected from the group consisting of: wherein alkyl, alkylene, cycloalkyl and heterocycloalkyl are unsubstituted or substituted with halogen, CN, oxo, hydroxy, COH, CO-C 1~4 -Alkyl, CONHCH2CO2H, CONH(CH2)2SO3H, C 1~4 -Alkyl, Halo-C 1~4 -Alkyl, OC 1~4 -Alkyl and O-Halo-C 1~4 -substituted with 1 to 6 substituents independently selected from alkyl; wherein two adjacent substituents on the arylene moiety and the heteroarylene moiety may form a 5- to 8-membered partially unsaturated ring which may contain 1 to 3 heteroatoms independently selected from O, S, or N; This further ring may be unsubstituted or may be substituted with halogen, CN, oxo, OH, CO2H, CO2-C 1~4 -Alkyl, C 1~4 -Alkyl, Halo-C 1~4 -Alkyl, OC 1~4 -Alkyl and O-Halo-C 1~4 -substituted with 1 to 4 substituents independently selected from alkyl; R 1 H, halogen, CN, SF5, NO2, oxo, C 1~4 -Alkyl, C 0~6 -Alkylene-OR 41 , Y.C. 0~6 -Alkylene-(3-6 membered cycloalkyl), YC 0~6 -Alkylene-(3-6 membered heterocycloalkyl), YC 0~6 -alkylene-(6-membered aryl), YC 0~6 -alkylene-(5-6 membered heteroaryl), C 0~6 -Alkylene-S(=O)(-R41 )=NR 75 , XC 1~6 -Alkylene-S(=O)(-R 41 )=NR 75 , C 0~6 -Alkylene-S(O) n R 41 , XC 1~6 -Alkylene-S(O) n R 41 , C 0~6 -Alkylene-S(=NR 71 )R 41 , XC 1~6 -Alkylene-S(=NR 71 )R 41 , C 0~6 -Alkylene-S(O)(=NR 71 )R 41 , XC 1~6 -Alkylene-S(O)(=NR 71 )R 41 , C 0~6 -Alkylene-S(=NR 71 )2R 41 , XC 1~6 -Alkylene-S(=NR 71 )2R 41 , C 0~6 -Alkylene-NR 41 S(O)2R 41 , XC 1~6 -Alkylene-NR 41 S(O)2R 41 , C 0~6 -Alkylene-S(O)NR 41 R 42 , XC 1~6 -Alkylene-S(O)NR 41 R 42 , C 0~6 -Alkylene-NR 41 S(O)NR 41 R 42 , XC 1~6 -Alkylene-NR 41 S(O)NR 41 R 42 , C 0~6 -Alkylene-SO3R 41 , XC 1~6 -Alkylene-SO3R 41 , C0~6 -Alkylene-CO2R 41 , XC 1~6 -Alkylene-CO2R 41 , C 0~6 -Alkylene-O-COR 41 , XC 1~6 -Alkylene-O-COR 41 , C 0~6 -Alkylene-CONR 41 R 42 , XC 1~6 -Alkylene-CONR 41 R 42 , C 0~6 -Alkylene-CONR 41 OR 41 , XC 1~6 -Alkylene-CONR 41 OR 41 , C 0~6 -Alkylene-CONR 41 SO2R 41 , XC 1~6 -Alkylene-CONR 41 SO2R 41 , C 0~6 -Alkylene-NR 41 -COR 41 , XC 1~6 -C 0~6 -Alkylene-NR 41 -COR 41 , C 0~6 -Alkylene-NR 41 -CONR 41 R 42 , XC 1~6 -Alkylene-NR 41 -CONR 41 R 42 , C 0~6 -Alkylene-O-CONR 41 R 42 , XC 1~6 -Alkylene-O-CONR 41 R 42 , C 0~6 -Alkylene-NR 41 -CO2R 41 , XC 1~6 -Alkylene-NR 41 -CO2R 41 , C 0~6-Alkylene-NR 41 R 42 , XC 1~6 -Alkylene-NR 41 R 42 is selected from the group consisting of wherein alkyl, alkylene, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are unsubstituted or substituted with halogen, CN, oxo, hydroxy, COH, CO-C 1~4 -Alkyl, CONHCH2CO2H, CONH(CH2)2SO3H, C 1~4 -Alkyl, Halo-C 1~4 -Alkyl, OC 1~4 -Alkyl and O-Halo-C 1~4 -substituted with 1 to 6 substituents independently selected from alkyl; wherein two adjacent substituents on the aryl and heteroaryl moieties may form a 5-8 membered partially unsaturated ring which may contain 1-3 heteroatoms independently selected from O, S or N; This further ring may be unsubstituted or may be substituted with halogen, CN, oxo, OH, CO2H, CO2-C 1~4 -Alkyl, CONHCH2CO2H, CONH(CH2)2SO3H, C 1~4 -Alkyl, Halo-C 1~4 -Alkyl, OC 1~4 -Alkyl and O-Halo-C 1~4 -substituted with 1 to 4 substituents independently selected from alkyl; R 11 , R 12 , R 21 , R 22 , R 31 , R 32 , R 41 , R 42 , R 51 are independently H and C 1~4 -alkyl, wherein alkyl is unsubstituted or is substituted with halogen, CN, C 1~4 -Alkyl, Halo-C 1~4-Alkyl, 3- to 6-membered cycloalkyl, halo-(3- to 6-membered cycloalkyl), 3- to 6-membered heterocycloalkyl, halo-(3- to 6-membered heterocycloalkyl), OH, oxo, CO2H, CO2-C 1~4 -Alkyl, CONHCH2CO2H, CONH(CH2)2SO3H, SO3H, OC 1~4 -Alkyl and O-Halo-C 1~4 -substituted with 1 to 3 substituents independently selected from alkyl; or R 11 and R 12 , R 21 and R 22 , R 31 and R 32 , R 41 and R 42 each, when taken together with the nitrogen to which they are attached, completes a 3- to 6-membered ring containing carbon atoms and optionally containing 1 or 2 heteroatoms independently selected from O, S or N; The newly formed ring may be unsubstituted or may contain halogen, CN, C 1~4 -Alkyl, Halo-C 1~4 -Alkyl, 3- to 6-membered cycloalkyl, halo-(3- to 6-membered cycloalkyl), 3- to 6-membered heterocycloalkyl, halo-(3- to 6-membered heterocycloalkyl), OH, oxo, CO2H, CO2-C 1~4 -Alkyl, CONHCH2CO2H, CONH(CH2)2SO3H, SO3H, OC 1~4 -Alkyl and O-Halo-C 1~4 -substituted with 1 to 3 substituents independently selected from alkyl; R 71 are independently H, CN, NO2, C 1~4 -Alkyl, and C(O)-OC 1~4 -alkyl, wherein alkyl is unsubstituted or is substituted with halogen, CN, C 1~4 -Alkyl, Halo-C 1~4 -Alkyl, 3- to 6-membered cycloalkyl, halo-(3- to 6-membered cycloalkyl), 3- to 6-membered heterocycloalkyl, halo-(3- to 6-membered heterocycloalkyl), OH, oxo, CO2H, CO2-C1~4 -Alkyl, CONHCH2CO2H, CONH(CH2)2SO3H, SO3H, OC 1~4 -Alkyl and O-Halo-C 1~4 -substituted with 1 to 3 substituents independently selected from alkyl; R 75 are independently, C 1~4 selected from alkyl, 3- to 6-membered cycloalkyl, 3- to 6-membered heterocycloalkyl, 6-membered aryl, and 5- to 6-membered heteroaryl; wherein alkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl are unsubstituted or substituted with 1 to 3 substituents independently selected from halogen, CN, Me, Et, CHF, CF, OH, oxo, COH, CONHCHCOH, CONH(CH)SOH, SOH, OMe, OEt, OCHF, and OCF; X is independently O, NR 51 , S(O) n , S(=NR 71 ), S(O)(=NR 71 ) and S(=NR 71 )2 is selected, Y is independently a bond, O, or NR 51 , S(O) n , S(=NR 71 ), S(O)(=NR 71 ) and S(=NR 71 )2 is selected, n is independently selected from 0 to 2; however, [ka] The structure of the method is excluded.

[0172] Embodiment II-2. 1. Use of a compound in the treatment of a metabolic disorder associated with dyslipidemia or impaired lipid homeostasis, the compound being represented by formula (I): [ka] its glycine conjugates, taurine conjugates, enantiomers, diastereomers, tautomers, N-oxides, solvates, prodrugs, and pharmaceutically acceptable salts thereof; During the ceremony, [ka] is a fused 5- to 6-membered ring forming a 6-membered aryl or a 5- to 6-membered heteroaryl containing 1 to 3 heteroatoms independently selected from N, O, and S, the ring being unsubstituted or substituted with halogen, CN, SF, NO, C 1~6 -Alkyl, oxo, C 0~6 -Alkylene-OR 11 , C 0~6 -Alkylene-(3- to 6-membered cycloalkyl), C 0~6 -alkylene-(3- to 6-membered heterocycloalkyl), C 0~6 -Alkylene-S(O) n R 11 , C 0~6 -Alkylene-NR 11 S(O)2R 11 , C 0~6 -Alkylene-S(O)NR 11 R 12 , C 0~6 -Alkylene-NR 11 S(O)NR 11 R 12 , C 0~6 -Alkylene-CO2R 11 , O.C. 1~6 -Alkylene-CO2R 11 , C 0~6 -Alkylene-O-COR 11 , C 0~6 -Alkylene-CONR 11 R 12 , C 0~6 -Alkylene-NR 11 -COR 11 , C 0~6 -Alkylene-NR 11 -CONR 11 R 12 , C 0~6 -Alkylene-O-CONR 11 R 12 , C0~6 -Alkylene-NR 11 -CO2R 11 and C 0~6 -Alkylene-NR 11 R 12 and is substituted with 1 to 4 substituents independently selected from the group consisting of: wherein alkyl, alkylene, cycloalkyl, and heterocycloalkyl are unsubstituted or substituted with halogen, CN, oxo, hydroxy, COH, CO-C 1~4 -Alkyl, CONHCH2CO2H, CONH(CH2)2SO3H, C 1~4 -Alkyl, Halo-C 1~4 -Alkyl, OC 1~4 -Alkyl and O-Halo-C 1~4 -substituted with 1 to 6 substituents independently selected from alkyl; wherein two adjacent substituents on the aryl or heteroaryl moiety may form a 5-8 membered partially unsaturated ring which may contain 1-3 heteroatoms independently selected from O, S or N; The newly formed ring may be unsubstituted or may contain halogen, CN, C 1~4 -Alkyl, Halo-C 1~4 -Alkyl, 3- to 6-membered cycloalkyl, halo-(3- to 6-membered cycloalkyl), 3- to 6-membered heterocycloalkyl, halo-(3- to 6-membered heterocycloalkyl), OH, oxo, CO2H, CO2-C 1~4 -Alkyl, CONHCH2CO2H, CONH(CH2)2SO3H, OC 1~4 -Alkyl and O-Halo-C 1~4 -substituted with 1 to 3 substituents independently selected from alkyl; [ka] is selected from the group consisting of 3- to 10-membered cycloalkyl, 3- to 10-membered heterocycloalkyl containing 1-3 heteroatoms independently selected from N, O, and S, 6- to 14-membered aryl, and 5- to 14-membered heteroaryl containing 1-4 heteroatoms independently selected from N, O, and S; wherein cycloalkyl, heterocycloalkyl, aryl and heteroaryl are unsubstituted or substituted with halogen, CN, SF, NO, oxo, C 1~4 -Alkyl, C 0~6 -Alkylene-OR 21 , C 0~6 -Alkylene-(3- to 6-membered cycloalkyl), C 0~6 -alkylene-(3- to 6-membered heterocycloalkyl), C 0~6 -Alkylene-S(O) n R 21 , C 0~6 -Alkylene-NR 21 S(O)2R 21 , C 0~6 -Alkylene-S(O)NR 21 R 22 , C 0~6 -Alkylene-NR 21 S(O)NR 21 R 22 , C 0~6 -Alkylene-CO2R 21 , O.C. 1~6 -Alkylene-CO2R 21 , C 0~6 -Alkylene-O-COR 21 , C 0~6 -Alkylene-CONR 21 R 22 , C 0~6 -Alkylene-NR 21 -COR 21 , C 0~6 -Alkylene-NR 21 -CONR 21 R 22 , C 0~6 -Alkylene-O-CONR 21 R 22 , C 0~6 -Alkylene-NR 21 -CO2R 21 and C 0~6 -Alkylene-NR 21 R 22 and is substituted with 1 to 6 substituents independently selected from the group consisting of: wherein alkyl, alkylene, cycloalkyl and heterocycloalkyl are unsubstituted or substituted with halogen, CN, oxo, hydroxy, COH, CO-C 1~4 -Alkyl, CONHCH2CO2H, CONH(CH2)2SO3H, C 1~4 -Alkyl, Halo-C 1~4 -Alkyl, OC 1~4 -Alkyl and O-Halo-C 1~4 -substituted with 1 to 6 substituents independently selected from alkyl; wherein two adjacent substituents on the aryl or heteroaryl moiety may form a 5-8 membered partially unsaturated ring which may contain 1-3 heteroatoms independently selected from O, S or N; This further ring may be unsubstituted or may be substituted with halogen, CN, oxo, OH, CO2H, CO2-C 1~4 -Alkyl, CONHCH2CO2H, CONH(CH2)2SO3H, C 1~4 -Alkyl, Halo-C 1~4 -Alkyl, OC 1~4 -Alkyl and O-Halo-C 1~4 -substituted with 1 to 4 substituents independently selected from alkyl; wherein two adjacent substituents on the cycloalkyl or heterocycloalkyl moiety may form a 5- to 6-membered unsaturated ring which may contain 1 to 3 heteroatoms independently selected from O, S, or N; This further ring may be unsubstituted or may be substituted with halogen, CN, oxo, OH, CO2H, CO2-C 1~4 -Alkyl, CONHCH2CO2H, CONH(CH2)2SO3H, C 1~4 -Alkyl, Halo-C 1~4 -Alkyl, OC 1~4 -Alkyl and O-Halo-C 1~4 -substituted with 1 to 4 substituents independently selected from alkyl; [ka] is selected from the group consisting of 6- or 10-membered aryl and 5- to 10-membered heteroaryl containing 1-3 heteroatoms independently selected from N, O, and S; wherein cycloalkyl, heterocycloalkyl, aryl and heteroaryl are unsubstituted or substituted with halogen, CN, SF, NO, oxo, C 1~4 -Alkyl, C 0~6 -Alkylene-OR 31 , C 0~6 -Alkylene-(3- to 6-membered cycloalkyl), C 0~6 -alkylene-(3- to 6-membered heterocycloalkyl), C 0~6 -alkylene-(6-membered aryl), C 0~6 -alkylene-(5-6 membered heteroaryl), C 0~6 -Alkylene-S(O) n R 31 , C 0~6 -Alkylene-NR 31 S(O)2R 31 , C 0~6 -Alkylene-S(O)NR 31 R 32 , C 0~6 -Alkylene-NR 31 S(O)NR 31 R 32 , C 0~6 -Alkylene-CO2R 31 , O.C. 1~6 -Alkylene-CO2R 31 , C 0~6 -Alkylene-O-COR 31 , C 0~6 -Alkylene-CONR 31 R 32 , C 0~6 -Alkylene-NR 31 -COR 31 , C 0~6 -Alkylene-NR 31 -CONR 31 R 32 , C 0~6 -Alkylene-O-CONR 31 R 32 , C 0~6 -Alkylene-NR 31 -CO2R 31 and C0~6 -Alkylene-NR 31 R 32 and is substituted with 1 to 4 substituents independently selected from the group consisting of: wherein alkyl, alkylene, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are unsubstituted or substituted with halogen, CN, oxo, hydroxy, COH, CO-C 1~4 -Alkyl, CONHCH2CO2H, CONH(CH2)2SO3H, C 1~4 -Alkyl, Halo-C 1~4 -Alkyl, OC 1~4 -Alkyl and O-Halo-C 1~4 -substituted with 1 to 6 substituents independently selected from alkyl; wherein two adjacent substituents on the aryl or heteroaryl moiety may form a 5-8 membered partially unsaturated ring which may contain 1-3 heteroatoms independently selected from O, S or N; This further ring may be unsubstituted or may be substituted with halogen, CN, oxo, OH, CO2H, CO2-C 1~4 -Alkyl, CONHCH2CO2H, CONH(CH2)2SO3H, C 1~4 -Alkyl, Halo-C 1~4 -Alkyl, OC 1~4 -Alkyl and O-Halo-C 1~4 -substituted with 1 to 4 substituents independently selected from alkyl; [ka] is selected from the group consisting of 3- to 10-membered cycloalkyl, 3- to 10-membered heterocycloalkyl containing 1-3 heteroatoms independently selected from N, O, and S, 6- to 14-membered aryl, and 5- to 14-membered heteroaryl containing 1-4 heteroatoms independently selected from N, O, and S; wherein cycloalkyl, heterocycloalkyl, aryl and heteroaryl are unsubstituted or substituted with halogen, CN, SF, NO, oxo, C 1~4 -Alkyl, C 0~6 -Alkylene-OR 21 , C0~6 -Alkylene-(3- to 6-membered cycloalkyl), C 0~6 -alkylene-(3- to 6-membered heterocycloalkyl), C 0~6 -Alkylene-S(O) n R 21 , C 0~6 -Alkylene-NR 21 S(O)2R 21 , C 0~6 -Alkylene-S(O)NR 21 R 22 , C 0~6 -Alkylene-NR 21 S(O)NR 21 R 22 , C 0~6 -Alkylene-CR 41 (=N-OR 41 ), C 0~6 -Alkylene-CO2R 21 , O.C. 1~6 -Alkylene-CO2R 21 , C 0~6 -Alkylene-O-COR 21 , C 0~6 -Alkylene-CONR 21 R 22 , C 0~6 -Alkylene-NR 21 -COR 21 , C 0~6 -Alkylene-NR 21 -CONR 21 R 22 , C 0~6 -Alkylene-O-CONR 21 R 22 , C 0~6 -Alkylene-NR 21 -CO2R 21 and C 0~6 -Alkylene-NR 21 R 22 and is substituted with 1 to 6 substituents independently selected from the group consisting of: wherein alkyl, alkylene, cycloalkyl and heterocycloalkyl are unsubstituted or substituted with halogen, CN, oxo, hydroxy, COH, CO-C 1~4 -Alkyl, CONHCH2CO2H, CONH(CH2)2SO3H, CO-OC 1~4-Alkyl, C 1~4 -Alkyl, Halo-C 1~4 -Alkyl, OC 1~4 -Alkyl and O-Halo-C 1~4 -substituted with 1 to 6 substituents independently selected from alkyl; wherein two adjacent substituents on the aryl or heteroaryl moiety may form a 5-8 membered partially unsaturated ring which may contain 1-3 heteroatoms independently selected from O, S or N; This further ring may be unsubstituted or may be substituted with halogen, CN, oxo, OH, CO2H, CO2-C 1~4 -Alkyl, CONHCH2CO2H, CONH(CH2)2SO3H, C 1~4 -Alkyl, Halo-C 1~4 -Alkyl, OC 1~4 -Alkyl and O-Halo-C 1~4 -substituted with 1 to 4 substituents independently selected from alkyl; wherein two adjacent substituents on the cycloalkyl or heterocycloalkyl moiety may form a 5- to 6-membered unsaturated ring which may contain 1 to 3 heteroatoms independently selected from O, S, or N; This further ring may be unsubstituted or may be substituted with halogen, CN, oxo, OH, CO2H, CO2-C 1~4 -Alkyl, CONHCH2CO2H, CONH(CH2)2SO3H, C 1~4 -Alkyl, Halo-C 1~4 -Alkyl, OC 1~4 -Alkyl and O-Halo-C 1~4 -substituted with 1 to 4 substituents independently selected from alkyl; During the ceremony, [ka] teeth, [ka] or a further ring fused in a 1,2-orientation, L is a bond, C1~6 -Alkylene, C 2~6 -Alkenylene, C 2~6 - selected from the group consisting of alkynylene, 3- to 10-membered cycloalkylene, 3- to 10-membered heterocycloalkylene containing 1-4 heteroatoms independently selected from N, O and S, 6- or 10-membered arylene, and 5- to 10-membered heteroarylene containing 1-4 heteroatoms independently selected from N, O and S; wherein alkylene, alkenylene, alkynylene, cycloalkylene, heterocycloalkylene, arylene and heteroarylene are unsubstituted or substituted with halogen, CN, SF, NO, oxo, C 1~4 -Alkyl, C 0~6 -Alkylene-OR 41 , C 0~6 -Alkylene-(3- to 6-membered cycloalkyl), C 0~6 -alkylene-(3- to 6-membered heterocycloalkyl), C 0~6 -Alkylene-S(O) n R 41 , C 0~6 -Alkylene-NR 41 S(O)2R 41 , C 0~6 -Alkylene-S(O)NR 41 R 42 , C 0~6 -Alkylene-NR 41 S(O)NR 41 R 42 , C 0~6 -Alkylene-CO2R 41 , O.C. 1~6 -Alkylene-CO2R 41 , C 0~6 -Alkylene-O-COR 41 , C 0~6 -Alkylene-CONR 41 R 42 , C 0~6 -Alkylene-NR 41 -COR 41 , C 0~6 -Alkylene-NR 41 -CONR 41 R 42 , C 0~6 -Alkylene-O-CONR41 R 42 , C 0~6 -Alkylene-NR 41 -CO2R 41 and C 0~6 -Alkylene-NR 41 R 42 and is substituted with 1 to 6 substituents independently selected from the group consisting of: wherein alkyl, alkylene, cycloalkyl and heterocycloalkyl are unsubstituted or substituted with halogen, CN, oxo, hydroxy, COH, CO-C 1~4 -Alkyl, CONHCH2CO2H, CONH(CH2)2SO3H, C 1~4 -Alkyl, Halo-C 1~4 -Alkyl, OC 1~4 -Alkyl and O-Halo-C 1~4 -substituted with 1 to 6 substituents independently selected from alkyl; wherein two adjacent substituents on the arylene moiety and the heteroarylene moiety may form a 5- to 8-membered partially unsaturated ring which may contain 1 to 3 heteroatoms independently selected from O, S, or N; This further ring may be unsubstituted or may be substituted with halogen, CN, oxo, OH, CO2H, CO2-C 1~4 -Alkyl, C 1~4 -Alkyl, Halo-C 1~4 -Alkyl, OC 1~4 -Alkyl and O-Halo-C 1~4 -substituted with 1 to 4 substituents independently selected from alkyl; R 1 H, halogen, CN, SF5, NO2, oxo, C 1~4 -Alkyl, C 0~6 -Alkylene-OR 41 , Y.C. 0~6 -Alkylene-(3-6 membered cycloalkyl), YC 0~6 -Alkylene-(3-6 membered heterocycloalkyl), YC 0~6 -alkylene-(6-membered aryl), YC 0~6 -alkylene-(5-6 membered heteroaryl), C 0~6 -Alkylene-S(=O)(-R41 )=NR 75 , XC 1~6 -Alkylene-S(=O)(-R 41 )=NR 75 , C 0~6 -Alkylene-S(O) n R 41 , XC 1~6 -Alkylene-S(O) n R 41 , C 0~6 -Alkylene-S(=NR 71 )R 41 , XC 1~6 -Alkylene-S(=NR 71 )R 41 , C 0~6 -Alkylene-S(O)(=NR 71 )R 41 , XC 1~6 -Alkylene-S(O)(=NR 71 )R 41 , C 0~6 -Alkylene-S(=NR 71 )2R 41 , XC 1~6 -Alkylene-S(=NR 71 )2R 41 , C 0~6 -Alkylene-NR 41 S(O)2R 41 , XC 1~6 -Alkylene-NR 41 S(O)2R 41 , C 0~6 -Alkylene-S(O)NR 41 R 42 , XC 1~6 -Alkylene-S(O)NR 41 R 42 , C 0~6 -Alkylene-NR 41 S(O)NR 41 R 42 , XC 1~6 -Alkylene-NR 41 S(O)NR 41 R 42 , C 0~6 -Alkylene-SO3R 41 , XC 1~6 -Alkylene-SO3R 41 , C0~6 -Alkylene-CO2R 41 , XC 1~6 -Alkylene-CO2R 41 , C 0~6 -Alkylene-O-COR 41 , XC 1~6 -Alkylene-O-COR 41 , C 0~6 -Alkylene-CONR 41 R 42 , XC 1~6 -Alkylene-CONR 41 R 42 , C 0~6 -Alkylene-CONR 41 OR 41 , XC 1~6 -Alkylene-CONR 41 OR 41 , C 0~6 -Alkylene-CONR 41 SO2R 41 , XC 1~6 -Alkylene-CONR 41 SO2R 41 , C 0~6 -Alkylene-NR 41 -COR 41 , XC 1~6 -C 0~6 -Alkylene-NR 41 -COR 41 , C 0~6 -Alkylene-NR 41 -CONR 41 R 42 , XC 1~6 -Alkylene-NR 41 -CONR 41 R 42 , C 0~6 -Alkylene-O-CONR 41 R 42 , XC 1~6 -Alkylene-O-CONR 41 R 42 , C 0~6 -Alkylene-NR 41 -CO2R 41 , XC 1~6 -Alkylene-NR 41 -CO2R 41 , C 0~6-Alkylene-NR 41 R 42 , XC 1~6 -Alkylene-NR 41 R 42 is selected from the group consisting of wherein alkyl, alkylene, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are unsubstituted or substituted with halogen, CN, oxo, hydroxy, COH, CO-C 1~4 -Alkyl, CONHCH2CO2H, CONH(CH2)2SO3H, C 1~4 -Alkyl, Halo-C 1~4 -Alkyl, OC 1~4 -Alkyl and O-Halo-C 1~4 -substituted with 1 to 6 substituents independently selected from alkyl; wherein two adjacent substituents on the aryl and heteroaryl moieties may form a 5-8 membered partially unsaturated ring which may contain 1-3 heteroatoms independently selected from O, S or N; This further ring may be unsubstituted or may be substituted with halogen, CN, oxo, OH, CO2H, CO2-C 1~4 -Alkyl, CONHCH2CO2H, CONH(CH2)2SO3H, C 1~4 -Alkyl, Halo-C 1~4 -Alkyl, OC 1~4 -Alkyl and O-Halo-C 1~4 -substituted with 1 to 4 substituents independently selected from alkyl; R 11 , R 12 , R 21 , R 22 , R 31 , R 32 , R 41 , R 42 , R 51 are independently H and C 1~4 -alkyl, wherein alkyl is unsubstituted or is substituted with halogen, CN, C 1~4 -Alkyl, Halo-C 1~4-Alkyl, 3- to 6-membered cycloalkyl, halo-(3- to 6-membered cycloalkyl), 3- to 6-membered heterocycloalkyl, halo-(3- to 6-membered heterocycloalkyl), OH, oxo, CO2H, CO2-C 1~4 -Alkyl, CONHCH2CO2H, CONH(CH2)2SO3H, SO3H, OC 1~4 -Alkyl and O-Halo-C 1~4 -substituted with 1 to 3 substituents independently selected from alkyl; or R 11 and R 12 , R 21 and R 22 , R 31 and R 32 , R 41 and R 42 each, when taken together with the nitrogen to which they are attached, completes a 3- to 6-membered ring containing carbon atoms and optionally containing 1 or 2 heteroatoms independently selected from O, S or N; The newly formed ring may be unsubstituted or may contain halogen, CN, C 1~4 -Alkyl, Halo-C 1~4 -Alkyl, 3- to 6-membered cycloalkyl, halo-(3- to 6-membered cycloalkyl), 3- to 6-membered heterocycloalkyl, halo-(3- to 6-membered heterocycloalkyl), OH, oxo, CO2H, CO2-C 1~4 -Alkyl, CONHCH2CO2H, CONH(CH2)2SO3H, SO3H, OC 1~4 -Alkyl and O-Halo-C 1~4 -substituted with 1 to 3 substituents independently selected from alkyl; R 71 are independently H, CN, NO2, C 1~4 -Alkyl, and C(O)-OC 1~4 -alkyl, wherein alkyl is unsubstituted or is substituted with halogen, CN, C 1~4 -Alkyl, Halo-C 1~4 -Alkyl, 3- to 6-membered cycloalkyl, halo-(3- to 6-membered cycloalkyl), 3- to 6-membered heterocycloalkyl, halo-(3- to 6-membered heterocycloalkyl), OH, oxo, CO2H, CO2-C1~4 -Alkyl, CONHCH2CO2H, CONH(CH2)2SO3H, SO3H, OC 1~4 -Alkyl and O-Halo-C 1~4 -substituted with 1 to 3 substituents independently selected from alkyl; R 75 are independently, C 1~4 selected from alkyl, 3- to 6-membered cycloalkyl, 3- to 6-membered heterocycloalkyl, 6-membered aryl, and 5- to 6-membered heteroaryl; wherein alkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl are unsubstituted or substituted with 1 to 3 substituents independently selected from halogen, CN, Me, Et, CHF, CF, OH, oxo, COH, CONHCHCOH, CONH(CH)SOH, SOH, OMe, OEt, OCHF, and OCF; X is independently O, NR 51 , S(O) n , S(=NR 71 ), S(O)(=NR 71 ) and S(=NR 71 )2 is selected, Y is independently a bond, O, or NR 51 , S(O) n , S(=NR 71 ), S(O)(=NR 71 ) and S(=NR 71 )2 is selected, n is independently selected from 0 to 2; however, [ka] The structure of the use is excluded.

[0173] Embodiment II-3. 1. Use of a compound in the manufacture of a medicament for treating a metabolic disorder associated with dyslipidemia or impaired lipid homeostasis, wherein the compound is a compound represented by formula (I): [ka] its glycine conjugates, taurine conjugates, enantiomers, diastereomers, tautomers, N-oxides, solvates, prodrugs, and pharmaceutically acceptable salts thereof; During the ceremony, [ka] is a fused 5- to 6-membered ring forming a 6-membered aryl or a 5- to 6-membered heteroaryl containing 1 to 3 heteroatoms independently selected from N, O, and S, the ring being unsubstituted or substituted with halogen, CN, SF, NO, C 1~6 -Alkyl, oxo, C 0~6 -Alkylene-OR 11 , C 0~6 -Alkylene-(3- to 6-membered cycloalkyl), C 0~6 -alkylene-(3- to 6-membered heterocycloalkyl), C 0~6 -Alkylene-S(O) n R 11 , C 0~6 -Alkylene-NR 11 S(O)2R 11 , C 0~6 -Alkylene-S(O)NR 11 R 12 , C 0~6 -Alkylene-NR 11 S(O)NR 11 R 12 , C 0~6 -Alkylene-CO2R 11 , O.C. 1~6 -Alkylene-CO2R 11 , C 0~6 -Alkylene-O-COR 11 , C 0~6 -Alkylene-CONR 11 R 12 , C 0~6 -Alkylene-NR 11 -COR 11 , C 0~6 -Alkylene-NR 11 -CONR 11 R 12 , C 0~6 -Alkylene-O-CONR 11 R 12 , C0~6 -Alkylene-NR 11 -CO2R 11 and C 0~6 -Alkylene-NR 11 R 12 and is substituted with 1 to 4 substituents independently selected from the group consisting of: wherein alkyl, alkylene, cycloalkyl, and heterocycloalkyl are unsubstituted or substituted with halogen, CN, oxo, hydroxy, COH, CO-C 1~4 -Alkyl, CONHCH2CO2H, CONH(CH2)2SO3H, C 1~4 -Alkyl, Halo-C 1~4 -Alkyl, OC 1~4 -Alkyl and O-Halo-C 1~4 -substituted with 1 to 6 substituents independently selected from alkyl; wherein two adjacent substituents on the aryl or heteroaryl moiety may form a 5-8 membered partially unsaturated ring which may contain 1-3 heteroatoms independently selected from O, S or N; The newly formed ring may be unsubstituted or may contain halogen, CN, C 1~4 -Alkyl, Halo-C 1~4 -Alkyl, 3- to 6-membered cycloalkyl, halo-(3- to 6-membered cycloalkyl), 3- to 6-membered heterocycloalkyl, halo-(3- to 6-membered heterocycloalkyl), OH, oxo, CO2H, CO2-C 1~4 -Alkyl, CONHCH2CO2H, CONH(CH2)2SO3H, OC 1~4 -Alkyl and O-Halo-C 1~4 -substituted with 1 to 3 substituents independently selected from alkyl; [ka] is selected from the group consisting of 3- to 10-membered cycloalkyl, 3- to 10-membered heterocycloalkyl containing 1-3 heteroatoms independently selected from N, O, and S, 6- to 14-membered aryl, and 5- to 14-membered heteroaryl containing 1-4 heteroatoms independently selected from N, O, and S; wherein cycloalkyl, heterocycloalkyl, aryl and heteroaryl are unsubstituted or substituted with halogen, CN, SF, NO, oxo, C 1~4 -Alkyl, C 0~6 -Alkylene-OR 21 , C 0~6 -Alkylene-(3- to 6-membered cycloalkyl), C 0~6 -alkylene-(3- to 6-membered heterocycloalkyl), C 0~6 -Alkylene-S(O) n R 21 , C 0~6 -Alkylene-NR 21 S(O)2R 21 , C 0~6 -Alkylene-S(O)NR 21 R 22 , C 0~6 -Alkylene-NR 21 S(O)NR 21 R 22 , C 0~6 -Alkylene-CO2R 21 , O.C. 1~6 -Alkylene-CO2R 21 , C 0~6 -Alkylene-O-COR 21 , C 0~6 -Alkylene-CONR 21 R 22 , C 0~6 -Alkylene-NR 21 -COR 21 , C 0~6 -Alkylene-NR 21 -CONR 21 R 22 , C 0~6 -Alkylene-O-CONR 21 R 22 , C 0~6 -Alkylene-NR 21 -CO2R 21 and C 0~6 -Alkylene-NR 21 R 22 and is substituted with 1 to 6 substituents independently selected from the group consisting of: wherein alkyl, alkylene, cycloalkyl and heterocycloalkyl are unsubstituted or substituted with halogen, CN, oxo, hydroxy, COH, CO-C 1~4 -Alkyl, CONHCH2CO2H, CONH(CH2)2SO3H, C 1~4 -Alkyl, Halo-C 1~4 -Alkyl, OC 1~4 -Alkyl and O-Halo-C 1~4 -substituted with 1 to 6 substituents independently selected from alkyl; wherein two adjacent substituents on the aryl or heteroaryl moiety may form a 5-8 membered partially unsaturated ring which may contain 1-3 heteroatoms independently selected from O, S or N; This further ring may be unsubstituted or may be substituted with halogen, CN, oxo, OH, CO2H, CO2-C 1~4 -Alkyl, CONHCH2CO2H, CONH(CH2)2SO3H, C 1~4 -Alkyl, Halo-C 1~4 -Alkyl, OC 1~4 -Alkyl and O-Halo-C 1~4 -substituted with 1 to 4 substituents independently selected from alkyl; wherein two adjacent substituents on the cycloalkyl or heterocycloalkyl moiety may form a 5- to 6-membered unsaturated ring which may contain 1 to 3 heteroatoms independently selected from O, S, or N; This further ring may be unsubstituted or may be substituted with halogen, CN, oxo, OH, CO2H, CO2-C 1~4 -Alkyl, CONHCH2CO2H, CONH(CH2)2SO3H, C 1~4 -Alkyl, Halo-C 1~4 -Alkyl, OC 1~4 -Alkyl and O-Halo-C 1~4 -substituted with 1 to 4 substituents independently selected from alkyl; [ka] is selected from the group consisting of 6- or 10-membered aryl and 5- to 10-membered heteroaryl containing 1-3 heteroatoms independently selected from N, O, and S; wherein cycloalkyl, heterocycloalkyl, aryl and heteroaryl are unsubstituted or substituted with halogen, CN, SF, NO, oxo, C 1~4 -Alkyl, C 0~6 -Alkylene-OR 31 , C 0~6 -Alkylene-(3- to 6-membered cycloalkyl), C 0~6 -alkylene-(3- to 6-membered heterocycloalkyl), C 0~6 -alkylene-(6-membered aryl), C 0~6 -alkylene-(5-6 membered heteroaryl), C 0~6 -Alkylene-S(O) n R 31 , C 0~6 -Alkylene-NR 31 S(O)2R 31 , C 0~6 -Alkylene-S(O)NR 31 R 32 , C 0~6 -Alkylene-NR 31 S(O)NR 31 R 32 , C 0~6 -Alkylene-CO2R 31 , O.C. 1~6 -Alkylene-CO2R 31 , C 0~6 -Alkylene-O-COR 31 , C 0~6 -Alkylene-CONR 31 R 32 , C 0~6 -Alkylene-NR 31 -COR 31 , C 0~6 -Alkylene-NR 31 -CONR 31 R 32 , C 0~6 -Alkylene-O-CONR 31 R 32 , C 0~6 -Alkylene-NR 31 -CO2R 31 and C0~6 -Alkylene-NR 31 R 32 and is substituted with 1 to 4 substituents independently selected from the group consisting of: wherein alkyl, alkylene, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are unsubstituted or substituted with halogen, CN, oxo, hydroxy, COH, CO-C 1~4 -Alkyl, CONHCH2CO2H, CONH(CH2)2SO3H, C 1~4 -Alkyl, Halo-C 1~4 -Alkyl, OC 1~4 -Alkyl and O-Halo-C 1~4 -substituted with 1 to 6 substituents independently selected from alkyl; wherein two adjacent substituents on the aryl or heteroaryl moiety may form a 5-8 membered partially unsaturated ring which may contain 1-3 heteroatoms independently selected from O, S or N; This further ring may be unsubstituted or may be substituted with halogen, CN, oxo, OH, CO2H, CO2-C 1~4 -Alkyl, CONHCH2CO2H, CONH(CH2)2SO3H, C 1~4 -Alkyl, Halo-C 1~4 -Alkyl, OC 1~4 -Alkyl and O-Halo-C 1~4 -substituted with 1 to 4 substituents independently selected from alkyl; [ka] is selected from the group consisting of 3- to 10-membered cycloalkyl, 3- to 10-membered heterocycloalkyl containing 1-3 heteroatoms independently selected from N, O, and S, 6- to 14-membered aryl, and 5- to 14-membered heteroaryl containing 1-4 heteroatoms independently selected from N, O, and S; wherein cycloalkyl, heterocycloalkyl, aryl and heteroaryl are unsubstituted or substituted with halogen, CN, SF, NO, oxo, C 1~4 -Alkyl, C 0~6 -Alkylene-OR 21 , C0~6 -Alkylene-(3- to 6-membered cycloalkyl), C 0~6 -alkylene-(3- to 6-membered heterocycloalkyl), C 0~6 -Alkylene-S(O) n R 21 , C 0~6 -Alkylene-NR 21 S(O)2R 21 , C 0~6 -Alkylene-S(O)NR 21 R 22 , C 0~6 -Alkylene-NR 21 S(O)NR 21 R 22 , C 0~6 -Alkylene-CR 41 (=N-OR 41 ), C 0~6 -Alkylene-CO2R 21 , O.C. 1~6 -Alkylene-CO2R 21 , C 0~6 -Alkylene-O-COR 21 , C 0~6 -Alkylene-CONR 21 R 22 , C 0~6 -Alkylene-NR 21 -COR 21 , C 0~6 -Alkylene-NR 21 -CONR 21 R 22 , C 0~6 -Alkylene-O-CONR 21 R 22 , C 0~6 -Alkylene-NR 21 -CO2R 21 and C 0~6 -Alkylene-NR 21 R 22 and is substituted with 1 to 6 substituents independently selected from the group consisting of: wherein alkyl, alkylene, cycloalkyl and heterocycloalkyl are unsubstituted or substituted with halogen, CN, oxo, hydroxy, COH, CO-C 1~4 -Alkyl, CONHCH2CO2H, CONH(CH2)2SO3H, CO-OC 1~4-Alkyl, C 1~4 -Alkyl, Halo-C 1~4 -Alkyl, OC 1~4 -Alkyl and O-Halo-C 1~4 -substituted with 1 to 6 substituents independently selected from alkyl; wherein two adjacent substituents on the aryl or heteroaryl moiety may form a 5-8 membered partially unsaturated ring which may contain 1-3 heteroatoms independently selected from O, S or N; This further ring may be unsubstituted or may be substituted with halogen, CN, oxo, OH, CO2H, CO2-C 1~4 -Alkyl, CONHCH2CO2H, CONH(CH2)2SO3H, C 1~4 -Alkyl, Halo-C 1~4 -Alkyl, OC 1~4 -Alkyl and O-Halo-C 1~4 -substituted with 1 to 4 substituents independently selected from alkyl; wherein two adjacent substituents on the cycloalkyl or heterocycloalkyl moiety may form a 5- to 6-membered unsaturated ring which may contain 1 to 3 heteroatoms independently selected from O, S, or N; This further ring may be unsubstituted or may be substituted with halogen, CN, oxo, OH, CO2H, CO2-C 1~4 -Alkyl, CONHCH2CO2H, CONH(CH2)2SO3H, C 1~4 -Alkyl, Halo-C 1~4 -Alkyl, OC 1~4 -Alkyl and O-Halo-C 1~4 -substituted with 1 to 4 substituents independently selected from alkyl; During the ceremony, [ka] teeth, [ka] or a further ring fused in a 1,2-orientation, L is a bond, C1~6 -Alkylene, C 2~6 -Alkenylene, C 2~6 - selected from the group consisting of alkynylene, 3- to 10-membered cycloalkylene, 3- to 10-membered heterocycloalkylene containing 1-4 heteroatoms independently selected from N, O and S, 6- or 10-membered arylene, and 5- to 10-membered heteroarylene containing 1-4 heteroatoms independently selected from N, O and S; wherein alkylene, alkenylene, alkynylene, cycloalkylene, heterocycloalkylene, arylene and heteroarylene are unsubstituted or substituted with halogen, CN, SF, NO, oxo, C 1~4 -Alkyl, C 0~6 -Alkylene-OR 41 , C 0~6 -Alkylene-(3- to 6-membered cycloalkyl), C 0~6 -alkylene-(3- to 6-membered heterocycloalkyl), C 0~6 -Alkylene-S(O) n R 41 , C 0~6 -Alkylene-NR 41 S(O)2R 41 , C 0~6 -Alkylene-S(O)NR 41 R 42 , C 0~6 -Alkylene-NR 41 S(O)NR 41 R 42 , C 0~6 -Alkylene-CO2R 41 , O.C. 1~6 -Alkylene-CO2R 41 , C 0~6 -Alkylene-O-COR 41 , C 0~6 -Alkylene-CONR 41 R 42 , C 0~6 -Alkylene-NR 41 -COR 41 , C 0~6 -Alkylene-NR 41 -CONR 41 R 42 , C 0~6 -Alkylene-O-CONR41 R 42 , C 0~6 -Alkylene-NR 41 -CO2R 41 and C 0~6 -Alkylene-NR 41 R 42 and is substituted with 1 to 6 substituents independently selected from the group consisting of: wherein alkyl, alkylene, cycloalkyl and heterocycloalkyl are unsubstituted or substituted with halogen, CN, oxo, hydroxy, COH, CO-C 1~4 -Alkyl, CONHCH2CO2H, CONH(CH2)2SO3H, C 1~4 -Alkyl, Halo-C 1~4 -Alkyl, OC 1~4 -Alkyl and O-Halo-C 1~4 -substituted with 1 to 6 substituents independently selected from alkyl; wherein two adjacent substituents on the arylene moiety and the heteroarylene moiety may form a 5- to 8-membered partially unsaturated ring which may contain 1 to 3 heteroatoms independently selected from O, S, or N; This further ring may be unsubstituted or may be substituted with halogen, CN, oxo, OH, CO2H, CO2-C 1~4 -Alkyl, C 1~4 -Alkyl, Halo-C 1~4 -Alkyl, OC 1~4 -Alkyl and O-Halo-C 1~4 -substituted with 1 to 4 substituents independently selected from alkyl; R 1 H, halogen, CN, SF5, NO2, oxo, C 1~4 -Alkyl, C 0~6 -Alkylene-OR 41 , Y.C. 0~6 -Alkylene-(3-6 membered cycloalkyl), YC 0~6 -Alkylene-(3-6 membered heterocycloalkyl), YC 0~6 -alkylene-(6-membered aryl), YC 0~6 -alkylene-(5-6 membered heteroaryl), C 0~6 -Alkylene-S(=O)(-R41 )=NR 75 , XC 1~6 -Alkylene-S(=O)(-R 41 )=NR 75 , C 0~6 -Alkylene-S(O) n R 41 , XC 1~6 -Alkylene-S(O) n R 41 , C 0~6 -Alkylene-S(=NR 71 )R 41 , XC 1~6 -Alkylene-S(=NR 71 )R 41 , C 0~6 -Alkylene-S(O)(=NR 71 )R 41 , XC 1~6 -Alkylene-S(O)(=NR 71 )R 41 , C 0~6 -Alkylene-S(=NR 71 )2R 41 , XC 1~6 -Alkylene-S(=NR 71 )2R 41 , C 0~6 -Alkylene-NR 41 S(O)2R 41 , XC 1~6 -Alkylene-NR 41 S(O)2R 41 , C 0~6 -Alkylene-S(O)NR 41 R 42 , XC 1~6 -Alkylene-S(O)NR 41 R 42 , C 0~6 -Alkylene-NR 41 S(O)NR 41 R 42 , XC 1~6 -Alkylene-NR 41 S(O)NR 41 R 42 , C 0~6 -Alkylene-SO3R 41 , XC 1~6 -Alkylene-SO3R 41 , C0~6 -Alkylene-CO2R 41 , XC 1~6 -Alkylene-CO2R 41 , C 0~6 -Alkylene-O-COR 41 , XC 1~6 -Alkylene-O-COR 41 , C 0~6 -Alkylene-CONR 41 R 42 , XC 1~6 -Alkylene-CONR 41 R 42 , C 0~6 -Alkylene-CONR 41 OR 41 , XC 1~6 -Alkylene-CONR 41 OR 41 , C 0~6 -Alkylene-CONR 41 SO2R 41 , XC 1~6 -Alkylene-CONR 41 SO2R 41 , C 0~6 -Alkylene-NR 41 -COR 41 , XC 1~6 -C 0~6 -Alkylene-NR 41 -COR 41 , C 0~6 -Alkylene-NR 41 -CONR 41 R 42 , XC 1~6 -Alkylene-NR 41 -CONR 41 R 42 , C 0~6 -Alkylene-O-CONR 41 R 42 , XC 1~6 -Alkylene-O-CONR 41 R 42 , C 0~6 -Alkylene-NR 41 -CO2R 41 , XC 1~6 -Alkylene-NR 41 -CO2R 41 , C 0~6-Alkylene-NR 41 R 42 , XC 1~6 -Alkylene-NR 41 R 42 is selected from the group consisting of wherein alkyl, alkylene, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are unsubstituted or substituted with halogen, CN, oxo, hydroxy, COH, CO-C 1~4 -Alkyl, CONHCH2CO2H, CONH(CH2)2SO3H, C 1~4 -Alkyl, Halo-C 1~4 -Alkyl, OC 1~4 -Alkyl and O-Halo-C 1~4 -substituted with 1 to 6 substituents independently selected from alkyl; wherein two adjacent substituents on the aryl and heteroaryl moieties may form a 5-8 membered partially unsaturated ring which may contain 1-3 heteroatoms independently selected from O, S or N; This further ring may be unsubstituted or may be substituted with halogen, CN, oxo, OH, CO2H, CO2-C 1~4 -Alkyl, CONHCH2CO2H, CONH(CH2)2SO3H, C 1~4 -Alkyl, Halo-C 1~4 -Alkyl, OC 1~4 -Alkyl and O-Halo-C 1~4 -substituted with 1 to 4 substituents independently selected from alkyl; R 11 , R 12 , R 21 , R 22 , R 31 , R 32 , R 41 , R 42 , R 51 are independently H and C 1~4 -alkyl, wherein alkyl is unsubstituted or is substituted with halogen, CN, C 1~4 -Alkyl, Halo-C 1~4-Alkyl, 3- to 6-membered cycloalkyl, halo-(3- to 6-membered cycloalkyl), 3- to 6-membered heterocycloalkyl, halo-(3- to 6-membered heterocycloalkyl), OH, oxo, CO2H, CO2-C 1~4 -Alkyl, CONHCH2CO2H, CONH(CH2)2SO3H, SO3H, OC 1~4 -Alkyl and O-Halo-C 1~4 -substituted with 1 to 3 substituents independently selected from alkyl; or R 11 and R 12 , R 21 and R 22 , R 31 and R 32 , R 41 and R 42 each, when taken together with the nitrogen to which they are attached, completes a 3- to 6-membered ring containing carbon atoms and optionally containing 1 or 2 heteroatoms independently selected from O, S or N; The newly formed ring may be unsubstituted or may contain halogen, CN, C 1~4 -Alkyl, Halo-C 1~4 -Alkyl, 3- to 6-membered cycloalkyl, halo-(3- to 6-membered cycloalkyl), 3- to 6-membered heterocycloalkyl, halo-(3- to 6-membered heterocycloalkyl), OH, oxo, CO2H, CO2-C 1~4 -Alkyl, CONHCH2CO2H, CONH(CH2)2SO3H, SO3H, OC 1~4 -Alkyl and O-Halo-C 1~4 -substituted with 1 to 3 substituents independently selected from alkyl; R 71 are independently H, CN, NO2, C 1~4 -Alkyl, and C(O)-OC 1~4 -alkyl, wherein alkyl is unsubstituted or is substituted with halogen, CN, C 1~4 -Alkyl, Halo-C 1~4 -Alkyl, 3- to 6-membered cycloalkyl, halo-(3- to 6-membered cycloalkyl), 3- to 6-membered heterocycloalkyl, halo-(3- to 6-membered heterocycloalkyl), OH, oxo, CO2H, CO2-C1~4 -Alkyl, CONHCH2CO2H, CONH(CH2)2SO3H, SO3H, OC 1~4 -Alkyl and O-Halo-C 1~4 -substituted with 1 to 3 substituents independently selected from alkyl; R 75 are independently, C 1~4 selected from alkyl, 3- to 6-membered cycloalkyl, 3- to 6-membered heterocycloalkyl, 6-membered aryl, and 5- to 6-membered heteroaryl; wherein alkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl are unsubstituted or substituted with 1 to 3 substituents independently selected from halogen, CN, Me, Et, CHF, CF, OH, oxo, COH, CONHCHCOH, CONH(CH)SOH, SOH, OMe, OEt, OCHF, and OCF; X is independently O, NR 51 , S(O) n , S(=NR 71 ), S(O)(=NR 71 ) and S(=NR 71 )2 is selected, Y is independently a bond, O, or NR 51 , S(O) n , S(=NR 71 ), S(O)(=NR 71 ) and S(=NR 71 )2 is selected, n is independently selected from 0 to 2; however, [ka] The structure of the use is excluded.

[0174] Embodiment II-4. 1. A compound for use in the treatment of metabolic disorders associated with dyslipidemia or impaired lipid homeostasis, the compound having formula (I): [ka] its glycine conjugates, taurine conjugates, enantiomers, diastereomers, tautomers, N-oxides, solvates, prodrugs, and pharmaceutically acceptable salts thereof; During the ceremony, [ka] is a fused 5- to 6-membered ring forming a 6-membered aryl or a 5- to 6-membered heteroaryl containing 1 to 3 heteroatoms independently selected from N, O, and S, the ring being unsubstituted or substituted with halogen, CN, SF, NO, C 1~6 -Alkyl, oxo, C 0~6 -Alkylene-OR 11 , C 0~6 -Alkylene-(3- to 6-membered cycloalkyl), C 0~6 -alkylene-(3- to 6-membered heterocycloalkyl), C 0~6 -Alkylene-S(O) n R 11 , C 0~6 -Alkylene-NR 11 S(O)2R 11 , C 0~6 -Alkylene-S(O)NR 11 R 12 , C 0~6 -Alkylene-NR 11 S(O)NR 11 R 12 , C 0~6 -Alkylene-CO2R 11 , O.C. 1~6 -Alkylene-CO2R 11 , C 0~6 -Alkylene-O-COR 11 , C 0~6 -Alkylene-CONR 11 R 12 , C 0~6 -Alkylene-NR 11 -COR 11 , C 0~6 -Alkylene-NR 11 -CONR 11 R 12 , C 0~6 -Alkylene-O-CONR 11 R 12 , C0~6 -Alkylene-NR 11 -CO2R 11 and C 0~6 -Alkylene-NR 11 R 12 and is substituted with 1 to 4 substituents independently selected from the group consisting of: wherein alkyl, alkylene, cycloalkyl, and heterocycloalkyl are unsubstituted or substituted with halogen, CN, oxo, hydroxy, COH, CO-C 1~4 -Alkyl, CONHCH2CO2H, CONH(CH2)2SO3H, C 1~4 -Alkyl, Halo-C 1~4 -Alkyl, OC 1~4 -Alkyl and O-Halo-C 1~4 -substituted with 1 to 6 substituents independently selected from alkyl; wherein two adjacent substituents on the aryl or heteroaryl moiety may form a 5-8 membered partially unsaturated ring which may contain 1-3 heteroatoms independently selected from O, S or N; The newly formed ring may be unsubstituted or may contain halogen, CN, C 1~4 -Alkyl, Halo-C 1~4 -Alkyl, 3- to 6-membered cycloalkyl, halo-(3- to 6-membered cycloalkyl), 3- to 6-membered heterocycloalkyl, halo-(3- to 6-membered heterocycloalkyl), OH, oxo, CO2H, CO2-C 1~4 -Alkyl, CONHCH2CO2H, CONH(CH2)2SO3H, OC 1~4 -Alkyl and O-Halo-C 1~4 -substituted with 1 to 3 substituents independently selected from alkyl; [ka] is selected from the group consisting of 3- to 10-membered cycloalkyl, 3- to 10-membered heterocycloalkyl containing 1-3 heteroatoms independently selected from N, O, and S, 6- to 14-membered aryl, and 5- to 14-membered heteroaryl containing 1-4 heteroatoms independently selected from N, O, and S; wherein cycloalkyl, heterocycloalkyl, aryl and heteroaryl are unsubstituted or substituted with halogen, CN, SF, NO, oxo, C 1~4 -Alkyl, C 0~6 -Alkylene-OR 21 , C 0~6 -Alkylene-(3- to 6-membered cycloalkyl), C 0~6 -alkylene-(3- to 6-membered heterocycloalkyl), C 0~6 -Alkylene-S(O) n R 21 , C 0~6 -Alkylene-NR 21 S(O)2R 21 , C 0~6 -Alkylene-S(O)NR 21 R 22 , C 0~6 -Alkylene-NR 21 S(O)NR 21 R 22 , C 0~6 -Alkylene-CO2R 21 , O.C. 1~6 -Alkylene-CO2R 21 , C 0~6 -Alkylene-O-COR 21 , C 0~6 -Alkylene-CONR 21 R 22 , C 0~6 -Alkylene-NR 21 -COR 21 , C 0~6 -Alkylene-NR 21 -CONR 21 R 22 , C 0~6 -Alkylene-O-CONR 21 R 22 , C 0~6 -Alkylene-NR 21 -CO2R 21 and C 0~6 -Alkylene-NR 21 R 22 and is substituted with 1 to 6 substituents independently selected from the group consisting of: wherein alkyl, alkylene, cycloalkyl and heterocycloalkyl are unsubstituted or substituted with halogen, CN, oxo, hydroxy, COH, CO-C 1~4 -Alkyl, CONHCH2CO2H, CONH(CH2)2SO3H, C 1~4 -Alkyl, Halo-C 1~4 -Alkyl, OC 1~4 -Alkyl and O-Halo-C 1~4 -substituted with 1 to 6 substituents independently selected from alkyl; wherein two adjacent substituents on the aryl or heteroaryl moiety may form a 5-8 membered partially unsaturated ring which may contain 1-3 heteroatoms independently selected from O, S or N; This further ring may be unsubstituted or may be substituted with halogen, CN, oxo, OH, CO2H, CO2-C 1~4 -Alkyl, CONHCH2CO2H, CONH(CH2)2SO3H, C 1~4 -Alkyl, Halo-C 1~4 -Alkyl, OC 1~4 -Alkyl and O-Halo-C 1~4 -substituted with 1 to 4 substituents independently selected from alkyl; wherein two adjacent substituents on the cycloalkyl or heterocycloalkyl moiety may form a 5- to 6-membered unsaturated ring which may contain 1 to 3 heteroatoms independently selected from O, S, or N; This further ring may be unsubstituted or may be substituted with halogen, CN, oxo, OH, CO2H, CO2-C 1~4 -Alkyl, CONHCH2CO2H, CONH(CH2)2SO3H, C 1~4 -Alkyl, Halo-C 1~4 -Alkyl, OC 1~4 -Alkyl and O-Halo-C 1~4 -substituted with 1 to 4 substituents independently selected from alkyl; [ka] is selected from the group consisting of 6- or 10-membered aryl and 5- to 10-membered heteroaryl containing 1-3 heteroatoms independently selected from N, O, and S; wherein cycloalkyl, heterocycloalkyl, aryl and heteroaryl are unsubstituted or substituted with halogen, CN, SF, NO, oxo, C 1~4 -Alkyl, C 0~6 -Alkylene-OR 31 , C 0~6 -Alkylene-(3- to 6-membered cycloalkyl), C 0~6 -alkylene-(3- to 6-membered heterocycloalkyl), C 0~6 -alkylene-(6-membered aryl), C 0~6 -alkylene-(5-6 membered heteroaryl), C 0~6 -Alkylene-S(O) n R 31 , C 0~6 -Alkylene-NR 31 S(O)2R 31 , C 0~6 -Alkylene-S(O)NR 31 R 32 , C 0~6 -Alkylene-NR 31 S(O)NR 31 R 32 , C 0~6 -Alkylene-CO2R 31 , O.C. 1~6 -Alkylene-CO2R 31 , C 0~6 -Alkylene-O-COR 31 , C 0~6 -Alkylene-CONR 31 R 32 , C 0~6 -Alkylene-NR 31 -COR 31 , C 0~6 -Alkylene-NR 31 -CONR 31 R 32 , C 0~6 -Alkylene-O-CONR 31 R 32 , C 0~6 -Alkylene-NR 31 -CO2R 31 and C0~6 -Alkylene-NR 31 R 32 and is substituted with 1 to 4 substituents independently selected from the group consisting of: wherein alkyl, alkylene, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are unsubstituted or substituted with halogen, CN, oxo, hydroxy, COH, CO-C 1~4 -Alkyl, CONHCH2CO2H, CONH(CH2)2SO3H, C 1~4 -Alkyl, Halo-C 1~4 -Alkyl, OC 1~4 -Alkyl and O-Halo-C 1~4 -substituted with 1 to 6 substituents independently selected from alkyl; wherein two adjacent substituents on the aryl or heteroaryl moiety may form a 5-8 membered partially unsaturated ring which may contain 1-3 heteroatoms independently selected from O, S or N; This further ring may be unsubstituted or may be substituted with halogen, CN, oxo, OH, CO2H, CO2-C 1~4 -Alkyl, CONHCH2CO2H, CONH(CH2)2SO3H, C 1~4 -Alkyl, Halo-C 1~4 -Alkyl, OC 1~4 -Alkyl and O-Halo-C 1~4 -substituted with 1 to 4 substituents independently selected from alkyl; [ka] is selected from the group consisting of 3- to 10-membered cycloalkyl, 3- to 10-membered heterocycloalkyl containing 1-3 heteroatoms independently selected from N, O, and S, 6- to 14-membered aryl, and 5- to 14-membered heteroaryl containing 1-4 heteroatoms independently selected from N, O, and S; wherein cycloalkyl, heterocycloalkyl, aryl and heteroaryl are unsubstituted or substituted with halogen, CN, SF, NO, oxo, C 1~4 -Alkyl, C 0~6 -Alkylene-OR 21 , C0~6 -Alkylene-(3- to 6-membered cycloalkyl), C 0~6 -alkylene-(3- to 6-membered heterocycloalkyl), C 0~6 -Alkylene-S(O) n R 21 , C 0~6 -Alkylene-NR 21 S(O)2R 21 , C 0~6 -Alkylene-S(O)NR 21 R 22 , C 0~6 -Alkylene-NR 21 S(O)NR 21 R 22 , C 0~6 -Alkylene-CR 41 (=N-OR 41 ), C 0~6 -Alkylene-CO2R 21 , O.C. 1~6 -Alkylene-CO2R 21 , C 0~6 -Alkylene-O-COR 21 , C 0~6 -Alkylene-CONR 21 R 22 , C 0~6 -Alkylene-NR 21 -COR 21 , C 0~6 -Alkylene-NR 21 -CONR 21 R 22 , C 0~6 -Alkylene-O-CONR 21 R 22 , C 0~6 -Alkylene-NR 21 -CO2R 21 and C 0~6 -Alkylene-NR 21 R 22 and is substituted with 1 to 6 substituents independently selected from the group consisting of: wherein alkyl, alkylene, cycloalkyl and heterocycloalkyl are unsubstituted or substituted with halogen, CN, oxo, hydroxy, COH, CO-C 1~4 -Alkyl, CONHCH2CO2H, CONH(CH2)2SO3H, CO-OC 1~4-Alkyl, C 1~4 -Alkyl, Halo-C 1~4 -Alkyl, OC 1~4 -Alkyl and O-Halo-C 1~4 -substituted with 1 to 6 substituents independently selected from alkyl; wherein two adjacent substituents on the aryl or heteroaryl moiety may form a 5-8 membered partially unsaturated ring which may contain 1-3 heteroatoms independently selected from O, S or N; This further ring may be unsubstituted or may be substituted with halogen, CN, oxo, OH, CO2H, CO2-C 1~4 -Alkyl, CONHCH2CO2H, CONH(CH2)2SO3H, C 1~4 -Alkyl, Halo-C 1~4 -Alkyl, OC 1~4 -Alkyl and O-Halo-C 1~4 -substituted with 1 to 4 substituents independently selected from alkyl; wherein two adjacent substituents on the cycloalkyl or heterocycloalkyl moiety may form a 5- to 6-membered unsaturated ring which may contain 1 to 3 heteroatoms independently selected from O, S, or N; This further ring may be unsubstituted or may be substituted with halogen, CN, oxo, OH, CO2H, CO2-C 1~4 -Alkyl, CONHCH2CO2H, CONH(CH2)2SO3H, C 1~4 -Alkyl, Halo-C 1~4 -Alkyl, OC 1~4 -Alkyl and O-Halo-C 1~4 -substituted with 1 to 4 substituents independently selected from alkyl; During the ceremony, [ka] teeth, [ka] or a further ring fused in a 1,2-orientation, L is a bond, C1~6 -Alkylene, C 2~6 -Alkenylene, C 2~6 - selected from the group consisting of alkynylene, 3- to 10-membered cycloalkylene, 3- to 10-membered heterocycloalkylene containing 1-4 heteroatoms independently selected from N, O and S, 6- or 10-membered arylene, and 5- to 10-membered heteroarylene containing 1-4 heteroatoms independently selected from N, O and S; wherein alkylene, alkenylene, alkynylene, cycloalkylene, heterocycloalkylene, arylene and heteroarylene are unsubstituted or substituted with halogen, CN, SF, NO, oxo, C 1~4 -Alkyl, C 0~6 -Alkylene-OR 41 , C 0~6 -Alkylene-(3- to 6-membered cycloalkyl), C 0~6 -alkylene-(3- to 6-membered heterocycloalkyl), C 0~6 -Alkylene-S(O) n R 41 , C 0~6 -Alkylene-NR 41 S(O)2R 41 , C 0~6 -Alkylene-S(O)NR 41 R 42 , C 0~6 -Alkylene-NR 41 S(O)NR 41 R 42 , C 0~6 -Alkylene-CO2R 41 , O.C. 1~6 -Alkylene-CO2R 41 , C 0~6 -Alkylene-O-COR 41 , C 0~6 -Alkylene-CONR 41 R 42 , C 0~6 -Alkylene-NR 41 -COR 41 , C 0~6 -Alkylene-NR 41 -CONR 41 R 42 , C 0~6 -Alkylene-O-CONR41 R 42 , C 0~6 -Alkylene-NR 41 -CO2R 41 and C 0~6 -Alkylene-NR 41 R 42 and is substituted with 1 to 6 substituents independently selected from the group consisting of: wherein alkyl, alkylene, cycloalkyl and heterocycloalkyl are unsubstituted or substituted with halogen, CN, oxo, hydroxy, COH, CO-C 1~4 -Alkyl, CONHCH2CO2H, CONH(CH2)2SO3H, C 1~4 -Alkyl, Halo-C 1~4 -Alkyl, OC 1~4 -Alkyl and O-Halo-C 1~4 -substituted with 1 to 6 substituents independently selected from alkyl; wherein two adjacent substituents on the arylene moiety and the heteroarylene moiety may form a 5- to 8-membered partially unsaturated ring which may contain 1 to 3 heteroatoms independently selected from O, S, or N; This further ring may be unsubstituted or may be substituted with halogen, CN, oxo, OH, CO2H, CO2-C 1~4 -Alkyl, C 1~4 -Alkyl, Halo-C 1~4 -Alkyl, OC 1~4 -Alkyl and O-Halo-C 1~4 -substituted with 1 to 4 substituents independently selected from alkyl; R 1 H, halogen, CN, SF5, NO2, oxo, C 1~4 -Alkyl, C 0~6 -Alkylene-OR 41 , Y.C. 0~6 -Alkylene-(3-6 membered cycloalkyl), YC 0~6 -Alkylene-(3-6 membered heterocycloalkyl), YC 0~6 -alkylene-(6-membered aryl), YC 0~6 -alkylene-(5-6 membered heteroaryl), C 0~6 -Alkylene-S(=O)(-R41 )=NR 75 , XC 1~6 -Alkylene-S(=O)(-R 41 )=NR 75 , C 0~6 -Alkylene-S(O) n R 41 , XC 1~6 -Alkylene-S(O) n R 41 , C 0~6 -Alkylene-S(=NR 71 )R 41 , XC 1~6 -Alkylene-S(=NR 71 )R 41 , C 0~6 -Alkylene-S(O)(=NR 71 )R 41 , XC 1~6 -Alkylene-S(O)(=NR 71 )R 41 , C 0~6 -Alkylene-S(=NR 71 )2R 41 , XC 1~6 -Alkylene-S(=NR 71 )2R 41 , C 0~6 -Alkylene-NR 41 S(O)2R 41 , XC 1~6 -Alkylene-NR 41 S(O)2R 41 , C 0~6 -Alkylene-S(O)NR 41 R 42 , XC 1~6 -Alkylene-S(O)NR 41 R 42 , C 0~6 -Alkylene-NR 41 S(O)NR 41 R 42 , XC 1~6 -Alkylene-NR 41 S(O)NR 41 R 42 , C 0~6 -Alkylene-SO3R 41 , XC 1~6 -Alkylene-SO3R 41 , C0~6 -Alkylene-CO2R 41 , XC 1~6 -Alkylene-CO2R 41 , C 0~6 -Alkylene-O-COR 41 , XC 1~6 -Alkylene-O-COR 41 , C 0~6 -Alkylene-CONR 41 R 42 , XC 1~6 -Alkylene-CONR 41 R 42 , C 0~6 -Alkylene-CONR 41 OR 41 , XC 1~6 -Alkylene-CONR 41 OR 41 , C 0~6 -Alkylene-CONR 41 SO2R 41 , XC 1~6 -Alkylene-CONR 41 SO2R 41 , C 0~6 -Alkylene-NR 41 -COR 41 , XC 1~6 -C 0~6 -Alkylene-NR 41 -COR 41 , C 0~6 -Alkylene-NR 41 -CONR 41 R 42 , XC 1~6 -Alkylene-NR 41 -CONR 41 R 42 , C 0~6 -Alkylene-O-CONR 41 R 42 , XC 1~6 -Alkylene-O-CONR 41 R 42 , C 0~6 -Alkylene-NR 41 -CO2R 41 , XC 1~6 -Alkylene-NR 41 -CO2R 41 , C 0~6-Alkylene-NR 41 R 42 , XC 1~6 -Alkylene-NR 41 R 42 is selected from the group consisting of wherein alkyl, alkylene, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are unsubstituted or substituted with halogen, CN, oxo, hydroxy, COH, CO-C 1~4 -Alkyl, CONHCH2CO2H, CONH(CH2)2SO3H, C 1~4 -Alkyl, Halo-C 1~4 -Alkyl, OC 1~4 -Alkyl and O-Halo-C 1~4 -substituted with 1 to 6 substituents independently selected from alkyl; wherein two adjacent substituents on the aryl and heteroaryl moieties may form a 5-8 membered partially unsaturated ring which may contain 1-3 heteroatoms independently selected from O, S or N; This further ring may be unsubstituted or may be substituted with halogen, CN, oxo, OH, CO2H, CO2-C 1~4 -Alkyl, CONHCH2CO2H, CONH(CH2)2SO3H, C 1~4 -Alkyl, Halo-C 1~4 -Alkyl, OC 1~4 -Alkyl and O-Halo-C 1~4 -substituted with 1 to 4 substituents independently selected from alkyl; R 11 , R 12 , R 21 , R 22 , R 31 , R 32 , R 41 , R 42 , R 51 are independently H and C 1~4 -alkyl, wherein alkyl is unsubstituted or is substituted with halogen, CN, C 1~4 -Alkyl, Halo-C 1~4-Alkyl, 3- to 6-membered cycloalkyl, halo-(3- to 6-membered cycloalkyl), 3- to 6-membered heterocycloalkyl, halo-(3- to 6-membered heterocycloalkyl), OH, oxo, CO2H, CO2-C 1~4 -Alkyl, CONHCH2CO2H, CONH(CH2)2SO3H, SO3H, OC 1~4 -Alkyl and O-Halo-C 1~4 -substituted with 1 to 3 substituents independently selected from alkyl; or R 11 and R 12 , R 21 and R 22 , R 31 and R 32 , R 41 and R 42 each, when taken together with the nitrogen to which they are attached, completes a 3- to 6-membered ring containing carbon atoms and optionally containing 1 or 2 heteroatoms independently selected from O, S or N; The newly formed ring may be unsubstituted or may contain halogen, CN, C 1~4 -Alkyl, Halo-C 1~4 -Alkyl, 3- to 6-membered cycloalkyl, halo-(3- to 6-membered cycloalkyl), 3- to 6-membered heterocycloalkyl, halo-(3- to 6-membered heterocycloalkyl), OH, oxo, CO2H, CO2-C 1~4 -Alkyl, CONHCH2CO2H, CONH(CH2)2SO3H, SO3H, OC 1~4 -Alkyl and O-Halo-C 1~4 -substituted with 1 to 3 substituents independently selected from alkyl; R 71 are independently H, CN, NO2, C 1~4 -Alkyl, and C(O)-OC 1~4 -alkyl, wherein alkyl is unsubstituted or is substituted with halogen, CN, C 1~4 -Alkyl, Halo-C 1~4 -Alkyl, 3- to 6-membered cycloalkyl, halo-(3- to 6-membered cycloalkyl), 3- to 6-membered heterocycloalkyl, halo-(3- to 6-membered heterocycloalkyl), OH, oxo, CO2H, CO2-C1~4 -Alkyl, CONHCH2CO2H, CONH(CH2)2SO3H, SO3H, OC 1~4 -Alkyl and O-Halo-C 1~4 -substituted with 1 to 3 substituents independently selected from alkyl; R 75 are independently, C 1~4 selected from alkyl, 3- to 6-membered cycloalkyl, 3- to 6-membered heterocycloalkyl, 6-membered aryl, and 5- to 6-membered heteroaryl; wherein alkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl are unsubstituted or substituted with 1 to 3 substituents independently selected from halogen, CN, Me, Et, CHF, CF, OH, oxo, COH, CONHCHCOH, CONH(CH)SOH, SOH, OMe, OEt, OCHF, and OCF; X is independently O, NR 51 , S(O) n , S(=NR 71 ), S(O)(=NR 71 ) and S(=NR 71 )2 is selected, Y is independently a bond, O, or NR 51 , S(O) n , S(=NR 71 ), S(O)(=NR 71 ) and S(=NR 71 )2 is selected, n is independently selected from 0 to 2; however, [ka] The structure of the compound is excluded.

[0175] Embodiment II-5. A medicament for treating a metabolic disorder associated with dyslipidemia or impaired lipid homeostasis, the medicament comprising a compound represented by formula (I): [ka] glycine conjugates, taurine conjugates, enantiomers, diastereomers, tautomers, N-oxides, solvates, prodrugs, and pharmaceutically acceptable salts thereof, During the ceremony, [ka] is a fused 5- to 6-membered ring forming a 6-membered aryl or a 5- to 6-membered heteroaryl containing 1 to 3 heteroatoms independently selected from N, O, and S, the ring being unsubstituted or substituted with halogen, CN, SF, NO, C 1~6 -Alkyl, oxo, C 0~6 -Alkylene-OR 11 , C 0~6 -Alkylene-(3- to 6-membered cycloalkyl), C 0~6 -alkylene-(3- to 6-membered heterocycloalkyl), C 0~6 -Alkylene-S(O) n R 11 , C 0~6 -Alkylene-NR 11 S(O)2R 11 , C 0~6 -Alkylene-S(O)NR 11 R 12 , C 0~6 -Alkylene-NR 11 S(O)NR 11 R 12 , C 0~6 -Alkylene-CO2R 11 , O.C. 1~6 -Alkylene-CO2R 11 , C 0~6 -Alkylene-O-COR 11 , C 0~6 -Alkylene-CONR 11 R 12 , C 0~6 -Alkylene-NR 11 -COR 11 , C 0~6 -Alkylene-NR 11 -CONR 11 R 12 , C 0~6 -Alkylene-O-CONR 11 R 12 , C0~6 -Alkylene-NR 11 -CO2R 11 and C 0~6 -Alkylene-NR 11 R 12 and is substituted with 1 to 4 substituents independently selected from the group consisting of: wherein alkyl, alkylene, cycloalkyl, and heterocycloalkyl are unsubstituted or substituted with halogen, CN, oxo, hydroxy, COH, CO-C 1~4 -Alkyl, CONHCH2CO2H, CONH(CH2)2SO3H, C 1~4 -Alkyl, Halo-C 1~4 -Alkyl, OC 1~4 -Alkyl and O-Halo-C 1~4 -substituted with 1 to 6 substituents independently selected from alkyl; wherein two adjacent substituents on the aryl or heteroaryl moiety may form a 5-8 membered partially unsaturated ring which may contain 1-3 heteroatoms independently selected from O, S or N; The newly formed ring may be unsubstituted or may contain halogen, CN, C 1~4 -Alkyl, Halo-C 1~4 -Alkyl, 3- to 6-membered cycloalkyl, halo-(3- to 6-membered cycloalkyl), 3- to 6-membered heterocycloalkyl, halo-(3- to 6-membered heterocycloalkyl), OH, oxo, CO2H, CO2-C 1~4 -Alkyl, CONHCH2CO2H, CONH(CH2)2SO3H, OC 1~4 -Alkyl and O-Halo-C 1~4 -substituted with 1 to 3 substituents independently selected from alkyl; [ka] is selected from the group consisting of 3- to 10-membered cycloalkyl, 3- to 10-membered heterocycloalkyl containing 1-3 heteroatoms independently selected from N, O, and S, 6- to 14-membered aryl, and 5- to 14-membered heteroaryl containing 1-4 heteroatoms independently selected from N, O, and S; wherein cycloalkyl, heterocycloalkyl, aryl and heteroaryl are unsubstituted or substituted with halogen, CN, SF, NO, oxo, C 1~4 -Alkyl, C 0~6 -Alkylene-OR 21 , C 0~6 -Alkylene-(3- to 6-membered cycloalkyl), C 0~6 -alkylene-(3- to 6-membered heterocycloalkyl), C 0~6 -Alkylene-S(O) n R 21 , C 0~6 -Alkylene-NR 21 S(O)2R 21 , C 0~6 -Alkylene-S(O)NR 21 R 22 , C 0~6 -Alkylene-NR 21 S(O)NR 21 R 22 , C 0~6 -Alkylene-CO2R 21 , O.C. 1~6 -Alkylene-CO2R 21 , C 0~6 -Alkylene-O-COR 21 , C 0~6 -Alkylene-CONR 21 R 22 , C 0~6 -Alkylene-NR 21 -COR 21 , C 0~6 -Alkylene-NR 21 -CONR 21 R 22 , C 0~6 -Alkylene-O-CONR 21 R 22 , C 0~6 -Alkylene-NR 21 -CO2R 21 and C 0~6 -Alkylene-NR 21 R 22 and is substituted with 1 to 6 substituents independently selected from the group consisting of: wherein alkyl, alkylene, cycloalkyl and heterocycloalkyl are unsubstituted or substituted with halogen, CN, oxo, hydroxy, COH, CO-C 1~4 -Alkyl, CONHCH2CO2H, CONH(CH2)2SO3H, C 1~4 -Alkyl, Halo-C 1~4 -Alkyl, OC 1~4 -Alkyl and O-Halo-C 1~4 -substituted with 1 to 6 substituents independently selected from alkyl; wherein two adjacent substituents on the aryl or heteroaryl moiety may form a 5-8 membered partially unsaturated ring which may contain 1-3 heteroatoms independently selected from O, S or N; This further ring may be unsubstituted or may be substituted with halogen, CN, oxo, OH, CO2H, CO2-C 1~4 -Alkyl, CONHCH2CO2H, CONH(CH2)2SO3H, C 1~4 -Alkyl, Halo-C 1~4 -Alkyl, OC 1~4 -Alkyl and O-Halo-C 1~4 -substituted with 1 to 4 substituents independently selected from alkyl; wherein two adjacent substituents on the cycloalkyl or heterocycloalkyl moiety may form a 5- to 6-membered unsaturated ring which may contain 1 to 3 heteroatoms independently selected from O, S, or N; This further ring may be unsubstituted or may be substituted with halogen, CN, oxo, OH, CO2H, CO2-C 1~4 -Alkyl, CONHCH2CO2H, CONH(CH2)2SO3H, C 1~4 -Alkyl, Halo-C 1~4 -Alkyl, OC 1~4 -Alkyl and O-Halo-C 1~4 -substituted with 1 to 4 substituents independently selected from alkyl; [ka] is selected from the group consisting of 6- or 10-membered aryl and 5- to 10-membered heteroaryl containing 1-3 heteroatoms independently selected from N, O, and S; wherein cycloalkyl, heterocycloalkyl, aryl and heteroaryl are unsubstituted or substituted with halogen, CN, SF, NO, oxo, C 1~4 -Alkyl, C 0~6 -Alkylene-OR 31 , C 0~6 -Alkylene-(3- to 6-membered cycloalkyl), C 0~6 -alkylene-(3- to 6-membered heterocycloalkyl), C 0~6 -alkylene-(6-membered aryl), C 0~6 -alkylene-(5-6 membered heteroaryl), C 0~6 -Alkylene-S(O) n R 31 , C 0~6 -Alkylene-NR 31 S(O)2R 31 , C 0~6 -Alkylene-S(O)NR 31 R 32 , C 0~6 -Alkylene-NR 31 S(O)NR 31 R 32 , C 0~6 -Alkylene-CO2R 31 , O.C. 1~6 -Alkylene-CO2R 31 , C 0~6 -Alkylene-O-COR 31 , C 0~6 -Alkylene-CONR 31 R 32 , C 0~6 -Alkylene-NR 31 -COR 31 , C 0~6 -Alkylene-NR 31 -CONR 31 R 32 , C 0~6 -Alkylene-O-CONR 31 R 32 , C 0~6 -Alkylene-NR 31 -CO2R 31 and C0~6 -Alkylene-NR 31 R 32 and is substituted with 1 to 4 substituents independently selected from the group consisting of: wherein alkyl, alkylene, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are unsubstituted or substituted with halogen, CN, oxo, hydroxy, COH, CO-C 1~4 -Alkyl, CONHCH2CO2H, CONH(CH2)2SO3H, C 1~4 -Alkyl, Halo-C 1~4 -Alkyl, OC 1~4 -Alkyl and O-Halo-C 1~4 -substituted with 1 to 6 substituents independently selected from alkyl; wherein two adjacent substituents on the aryl or heteroaryl moiety may form a 5-8 membered partially unsaturated ring which may contain 1-3 heteroatoms independently selected from O, S or N; This further ring may be unsubstituted or may be substituted with halogen, CN, oxo, OH, CO2H, CO2-C 1~4 -Alkyl, CONHCH2CO2H, CONH(CH2)2SO3H, C 1~4 -Alkyl, Halo-C 1~4 -Alkyl, OC 1~4 -Alkyl and O-Halo-C 1~4 -substituted with 1 to 4 substituents independently selected from alkyl; [ka] is selected from the group consisting of 3- to 10-membered cycloalkyl, 3- to 10-membered heterocycloalkyl containing 1-3 heteroatoms independently selected from N, O, and S, 6- to 14-membered aryl, and 5- to 14-membered heteroaryl containing 1-4 heteroatoms independently selected from N, O, and S; wherein cycloalkyl, heterocycloalkyl, aryl and heteroaryl are unsubstituted or substituted with halogen, CN, SF, NO, oxo, C 1~4 -Alkyl, C 0~6 -Alkylene-OR 21 , C0~6 -Alkylene-(3- to 6-membered cycloalkyl), C 0~6 -alkylene-(3- to 6-membered heterocycloalkyl), C 0~6 -Alkylene-S(O) n R 21 , C 0~6 -Alkylene-NR 21 S(O)2R 21 , C 0~6 -Alkylene-S(O)NR 21 R 22 , C 0~6 -Alkylene-NR 21 S(O)NR 21 R 22 , C 0~6 -Alkylene-CR 41 (=N-OR 41 ), C 0~6 -Alkylene-CO2R 21 , O.C. 1~6 -Alkylene-CO2R 21 , C 0~6 -Alkylene-O-COR 21 , C 0~6 -Alkylene-CONR 21 R 22 , C 0~6 -Alkylene-NR 21 -COR 21 , C 0~6 -Alkylene-NR 21 -CONR 21 R 22 , C 0~6 -Alkylene-O-CONR 21 R 22 , C 0~6 -Alkylene-NR 21 -CO2R 21 and C 0~6 -Alkylene-NR 21 R 22 and is substituted with 1 to 6 substituents independently selected from the group consisting of: wherein alkyl, alkylene, cycloalkyl and heterocycloalkyl are unsubstituted or substituted with halogen, CN, oxo, hydroxy, COH, CO-C 1~4 -Alkyl, CONHCH2CO2H, CONH(CH2)2SO3H, CO-OC 1~4-Alkyl, C 1~4 -Alkyl, Halo-C 1~4 -Alkyl, OC 1~4 -Alkyl and O-Halo-C 1~4 -substituted with 1 to 6 substituents independently selected from alkyl; wherein two adjacent substituents on the aryl or heteroaryl moiety may form a 5-8 membered partially unsaturated ring which may contain 1-3 heteroatoms independently selected from O, S or N; This further ring may be unsubstituted or may be substituted with halogen, CN, oxo, OH, CO2H, CO2-C 1~4 -Alkyl, CONHCH2CO2H, CONH(CH2)2SO3H, C 1~4 -Alkyl, Halo-C 1~4 -Alkyl, OC 1~4 -Alkyl and O-Halo-C 1~4 -substituted with 1 to 4 substituents independently selected from alkyl; wherein two adjacent substituents on the cycloalkyl or heterocycloalkyl moiety may form a 5- to 6-membered unsaturated ring which may contain 1 to 3 heteroatoms independently selected from O, S, or N; This further ring may be unsubstituted or may be substituted with halogen, CN, oxo, OH, CO2H, CO2-C 1~4 -Alkyl, CONHCH2CO2H, CONH(CH2)2SO3H, C 1~4 -Alkyl, Halo-C 1~4 -Alkyl, OC 1~4 -Alkyl and O-Halo-C 1~4 -substituted with 1 to 4 substituents independently selected from alkyl; During the ceremony, [ka] teeth, [ka] or a further ring fused in a 1,2-orientation, L is a bond, C1~6 -Alkylene, C 2~6 -Alkenylene, C 2~6 - selected from the group consisting of alkynylene, 3- to 10-membered cycloalkylene, 3- to 10-membered heterocycloalkylene containing 1-4 heteroatoms independently selected from N, O and S, 6- or 10-membered arylene, and 5- to 10-membered heteroarylene containing 1-4 heteroatoms independently selected from N, O and S; wherein alkylene, alkenylene, alkynylene, cycloalkylene, heterocycloalkylene, arylene and heteroarylene are unsubstituted or substituted with halogen, CN, SF, NO, oxo, C 1~4 -Alkyl, C 0~6 -Alkylene-OR 41 , C 0~6 -Alkylene-(3- to 6-membered cycloalkyl), C 0~6 -alkylene-(3- to 6-membered heterocycloalkyl), C 0~6 -Alkylene-S(O) n R 41 , C 0~6 -Alkylene-NR 41 S(O)2R 41 , C 0~6 -Alkylene-S(O)NR 41 R 42 , C 0~6 -Alkylene-NR 41 S(O)NR 41 R 42 , C 0~6 -Alkylene-CO2R 41 , O.C. 1~6 -Alkylene-CO2R 41 , C 0~6 -Alkylene-O-COR 41 , C 0~6 -Alkylene-CONR 41 R 42 , C 0~6 -Alkylene-NR 41 -COR 41 , C 0~6 -Alkylene-NR 41 -CONR 41 R 42 , C 0~6 -Alkylene-O-CONR41 R 42 , C 0~6 -Alkylene-NR 41 -CO2R 41 and C 0~6 -Alkylene-NR 41 R 42 and is substituted with 1 to 6 substituents independently selected from the group consisting of: wherein alkyl, alkylene, cycloalkyl and heterocycloalkyl are unsubstituted or substituted with halogen, CN, oxo, hydroxy, COH, CO-C 1~4 -Alkyl, CONHCH2CO2H, CONH(CH2)2SO3H, C 1~4 -Alkyl, Halo-C 1~4 -Alkyl, OC 1~4 -Alkyl and O-Halo-C 1~4 -substituted with 1 to 6 substituents independently selected from alkyl; wherein two adjacent substituents on the arylene moiety and the heteroarylene moiety may form a 5- to 8-membered partially unsaturated ring which may contain 1 to 3 heteroatoms independently selected from O, S, or N; This further ring may be unsubstituted or may be substituted with halogen, CN, oxo, OH, CO2H, CO2-C 1~4 -Alkyl, C 1~4 -Alkyl, Halo-C 1~4 -Alkyl, OC 1~4 -Alkyl and O-Halo-C 1~4 -substituted with 1 to 4 substituents independently selected from alkyl; R 1 H, halogen, CN, SF5, NO2, oxo, C 1~4 -Alkyl, C 0~6 -Alkylene-OR 41 , Y.C. 0~6 -Alkylene-(3-6 membered cycloalkyl), YC 0~6 -Alkylene-(3-6 membered heterocycloalkyl), YC 0~6 -alkylene-(6-membered aryl), YC 0~6 -alkylene-(5-6 membered heteroaryl), C 0~6 -Alkylene-S(=O)(-R41 )=NR 75 , XC 1~6 -Alkylene-S(=O)(-R 41 )=NR 75 , C 0~6 -Alkylene-S(O) n R 41 , XC 1~6 -Alkylene-S(O) n R 41 , C 0~6 -Alkylene-S(=NR 71 )R 41 , XC 1~6 -Alkylene-S(=NR 71 )R 41 , C 0~6 -Alkylene-S(O)(=NR 71 )R 41 , XC 1~6 -Alkylene-S(O)(=NR 71 )R 41 , C 0~6 -Alkylene-S(=NR 71 )2R 41 , XC 1~6 -Alkylene-S(=NR 71 )2R 41 , C 0~6 -Alkylene-NR 41 S(O)2R 41 , XC 1~6 -Alkylene-NR 41 S(O)2R 41 , C 0~6 -Alkylene-S(O)NR 41 R 42 , XC 1~6 -Alkylene-S(O)NR 41 R 42 , C 0~6 -Alkylene-NR 41 S(O)NR 41 R 42 , XC 1~6 -Alkylene-NR 41 S(O)NR 41 R 42 , C 0~6 -Alkylene-SO3R 41 , XC 1~6 -Alkylene-SO3R 41 , C0~6 -Alkylene-CO2R 41 , XC 1~6 -Alkylene-CO2R 41 , C 0~6 -Alkylene-O-COR 41 , XC 1~6 -Alkylene-O-COR 41 , C 0~6 -Alkylene-CONR 41 R 42 , XC 1~6 -Alkylene-CONR 41 R 42 , C 0~6 -Alkylene-CONR 41 OR 41 , XC 1~6 -Alkylene-CONR 41 OR 41 , C 0~6 -Alkylene-CONR 41 SO2R 41 , XC 1~6 -Alkylene-CONR 41 SO2R 41 , C 0~6 -Alkylene-NR 41 -COR 41 , XC 1~6 -C 0~6 -Alkylene-NR 41 -COR 41 , C 0~6 -Alkylene-NR 41 -CONR 41 R 42 , XC 1~6 -Alkylene-NR 41 -CONR 41 R 42 , C 0~6 -Alkylene-O-CONR 41 R 42 , XC 1~6 -Alkylene-O-CONR 41 R 42 , C 0~6 -Alkylene-NR 41 -CO2R 41 , XC 1~6 -Alkylene-NR 41 -CO2R 41 , C 0~6-Alkylene-NR 41 R 42 , XC 1~6 -Alkylene-NR 41 R 42 is selected from the group consisting of wherein alkyl, alkylene, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are unsubstituted or substituted with halogen, CN, oxo, hydroxy, COH, CO-C 1~4 -Alkyl, CONHCH2CO2H, CONH(CH2)2SO3H, C 1~4 -Alkyl, Halo-C 1~4 -Alkyl, OC 1~4 -Alkyl and O-Halo-C 1~4 -substituted with 1 to 6 substituents independently selected from alkyl; wherein two adjacent substituents on the aryl and heteroaryl moieties may form a 5-8 membered partially unsaturated ring which may contain 1-3 heteroatoms independently selected from O, S or N; This further ring may be unsubstituted or may be substituted with halogen, CN, oxo, OH, CO2H, CO2-C 1~4 -Alkyl, CONHCH2CO2H, CONH(CH2)2SO3H, C 1~4 -Alkyl, Halo-C 1~4 -Alkyl, OC 1~4 -Alkyl and O-Halo-C 1~4 -substituted with 1 to 4 substituents independently selected from alkyl; R 11 , R 12 , R 21 , R 22 , R 31 , R 32 , R 41 , R 42 , R 51 are independently H and C 1~4 -alkyl, wherein alkyl is unsubstituted or is substituted with halogen, CN, C 1~4 -Alkyl, Halo-C 1~4-Alkyl, 3- to 6-membered cycloalkyl, halo-(3- to 6-membered cycloalkyl), 3- to 6-membered heterocycloalkyl, halo-(3- to 6-membered heterocycloalkyl), OH, oxo, CO2H, CO2-C 1~4 -Alkyl, CONHCH2CO2H, CONH(CH2)2SO3H, SO3H, OC 1~4 -Alkyl and O-Halo-C 1~4 -substituted with 1 to 3 substituents independently selected from alkyl; or R 11 and R 12 , R 21 and R 22 , R 31 and R 32 , R 41 and R 42 each, when taken together with the nitrogen to which they are attached, completes a 3- to 6-membered ring containing carbon atoms and optionally containing 1 or 2 heteroatoms independently selected from O, S or N; The newly formed ring may be unsubstituted or may contain halogen, CN, C 1~4 -Alkyl, Halo-C 1~4 -Alkyl, 3- to 6-membered cycloalkyl, halo-(3- to 6-membered cycloalkyl), 3- to 6-membered heterocycloalkyl, halo-(3- to 6-membered heterocycloalkyl), OH, oxo, CO2H, CO2-C 1~4 -Alkyl, CONHCH2CO2H, CONH(CH2)2SO3H, SO3H, OC 1~4 -Alkyl and O-Halo-C 1~4 -substituted with 1 to 3 substituents independently selected from alkyl; R 71 are independently H, CN, NO2, C 1~4 -Alkyl, and C(O)-OC 1~4 -alkyl, wherein alkyl is unsubstituted or is substituted with halogen, CN, C 1~4 -Alkyl, Halo-C 1~4 -Alkyl, 3- to 6-membered cycloalkyl, halo-(3- to 6-membered cycloalkyl), 3- to 6-membered heterocycloalkyl, halo-(3- to 6-membered heterocycloalkyl), OH, oxo, CO2H, CO2-C1~4 -Alkyl, CONHCH2CO2H, CONH(CH2)2SO3H, SO3H, OC 1~4 -Alkyl and O-Halo-C 1~4 -substituted with 1 to 3 substituents independently selected from alkyl; R 75 are independently, C 1~4 selected from alkyl, 3- to 6-membered cycloalkyl, 3- to 6-membered heterocycloalkyl, 6-membered aryl, and 5- to 6-membered heteroaryl; wherein alkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl are unsubstituted or substituted with 1 to 3 substituents independently selected from halogen, CN, Me, Et, CHF, CF, OH, oxo, COH, CONHCHCOH, CONH(CH)SOH, SOH, OMe, OEt, OCHF, and OCF; X is independently O, NR 51 , S(O) n , S(=NR 71 ), S(O)(=NR 71 ) and S(=NR 71 )2 is selected, Y is independently a bond, O, or NR 51 , S(O) n , S(=NR 71 ), S(O)(=NR 71 ) and S(=NR 71 )2 is selected, n is independently selected from 0 to 2; however, [ka] The structure of is excluded, pharmaceuticals.

[0176] Embodiment II-6. [ka] teeth, [ka] is selected from During the ceremony, [ka] is unsubstituted or is F, Cl, Br, CN, OH, oxo, C 1~4 -Alkyl, Halo-C 1~4 -Alkyl, OC 1~4 -Alkyl, O-Halo-C 1~4 -Alkyl, NH2, NHC 1~4 -Alkyl, N(C 1~4 -Alkyl)2, SO2-C 1~4 -Alkyl, and SO2-Halo-C 1~4 The method, use, compound, or medicament of any one of embodiments II-1 to II-5, wherein the compound is substituted with 1 to 3 substituents independently selected from the group consisting of -alkyl.

[0177] Embodiment II-7. [ka] is phenyl, naphthyl, pyridyl, pyrimidinyl, thiophenyl, thiazolyl, cyclopentyl, cyclohexyl, bicyclo[1.1.1]pentyl, bicyclo[2.2.2]octyl, bicyclo[2.2.1]heptyl, pentacyclo[4.2.0.0 2,5 .0 3,8 .0 4,7 octyl, and piperidinyl; wherein the ring is unsubstituted or substituted with F, Cl, Br, CN, OH, oxo, C 1~4 -Alkyl, Halo-C 1~4 -Alkyl, OC 1~4 -Alkyl, O-Halo-C 1~4 -Alkyl, C 1~4 -Alkyl-OH, and halo-C 1~4 The method, use, compound, or medicament according to any one of embodiments II-1 to II-6, wherein the phenyl ring is substituted with 1 to 3 substituents independently selected from the group consisting of -alkyl-OH, and two adjacent substituents on the phenyl ring may be taken together to form a -(CH2)3-, -(CH2)4-, -OCF2O-, and -OCHO- group.

[0178] Embodiment II-8. [ka] is selected from phenyl, pyridyl and thiophenyl, wherein phenyl, pyridyl and thiophenyl are unsubstituted or selected from F, Cl, CN, OH, oxo, C 1~4 -Alkyl, Halo-C 1~4 -Alkyl, OC 1~4 -Alkyl and O-Halo-C 1~4 -alkyl; and the residue -LR 1 teeth, [ka] and L is not a bond.

[0179] Embodiment II-9. -LR 1 teeth, [ka] is selected from wherein the ring is unsubstituted or is selected from the group consisting of F, Cl, Br, CN, OH, oxo, C 1~4 -Alkyl, Halo-C 1~4 -Alkyl, OC 1~4 -Alkyl, O-Halo-C 1~4 -Alkyl, C 1~4 -Alkyl-OH, Halo-C 1~4 -Alkyl-OH, SO2-C 1~4 -Alkyl and SO2-Halo-C 1~4-alkyl, and two adjacent substituents on the phenyl ring may be taken together to form a -(CH2)3-, -(CH2)4-, -OCF2O-, and -OCHO group;

[0180] Embodiment II-10. R 1 The method, use, compound, or medicament according to any one of embodiments II-1 to II-9, wherein is selected from CO2H, tetrazole, CH2CO2H, OCH2CO2H, SO2CH2CO2H, CHMeCO2H, CMe2CO2H, C(OH)MeCO2H, CONHSO2Me, and CONH(OH), and optionally their glycine and taurine conjugates.

[0181] Embodiment II-11. [ka] teeth, [ka] is selected from the group consisting of R 2 are Me, F, Cl, CN, Me, CHO, CHF2, CF3, SO2Me, [ka] is selected from During the ceremony, [ka] The method, use, compound, or medicament of any one of embodiments II-1 to II-10, wherein

[0182] Embodiment II-12. [ka] teeth, [ka] The method, use, compound, or medicament according to any one of embodiments II-1 to II-11, selected from the group consisting of:

[0183] Embodiment II-13. The method, use, compound, or medicament according to any one of embodiments II-1 to II-12, wherein formula (I) contains a substituent selected from the group consisting of CO2H, tetrazole, CONHSO2Me, and CONH(OH), and optionally glycine and taurine conjugates thereof.

[0184] Embodiment II-14. LR 1 teeth, [ka] wherein the ring is unsubstituted or substituted with F, Cl, Br, CN, OH, oxo, C 1~4 -Alkyl, Halo-C 1~4 -Alkyl, OC 1~4 -Alkyl, O-Halo-C 1~4 -Alkyl, C 1~4 -Alkyl-OH, Halo-C 1~4 -Alkyl-OH, SO2-C 1~4 -Alkyl and SO2-Halo-C 1~4 The method, use, compound, or medicament according to any one of embodiments II-1 to II-13, wherein the phenyl ring is further substituted with 1 to 4 substituents independently selected from the group consisting of -alkyl, -(CH2)3-, -(CH2)4-, -OCF2O-, and -OCHO- groups, wherein two adjacent substituents on the phenyl ring may be taken together to form -(CH2)3-, -(CH2)4-, -OCF2O-, and -OCHO- groups.

[0185] Embodiment II-15. R 1 is C 0~6 -Alkylene-CO2R 41 Or C0~6 -Alkylene-CONR 41 R 42 The method, use, compound or medicament according to any one of embodiments II-1 to II-104, wherein the compound is hydroxybenzoate, ...

[0186] Embodiment II-16. R 1 The method, use, compound, or medicament according to any one of embodiments II-1 to II-15, wherein is COOH, or a glycine or taurine conjugate thereof.

[0187] Embodiment II-17. R 1 is C 0~6 -Alkylene-CONR 41 R 42 16. The method, use, compound or medicament according to any one of embodiments II-1 to 15, wherein

[0188] Embodiment II-18. R 41 and R 42 are independently H and C 1~4 alkyl, C 1~4 The method, use, compound, or medicament according to any one of embodiments II-17, wherein the alkyl is unsubstituted or substituted with CO2H.

[0189] Embodiment II-19. -CLR 1 teeth, [ka] or a glycine or taurine conjugate thereof.

[0190] Embodiment II-20. The method, use, compound, or medicament according to any one of embodiments II-1 to I-19, wherein the compound is a glycine conjugate.

[0191] Embodiment II-21. The compound is [ka] or a pharmaceutically acceptable salt thereof.

[0192] Embodiment II-22. The method, use, compound, or medicament according to any one of embodiments II-1 to II-21, wherein the compound is: [ka]

[0193] Embodiment II-23. The compound is [ka] or a glycine conjugate thereof.

[0194] Embodiment II-24. The compound is [ka] or a pharmaceutically acceptable salt thereof.

[0195] Embodiment II-25. The method, use, compound, or medicament of any one of embodiments II-1 to II-24, wherein the compound is: [ka]

[0196] Embodiment II-26. The method, use, compound, or medicament according to any one of embodiments II-1 to II-25, wherein the method is for treating dyslipidemia.

[0197] Embodiment II-27. The method, use, compound, or medicament of any one of embodiments II-1 to II-256, wherein the dyslipidemia is hypertriglyceridemia (HTG), severe hypertriglyceridemia (SHTG), familial hypercholesterolemia, heterozygous familial hypercholesterolemia, homozygous familial hypercholesterolemia, familial chylomicronemia syndrome, mixed disorder chylomicronemia, hypercholesterolemia, familial combined hyperlipidemia, familial dysbetalipoproteinemia, or mixed dyslipidemia.

[0198] Embodiment II-28. The method, use, compound or medicament according to any one of embodiments II-1 to II-27, wherein the dyslipidemia is severe hypertriglyceridemia (SHTG).

[0199] Embodiment II-29. The method, use, compound or medicament according to any one of embodiments II-1 to II-28, wherein the dyslipidemia is characterized by abnormal levels of one or more lipids and / or apolipoproteins.

[0200] Embodiment II-30. The method, use, compound or medicament of any one of embodiments II-1 to II-29, wherein the dyslipidemia is characterized by elevated levels of total cholesterol, LDL cholesterol, triglycerides (TG), or any combination of the foregoing.

[0201] Embodiment II-31. The method, use, compound or medicament according to any one of embodiments II-1 to II-30, wherein the dyslipidemia is characterized by reduced levels of HDL cholesterol.

[0202] Embodiment II-32. The method, use, compound, or medicament according to any one of embodiments II-1 to II-31, wherein the method reduces the risk of pancreatitis in the subject.

[0203] Embodiment II-33. The method, use, compound or medicament according to any one of embodiments II-1 to II-25, wherein the method is for treating a metabolic disorder associated with impaired lipid homeostasis.

[0204] Embodiment II-34. The method, use, compound or medicament according to any one of embodiments II-1 to II-25 and II-33, wherein the method comprises treating a metabolic disorder associated with impaired de novo lipogenesis.

[0205] Embodiment II-35. The method, use, compound, or medicament of any one of embodiments II-1 to II-25 and II-33 to II-34, wherein the method comprises treating non-alcoholic fatty liver disease (NAFLD) or non-alcoholic steatohepatitis (NASH) in a subject in need thereof, wherein the subject has a glucokinase regulatory protein (GCKR) phenotype.

[0206] Embodiment II-36. The method, use, compound or medicament of embodiment II-34, wherein de novo lipogenesis is enhanced in the subject.

[0207] Embodiment II-37. The method, use, compound or medicament of embodiment II-34 or embodiment II-35, wherein expression of lipogenic genes in the subject and / or lipid accumulation in the subject is reduced.

[0208] Embodiment II-38. The method, use, compound, or medicament of any one of embodiments II-1 to II-37, wherein the subject is administered 0.1 to 25 mg / day of the compound of formula (I), or its glycine conjugates, taurine conjugates, enantiomers, diastereomers, tautomers, N-oxides, solvates, prodrugs, and pharmaceutically acceptable salts.

[0209] Embodiment II-39. The method, use, compound, or medicament of embodiment II-38, wherein 5 to 15 mg of the compound is administered.

[0210] Experimental Section As described in WO 2020 / 002611, the compounds of the present disclosure can be prepared by a combination of methods known in the art, including the procedures described in Schemes I-V below.

[0211] The synthetic route shown in Scheme I begins with the preparation of alkyne Ic via Sonogashira coupling. The free amino group of Ic is then reacted with sulfonyl chloride Id in the presence of a suitable base and a suitable solvent to give alkyne sulfonamide Ie. Ie undergoes cyclization and concomitant reaction with aromatic halide If in the presence of a suitable catalyst (e.g., Pd catalyst), a suitable solvent, and temperature to give compound (I) of the present disclosure. The reaction of R with standard methods known to those skilled in the art (e.g., ester hydrolysis, amide bond formation) can be carried out. 1 Further manipulation of the functional groups present in Ic can lead to additional compounds of the present disclosure. Alternatively, alkyne amine Ic can be converted to alkyne trifluoroacetamide Ig, which can also undergo the aforementioned cyclization and concomitant reaction with aromatic halide If to give intermediate Ih, which has an unsubstituted NH. Reaction with sulfonyl chloride Id in the presence of a suitable base and a suitable solvent also gives compounds of formula (I). [ka] Scheme I: Synthesis of compounds of the present disclosure.

[0212] A variation of the pathway shown in Scheme I is shown in Scheme II. Reaction of alkynesulfonamide Ie in the presence of NIS affords iodide intermediate II-b, which can be a substrate for Suzuki coupling to give compound (I). Alternatively, cyclization of alkynesulfonamide Ie in the presence of a suitable catalyst (e.g., a Pd catalyst), a suitable solvent, and temperature, but in the absence of halide If, ​​affords intermediate II-d, which is unsubstituted at the 3-position. Reaction with NBS affords brominated intermediate II-e, which is also a substrate for Suzuki coupling to give compounds of formula (I). [ka] Scheme II: Synthetic route to compounds of the present disclosure by introduction of moiety D via Suzuki coupling.

[0213] A further variation of the synthetic route shown in Schemes I and II is shown in Scheme III. In the presence of B2Pin2, a suitable catalyst (e.g., a Pd catalyst), a suitable solvent, additives, and temperature, intermediate Ie can undergo cyclization and the concomitant formation of 3-pinacolylboronic ester III-b, which can be a substrate for a Suzuki coupling reaction to give compounds of the present disclosure having formula (I). [ka] Scheme III: An alternative synthetic route to compounds of the present disclosure by introduction of D via Suzuki coupling.

[0214] In Scheme IV, the right-hand moiety -LR is added to the compounds of the present disclosure. 1This figure shows a synthetic route for the subsequent introduction of Ia. Sonogashira coupling of Ia with bromine-iodinated aromatic IV-a gives bromine-alkyne amine IV-b, which can be converted to sulfonamide IV-c. These can undergo cyclization and concomitant reaction with aromatic bromide IV-d in the presence of a suitable catalyst (e.g., Pd catalyst), suitable solvent, and temperature to give further intermediate IV-e, with bromine substitution on ring C. Finally, intermediate IV-e can be used as a substrate for Suzuki coupling to give compounds of formula (I). [ka] Scheme IV: -LR via Suzuki coupling 1 Synthetic routes for compounds of the present disclosure by the final introduction of

[0215] Scheme V summarizes a synthetic route for preparing compounds of the present disclosure, starting from a preformed central pyrrolo-fused bicyclic aromatic ring. N-protected 2-pinacolylboronic ester Va can undergo Suzuki coupling with halide Vb to give intermediate Vc. Bromination with NBS gives 3-bromo intermediate Vd, which is converted to further N-protected intermediate Ve after a second Suzuki coupling. Starting with N-protected 3-pinacolylboronic ester Va, a first Suzuki coupling, followed by bromination at the 2-position, and then a second Suzuki coupling similarly gives intermediate Ve. After deprotection and reaction of the free NH with sulfonyl chloride Id in the presence of a suitable base and solvent, compound (I) is obtained. [ka] Scheme V: Synthesis of compounds of the present disclosure starting from a preformed core aromatic.

[0216] Exemplary Compound Set 1 Exemplary compounds are shown below. [Table 9-1] [Table 9-2] [Table 9-3]

[0217] Exemplary Compound Set 2 Exemplary compounds are shown below. [Table 10-1] [Table 10-2]

[0218] Exemplary Compound Set 3 Exemplary compounds are shown below. [Table 11-1] [Table 11-2] [Table 11-3] [Table 11-4] [Table 11-5] [Table 11-6] [Table 11-7] [Table 11-8] [Table 11-9] [Table 11-10] [Table 11-11] [Table 11-12] [Table 11-13] [Table 11-14] [Table 11-15] [Table 11-16] [Table 11-17] [Table 11-18] [Table 11-19] [Table 11-20] [Table 11-21]

[0219] Exemplary Compound Set 4 Exemplary compounds are shown below. [Table 12]

[0220] Exemplary Compound Set 5 Exemplary compounds are shown below. [Table 13-1] [Table 13-2] [Table 13-3]

[0221] Set 6 of exemplary compounds Exemplary compounds are shown below. [Table 14]

[0222] Exemplary Compound Set 8 Exemplary compounds are shown below. [Table 15-1] [Table 15-2]

[0223] Set 10 of exemplary compounds Exemplary compounds are shown below. [Table 16-1] [Table 16-2]

[0224] Exemplary Compound Set 11 Exemplary compounds are shown below. [Table 17-1] [Table 17-2] [Table 17-3] [Table 17-4] [Table 17-5] [Table 17-6] [Table 17-7] [Table 17-8] [Table 17-9] [Table 17-10] [Table 17-11] [Table 17-12] [Table 17-13] [Table 17-14] [Table 17-15] [Table 17-16] [Table 17-17] [Table 17-18]

[0225] Set 12 of exemplary compounds Exemplary compounds are shown below. [Table 18-1] [Table 18-2] [Table 18-3]

[0226] Set 13 of exemplary compounds Exemplary compounds are shown below. [Table 19]

[0227] Set 15 of exemplary compounds Exemplary compounds are shown below. [Table 20-1] [Table 20-2]

[0228] Set 17 of exemplary compounds Exemplary compounds are shown below. [ka]

[0229] Set 19 of exemplary compounds Exemplary compounds are shown below. [ka]

[0230] Set of 20 exemplary compounds Exemplary compounds are shown below. [Table 21-1] [Table 21-2] [Table 21-3] [Table 21-4]

[0231] Set 21 of exemplary compounds Exemplary compounds are shown below. [Table 22]

[0232] Set 22 of exemplary compounds Exemplary compounds are shown below. [ka]

[0233] Set 23 of exemplary compounds Exemplary compounds are shown below. [Table 23]

[0234] Set of 24 exemplary compounds Exemplary compounds are shown below. [ka]

[0235] Set of 25 exemplary compounds Exemplary compounds are shown below. [ka]

[0236] Set of 26 exemplary compounds Exemplary compounds are shown below. [Table 24]

[0237] Set of 27 exemplary compounds Exemplary compounds are shown below. [Table 25]

[0238] Set of 28 exemplary compounds Exemplary compounds are shown below. [ka]

[0239] Set of 30 exemplary compounds Exemplary compounds are shown below. [Table 26-1] [Table 26-2] [Table 26-3] [Table 26-4] [Table 26-5]

[0240] Set of 31 exemplary compounds Exemplary compounds are shown below. [ka]

[0241] Set 32 ​​of exemplary compounds Exemplary compounds are shown below. [Table 27-1] [Table 27-2]

[0242] Set of 36 exemplary compounds Exemplary compounds are shown below. [Table 28]

[0243] Set 37 of exemplary compounds Exemplary compounds are shown below. [Table 29]

[0244] Exemplary Compounds 41 / 1 and 41 / 2 Exemplary compounds are shown below. [ka] Separation of 2-chloro-3'-(3-(2-cyano-6-methylphenyl)-1-((4-(difluoro-methyl)phenyl)sulfonyl)-5-fluoro-1H-indol-2-yl)-[1,1'-biphenyl]-4-carboxylic acid into atropisomers (41 / 1 and 41 / 2)

[0245] Set of 44 exemplary compounds Exemplary compounds are shown below. [ka] [Example]

[0246] Biological Examples Compound stock solutions Test compounds were typically dissolved, tested, and stored as 20 mM stock solutions in DMSO.

[0247] Because sulfonylacetic acid derivatives tend to decarboxylate under these conditions, these stock solutions were prepared, tested, and stored as 20 mM DMSO stock solutions containing 100 mM trifluoroacetic acid (5 equivalents). The sulfonylacetic acid derivatives can be stored as solids at room temperature for long periods of time, as reported by Griesbrecht et al. (Synlett 2010:374) or Faucher et al. (J. Med. Chem. 2004;47:18).

[0248] TR-FRETβ activity assay Recombinant GST-LXRβ ligand-binding domain (LBD, amino acids 156–461, NP009052, SEQ ID NO: 4) was expressed in Escherichia coli (E. coli) and purified by glutathione-Sepharose affinity chromatography. The N-terminally biotinylated NCoA3 coactivator peptide (SEQ ID NO: 7) was chemically synthesized (Eurogentec). Assays were performed in a 384-well format (final assay volume 25 μL / well) in Tris / HCl buffer (pH 6.8) containing KCl, bovine serum albumin, Triton-X-100, and 1 μM 24(S)-25-epoxycholesterol as an LXR-prestimulation agonist. Assay buffer was supplied, and test articles (potential LXR inverse agonists) were titrated to give final assay concentrations of 50 μM, 16.7 μM, 5.6 μM, 1.9 μM, 0.6 μM, 0.2 μM, 0.07 μM, 0.02 μM, 0.007 μM, and 0.002 μM, including one vehicle control. Finally, detection mixture was added containing anti-GST-Tb cryptate (CisBio, 610SAXLB) and streptavidin-XL665 (CisBio, 610SAXLB) as the fluorescence donor and acceptor, respectively, plus the coactivator peptide and LXRβ-LBD protein (SEQ ID NO: 4). The reactions were mixed thoroughly, equilibrated at 4°C for 1 hour, and the proximity of LXRβ and the coactivator peptide was detected by measuring fluorescence in a VictorX4 multiplate reader (PerkinElmer Life Sciences) using 340 nm as the excitation wavelength and 615 and 665 nm as emission wavelengths. Assays were performed in triplicate.

[0249] Final assay concentrations of components: 240 mM KCl, 1 μg / μL BSA, 0.002% Triton-X-100, 125 pg / μL anti-GST-Tb cryptate, 2.5 ng / μL streptavidin-XL665, coactivator peptide (400 nM), LXRβ protein (530 μg / mL, i.e., 76 nM).

[0250] Transient transformation assay of LXR Gal4 reporter The activity status of LXRα and LXRβ was determined by detecting their interactions with coactivator and corepressor proteins in mammalian two-hybrid experiments (M2H). To this end, the full-length (FL) protein of LXRα (amino acids 1-447, NP005684, SEQ ID NO:1) or LXRβ (amino acids 1-461, NP009052, SEQ ID NO:2), or the ligand-binding domain (LBD) of LXRα (amino acids 155-447, SEQ ID NO:3) or LXRβ (amino acids 156-461, SEQ ID NO:4) was expressed from pCMV-AD (Stratagene) via transient transfection as a fusion to the transcriptional activation domain of NFkB. As cofactors, either the domain of steroid receptor coactivator 1 (SRC1, amino acids 552–887, SEQ ID NO: 5) or the domain of the corepressor NCoR (amino acids 1906–2312, NP006302, SEQ ID NO: 6) was expressed as a fusion to the DNA-binding domain of the yeast transcription factor GAL4 (derived from pCMV-BD, Stratagene). The interaction was monitored by activation of a coexpressed firefly luciferase reporter gene under the control of a promoter containing repeated GAL4 response elements (vector pFRLuc, Stratagene). Transformation efficiency was controlled via cotransfection of a constitutively active pRL-CMV Renilla luciferase reporter (Promega). HEK293 cells were grown in Minimum Essential Medium (MEM) containing 2 mM L-glutamine and Earle's Balanced Salt Solution supplemented with 8.3% fetal bovine serum, 0.1 mM non-essential amino acids, and 1 mM sodium pyruvate at 37°C in 5% CO. 3.5 × 10 4Cells / well were plated in 96-well cell culture plates in growth medium supplemented with 8.3% fetal bovine serum for 16–20 h until approximately 90% confluent. For transfection, the medium was removed, and the LXR and cofactor expression plasmids, as well as the reporter plasmid, were added to 30 μL of OPTIMEM / well containing polyethyleneimine (PEI) as a vehicle. Typical amounts of plasmids transfected per well were as follows: pCMV-AD-LXR (5 ng), pCMV-BD-cofactor (5 ng), pFR-Luc (100 ng), and pRL-CMV (0.5 ng). Compound stocks were prepared in DMSO and prediluted in MEM to a total volume of 120 μL, and added 4 h after the transfection mixture (the final concentration of vehicle did not exceed 0.2%). Cells were further incubated for 16 hours, lysed in 1x Passive Lysis Buffer (Promega) for 10 minutes, and firefly and Renilla luciferase activities were measured sequentially in the same cell extracts using buffers containing D-luciferin and coelenterazine, respectively. Luminescence was measured using a BMG luminometer. Substance Company Catalog Number HEK293 cells DSMZ ACC305 MEM Sigma-Aldrich M2279 OPTIMEM Life Technologies 11058-021 FCS Sigma-Aldrich F7542 Glutamax Invitrogen 35050038 Pen / Strep Sigma Aldrich P4333 Sodium pyruvate Sigma Aldrich S8636 Non-essential amino acids Sigma Aldrich M7145 Trypsin Sigma Aldrich T3924 PBS Sigma Aldrich D8537 PEI Sigma Aldrich 40.872-7 Passive Lysis Buffer (5x) Promega E1941 D-Luciferin PJK 260150 Coelenterazine PJK 26035 [Table 1-1] [Table 1-2] [Table 1-3] [Table 1-4] [Table 1-5] [Table 1-6]

[0251] Pharmacokinetics The pharmacokinetics of the compounds was evaluated in mice after single and oral administration. Exposure in blood / plasma and liver was measured by LC-MS.

[0252] The study design was as follows: Animal: C57 / bl6 / J (Janvier Institute) male Diet: Standard rodent chow Dose: 20mg / kg Animal handling: Animals should be deprived of food for at least 12 hours prior to dosing. Design: Single dose oral administration, n=3 animals per group Sacrifice: designated time points (4, 12, or 24 hours) after dosing Biological analysis: LC-MS of liver and blood / plasma samples [Table 2]

[0253] While structurally unrelated LXR inverse agonists GSK2033 and SR9238 have been shown to be orally bioavailable, the compounds of the present disclosure have been found to be orally bioavailable and effectively reach the target tissue, the liver, thereby minimizing undesirable systemic exposure.

[0254] Short-term HFD mouse model: The in vivo transcriptional regulation of several LXR target genes by LXR regulators was assessed in mice.

[0255] For this study, C57BL / 6J mice were purchased at 8 weeks of age from the Elevage Janvier Laboratory (Rennes, France). After a two-week acclimatization period, animals were pre-fed for 5 days with a high-fat diet (HFD) containing 60 kcal of fat combined with 1% (w / w) high cholesterol (Sigma-Aldrich, St. Louis, MO) (Ssniff Spezialdiaten GmbH, Surwit EF D12330 mod, catalog number E15771-34, Germany). Animals were maintained on this diet throughout treatment with LXR modulators. Test compounds were formulated in 0.5% hydroxypropylmethylcellulose (HPMC) and administered by oral gavage at three doses (1.5–20 mg / kg each) according to the following schedule: on day one, animals received treatments in the morning and evening (approximately 5:00 PM); on day two, after a 4-hour fast, animals received a final treatment in the morning and were sacrificed 4 hours later. Animal work was carried out in accordance with the German national guidelines for animal care.

[0256] At the end of the study, livers were harvested, immersed in ice-cold PBS for 30 seconds, and cut into appropriate pieces. The sections were quickly frozen in liquid nitrogen and stored at -80°C. For clinical chemistry analysis of plasma, alanine aminotransferase (ALT, IU / mL), cholesterol (CHOL, mg / dL), and triglycerides (TG, mg / dL) were determined using a fully automated benchtop analyzer (Respons® 910, DiaSys Greiner GmbH, Flacht, Germany) with the system kit provided by the manufacturer.

[0257] Analysis of gene expression in liver tissue. To obtain total RNA from frozen liver tissue, samples (25 mg of liver tissue) were first homogenized in RLA buffer (4 M guanidine thiocyanate, 10 mM Tris, 0.97% w:v β-mercaptoethanol). RNA was prepared using the SV96 Total RNA Isolation System (Promega, Madison, WI, USA) according to the manufacturer's instructions. cDNA was synthesized from 0.8–1 μg of total RNA using All-in-One cDNA Supermix reverse transcriptase (Absource Diagnostics, Munich, Germany). Quantitative PCR was performed and analyzed using Primetime Gene Expression Master Mix (Integrated DNA Technologies, Coralville, IA, USA) and an ABI 7900HT Sequence Detection System in 384 format (Applied Biosystems, Foster City, IA, USA). The expression of the following genes was analyzed: stearoyl-CoA desaturase 1 (Scd1), fatty acid synthase (Fas), and sterol regulatory element-binding protein 1 (Srebp1). Specific primer and probe sequences (commercially available) are listed in Table 3. qPCR was performed at 95°C for 3 minutes, followed by 40 cycles of 95°C for 15 seconds and 60°C for 30 seconds. All samples were run in duplicate from the same RT (reverse transcription) reaction. Gene expression was expressed in arbitrary units and normalized to the mRNA of the housekeeping gene TATA box-binding protein (Tbp) using the comparative Ct method. [Table 3] [Table 4-1] [Table 4-2]

[0258] Three oral doses of the disclosed compound in mice over two days (morning and evening on the first day, morning on the second day) resulted in high liver exposure with favorable liver-to-plasma ratios. Liver LXR target genes were effectively suppressed. These genes are involved in the transcriptional regulation of de novo hepatic lipogenesis (Wang et al., Nat. Rev. Mol. Cell Biol. 2015;16:678). Suppression of these genes resulted in a reduction of liver fat (liver triglycerides).

[0259] Comparative Example [ka] Comparative examples show that it can be advantageous if the cyclic moiety at the 3-position of the indole (or analogue) has at least one substituent in the 1,2-orientation (ortho-substitution).

[0260] Nonclinical Pharmacology Major Pharmacodynamics The activity and efficacy of compound 21 / 3 and its close structural analog, compound precursor 6 / 3, were evaluated across a range of in vitro and in vivo pharmacological tests.

[0261] As shown herein, compound 21 / 3 and compound precursor 6 / 3 are shown below. [ka]

[0262] In Vitro Testing Compound 21 / 3 and compound precursor 6 / 3 are potent inhibitors of LXRα and LXRβ The potency of compound 21 / 3 and its analog, compound precursor 6 / 3, against LXRα and LXRβ was assessed in biochemical binding assays, cellular mammalian two-hybrid (M2H) interaction assays to assess nuclear receptor corepressor (NCOR) recruitment, and cellular reporter assays to assess transcriptional activity (Table 5). Compound 21 / 3 exhibited half maximal effective concentrations (EC) of 7–15 nM across all assays. 50 ) showed comparable binding and inhibition of LXRα and LXRβ activity. Compound precursor 6 / 3 had a similar profile to compound 21 / 3 but was more potent in cellular M2H and reporter assays. [Table 5]

[0263] Compound 21 / 3 reduces lipid accumulation in primary human hepatocytes and hepatic organoids It is hypothesized that inhibition of LXR activity in hepatocytes reduces intracellular TG accumulation via inhibition of DNL. The effect of Compound 21 / 3 on lipid accumulation in human primary Upcyte hepatocytes was evaluated. Briefly, human primary Upcyte hepatocytes were cultured for 5 days in a medium containing high concentrations of sugar (25 mM) and palmitate (100 nM) in the presence or absence of Compound 21 / 3, and intracellular lipids were measured by BODIPY staining. Compound 21 / 3 had an EC of 289 ± 34 nM. 50 Compound 21 / 3 reduced lipid accumulation in a dose-dependent manner (Figure 1). Figure 1 shows a representative dose-response curve of relative fluorescence intensity normalized to dimethyl sulfoxide (DMSO) control in Upcyte hepatocytes treated with a dose range of Compound 21 / 3. Data are presented as mean ± SD. n = 2 wells per treatment, N = 8 experiments. Figure 1 shows that Compound 21 / 3 reduces lipid droplet accumulation in human primary Upcyte® hepatocytes.

[0264] The activity of compound 21 / 3 was also evaluated in induced pluripotent stem cell (iPSC)-derived human hepatic organoid (HLO) models established from human donors with different genetic backgrounds, including those with known genetic risk variants for NASH (Ouchi, Togo, et al., 2019). Exposing HLOs to high concentrations of lipids induced a reproducible fatty NASH phenotype (sHLO) with increased expression of DNL genes, including NR1H3, the gene encoding LXRα (Figure 2A) (Ouchi, Togo, et al., 2019; Minniti, Pedrelli, et al., 2020). Compound 21 / 3 dose-dependently reduced intracellular lipid content in patient-derived sHLOs (Figure 2B). Mutations in GCKR have been associated with increased blood lipids, hepatic DNL, ​​and diseases including diabetes and NASH (Fernandes Silva, Vangipurapu, et al., 2019). Compound 21 / 3 also suppressed the expression of DNL-related genes in sHLOs derived from homozygous carriers of either the wild-type (CC) or mutant (TT) alleles of GCKR, supporting the potential therapeutic benefit of compound 21 / 3 in patients with elevated hepatic DNL (Figure 2C). Figures 2A-2C show that compound 21 / 3 reduces lipid droplet accumulation and lipogenic gene expression in fatty human liver organoids.

[0265] In Vivo Testing Compound 21 / 3 and Compound Precursor 6 / 3 Have Beneficial Effects on Whole-Body and Hepatic Lipid Homeostasis, Insulin Sensitivity, and Liver Fibrosis in Nonclinical Rodent Models The efficacy of compound 21 / 3 and compound precursor 6 / 3 was evaluated in diet-induced obese (DIO) mouse and rat models. Despite comparable in vitro potency, compound 21 / 3 and compound precursor 6 / 3 demonstrate distinct pharmacology in vivo, with compound 21 / 3 exhibiting lower plasma exposure and higher, more sustained liver exposure than compound precursor 6 / 3 (Figure 3A-B). As a result of the greater liver burden, mice treated with a single dose of compound 21 / 3, but not compound precursor 6 / 3, demonstrated sustained target engagement in the liver 24 h after administration (assessed by LXR target gene expression) (Figure 3C). Figures 3A-C show that compound 21 / 3 and compound precursor 6 / 3 demonstrate distinct pharmacology in vivo.

[0266] Compound 21 / 3 improves hepatic and whole-body lipid homeostasis in metabolically deficient rodents The efficacy of compound 21 / 3 was evaluated in three metabolically dysfunctional rodent models, including DIO mice, HFD-fed ZDF rats, and HFD-fed SD rats (Figures 4 and 5). Briefly, DIO mice were fed an HFD (60% kcal from fat) for 14 weeks and treated with compound 21 / 3 (0.3 and 1 mg / kg once daily by oral gavage) for 3 weeks, while ZDF rats and SD rats were fed an HFD for 2 weeks and then treated with compound 21 / 3 (0.1 and 1 mg / kg once daily by oral gavage) for 2 or 3 weeks, respectively. Figure 4 shows that compound 21 / 3 reduces tg in liver and plasma in multiple metabolically dysfunctional rodent models. Figure 5 shows that compound 21 / 3 lowers plasma total cholesterol and alters cholesterol-related gene expression in the liver and intestine, but not in the periphery.

[0267] Compound 21 / 3 dose-dependently reduced the expression of DNL genes, including Srebp1c, Fasn, Acaca (ACC1), and Scd1, in all three models (Figure 4A). Compound 21 / 3 dose-dependently reduced hepatic TG levels in DIO mice, HFD-fed ZDF rats, and HFD-fed SD rats, with maximum reductions of 65% (p ≤ 0.001), 49% (p ≤ 0.01), and 42% (p = 0.07), respectively, compared with vehicle (Figure 4B). Compound 21 / 3 also reduced plasma TG levels in all three models (Figure 4C). In HFD-fed ZDF and SD rats, which had significant diet-induced hypertriglyceridemia, the highest dose of compound 21 / 3 (1 mg / kg) reduced plasma TG levels by 96% and 59%, respectively, compared with vehicle (p ≤ 0.05).

[0268] In addition to the effects of compound 21 / 3 on hepatic DNL, ​​the reduction in plasma TG observed in these models may be mediated by a decrease in intestinal TG absorption and an increase in the clearance of TG-containing lipoproteins from the blood. Indeed, compound 21 / 3 dose-dependently reduced intestinal Srebp1c expression in DIO mice (Figure 4D) and HFD-fed ZDF and SD rats (data not shown). Furthermore, LXR inhibition with compound precursor 6 / 3 significantly reduced intestinal Srebp1c expression in HFD-fed mice. 3Compound 21 / 3 reduced intestinal lipid absorption, as measured by reduced uptake of H-labeled triolein tracer (Figure 4E). Furthermore, compound 21 / 3 reduced the hepatic expression and plasma levels of ANGPTL3, an inhibitor of LPL, a key enzyme involved in the clearance of triglyceride-rich lipoproteins from the blood (Figure 4F). Loss-of-function variants of ANGPTL3 are associated with reduced serum lipids and a reduced risk of CAD (Dewey, Gusarova, et al., 2017). Similarly, hepatic expression of Angptl3, Angptl4, and Angptl8, as well as apoC1 (ApoC1), apoC2 (ApoC2), and apoC3 (ApoC3), another inhibitor of LPL, was suppressed in HFD-fed ZDF rats treated with compound precursor 6 / 3 (Figure 4G). As with ANGPTL3, large-scale genetic studies have demonstrated that loss-of-function variants in apoC3 (ApoC3) are associated with approximately 40% reductions in plasma TG and a 40% reduction in CAD incidence (Crosby, Peloso et al., 2014).

[0269] In DIO mice and HFD-fed ZDF rats, where plasma total cholesterol levels are significantly elevated, compound 21 / 3 also dose-dependently reduced plasma total cholesterol (TC) by 49% and 67%, respectively, at the end of treatment compared with vehicle values ​​(p ≤ 0.05) (Figure 5A). However, compound 21 / 3 caused a statistically significant increase in hepatic TC, particularly in the high-dose group (Figure 5B). Importantly, these changes in hepatic cholesterol were not associated with substantial elevations in liver biochemistry, including plasma ALT or aspartate aminotransferase (AST), compared with vehicle treatment (Figure 5C-D). Furthermore, the cholesterol content of the diet of these rodents was very high (up to 1%), likely enhancing this pharmacological effect.

[0270] Compound 21 / 3 dose-dependently reduced the expression of cholesterol synthesis (Hmgcr) and metabolism (Cyp7a1) enzymes in the liver and cholesterol efflux transporters (Abca1, Abcg5, and Abcg8) in the intestine (Figure 5E). However, compound 21 / 3 did not alter the expression of the cholesterol efflux transporters Abca1 and Abcg1 in the buffy coat, a fraction of collected blood that primarily contains leukocytes. These data indicate that compound 21 / 3 acts primarily in the liver and intestine and does not inhibit LXR activity in peripheral tissues involved in reverse cholesterol transport and associated with atherogenic risk (Rader and Ikewaki, 1996).

[0271] Because the characteristics of cholesterol metabolism differ between rodents and humans, we further explored the effects of compound 21 / 3 on lipid metabolism in a more relevant preclinical model by utilizing a humanized liver chimeric PXB® mouse model (Tateno, Yoshizane, et al., 2004). Briefly, PXB® mice were treated with either vehicle or compound 21 / 3 (1 mg / kg once daily by oral gavage) for 8 days. Pharmacokinetic (PK) data from this study are presented herein. Despite short-term (8-day) administration, compound 21 / 3 tended to reduce both hepatic TG and TC content (Figure 6A). Furthermore, hepatic expression of genes involved in cholesterol and TG metabolism was significantly reduced in compound 21 / 3-treated mice compared to vehicle (Figure 6B). Specifically, compound 21 / 3 reduced the expression of the cholesterol synthesis gene HMGCR, as well as genes that reduce hepatic uptake of LDL-C (PCSK9, IDOL) and cholesterol conversion to bile acids (CYP7A1). As expected, significant reductions in ANGPTL3 and DNL-related genes (SREBP1C, ACACA, FASN, SCD1) were also observed. Figure 6 shows that compound 21 / 3 demonstrates target engagement in humanized liver chimeric mice.

[0272] These data provide strong support for the therapeutic potential of compound 21 / 3 to regulate lipid homeostasis in the human liver.

[0273] In summary, compound 21 / 3 improves hepatic and whole-body lipid homeostasis in multiple metabolically impaired rodent models, resulting in significant reductions in hepatic TG content and blood TG and cholesterol levels. Due to its preferential hepatic uptake after oral administration, the effects of compound 21 / 3 are primarily limited to the liver and intestine, thereby avoiding inhibition of reverse cholesterol transport. Therefore, these data suggest that liver-selective LXR inhibition using compound 21 / 3 may have both cardio- and hepatoprotective properties.

[0274] Inverse agonism of LXR has beneficial effects on whole-body insulin sensitivity The effects of chronic administration of compound 21 / 3 and compound precursor 6 / 3 were evaluated in DIO mice and HFD-fed ZDF rats, respectively. Briefly, C57BL / 6 mice were fed an HFD for 16 weeks and then treated with compound precursor 6 / 3 (5 mg / kg) or pioglitazone (30 mg / kg, positive control) by oral gavage once daily. After 4 weeks of treatment, a two-phase hyperinsulinemic-euglycemic clamp with radiotracer injection was performed to monitor glucose disposal and hepatic glucose production. The glucose infusion rate, the rate at which glucose is infused to maintain euglycemia, was significantly higher in mice treated with compound precursor 6 / 3 compared to vehicle at both insulin infusion phases (8 and 18 mU / kg / min) and was noninferior to pioglitazone, demonstrating enhanced whole-body insulin sensitivity (Figure 7A-B). These changes were associated with decreased hepatic glucose production in mice treated with Compound Precursor 6 / 3, which was more evident during an 8 mU / kg / min insulin infusion (Figure 7B). Muscle glucose utilization measured at the end of the clamp was also significantly higher with Compound Precursor 6 / 3 than with vehicle (Figure 7C).

[0275] Five weeks of treatment with Compound 21 / 3 (15 mg / kg once daily by oral gavage) also improved glucose homeostasis in HFD-fed ZDF rats. Glucose tolerance, as measured by oral glucose tolerance test after 4 weeks of treatment, was significantly improved by Compound 21 / 3 at all time points assayed (Figure 7D). Furthermore, immunostaining of pancreatic sections from animals treated with Compound 21 / 3 demonstrated more pronounced staining for insulin compared with vehicle-treated mice, suggesting that Compound 21 / 3 may have a protective effect on pancreatic β cells (Figure 7E).

[0276] These data demonstrate that inverse agonism of LXR using compound 21 / 3 (or its analog compound precursor 6 / 3) can improve insulin action in metabolic tissues such as liver and muscle and prevent pancreatic beta-cell loss. In addition to beneficial effects on liver and blood lipids, the improvement in insulin sensitivity by compound 21 / 3 may provide additional cardioprotective benefits. Figure 7 shows that inverse agonism of LXR improves insulin sensitivity and preserves pancreatic beta-cell mass.

[0277] Inverse agonism of LXR has beneficial effects on fibrosis progression, fibrosis formation, and hepatic steatosis in a rodent model of NASH with advanced fibrosis The CDHFD model of NASH is characterized by reduced hepatic phosphatidylcholine synthesis and impaired TG secretion in VLDL particles, leading to hepatic lipid accumulation, inflammation, oxidative stress, and severe fibrosis. Liver injury in CDHFD-fed rats can be exacerbated by further inducing hypoxia with sodium nitrate (Takayama, Egashira, et al., 2009). Wistar Han rats were treated with CDHFD / sodium nitrate for a total of 12 weeks and administered compound precursor 6 / 3 (5 mg / kg once daily by oral gavage) from weeks 6 to 12. Compound precursor 6 / 3 significantly reduced fibrosis, as assessed histologically by picrosirus red (PSR) staining, which identifies collagen fibers deposited in the liver (Figure 8A). Furthermore, compared with vehicle treatment, compound precursor 6 / 3 reduced hepatic hydroxyproline and collagen content by 64% (p ≤ 0.001) and 50% (p ≤ 0.001), respectively (Figure 8B-C). Compound precursor 6 / 3 also reduced hepatic TG content (Figure 8D) and the hepatic expression of genes involved in DNL (Srebp1c, Scd1, Fasn) and genes involved in fibrogenesis and hepatic stellate cell activation (Timp1, Col1a1, Acta2) (Figure 8E). Figure 8 shows that compound precursor 6 / 3 reduces steatosis and the progression of liver fibrosis in a rat CDHFD model.

[0278] Overall, preclinical pivotal pharmacological studies demonstrate that liver-targeted LXR inhibition with compound 21 / 3 or its analog, compound precursor 6 / 3, has beneficial therapeutic effects on plasma triglyceride and cholesterol concentrations, hepatic triglyceride content, insulin sensitivity, and liver fibrosis across multiple rodent models. The limited systemic effects of compound 21 / 3, due to its preferential distribution to the liver and intestine, avoid the risk of systemic LXR inhibition, which could result in inhibition of reverse cholesterol transport and potentially atherogenic effects. These data provide a strong rationale for evaluating compound 21 / 3 to treat subjects with severe dyslipidemia and NASH, suggesting that compound 21 / 3 may be cardioprotective in these subjects due to its benefits on lipid and glucose metabolism.

[0279] A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single and Multiple Ascending Doses of Compound 21 / 3 in Healthy Subjects the purpose The primary objectives are to evaluate the safety and tolerability of escalating single and multiple doses of Compound 21 / 3 and to characterize the pharmacokinetics (PK) of single and multiple doses of Compound 21 / 3 and its metabolites. Secondary objectives are to assess the pharmacodynamics (PD) of inverse agonism of liver X receptors (LXRs) by Compound 21 / 3 as measured by metabolic parameters including serum biomarkers of fasting lipids and de novo lipogenesis (DNL), to characterize the dose and / or exposure-response relationship of Compound 21 / 3 with respect to PD markers, to evaluate exploratory biomarkers, and to evaluate the effect of fasted vs. fed dosing on the PK profile of Compound 21 / 3.

[0280] Study design A double-blind, placebo-controlled, single- and multiple-ascending-dose FIH Phase 1 study was conducted to evaluate the safety, tolerability, PK, and PD of Compound 21 / 3 in healthy adult subjects. A total of up to 150 subjects were enrolled, including 100 subjects in Parts A and B and up to 50 subjects in the adaptive cohort in Part C. Within each cohort, 10 subjects were randomized, including eight subjects randomized to Compound 21 / 3 and two subjects randomized to PTM (matched placebo). For single-dose cohorts in Part A and any Part C cohorts evaluating a higher total daily dose than previously estimated, safety and tolerability data collected through Day 2 from two index subjects, one randomized to Compound 21 / 3 and one randomized to PTM, were evaluated prior to dosing for the remaining subjects in each cohort.

[0281] A nearly uniform distribution of healthy male and non-pregnant, non-lactating female subjects aged 18-55 years was enrolled in this study. No significant medical conditions were identified by medical history, physical examination, or laboratory assessment. Subjects were not permitted to participate in multiple cohorts of the study. Within each MAD cohort, attempts were made to increase the number of subjects with elevated TG and / or LDL-C to ≥3. After completion of screening and admission evaluations, eligible subjects were enrolled on Day -1. Safety and tolerability assessments, including adverse event (AE) monitoring, clinical laboratory tests, physical examinations, and ECG evaluations, were conducted throughout the study.

[0282] The duration of administration was 1 day for the SAD cohort in Parts A and C and 14 days for the MAD cohort in Parts B and C. For all subjects within the MAD cohort, subjects also received PTM on Day -1.

[0283] The overall post-screening study duration was up to 18 days for Part A and up to 32 days for Parts B and C.

[0284] The study proceeded in three parts, with progression within and between parts governed by review of safety and any available and relevant PK and / or PD data, and application of stopping rules. The sponsor was permitted to choose not to initiate any or all of the adaptive cohorts in Part C if deemed unnecessary based on observations in Parts A and B. The overall study design and the design of each part are described herein, and the study schemes are presented in Figure 9 for the SAD cohorts in Parts A and C and Figure 10 for the MAD cohorts in Parts B and C.

[0285] Intensive PK sampling was performed over 72 hours post-dose on Days 1 (SAD and MAD) and 14 (MAD). Plasma concentrations of Compound 21 / 3 were determined using a validated liquid chromatography-tandem mass spectrometry assay. PK parameters were estimated via non-compartmental methods using Pheonix® WinNonlin® 6.2.1 and 8.3.4 (Certara, LP, Princeton, NJ).

[0286] Lipid parameters, including apolipoprotein B (apoB), were assessed by NMR LipoProfile® (Labcorp, Burlington, NC). Plasma apoC3 (ApoC3) and ANGPTL3 were assessed by ELISA (360biolabs, Melbourne, Australia). Peripheral reverse cholesterol transport (RCT) was assessed by evaluating changes in ABCA1 / ABCG1 expression in PBMCs (Gnomix, Bedford Park, Australia) pre- and 4 h post-dose on days 1 and 14.

[0287] The following table shows subject enrollment and demographic characteristics for the SAD cohort. [Table 30]

[0288] The table below shows subject enrollment and demographic characteristics for the MAD cohort. [Table 31]

[0289] Part A: Single Ascending Dose (SAD) (Cohorts 1-5) Part A evaluated the safety, tolerability, PK, and PD of single ascending doses of oral Compound 21 / 3 or placebo under fed conditions. Part A progressed with up to five dose-escalation cohorts and was governed by consideration of safety, tolerability, and any available and relevant PK and / or PD data, as well as study-specific discontinuation criteria. Planned study treatments within each cohort are provided in Table 6 below. [Table 6]

[0290] Within each cohort, 10 unique subjects were randomized 4:1 to receive either Compound 21 / 3 (N=8) or PTM (N=2) in a blinded fashion. In Part A, all study medications were administered in the morning after a standard meal.

[0291] At the start of each cohort in Part A, prior to randomization of the entire cohort, two index subjects were randomized: one to compound 21 / 3 at the dose evaluated within the planned cohort and one to the corresponding PTM. Enrollment and randomization of the remaining eight subjects in each cohort was determined upon evaluation of all safety and tolerability data through Day 2 for these two index subjects.

[0292] For cohorts 2-5, initiation of single-dose administration was permitted after evaluation of cumulative blinded safety data through Day 4 after the single-dose administration of the preceding cohort and any relevant and available PK and / or PD data.

[0293] A schematic representation of activity within the Part A cohort is shown in Figure 9. The Adaptive SAD cohort in Part C will follow the same study scheme.

[0294] Part B: Multiple Ascending Dose (MAD) (Cohorts 6-10) Part B evaluated the safety, tolerability, PK, and PD of multiple ascending doses of oral Compound 21 / 3 or placebo under fed conditions. Part B will proceed with up to five dose-escalation cohorts and will be governed by consideration of safety, tolerability, and any available and relevant PK and / or PD data, as well as study-specific discontinuation criteria. The planned study treatments within each cohort are provided in Table 7 below. [Table 7]

[0295] Attempts were made to enroll at least three subjects in each MAD cohort with TG ≥ 150 mg / dL and / or low-density lipoprotein cholesterol (LDL-C) ≥ 130 mg / dL at screening.

[0296] Within each cohort, 10 unique subjects were randomized 4:1 to receive either Compound 21 / 3 (N=8) or PTM (N=2) QD in a blinded fashion for 14 days.

[0297] Part B (Cohort 6) began after evaluation of cumulative safety, tolerability, and any relevant and available PK and / or PD data (through Day 4) from all subjects enrolled in Cohort 3 of Part A.

[0298] For Cohorts 7-10, dosing began after evaluation of cumulative safety, tolerability, and any relevant and available PK and / or PD data from all subjects enrolled in the preceding cohorts in Part B through Day 14.

[0299] In Part B, all study medications will be administered in the morning after a standard meal.

[0300] Part C: Adaptive SAD and / or MAD (Cohorts 11–15) Part C included optional adaptive cohorts to evaluate the safety, tolerability, PK, and PD of single and / or multiple ascending doses of oral Compound 21 / 3 or placebo under fasted or fed conditions. Based on available safety, PK, and / or PD data generated in Parts A and B, doses in Part C (Cohorts 11-15) will be selected, if applicable, up to a total daily dose of 50 mg. Planned study treatments within each cohort are provided in Table 8 below. [Table 8]

[0301] Part C progressed with up to five dose-escalation cohorts and was governed by review of safety, tolerability, and any available and relevant PK and / or PD data generated from the preceding Parts A, B, and / or C cohorts, as appropriate.

[0302] Attempts were made to enroll at least three subjects in each cohort with TG ≥ 150 mg / dL and / or low-density lipoprotein cholesterol (LDL-C) ≥ 130 mg / dL at screening.

[0303] Within each cohort, 10 unique subjects were randomized 4:1 to receive a maximum total daily dose of 50 mg of Compound 21 / 3 (N=8) or PTM (N=2) for either 1 day (as in Part A) or 14 days (as in Part B).

[0304] The dosing frequency (QD or BID for the MAD cohort) and fasted vs. fed state (for the SAD or MAD cohort) may also be varied for Parts A and B. If dosing is administered in the fed state, the standard meal conditions may also be optionally varied. The QD dose was administered in the morning after a standard meal, and the BID dose was administered after a standard morning meal and an evening snack, with the second dose administered 12 hours (±10 minutes) after the morning dose. Once determined, the dose level, dosing duration, dosing frequency, and meal conditions remained consistent within a cohort. For any MAD cohort in Part C with BID dosing, both the morning and evening doses must be administered on Day 14.

[0305] If the total daily dose being evaluated was equal to or less than the dose already evaluated in Part B, multiple-dose adaptive cohorts in Part C were initiated in parallel with the preceding cohorts. If the total daily dose in any cohort exceeded the previously evaluated dose, the index dose was included, including one subject randomized to placebo and one subject randomized to Compound 21 / 3. Randomization of the remaining eight subjects within a cohort would be based on evaluation of all safety and tolerability data through Day 2 for these two index subjects. If the dose selected in two or more adaptive cohorts exceeded the dose evaluated in the preceding cohorts in Part B, these cohorts were conducted in a staggered fashion (lowest dose first), with the same stopping rules applied.

[0306] A schematic representation of activity within the MAD cohort in parts B and C is shown in Figure 10.

[0307] Dose escalation criteria SAD cohort in parts A and C At the start of each single-dose cohort in Part A and any single-dose cohort in Part C evaluating a total daily dose of Compound 21 / 3 higher than previously evaluated, two index subjects will be randomized, one to Compound 21 / 3 at the dose evaluated in the planned cohort and one to the corresponding PTM. Enrollment and randomization of the remaining eight subjects in each cohort will be determined upon evaluation of all safety and tolerability data through Day 2 for these two index subjects.

[0308] Initiation of single-dose dosing at the higher dose was determined by evaluation of safety through Day 4 and any relevant and available PK and / or PD data for all subjects enrolled in the preceding dosing cohort.

[0309] Part B MAD cohort Dosing in Cohort 3 of the SAD portion of the study (Part A) was completed before progression of the MAD portion of the study. Initiation of multiple dosing within Cohort 6 was determined by review of cumulative safety through Day 4 of Cohort 3 of Part A, and any relevant and available PK and / or PD data.

[0310] The decision to start subsequent multiple-dose cohorts at higher doses was made upon evaluation of all safety data through Day 14 from all subjects enrolled in the preceding multiple-dose cohort, as well as any relevant and available PK and / or PD data.

[0311] In both Part A and Part B, escalation to doses higher than those pre-tested may occur only in the absence of dose-limiting toxicity and / or failure to meet pre-specified discontinuation criteria.

[0312] Part C Indicated MAD Cohort Based on safety and available PK and / or PD data from the Part A and Part B (if applicable) cohorts, the dose of Compound 21 / 3 in Part C could be selected up to a total daily dose of 50 mg. If the total daily dose in any cohort in Part C exceeded the dose evaluated in any prior cohort, the index dose would be completed, including one subject randomized to placebo and one subject randomized to Compound 21 / 3. Randomization of the remaining eight subjects within the cohort was determined based on evaluation of all safety and tolerability data through Day 2 for these two index subjects. Furthermore, if the dose selected for two or more adaptive cohorts exceeded the dose evaluated in the prior cohort, the cohorts were conducted in a staggered fashion (lowest dose first), with the same stopping rules applied. Part C cohorts could be initiated in parallel with Part B cohorts if the total daily dose being evaluated was equal to or less than the dose already evaluated.

[0313] Sponsors may choose not to initiate any and all adaptive cohorts if deemed unnecessary.

[0314] Protocol-specific discontinuation criteria Targeted investigational drug discontinuation criteria The severity of AEs was graded using the Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v5.0).

[0315] The study drug should be discontinued in subjects who experience any of the following: Confirmed, treatment-emergent, treatment-related, serious AEs (SAEs) or ≥ Grade 3 AEs Severity of Adverse Events and Clinically Significant Laboratory Abnormalities ≥ Grade 3 as defined by the Common Terminology Criteria for Adverse Events (CTCAE) v5.0 (confirmed by repeat testing) Symptoms of drug-related hepatotoxicity confirmed by immediate repeat testing, and / or ALT or AST >5 x ULN, or ALT >3 x ULN, and total bilirubin >2 x ULN, or INR >1.5

[0316] The investigational product and / or investigational procedures may also be discontinued if: - Concurrent illnesses that, in the investigator's judgment, significantly affect the assessment of clinical status Unacceptable toxicity as defined in the Toxicity Management section of the protocol, or toxicity that, in the investigator's judgment, impairs the ability to continue study-specific procedures or is not in the subject's best interest - Requests to stop the target, regardless of the reason Non-compliance with the subject Pregnancy during the study Investigator's discretion Cancellation of the trial at the request of the investigator, a regulatory authority, or an Institutional Review Board (IRB) / Independent Ethics Committee (IEC).

[0317] Study-specific discontinuation criteria Dose escalation or study drug administration for a cohort may be interrupted, based on a full review of the clinical data by the Medical Monitor (MM) or designee, in consultation with the Investigator, if: One subject receiving Compound 21 / 3 experienced a treatment-emergent SAE that, in the opinion of the investigator, was deemed potentially related to the study drug. Two subjects receiving Compound 21 / 3 within one cohort experienced elevations in liver biochemistry tests confirmed by immediate repeat testing: ALT and / or AST >5xULN, or ALT >3xULN and total bilirubin >2xULN, or INR >1.5 Two or more subjects receiving Compound 21 / 3 experience the same AE of ≥ Grade 3 that, in the opinion of the investigator, is deemed potentially related to the study drug. Two or more subjects receiving Compound 21 / 3 experience clinically significant ≥ Grade 3 laboratory abnormalities of a similar nature (confirmed by repeat testing) that, in the opinion of the investigator, may be related to the study drug. The number and / or severity of AEs justifies discontinuation of the study The sponsor requests that the study be discontinued

[0318] The decision to restart the trial may be made in consultation with the sponsor, pending a comprehensive safety review.

[0319] Administration period The duration of treatment for each part was as follows: Part A (SAD): 1 day Part B (MAD): 15 days (including PTM administration to all subjects on Day -1) Part C (adaptive SAD and / or MAD): 1 day or 15 days (including PTM administration for all multiple-dose subjects on Day -1)

[0320] clinical restraint After screening and admission procedures, eligible subjects were confined to the study site until completion of assessments on day 4 (SAD cohort) or day 17 (MAD cohort), which began at the time of admission (day −1 for the SAD cohort and day −2 for the MAD cohort).

[0321] Subjects returned for an in-clinic follow-up visit 14 ± 2 days after the last dose (i.e., day 15 [± 2 days] for the SAD cohort and day 28 [± 2 days] for the MAD cohort).

[0322] Pharmacokinetic evaluation The plasma concentrations of compound 21 / 3 (and its metabolites, if applicable) were determined and PK was assessed. PK parameters will be estimated as necessary. Plasma concentrations of other metabolites may also be determined and PK explored.

[0323] Pharmacodynamic evaluation Blood and stool samples for assessment of PD biomarkers related to compound 21 / 3 and its mechanism of action were collected throughout the study.

[0324] Safety evaluation Safety assessments were conducted throughout the study.

[0325] Results: SAD cohort The plasma concentration-time profiles on day 1 of the SAD study are shown in Figure 11 and in the table below. [Table 32]

[0326] The SAD test shows: Compound 21 / 3 is rapidly absorbed and max occurred approximately 3 to 4 hours after administration. Short t consistent with rapid hepatic uptake 1 / 2 (approximately 2-3 hours) and low maximum plasma concentration (C max <7ng / mL). Plasma exposure increased less than dose-proportionally.

[0327] Results: MAD cohort The plasma concentration-time profiles on day 14 of the MAD study are shown in Figure 12 and in the table below. [Table 33]

[0328] The MAD test demonstrates: Average steady-state t of compound 21 / 3 1 / 2 ranged from 1.4 to 2.6 hours. AUC and C of compound 21 / 3 max increased less than dose-proportionally and was approximately 25-50% lower on day 14 compared with day 1 with fed-administration. With fasting dosing, exposure was similar on days 1 and 14 and approximately three times higher than with fed dosing.

[0329] Results: MAD Cohort - Safety and Tolerability Safety and tolerability results from the MAD trial are shown in the table below. [Table 34]

[0330] The MAD test demonstrates: Compound 21 / 3 at 0.5, 2, 6, and 12 mg for 14 days was well tolerated. All TEAEs in the Compound 21 / 3 cohort were non-serious, and all but one were mild in severity. Treatment-related TEAEs, all mild in severity and gastrointestinal in nature, occurred in three subjects treated with Compound 21 / 3 (abdominal discomfort and diarrhea [6 mg with food, n=1], abdominal pain and / or diarrhea [12 mg, n=2]) and one subject on placebo (nausea). A mild (Grade 1) transient increase in serum ALT was observed in one subject in the 6 mg Compound 21 / 3 group and four subjects in the 12 mg Compound 21 / 3 group (all fed). No other clinically significant laboratory abnormalities or changes in vital signs or ECG parameters.

[0331] Safety, pharmacokinetics, and lipid-lowering efficacy of oral liver-targeted liver X receptor (LXR) inverse agonists in healthy volunteers background. Liver X receptors (LXRs) are oxysterol-activated nuclear hormone receptors that regulate cholesterol homeostasis and de novo lipogenesis. Compound 12 / 3 is an oral, liver-targeted inverse agonist of LXRα / β in development for severe hypertriglyceridemia (SHTG) and NASH.

[0332] method. In a randomized, double-blind, placebo-controlled Phase 1 study, healthy subjects (n=8 / 2 per cohort, Compound 21 / 3 vs. PBO) received single ascending doses (SAD) of Compound 21 / 3 (0.5, 2, 6, 12, or 20 mg) or multiple ascending doses (MAD) QD for 14 days (0.5, 2, 6, or 12 mg) fed or 6 mg fasted. Safety, PK, serum lipid parameters by NMR LipoProfile®, and gene expression in PBMCs were assessed.

[0333] result. The proportion of subjects experiencing adverse events (AEs) was 60% for PBO and 13-50% for Compound 21 / 3 in the SAD cohort (n=50), and 40% and 13-88%, respectively, in the MAD cohort (n=50). All AEs were mild, except for an unrelated Grade 2 thrombophlebitis in a subject receiving 2 mg of Compound 21 / 3. Compound 21 / 3 was rapidly absorbed (Tmax 2-4 hours) with a short steady-state half-life (T1 / 2 approximately 1.5-2.5 hours) and low maximum plasma concentrations (Cmax <7 ng / mL), consistent with rapid hepatic uptake. With fed administration, the AUC and Cmax of Compound 21 / 3 increased less than dose-proportionally and were 25-50% lower on Day 1 versus Day 14. With fasted administration, exposure was similar on Days 1 and 14 and approximately 3-fold higher than with fed administration. Significant dose-dependent decreases in serum triglycerides, total and LDL-C, total and small LDL particles, and the TG / HDL-C ratio, but not HDL-C, were observed with Compound 21 / 3 (Figures 13A-13H). In Figures 13A-13H, graphical representations show the median relative change (%) of pre-dose NMR Lipoprofile® parameters from Day 1 to Day 14. * indicates a change from baseline vs. placebo by Mann-Whitney test (p<0.05). Also shown are the combined Compound 21 / 3 6 mg fed and fasted groups (N=16), the Compound 21 / 3 0.5, 2, and 12 mg groups (N=8 each), and the combined placebo group (N=10).

[0334] Figure 13A shows the relative change (%) in triglycerides from day 1 to day 14 during the MAD phase of the study. Figure 13B shows the relative change (%) in total cholesterol from day 1 to day 14 during the MAD phase of the study. Figure 13C shows the relative change (%) in HDL-C from day 1 to day 14 during the MAD phase of the study. Figure 13D shows the relative change (%) in TG / HDL-C ratio from day 1 to day 14 during the MAD phase of the study. Figure 13E shows the relative change (%) in LDL-C from day 1 to day 14 during the MAD phase of the study. Figure 13F shows the relative change (%) in LDL particles from day 1 to day 14 during the MAD phase of the study. Figure 13G shows the relative change (%) in small LDL particles from day 1 to day 14 during the MAD phase of the study. FIG. 13H shows the relative change (%) in apoB from day 1 to day 14 during the MAD phase of the study.

[0335] In the MAD study, compound 21 / 3 reduces plasma apoC3 (ApoC3) and ANGPTL3, but does not affect peripheral RCT. Figure 14A shows the apoC3 (ApoC3) levels according to the dose of compound 21 / 3 and placebo from day 1 to day 14. Figure 14B shows the ANGPTL3 levels according to the dose of compound 21 / 3 and placebo from day 1 to day 14. Figure 14C shows the RCT gene levels according to the dose of compound 21 / 3 and placebo.

[0336] Reduction of apoC3 (ApoC3) and ANGTPL3 is expected to enhance lipoprotein lipase (LPL)-mediated clearance of triglyceride-rich lipoproteins. Compound 21 / 3 did not affect the expression of LXR target genes in PBMCs, including the RCT genes ABCA1 / ABCG1.

[0337] The MAD test demonstrates: Single and multiple daily doses of compound 21 / 3, a liver-targeted LXR inverse agonist, up to 20 mg / day for 14 days were safe and well tolerated in healthy subjects. The liver-targeted pharmacology of compound 21 / 3 was supported by its short half-life (approximately 1.5–2.5 hours), low systemic exposure, and lack of effect on the expression of genes involved in peripheral reverse cholesterol transport (i.e., ABCA1, ABCG1). Compound 21 / 3 caused significant dose-dependent improvements in atherogenic lipoproteins, including TG, total and LDL-C, LDL particles, and apoB, especially in subjects with elevated baseline values. The tolerability, PK profile, and lipid-lowering benefits of compound 21 / 3 were remarkable.

[0338] Therefore, this study demonstrates that Compound 21 / 3 is safe and well-tolerated in healthy subjects. The tolerability, PK profile, and lipid-lowering benefits of Compound 21 / 3 were remarkable. Compound 21 / 3 can target the liver, resulting in a short half-life and low systemic exposure, which in turn leads to low toxicity. Administration of Compound 21 / 3 resulted in significant dose-dependent improvements in atherogenic lipoproteins, including TG, total and LDL-C, LDL particles, and apoB, especially in subjects with elevated baseline values.

[0339] equivalent While this disclosure has been described in conjunction with the specific embodiments outlined above, many alternatives, modifications, and other variations thereof will be apparent to those skilled in the art, and all such alternatives, modifications, and variations are intended to fall within the spirit and scope of the disclosure.

Claims

1. 1. A method for treating a metabolic disorder associated with dyslipidemia or impaired lipid homeostasis in a subject in need thereof, comprising administering to a subject a compound of formula (I): 【Chemistry 171】 administering to a subject in need of said treatment an effective amount of a compound represented by its glycine conjugates, taurine conjugates, enantiomers, diastereomers, tautomers, N-oxides, solvates, prodrugs, and pharmaceutically acceptable salts; During the ceremony, 【Chemistry 172】 is a fused 5- to 6-membered ring forming a 6-membered aryl or a 5- to 6-membered heteroaryl containing 1-3 heteroatoms independently selected from N, O and S, the ring being unsubstituted or substituted with halogen, CN, SF ５ , NO ２ , C １～６ -Alkyl, oxo, C ０～６ -Alkylene-OR １１ , C ０～６ -alkylene-(3- to 6-membered cycloalkyl), C ０～６ -alkylene-(3- to 6-membered heterocycloalkyl), C ０～６ -Alkylene-S(O) ｎ R １１ , C ０～６ -Alkylene-NR １１ S (O) ２ R １１ , C ０～６ -Alkylene-S(O) ２ NR １１ R １２ , C ０～６ -Alkylene-NR １１ S (O) ２ NR １１ R １２ , C ０～６ -Alkylene-CO ２ R １１ , O-C １～６ -Alkylene-CO ２ R １１ , C ０～６ -Alkylene-O-COR １１ , C ０～６ -Alkylene-CONR １１ R １２ , C ０～６ -Alkylene-NR １１ -COR １１ , C ０～６ -Alkylene-NR １１ -CONR １１ R １２ , C ０～６ -Alkylene-O-CONR １１ R １２ , C ０～６ -Alkylene-NR １１ -CO ２ R １１ and C ０～６ -Alkylene-NR １１ R １２ and is substituted with 1 to 4 substituents independently selected from the group consisting of: wherein alkyl, alkylene, cycloalkyl, and heterocycloalkyl are unsubstituted or substituted with halogen, CN, oxo, hydroxy, CO ２ H, CO ２ -C １～４ -Alkyl, CONHCH ２ CO ２ H, CONH(CH ２ ) ２ SO ３ H, C １～４ -Alkyl, halo-C １～４ -alkyl, O—C １～４ -Alkyl and O-halo-C １～４ -substituted with 1 to 6 substituents independently selected from alkyl; wherein two adjacent substituents on the aryl or heteroaryl moiety may form a 5-8 membered partially unsaturated ring which may contain 1-3 heteroatoms independently selected from O, S or N; The newly formed ring may be unsubstituted or may contain halogen, CN, C １～４ -Alkyl, halo-C １～４ -alkyl, 3- to 6-membered cycloalkyl, halo-(3- to 6-membered cycloalkyl), 3- to 6-membered heterocycloalkyl, halo-(3- to 6-membered heterocycloalkyl), OH, oxo, CO ２ H, CO ２ -C １～４ -Alkyl, CONHCH ２ CO ２ H, CONH(CH ２ ) ２ SO ３ H, O-C １～４ -Alkyl and O-halo-C １～４ -substituted with 1 to 3 substituents independently selected from alkyl; 【Chemistry 173】 is selected from the group consisting of 3- to 10-membered cycloalkyl, 3- to 10-membered heterocycloalkyl containing 1-3 heteroatoms independently selected from N, O and S, 6- to 14-membered aryl, and 5- to 14-membered heteroaryl containing 1-4 heteroatoms independently selected from N, O and S; wherein cycloalkyl, heterocycloalkyl, aryl and heteroaryl are unsubstituted or substituted with halogen, CN, SF ５ , NO ２ , oxo, C １～４ -Alkyl, C ０～６ -Alkylene-OR ２１ , C ０～６ -alkylene-(3- to 6-membered cycloalkyl), C ０－６ -alkylene-(3- to 6-membered heterocycloalkyl), C ０～６ -Alkylene-S(O) ｎ R ２１ , C ０～６ -Alkylene-NR ２１ S (O) ２ R ２１ , C ０～６ -Alkylene-S(O) ２ NR ２１ R ２２ , C ０～６ -Alkylene-NR ２１ S (O) ２ NR ２１ R ２２ , C ０～６ -Alkylene-CO ２ R ２１ , O-C １～６ -Alkylene-CO ２ R ２１ , C ０～６ -Alkylene-O-COR ２１ , C ０～６ -Alkylene-CONR ２１ R ２２ , C ０～６ -Alkylene-NR ２１ -COR ２１ , C ０～６ -Alkylene-NR ２１ -CONR ２１ R ２２ , C ０～６ -Alkylene-O-CONR ２１ R ２２ , C ０～６ -Alkylene-NR ２１ -CO ２ R ２１ and C ０～６ -Alkylene-NR ２１ R ２２ and is substituted with 1 to 6 substituents independently selected from the group consisting of: wherein alkyl, alkylene, cycloalkyl and heterocycloalkyl are unsubstituted or substituted with halogen, CN, oxo, hydroxy, CO ２ H, CO ２ -C １～４ -Alkyl, CONHCH ２ CO ２ H, CONH(CH ２ ) ２ SO ３ H, C １～４ -Alkyl, halo-C １～４ -alkyl, O—C １～４ -Alkyl and O-halo-C １～４ -substituted with 1 to 6 substituents independently selected from alkyl; wherein two adjacent substituents on the aryl or heteroaryl moiety may form a 5-8 membered partially unsaturated ring which may contain 1-3 heteroatoms independently selected from O, S or N; This further ring may be unsubstituted or may be substituted with halogen, CN, oxo, OH, CO ２ H, CO ２ -C １～４ -Alkyl, CONHCH ２ CO ２ H, CONH(CH ２ ) ２ SO ３ H, C １～４ -Alkyl, halo-C １～４ -alkyl, O—C １～４ -Alkyl and O-halo-C １～４ -substituted with 1 to 4 substituents independently selected from alkyl; wherein two adjacent substituents on the cycloalkyl or heterocycloalkyl moiety may form a 5-6 membered unsaturated ring which may contain 1 to 3 heteroatoms independently selected from O, S or N; This further ring may be unsubstituted or may be substituted with halogen, CN, oxo, OH, CO ２ H, CO ２ -C １～４ -Alkyl, CONHCH ２ CO ２ H, CONH(CH ２ ) ２ SO ３ H, C １～４ -Alkyl, halo-C １～４ -alkyl, O—C １～４ -Alkyl and O-halo-C １～４ -substituted with 1 to 4 substituents independently selected from alkyl; 【Chemistry 174】 is selected from the group consisting of 6- or 10-membered aryl and 5- to 10-membered heteroaryl containing 1-3 heteroatoms independently selected from N, O and S; wherein cycloalkyl, heterocycloalkyl, aryl and heteroaryl are unsubstituted or substituted with halogen, CN, SF ５ , NO ２ , oxo, C １～４ -Alkyl, C ０～６ -Alkylene-OR ３１ , C ０～６ -alkylene-(3- to 6-membered cycloalkyl), C ０～６ -alkylene-(3- to 6-membered heterocycloalkyl), C ０～６ -alkylene-(6-membered aryl), C ０～６ -alkylene-(5- to 6-membered heteroaryl), C ０～６ -Alkylene-S(O) ｎ R ３１ , C ０～６ -Alkylene-NR ３１ S (O) ２ R ３１ , C ０～６ -Alkylene-S(O) ２ NR ３１ R ３２ , C ０～６ -Alkylene-NR ３１ S (O) ２ NR ３１ R ３２ , C ０～６ -Alkylene-CO ２ R ３１ , O-C １～６ -Alkylene-CO ２ R ３１ , C ０～６ -Alkylene-O-COR ３１ , C ０～６ -Alkylene-CONR ３１ R ３２ , C ０～６ -Alkylene-NR ３１ -COR ３１ , C ０～６ -Alkylene-NR ３１ -CONR ３１ R ３２ , C ０～６ -Alkylene-O-CONR ３１ R ３２ , C ０～６ -Alkylene-NR ３１ -CO ２ R ３１ and C ０～６ -Alkylene-NR ３１ R ３２ and is substituted with 1 to 4 substituents independently selected from the group consisting of: wherein alkyl, alkylene, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are unsubstituted or substituted with halogen, CN, oxo, hydroxy, CO ２ H, CO ２ -C １～４ -Alkyl, CONHCH ２ CO ２ H, CONH(CH ２ ) ２ SO ３ H, C １～４ -Alkyl, halo-C １～４ -alkyl, O—C １～４ -Alkyl and O-halo-C １～４ -substituted with 1 to 6 substituents independently selected from alkyl; wherein two adjacent substituents on the aryl or heteroaryl moiety may form a 5-8 membered partially unsaturated ring which may contain 1-3 heteroatoms independently selected from O, S or N; This further ring may be unsubstituted or may be substituted with halogen, CN, oxo, OH, CO ２ H, CO ２ -C １～４ -Alkyl, CONHCH ２ CO ２ H, CONH(CH ２ ) ２ SO ３ H, C １～４ -Alkyl, halo-C １～４ -alkyl, O—C １～４ -Alkyl and O-halo-C １～４ -substituted with 1 to 4 substituents independently selected from alkyl; 【Chemistry 175】 is selected from the group consisting of 3- to 10-membered cycloalkyl, 3- to 10-membered heterocycloalkyl containing 1-3 heteroatoms independently selected from N, O and S, 6- to 14-membered aryl, and 5- to 14-membered heteroaryl containing 1-4 heteroatoms independently selected from N, O and S; wherein cycloalkyl, heterocycloalkyl, aryl and heteroaryl are unsubstituted or substituted with halogen, CN, SF ５ , NO ２ , oxo, C １～４ -Alkyl, C ０～６ -Alkylene-OR ２１ , C ０～６ -alkylene-(3- to 6-membered cycloalkyl), C ０～６ -alkylene-(3- to 6-membered heterocycloalkyl), C ０～６ -Alkylene-S(O) ｎ R ２１ , C ０～６ -Alkylene-NR ２１ S (O) ２ R ２１ , C ０～６ -Alkylene-S(O) ２ NR ２１ R ２２ , C ０～６ -Alkylene-NR ２１ S (O) ２ NR ２１ R ２２ , C ０～６ -Alkylene-CR ４１ (=N-OR ４１ ), C ０～６ -Alkylene-CO ２ R ２１ , O-C １～６ -Alkylene-CO ２ R ２１ , C ０～６ -Alkylene-O-COR ２１ , C ０～６ -Alkylene-CONR ２１ R ２２ , C ０～６ -Alkylene-NR ２１ -COR ２１ , C ０～６ -Alkylene-NR ２１ -CONR ２１ R ２２ , C ０～６ -Alkylene-O-CONR ２１ R ２２ , C ０～６ -Alkylene-NR ２１ -CO ２ R ２１ and C ０～６ -Alkylene-NR ２１ R ２２ and is substituted with 1 to 6 substituents independently selected from the group consisting of: wherein alkyl, alkylene, cycloalkyl and heterocycloalkyl are unsubstituted or substituted with halogen, CN, oxo, hydroxy, CO ２ H, CO ２ -C １～４ -Alkyl, CONHCH ２ CO ２ H, CONH(CH ２ ) ２ SO ３ H, CO-OC １～４ -Alkyl, C １～４ -Alkyl, halo-C １～４ -alkyl, O—C １～４ -Alkyl and O-halo-C １～４ -substituted with 1 to 6 substituents independently selected from alkyl; wherein two adjacent substituents on the aryl or heteroaryl moiety may form a 5-8 membered partially unsaturated ring which may contain 1-3 heteroatoms independently selected from O, S or N; This further ring may be unsubstituted or may be substituted with halogen, CN, oxo, OH, CO ２ H, CO ２ -C １～４ -Alkyl, CONHCH ２ CO ２ H, CONH(CH ２ ) ２ SO ３ H, C １～４ -Alkyl, halo-C １～４ -alkyl, O—C １～４ -Alkyl and O-halo-C １～４ -substituted with 1 to 4 substituents independently selected from alkyl; wherein two adjacent substituents on the cycloalkyl or heterocycloalkyl moiety may form a 5-6 membered unsaturated ring which may contain 1 to 3 heteroatoms independently selected from O, S or N; This further ring may be unsubstituted or may be substituted with halogen, CN, oxo, OH, CO ２ H, CO ２ -C １～４ -Alkyl, CONHCH ２ CO ２ H, CONH(CH ２ ) ２ SO ３ H, C １～４ -Alkyl, halo-C １～４ -alkyl, O—C １～４ -Alkyl and O-halo-C １～４ -substituted with 1 to 4 substituents independently selected from alkyl; During the ceremony, 【Chemistry 176】 teeth, 【Chemistry 177】 or a further ring fused in a 1,2-orientation, L is a bond, C １～６ - alkylene, C ２～６ -Alkenylene, C ２～６ - selected from the group consisting of alkynylene, 3- to 10-membered cycloalkylene, 3- to 10-membered heterocycloalkylene containing 1-4 heteroatoms independently selected from N, O and S, 6- or 10-membered arylene, and 5- to 10-membered heteroarylene containing 1-4 heteroatoms independently selected from N, O and S; wherein alkylene, alkenylene, alkynylene, cycloalkylene, heterocycloalkylene, arylene and heteroarylene are unsubstituted or substituted with halogen, CN, SF ５ , NO ２ , oxo, C １～４ -Alkyl, C ０～６ -Alkylene-OR ４１ , C ０～６ -alkylene-(3- to 6-membered cycloalkyl), C ０～６ -alkylene-(3- to 6-membered heterocycloalkyl), C ０～６ -Alkylene-S(O) ｎ R ４１ , C ０～６ -Alkylene-NR ４１ S (O) ２ R ４１ , C ０～６ -Alkylene-S(O) ２ NR ４１ R ４２ , C ０～６ -Alkylene-NR ４１ S (O) ２ NR ４１ R ４２ , C ０～６ -Alkylene-CO ２ R ４１ , O-C １～６ -Alkylene-CO ２ R ４１ , C ０～６ -Alkylene-O-COR ４１ , C ０～６ -Alkylene-CONR ４１ R ４２ , C ０～６ -Alkylene-NR ４１ -COR ４１ , C ０～６ -Alkylene-NR ４１ -CONR ４１ R ４２ , C ０～６ -Alkylene-O-CONR ４１ R ４２ , C ０～６ -Alkylene-NR ４１ -CO ２ R ４１ and C ０～６ -Alkylene-NR ４１ R ４２ and is substituted with 1 to 6 substituents independently selected from the group consisting of: wherein alkyl, alkylene, cycloalkyl and heterocycloalkyl are unsubstituted or substituted with halogen, CN, oxo, hydroxy, CO ２ H, CO ２ -C １～４ -Alkyl, CONHCH ２ CO ２ H, CONH(CH ２ ) ２ SO ３ H, C １～４ -Alkyl, halo-C １～４ -alkyl, O—C １～４ -Alkyl and O-halo-C １～４ -substituted with 1 to 6 substituents independently selected from alkyl; wherein two adjacent substituents on the arylene and heteroarylene moieties may form a 5-8 membered partially unsaturated ring which may contain 1 to 3 heteroatoms independently selected from O, S, or N; This further ring may be unsubstituted or may be substituted with halogen, CN, oxo, OH, CO ２ H, CO ２ -C １～４ -Alkyl, C １～４ -Alkyl, halo-C １～４ -alkyl, O—C １～４ -Alkyl and O-halo-C １～４ -substituted with 1 to 4 substituents independently selected from alkyl; R １ is H, halogen, CN, SF ５ , NO ２ , oxo, C １～４ -Alkyl, C ０～６ -Alkylene-OR ４１ , Y.-C. ０～６ -alkylene-(3- to 6-membered cycloalkyl), Y-C ０～６ -alkylene-(3- to 6-membered heterocycloalkyl), Y—C ０～６ -alkylene-(6-membered aryl), Y-C ０～６ -alkylene-(5- to 6-membered heteroaryl), C ０～６ -Alkylene-S(=O)(-R ４１ ) = N-R ７５ , X-C １～６ -Alkylene-S(=O)(-R ４１ ) = N-R ７５ , C ０～６ -Alkylene-S(O) ｎ R ４１ , X-C １～６ -Alkylene-S(O) ｎ R ４１ , C ０～６ -Alkylene-S(=NR ７１ ) R ４１ , X-C １～６ -Alkylene-S(=NR ７１ ) R ４１ , C ０～６ -Alkylene-S(O)(=NR ７１ ) R ４１ , X-C １～６ -Alkylene-S(O)(=NR ７１ ) R ４１ , C ０～６ -Alkylene-S(=NR ７１ ) ２ R ４１ , X-C １～６ -Alkylene-S(=NR ７１ ) ２ R ４１ , C ０～６ -Alkylene-NR ４１ S (O) ２ R ４１ , X-C １～６ -Alkylene-NR ４１ S (O) ２ R ４１ , C ０～６ -Alkylene-S(O) ２ NR ４１ R ４２ , X-C １～６ -Alkylene-S(O) ２ NR ４１ R ４２ , C ０～６ -Alkylene-NR ４１ S (O) ２ NR ４１ R ４２ , X-C １～６ -Alkylene-NR ４１ S (O) ２ NR ４１ R ４２ , C ０～６ -Alkylene-SO ３ R ４１ , X-C １～６ -Alkylene-SO ３ R ４１ , C ０～６ -Alkylene-CO ２ R ４１ , X-C １～６ -Alkylene-CO ２ R ４１ , C ０～６ -Alkylene-O-COR ４１ , X-C １～６ -Alkylene-O-COR ４１ , C ０～６ -Alkylene-CONR ４１ R ４２ , X-C １～６ -Alkylene-CONR ４１ R ４２ , C ０～６ -Alkylene-CONR ４１ OR ４１ , X-C １～６ -Alkylene-CONR ４１ OR ４１ , C ０～６ -Alkylene-CONR ４１ SO ２ R ４１ , X-C １～６ -Alkylene-CONR ４１ SO ２ R ４１ , C ０～６ -Alkylene-NR ４１ -COR ４１ , X-C １～６ -C ０～６ -Alkylene-NR ４１ -COR ４１ , C ０～６ -Alkylene-NR ４１ -CONR ４１ R ４２ , X-C １～６ -Alkylene-NR ４１ -CONR ４１ R ４２ , C ０～６ -Alkylene-O-CONR ４１ R ４２ , X-C １～６ -Alkylene-O-CONR ４１ R ４２ , C ０～６ -Alkylene-NR ４１ -CO ２ R ４１ , X-C １～６ -Alkylene-NR ４１ -CO ２ R ４１ , C ０～６ -Alkylene-NR ４１ R ４２ , X-C １～６ -Alkylene-NR ４１ R ４２ is selected from the group consisting of wherein alkyl, alkylene, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are unsubstituted or substituted with halogen, CN, oxo, hydroxy, CO ２ H, CO ２ -C １～４ -Alkyl, CONHCH ２ CO ２ H, CONH(CH ２ ) ２ SO ３ H, C １～４ -Alkyl, halo-C １～４ -alkyl, O—C １～４ -Alkyl and O-halo-C １～４ -substituted with 1 to 6 substituents independently selected from alkyl; wherein two adjacent substituents on the aryl and heteroaryl moieties may form a 5-8 membered partially unsaturated ring which may contain 1-3 heteroatoms independently selected from O, S or N; This further ring may be unsubstituted or may be substituted with halogen, CN, oxo, OH, CO ２ H, CO ２ -C １～４ -Alkyl, CONHCH ２ CO ２ H, CONH(CH ２ ) ２ SO ３ H, C １～４ -Alkyl, halo-C １～４ -alkyl, O—C １～４ -Alkyl and O-halo-C １～４ -substituted with 1 to 4 substituents independently selected from alkyl; R １１ , R １２ , R ２１ , R ２２ , R ３１ , R ３２ , R ４１ , R ４２ , R ５１ are independently H and C １～４ - alkyl, wherein alkyl is unsubstituted or substituted with halogen, CN, C １～４ -Alkyl, halo-C １～４ -alkyl, 3- to 6-membered cycloalkyl, halo-(3- to 6-membered cycloalkyl), 3- to 6-membered heterocycloalkyl, halo-(3- to 6-membered heterocycloalkyl), OH, oxo, CO ２ H, CO ２ -C １～４ -Alkyl, CONHCH ２ CO ２ H, CONH(CH ２ ) ２ SO ３ H, SO ３ H, O-C １～４ -Alkyl and O-halo-C １～４ -substituted with 1 to 3 substituents independently selected from alkyl; or R １１ and R １２ , R ２１ and R ２２ , R ３１ and R ３２ , R ４１ and R ４２ each, when taken together with the nitrogen to which they are attached, completes a 3- to 6-membered ring containing carbon atoms and optionally containing 1 or 2 heteroatoms independently selected from O, S or N; The newly formed ring is unsubstituted or contains halogen, CN, C １～４ -Alkyl, halo-C １～４ -alkyl, 3- to 6-membered cycloalkyl, halo-(3- to 6-membered cycloalkyl), 3- to 6-membered heterocycloalkyl, halo-(3- to 6-membered heterocycloalkyl), OH, oxo, CO ２ H, CO ２ -C １～４ -Alkyl, CONHCH ２ CO ２ H, CONH(CH ２ ) ２ SO ３ H, SO ３ H, O-C １～４ -Alkyl and O-halo-C １～４ -substituted with 1 to 3 substituents independently selected from alkyl; R ７１ are independently H, CN, NO ２ , C １～４ -alkyl, and C(O)-OC １～４ - alkyl, wherein alkyl is unsubstituted or substituted with halogen, CN, C １～４ -Alkyl, halo-C １～４ -alkyl, 3- to 6-membered cycloalkyl, halo-(3- to 6-membered cycloalkyl), 3- to 6-membered heterocycloalkyl, halo-(3- to 6-membered heterocycloalkyl), OH, oxo, CO ２ H, CO ２ -C １～４ -Alkyl, CONHCH ２ CO ２ H, CONH(CH ２ ) ２ SO ３ H, SO ３ H, O-C １～４ -Alkyl and O-halo-C １～４ -substituted with 1 to 3 substituents independently selected from alkyl; R ７５ are independently １～４ selected from alkyl, 3- to 6-membered cycloalkyl, 3- to 6-membered heterocycloalkyl, 6-membered aryl, and 5- to 6-membered heteroaryl; wherein alkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are unsubstituted or substituted with halogen, CN, Me, Et, CHF ２ , C.F. ３ , OH, oxo, CO ２ H, CONHCH ２ CO ２ H, CONH(CH ２ ) ２ SO ３ H, SO ３ H, OMe, OEt, OCHF ２ and OCF ３ and is substituted with 1 to 3 substituents independently selected from X is independently O, NR ５１ , S(O) ｎ , S (= NR ７１ ), S(O)(=NR ７１ ) and S(=NR ７１ ) ２ is selected from Y is independently a bond, O, NR ５１ , S(O) ｎ , S (= NR ７１ ), S(O)(=NR ７１ ) and S(=NR ７１ ) ２ is selected from n is independently selected from 0 to 2; however, 【Chemistry 178】 The structure of the method is excluded.

2. 1. Use of a compound in the treatment of metabolic disorders associated with dyslipidemia or impaired lipid homeostasis, said compound being represented by formula (I): 【Chemistry 179】 its glycine conjugates, taurine conjugates, enantiomers, diastereomers, tautomers, N-oxides, solvates, prodrugs, and pharmaceutically acceptable salts thereof; During the ceremony, 【Chemistry 180】 is a fused 5- to 6-membered ring forming a 6-membered aryl or a 5- to 6-membered heteroaryl containing 1-3 heteroatoms independently selected from N, O and S, the ring being unsubstituted or substituted with halogen, CN, SF ５ , NO ２ , C １～６ -Alkyl, oxo, C ０～６ -Alkylene-OR １１ , C ０～６ -alkylene-(3- to 6-membered cycloalkyl), C ０～６ -alkylene-(3- to 6-membered heterocycloalkyl), C ０～６ -Alkylene-S(O) ｎ R １１ , C ０～６ -Alkylene-NR １１ S (O) ２ R １１ , C ０～６ -Alkylene-S(O) ２ NR １１ R １２ , C ０～６ -Alkylene-NR １１ S (O) ２ NR １１ R １２ , C ０～６ -Alkylene-CO ２ R １１ , O-C １～６ -Alkylene-CO ２ R １１ , C ０～６ -Alkylene-O-COR １１ , C ０～６ -Alkylene-CONR １１ R １２ , C ０～６ -Alkylene-NR １１ -COR １１ , C ０～６ -Alkylene-NR １１ -CONR １１ R １２ , C ０～６ -Alkylene-O-CONR １１ R １２ , C ０～６ -Alkylene-NR １１ -CO ２ R １１ and C ０～６ -Alkylene-NR １１ R １２ and is substituted with 1 to 4 substituents independently selected from the group consisting of: wherein alkyl, alkylene, cycloalkyl, and heterocycloalkyl are unsubstituted or substituted with halogen, CN, oxo, hydroxy, CO ２ H, CO ２ -C １～４ -Alkyl, CONHCH ２ CO ２ H, CONH(CH ２ ) ２ SO ３ H, C １～４ -Alkyl, halo-C １～４ -alkyl, O—C １～４ -Alkyl and O-halo-C １～４ -substituted with 1 to 6 substituents independently selected from alkyl; wherein two adjacent substituents on the aryl or heteroaryl moiety may form a 5-8 membered partially unsaturated ring which may contain 1-3 heteroatoms independently selected from O, S or N; The newly formed ring may be unsubstituted or may contain halogen, CN, C １～４ -Alkyl, halo-C １～４ -alkyl, 3- to 6-membered cycloalkyl, halo-(3- to 6-membered cycloalkyl), 3- to 6-membered heterocycloalkyl, halo-(3- to 6-membered heterocycloalkyl), OH, oxo, CO ２ H, CO ２ -C １～４ -Alkyl, CONHCH ２ CO ２ H, CONH(CH ２ ) ２ SO ３ H, O-C １～４ -Alkyl and O-halo-C １～４ -substituted with 1 to 3 substituents independently selected from alkyl; 【Chemistry 181】 is selected from the group consisting of 3- to 10-membered cycloalkyl, 3- to 10-membered heterocycloalkyl containing 1-3 heteroatoms independently selected from N, O and S, 6- to 14-membered aryl, and 5- to 14-membered heteroaryl containing 1-4 heteroatoms independently selected from N, O and S; wherein cycloalkyl, heterocycloalkyl, aryl and heteroaryl are unsubstituted or substituted with halogen, CN, SF ５ , NO ２ , oxo, C １～４ -Alkyl, C ０～６ -Alkylene-OR ２１ , C ０～６ -alkylene-(3- to 6-membered cycloalkyl), C ０－６ -alkylene-(3- to 6-membered heterocycloalkyl), C ０～６ -Alkylene-S(O) ｎ R ２１ , C ０～６ -Alkylene-NR ２１ S (O) ２ R ２１ , C ０～６ -Alkylene-S(O) ２ NR ２１ R ２２ , C ０～６ -Alkylene-NR ２１ S (O) ２ NR ２１ R ２２ , C ０～６ -Alkylene-CO ２ R ２１ , O-C １～６ -Alkylene-CO ２ R ２１ , C ０～６ -Alkylene-O-COR ２１ , C ０～６ -Alkylene-CONR ２１ R ２２ , C ０～６ -Alkylene-NR ２１ -COR ２１ , C ０～６ -Alkylene-NR ２１ -CONR ２１ R ２２ , C ０～６ -Alkylene-O-CONR ２１ R ２２ , C ０～６ -Alkylene-NR ２１ -CO ２ R ２１ and C ０～６ -Alkylene-NR ２１ R ２２ and is substituted with 1 to 6 substituents independently selected from the group consisting of: wherein alkyl, alkylene, cycloalkyl and heterocycloalkyl are unsubstituted or substituted with halogen, CN, oxo, hydroxy, CO ２ H, CO ２ -C １～４ -Alkyl, CONHCH ２ CO ２ H, CONH(CH ２ ) ２ SO ３ H, C １～４ -Alkyl, halo-C １～４ -alkyl, O—C １～４ -Alkyl and O-halo-C １～４ -substituted with 1 to 6 substituents independently selected from alkyl; wherein two adjacent substituents on the aryl or heteroaryl moiety may form a 5-8 membered partially unsaturated ring which may contain 1-3 heteroatoms independently selected from O, S or N; This further ring may be unsubstituted or may be substituted with halogen, CN, oxo, OH, CO ２ H, CO ２ -C １～４ -Alkyl, CONHCH ２ CO ２ H, CONH(CH ２ ) ２ SO ３ H, C １～４ -Alkyl, halo-C １～４ -alkyl, O—C １～４ -Alkyl and O-halo-C １～４ -substituted with 1 to 4 substituents independently selected from alkyl; wherein two adjacent substituents on the cycloalkyl or heterocycloalkyl moiety may form a 5-6 membered unsaturated ring which may contain 1 to 3 heteroatoms independently selected from O, S or N; This further ring may be unsubstituted or may be substituted with halogen, CN, oxo, OH, CO ２ H, CO ２ -C １～４ -Alkyl, CONHCH ２ CO ２ H, CONH(CH ２ ) ２ SO ３ H, C １～４ -Alkyl, halo-C １～４ -alkyl, O—C １～４ -Alkyl and O-halo-C １～４ -substituted with 1 to 4 substituents independently selected from alkyl; 【Chemistry 182】 is selected from the group consisting of 6- or 10-membered aryl and 5- to 10-membered heteroaryl containing 1-3 heteroatoms independently selected from N, O and S; wherein cycloalkyl, heterocycloalkyl, aryl and heteroaryl are unsubstituted or substituted with halogen, CN, SF ５ , NO ２ , oxo, C １～４ -Alkyl, C ０～６ -Alkylene-OR ３１ , C ０～６ -alkylene-(3- to 6-membered cycloalkyl), C ０～６ -alkylene-(3- to 6-membered heterocycloalkyl), C ０～６ -alkylene-(6-membered aryl), C ０～６ -alkylene-(5- to 6-membered heteroaryl), C ０～６ -Alkylene-S(O) ｎ R ３１ , C ０～６ -Alkylene-NR ３１ S (O) ２ R ３１ , C ０～６ -Alkylene-S(O) ２ NR ３１ R ３２ , C ０～６ -Alkylene-NR ３１ S (O) ２ NR ３１ R ３２ , C ０～６ -Alkylene-CO ２ R ３１ , O-C １～６ -Alkylene-CO ２ R ３１ , C ０～６ -Alkylene-O-COR ３１ , C ０～６ -Alkylene-CONR ３１ R ３２ , C ０～６ -Alkylene-NR ３１ -COR ３１ , C ０～６ -Alkylene-NR ３１ -CONR ３１ R ３２ , C ０～６ -Alkylene-O-CONR ３１ R ３２ , C ０～６ -Alkylene-NR ３１ -CO ２ R ３１ and C ０～６ -Alkylene-NR ３１ R ３２ and is substituted with 1 to 4 substituents independently selected from the group consisting of: wherein alkyl, alkylene, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are unsubstituted or substituted with halogen, CN, oxo, hydroxy, CO ２ H, CO ２ -C １～４ -Alkyl, CONHCH ２ CO ２ H, CONH(CH ２ ) ２ SO ３ H, C １～４ -Alkyl, halo-C １～４ -alkyl, O—C １～４ -Alkyl and O-halo-C １～４ -substituted with 1 to 6 substituents independently selected from alkyl; wherein two adjacent substituents on the aryl or heteroaryl moiety may form a 5-8 membered partially unsaturated ring which may contain 1-3 heteroatoms independently selected from O, S or N; This further ring may be unsubstituted or may be substituted with halogen, CN, oxo, OH, CO ２ H, CO ２ -C １～４ -Alkyl, CONHCH ２ CO ２ H, CONH(CH ２ ) ２ SO ３ H, C １～４ -Alkyl, halo-C １～４ -alkyl, O—C １～４ -Alkyl and O-halo-C １～４ -substituted with 1 to 4 substituents independently selected from alkyl; 【Chemistry 183】 is selected from the group consisting of 3- to 10-membered cycloalkyl, 3- to 10-membered heterocycloalkyl containing 1-3 heteroatoms independently selected from N, O and S, 6- to 14-membered aryl, and 5- to 14-membered heteroaryl containing 1-4 heteroatoms independently selected from N, O and S; wherein cycloalkyl, heterocycloalkyl, aryl and heteroaryl are unsubstituted or substituted with halogen, CN, SF ５ , NO ２ , oxo, C １～４ -Alkyl, C ０～６ -Alkylene-OR ２１ , C ０～６ -alkylene-(3- to 6-membered cycloalkyl), C ０～６ -alkylene-(3- to 6-membered heterocycloalkyl), C ０～６ -Alkylene-S(O) ｎ R ２１ , C ０～６ -Alkylene-NR ２１ S (O) ２ R ２１ , C ０～６ -Alkylene-S(O) ２ NR ２１ R ２２ , C ０～６ -Alkylene-NR ２１ S (O) ２ NR ２１ R ２２ , C ０～６ -Alkylene-CR ４１ (=N-OR ４１ ), C ０～６ -Alkylene-CO ２ R ２１ , O-C １～６ -Alkylene-CO ２ R ２１ , C ０～６ -Alkylene-O-COR ２１ , C ０～６ -Alkylene-CONR ２１ R ２２ , C ０～６ -Alkylene-NR ２１ -COR ２１ , C ０～６ -Alkylene-NR ２１ -CONR ２１ R ２２ , C ０～６ -Alkylene-O-CONR ２１ R ２２ , C ０～６ -Alkylene-NR ２１ -CO ２ R ２１ and C ０～６ -Alkylene-NR ２１ R ２２ and is substituted with 1 to 6 substituents independently selected from the group consisting of: wherein alkyl, alkylene, cycloalkyl and heterocycloalkyl are unsubstituted or substituted with halogen, CN, oxo, hydroxy, CO ２ H, CO ２ -C １～４ -Alkyl, CONHCH ２ CO ２ H, CONH(CH ２ ) ２ SO ３ H, CO-OC １～４ -Alkyl, C １～４ -Alkyl, halo-C １～４ -alkyl, O—C １～４ -Alkyl and O-halo-C １～４ -substituted with 1 to 6 substituents independently selected from alkyl; wherein two adjacent substituents on the aryl or heteroaryl moiety may form a 5-8 membered partially unsaturated ring which may contain 1-3 heteroatoms independently selected from O, S or N; This further ring may be unsubstituted or may be substituted with halogen, CN, oxo, OH, CO ２ H, CO ２ -C １～４ -Alkyl, CONHCH ２ CO ２ H, CONH(CH ２ ) ２ SO ３ H, C １～４ -Alkyl, halo-C １～４ -alkyl, O—C １～４ -Alkyl and O-halo-C １～４ -substituted with 1 to 4 substituents independently selected from alkyl; wherein two adjacent substituents on the cycloalkyl or heterocycloalkyl moiety may form a 5-6 membered unsaturated ring which may contain 1 to 3 heteroatoms independently selected from O, S or N; This further ring may be unsubstituted or may be substituted with halogen, CN, oxo, OH, CO ２ H, CO ２ -C １～４ -Alkyl, CONHCH ２ CO ２ H, CONH(CH ２ ) ２ SO ３ H, C １～４ -Alkyl, halo-C １～４ -alkyl, O—C １～４ -Alkyl and O-halo-C １～４ -substituted with 1 to 4 substituents independently selected from alkyl; During the ceremony, 【Chemistry 184】 teeth, 【Chemistry 185】 or a further ring fused in a 1,2-orientation, L is a bond, C １～６ - alkylene, C ２～６ -Alkenylene, C ２～６ - selected from the group consisting of alkynylene, 3- to 10-membered cycloalkylene, 3- to 10-membered heterocycloalkylene containing 1-4 heteroatoms independently selected from N, O and S, 6- or 10-membered arylene, and 5- to 10-membered heteroarylene containing 1-4 heteroatoms independently selected from N, O and S; wherein alkylene, alkenylene, alkynylene, cycloalkylene, heterocycloalkylene, arylene and heteroarylene are unsubstituted or substituted with halogen, CN, SF ５ , NO ２ , oxo, C １～４ -Alkyl, C ０～６ -Alkylene-OR ４１ , C ０～６ -alkylene-(3- to 6-membered cycloalkyl), C ０～６ -alkylene-(3- to 6-membered heterocycloalkyl), C ０～６ -Alkylene-S(O) ｎ R ４１ , C ０～６ -Alkylene-NR ４１ S (O) ２ R ４１ , C ０～６ -Alkylene-S(O) ２ NR ４１ R ４２ , C ０～６ -Alkylene-NR ４１ S (O) ２ NR ４１ R ４２ , C ０～６ -Alkylene-CO ２ R ４１ , O-C １～６ -Alkylene-CO ２ R ４１ , C ０～６ -Alkylene-O-COR ４１ , C ０～６ -Alkylene-CONR ４１ R ４２ , C ０～６ -Alkylene-NR ４１ -COR ４１ , C ０～６ -Alkylene-NR ４１ -CONR ４１ R ４２ , C ０～６ -Alkylene-O-CONR ４１ R ４２ , C ０～６ -Alkylene-NR ４１ -CO ２ R ４１ and C ０～６ -Alkylene-NR ４１ R ４２ and is substituted with 1 to 6 substituents independently selected from the group consisting of: wherein alkyl, alkylene, cycloalkyl and heterocycloalkyl are unsubstituted or substituted with halogen, CN, oxo, hydroxy, CO ２ H, CO ２ -C １～４ -Alkyl, CONHCH ２ CO ２ H, CONH(CH ２ ) ２ SO ３ H, C １～４ -Alkyl, halo-C １～４ -alkyl, O—C １～４ -Alkyl and O-halo-C １～４ -substituted with 1 to 6 substituents independently selected from alkyl; wherein two adjacent substituents on the arylene and heteroarylene moieties may form a 5-8 membered partially unsaturated ring which may contain 1 to 3 heteroatoms independently selected from O, S, or N; This further ring may be unsubstituted or may be substituted with halogen, CN, oxo, OH, CO ２ H, CO ２ -C １～４ -Alkyl, C １～４ -Alkyl, halo-C １～４ -alkyl, O—C １～４ -Alkyl and O-halo-C １～４ -substituted with 1 to 4 substituents independently selected from alkyl; R １ is H, halogen, CN, SF ５ , NO ２ , oxo, C １～４ -Alkyl, C ０～６ -Alkylene-OR ４１ , Y.-C. ０～６ -alkylene-(3- to 6-membered cycloalkyl), Y-C ０～６ -alkylene-(3- to 6-membered heterocycloalkyl), Y—C ０～６ -alkylene-(6-membered aryl), Y-C ０～６ -alkylene-(5- to 6-membered heteroaryl), C ０～６ -Alkylene-S(=O)(-R ４１ ) = N-R ７５ , X-C １～６ -Alkylene-S(=O)(-R ４１ ) = N-R ７５ , C ０～６ -Alkylene-S(O) ｎ R ４１ , X-C １～６ -Alkylene-S(O) ｎ R ４１ , C ０～６ -Alkylene-S(=NR ７１ ) R ４１ , X-C １～６ -Alkylene-S(=NR ７１ ) R ４１ , C ０～６ -Alkylene-S(O)(=NR ７１ ) R ４１ , X-C １～６ -Alkylene-S(O)(=NR ７１ ) R ４１ , C ０～６ -Alkylene-S(=NR ７１ ) ２ R ４１ , X-C １～６ -Alkylene-S(=NR ７１ ) ２ R ４１ , C ０～６ -Alkylene-NR ４１ S (O) ２ R ４１ , X-C １～６ -Alkylene-NR ４１ S (O) ２ R ４１ , C ０～６ -Alkylene-S(O) ２ NR ４１ R ４２ , X-C １～６ -Alkylene-S(O) ２ NR ４１ R ４２ , C ０～６ -Alkylene-NR ４１ S (O) ２ NR ４１ R ４２ , X-C １～６ -Alkylene-NR ４１ S (O) ２ NR ４１ R ４２ , C ０～６ -Alkylene-SO ３ R ４１ , X-C １～６ -Alkylene-SO ３ R ４１ , C ０～６ -Alkylene-CO ２ R ４１ , X-C １～６ -Alkylene-CO ２ R ４１ , C ０～６ -Alkylene-O-COR ４１ , X-C １～６ -Alkylene-O-COR ４１ , C ０～６ -Alkylene-CONR ４１ R ４２ , X-C １～６ -Alkylene-CONR ４１ R ４２ , C ０～６ -Alkylene-CONR ４１ OR ４１ , X-C １～６ -Alkylene-CONR ４１ OR ４１ , C ０～６ -Alkylene-CONR ４１ SO ２ R ４１ , X-C １～６ -Alkylene-CONR ４１ SO ２ R ４１ , C ０～６ -Alkylene-NR ４１ -COR ４１ , X-C １～６ -C ０～６ -Alkylene-NR ４１ -COR ４１ , C ０～６ -Alkylene-NR ４１ -CONR ４１ R ４２ , X-C １～６ -Alkylene-NR ４１ -CONR ４１ R ４２ , C ０～６ -Alkylene-O-CONR ４１ R ４２ , X-C １～６ -Alkylene-O-CONR ４１ R ４２ , C ０～６ -Alkylene-NR ４１ -CO ２ R ４１ , X-C １～６ -Alkylene-NR ４１ -CO ２ R ４１ , C ０～６ -Alkylene-NR ４１ R ４２ , X-C １～６ -Alkylene-NR ４１ R ４２ is selected from the group consisting of wherein alkyl, alkylene, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are unsubstituted or substituted with halogen, CN, oxo, hydroxy, CO ２ H, CO ２ -C １～４ -Alkyl, CONHCH ２ CO ２ H, CONH(CH ２ ) ２ SO ３ H, C １～４ -Alkyl, halo-C １～４ -alkyl, O—C １～４ -Alkyl and O-halo-C １～４ -substituted with 1 to 6 substituents independently selected from alkyl; wherein two adjacent substituents on the aryl and heteroaryl moieties may form a 5-8 membered partially unsaturated ring which may contain 1-3 heteroatoms independently selected from O, S or N; This further ring may be unsubstituted or may be substituted with halogen, CN, oxo, OH, CO ２ H, CO ２ -C １～４ -Alkyl, CONHCH ２ CO ２ H, CONH(CH ２ ) ２ SO ３ H, C １～４ -Alkyl, halo-C １～４ -alkyl, O—C １～４ -Alkyl and O-halo-C １～４ -substituted with 1 to 4 substituents independently selected from alkyl; R １１ , R １２ , R ２１ , R ２２ , R ３１ , R ３２ , R ４１ , R ４２ , R ５１ are independently H and C １～４ - alkyl, wherein alkyl is unsubstituted or substituted with halogen, CN, C １～４ -Alkyl, halo-C １～４ -alkyl, 3- to 6-membered cycloalkyl, halo-(3- to 6-membered cycloalkyl), 3- to 6-membered heterocycloalkyl, halo-(3- to 6-membered heterocycloalkyl), OH, oxo, CO ２ H, CO ２ -C １～４ -Alkyl, CONHCH ２ CO ２ H, CONH(CH ２ ) ２ SO ３ H, SO ３ H, O-C １～４ -Alkyl and O-halo-C １～４ -substituted with 1 to 3 substituents independently selected from alkyl; or R １１ and R １２ , R ２１ and R ２２ , R ３１ and R ３２ , R ４１ and R ４２ each, when taken together with the nitrogen to which they are attached, completes a 3- to 6-membered ring containing carbon atoms and optionally containing 1 or 2 heteroatoms independently selected from O, S or N; The newly formed ring is unsubstituted or contains halogen, CN, C １～４ -Alkyl, halo-C １～４ -alkyl, 3- to 6-membered cycloalkyl, halo-(3- to 6-membered cycloalkyl), 3- to 6-membered heterocycloalkyl, halo-(3- to 6-membered heterocycloalkyl), OH, oxo, CO ２ H, CO ２ -C １～４ -Alkyl, CONHCH ２ CO ２ H, CONH(CH ２ ) ２ SO ３ H, SO ３ H, O-C １～４ -Alkyl and O-halo-C １～４ -substituted with 1 to 3 substituents independently selected from alkyl; R ７１ are independently H, CN, NO ２ , C １～４ -alkyl, and C(O)-OC １～４ - alkyl, wherein alkyl is unsubstituted or substituted with halogen, CN, C １～４ -Alkyl, halo-C １～４ -alkyl, 3- to 6-membered cycloalkyl, halo-(3- to 6-membered cycloalkyl), 3- to 6-membered heterocycloalkyl, halo-(3- to 6-membered heterocycloalkyl), OH, oxo, CO ２ H, CO ２ -C １～４ -Alkyl, CONHCH ２ CO ２ H, CONH(CH ２ ) ２ SO ３ H, SO ３ H, O-C １～４ -Alkyl and O-halo-C １～４ -substituted with 1 to 3 substituents independently selected from alkyl; R ７５ are independently １～４ selected from alkyl, 3- to 6-membered cycloalkyl, 3- to 6-membered heterocycloalkyl, 6-membered aryl, and 5- to 6-membered heteroaryl; wherein alkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are unsubstituted or substituted with halogen, CN, Me, Et, CHF ２ , C.F. ３ , OH, oxo, CO ２ H, CONHCH ２ CO ２ H, CONH(CH ２ ) ２ SO ３ H, SO ３ H, OMe, OEt, OCHF ２ and OCF ３ and is substituted with 1 to 3 substituents independently selected from X is independently O, NR ５１ , S(O) ｎ , S (= NR ７１ ), S(O)(=NR ７１ ) and S(=NR ７１ ) ２ is selected from Y is independently a bond, O, NR ５１ , S(O) ｎ , S (= NR ７１ ), S(O)(=NR ７１ ) and S(=NR ７１ ) ２ is selected from n is independently selected from 0 to 2; however, 【Chemical 186】 The structure of the use is excluded.

3. 1. Use of a compound in the manufacture of a medicament for treating a metabolic disorder associated with dyslipidemia or impaired lipid homeostasis, said compound comprising a compound of formula (I): 【Chemistry 187】 its glycine conjugates, taurine conjugates, enantiomers, diastereomers, 213 tautomers, N-oxides, solvates, prodrugs, and pharmaceutically acceptable salts; During the ceremony, 【Chemical 188】 is a fused 5- to 6-membered ring forming a 6-membered aryl or a 5- to 6-membered heteroaryl containing 1-3 heteroatoms independently selected from N, O and S, the ring being unsubstituted or substituted with halogen, CN, SF ５ , NO ２ , C １～６ -Alkyl, oxo, C ０～６ -Alkylene-OR １１ , C ０～６ -alkylene-(3- to 6-membered cycloalkyl), C ０～６ -alkylene-(3- to 6-membered heterocycloalkyl), C ０～６ -Alkylene-S(O) ｎ R １１ , C ０～６ -Alkylene-NR １１ S (O) ２ R １１ , C ０～６ -Alkylene-S(O) ２ NR １１ R １２ , C ０～６ -Alkylene-NR １１ S (O) ２ NR １１ R １２ , C ０～６ -Alkylene-CO ２ R １１ , O-C １～６ -Alkylene-CO ２ R １１ , C ０～６ -Alkylene-O-COR １１ , C ０～６ -Alkylene-CONR １１ R １２ , C ０～６ -Alkylene-NR １１ -COR １１ , C ０～６ -Alkylene-NR １１ -CONR １１ R １２ , C ０～６ -Alkylene-O-CONR １１ R １２ , C ０～６ -Alkylene-NR １１ -CO ２ R １１ and C ０～６ -Alkylene-NR １１ R １２ and is substituted with 1 to 4 substituents independently selected from the group consisting of: wherein alkyl, alkylene, cycloalkyl, and heterocycloalkyl are unsubstituted or substituted with halogen, CN, oxo, hydroxy, CO ２ H, CO ２ -C １～４ -Alkyl, CONHCH ２ CO ２ H, CONH(CH ２ ) ２ SO ３ H, C １～４ -Alkyl, halo-C １～４ -alkyl, O—C １～４ -Alkyl and O-halo-C １～４ -substituted with 1 to 6 substituents independently selected from alkyl; wherein two adjacent substituents on the aryl or heteroaryl moiety may form a 5-8 membered partially unsaturated ring which may contain 1-3 heteroatoms independently selected from O, S or N; The newly formed ring may be unsubstituted or may contain halogen, CN, C １～４ -Alkyl, halo-C １～４ -alkyl, 3- to 6-membered cycloalkyl, halo-(3- to 6-membered cycloalkyl), 3- to 6-membered heterocycloalkyl, halo-(3- to 6-membered heterocycloalkyl), OH, oxo, CO ２ H, CO ２ -C １～４ -Alkyl, CONHCH ２ CO ２ H, CONH(CH ２ ) ２ SO ３ H, O-C １～４ -Alkyl and O-halo-C １～４ -substituted with 1 to 3 substituents independently selected from alkyl; 【Chemical 189】 is selected from the group consisting of 3- to 10-membered cycloalkyl, 3- to 10-membered heterocycloalkyl containing 1-3 heteroatoms independently selected from N, O and S, 6- to 14-membered aryl, and 5- to 14-membered heteroaryl containing 1-4 heteroatoms independently selected from N, O and S; wherein cycloalkyl, heterocycloalkyl, aryl and heteroaryl are unsubstituted or substituted with halogen, CN, SF ５ , NO ２ , oxo, C １～４ -Alkyl, C ０～６ -Alkylene-OR ２１ , C ０～６ -alkylene-(3- to 6-membered cycloalkyl), C ０－６ -alkylene-(3- to 6-membered heterocycloalkyl), C ０～６ -Alkylene-S(O) ｎ R ２１ , C ０～６ -Alkylene-NR ２１ S (O) ２ R ２１ , C ０～６ -Alkylene-S(O) ２ NR ２１ R ２２ , C ０～６ -Alkylene-NR ２１ S (O) ２ NR ２１ R ２２ , C ０～６ -Alkylene-CO ２ R ２１ , O-C １～６ -Alkylene-CO ２ R ２１ , C ０～６ -Alkylene-O-COR ２１ , C ０～６ -Alkylene-CONR ２１ R ２２ , C ０～６ -Alkylene-NR ２１ -COR ２１ , C ０～６ -Alkylene-NR ２１ -CONR ２１ R ２２ , C ０～６ -Alkylene-O-CONR ２１ R ２２ , C ０～６ -Alkylene-NR ２１ -CO ２ R ２１ and C ０～６ -Alkylene-NR ２１ R ２２ and is substituted with 1 to 6 substituents independently selected from the group consisting of: wherein alkyl, alkylene, cycloalkyl and heterocycloalkyl are unsubstituted or substituted with halogen, CN, oxo, hydroxy, CO ２ H, CO ２ -C １～４ -Alkyl, CONHCH ２ CO ２ H, CONH(CH ２ ) ２ SO ３ H, C １～４ -Alkyl, halo-C １～４ -alkyl, O—C １～４ -Alkyl and O-halo-C １～４ -substituted with 1 to 6 substituents independently selected from alkyl; wherein two adjacent substituents on the aryl or heteroaryl moiety may form a 5-8 membered partially unsaturated ring which may contain 1-3 heteroatoms independently selected from O, S or N; This further ring may be unsubstituted or may be substituted with halogen, CN, oxo, OH, CO ２ H, CO ２ -C １～４ -Alkyl, CONHCH ２ CO ２ H, CONH(CH ２ ) ２ SO ３ H, C １～４ -Alkyl, halo-C １～４ -alkyl, O—C １～４ -Alkyl and O-halo-C １～４ -substituted with 1 to 4 substituents independently selected from alkyl; wherein two adjacent substituents on the cycloalkyl or heterocycloalkyl moiety may form a 5-6 membered unsaturated ring which may contain 1 to 3 heteroatoms independently selected from O, S or N; This further ring may be unsubstituted or may be substituted with halogen, CN, oxo, OH, CO ２ H, CO ２ -C １～４ -Alkyl, CONHCH ２ CO ２ H, CONH(CH ２ ) ２ SO ３ H, C １～４ -Alkyl, halo-C １～４ -alkyl, O—C １～４ -Alkyl and O-halo-C １～４ -substituted with 1 to 4 substituents independently selected from alkyl; 【Chemistry 190】 is selected from the group consisting of 6- or 10-membered aryl and 5- to 10-membered heteroaryl containing 1-3 heteroatoms independently selected from N, O and S; wherein cycloalkyl, heterocycloalkyl, aryl and heteroaryl are unsubstituted or substituted with halogen, CN, SF ５ , NO ２ , oxo, C １～４ -Alkyl, C ０～６ -Alkylene-OR ３１ , C ０～６ -alkylene-(3- to 6-membered cycloalkyl), C ０～６ -alkylene-(3- to 6-membered heterocycloalkyl), C ０～６ -alkylene-(6-membered aryl), C ０～６ -alkylene-(5- to 6-membered heteroaryl), C ０～６ -Alkylene-S(O) ｎ R ３１ , C ０～６ -Alkylene-NR ３１ S (O) ２ R ３１ , C ０～６ -Alkylene-S(O) ２ NR ３１ R ３２ , C ０～６ -Alkylene-NR ３１ S (O) ２ NR ３１ R ３２ , C ０～６ -Alkylene-CO ２ R ３１ , O-C １～６ -Alkylene-CO ２ R ３１ , C ０～６ -Alkylene-O-COR ３１ , C ０～６ -Alkylene-CONR ３１ R ３２ , C ０～６ -Alkylene-NR ３１ -COR ３１ , C ０～６ -Alkylene-NR ３１ -CONR ３１ R ３２ , C ０～６ -Alkylene-O-CONR ３１ R ３２ , C ０～６ -Alkylene-NR ３１ -CO ２ R ３１ and C ０～６ -Alkylene-NR ３１ R ３２ and is substituted with 1 to 4 substituents independently selected from the group consisting of: wherein alkyl, alkylene, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are unsubstituted or substituted with halogen, CN, oxo, hydroxy, CO ２ H, CO ２ -C １～４ -Alkyl, CONHCH ２ CO ２ H, CONH(CH ２ ) ２ SO ３ H, C １～４ -Alkyl, halo-C １～４ -alkyl, O—C １～４ -Alkyl and O-halo-C １～４ -substituted with 1 to 6 substituents independently selected from alkyl; wherein two adjacent substituents on the aryl or heteroaryl moiety may form a 5-8 membered partially unsaturated ring which may contain 1-3 heteroatoms independently selected from O, S or N; This further ring may be unsubstituted or may be substituted with halogen, CN, oxo, OH, CO ２ H, CO ２ -C １～４ -Alkyl, CONHCH ２ CO ２ H, CONH(CH ２ ) ２ SO ３ H, C １～４ -Alkyl, halo-C １～４ -alkyl, O—C １～４ -Alkyl and O-halo-C １～４ -substituted with 1 to 4 substituents independently selected from alkyl; 【Chemistry 191】 is selected from the group consisting of 3- to 10-membered cycloalkyl, 3- to 10-membered heterocycloalkyl containing 1-3 heteroatoms independently selected from N, O and S, 6- to 14-membered aryl, and 5- to 14-membered heteroaryl containing 1-4 heteroatoms independently selected from N, O and S; wherein cycloalkyl, heterocycloalkyl, aryl and heteroaryl are unsubstituted or substituted with halogen, CN, SF ５ , NO ２ , oxo, C １～４ -Alkyl, C ０～６ -Alkylene-OR ２１ , C ０～６ -alkylene-(3- to 6-membered cycloalkyl), C ０～６ -alkylene-(3- to 6-membered heterocycloalkyl), C ０～６ -Alkylene-S(O) ｎ R ２１ , C ０～６ -Alkylene-NR ２１ S (O) ２ R ２１ , C ０～６ -Alkylene-S(O) ２ NR ２１ R ２２ , C ０～６ -Alkylene-NR ２１ S (O) ２ NR ２１ R ２２ , C ０～６ -Alkylene-CR ４１ (=N-OR ４１ ), C ０～６ -Alkylene-CO ２ R ２１ , O-C １～６ -Alkylene-CO ２ R ２１ , C ０～６ -Alkylene-O-COR ２１ , C ０～６ -Alkylene-CONR ２１ R ２２ , C ０～６ -Alkylene-NR ２１ -COR ２１ , C ０～６ -Alkylene-NR ２１ -CONR ２１ R ２２ , C ０～６ -Alkylene-O-CONR ２１ R ２２ , C ０～６ -Alkylene-NR ２１ -CO ２ R ２１ and C ０～６ -Alkylene-NR ２１ R ２２ and is substituted with 1 to 6 substituents independently selected from the group consisting of: wherein alkyl, alkylene, cycloalkyl and heterocycloalkyl are unsubstituted or substituted with halogen, CN, oxo, hydroxy, CO ２ H, CO ２ -C １～４ -Alkyl, CONHCH ２ CO ２ H, CONH(CH ２ ) ２ SO ３ H, CO-OC １～４ -Alkyl, C １～４ -Alkyl, halo-C １～４ -alkyl, O—C １～４ -Alkyl and O-halo-C １～４ -substituted with 1 to 6 substituents independently selected from alkyl; wherein two adjacent substituents on the aryl or heteroaryl moiety may form a 5-8 membered partially unsaturated ring which may contain 1-3 heteroatoms independently selected from O, S or N; This further ring may be unsubstituted or may be substituted with halogen, CN, oxo, OH, CO ２ H, CO ２ -C １～４ -Alkyl, CONHCH ２ CO ２ H, CONH(CH ２ ) ２ SO ３ H, C １～４ -Alkyl, halo-C １～４ -alkyl, O—C １～４ -Alkyl and O-halo-C １～４ -substituted with 1 to 4 substituents independently selected from alkyl; wherein two adjacent substituents on the cycloalkyl or heterocycloalkyl moiety may form a 5-6 membered unsaturated ring which may contain 1 to 3 heteroatoms independently selected from O, S or N; This further ring may be unsubstituted or may be substituted with halogen, CN, oxo, OH, CO ２ H, CO ２ -C １～４ -Alkyl, CONHCH ２ CO ２ H, CONH(CH ２ ) ２ SO ３ H, C １～４ -Alkyl, halo-C １～４ -alkyl, O—C １～４ -Alkyl and O-halo-C １～４ -substituted with 1 to 4 substituents independently selected from alkyl; During the ceremony, 【Chemistry 192】 teeth, 【Chemistry 193】 or a further ring fused in a 1,2-orientation, L is a bond, C １～６ - alkylene, C ２～６ -Alkenylene, C ２～６ - selected from the group consisting of alkynylene, 3- to 10-membered cycloalkylene, 3- to 10-membered heterocycloalkylene containing 1-4 heteroatoms independently selected from N, O and S, 6- or 10-membered arylene, and 5- to 10-membered heteroarylene containing 1-4 heteroatoms independently selected from N, O and S; wherein alkylene, alkenylene, alkynylene, cycloalkylene, heterocycloalkylene, arylene and heteroarylene are unsubstituted or substituted with halogen, CN, SF ５ , NO ２ , oxo, C １～４ -Alkyl, C ０～６ -Alkylene-OR ４１ , C ０～６ -alkylene-(3- to 6-membered cycloalkyl), C ０～６ -alkylene-(3- to 6-membered heterocycloalkyl), C ０～６ -Alkylene-S(O) ｎ R ４１ , C ０～６ -Alkylene-NR ４１ S (O) ２ R ４１ , C ０～６ -Alkylene-S(O) ２ NR ４１ R ４２ , C ０～６ -Alkylene-NR ４１ S (O) ２ NR ４１ R ４２ , C ０～６ -Alkylene-CO ２ R ４１ , O-C １～６ -Alkylene-CO ２ R ４１ , C ０～６ -Alkylene-O-COR ４１ , C ０～６ -Alkylene-CONR ４１ R ４２ , C ０～６ -Alkylene-NR ４１ -COR ４１ , C ０～６ -Alkylene-NR ４１ -CONR ４１ R ４２ , C ０～６ -Alkylene-O-CONR ４１ R ４２ , C ０～６ -Alkylene-NR ４１ -CO ２ R ４１ and C ０～６ -Alkylene-NR ４１ R ４２ and is substituted with 1 to 6 substituents independently selected from the group consisting of: wherein alkyl, alkylene, cycloalkyl and heterocycloalkyl are unsubstituted or substituted with halogen, CN, oxo, hydroxy, CO ２ H, CO ２ -C １～４ -Alkyl, CONHCH ２ CO ２ H, CONH(CH ２ ) ２ SO ３ H, C １～４ -Alkyl, halo-C １～４ -alkyl, O—C １～４ -Alkyl and O-halo-C １～４ -substituted with 1 to 6 substituents independently selected from alkyl; wherein two adjacent substituents on the arylene and heteroarylene moieties may form a 5-8 membered partially unsaturated ring which may contain 1 to 3 heteroatoms independently selected from O, S or N; This further ring may be unsubstituted or may be substituted with halogen, CN, oxo, OH, CO ２ H, CO ２ -C １～４ -Alkyl, C １～４ -Alkyl, halo-C １～４ -alkyl, O—C １～４ -Alkyl and O-halo-C １～４ -substituted with 1 to 4 substituents independently selected from alkyl; R １ is H, halogen, CN, SF ５ , NO ２ , oxo, C １～４ -Alkyl, C ０～６ -Alkylene-OR ４１ , Y.-C. ０～６ -alkylene-(3- to 6-membered cycloalkyl), Y-C ０～６ -alkylene-(3- to 6-membered heterocycloalkyl), Y—C ０～６ -alkylene-(6-membered aryl), Y-C ０～６ -alkylene-(5- to 6-membered heteroaryl), C ０～６ -Alkylene-S(=O)(-R ４１ ) = N-R ７５ , X-C １～６ -Alkylene-S(=O)(-R ４１ ) = N-R ７５ , C ０～６ -Alkylene-S(O) ｎ R ４１ , X-C １～６ -Alkylene-S(O) ｎ R ４１ , C ０～６ -Alkylene-S(=NR ７１ ) R ４１ , X-C １～６ -Alkylene-S(=NR ７１ ) R ４１ , C ０～６ -Alkylene-S(O)(=NR ７１ ) R ４１ , X-C １～６ -Alkylene-S(O)(=NR ７１ ) R ４１ , C ０～６ -Alkylene-S(=NR ７１ ) ２ R ４１ , X-C １～６ -Alkylene-S(=NR ７１ ) ２ R ４１ , C ０～６ -Alkylene-NR ４１ S (O) ２ R ４１ , X-C １～６ -Alkylene-NR ４１ S (O) ２ R ４１ , C ０～６ -Alkylene-S(O) ２ NR ４１ R ４２ , X-C １～６ -Alkylene-S(O) ２ NR ４１ R ４２ , C ０～６ -Alkylene-NR ４１ S (O) ２ NR ４１ R ４２ , X-C １～６ -Alkylene-NR ４１ S (O) ２ NR ４１ R ４２ , C ０～６ -Alkylene-SO ３ R ４１ , X-C １～６ -Alkylene-SO ３ R ４１ , C ０～６ -Alkylene-CO ２ R ４１ , X-C １～６ -Alkylene-CO ２ R ４１ , C ０～６ -Alkylene-O-COR ４１ , X-C １～６ -Alkylene-O-COR ４１ , C ０～６ -Alkylene-CONR ４１ R ４２ , X-C １～６ -Alkylene-CONR ４１ R ４２ , C ０～６ -Alkylene-CONR ４１ OR ４１ , X-C １～６ -Alkylene-CONR ４１ OR ４１ , C ０～６ -Alkylene-CONR ４１ SO ２ R ４１ , X-C １～６ -Alkylene-CONR ４１ SO ２ R ４１ , C ０～６ -Alkylene-NR ４１ -COR ４１ , X-C １～６ -C ０～６ -Alkylene-NR ４１ -COR ４１ , C ０～６ -Alkylene-NR ４１ -CONR ４１ R ４２ , X-C １～６ -Alkylene-NR ４１ -CONR ４１ R ４２ , C ０～６ -Alkylene-O-CONR ４１ R ４２ , X-C １～６ -Alkylene-O-CONR ４１ R ４２ , C ０～６ -Alkylene-NR ４１ -CO ２ R ４１ , X-C １～６ -Alkylene-NR ４１ -CO ２ R ４１ , C ０～６ -Alkylene-NR ４１ R ４２ , X-C １～６ -Alkylene-NR ４１ R ４２ is selected from the group consisting of wherein alkyl, alkylene, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are unsubstituted or substituted with halogen, CN, oxo, hydroxy, CO ２ H, CO ２ -C １～４ -Alkyl, CONHCH ２ CO ２ H, CONH(CH ２ ) ２ SO ３ H, C １～４ -Alkyl, halo-C １～４ -alkyl, O—C １～４ -Alkyl and O-halo-C １～４ -substituted with 1 to 6 substituents independently selected from alkyl; wherein two adjacent substituents on the aryl and heteroaryl moieties may form a 5-8 membered partially unsaturated ring which may contain 1-3 heteroatoms independently selected from O, S or N; This further ring may be unsubstituted or may be substituted with halogen, CN, oxo, OH, CO ２ H, CO ２ -C １～４ -Alkyl, CONHCH ２ CO ２ H, CONH(CH ２ ) ２ SO ３ H, C １～４ -Alkyl, halo-C １～４ -alkyl, O—C １～４ -Alkyl and O-halo-C １～４ -substituted with 1 to 4 substituents independently selected from alkyl; R １１ , R １２ , R ２１ , R ２２ , R ３１ , R ３２ , R ４１ , R ４２ , R ５１ are independently H and C １～４ - alkyl, wherein alkyl is unsubstituted or substituted with halogen, CN, C １～４ -Alkyl, halo-C １～４ -alkyl, 3- to 6-membered cycloalkyl, halo-(3- to 6-membered cycloalkyl), 3- to 6-membered heterocycloalkyl, halo-(3- to 6-membered heterocycloalkyl), OH, oxo, CO ２ H, CO ２ -C １～４ -Alkyl, CONHCH ２ CO ２ H, CONH(CH ２ ) ２ SO ３ H, SO ３ H, O-C １～４ -Alkyl and O-halo-C １～４ -substituted with 1 to 3 substituents independently selected from alkyl; or R １１ and R １２ , R ２１ and R ２２ , R ３１ and R ３２ , R ４１ and R ４２ each, when taken together with the nitrogen to which they are attached, completes a 3- to 6-membered ring containing carbon atoms and optionally containing 1 or 2 heteroatoms independently selected from O, S or N; The newly formed ring is unsubstituted or contains halogen, CN, C １～４ -Alkyl, halo-C １～４ -alkyl, 3- to 6-membered cycloalkyl, halo-(3- to 6-membered cycloalkyl), 3- to 6-membered heterocycloalkyl, halo-(3- to 6-membered heterocycloalkyl), OH, oxo, CO ２ H, CO ２ -C １～４ -Alkyl, CONHCH ２ CO ２ H, CONH(CH ２ ) ２ SO ３ H, SO ３ H, O-C １～４ -Alkyl and O-halo-C １～４ -substituted with 1 to 3 substituents independently selected from alkyl; R ７１ are independently H, CN, NO ２ , C １～４ -alkyl, and C(O)-OC １～４ - alkyl, wherein alkyl is unsubstituted or substituted with halogen, CN, C １～４ -Alkyl, halo-C １～４ -alkyl, 3- to 6-membered cycloalkyl, halo-(3- to 6-membered cycloalkyl), 3- to 6-membered heterocycloalkyl, halo-(3- to 6-membered heterocycloalkyl), OH, oxo, CO ２ H, CO ２ -C １～４ -Alkyl, CONHCH ２ CO ２ H, CONH(CH ２ ) ２ SO ３ H, SO ３ H, O-C １～４ -Alkyl and O-halo-C １～４ -substituted with 1 to 3 substituents independently selected from alkyl; R ７５ are independently １～４ selected from alkyl, 3- to 6-membered cycloalkyl, 3- to 6-membered heterocycloalkyl, 6-membered aryl, and 5- to 6-membered heteroaryl; wherein alkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl are unsubstituted or substituted with halogen, CN, Me, Et, CHF ２ , C.F. ３ , OH, oxo, CO ２ H, CONHCH ２ CO ２ H, CONH(CH ２ ) ２ SO ３ H, SO ３ H, OMe, Oet, OCHF ２ , and OCF ３ and is substituted with 1 to 3 substituents independently selected from X is independently O, NR ５１ , S(O) ｎ , S (= NR ７１ ), S(O)(=NR ７１ ) and S(=NR ７１ ) ２ is selected from Y is independently a bond, O, NR ５１ , S(O) ｎ , S (= NR ７１ ), S(O)(=NR ７１ ) and S(=NR ７１ ) ２ is selected from n is independently selected from 0 to 2; however, 【Chemistry 194】 The structure of the use is excluded.

4. 1. A compound for use in the treatment of metabolic disorders associated with dyslipidemia or impaired lipid homeostasis, said compound having formula (I): 【Chemistry 195】 its glycine conjugates, taurine conjugates, enantiomers, diastereomers, tautomers, N-oxides, solvates, prodrugs, and pharmaceutically acceptable salts thereof; During the ceremony, 【Chemistry 196】 is a fused 5- to 6-membered ring forming a 6-membered aryl or a 5- to 6-membered heteroaryl containing 1-3 heteroatoms independently selected from N, O and S, the ring being unsubstituted or substituted with halogen, CN, SF ５ , NO ２ , C １～６ -Alkyl, oxo, C ０～６ -Alkylene-OR １１ , C ０～６ -alkylene-(3- to 6-membered cycloalkyl), C ０～６ -alkylene-(3- to 6-membered heterocycloalkyl), C ０～６ -Alkylene-S(O) ｎ R １１ , C ０～６ -Alkylene-NR １１ S (O) ２ R １１ , C ０～６ -Alkylene-S(O) ２ NR １１ R １２ , C ０～６ -Alkylene-NR １１ S (O) ２ NR １１ R １２ , C ０～６ -Alkylene-CO ２ R １１ , O-C １～６ -Alkylene-CO ２ R １１ , C ０～６ -Alkylene-O-COR １１ , C ０～６ -Alkylene-CONR １１ R １２ , C ０～６ -Alkylene-NR １１ -COR １１ , C ０～６ -Alkylene-NR １１ -CONR １１ R １２ , C ０～６ -Alkylene-O-CONR １１ R １２ , C ０～６ -Alkylene-NR １１ -CO ２ R １１ and C ０～６ -Alkylene-NR １１ R １２ and is substituted with 1 to 4 substituents independently selected from the group consisting of: wherein alkyl, alkylene, cycloalkyl, and heterocycloalkyl are unsubstituted or substituted with halogen, CN, oxo, hydroxy, CO ２ H, CO ２ -C １～４ -Alkyl, CONHCH ２ CO ２ H, CONH(CH ２ ) ２ SO ３ H, C １～４ -Alkyl, halo-C １～４ -alkyl, O—C １～４ -Alkyl and O-halo-C １～４ -substituted with 1 to 6 substituents independently selected from alkyl; wherein two adjacent substituents on the aryl or heteroaryl moiety may form a 5-8 membered partially unsaturated ring which may contain 1-3 heteroatoms independently selected from O, S or N; The newly formed ring may be unsubstituted or may contain halogen, CN, C １～４ -Alkyl, halo-C １～４ -alkyl, 3- to 6-membered cycloalkyl, halo-(3- to 6-membered cycloalkyl), 3- to 6-membered heterocycloalkyl, halo-(3- to 6-membered heterocycloalkyl), OH, oxo, CO ２ H, CO ２ -C １～４ -Alkyl, CONHCH ２ CO ２ H, CONH(CH ２ ) ２ SO ３ H, O-C １～４ -Alkyl and O-halo-C １～４ -substituted with 1 to 3 substituents independently selected from alkyl; 【Chemistry 197】 is selected from the group consisting of 3- to 10-membered cycloalkyl, 3- to 10-membered heterocycloalkyl containing 1-3 heteroatoms independently selected from N, O and S, 6- to 14-membered aryl, and 5- to 14-membered heteroaryl containing 1-4 heteroatoms independently selected from N, O and S; wherein cycloalkyl, heterocycloalkyl, aryl and heteroaryl are unsubstituted or substituted with halogen, CN, SF ５ , NO ２ , oxo, C １～４ -Alkyl, C ０～６ -Alkylene-OR ２１ , C ０～６ -alkylene-(3- to 6-membered cycloalkyl), C ０－６ -alkylene-(3- to 6-membered heterocycloalkyl), C ０～６ -Alkylene-S(O) ｎ R ２１ , C ０～６ -Alkylene-NR ２１ S (O) ２ R ２１ , C ０～６ -Alkylene-S(O) ２ NR ２１ R ２２ , C ０～６ -Alkylene-NR ２１ S (O) ２ NR ２１ R ２２ , C ０～６ -Alkylene-CO ２ R ２１ , O-C １～６ -Alkylene-CO ２ R ２１ , C ０～６ -Alkylene-O-COR ２１ , C ０～６ -Alkylene-CONR ２１ R ２２ , C ０～６ -Alkylene-NR ２１ -COR ２１ , C ０～６ -Alkylene-NR ２１ -CONR ２１ R ２２ , C ０～６ -Alkylene-O-CONR ２１ R ２２ , C ０～６ -Alkylene-NR ２１ -CO ２ R ２１ and C ０～６ -Alkylene-NR ２１ R ２２ and is substituted with 1 to 6 substituents independently selected from the group consisting of: wherein alkyl, alkylene, cycloalkyl and heterocycloalkyl are unsubstituted or substituted with halogen, CN, oxo, hydroxy, CO ２ H, CO ２ -C １～４ -Alkyl, CONHCH ２ CO ２ H, CONH(CH ２ ) ２ SO ３ H, C １～４ -Alkyl, halo-C １～４ -alkyl, O—C １～４ -Alkyl and O-halo-C １～４ -substituted with 1 to 6 substituents independently selected from alkyl; wherein two adjacent substituents on the aryl or heteroaryl moiety may form a 5-8 membered partially unsaturated ring which may contain 1-3 heteroatoms independently selected from O, S or N; This further ring may be unsubstituted or may be substituted with halogen, CN, oxo, OH, CO ２ H, CO ２ -C １～４ -Alkyl, CONHCH ２ CO ２ H, CONH(CH ２ ) ２ SO ３ H, C １～４ -Alkyl, halo-C １～４ -alkyl, O—C １～４ -Alkyl and O-halo-C １～４ -substituted with 1 to 4 substituents independently selected from alkyl; wherein two adjacent substituents on the cycloalkyl or heterocycloalkyl moiety may form a 5-6 membered unsaturated ring which may contain 1 to 3 heteroatoms independently selected from O, S or N; This further ring may be unsubstituted or may be substituted with halogen, CN, oxo, OH, CO ２ H, CO ２ -C １～４ -Alkyl, CONHCH ２ CO ２ H, CONH(CH ２ ) ２ SO ３ H, C １～４ -Alkyl, halo-C １～４ -alkyl, O—C １～４ -Alkyl and O-halo-C １～４ -substituted with 1 to 4 substituents independently selected from alkyl; 【Chemistry 198】 is selected from the group consisting of 6- or 10-membered aryl and 5- to 10-membered heteroaryl containing 1-3 heteroatoms independently selected from N, O and S; wherein cycloalkyl, heterocycloalkyl, aryl and heteroaryl are unsubstituted or substituted with halogen, CN, SF ５ , NO ２ , oxo, C １～４ -Alkyl, C ０～６ -Alkylene-OR ３１ , C ０～６ -alkylene-(3- to 6-membered cycloalkyl), C ０～６ -alkylene-(3- to 6-membered heterocycloalkyl), C ０～６ -alkylene-(6-membered aryl), C ０～６ -alkylene-(5- to 6-membered heteroaryl), C ０～６ -Alkylene-S(O) ｎ R ３１ , C ０～６ -Alkylene-NR ３１ S (O) ２ R ３１ , C ０～６ -Alkylene-S(O) ２ NR ３１ R ３２ , C ０～６ -Alkylene-NR ３１ S (O) ２ NR ３１ R ３２ , C ０～６ -Alkylene-CO ２ R ３１ , O-C １～６ -Alkylene-CO ２ R ３１ , C ０～６ -Alkylene-O-COR ３１ , C ０～６ -Alkylene-CONR ３１ R ３２ , C ０～６ -Alkylene-NR ３１ -COR ３１ , C ０～６ -Alkylene-NR ３１ -CONR ３１ R ３２ , C ０～６ -Alkylene-O-CONR ３１ R ３２ , C ０～６ -Alkylene-NR ３１ -CO ２ R ３１ and C ０～６ -Alkylene-NR ３１ R ３２ and is substituted with 1 to 4 substituents independently selected from the group consisting of: wherein alkyl, alkylene, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are unsubstituted or substituted with halogen, CN, oxo, hydroxy, CO ２ H, CO ２ -C １～４ -Alkyl, CONHCH ２ CO ２ H, CONH(CH ２ ) ２ SO ３ H, C １～４ -Alkyl, halo-C １～４ -alkyl, O—C １～４ -Alkyl and O-halo-C １～４ -substituted with 1 to 6 substituents independently selected from alkyl; wherein two adjacent substituents on the aryl or heteroaryl moiety may form a 5-8 membered partially unsaturated ring which may contain 1-3 heteroatoms independently selected from O, S or N; This further ring may be unsubstituted or may be substituted with halogen, CN, oxo, OH, CO ２ H, CO ２ -C １～４ -Alkyl, CONHCH ２ CO ２ H, CONH(CH ２ ) ２ SO ３ H, C １～４ -Alkyl, halo-C １～４ -alkyl, O—C １～４ -Alkyl and O-halo-C １～４ -substituted with 1 to 4 substituents independently selected from alkyl; 【Chemistry 199】 is selected from the group consisting of 3- to 10-membered cycloalkyl, 3- to 10-membered heterocycloalkyl containing 1-3 heteroatoms independently selected from N, O and S, 6- to 14-membered aryl, and 5- to 14-membered heteroaryl containing 1-4 heteroatoms independently selected from N, O and S; wherein cycloalkyl, heterocycloalkyl, aryl and heteroaryl are unsubstituted or substituted with halogen, CN, SF ５ , NO ２ , oxo, C １～４ -Alkyl, C ０～６ -Alkylene-OR ２１ , C ０～６ -alkylene-(3- to 6-membered cycloalkyl), C ０～６ -alkylene-(3- to 6-membered heterocycloalkyl), C ０～６ -Alkylene-S(O) ｎ R ２１ , C ０～６ -Alkylene-NR ２１ S (O) ２ R ２１ , C ０～６ -Alkylene-S(O) ２ NR ２１ R ２２ , C ０～６ -Alkylene-NR ２１ S (O) ２ NR ２１ R ２２ , C ０～６ -Alkylene-CR ４１ (=N-OR ４１ ), C ０～６ -Alkylene-CO ２ R ２１ , O-C １～６ -Alkylene-CO ２ R ２１ , C ０～６ -Alkylene-O-COR ２１ , C ０～６ -Alkylene-CONR ２１ R ２２ , C ０～６ -Alkylene-NR ２１ -COR ２１ , C ０～６ -Alkylene-NR ２１ -CONR ２１ R ２２ , C ０～６ -Alkylene-O-CONR ２１ R ２２ , C ０～６ -Alkylene-NR ２１ -CO ２ R ２１ and C ０～６ -Alkylene-NR ２１ R ２２ and is substituted with 1 to 6 substituents independently selected from the group consisting of: wherein alkyl, alkylene, cycloalkyl and heterocycloalkyl are unsubstituted or substituted with halogen, CN, oxo, hydroxy, CO ２ H, CO ２ -C １～４ -Alkyl, CONHCH ２ CO ２ H, CONH(CH ２ ) ２ SO ３ H, CO-OC １～４ -Alkyl, C １～４ -Alkyl, halo-C １～４ -alkyl, O—C １～４ -Alkyl and O-halo-C １～４ -substituted with 1 to 6 substituents independently selected from alkyl; wherein two adjacent substituents on the aryl or heteroaryl moiety may form a 5-8 membered partially unsaturated ring which may contain 1-3 heteroatoms independently selected from O, S or N; This further ring may be unsubstituted or may be substituted with halogen, CN, oxo, OH, CO ２ H, CO ２ -C １～４ -Alkyl, CONHCH ２ CO ２ H, CONH(CH ２ ) ２ SO ３ H, C １～４ -Alkyl, halo-C １～４ -alkyl, O—C １～４ -Alkyl and O-halo-C １～４ -substituted with 1 to 4 substituents independently selected from alkyl; wherein two adjacent substituents on the cycloalkyl or heterocycloalkyl moiety may form a 5-6 membered unsaturated ring which may contain 1 to 3 heteroatoms independently selected from O, S or N; This further ring may be unsubstituted or may be substituted with halogen, CN, oxo, OH, CO ２ H, CO ２ -C １～４ -Alkyl, CONHCH ２ CO ２ H, CONH(CH ２ ) ２ SO ３ H, C １～４ -Alkyl, halo-C １～４ -alkyl, O—C １～４ -Alkyl and O-halo-C １～４ -substituted with 1 to 4 substituents independently selected from alkyl; During the ceremony, 【Chemistry 200】 teeth, 【Chemical Engineering 201】 or a further ring fused in a 1,2-orientation, L is a bond, C １～６ - alkylene, C ２～６ -Alkenylene, C ２～６ - selected from the group consisting of alkynylene, 3- to 10-membered cycloalkylene, 3- to 10-membered heterocycloalkylene containing 1-4 heteroatoms independently selected from N, O and S, 6- or 10-membered arylene, and 5- to 10-membered heteroarylene containing 1-4 heteroatoms independently selected from N, O and S; wherein alkylene, alkenylene, alkynylene, cycloalkylene, heterocycloalkylene, arylene and heteroarylene are unsubstituted or substituted with halogen, CN, SF ５ , NO ２ , oxo, C １～４ -Alkyl, C ０～６ -Alkylene-OR ４１ , C ０～６ -alkylene-(3- to 6-membered cycloalkyl), C ０～６ -alkylene-(3- to 6-membered heterocycloalkyl), C ０～６ -Alkylene-S(O) ｎ R ４１ , C ０～６ -Alkylene-NR ４１ S (O) ２ R ４１ , C ０～６ -Alkylene-S(O) ２ NR ４１ R ４２ , C ０～６ -Alkylene-NR ４１ S (O) ２ NR ４１ R ４２ , C ０～６ -Alkylene-CO ２ R ４１ , O-C １～６ -Alkylene-CO ２ R ４１ , C ０～６ -Alkylene-O-COR ４１ , C ０～６ -Alkylene-CONR ４１ R ４２ , C ０～６ -Alkylene-NR ４１ -COR ４１ , C ０～６ -Alkylene-NR ４１ -CONR ４１ R ４２ , C ０～６ -Alkylene-O-CONR ４１ R ４２ , C ０～６ -Alkylene-NR ４１ -CO ２ R ４１ and C ０～６ -Alkylene-NR ４１ R ４２ and is substituted with 1 to 6 substituents independently selected from the group consisting of: wherein alkyl, alkylene, cycloalkyl and heterocycloalkyl are unsubstituted or substituted with halogen, CN, oxo, hydroxy, CO ２ H, CO ２ -C １～４ -Alkyl, CONHCH ２ CO ２ H, CONH(CH ２ ) ２ SO ３ H, C １～４ -Alkyl, halo-C １～４ -alkyl, O—C １～４ -Alkyl and O-halo-C １～４ -substituted with 1 to 6 substituents independently selected from alkyl; wherein two adjacent substituents on the arylene and heteroarylene moieties may form a 5-8 membered partially unsaturated ring which may contain 1 to 3 heteroatoms independently selected from O, S, or N; This further ring may be unsubstituted or may be substituted with halogen, CN, oxo, OH, CO ２ H, CO ２ -C １～４ -Alkyl, C １～４ -Alkyl, halo-C １～４ -alkyl, O—C １～４ -Alkyl and O-halo-C １～４ -substituted with 1 to 4 substituents independently selected from alkyl; R １ is H, halogen, CN, SF ５ , NO ２ , oxo, C １～４ -Alkyl, C ０～６ -Alkylene-OR ４１ , Y.-C. ０～６ -alkylene-(3- to 6-membered cycloalkyl), Y-C ０～６ -alkylene-(3- to 6-membered heterocycloalkyl), Y—C ０～６ -alkylene-(6-membered aryl), Y-C ０～６ -alkylene-(5- to 6-membered heteroaryl), C ０～６ -Alkylene-S(=O)(-R ４１ ) = N-R ７５ , X-C １～６ -Alkylene-S(=O)(-R ４１ ) = N-R ７５ , C ０～６ -Alkylene-S(O) ｎ R ４１ , X-C １～６ -Alkylene-S(O) ｎ R ４１ , C ０～６ -Alkylene-S(=NR ７１ ) R ４１ , X-C １～６ -Alkylene-S(=NR ７１ ) R ４１ , C ０～６ -Alkylene-S(O)(=NR ７１ ) R ４１ , X-C １～６ -Alkylene-S(O)(=NR ７１ ) R ４１ , C ０～６ -Alkylene-S(=NR ７１ ) ２ R ４１ , X-C １～６ -Alkylene-S(=NR ７１ ) ２ R ４１ , C ０～６ -Alkylene-NR ４１ S (O) ２ R ４１ , X-C １～６ -Alkylene-NR ４１ S (O) ２ R ４１ , C ０～６ -Alkylene-S(O) ２ NR ４１ R ４２ , X-C １～６ -Alkylene-S(O) ２ NR ４１ R ４２ , C ０～６ -Alkylene-NR ４１ S (O) ２ NR ４１ R ４２ , X-C １～６ -Alkylene-NR ４１ S (O) ２ NR ４１ R ４２ , C ０～６ -Alkylene-SO ３ R ４１ , X-C １～６ -Alkylene-SO ３ R ４１ , C ０～６ -Alkylene-CO ２ R ４１ , X-C １～６ -Alkylene-CO ２ R ４１ , C ０～６ -Alkylene-O-COR ４１ , X-C １～６ -Alkylene-O-COR ４１ , C ０～６ -Alkylene-CONR ４１ R ４２ , X-C １～６ -Alkylene-CONR ４１ R ４２ , C ０～６ -Alkylene-CONR ４１ OR ４１ , X-C １～６ -Alkylene-CONR ４１ OR ４１ , C ０～６ -Alkylene-CONR ４１ SO ２ R ４１ , X-C １～６ -Alkylene-CONR ４１ SO ２ R ４１ , C ０～６ -Alkylene-NR ４１ -COR ４１ , X-C １～６ -C ０～６ -Alkylene-NR ４１ -COR ４１ , C ０～６ -Alkylene-NR ４１ -CONR ４１ R ４２ , X-C １～６ -Alkylene-NR ４１ -CONR ４１ R ４２ , C ０～６ -Alkylene-O-CONR ４１ R ４２ , X-C １～６ -Alkylene-O-CONR ４１ R ４２ , C ０～６ -Alkylene-NR ４１ -CO ２ R ４１ , X-C １～６ -Alkylene-NR ４１ -CO ２ R ４１ , C ０～６ -Alkylene-NR ４１ R ４２ , X-C １～６ -Alkylene-NR ４１ R ４２ is selected from the group consisting of wherein alkyl, alkylene, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are unsubstituted or substituted with halogen, CN, oxo, hydroxy, CO ２ H, CO ２ -C １～４ -Alkyl, CONHCH ２ CO ２ H, CONH(CH ２ ) ２ SO ３ H, C １～４ -Alkyl, halo-C １～４ -alkyl, O—C １～４ -Alkyl and O-halo-C １～４ -substituted with 1 to 6 substituents independently selected from alkyl; wherein two adjacent substituents on the aryl and heteroaryl moieties may form a 5-8 membered partially unsaturated ring which may contain 1-3 heteroatoms independently selected from O, S or N; This further ring may be unsubstituted or may be substituted with halogen, CN, oxo, OH, CO ２ H, CO ２ -C １～４ -Alkyl, CONHCH ２ CO ２ H, CONH(CH ２ ) ２ SO ３ H, C １～４ -Alkyl, halo-C １～４ -alkyl, O—C １～４ -Alkyl and O-halo-C １～４ -substituted with 1 to 4 substituents independently selected from alkyl; R １１ , R １２ , R ２１ , R ２２ , R ３１ , R ３２ , R ４１ , R ４２ , R ５１ are independently H and C １～４ - alkyl, wherein alkyl is unsubstituted or substituted with halogen, CN, C １～４ -Alkyl, halo-C １～４ -alkyl, 3- to 6-membered cycloalkyl, halo-(3- to 6-membered cycloalkyl), 3- to 6-membered heterocycloalkyl, halo-(3- to 6-membered heterocycloalkyl), OH, oxo, CO ２ H, CO ２ -C １～４ -Alkyl, CONHCH ２ CO ２ H, CONH(CH ２ ) ２ SO ３ H, SO ３ H, O-C １～４ -Alkyl and O-halo-C １～４ -substituted with 1 to 3 substituents independently selected from alkyl; or R １１ and R １２ , R ２１ and R ２２ , R ３１ and R ３２ , R ４１ and R ４２ each, when taken together with the nitrogen to which they are attached, completes a 3- to 6-membered ring containing carbon atoms and optionally containing 1 or 2 heteroatoms independently selected from O, S or N; The newly formed ring is unsubstituted or contains halogen, CN, C １～４ -Alkyl, halo-C １～４ -alkyl, 3- to 6-membered cycloalkyl, halo-(3- to 6-membered cycloalkyl), 3- to 6-membered heterocycloalkyl, halo-(3- to 6-membered heterocycloalkyl), OH, oxo, CO ２ H, CO ２ -C １～４ -Alkyl, CONHCH ２ CO ２ H, CONH(CH ２ ) ２ SO ３ H, SO ３ H, O-C １～４ -Alkyl and O-halo-C １～４ -substituted with 1 to 3 substituents independently selected from alkyl; R ７１ are independently H, CN, NO ２ , C １～４ -alkyl, and C(O)-OC １～４ - alkyl, wherein alkyl is unsubstituted or substituted with halogen, CN, C １～４ -Alkyl, halo-C １～４ -alkyl, 3- to 6-membered cycloalkyl, halo-(3- to 6-membered cycloalkyl), 3- to 6-membered heterocycloalkyl, halo-(3- to 6-membered heterocycloalkyl), OH, oxo, CO ２ H, CO ２ -C １～４ -Alkyl, CONHCH ２ CO ２ H, CONH(CH ２ ) ２ SO ３ H, SO ３ H, O-C １～４ -Alkyl and O-halo-C １～４ -substituted with 1 to 3 substituents independently selected from alkyl; R ７５ are independently １～４ selected from alkyl, 3- to 6-membered cycloalkyl, 3- to 6-membered heterocycloalkyl, 6-membered aryl, and 5- to 6-membered heteroaryl; wherein alkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are unsubstituted or substituted with halogen, CN, Me, Et, CHF ２ , C.F. ３ , OH, oxo, CO ２ H, CONHCH ２ CO ２ H, CONH(CH ２ ) ２ SO ３ H, SO ３ H, OMe, OEt, OCHF ２ and OCF ３ and is substituted with 1 to 3 substituents independently selected from X is independently O, NR ５１ , S(O) ｎ , S (= NR ７１ ), S(O)(=NR ７１ ) and S(=NR ７１ ) ２ is selected from Y is independently a bond, O, NR ５１ , S(O) ｎ , S (= NR ７１ ), S(O)(=NR ７１ ) and S(=NR ７１ ) ２ is selected from n is independently selected from 0 to 2; however, 【Chemical Engineering 202】 The structure of the compound is excluded.

5. A medicament for treating metabolic disorders associated with dyslipidemia or impaired lipid homeostasis, the medicament comprising a compound represented by formula (I): 【Chemical 203】 glycine conjugates, taurine conjugates, enantiomers, diastereomers, tautomers, N-oxides, solvates, prodrugs, and pharmaceutically acceptable salts thereof, During the ceremony, 【Chemical 204】 is a fused 5- to 6-membered ring forming a 6-membered aryl or a 5- to 6-membered heteroaryl containing 1-3 heteroatoms independently selected from N, O and S, the ring being unsubstituted or substituted with halogen, CN, SF ５ , NO ２ , C １～６ -Alkyl, oxo, C ０～６ -Alkylene-OR １１ , C ０～６ -alkylene-(3- to 6-membered cycloalkyl), C ０～６ -alkylene-(3- to 6-membered heterocycloalkyl), C ０～６ -Alkylene-S(O) ｎ R １１ , C ０～６ -Alkylene-NR １１ S (O) ２ R １１ , C ０～６ -Alkylene-S(O) ２ NR １１ R １２ , C ０～６ -Alkylene-NR １１ S (O) ２ NR １１ R １２ , C ０～６ -Alkylene-CO ２ R １１ , O-C １～６ -Alkylene-CO ２ R １１ , C ０～６ -Alkylene-O-COR １１ , C ０～６ -Alkylene-CONR １１ R １２ , C ０～６ -Alkylene-NR １１ -COR １１ , C ０～６ -Alkylene-NR １１ -CONR １１ R １２ , C ０～６ -Alkylene-O-CONR １１ R １２ , C ０～６ -Alkylene-NR １１ -CO ２ R １１ and C ０～６ -Alkylene-NR １１ R １２ and is substituted with 1 to 4 substituents independently selected from the group consisting of: wherein alkyl, alkylene, cycloalkyl, and heterocycloalkyl are unsubstituted or substituted with halogen, CN, oxo, hydroxy, CO ２ H, CO ２ -C １～４ -Alkyl, CONHCH ２ CO ２ H, CONH(CH ２ ) ２ SO ３ H, C １～４ -Alkyl, halo-C １～４ -alkyl, O—C １～４ -Alkyl and O-halo-C １～４ -substituted with 1 to 6 substituents independently selected from alkyl; wherein two adjacent substituents on the aryl or heteroaryl moiety may form a 5-8 membered partially unsaturated ring which may contain 1-3 heteroatoms independently selected from O, S or N; The newly formed ring may be unsubstituted or may contain halogen, CN, C １～４ -Alkyl, halo-C １～４ -alkyl, 3- to 6-membered cycloalkyl, halo-(3- to 6-membered cycloalkyl), 3- to 6-membered heterocycloalkyl, halo-(3- to 6-membered heterocycloalkyl), OH, oxo, CO ２ H, CO ２ -C １～４ -Alkyl, CONHCH ２ CO ２ H, CONH(CH ２ ) ２ SO ３ H, O-C １～４ -Alkyl and O-halo-C １～４ -substituted with 1 to 3 substituents independently selected from alkyl; 【Chemical 205】 is selected from the group consisting of 3- to 10-membered cycloalkyl, 3- to 10-membered heterocycloalkyl containing 1-3 heteroatoms independently selected from N, O and S, 6- to 14-membered aryl, and 5- to 14-membered heteroaryl containing 1-4 heteroatoms independently selected from N, O and S; wherein cycloalkyl, heterocycloalkyl, aryl and heteroaryl are unsubstituted or substituted with halogen, CN, SF ５ , NO ２ , oxo, C １～４ -Alkyl, C ０～６ -Alkylene-OR ２１ , C ０～６ -alkylene-(3- to 6-membered cycloalkyl), C ０－６ -alkylene-(3- to 6-membered heterocycloalkyl), C ０～６ -Alkylene-S(O) ｎ R ２１ , C ０～６ -Alkylene-NR ２１ S (O) ２ R ２１ , C ０～６ -Alkylene-S(O) ２ NR ２１ R ２２ , C ０～６ -Alkylene-NR ２１ S (O) ２ NR ２１ R ２２ , C ０～６ -Alkylene-CO ２ R ２１ , O-C １～６ -Alkylene-CO ２ R ２１ , C ０～６ -Alkylene-O-COR ２１ , C ０～６ -Alkylene-CONR ２１ R ２２ , C ０～６ -Alkylene-NR ２１ -COR ２１ , C ０～６ -Alkylene-NR ２１ -CONR ２１ R ２２ , C ０～６ -Alkylene-O-CONR ２１ R ２２ , C ０～６ -Alkylene-NR ２１ -CO ２ R ２１ and C ０～６ -Alkylene-NR ２１ R ２２ and is substituted with 1 to 6 substituents independently selected from the group consisting of: wherein alkyl, alkylene, cycloalkyl and heterocycloalkyl are unsubstituted or substituted with halogen, CN, oxo, hydroxy, CO ２ H, CO ２ -C １～４ -Alkyl, CONHCH ２ CO ２ H, CONH(CH ２ ) ２ SO ３ H, C １～４ -Alkyl, halo-C １～４ -alkyl, O—C １～４ -Alkyl and O-halo-C １～４ -substituted with 1 to 6 substituents independently selected from alkyl; wherein two adjacent substituents on the aryl or heteroaryl moiety may form a 5-8 membered partially unsaturated ring which may contain 1-3 heteroatoms independently selected from O, S or N; This further ring may be unsubstituted or may be substituted with halogen, CN, oxo, OH, CO ２ H, CO ２ -C １～４ -Alkyl, CONHCH ２ CO ２ H, CONH(CH ２ ) ２ SO ３ H, C １～４ -Alkyl, halo-C １～４ -alkyl, O—C １～４ -Alkyl and O-halo-C １～４ -substituted with 1 to 4 substituents independently selected from alkyl; wherein two adjacent substituents on the cycloalkyl or heterocycloalkyl moiety may form a 5-6 membered unsaturated ring which may contain 1 to 3 heteroatoms independently selected from O, S or N; This further ring may be unsubstituted or may be substituted with halogen, CN, oxo, OH, CO ２ H, CO ２ -C １～４ -Alkyl, CONHCH ２ CO ２ H, CONH(CH ２ ) ２ SO ３ H, C １～４ -Alkyl, halo-C １～４ -alkyl, O—C １～４ -Alkyl and O-halo-C １～４ -substituted with 1 to 4 substituents independently selected from alkyl; 【Chemical 206】 is selected from the group consisting of 6- or 10-membered aryl and 5- to 10-membered heteroaryl containing 1-3 heteroatoms independently selected from N, O and S; wherein cycloalkyl, heterocycloalkyl, aryl and heteroaryl are unsubstituted or substituted with halogen, CN, SF ５ , NO ２ , oxo, C １～４ -Alkyl, C ０～６ -Alkylene-OR ３１ , C ０～６ -alkylene-(3- to 6-membered cycloalkyl), C ０～６ -alkylene-(3- to 6-membered heterocycloalkyl), C ０～６ -alkylene-(6-membered aryl), C ０～６ -alkylene-(5- to 6-membered heteroaryl), C ０～６ -Alkylene-S(O) ｎ R ３１ , C ０～６ -Alkylene-NR ３１ S (O) ２ R ３１ , C ０～６ -Alkylene-S(O) ２ NR ３１ R ３２ , C ０～６ -Alkylene-NR ３１ S (O) ２ NR ３１ R ３２ , C ０～６ -Alkylene-CO ２ R ３１ , O-C １～６ -Alkylene-CO ２ R ３１ , C ０～６ -Alkylene-O-COR ３１ , C ０～６ -Alkylene-CONR ３１ R ３２ , C ０～６ -Alkylene-NR ３１ -COR ３１ , C ０～６ -Alkylene-NR ３１ -CONR ３１ R ３２ , C ０～６ -Alkylene-O-CONR ３１ R ３２ , C ０～６ -Alkylene-NR ３１ -CO ２ R ３１ and C ０～６ -Alkylene-NR ３１ R ３２ and is substituted with 1 to 4 substituents independently selected from the group consisting of: wherein alkyl, alkylene, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are unsubstituted or substituted with halogen, CN, oxo, hydroxy, CO ２ H, CO ２ -C １～４ -Alkyl, CONHCH ２ CO ２ H, CONH(CH ２ ) ２ SO ３ H, C １～４ -Alkyl, halo-C １～４ -alkyl, O—C １～４ -Alkyl and O-halo-C １～４ -substituted with 1 to 6 substituents independently selected from alkyl; wherein two adjacent substituents on the aryl or heteroaryl moiety may form a 5-8 membered partially unsaturated ring which may contain 1-3 heteroatoms independently selected from O, S or N; This further ring may be unsubstituted or may be substituted with halogen, CN, oxo, OH, CO ２ H, CO ２ -C １～４ -Alkyl, CONHCH ２ CO ２ H, CONH(CH ２ ) ２ SO ３ H, C １～４ -Alkyl, halo-C １～４ -alkyl, O—C １～４ -Alkyl and O-halo-C １～４ -substituted with 1 to 4 substituents independently selected from alkyl; 【Chemical 207】 is selected from the group consisting of 3- to 10-membered cycloalkyl, 3- to 10-membered heterocycloalkyl containing 1-3 heteroatoms independently selected from N, O and S, 6- to 14-membered aryl, and 5- to 14-membered heteroaryl containing 1-4 heteroatoms independently selected from N, O and S; wherein cycloalkyl, heterocycloalkyl, aryl and heteroaryl are unsubstituted or substituted with halogen, CN, SF ５ , NO ２ , oxo, C １～４ -Alkyl, C ０～６ -Alkylene-OR ２１ , C ０～６ -alkylene-(3- to 6-membered cycloalkyl), C ０～６ -alkylene-(3- to 6-membered heterocycloalkyl), C ０～６ -Alkylene-S(O) ｎ R ２１ , C ０～６ -Alkylene-NR ２１ S (O) ２ R ２１ , C ０～６ -Alkylene-S(O) ２ NR ２１ R ２２ , C ０～６ -Alkylene-NR ２１ S (O) ２ NR ２１ R ２２ , C ０～６ -Alkylene-CR ４１ (=N-OR ４１ ), C ０～６ -Alkylene-CO ２ R ２１ , O-C １～６ -Alkylene-CO ２ R ２１ , C ０～６ -Alkylene-O-COR ２１ , C ０～６ -Alkylene-CONR ２１ R ２２ , C ０～６ -Alkylene-NR ２１ -COR ２１ , C ０～６ -Alkylene-NR ２１ -CONR ２１ R ２２ , C ０～６ -Alkylene-O-CONR ２１ R ２２ , C ０～６ -Alkylene-NR ２１ -CO ２ R ２１ and C ０～６ -Alkylene-NR ２１ R ２２ and is substituted with 1 to 6 substituents independently selected from the group consisting of: wherein alkyl, alkylene, cycloalkyl and heterocycloalkyl are unsubstituted or substituted with halogen, CN, oxo, hydroxy, CO ２ H, CO ２ -C １～４ -Alkyl, CONHCH ２ CO ２ H, CONH(CH ２ ) ２ SO ３ H, CO-OC １～４ -Alkyl, C １～４ -Alkyl, halo-C １～４ -alkyl, O—C １～４ -Alkyl and O-halo-C １～４ -substituted with 1 to 6 substituents independently selected from alkyl; wherein two adjacent substituents on the aryl or heteroaryl moiety may form a 5-8 membered partially unsaturated ring which may contain 1-3 heteroatoms independently selected from O, S or N; This further ring may be unsubstituted or may be substituted with halogen, CN, oxo, OH, CO ２ H, CO ２ -C １～４ -Alkyl, CONHCH ２ CO ２ H, CONH(CH ２ ) ２ SO ３ H, C １～４ -Alkyl, halo-C １～４ -alkyl, O—C １～４ -Alkyl and O-halo-C １～４ -substituted with 1 to 4 substituents independently selected from alkyl; wherein two adjacent substituents on the cycloalkyl or heterocycloalkyl moiety may form a 5-6 membered unsaturated ring which may contain 1 to 3 heteroatoms independently selected from O, S or N; This further ring may be unsubstituted or may be substituted with halogen, CN, oxo, OH, CO ２ H, CO ２ -C １～４ -Alkyl, CONHCH ２ CO ２ H, CONH(CH ２ ) ２ SO ３ H, C １～４ -Alkyl, halo-C １～４ -alkyl, O—C １～４ -Alkyl and O-halo-C １～４ -substituted with 1 to 4 substituents independently selected from alkyl; During the ceremony, 【Chemical 208】 teeth, 【Chemical Engineering 209】 or a further ring fused in a 1,2-orientation, L is a bond, C １～６ - alkylene, C ２～６ -Alkenylene, C ２～６ - selected from the group consisting of alkynylene, 3- to 10-membered cycloalkylene, 3- to 10-membered heterocycloalkylene containing 1-4 heteroatoms independently selected from N, O and S, 6- or 10-membered arylene, and 5- to 10-membered heteroarylene containing 1-4 heteroatoms independently selected from N, O and S; wherein alkylene, alkenylene, alkynylene, cycloalkylene, heterocycloalkylene, arylene and heteroarylene are unsubstituted or substituted with halogen, CN, SF ５ , NO ２ , oxo, C １～４ -Alkyl, C ０～６ -Alkylene-OR ４１ , C ０～６ -alkylene-(3- to 6-membered cycloalkyl), C ０～６ -alkylene-(3- to 6-membered heterocycloalkyl), C ０～６ -Alkylene-S(O) ｎ R ４１ , C ０～６ -Alkylene-NR ４１ S (O) ２ R ４１ , C ０～６ -Alkylene-S(O) ２ NR ４１ R ４２ , C ０～６ -Alkylene-NR ４１ S (O) ２ NR ４１ R ４２ , C ０～６ -Alkylene-CO ２ R ４１ , O-C １～６ -Alkylene-CO ２ R ４１ , C ０～６ -Alkylene-O-COR ４１ , C ０～６ -Alkylene-CONR ４１ R ４２ , C ０～６ -Alkylene-NR ４１ -COR ４１ , C ０～６ -Alkylene-NR ４１ -CONR ４１ R ４２ , C ０～６ -Alkylene-O-CONR ４１ R ４２ , C ０～６ -Alkylene-NR ４１ -CO ２ R ４１ and C ０～６ -Alkylene-NR ４１ R ４２ and is substituted with 1 to 6 substituents independently selected from the group consisting of: wherein alkyl, alkylene, cycloalkyl and heterocycloalkyl are unsubstituted or substituted with halogen, CN, oxo, hydroxy, CO ２ H, CO ２ -C １～４ -Alkyl, CONHCH ２ CO ２ H, CONH(CH ２ ) ２ SO ３ H, C １～４ -Alkyl, halo-C １～４ -alkyl, O—C １～４ -Alkyl and O-halo-C １～４ -substituted with 1 to 6 substituents independently selected from alkyl; wherein two adjacent substituents on the arylene and heteroarylene moieties may form a 5-8 membered partially unsaturated ring which may contain 1 to 3 heteroatoms independently selected from O, S, or N; This further ring may be unsubstituted or may be substituted with halogen, CN, oxo, OH, CO ２ H, CO ２ -C １～４ -Alkyl, C １～４ -Alkyl, halo-C １～４ -alkyl, O—C １～４ -Alkyl and O-halo-C １～４ -substituted with 1 to 4 substituents independently selected from alkyl; R １ is H, halogen, CN, SF ５ , NO ２ , oxo, C １～４ -Alkyl, C ０～６ -Alkylene-OR ４１ , Y.-C. ０～６ -alkylene-(3- to 6-membered cycloalkyl), Y-C ０～６ -alkylene-(3- to 6-membered heterocycloalkyl), Y—C ０～６ -alkylene-(6-membered aryl), Y-C ０～６ -alkylene-(5- to 6-membered heteroaryl), C ０～６ -Alkylene-S(=O)(-R ４１ ) = N-R ７５ , X-C １～６ -Alkylene-S(=O)(-R ４１ ) = N-R ７５ , C ０～６ -Alkylene-S(O) ｎ R ４１ , X-C １～６ -Alkylene-S(O) ｎ R ４１ , C ０～６ -Alkylene-S(=NR ７１ ) R ４１ , X-C １～６ -Alkylene-S(=NR ７１ ) R ４１ , C ０～６ -Alkylene-S(O)(=NR ７１ ) R ４１ , X-C １～６ -Alkylene-S(O)(=NR ７１ ) R ４１ , C ０～６ -Alkylene-S(=NR ７１ ) ２ R ４１ , X-C １～６ -Alkylene-S(=NR ７１ ) ２ R ４１ , C ０～６ -Alkylene-NR ４１ S (O) ２ R ４１ , X-C １～６ -Alkylene-NR ４１ S (O) ２ R ４１ , C ０～６ -Alkylene-S(O) ２ NR ４１ R ４２ , X-C １～６ -Alkylene-S(O) ２ NR ４１ R ４２ , C ０～６ -Alkylene-NR ４１ S (O) ２ NR ４１ R ４２ , X-C １～６ -Alkylene-NR ４１ S (O) ２ NR ４１ R ４２ , C ０～６ -Alkylene-SO ３ R ４１ , X-C １～６ -Alkylene-SO ３ R ４１ , C ０～６ -Alkylene-CO ２ R ４１ , X-C １～６ -Alkylene-CO ２ R ４１ , C ０～６ -Alkylene-O-COR ４１ , X-C １～６ -Alkylene-O-COR ４１ , C ０～６ -Alkylene-CONR ４１ R ４２ , X-C １～６ -Alkylene-CONR ４１ R ４２ , C ０～６ -Alkylene-CONR ４１ OR ４１ , X-C １～６ -Alkylene-CONR ４１ OR ４１ , C ０～６ -Alkylene-CONR ４１ SO ２ R ４１ , X-C １～６ -Alkylene-CONR ４１ SO ２ R ４１ , C ０～６ -Alkylene-NR ４１ -COR ４１ , X-C １～６ -C ０～６ -Alkylene-NR ４１ -COR ４１ , C ０～６ -Alkylene-NR ４１ -CONR ４１ R ４２ , X-C １～６ -Alkylene-NR ４１ -CONR ４１ R ４２ , C ０～６ -Alkylene-O-CONR ４１ R ４２ , X-C １～６ -Alkylene-O-CONR ４１ R ４２ , C ０～６ -Alkylene-NR ４１ -CO ２ R ４１ , X-C １～６ -Alkylene-NR ４１ -CO ２ R ４１ , C ０～６ -Alkylene-NR ４１ R ４２ , X-C １～６ -Alkylene-NR ４１ R ４２ is selected from the group consisting of wherein alkyl, alkylene, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are unsubstituted or substituted with halogen, CN, oxo, hydroxy, CO ２ H, CO ２ -C １～４ -Alkyl, CONHCH ２ CO ２ H, CONH(CH ２ ) ２ SO ３ H, C １～４ -Alkyl, halo-C １～４ -alkyl, O—C １～４ -Alkyl and O-halo-C １～４ -substituted with 1 to 6 substituents independently selected from alkyl; wherein two adjacent substituents on the aryl and heteroaryl moieties may form a 5-8 membered partially unsaturated ring which may contain 1-3 heteroatoms independently selected from O, S or N; This further ring may be unsubstituted or may be substituted with halogen, CN, oxo, OH, CO ２ H, CO ２ -C １～４ -Alkyl, CONHCH ２ CO ２ H, CONH(CH ２ ) ２ SO ３ H, C １～４ -Alkyl, halo-C １～４ -alkyl, O—C １～４ -Alkyl and O-halo-C １～４ -substituted with 1 to 4 substituents independently selected from alkyl; R １１ , R １２ , R ２１ , R ２２ , R ３１ , R ３２ , R ４１ , R ４２ , R ５１ are independently H and C １～４ - alkyl, wherein alkyl is unsubstituted or substituted with halogen, CN, C １～４ -Alkyl, halo-C １～４ -alkyl, 3- to 6-membered cycloalkyl, halo-(3- to 6-membered cycloalkyl), 3- to 6-membered heterocycloalkyl, halo-(3- to 6-membered heterocycloalkyl), OH, oxo, CO ２ H, CO ２ -C １～４ -Alkyl, CONHCH ２ CO ２ H, CONH(CH ２ ) ２ SO ３ H, SO ３ H, O-C １～４ -Alkyl and O-halo-C １～４ -substituted with 1 to 3 substituents independently selected from alkyl; or R １１ and R １２ , R ２１ and R ２２ , R ３１ and R ３２ , R ４１ and R ４２ each, when taken together with the nitrogen to which they are attached, completes a 3- to 6-membered ring containing carbon atoms and optionally containing 1 or 2 heteroatoms independently selected from O, S or N; The newly formed ring is unsubstituted or contains halogen, CN, C １～４ -Alkyl, halo-C １～４ -alkyl, 3- to 6-membered cycloalkyl, halo-(3- to 6-membered cycloalkyl), 3- to 6-membered heterocycloalkyl, halo-(3- to 6-membered heterocycloalkyl), OH, oxo, CO ２ H, CO ２ -C １～４ -Alkyl, CONHCH ２ CO ２ H, CONH(CH ２ ) ２ SO ３ H, SO ３ H, O-C １～４ -Alkyl and O-halo-C １～４ -substituted with 1 to 3 substituents independently selected from alkyl; R ７１ are independently H, CN, NO ２ , C １～４ -alkyl, and C(O)-OC １～４ - alkyl, wherein alkyl is unsubstituted or substituted with halogen, CN, C １～４ -Alkyl, halo-C １～４ -alkyl, 3- to 6-membered cycloalkyl, halo-(3- to 6-membered cycloalkyl), 3- to 6-membered heterocycloalkyl, halo-(3- to 6-membered heterocycloalkyl), OH, oxo, CO ２ H, CO ２ -C １～４ -Alkyl, CONHCH ２ CO ２ H, CONH(CH ２ ) ２ SO ３ H, SO ３ H, O-C １～４ -Alkyl and O-halo-C １～４ -substituted with 1 to 3 substituents independently selected from alkyl; R ７５ are independently １～４ selected from alkyl, 3- to 6-membered cycloalkyl, 3- to 6-membered heterocycloalkyl, 6-membered aryl, and 5- to 6-membered heteroaryl; wherein alkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are unsubstituted or substituted with halogen, CN, Me, Et, CHF ２ , C.F. ３ , OH, oxo, CO ２ H, CONHCH ２ CO ２ H, CONH(CH ２ ) ２ SO ３ H, SO ３ H, OMe, OEt, OCHF ２ and OCF ３ and is substituted with 1 to 3 substituents independently selected from X is independently O, NR ５１ , S(O) ｎ , S (= NR ７１ ), S(O)(=NR ７１ ) and S(=NR ７１ ) ２ is selected from Y is independently a bond, O, NR ５１ , S(O) ｎ , S (= NR ７１ ), S(O)(=NR ７１ ) and S(=NR ７１ ) ２ is selected from n is independently selected from 0 to 2; however, 【Chemical 210】 The structure of is excluded, pharmaceuticals. 【Request Item 6】 【Chemistry 211】 teeth, 【Chemical Engineering 212】 is selected from During the ceremony, 【Chemistry 213】 is unsubstituted or is selected from the group consisting of F, Cl, Br, CN, OH, oxo, C １～４ -Alkyl, halo-C １～４ -alkyl, O—C １～４ -alkyl, O-halo-C １～４ -Alkyl, NH ２ , N.H.C. １～４ -Alkyl, N(C １～４ -alkyl) ２ , S.O. ２ -C １～４ -Alkyl, and SO ２ -Halo-C １～４ 6. The method, use, compound, or medicament of any one of claims 1 to 5, wherein the aryl group is substituted with 1 to 3 substituents independently selected from the group consisting of -alkyl. 【Request Item 7】 【Chemistry 214】 is phenyl, naphthyl, pyridyl, pyrimidinyl, thiophenyl, thiazolyl, cyclopentyl, cyclohexyl, bicyclo[1.1.1]pentyl, bicyclo[2.2.2]octyl, bicyclo[2.2.1]heptyl, pentacyclo[4.2.0.0] ２，５ .0 ３，８ .0 ４，７ ]octyl, and piperidinyl; wherein the ring is unsubstituted or substituted with F, Cl, Br, CN, OH, oxo, C １～４ -Alkyl, halo-C １～４ -alkyl, O—C １～４ -alkyl, O-halo-C １～４ -Alkyl, C １～４ -alkyl-OH, and halo-C １～４ -alkyl-OH, and two adjacent substituents on the phenyl ring taken together form -(CH ２ ) ３ -, -(CH ２ ) ４ -, -OCF ２ O- and -OCH ２ The method, use, compound or medicament according to any one of claims 1 to 6, wherein an O-group may be formed. 【Request Item 8】 【Chemistry 215】 is selected from phenyl, pyridyl and thiophenyl, wherein phenyl, pyridyl and thiophenyl are unsubstituted or selected from F, Cl, CN, OH, oxo, C １～４ -Alkyl, halo-C １～４ -alkyl, O—C １～４ -Alkyl and O-halo-C １～４ -alkyl, and the residue -L-R １ teeth, 【Chemical 216】 and L is not a bond.

9. -L-R １ teeth, 【Chemical 217】 is selected from wherein the ring is unsubstituted or is selected from the group consisting of F, Cl, Br, CN, OH, oxo, C １～４ -Alkyl, halo-C １～４ -alkyl, O—C １～４ -alkyl, O-halo-C １～４ -Alkyl, C １～４ -Alkyl-OH, halo-C １～４ -Alkyl-OH, SO ２ -C １～４ -Alkyl and SO ２ -Halo-C １～４ -alkyl, and two adjacent substituents on the phenyl ring taken together form -(CH ２ ) ３ -, -(CH ２ ) ４ -, -OCF ２ O- and -OCH ２ 9. The method, use, compound or medicament according to any one of claims 1 to 8, which may form an O group.

10. R １ is CO ２ H, tetrazole, CH ２ CO ２ H, OCH ２ CO ２ H, SO ２ CH ２ CO ２ H, CHMeCO ２ H, CMe ２ CO ２ H,C(OH)MeCO ２ H, CONHSO ２ 10. The method, use, compound or medicament of any one of claims 1 to 9, wherein the hydroxybenzoate is selected from Me, and CONH(OH), and optionally glycine and taurine conjugates thereof. 【Request Item 11】 【Chemistry 218】 teeth, 【Chemical 219】 is selected from the group consisting of R ２ は、Me、F、Cl、CN、Me、CHO、CHF ２ CF ３ So ２ Me 【Chemical 220】 is selected from During the ceremony, 【Chemistry 221】 is F, Cl, CN, Me, OMe, CHO, CHF ２ and C.F. ３ The method, use, compound, or medicament according to any one of claims 1 to 10, optionally further substituted with 1 to 2 substituents selected from the group consisting of: 【Request Item 12】 【Chemistry 222】 teeth, 【Chemistry 223】 12. The method, use, compound or medicament of any one of claims 1 to 11, selected from the group consisting of:

13. Formula (I) is CO ２ H, tetrazole, CONHSO ２ 13. The method, use, compound or medicament of any one of claims 1 to 12, containing a substituent selected from the group consisting of Me, and CONH(OH), and optionally glycine and taurine conjugates thereof.

14. L-R １ teeth, 【Chemistry 224】 wherein the ring is unsubstituted or substituted with F, Cl, Br, CN, OH, oxo, C １～４ -Alkyl, halo-C １～４ -alkyl, O—C １～４ -alkyl, O-halo-C １～４ -Alkyl, C １～４ -Alkyl-OH, halo-C １～４ -Alkyl-OH, SO ２ -C １～４ -Alkyl and SO ２ -Halo-C １～４ -alkyl, wherein two adjacent substituents on the phenyl ring are taken together to form -(CH ２ ) ３ -, -(CH ２ ) ４ -, -OCF ２ O- and -OCH ２ The method, use, compound or medicament according to any one of claims 1 to 13, which may form an O-group.

15. R １ is C ０～６ -Alkylene-CO ２ R4 １ Or C ０～６ -Alkylene-CONR ４１ R ４２ 15. The method, use, compound, or medicament according to any one of claims 1 to 14, wherein the compound is benzophenone-3, benzophenone-4, benzotriazole-3, benzotriazole-4 ...

16. R １ The method, use, compound or medicament according to any one of claims 1 to 15, wherein is COOH, or a glycine or taurine conjugate thereof.

17. R １ is C ０～６ -Alkylene-CONR ４１ R ４２ The method, use, compound or medicament according to any one of claims 1 to 15, wherein

18. R ４１ and R ４２ are independently H and C １～４ alkyl, C １～４ The alkyl is unsubstituted or CO ２ 18. The method of claim 17, wherein said alkyl group is substituted with H.

19. -C-L-R １ teeth, 【Chemical 225】 19. The method, use, compound, or medicament according to any one of claims 1 to 18, wherein the compound is a glycine conjugate or a taurine conjugate thereof.

20. 20. The method, use, compound or medicament of any one of claims 1 to 19, wherein said compound is a glycine conjugate.

21. The compound is 【Chemistry 226】 21. The method, use, compound or medicament of any one of claims 1 to 20, which is or a pharmaceutically acceptable salt thereof.

22. 22. The method, use, compound or medicament of any one of claims 1 to 21, wherein the compound is: 【Chemistry 227】

23. The compound is 【Chemistry 228】 21. The method, use, compound or medicament according to any one of claims 1 to 20, which is a glycine conjugate thereof.

24. The compound is 【Chemistry 229】 24. The method, use, compound or medicament of any one of claims 1 to 23, which is or a pharmaceutically acceptable salt thereof.

25. 25. The method, use, compound or medicament of any one of claims 1 to 24, wherein the compound is: 【Chemistry 230】

26. 26. The method, use, compound or medicament of any one of claims 1 to 25, wherein the method is for treating dyslipidemia.

27. 27. The method, use, compound, or medicament of any one of claims 1 to 26, wherein the dyslipidemia is hypertriglyceridemia (HTG), severe hypertriglyceridemia (SHTG), familial hypercholesterolemia, heterozygous familial hypercholesterolemia, homozygous familial hypercholesterolemia, familial chylomicronemia syndrome, mixed disorder chylomicronemia, hypercholesterolemia, familial combined hyperlipidemia, familial dysbetalipoproteinemia, or mixed dyslipidemia.

28. 28. The method, use, compound or medicament of any one of claims 1 to 27, wherein said dyslipidemia is severe hypertriglyceridemia (SHTG).

29. 29. The method, use, compound or medicament of any one of claims 1 to 28, wherein said dyslipidemia is characterized by abnormal concentrations of one or more lipids and / or apolipoproteins.

30. 30. The method, use, compound or medicament of any one of claims 1 to 29, wherein said dyslipidemia is characterized by elevated levels of total cholesterol, LDL cholesterol, triglycerides (TG), or any combination of the foregoing.

31. 31. The method, use, compound or medicament of any one of claims 1 to 30, wherein said dyslipidemia is characterized by reduced levels of HDL cholesterol.

32. 32. The method, use, compound or medicament of any one of claims 1 to 31, wherein said method reduces the risk of pancreatitis in said subject.

33. 26. The method, use, compound or medicament of any one of claims 1 to 25, wherein said method is for treating a metabolic disorder associated with impaired lipid homeostasis.

34. 34. The method, use, compound or medicament of any one of claims 1 to 25 and 33, wherein said method comprises treating a metabolic disorder associated with a disorder in de novo lipogenesis.

35. 35. The method, use, compound, or medicament of any one of claims 1-25 and 33-34, wherein the method comprises treating non-alcoholic fatty liver disease (NAFLD) or non-alcoholic steatohepatitis (NASH) in a subject in need thereof, wherein the subject has a glucokinase regulatory protein (GCKR) phenotype.

36. 35. The method, use, compound or medicament of claim 34, wherein de novo lipogenesis is enhanced in the subject.

37. 36. The method, use, compound or medicament of claim 34 or claim 35, wherein the expression of lipogenic genes in said subject and / or lipid accumulation in said subject is reduced.

38. 38. The method, use, compound, or medicament of any one of claims 1 to 37, wherein the subject is administered 0.1 to 25 mg per day of the compound of formula (I), or its glycine conjugates, taurine conjugates, enantiomers, diastereomers, tautomers, N-oxides, solvates, prodrugs, and pharmaceutically acceptable salts.

39. 39. The method, use, compound or medicament of claim 38, wherein 5 to 15 mg of the compound is administered.

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