Compounds which bind to pnpla3i148m and their use to treat liver diseases

Abstract

The invention relates to compounds of Formula (I), and pharmaceutically acceptable salts and isomers of such compounds, which bind to patatin-like phospholipase domain-containing protein 3 (PNPLA3) mutation PNPLA3I148M, (I) pharmaceutical compositions comprising a compound of Formula (I), or pharmaceutically acceptable salts thereof, and their use in methods for the treatment of diseases associated with PNPLA3I148M.

Description

[0001] COMPOUNDS WHICH BIND TO PNPLA3I148M AND THEIR USE TO TREAT LIVER DISEASES

[0002] FIELD OF THE INVENTION

[0003] The present invention relates to compounds, and pharmaceutically acceptable salts and isomers of such compounds, which bind to patatin-like phospholipase domain-containing protein 3 (PNPLA3) mutation PNPLA3I148M. In addition, the invention relates to pharmaceutical compositions and combinations comprising such compounds and to their use in methods for the treatment of diseases associated with PNPLA3I148M.

[0004] BACKGROUND OF THE INVENTION

[0005] Patatin-like phospholipase-domain-containing 2 (PNPLA2; also known as adipose triglyceride lipase, ATGL) and PNPLA3 (also known as adiponutrin) are encoded by close paralogues and appear to have opposite functions on triglycerides (TAGs) mobilization and storage. The human PNPLA3 gene is expressed in the liver and highly induced during the fed state and is likely important in lipid partitioning in times of nutrient surplus, which is in contrast to PNPLA2, the primary triglyceride (TAG) lipase activated in times of energetic need (e.g. fasting) (Wilson et al., 2006).

[0006] Nonalcoholic fatty liver disease (NAFLD) is a spectrum of conditions that begins as the benign state of hepatic steatosis and progresses in a subset of patients to severe states including nonalcoholic steatohepatitis (NASH), cirrhosis with liver fibrosis and hepatocellular carcinoma (HOC). Recently, non-alcoholic fatty liver disease (NAFLD) was renamed to metabolic dysfunction-associated steatotic liver disease (MASLD), and subsequently nonalcoholic steatohepatitis (NASH) was renamed to metabolic dysfunction-associated steatohepatitis (MASH) (Rinella et all, 2023).

[0007] Global prevalence of NAFLD is estimated to be about 25% and constantly increasing (Younossi et al., 2018; Younossi and Henry, 2021). In Western markets, there are currently no approved medicines to treat NAFLD. Gastric bypass surgery and / or weight loss of greater than 10% are the therapies with the most clinical benefit (Lassailly et al., 2015; Lassailly et al., 2020).

[0008] Predicting who will progress from steatosis to NASH, cirrhosis, and HOC is challenging. In 2008, a genome wide association studies (GWAS) identified a nonsynonymous variant in a gene encoding PNPLA3 that is causal for developing steatosis and increasing the risk for NASH progression (Romeo et aL, 2008). The identified variant (rs738409) results in a change of the amino acid sequence at position 148 replacing an isoleucine with a methionine (I148M). Subsequent GWAS studies identified additional genes and at the same time corroborated the dominant effect of the PNPLA3I148M variant (reviewed by (Trepo and Valenti, 2020)). Prevalence for PNPLA3I148M variant varies around the globe with the highest allele frequency in Mexico and Hispanic Americans with more than 50% (Younossi et al., 2018). PNPLA3I148M is also strongly associated with progression to severe liver disease in alcoholic steatohepatitis, viral hepatitis, Wilson’s disease, hereditary hemochromatosis, autoimmune hepatitis, and primary sclerosing cholangitis (Dongiovanni et aL, 2013; Mederacke et al., 2020). NASH caused by PNPLA3I148M is inherited in an autosomal dominant pattern with penetrance influenced by obesity and diabetes.

[0009] Neither overexpression of the wild type allele nor gene deletion causes a disease phenotype in mice. In contrast, over expression of the human PNPLA3I148M in the mouse liver under the control of an albumin promoter coupled with a high sucrose diet results in elevated hepatic triglyceride levels and NAFLD-related phenotypes (Li et aL, 2012; Smagris et aL, 2015). A reduced proteasomal degradation of PNPLA3 on the lipid droplets has been suggested as a possible pathophysiological mechanism causing this phenotype (BasuRay et aL, 2017; BasuRay et aL, 2019). a / p-hydrolase-domain-containing 5 (ABHD5; also known as CGI-58) is an essential coactivator of PNPLA2. Accumulation of PNPLA3I148M on lipid droplets interferes with TAG hydrolysis by sequestering ABHD5 (CGI-58) on lipid droplets, and as a result limits cofactor availability for activation of ATGL (PNPLA2), which results in an increase in hepatic TG levels. (Yang, W. et. aL, 2019).

[0010] Linden et aL were the first to demonstrate that liver targeted silencing using an antisense oligonucleotide (ASO) of a human PNPLA3I148M mutation expressed in a mouse knock-in model reduced liver steatosis and several other NASH relevant features such as hepatic inflammation and fibrosis (Linden et al., 2019). However, to date the use of small molecule binders to PNPLA3I148M to treat liver disease have yet to be described.

[0011] References

[0012] BasuRay, S., Smagris, E., Cohen, J.C., and Hobbs, H.H. (2017). The PNPLA3 variant associated with fatty liver disease (I148M) accumulates on lipid droplets by evading ubiquitylation. Hepatology 66, 1111 -1124.

[0013] BasuRay, S., Wang, Y., Smagris, E., Cohen, J.C., and Hobbs, H.H. (2019). Accumulation of PNPLA3 on lipid droplets is the basis of associated hepatic steatosis. Proc Natl Acad Sci U S A 116, 9521 -9526.

[0014] Dongiovanni, P., Donati, B., Fares, R., Lombardi, R., Mancina, R.M., Romeo, S., and Valenti, L. (2013). PNPLA3I148M polymorphism and progressive liver disease. World J Gastroenterol 19, 6969-6978.

[0015] Lassailly, G., Caiazzo, R., Buob, D., Pigeyre, M., Verkindt, H., Labreuche, J., Raverdy, V., Leteurtre, E., Dharancy, S., Louvet, A., etal. (2015). Bariatric Surgery Reduces Features of Nonalcoholic Steatohepatitis in Morbidly Obese Patients. Gastroenterology 149, 379-388; quiz e315-376. Lassailly, G., Caiazzo, R., Ntandja-Wandji, L.C., Gnemmi, V., Baud, G., Verkindt, H., Ningarhari, M., Louvet, A., Leteurtre, E., Raverdy, V., et al. (2020). Bariatric Surgery Provides Long-term Resolution of Nonalcoholic Steatohepatitis and Regression of Fibrosis. Gastroenterology 159, 1290-1301 e1295.

[0016] Li, J.Z., Huang, Y., Karaman, R., Ivanova, P.T., Brown, H.A., Roddy, T., Castro-Perez, J., Cohen, J.C., and Hobbs, H.H. (2012). Chronic overexpression of PNPLA3I148M in mouse liver causes hepatic steatosis. J Clin Invest 122, 4130-4144.

[0017] Linden, D., Ahnmark, A., Pingitore, P., Ciociola, E., Ahlstedt, I., Andreasson, A.C., Sasidharan, K., Madeyski-Bengtson, K., Zurek, M., Mancina, R.M., et al. (2019). Pnpla3 silencing with antisense oligonucleotides ameliorates nonalcoholic steatohepatitis and fibrosis in PNPLA3I148M knock-in mice. Mol Metab 22, 49-61.

[0018] Mederacke, Y.S., Kirstein, M.M., Grosshennig, A., Marhenke, S., Metzler, F., Manns, M.P., Vogel, A., and Mederacke, I. (2020). The PNPLA3 rs738409 GG genotype is associated with poorer prognosis in 239 patients with autoimmune hepatitis. Aliment Pharmacol Ther 5 / , 1160- 1168.

[0019] Romeo, S., Kozlitina, J., Xing, C., Pertsemlidis, A., Cox, D., Pennacchio, L.A., Boerwinkle, E., Cohen, J.C., and Hobbs, H.H. (2008). Genetic variation in PNPLA3 confers susceptibility to nonalcoholic fatty liver disease. Nat Genet 40, 1461-1465.

[0020] Smagris, E., BasuRay, S., Li, J., Huang, Y., Lai, K.M., Gromada, J., Cohen, J.C., and Hobbs, H.H. (2015). PNPLA3I148M knockin mice accumulate PNPLA3 on lipid droplets and develop hepatic steatosis. Hepatology 61, 108-118.

[0021] Trepo, E., and Valenti, L. (2020). Update on NAFLD genetics: From new variants to the clinic. J Hepatol 72, 1196-1209.

[0022] Wilson, P.A., Gardner, S.D., Lambie, N.M., Commans, S.A., and Crowther, D.J. (2006). Characterization of the human patatin-like phospholipase family. J Lipid Res 47, 1940-1949. Younossi, Z., Anstee, Q.M., Marietti, M., Hardy, T., Henry, L., Eslam, M., George, J., and Bugianesi, E. (2018). Global burden of NAFLD and NASH: trends, predictions, risk factors and prevention. Nat Rev Gastroenterol Hepatol 15, 11 -20.

[0023] Younossi, Z.M., and Henry, L. (2021 ). Epidemiology of non-alcoholic fatty liver disease and hepatocellular carcinoma. JHEP Rep 3, 100305.

[0024] Yang Wang, Nora Kory, Soumik BasuRay, Jonathan C. Cohen, and Helen H. Hobbs. (2019). PNPLA3, CGI-58, and Inhibition of Hepatic Triglyceride Hydrolysis in Mice. Hepatology, 69(6): 2427-2441 .

[0025] Renella, M.E. et al, A multisociety Delphi consensus statement on new fatty liver disease nomenclature, Hepatology, 2023, 78: 1966-1986.

[0026] SUMMARY OF THE INVENTION There remains the need for low molecular weight compounds which bind to PNPLA3I148M, thereby normalizing lipolysis and can therefore be used to treat a wide range of liver diseases related to the pathophysiology of PNPLA3I148M.

[0027] Provided herein are compounds which bind to PNPLA3I148M, thereby normalizing lipolysis, and therefore such compounds can be used to treat a PNPLA3I148M associated disease. In an embodiment of this aspect the PNPLA3I148M associated disease is a liver disease. In another embodiment of this aspect, the PNPLA3I148M associated disease is a metabolic dysfunction-associated steatotic liver disease (MASLD). In another embodiment of this aspect, the PNPLA3I148M associated disease is a nonalcoholic fatty liver disease (NAFLD). In another embodiment of this aspect, the PNPLA3I148M associated disease is an alcoholic liver disease (ALD). In an embodiment of this aspect the PNPLA3I148M associated disease is metabolic dysfunction-associated steatohepatitis (MASH), nonalcoholic steatohepatitis (NASH), alcoholic steatohepatitis (ASH), cirrhosis with liver fibrosis or hepatocellular carcinoma (HCC). In an embodiment of this aspect the PNPLA3I148M associated disease is metabolic dysfunction-associated steatohepatitis (MASH). In an embodiment of this aspect the PNPLA3I148M associated disease is nonalcoholic steatohepatitis (NASH). In an embodiment of this aspect the PNPLA3I148M associated disease is alcoholic steatohepatitis (ASH). In an embodiment of this aspect the PNPLA3I148M associated disease cirrhosis with liver fibrosis or hepatocellular carcinoma (HCC).

[0028] Furthermore, provided herein are compounds which bind to PNPLA3I148M, thereby disrupting the complex of ABHD5 and PNPLA3I148M (i.e. PNPLA3I148M-ABHD5), which results in normalizing lipolysis, and therefore, such compounds can be used to treat a PNPLA3I148M associated disease. In an embodiment of this aspect the PNPLA3I148M associated disease is a liver disease. In another embodiment of this aspect, the PNPLA3I148M associated disease is a metabolic dysfunction-associated steatotic liver disease (MASLD). In another embodiment of this aspect, the PNPLA3I148M associated disease is a nonalcoholic fatty liver disease (NAFLD). In another embodiment of this aspect, the PNPLA3I148M associated disease is an alcoholic liver disease (ALD). In an embodiment of this aspect the PNPLA3I148M associated disease is metabolic dysfunction-associated steatohepatitis (MASH), nonalcoholic steatohepatitis (NASH), alcoholic steatohepatitis (ASH), cirrhosis with liver fibrosis or hepatocellular carcinoma (HCC). In an embodiment of this aspect the PNPLA3I148M associated disease is metabolic dysfunction-associated steatohepatitis (MASH). In an embodiment of this aspect the PNPLA3I148M associated disease is nonalcoholic steatohepatitis (NASH). In an embodiment of this aspect the PNPLA3I148M associated disease is alcoholic steatohepatitis (ASH). In an embodiment of this aspect the PNPLA3I148M associated disease cirrhosis with liver fibrosis or hepatocellular carcinoma (HCC). In one aspect, the compounds provided herein which bind to PNPLA3I148M are compounds having the structure of Formula (I), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof: wherein RA, Li, X, Y, R5, Zi, Z2, Z3, Z4, Z5, L2and R8are as defined herein.

[0029] In another aspect disclosed herein is a pharmaceutical composition comprising a compound of Formula (I), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, and one or more pharmaceutically acceptable carriers.

[0030] In another aspect disclosed herein is a pharmaceutical composition comprising a therapeutically effective amount of a compound of Formula (I), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, and one or more pharmaceutically acceptable carriers.

[0031] In another aspect disclosed herein is a pharmaceutical composition comprising a compound of Formula (I), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, and one or more therapeutically active agents.

[0032] In another aspect disclosed herein is a pharmaceutical composition comprising a therapeutically effective amount of a compound of Formula (I), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, and one or more therapeutically active agents.

[0033] In another aspect disclosed herein is a pharmaceutical composition comprising a compound of Formula (I), or a pharmaceutically acceptable acid addition salt thereof, or a stereoisomer thereof, or a pharmaceutically acceptable acid addition salt of a stereoisomer thereof, and one or more pharmaceutically acceptable carriers.

[0034] In another aspect disclosed herein is a pharmaceutical composition comprising a therapeutically effective amount of a compound of Formula (I), or a pharmaceutically acceptable acid addition salt thereof, or a stereoisomer thereof, or a pharmaceutically acceptable acid addition salt of a stereoisomer thereof, and one or more pharmaceutically acceptable carriers.

[0035] In another aspect disclosed herein is a pharmaceutical composition comprising a compound of Formula (I), or a pharmaceutically acceptable acid addition salt thereof, or a stereoisomer thereof, or a pharmaceutically acceptable acid addition salt of a stereoisomer thereof, and one or more therapeutically active agents. In another aspect disclosed herein is a pharmaceutical composition comprising a therapeutically effective amount of a compound of Formula (I), or a pharmaceutically acceptable acid addition salt thereof, or a stereoisomer thereof, or a pharmaceutically acceptable acid addition salt of a stereoisomer thereof, and one or more therapeutically active agents.

[0036] In another aspect disclosed herein is a pharmaceutical combination comprising a compound of Formula (I), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, and one or more therapeutically active agents.

[0037] In another aspect disclosed herein is a pharmaceutical combination comprising a therapeutically effective amount of a compound of Formula (I), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, and one or more therapeutically active agents.

[0038] In another aspect disclosed herein is a compound of Formula (I), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof for use as a medicament.

[0039] In another aspect disclosed herein is a compound of Formula (I), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof for use in treating a PNPLA3I148M associated disease. In an embodiment of this aspect the PNPLA3I148M associated disease is a liver disease. In another embodiment of this aspect, the PNPLA3I148M associated disease is a metabolic dysfunction -associated steatotic liver disease (MASLD). In another embodiment of this aspect, the PNPLA3I148M associated disease is a nonalcoholic fatty liver disease (NAFLD). In another embodiment of this aspect, the PNPLA3I148M associated disease is an alcoholic liver disease (ALD). In an embodiment of this aspect the PNPLA3I148M associated disease is metabolic dysfunction- associated steatohepatitis (MASH), nonalcoholic steatohepatitis (NASH), alcoholic steatohepatitis (ASH), cirrhosis with liver fibrosis or hepatocellular carcinoma (HCC). In an embodiment of this aspect the PNPLA3I148M associated disease is metabolic dysfunction- associated steatohepatitis (MASH). In an embodiment of this aspect the PNPLA3I148M associated disease is nonalcoholic steatohepatitis (NASH). In an embodiment of this aspect the PNPLA3I148M associated disease is alcoholic steatohepatitis (ASH). In an embodiment of this aspect the PNPLA3I148M associated disease cirrhosis with liver fibrosis or hepatocellular carcinoma (HCC).

[0040] In another aspect disclosed herein is the use of a compound of Formula (I), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof for the treatment of a PNPLA3I148M associated disease. In an embodiment of this aspect the PNPLA3I148M associated disease is a liver disease. In another embodiment of this aspect, the PNPLA3I148M associated disease is a metabolic dysfunction-associated steatotic liver disease (MASLD). In another embodiment of this aspect, the PNPLA3I148M associated disease is a nonalcoholic fatty liver disease (NAFLD). In another embodiment of this aspect, the PNPLA3I148M associated disease is an alcoholic liver disease (ALD). In an embodiment of this aspect the PNPLA3I148M associated disease is metabolic dysfunction-associated steatohepatitis (MASH), nonalcoholic steatohepatitis (NASH), alcoholic steatohepatitis (ASH), cirrhosis with liver fibrosis or hepatocellular carcinoma (HCC). In an embodiment of this aspect the PNPLA3I148M associated disease is metabolic dysfunction-associated steatohepatitis (MASH). In an embodiment of this aspect the PNPLA3I148M associated disease is nonalcoholic steatohepatitis (NASH). In an embodiment of this aspect the PNPLA3I148M associated disease is alcoholic steatohepatitis (ASH). In an embodiment of this aspect the PNPLA3I148M associated disease cirrhosis with liver fibrosis or hepatocellular carcinoma (HCC).

[0041] In another aspect disclosed herein is the use of a compound of Formula (I), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof in the manufacture of a medicament for the treatment of a PNPLA3I148M associated disease. In an embodiment of this aspect the PNPLA3I148M associated disease is a liver disease. In another embodiment of this aspect, the PNPLA3I148M associated disease is a metabolic dysfunction-associated steatotic liver disease (MASLD). In another embodiment of this aspect, the PNPLA3I148M associated disease is a nonalcoholic fatty liver disease (NAFLD). In an embodiment of this aspect the PNPLA3I148M associated disease is metabolic dysfunction-associated steatohepatitis (MASH), nonalcoholic steatohepatitis (NASH), alcoholic steatohepatitis (ASH), cirrhosis with liver fibrosis or hepatocellular carcinoma (HCC). In an embodiment of this aspect the PNPLA3I148M associated disease is metabolic dysfunction-associated steatohepatitis (MASH). In an embodiment of this aspect the PNPLA3I148M associated disease is nonalcoholic steatohepatitis (NASH). In an embodiment of this aspect the PNPLA3I148M associated disease is alcoholic steatohepatitis (ASH). In an embodiment of this aspect the PNPLA3I148M associated disease cirrhosis with liver fibrosis or hepatocellular carcinoma (HCC).

[0042] In another aspect disclosed herein is a method for treating a PNPLA3I148M associated disease comprising administering to a subject in need thereof a compound of Formula (I), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof. In an embodiment of this aspect the PNPLA3I148M associated disease is a liver disease. In another embodiment of this aspect, the PNPLA3I148M associated disease is a metabolic dysfunction-associated steatotic liver disease (MASLD). In another embodiment of this aspect, the PNPLA3I148M associated disease is a nonalcoholic fatty liver disease (NAFLD). In another embodiment of this aspect, the PNPLA3I148M associated disease is an alcoholic liver disease (ALD). In an embodiment of this aspect the PNPLA3I148M associated disease is metabolic dysfunction-associated steatohepatitis (MASH), nonalcoholic steatohepatitis (NASH), alcoholic steatohepatitis (ASH), cirrhosis with liver fibrosis or hepatocellular carcinoma (HCC). In an embodiment of this aspect the PNPLA3I148M associated disease is metabolic dysfunction-associated steatohepatitis (MASH). In an embodiment of this aspect the PNPLA3I148M associated disease is nonalcoholic steatohepatitis (NASH). In an embodiment of this aspect the PNPLA3I148M associated disease is alcoholic steatohepatitis (ASH). In an embodiment of this aspect the PNPLA3I148M associated disease cirrhosis with liver fibrosis or hepatocellular carcinoma (HCC).

[0043] In another aspect disclosed herein is a method for treating a PNPLA3I148M associated disease comprising administering to a subject in need thereof a therapeutically effective amount of a compound of Formula (I), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof. In an embodiment of this aspect the PNPLA3I148M associated disease is a liver disease. In another embodiment of this aspect, the PNPLA3I148M associated disease is a metabolic dysfunction-associated steatotic liver disease (MASLD). In another embodiment of this aspect, the PNPLA3I148M associated disease is a nonalcoholic fatty liver disease (NAFLD). In another embodiment of this aspect, the PNPLA3I148M associated disease is an alcoholic liver disease (ALD). In an embodiment of this aspect the PNPLA3I148M associated disease is metabolic dysfunction- associated steatohepatitis (MASH), nonalcoholic steatohepatitis (NASH), alcoholic steatohepatitis (ASH), cirrhosis with liver fibrosis or hepatocellular carcinoma (HCC). In an embodiment of this aspect the PNPLA3I148M associated disease is metabolic dysfunction- associated steatohepatitis (MASH). In an embodiment of this aspect the PNPLA3I148M associated disease is nonalcoholic steatohepatitis (NASH). In an embodiment of this aspect the PNPLA3I148M associated disease is alcoholic steatohepatitis (ASH). In an embodiment of this aspect the PNPLA3I148M associated disease cirrhosis with liver fibrosis or hepatocellular carcinoma (HCC).

[0044] In another aspect disclosed herein is a method for normalizing lipolysis by administering to a subject in need thereof of a compound of Formula (I), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof.

[0045] In another aspect disclosed herein is a method for normalizing lipolysis by administering to a subject in need thereof a therapeutically effective amount of a compound of Formula (I), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof.

[0046] In another aspect disclosed herein is a method for normalizing lipolysis by disrupting a PNPLA3I148M-ABHD5 complex, wherein the method comprises administering to a subject in need thereof a compound of Formula (I), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof.

[0047] In another aspect disclosed herein is a method for normalizing lipolysis by disrupting a PNPLA3I148M-ABHD5 complex, wherein the method comprises administering to a subject in need thereof a therapeutically effective amount of a compound of Formula (I), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof.

[0048] In another aspect disclosed herein is a method for treating a PNPLA3I148M associated disease by normalizing lipolysis, wherein the method comprises administering to a subject in need thereof of a compound of Formula (I), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof. In an embodiment of this aspect the PNPLA3I148M associated disease is a liver disease. In another embodiment of this aspect, the PNPLA3I148M associated disease is a metabolic dysfunction- associated steatotic liver disease (MASLD). In another embodiment of this aspect, the PNPLA3I148M associated disease is a nonalcoholic fatty liver disease (NAFLD). In another embodiment of this aspect, the PNPLA3I148M associated disease is an alcoholic liver disease (ALD). In an embodiment of this aspect the PNPLA3I148M associated disease is metabolic dysfunction-associated steatohepatitis (MASH), nonalcoholic steatohepatitis (NASH), alcoholic steatohepatitis (ASH), cirrhosis with liver fibrosis or hepatocellular carcinoma (HCC). In an embodiment of this aspect the PNPLA3I148M associated disease is metabolic dysfunction- associated steatohepatitis (MASH). In an embodiment of this aspect the PNPLA3I148M associated disease is nonalcoholic steatohepatitis (NASH). In an embodiment of this aspect the PNPLA3I148M associated disease is alcoholic steatohepatitis (ASH). In an embodiment of this aspect the PNPLA3I148M associated disease cirrhosis with liver fibrosis or hepatocellular carcinoma (HCC).

[0049] In another aspect disclosed herein is a method for treating a PNPLA3I148M associated disease by normalizing lipolysis, wherein the method comprises administering to a subject in need thereof a therapeutically effective amount of a compound of Formula (I), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof. In an embodiment of this aspect the PNPLA3I148M associated disease is a liver disease. In another embodiment of this aspect, the PNPLA3I148M associated disease is a metabolic dysfunction-associated steatotic liver disease (MASLD). In another embodiment of this aspect, the PNPLA3I148M associated disease is a nonalcoholic fatty liver disease (NAFLD). In another embodiment of this aspect, the PNPLA3I148M associated disease is an alcoholic liver disease (ALD). In an embodiment of this aspect the PNPLA3I148M associated disease is metabolic dysfunction-associated steatohepatitis (MASH), nonalcoholic steatohepatitis (NASH), alcoholic steatohepatitis (ASH), cirrhosis with liver fibrosis or hepatocellular carcinoma (HCC). In an embodiment of this aspect the PNPLA3I148M associated disease is metabolic dysfunction-associated steatohepatitis (MASH). In an embodiment of this aspect the PNPLA3I148M associated disease is nonalcoholic steatohepatitis (NASH). In an embodiment of this aspect the PNPLA3I148M associated disease is alcoholic steatohepatitis (ASH). In an embodiment of this aspect the PNPLA3I148M associated disease cirrhosis with liver fibrosis or hepatocellular carcinoma (HCC).

[0050] In another aspect, provided herein are intermediate compounds useful for making the compounds of Formula (I) as defined herein, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof.

[0051] In certain embodiments, the compounds of Formula (I) may bind to patatin-like phospholipase domain-containing protein 3 (PNPLA3).

[0052] BRIEF DESCRIPTION OF THE FIGURES

[0053] Figure 1 : illustrates a representative powder X-ray diffractogram (XRPD) curve of (S)-N-(6-(3- (4,4-difluoropyrrolidin-2-yl)-1 H-1 ,2,4-triazol-1-yl)-5-fluoropyridin-3-yl)-2-(5-methyl-3- (trifluoromethyl)-l H-pyrazol-1-yl)acetamide monohydrate.

[0054] Figure 2: illustrates a representative differential scanning calorimetry (DSC) curve of (S)-N-(6- (3-(4,4-difluoropyrrolidin-2-yl)-1 H-1 ,2,4-triazol-1-yl)-5-fluoropyridin-3-yl)-2-(5-methyl-3- (trifluoromethyl)-l H-pyrazol-1-yl)acetamide monohydrate.

[0055] Figure 3: illustrates a representative thermogravimetric analysis (TGA) curve of (S)-N-(6-(3- (4,4-difluoropyrrolidin-2-yl)-1 H-1 ,2,4-triazol-1-yl)-5-fluoropyridin-3-yl)-2-(5-methyl-3- (trifluoromethyl)-l H-pyrazol-1-yl)acetamide monohydrate.

[0056] DETAILED DESCRIPTION OF THE INVENTION

[0057] Definitions

[0058] The term “alkyl,” as used herein, refers to a saturated branched or straight chain hydrocarbon. In certain embodiments an alkyl group is a "Ci-C2alkyl", "Ci-C3alkyl" or "Ci- C4alkyl" group, wherein the terms "Ci-Czalkyl", "Ci-C3alkyl" and "Ci-C4alkyl", as used herein, refer to the alkyl group containing at least 1 , and at most 2, 3 or 4 carbon atoms, respectively. "Ci-C2alkyl" groups are methyl and ethyl. Non-limiting examples of "Ci-C3alkyl" groups include methyl, ethyl, n-propyl, and isopropyl. Non-limiting examples of "Ci-C4alkyl" groups include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl and tert-butyl.

[0059] The term “alkenyl,” as used herein, refers to a partially saturated branched or straight hydrocarbon chain having one more double bonds. In certain embodiments an alkenyl group is a "C2-C3alkenyl", "C2-C4alkenyl", "C2-C5alkenyl", "C2-C6alkenyl", "C2-C7alkenyl", ''C2-C8alkenyl", "C2-C9alkenyl" or "C2-Cioalkenyl", wherein the terms "C2-C3alkenyl", "C2-C4alkenyl", ”C2- Csalkenyl", "C2-C6alkenyl", "C2-C7alkenyl", "C2-C8alkenyl", "C2-Cgalkenyl" and "C2-Cioalkenyl", as used herein, refer to an alkenyl group containing at least 2, and at most 3, 4, 5, 6, 7, 8, 9 or 10 carbon atoms, respectively. Non-limiting examples of alkenyl groups include ethenyl, n- propenyl, isopropenyl, n-butenyl, isobutenyl, sec-butenyl, terf-butenyl, n-pentenyl, isopentenyl, n-hexenyl, n-heptenyl, n-octenyl, n-nonenyl and n-decenyl.

[0060] The term “alkynyl,” as used herein, refers to a partially saturated branched or straight hydrocarbon chain having one more triple bonds. In certain embodiments an alkynyl group is a "C2-C3alkynyl", "C2-C4alkynyl", "C2-C5alkynyl", "C2-C6alkynyl", "C2-C7alkynyl", "C2-C8alkynyl", "C2-C9alkynyl" or "C2-Cioalkynyl", wherein the terms "C2-C3alkynyl", "C2-C4alkynyl", "C2- Csalkynyl", "C2-C6alkynyl", "C2-C7alkynyl", "C2-C8alkynyl", "C2-C9alkynyl" and "C2-Cioalkynyl", as used herein, refer to an alkynyl group containing at least 2, and at most 3, 4, 5, 6, 7, 8, 9 or 10 carbon atoms, respectively. Non-limiting examples of alkynyl groups include ethynyl, propynyl, butynyl, sec-butynyl, n-pentynyl, isopentynyl, n-hexynyl, n-heptynyl, n-octynyl, n-nonynyl and n- decynyl.

[0061] The term "alkoxy", as used herein, refers to -O-alkyl, wherein the "alkyl" group is as defined herein. In certain embodiments an alkoxy group is a "Ci-C2alkoxy", "Ci-C3alkoxy" or "Cr C4alkoxy", wherein the terms "Ci-C2alkoxy", "Ci-Csalkoxy" and "Ci-C4alkoxy", as used herein, refer to -O-CrC2alkyl, -O-C Csalkyl or -O-Ci-C4alkyl, respectively. "Ci-C2alkoxy" groups are methoxy and ethoxy. Non-limiting examples of "CrCsalkoxy" groups include methoxy, ethoxy, n-propoxy and isopropoxy. Non-limiting examples of "CrC4alkoxy" groups include methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy and tert-butoxy.

[0062] The term “diCi-C4alkylamino”, as used herein, refers to a -NR2group, where each R is a Cr C4alky.

[0063] The term “C3-C4cycloalkyl” as used herein, refers to a saturated, monocyclic hydrocarbon ring system having 3 to 4 carbon atoms as ring members. Non-limiting examples of such “C3- C4cycloalkyl” groups include cyclopropyl and cyclobutyl.

[0064] The term “C3-Cecycloalkyl” as used herein, refers to a saturated, monocyclic hydrocarbon ring system having 3 to 6 carbon atoms as ring members. Non-limiting examples of such “C3- Cecycloalkyl” groups include cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl.

[0065] The term “Cs-Cscycloalkyl” as used herein, refers to a saturated, monocyclic hydrocarbon ring system having 3 to 8 carbon atoms as ring members. Non-limiting examples of such “C3- C8cycloalkyl” groups include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl and cyclooctyl.

[0066] The term "Ci-C4fluoroalkyl" as used herein, refer to the respective "Ci-C4alkyl", as defined herein, wherein at least one of the hydrogen atoms of the "Ci-C4alkyl" is replaced by a fluoro atom. The Ci-C4fluoroalkyl groups can be monoCi -C4fluoroalkyl, wherein such Ci-C4fluoroalkyl groups have one fluoro atom. Additionally, the Ci-C4fluoroalkyl groups can be diCi-C4fluoroalkyl wherein such C C4fluoroalkyl groups can have two fluoro atoms. Furthermore, the Cr C4fluoroalkyl groups can be polyCi-C4fluoroalkyl wherein such Ci-C4fluoroalkyl groups can have two or more fluoro atoms. Such polyCi -C4fluoroalkyl can be perfluoroCi -C4fluoroalkyl where all the hydrogen atoms of the respective Ci-C4alkyl have been replaced with fluoro atoms. Nonlimiting examples of “Ci-C4fluoroalkyl" groups include fluoromethyl, difluoromethyl, trifluoromethyl, fluoroethyl, difluoroethyl, trifluoroethyl, pentafluoroethyl, difluoropropyl and heptafluoropropyl.

[0067] The term "Ci-C4fluoroalkoxy" as used herein, refer to the respective "Ci-C4alkoxy", as defined herein, wherein at least one of the hydrogen atoms of the "Ci-C4alkyl" of the "Ci - C4alkoxy" is replaced by a fluoro atom. The Ci-C4fluoroalkoxy groups can be monoCi- C4fluoroalkoxy, wherein such Ci-C fluoroalkoxy groups have one fluoro atom. Additionally, the Ci-C4fluoroalkoxy groups can be diCi-C4fluoroalkoxy wherein such Ci-C4fluoroalkoxy groups can have two fluoro atoms. Furthermore, the Ci-C4fluoroalkoxy groups can be polyCi- C4fluoroalkoxy wherein such Ci-C4fluoroalkoxy groups can have two or more fluoro atoms. Such polyCi -C4fluoroalkoxy can be perfluoroCi -C4fluoroalkoxy where all the hydrogen atoms of the respective Ci-C alkyl have been replaced with fluoro atoms. Non-limiting examples of “Ci- C4fluoroalkoxy" groups include fluoromethoxy, difluoromethoxy, trifluoromethoxy, fluoroethoxy, difluoroethoxy, trifluoroethoxy, pentafluoroethoxy, difluoropropoxy and heptafluoropropoxy.

[0068] The term “CrC4hydroxyalkyl”, as used herein, refers to Ci-C4alkyl", as defined herein, wherein one or more hydrogen atoms of the "Ci-C4alkyl" is replaced by one or more hydroxy groups.

[0069] The term “carbonyl” as used herein, refers to a -C(=O)- group.

[0070] The term “cyano” as used herein, refers to a -CN group.

[0071] The term "halogen", as used herein, refer to fluoro (F), chloro (Cl), bromo (Br) and iodo (I). The term “5- to 6- membered monocyclic heteroaryl,” as used herein, refers to an aromatic, 5- or 6- membered monocyclic ring system wherein 1 , 2, 3 or 4 ring members are each independently selected from N, NR4, NR9, O and S, where R4and NR9are as defined herein. Non-limiting examples of 5- to 6- membered monocyclic heteroaryl groups, include furazanyl, furyl, imidazolyl, isoxazolyl, isothiazolyl, oxazolyl, oxadiazolyl, pyrazolyl, pyrrolyl, pyridyl, pyridazinyl, pyrazinyl, pyrimidinyl, thiazolyl, thiadiazolyl, thienyl, triazinyl, triazolyl and tetrazolyl.

[0072] The term “partially saturated 9-, 10-, 11- or 12-membered bicyclic carbocyclyl”, as used herein, refers to a fused bicyclic hydrocarbon ring structure having 9-, 10-, 11 - or 12 ring members which comprises one or more double bonds and is not aromatic.

[0073] The term “partially saturated 5- or 6-membered heterocyclyl”, as used herein, refers to a monocyclic ring structure having 5- or 6 ring members wherein 1 or 2 ring members are each independently selected from N, NR9, O and S, (where R9is as defined herein), and monocyclic ring structure comprises one or more double bonds and is not aromatic.

[0074] In certain embodiments, the term “partially saturated 5- or 6-membered heterocyclyl”, as used herein, may also refer to a monocyclic ring structure having 5- or 6 ring members wherein one ring member is S(=O)2 and 1 , 2 or 3 other ring members are each independently selected from N, NR9, O and S, (where R9is as defined herein), and monocyclic ring structure comprises one or more double bonds and is not aromatic.

[0075] The term “partially saturated 8-, 9-, 10-, 11 - or 12-membered fused bicyclic heterocyclyl”, as used herein, refers to a fused bicyclic ring structure having 8-, 9-, 10-, 11 - or 12 ring members wherein 1 , 2, 3 or 4 ring members are each independently selected from N, NR4, NR9, O and S, (where R4and R9are as defined herein), and the fused bicyclic ring structure comprises one or more double bonds. In particular, the partially saturated heterocyclyl is a 10 membered fused bicyclic heterocyclyl containing 1 , 2 or 3 ring members independently selected from N, NR4, R9, O and S, where R4and R9are as defined herein. Non-limiting examples of partially saturated 8-, 9-, 10-, 11 - or 12-membered fused bicyclic heterocyclyl groups, as used herein, include chromanyl, 3,4-dihydro-2H-benzo[b][1 ,4]oxazinyl, 6,7-dihydro-5H-pyrazolo[5,1 -b][1 ,3]oxazinyl, 3,4-dihydro-2H-pyrano[2,3-b]pyridinyl, 2,3-dihydrobenzofuranyl, 2,3- dihydrobenzo[b][1 ,4]dioxinyl, 1 ,4,5,6-tetrahydrocyclopenta[c]pyrazolyl, and 4,5,6,7-tetrahydro- 1 H-indazolyl. Other, non-limiting examples of heterocycloalkyl groups include dihydrobenzofuranyl, dihydrobenzo[c]thiophenyl, dihydrobenzothiophenyl, dihydrobenzoxazolyl, dihydrobenzthiazolyl, dihydrobenzimidazolyl, dihydrocinnolinyl, dihydrofurazanyl, dihydrofuryl, dihydroimidazolyl, dihydroindolyl, dihydroindolizinyl, dihydroindazolyl, dihydroisoindolyl, dihydroisoquinolinyl, dihydroisoxazolyl, dihydroisothiazolyl, dihydrooxazolyl, dihydrooxaindolyl, dihydrooxadiazolyl, dihydropyrazolyl, di hydropyrrolyl, dihydrophthalazinyl, dihydropyridyl, dihydropyridazinyl, dihydropyrazinyl, dihydropyrimidinyl, dihydroquinoxalinyl, dihydroquinolinyl, dihydroquinazolinyl, dihydrotetrazolyl, dihydrothiazolyl, dihydrothiadiazolyl, dihydrothienyl, dihydrotriazinyl, dihydrotriazolyl, tetrahydrobenzofuranyl, tetrahydrobenzo[c]thiophenyl, tetrahydrobenzothiophenyl, tetrahydrobenzoxazolyl, tetrahydrobenzthiazolyl, tetrahydrobenzimidazolyl, tetrahydrocinnolinyl, tetrahydroindolyl, tetrahydroindolizinyl, tetrahydroindazolyl, tetrahydroisoindolyl, tetrahydroisoquinolinyl, tetrahydrooxaindolyl, tetrahydrophthalazinyl, tetrahydropyridyl, tetrahydropyridazinyl, tetrahydropyrazinyl, tetrahydropyrimidinyl, tetrahydroquinoxalinyl, tetrahydroquinolinyl, tetrahydroquinazolinyl, tetrahydrotriazinyl, hexahydrobenzofuranyl, hexahydrobenzo[c]thiophenyl, hexahydrobenzothiophenyl, hexahydrobenzoxazolyl, hexahydrobenzthiazolyl, hexahydrobenzimidazolyl, hexahydrocinnolinyl, hexahydroindolyl , hexahydroindolizinyl, hexahydroindazolyl, hexahydroisoindolyl, hexahydroisoquinolinyl, hexahydrooxaindolyl, hexahydrophthalazinyl, hexahydroquinoxalinyl, hexahydroquinolinyl, hexahydroquinazolinyl, octahydrocinnolinyl, octahydroisoquinolinyl, octahydrophthalazinyl, octahydroquinoxalinyl, octahydroquinolinyl and octahydroquinazolinyl.

[0076] The term 6- or 7- membered fused bicyclic heterocyclyl, as used herein, refers to a fused bicyclic ring structure having 6- or 7- ring members wherein 1 or 2 ring members are each independently selected from N, NR9, O and S, (where R9is as defined herein), and the fused bicyclic ring structure comprises one or more double bonds and is not aromatic.

[0077] The term "4-, 5- or 6 membered heterocycloalkyl" as used herein, refers to a 4, 5 or 6 membered, saturated ring wherein 1 , 2 or 3 ring members are each independently selected from N, NR9, O and S, where R9is as defined herein. Non-limiting examples of 4-, 5- or 6 membered heterocycloalkyl groups, as used herein, include azetidinyl (which includes azetidin-1 -yl, azetidin-2-yl and azetidin-3-yl), pyrrolidinyl (which includes pyrrolidin-1 -yl, pyrrolidin-2-yl, pyrrolidin-3-yl, pyrrolidin-4-yl and pyrrolidin-5-yl), piperidinyl (which includes piperidin-1 -yl, piperidin-2-yl, piperidin-3-yl, piperidin-4-yl, piperidin-5-yl and piperidin-6-yl), piperazinyl (which includes piperazin-1 -yl, piperazin-2-yl, piperazin-3-yl, piperazin-4-yl, piperazin-5-yl and piperazin-6-yl) and pyrazolidinyl (which includes pyrazolidin-1 -yl, pyrazolidin-2-yl, pyrazolidin-3- yl, pyrazolidin-4-yl and pyrazolidin-5-yl).

[0078] The term "5 or 6 membered heterocycloalkyl" as used herein, refers to a 5 or 6 membered, saturated ring wherein 1 or 2 ring members are each independently selected from N, NR9, O and S, where R9is as defined herein. The heterocycloalkyl group can be attached to another group at a nitrogen or a carbon atom. Non-limiting examples of 5 or 6 membered heterocycloalkyl groups, as used herein, include pyrrolidinyl (which includes pyrrolidin-1 -yl, pyrrolidin-2-yl, pyrrolidin-3-yl, pyrrolidin-4-yl and pyrrolidin-5-yl), tetrahydrofuranyl (which includes tetrahydrofuran-2-yl, tetrahydrofuran-3-yl, tetrahydrofuran -4-yl and tetrahydrofuran-5- yl), tetrahydrothienyl (which includes tetrahydrothien-2-yl, tetrahydrothien-3-yl, tetrahydrothien- 4-yl and tetrahydrothien-5-yl), piperidinyl (which includes piperidin-1 -yl, piperidin-2-yl, piperidin- 3-yl, piperidin-4-yl, piperidin-5-yl and piperidin-6-yl), tetrahydropyranyl (which includes tetrahydropyran-2-yl, tetrahydropyran-3-yl, tetrahydropyran-4-yl, tetrahydropyran-5-yl and tetrahydropyran-6-yl), tetrahydrothiopyranyl (which includes tetrahydrothiopyran-2-yl, tetrahydrothiopyran-3-yl, tetrahydrothiopyran-4-yl, tetrahydrothiopyran-5-yl and tetrahydrothiopyran-6-yl), piperazinyl (which includes piperazin-1 -yl, piperazin-2-yl, piperazin-3- yl, piperazin-4-yl, piperazin-5-yl and piperazin-6-yl), morpholinyl (which includes morpholin-2-yl, morpholin-3-yl, morpholin-4-yl, morpholin-5-yl and morpholin-6-yl), thiomorpholinyl (which includes thiomorpholin-2-yl, thiomorpholin-3-yl, thiomorpholin-4-yl, thiomorpholin-5-yl and thiomorpholin-6-yl), dithianyl (which includes dithian-2-yl, dithian-3-yl, dithian-5-yl and dithian-6- yl), dioxolanyl (which includes dioxolan-2-yl, dioxolan-4-yl and dioxolan-5-yl), and pyrazolidinyl (which includes pyrazolidin-1 -yl, pyrazolidin-2-yl, pyrazolidin-3-yl, pyrazolidin-4-yl and pyrazolidin-5-yl).

[0079] In certain embodiments, the term "4-, 5- or 6 membered heterocycloalkyl" as used herein, may also refer to a 4, 5 or 6 membered, saturated ring wherein one ring member is S(=O)2, and 1 , 2 or 3 other ring members are each independently selected from N, NR9and O, where R9is as defined herein.

[0080] In certain embodiments, the term "4-, 5- or 6 membered heterocycloalkyl" as used herein, may also refer to a 4, 5 or 6 membered, saturated ring wherein one ring member is S(=O)2, S(=O) or S(=O)(=NH).

[0081] The term "6 membered heterocycloalkyl" as used herein, refers to a 6 membered, saturated ring wherein 1 or 2 ring members are each independently selected from N, NR9, O and S, where R9is as defined herein.

[0082] The phrase "a 6- membered heterocycloalkyl having 1 to 2 ring members independently selected from N, NR9, O and S, wherein the heterocycloalkyl has a Ci-Csalkyl bridge or a - CH2OCH2- bridge", as used herein refers to a 6 membered heterocycloalkyl which has a C1- Csalkyl bridge or a -CH2OCH2- bridge. By way of example,

[0083] The term “hydroxy” as used herein, refers to an -OH group.

[0084] The term “oxo” as used herein, refers to a -C(=O)- group.

[0085] The term “6-, 7-, 8-, 9- or 10- membered spiro bicyclic heterocycloalkyl”, as used herein refers to a bicyclic ring system having “6-, 7-, 8-, 9- or 10- ring members wherein the bicyclic ring system comprises two ring systems spiro attached to each other and wherein 1 ,2 or 3 ring members of the bicyclic ring system are each independently selected from N, NR9, O and S, where R9is as defined herein.

[0086] The term "spiro attached", as used herein, refers to the attachment of one ring system to another ring system via one carbon atom common to both rings.

[0087] The term “isomers”, as used herein, refers to different compounds that have the same molecular formula but differ in arrangement and configuration of the atoms. Also as used herein, the term “an optical isomer” or “a stereoisomer” refers to any of the various stereo isomeric configurations which may exist for a given compound of Formula (I) and includes geometric isomers. It is understood that a substituent may be attached at a chiral center of a carbon atom. The term "chiral" refers to molecules which have the property of non-superimposability on their mirror image partner, while the term "achiral" refers to molecules which are superimposable on their mirror image partner. Therefore, the invention includes enantiomers, diastereomers or racemates of the compound. “Enantiomers” are a pair of stereoisomers that are non- superimposable mirror images of each other. A 1 :1 mixture of a pair of enantiomers is a "racemic” mixture. The term is used to designate a racemic mixture where appropriate. "Diastereoisomers” are stereoisomers that have at least two asymmetric atoms, but which are not mirror-images of each other. The absolute stereochemistry is specified according to the Cahn- Ingold- Prelog R-S system. When a compound is a pure enantiomer the stereochemistry at each chiral carbon may be specified by either R or S. Resolved compounds whose absolute configuration is unknown can be designated (+) or (-) depending on the direction (dextro- or levorotatory) which they rotate plane polarized light at the wavelength of the sodium D line. Certain compounds described herein contain one or more asymmetric centers or axes and may thus give rise to enantiomers, diastereomers, and other stereoisomeric forms that may be defined, in terms of absolute stereochemistry, as (R)- or (S)-.

[0088] The terms “combination” or “pharmaceutical combination,” as used herein, refers to either a fixed combination in one dosage unit form, or a combined administration where a compound of Formula (I) and a combination partner (e.g. another drug as explained below, also referred to as “therapeutic agent” or “co-agent”) may be administered independently at the same time or separately within time intervals, especially where these time intervals allow that the combination partners show a cooperative, e.g. synergistic effect. The single components may be packaged in a kit or separately. One or both of the components (e.g., powders or liquids) may be reconstituted or diluted to a desired dose prior to administration. The terms “co-administration” or “combined administration” or the like as utilized herein are meant to encompass administration of the selected combination partner to a single subject in need thereof (e.g. a patient), and are intended to include treatment regimens in which the agents are not necessarily administered by the same route of administration or at the same time. The term “pharmaceutical combination” as used herein means a product that results from the mixing or combining of more than one therapeutic agent and includes both fixed and non-fixed combinations of the therapeutic agents. The term “fixed combination” means that the therapeutic agents, e.g. a compound of Formula (I) and a combination partner, are both administered to a patient simultaneously in the form of a single entity or dosage. The term “non-fixed combination” means that the therapeutic agents, e.g. a compound of Formula (I) and a combination partner, are both administered to a patient as separate entities either simultaneously, concurrently or sequentially with no specific time limits, wherein such administration provides therapeutically effective levels of the two compounds in the body of the patient. The latter also applies to cocktail therapy, e.g. the administration of three or more therapeutic agent.

[0089] The term "combination therapy" or "in combination with” or “pharmaceutical combination” refers to the administration of two or more therapeutic agents to treat a therapeutic condition or disorder described in the present disclosure. Such administration encompasses coadministration of these therapeutic agents in a substantially simultaneous manner, such as in a single capsule having a fixed ratio of active ingredients. Alternatively, such administration encompasses co-administration in multiple, or in separate containers (e.g., capsules, powders, and liquids) for each active ingredient. Powders and / or liquids may be reconstituted or diluted to a desired dose prior to administration. In addition, such administration also encompasses use of each type of therapeutic agent being administered prior to, concurrent with, or sequentially to each other with no specific time limits. In each case, the treatment regimen will provide beneficial effects of the drug combination in treating the conditions or disorders described herein.

[0090] As used herein the term “co-administer” refers to the presence of two active agents in the blood of an individual. Active agents that are co-administered can be concurrently or sequentially delivered.

[0091] The terms “composition” or “pharmaceutical composition,” as used herein, refers to a compound of Formula (I), or a pharmaceutically acceptable salt thereof, together with at least one pharmaceutically acceptable carrier, in a form suitable for oral or parenteral administration.

[0092] As used herein, the term "contacting" refers to the bringing together of the indicated moieties in an in vitro system or an in vivo system.

[0093] A "patient," "subject" or "individual" are used interchangeably and refer to either a human or non-human animal. The term includes mammals such as humans. Typically, the animal is a mammal. A "patient," "subject" or "individual" also refers to for example, primates (e.g., humans, male or female), cows, sheep, goats, horses, dogs, cats, rabbits, rats, mice, fish, birds and the like. In certain embodiments, the subject is a primate. Preferably, the "patient," "subject" or "individual" is a human.

[0094] As used herein, the term "pharmaceutically acceptable carrier" refers to a substance useful in the preparation or use of a pharmaceutical composition and includes, for example, suitable diluents, solvents, dispersion media, surfactants, antioxidants, preservatives, isotonic agents, buffering agents, emulsifiers, absorption delaying agents, salts, drug stabilizers, binders, excipients, disintegration agents, lubricants, wetting agents, sweetening agents, flavoring agents, dyes, and combinations thereof, as would be known to those skilled in the art (see, for example, Remington The Science and Practice of Pharmacy, 22ndEd. Pharmaceutical Press, 2013, pp. 1049-1070).

[0095] The phrase "pharmaceutically acceptable" indicates that the substance, composition or dosage form must be compatible chemically and / or toxicologically, with the other ingredients comprising a formulation, and / or the mammal being treated therewith.

[0096] The term “a subject in need of such treatment”, refers to a subject which would benefit biologically, medically or in quality of life from such treatment.

[0097] The term “therapeutically effective amount,” as used herein, refers to an amount of a compound of Formula (I) that will ameliorate symptoms, alleviate conditions, slow or delay disease progression, or elicit the biological or medical response of a subject.

[0098] As used herein, the term “treat”, “treating" or "treatment" of any disease or disorder, refers to the management and care of a patient for the purpose of combating the disease, condition, or disorder, or eliminating the disease, condition or disorder.

[0099] In addition, the terms "treatment," "treating," as used herein, refers to alleviating or ameliorating the disease or disorder (i.e., slowing or arresting the development of the disease or at least one of the clinical symptoms thereof); or alleviating or ameliorating at least one physical parameter or biomarker associated with the disease or disorder, including those which may not be discernible to the patient.

[0100] As used herein, a subject is “in need of’ a treatment if such subject would benefit biologically, medically or in quality of life from such treatment.

[0101] Unless specified otherwise, the terms “compound of the invention”, “compounds of the invention”, “compound of the present invention” or “compounds of the present invention” refers to a compound or compounds of Formula (I), or subformulae thereof, such as Formula (l-a), Formula (l-b), Formula (l-c), Formula (l-d), Formula (l-e), and Formula (l-f) and exemplified compounds, and salts thereof, as well as all stereoisomers (including diastereoisomers and enantiomers) thereof.

[0102] Unless specified otherwise, the phrase “compounds of Formula (I), or a subformula thereof,” as used herein refers to compounds having the structure of Formula (I) or the structure of a subformula selected from Formula (l-a), Formula (l-b), Formula (l-c), Formula (l-d), Formula (Ie), and Formula (l-f), and salts thereof, as well as all stereoisomers (including diastereoisomers and enantiomers) thereof.

[0103] R-i-

[0104] As used herein, wavy line, as depicted here “5”, is a symbol denoting the point of attachment of R, to other part of the molecule.

[0105] Compounds of the Invention

[0106] Provided herein are compounds which bind to PNPLA3I148M and have the structure of Formula (I), or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof: wherein:

[0107] -X=Y- is -CRx=CRy-, -CRX=N- or -N=CRy-;

[0108] Rxis H, D, halogen or Ci-C4alkyl;

[0109] Ryis H, D, halogen, -CN, CrC4alkyl, Ci-C4fluoroalkyl or CrC4alkoxy;

[0110] R5is H, halogen, -CN, CrC4alkyl, CrC4fluoroalkyl or CrC4alkoxy; RAis:

[0111] (i) phenyl which is unsubstituted or is substituted with 1 , 2, 3 or 4 R1groups;

[0112] (ii) a partially saturated 9-, 10-, 11 - or 12-membered bicyclic carbocyclyl which is unsubstituted or is substituted with 1 to 4 R1groups;

[0113] (iii) a 5- or 6- membered monocyclic heteroaryl having 1 , 2, 3 or 4 ring members independently selected from N, NR4, O and S, wherein the monocyclic heteroaryl is unsubstituted or is substituted with 1 , 2, 3 or 4 R1groups; or

[0114] (iv) a partially saturated 8-, 9-, 10-, 11 - or 12-membered fused bicyclic heterocyclyl having

[0115] 1 , 2, 3 or 4 ring members independently selected from N, NR4, O and S, wherein the fused bicyclic heterocyclyl is unsubstituted or is substituted with 1 , 2, 3 or 4 R1groups; each R1is independently selected from the group consisting of halogen, Ci-C4alkyl, C2- C4alkenyl, C2-C4alkynyl, Ci-C4alkoxy, Ci-C4alkoxycarbonyl, Cs-Cecycloalkyl, C1- C4fluoroalkyl, Ci-C4fluoroalkoxy, pentafluorosulfanyl, Ci-C4hydroxyalkyl, Ci-C4thioalkyl, azido, diCi-C4alkylamino, diCi-C4alkylaminocarbonyl, D, CD3, cyano, formyl, phenyl and a 5- to 6-membered heterocycloalkyl comprising 1 or 2 ring members independently selected from N, NR4, O and S; Li is a bond, -(CR2R3)P-, -(CR2R3)P-NR4-, -(CR2R3)P-O-, -NR4(CR2R3)q-, -(CR2R3)qNR4-, -O- (CR2R3)P- or -S-(CR2R3)P-;

[0116] R2is H, D, halogen or Ci-C4alkyl;

[0117] R3is H, D, halogen, Ci-C4alkyl, Ci-C4alkoxy, OH, amino or f-Boc-amino; or R2and R3, together with the C atom to which they are attached, are linked to form C3- C4cycloalkyl which is unsubstituted or is substituted with a single substituent selected from Ci-C4alkyl and oxo; each R4is independently selected from the group consisting of H and Ci-C4alkyl; p is 1 , 2 or 3; q is 0, 1 or 2;

[0118] Z1 is N or C; Z2is N or CRZ; Z3is N or CRZ; Z4is N or C; Z5is N or CRZ; wherein each Rzis independently selected from the group consisting of H, halogen, Cr C4alkyl and Ci-C4fluoroalkyl; and provided that at least two, and not more than four, of Z1 , Z2, Z3, Z4and Z5are N; l_2is a bond, -(CR5R7)n- or -(CR6R7)nO-*, where the * indicates the point of attachment to R8; each R6is independently selected from the group consisting of H, C C4alkyl, CrC4fluoroalkyl and Ci-C4hydroxyalkyl; each R7is independently selected from the group consisting of H, Ci-C4alkyl, Ci-C4fluoroalkyl and Ci-C4hydroxyalkyl; or R6and R7, together with the C atom to which they are attached, are linked to form C3- Cecycloalkyl, oxetanyl, tetrahydrofuranyl or tetrahydropyranyl; n is 1 , 2 or 3;

[0119] R8is:

[0120] (i) 4-, 5- or 6-membered heterocycloalkyl having 1 , 2 or 3 ring members independently selected from N, NR9, O and S, wherein the heterocycloalkyl is unsubstituted or is substituted with 1 , 2, 3 or 4 substituents each independently selected from -OH, -CN, - N(R10)2, halogen, Ci-C4fluoroalkyl, Ci-C4alkyl, Ci-C4alkoxy, oxo and a 5- or 6- membered monocyclic heteroaryl having 1 , 2, 3 or 4 ring members independently selected from N, NR9, O and S, wherein the monocyclic heteroaryl is unsubstituted;

[0121] (ii) 4-, 5- or 6-membered heterocycloalkyl wherein one ring member is S(=O)2, S(=O) or S(=O)(=NH), and wherein the heterocycloalkyl is unsubstituted or is substituted with 1 , 2, 3 or 4 substituents, each independently selected from -OH, Ci-C4alkyl and oxo;

[0122] (iii) 4-, 5- or 6-membered heterocycloalkyl wherein one ring member is S(=O)2or S(=O), and 1 , 2 or 3 other ring members are independently selected from N, NR9and O, and wherein the heterocycloalkyl is unsubstituted or is substituted with 1 , 2, 3 or 4 substituents each independently selected from C C4alkyl and oxo;

[0123] (iv) a partially saturated 5- or 6-membered heterocyclyl having 1 or 2 ring members independently selected from N, NR9, O and S, wherein the partially saturated heterocyclyl is unsubstituted or is substituted with 1 , 2, 3 or 4 substituents independently selected from -OH, CrC4alkyl, and oxo;

[0124] (v) a partially saturated 5- or 6-membered heterocyclyl wherein one ring member is S(=O)2and 1 , 2 or 3 other ring members are independently selected from N, NR9, O and S, wherein the partially saturated heterocyclyl is unsubstituted or is substituted with 1 , 2, 3 or 4 substituents independently selected from -OH, Ci-C4alkyl, and oxo;

[0125] (vi) a 5- or 6- membered monocyclic heteroaryl having 1 , 2, 3 or 4 ring members independently selected from N, NR9, O and S, wherein the monocyclic heteroaryl is unsubstituted or is substituted with 1 , 2, 3 or 4 substituents each independently selected from -OH, CrC4alkoxy and Ci-C4alkyl;

[0126] (vii) a 6- or 7-membered fused bicyclic heterocyclyl having 1 or 2 ring members independently selected from N, NR9, O and S, wherein the fused bicyclic heterocyclyl is unsubstituted or is substituted with 1 , 2, 3 or 4 substituents, each independently selected from -OH, -N(R10)2, CrC4alkyl-NH2, halogen, Ci-C4alkyl, and oxo;

[0127] (viii) a partially saturated 8-, 9-, 10-, 11 - or 1 -membered fused bicyclic heterocyclyl having 1 , 2, 3 or 4 ring members independently selected from N, NR9, O and S, wherein the fused bicyclic heterocyclyl is unsubstituted or is substituted with 1 , 2, 3 or 4 substituents, each independently selected from -OH, -N(R10)2, Ci-C4alkyl-NH2, halogen, Ci-C4alkyl, and oxo;

[0128] (ix) a 6-, 7-, 8-, 9- or 10- membered spiro bicyclic heterocycloakyl having 1 , 2 or 3 ring members independently selected from N, NR9, O and S, wherein the spiro bicyclic heterocycloakyl is unsubstituted or is substituted with 1 , 2, 3 or 4 substituents, each independently selected from -OH, -N(R10)2, Ci-C4alkyl-NH2, halogen, Ci-C4alkyl, and oxo;

[0129] (x) a 6- membered heterocycloalkyl having 1 to 2 ring members independently selected from N, NR9, O and S, wherein the heterocycloalkyl has a Ci-Csalkyl bridge or a - CH2OCH2- bridge;

[0130] (xi) phenyl which is unsubstituted or is substituted with 1 , 2, 3 or 4 substituents, each independently selected from -S(=O)2N(R10)2, -OH, -N(R10)2, Ci-C4alkyl-NH2, halogen and Ci-C4alkyl; or

[0131] (xii) C4-C8cycloalkyl which is unsubstituted or is substituted with 1 , 2, 3 or 4 substituents independently selected from -OH, -N(R10)2, -S(=O)2R10, C1 -C4alkyl-NH2, halogen, Cr C4alkoxy, Ci-C4alkyl, and oxo;

[0132] R9is H, Ci-C4alkyl, benzyl, Ci-C4alkyl-OR10, -C(=O)OR10or -C(=O)R10, and

[0133] R10is H or CrC4alkyl.

[0134] Further aspects and examples of the compounds of Formula (I) are provided in the following embodiments. It will be recognized that features specified in each embodiment may be combined with other specified features to provide further embodiments.

[0135] In an embodiment of compounds of Formula (I), or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof:

[0136] -X=Y- is -CRx=CRy-, -CRX=N- or -N=CRy-;

[0137] Rxis H, D, halogen or Ci-C4alkyl;

[0138] Ryis H, D, halogen, -CN, Ci-C4alkyl, Ci-C4fluoroalkyl or Ci-C4alkoxy;

[0139] R5is H, halogen, -CN, Ci-C4alkyl, Ci-C4fluoroalkyl or Ci-C4alkoxy;

[0140] RAis:

[0141] (i) phenyl which is unsubstituted or is substituted with 1 , 2, 3 or 4 R1groups;

[0142] (ii) a partially saturated 9-, 10-, 11 - or 12-membered bicyclic carbocyclyl which is unsubstituted or is substituted with 1 to 4 R1groups;

[0143] (iii) a 5- or 6- membered monocyclic heteroaryl having 1 , 2, 3 or 4 ring members independently selected from N, NR4, O and S, wherein the monocyclic heteroaryl is unsubstituted or is substituted with 1 , 2, 3 or 4 R1groups; or

[0144] (iv) a partially saturated 8-, 9-, 10-, 11 - or 12-membered fused bicyclic heterocyclyl having 1 , 2, 3 or 4 ring members independently selected from N, NR4, O and S, wherein the fused bicyclic heterocyclyl is unsubstituted or is substituted with 1 , 2, 3 or 4 R1groups; each R1is independently selected from the group consisting of halogen, Ci-C4alkyl, C2- C4alkenyl, C2-C4alkynyl, Ci-C4alkoxy, Ci-C4alkoxycarbonyl, Cs-Cecycloalkyl, C1- C4fluoroalkyl, Ci-C4fluoroalkoxy, pentafluorosulfanyl, Ci-C4hydroxyalkyl, Ci-C4thioalkyl, azido, diCi-C4alkylamino, diCi-C4alkylaminocarbonyl, D, CD3, cyano, formyl, phenyl and a 5- to 6-membered heterocycloalkyl comprising 1 or 2 ring members independently selected from N, NR4, O and S;

[0145] Li is a bond, -(CR2R3)P-, -(CR2R3)P-NR4-, -(CR2R3)P-O-, -NR4(CR2R3)q-, -(CR2R3)qNR4-, -O- (CR2R3)P- or -S-(CR2R3)P-;

[0146] R2is H, D, halogen or Ci-C4alkyl;

[0147] R3is H, D, halogen, Ci-C4alkyl, CrC4alkoxy, OH, amino or f-Boc-amino; or R2and R3, together with the C atom to which they are attached, are linked to form C3- C4cycloalkyl which is unsubstituted or is substituted with a single substituent selected from Ci-C4alkyl and oxo; each R4is independently selected from the group consisting of H and Ci-C4alkyl; p is 1 , 2 or 3; q is 0, 1 or 2;

[0148] Z1 is N, Z2is CRZ, Z3is N, Z4is C and Z5is N; or Z1 is N, Z2is CRZ, Z3is N, Z4 is C and Z5 is CRZ; or Zi is C, Z2 is CRZ, Z3 is N, Z4 is N and Z5 is CRZ; or Z1 is C, Z2 is N, Z3 is N, Z4 is N and Z5 is CRZ; or Z1 is N, Z2 is CRZ, Z3 is CRZ, Z4 is C and Z5 is N; each Rzis independently selected from the group consisting of H, halogen, Ci-C4alkyl and C1-

[0149] C4fluoroalkyl;

[0150] L2 is a bond, -(CR6R7)n- or -(CR6R7)nO-*, where the * indicates the point of attachment to R8; each R6is independently selected from the group consisting of H, Ci-C4alkyl, Ci-C4fluoroalkyl and Ci-C4hydroxyalkyl; each R7is independently selected from the group consisting of H, Ci-C4alkyl, Ci-C4fluoroalkyl and CrC4hydroxyalkyl; or R6and R7, together with the C atom to which they are attached, are linked to form C3- Cecycloalkyl, oxetanyl, tetrahydrofuranyl or tetrahydropyranyl; n is 1 , 2 or 3;

[0151] R8is:

[0152] (i) 4-, 5- or 6-membered heterocycloalkyl having 1 , 2 or 3 ring members independently selected from N, NR9, O and S, wherein the heterocycloalkyl is unsubstituted or is substituted with 1 , 2, 3 or 4 substituents each independently selected from -OH, -CN, - N(R10)2, halogen, Ci-C4fluoroalkyl, Ci-C4alkyl, Ci-C4alkoxy, oxo and a 5- or 6- membered monocyclic heteroaryl having 1 , 2, 3 or 4 ring members independently selected from N, NR9, O and S, wherein the monocyclic heteroaryl is unsubstituted;

[0153] (ii) 4-, 5- or 6-membered heterocycloalkyl wherein one ring member is S(=O)2, S(=O) or S(=O)(=NH), and wherein the heterocycloalkyl is unsubstituted or is substituted with 1 , 2, 3 or 4 substituents, each independently selected from -OH, Ci-C4alkyl and oxo;

[0154] (iii) 4-, 5- or 6-membered heterocycloalkyl wherein one ring member is S(=O)a or S(=O), and 1 , 2 or 3 other ring members are independently selected from N, NR9and O, and wherein the heterocycloalkyl is unsubstituted or is substituted with 1 , 2, 3 or 4 substituents each independently selected from CrC4alkyl and oxo;

[0155] (iv) a partially saturated 5- or 6-membered heterocyclyl having 1 or 2 ring members independently selected from N, NR9, O and S, wherein the partially saturated heterocyclyl is unsubstituted or is substituted with 1 , 2, 3 or 4 substituents independently selected from -OH, Ci-C4alkyl, and oxo;

[0156] (v) a partially saturated 5- or 6-membered heterocyclyl wherein one ring member is S(=O)2and 1 , 2 or 3 other ring members are independently selected from N, NR9, O and S, wherein the partially saturated heterocyclyl is unsubstituted or is substituted with 1 , 2, 3 or 4 substituents independently selected from -OH, Ci-C4alkyl, and oxo;

[0157] (vi) a 5- or 6- membered monocyclic heteroaryl having 1 , 2, 3 or 4 ring members independently selected from N, NR9, O and S, wherein the monocyclic heteroaryl is unsubstituted or is substituted with 1 , 2, 3 or 4 substituents each independently selected from -OH, CrC4alkoxy and Ci-C4alkyl;

[0158] (vii) a 6- or 7-membered fused bicyclic heterocyclyl having 1 or 2 ring members independently selected from N, NR9, O and S, wherein the fused bicyclic heterocyclyl is unsubstituted or is substituted with 1 , 2, 3 or 4 substituents, each independently selected from -OH, -N(R10)2, Ci-C4alkyl-NH2, halogen, Ci-C4alkyl, and oxo;

[0159] (viii) a partially saturated 8-, 9-, 10-, 11 - or 12-membered fused bicyclic heterocyclyl having 1 , 2, 3 or 4 ring members independently selected from N, NR9, O and S, wherein the fused bicyclic heterocyclyl is unsubstituted or is substituted with 1 , 2, 3 or 4 substituents, each independently selected from -OH, -N(R10)2, Ci-C4alkyl-NH2, halogen, Ci-C alkyl, and oxo;

[0160] (ix) a 6-, 7-, 8-, 9- or 10- membered spiro bicyclic heterocycloakyl having 1 , 2 or 3 ring members independently selected from N, NR9, O and S, wherein the spiro bicyclic heterocycloakyl is unsubstituted or is substituted with 1 , 2, 3 or 4 substituents, each independently selected from -OH, -N(R10)2, Ci-C4alkyl-NH2, halogen, Ci-C4alkyl, and oxo;

[0161] (x) a 6- membered heterocycloalkyl having 1 to 2 ring members independently selected from N, NR9, O and S, wherein the heterocycloalkyl has a Ci-Csalkyl bridge or a - CH2OCH2- bridge;

[0162] (xi) phenyl which is unsubstituted or is substituted with 1 , 2, 3 or 4 substituents, each independently selected from -S(=O)2N(R10)2, -OH, -N(R10)2, Ci-C4alkyl-NH2, halogen and Ci-C4alkyl; or

[0163] (xii) C4-C8cycloalkyl which is unsubstituted or is substituted with 1 , 2, 3 or 4 substituents independently selected from -OH, -N(R10)2, -S(=O)2R10, Ci-C4alkyl-NH2, halogen, C1- C4alkoxy, Ci-C4alkyl, and oxo;

[0164] R9is H, Ci-C4alkyl, benzyl, Ci-C4alkyl-OR10, -C(=O)OR10or -C(=O)R10, and

[0165] R10is H or Ci-C4alkyl.

[0166] In an embodiment of compounds of Formula (I), or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof:

[0167] -X=Y- is -CRx=CRv-, -CRX=N- or -N=CRy-;

[0168] Rxis H, D or halogen;

[0169] Ry is H, D, halogen or -CN;

[0170] R5is halogen or -CN;

[0171] RAis:

[0172] (i) phenyl which is substituted with 1 or 2 R1groups; (ii) a 5- or 6- membered monocyclic heteroaryl having 1 or 2 ring members independently selected from N and NR4, wherein the monocyclic heteroaryl is substituted with 1 or 2 R1groups; or

[0173] (iii) a partially saturated 8-, 9- or 10-membered fused bicyclic heterocyclyl having 1 , 2 or 3 ring member independently selected from N, NR4and O, wherein the fused bicyclic heterocyclyl is substituted with 1 , 2 or 3 R1groups; each R1is independently selected from the group consisting of halogen, D, CDs, Ci-C4alkyl, Ci- C4fluoroalkyl, Ci-C4fluorolkoxy, Cs-Cecycloalkyl and pentafluorosulfanyl;

[0174] Li is a bond, -(CR2R3)P-, -NR4(CR2R3)q- or -O-(CR2R3)P-;

[0175] R2is H, D or halogen;

[0176] R3is H, D, halogen, OH or Ci-C4alkyl; or R2and R3, together with the C atom to which they are attached, are linked to form C3- C4cycloalkyl which is unsubstituted

[0177] R4is H or Ci-C4alkyl;

[0178] P is 1 ; q is 0;

[0179] Z1 is N, Z2is CRZ, Z3is N, Z4is C and Z5is N; or Z1 is N, Z2is CRZ, Z3is N, Z4is C and Z5is CRZ; or Z1 is C, Z2is CRZ, Z3is N, Z4is N and Z5is CRZ; or Z1 is C, Z2is N, Z3is N, Z4is N and Z5is CRZ; each Rzis H; l_2is a bond, -(CR5R7)n- or -(CR6R7)nO-*, where the * indicates the point of attachment to R8; each R6is independently selected from the group consisting of H, Ci-C4alkyl, Ci-C4fluoroalkyl and Ci-C4hydroxyalkyl; each R7is independently selected from the group consisting of H, Ci-C4alkyl, Ci-C4fluoroalkyl and Ci-C4hydroxyalkyl; or R6and R7, together with the C atom to which they are attached, are linked to form tetrahydropyranyl; n is 1 or 2;

[0180] R8is:

[0181] (i) 4-, 5- or 6-membered heterocycloalkyl having 1 or 2 ring members independently selected from N, NR9, O and S, wherein the heterocycloalkyl is unsubstituted or is substituted with 1 , 2 or 3 substituents each independently selected from -OH, -CN, - N(R10)2, halogen, CrC4fluoroalkyl, Ci -C4alkyl, CrC4alkoxy, oxo and a 5- or 6- membered monocyclic heteroaryl having 1or 2 ring members independently selected from N and NR9, wherein the monocyclic heteroaryl is unsubstituted; (ii) 5- membered heterocycloalkyl wherein one ring member is S(=O)2, S(=O) or S(=O)(=NH), and wherein the heterocycloalkyl is unsubstituted or is substituted with a substituent selected from -OH and Ci-C4alkyl;

[0182] (iii) 6-membered heterocycloalkyl wherein one ring member is S(=O)2 or S(=O), and one other ring member is selected from N, NR9and O, and wherein the heterocycloalkyl is unsubstituted or is substituted with a substituent selected from Ci-C4alkyl;

[0183] (iv) a partially saturated 6-membered heterocyclyl having 1 or 2 ring members independently selected from N, NR9, O and S, wherein the partially saturated heterocyclyl is unsubstituted or is substituted with an oxo;

[0184] (v) a partially saturated 6-membered heterocyclyl wherein one ring member is S(=O)z and one other ring member is selected from N, NR4, and O, wherein the partially saturated heterocyclyl is unsubstituted or is substituted with an oxo;

[0185] (vi) a 5- or 6- membered monocyclic heteroaryl having 1 , 2, 3 or 4 ring members independently selected from N, NR9and O, wherein the monocyclic heteroaryl is unsubstituted or is substituted with a substituent selected from -OH, CrC4alkoxy and Ci-C4alkyl;

[0186] (vii) a 6- membered fused bicyclic heterocyclyl having 1 ring member selected from N and NR9, wherein the fused bicyclic heterocyclyl is unsubstituted or is substituted with an oxo;

[0187] (viii) a partially saturated 10- membered fused bicyclic heterocyclyl having 1 , 2, or 3 ring members independently selected from N, NR9, and O, wherein the fused bicyclic heterocyclyl is unsubstituted or is substituted with an oxo;

[0188] (ix) a 7- membered spiro bicyclic heterocycloakyl having 1 ring member selected from N, NR9, and O, wherein the spiro bicyclic heterocycloakyl is unsubstituted;

[0189] (x) a 6- membered heterocycloalkyl having 1 to 2 ring members independently selected from N, NR9and O, wherein the heterocycloalkyl has a Ci-Csalkyl bridge or a - CH2OCH2- bridge;

[0190] (xi) phenyl which is substituted with -S(=O)2N(R10)2; or

[0191] (xii) C4-C8cycloalkyl which is substituted with 1 , 2 or 3 substituents independently selected from -OH, -N(R10)2, -S(=O)2R10, Ci-C alkyl-NH2, halogen and Ci-C4alkoxy;

[0192] R9is H, Ci-C4alkyl, benzyl, Ci-C4alkyl-OR10, -C(=O)OR10or -C(=O)R10, and

[0193] R10is H or CrC alkyl.

[0194] In an embodiment of compounds of Formula (I), or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof:

[0195] -X=Y- is -CRx=CRy-, -CRX=N- or -N=CRy-; Rxis H or F;

[0196] Rv is H, F or CN;

[0197] R5is F, Cl or CN;

[0198] RAis:

[0199] (i) phenyl which is substituted with 1 to 2 R1groups;

[0200] (ii) pyrazolyl or pyridinyl, which are substituted with 1 or 2 R1groups; or

[0201] (iii) chromanyl, 3,4-dihydro-2H-pyrano[2,3-b]pyridinyl, 3,4-dihydro-2H- benzo[b][1 ,4]oxazinyl, 6,7-dihydro-5H-pyrazolo[5,1 -b][ 1 ,3]oxazinyl, 5,6- dihydrocyclopenta[c]pyrazol-1 (4H)-yl), 2,3-dihydrobenzo[b][1 ,4]dioxinyl , 4, 5,6,7- tetrahydro-1 H-indazolyl, 1 H-benzo[d]imidazolyl, or 2,3-dihydrobenzofuranyl, each of which is unsubstituted or are substituted with 1 or 2 R1group; each R1is independently selected from the group consisting of F, Cl, Br, methyl, isopropyl, t- butyl, cyclopropyl, -CF3, CHF2, CF2CF3, OCF3, and SF5;

[0202] Li is a bond, -(CR2R3)P-, -NR4(CR2R3)q- or -O-(CR2R3)P-;

[0203] R2is H or F;

[0204] R3is H, OH, F or methyl; or R2and R3, together with the C atom to which they are attached, are linked to form cyclopropyl which is unsubstituted;

[0205] R4is H, methyl or ethy; p is 1 ; q is 0;

[0206] Zi is N, Z2is CRZ, Z3is N, Z4is C and Z5is N; or Zi is N, Z2is CRZ, Z3is N, Z4is C and Z5is CRZ; or Zi is C, Z2is CRZ, Z3is N, Z4is N and Z5is CRZ; or Zi is C, Z2is N, Z3is N, Z4is N and Z5is CRZ; each Rzis H; l_2is a bond, -(CRsR7)n- or -(CR6R7)nO-*, where the * indicates the point of attachment to R8; each R6is independently selected from the group consisting of H, methyl, isopropyl, -CH2OH and CH2CF3; each R7is independently selected from the group consisting of H, methyl, isopropyl, -CH2OH and CH2CF3; or R6and R7, together with the C atom to which they are attached, are linked to form tetrahydropyranyl; n is 1 or 2;

[0207] R8is:

[0208] (i) 4-, 5- or 6-membered heterocycloalkyl having 1 or 2 ring members independently selected from N, NR9, O and S, wherein the heterocycloalkyl is unsubstituted or is substituted with 1 , 2 or 3 substituents each independently selected from -OH, -CN, NH2, F, CF3, methyl, methoxy, oxo and a 5- or 6- membered monocyclic heteroaryl having 1 or 2 ring members independently selected from N and NR9, wherein the monocyclic heteroaryl is unsubstituted;

[0209] (ii) 5- membered heterocycloalkyl wherein one ring member is S(=O)2, S(=O) or S(=O)(=NH), and wherein the heterocycloalkyl is unsubstituted or is substituted with a substituent selected from OH and methyl;

[0210] (iii) 6-membered heterocycloalkyl wherein one ring member is S(=O)2 or S(=O), and one other ring member is selected from N, NR9and O, and wherein the heterocycloalkyl is unsubstituted or is substituted with a methyl,

[0211] (iv) a partially saturated 6-membered heterocyclyl having 1 or 2 ring members independently selected from N, NR9, O and S, wherein the partially saturated heterocyclyl is unsubstituted or is substituted with an oxo;

[0212] (v) a partially saturated 6-membered heterocyclyl wherein one ring member is S(=O)2 and one other ring member is selected from N, NR4, and O, wherein the partially saturated heterocyclyl is unsubstituted or is substituted with an oxo;

[0213] (vi) a 5- or 6- membered monocyclic heteroaryl having 1 , 2, 3 or 4 ring members independently selected from N, NR9and O, wherein the monocyclic heteroaryl is unsubstituted or is substituted with a substituent selected from -OH methoxy and methyl;

[0214] (vii) a 6- membered fused bicyclic heterocyclyl having 1 ring member selected from N and NR9, wherein the fused bicyclic heterocyclyl is unsubstituted or is substituted with an oxo;

[0215] (viii) a partially saturated 10- membered fused bicyclic heterocyclyl having 1 , 2, or 3 ring members independently selected from N, NR9, and O, wherein the fused bicyclic heterocyclyl is unsubstituted or is substituted with an oxo;

[0216] (ix) a 7- membered spiro bicyclic heterocycloakyl having 1 ring member selected from N, NR9, and O, wherein the spiro bicyclic heterocycloakyl is unsubstituted;

[0217] (x) a 6- membered heterocycloalkyl having 1 to 2 ring members independently selected from N, NR9and O, wherein the heterocycloalkyl has a Ci-C3alkyl bridge or a - CH2OCH2- bridge;

[0218] (xi) phenyl which is substituted with -S(=O)2NH2; or

[0219] (xii) cyclobutyl, cyclopentyl, or cyclohexyl which is substituted with 1 , 2 or 3 substituents independently selected from -OH, -NH2, -S(=O)2CH3, -CH2NH2, F, and methoxy; and

[0220] R9is H, methyl, benzyl, -C(=O)CH3, -C(=O)O(CH3)3, CH2CH2OH or CH2CH2OCH3.

[0221] In an embodiment of compounds of Formula (I), or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof:

[0222] -X=Y- is -CRx=CRy-,or -CRX=N-;

[0223] Rxis H;

[0224] Ryis H, F or CN;

[0225] R5is F or CN;

[0226] RAis:

[0227] (i) phenyl which is substituted with 1 to 2 R1groups;

[0228] (ii) pyrazolyl or pyridinyl, which is substituted with 1 or 2 R1groups; or

[0229] (iii) chromanyl or 3,4-dihydro-2H-pyrano[2,3-b]pyridinyl, which are unsubstituted or are substituted with an R1group; each R1is independently selected from the group consisting of F, Cl, methyl, -CF3and SF5;

[0230] Li is a bond, -(CR2R3)P-, -NR4(CR2R3)q- or -O-(CR2R3)P-;

[0231] R2is H;

[0232] R3is H, OH or methyl;

[0233] R4is H, methyl or ethy;

[0234] P is 1 ; q is 0;

[0235] Zi is N, Z2is CRZ, Z3is N, Z4is C and Z5is N; or Zi is N, Z2is CRZ, Z3is N, Z4is C and Z5is CRZ; or Zi is C, Z2is CRZ, Z3is N, Z4is N and Z5is CRZ; or Zi is C, Z2is N, Z3is N, Z4is N and Z5is CRZ; each Rzis H; l_2is a bond, -(CR5R7)n- or -(CR6R7)nO-*, where the * indicates the point of attachment to R8; each R6is independently selected from the group consisting of H, methyl and -CH2OH; each R7is independently selected from the group consisting of H, methyl and -CH2OH; n is 1 or 2;

[0236] R8is:

[0237] (i) 4-, 5- or 6-membered heterocycloalkyl having 1 or 2 ring members independently selected from N, NR9, O and S, wherein the heterocycloalkyl is unsubstituted or is substituted with 1 , 2 or 3 substituents each independently selected from -OH, -CN, NH2, F, CF3, methyl, methoxy, oxo and a 5- or 6- membered monocyclic heteroaryl having 1 or 2 ring members independently selected from N and NR9, wherein the monocyclic heteroaryl is unsubstituted;

[0238] (ii) 5- membered heterocycloalkyl wherein one ring member is S(=O)2, S(=O) or S(=O)(=NH), and wherein the heterocycloalkyl is unsubstituted or is substituted with a substituent selected from OH and methyl; (iii) 6-membered heterocycloalkyl wherein one ring member is S(=O)2 or S(=O), and one other ring member is selected from N, NR9and O, and wherein the heterocycloalkyl is unsubstituted or is substituted with a methyl,

[0239] (iv) a partially saturated 6-membered heterocyclyl having 1 or 2 ring members independently selected from N, NR9, O and S, wherein the partially saturated heterocyclyl is unsubstituted or is substituted with an oxo;

[0240] (v) a partially saturated 6-membered heterocyclyl wherein one ring member is S(=O)2 and one other ring member is selected from N, NR4, and O, wherein the partially saturated heterocyclyl is unsubstituted or is substituted with an oxo;

[0241] (vi) a 5- or 6- membered monocyclic heteroaryl having 1 , 2, 3 or 4 ring members independently selected from N, NR9and O, wherein the monocyclic heteroaryl is unsubstituted or is substituted with a substituent selected from -OH methoxy and methyl;

[0242] (vii) a 6- membered fused bicyclic heterocyclyl having 1 ring member selected from N and NR9, wherein the fused bicyclic heterocyclyl is unsubstituted or is substituted with an oxo;

[0243] (viii) a partially saturated 10- membered fused bicyclic heterocyclyl having 1 , 2, or 3 ring members independently selected from N, NR9, and O, wherein the fused bicyclic heterocyclyl is unsubstituted or is substituted with an oxo;

[0244] (ix) a 7- membered spiro bicyclic heterocycloakyl having 1 ring member selected from N, NR9, and O, wherein the spiro bicyclic heterocycloakyl is unsubstituted;

[0245] (x) a 6- membered heterocycloalkyl having 1 to 2 ring members independently selected from N, NR9and O, wherein the heterocycloalkyl has a Ci-C3alkyl bridge or a - CH2OCH2- bridge;

[0246] (xi) phenyl which is substituted with -S(=O)2NH2; or

[0247] (xii) cyclobutyl, cyclopentyl, or cyclohexyl which is substituted with 1 , 2 or 3 substituents independently selected from -OH, -NH2, -S(=O)2CH3, -CH2NH2, F, and methoxy; and

[0248] R9is H, methyl, benzyl, -C(=O)CH3, -C(=O)O(CH3)3, CH2CH2OH or CH2CH2OCH3.

[0249] In an embodiment of compounds of Formula (I), the compounds provided herein are compounds of Formula (l-a) or Formula (l-b), or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof: wherein:

[0250] -X=Y- is -CRx=CRy-, -CRX=N- or -N=CRy-;

[0251] Rxis H, D, halogen or Ci-C4alkyl;

[0252] Ryis H, D, halogen, -CN, C1-C4alkyl, C1-C4fluoroalkyl or C1-C4alkoxy;

[0253] R5is H, halogen, -CN, C1-C4alkyl, C1-C4fluoroalkyl or C1-C4alkoxy; each R1is independently selected from the group consisting of halogen, Ci-C4alkyl, C2- C4alkenyl, C2-C4alkynyl, Ci-C4alkoxy, Ci-C4alkoxycarbonyl, C3-C6cycloalkyl, C1- C4fluoroalkyl, Ci-C4fluoroalkoxy, pentafluorosulfanyl, Ci-C4hydroxyalkyl, Ci-C4thioalkyl, azido, diCi-C4alkylamino, diCi-C4alkylaminocarbonyl, D, CD3, cyano, formyl, phenyl and a 5- to 6-membered heterocycloalkyl comprising 1 or 2 ring members independently selected from N, NR4, O and S;

[0254] Li is -(CR2R3)P-, -(CR2R3)p-NR4-, -(CR2R3)P-O-, -NR4(CR2R3)q-, -(CR2R3)qNR4-, -O-(CR2R3)P- or - S-(CR2R3)P-;

[0255] R2is H, D, halogen or Ci-C4alkyl;

[0256] R3is H, D, halogen, Ci-C4alkyl, Ci-C4alkoxy, OH, amino or t-Boc-amino; or R2and R3, together with the C atom to which they are attached, are linked to form C3- C4cycloalkyl which is unsubstituted or is substituted with a single substituent selected from Ci-C4alkyl and oxo; each R4is independently selected from the group consisting of H and C1-C4alkyl; p is 1 , 2 or 3; q is 0, 1 or 2;

[0257] Z1 is N or C; Z2is N or CRZ; Z3is N or CRZ; Z4is N or C; Z5is N or CRZ; wherein each Rzis independently selected from the group consisting of H, halogen, C1- C4alkyl and Ci-C4fluoroalkyl; and provided that at least two, and not more than four, of Z1 , Z2Zs, Z4and Z5are N; l_2is a bond, -(CR6R7)n- or -(CR6R7)nO-*, where the * indicates the point of attachment to R8; each R6is independently selected from the group consisting of H, Ci-C4alkyl, Ci-C4fluoroalkyl and CrC4hydroxyalkyl; each R7is independently selected from the group consisting of H, Ci-C4alkyl, Ci-C4fluoroalkyl and CrC4hydroxyalkyl; or R6and R7, together with the C atom to which they are attached, are linked to form C3- Cecycloalkyl, oxetanyl, tetrahydrofuranyl or tetrahydropyranyl; n is 1 , 2 or 3;

[0258] R8is: (i) 4-, 5- or 6-membered heterocycloalkyl having 1 , 2 or 3 ring members independently selected from N, NR9, O and S, wherein the heterocycloalkyl is unsubstituted or is substituted with 1 , 2, 3 or 4 substituents each independently selected from -OH, -CN, - N(R10)2, halogen, Ci-C4fluoroalkyl, Ci-C4alkyl, Ci-C4alkoxy, oxo and a 5- or 6- membered monocyclic heteroaryl having 1 , 2, 3 or 4 ring members independently selected from N, NR9, O and S, wherein the monocyclic heteroaryl is unsubstituted;

[0259] (ii) 4-, 5- or 6-membered heterocycloalkyl wherein one ring member is S(=O)2, S(=O) or S(=O)(=NH), and wherein the heterocycloalkyl is unsubstituted or is substituted with 1 , 2, 3 or 4 substituents, each independently selected from -OH, Ci-C4alkyl and oxo;

[0260] (iii) 4-, 5- or 6-membered heterocycloalkyl wherein one ring member is S(=O)2 or S(=O), and 1 , 2 or 3 other ring members are independently selected from N, NR9and O, and wherein the heterocycloalkyl is unsubstituted or is substituted with 1 , 2, 3 or 4 substituents each independently selected from CrC4alkyl and oxo;

[0261] (iv) a partially saturated 5- or 6-membered heterocyclyl having 1 or 2 ring members independently selected from N, NR9, O and S, wherein the partially saturated heterocyclyl is unsubstituted or is substituted with 1 , 2, 3 or 4 substituents independently selected from -OH, CrC4alkyl, and oxo;

[0262] (v) a partially saturated 5- or 6-membered heterocyclyl wherein one ring member is S(=O)2and 1 , 2 or 3 other ring members are independently selected from N, NR9, O and S, wherein the partially saturated heterocyclyl is unsubstituted or is substituted with 1 , 2, 3 or 4 substituents independently selected from -OH, Ci-C4alkyl, and oxo;

[0263] (vi) a 5- or 6- membered monocyclic heteroaryl having 1 , 2, 3 or 4 ring members independently selected from N, NR9, O and S, wherein the monocyclic heteroaryl is unsubstituted or is substituted with 1 , 2, 3 or 4 substituents each independently selected from -OH, Ci-C4alkoxy and Ci-C4alkyl;

[0264] (vii) a 6- or 7-membered fused bicyclic heterocyclyl having 1 or 2 ring members independently selected from N, NR9, O and S, wherein the fused bicyclic heterocyclyl is unsubstituted or is substituted with 1 , 2, 3 or 4 substituents, each independently selected from -OH, -N(R10)2, Ci-C4alkyl-NH2, halogen, Ci-C4alkyl, and oxo;

[0265] (viii) a partially saturated 8-, 9-, 10-, 11 - or 12-membered fused bicyclic heterocyclyl having 1 , 2, 3 or 4 ring members independently selected from N, NR9, O and S, wherein the fused bicyclic heterocyclyl is unsubstituted or is substituted with 1 , 2, 3 or 4 substituents, each independently selected from -OH, -N(R10)2, Ci-C4alkyl-NH2, halogen, Ci-C4alkyl, and oxo;

[0266] (ix) a 6-, 7-, 8-, 9- or 10- membered spiro bicyclic heterocycloakyl having 1 , 2 or 3 ring members independently selected from N, NR9, O and S, wherein the spiro bicyclic heterocycloakyl is unsubstituted or is substituted with 1 , 2, 3 or 4 substituents, each independently selected from -OH, -N(R10)2, Ci-C4alkyl-NH2, halogen, Ci-C4alkyl, and oxo;

[0267] (x) a 6- membered heterocycloalkyl having 1 to 2 ring members independently selected from N, NR9, O and S, wherein the heterocycloalkyl has a Ci-C3alkyl bridge or a - CH2OCH2- bridge;

[0268] (xi) phenyl which is unsubstituted or is substituted with 1 , 2, 3 or 4 substituents, each independently selected from -S(=O)2N(R10)2, -OH, -N(R10)2, Ci-C4alkyl-NH2, halogen and Ci-C4alkyl; or

[0269] (xii) C4-C8cycloalkyl which is unsubstituted or is substituted with 1 , 2, 3 or 4 substituents independently selected from -OH, -N(R10)2, -S(=O)2R10, Ci-C4alkyl-NH2, halogen, Ci- C4alkoxy, Ci-C4alkyl, and oxo;

[0270] R9is H, Ci-C4alkyl, benzyl, Ci-C4alkyl-OR10, -C(=O)OR10or -C(=O)R10, and

[0271] R10is H or CrC4alkyl.

[0272] In an embodiment of compounds of Formula (l-a) and Formula (l-b), or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof:

[0273] -X=Y- is -CRx=CRy-, -CRX=N- or -N=CRy-;

[0274] Rxis H, D, halogen or C1-C4alkyl;

[0275] Ryis H, D, halogen, -CN, C1-C4alkyl, CrC4fluoroalkyl or CrC4alkoxy;

[0276] R5is H, halogen, -CN, C1-C4alkyl, CrC4fluoroalkyl or C C4alkoxy; each R1is independently selected from the group consisting of halogen, C1-C4alkyl, C2- C4alkenyl, C2-C4alkynyl, Ci-C4alkoxy, Ci-C4alkoxycarbonyl, C3-C6cycloalkyl, Ci- C4fluoroalkyl, Ci-C4fluoroalkoxy, pentafluorosulfanyl, Ci-C4hydroxyalkyl, Ci-C4thioalkyl, azido, diCi-C4alkylamino, diCi-C4alkylaminocarbonyl, D, CD3, cyano, formyl, phenyl and a 5- to 6-membered heterocycloalkyl comprising 1 or 2 ring members independently selected from N, NR4, O and S;

[0277] Li is -(CR2R3)P-, -(CR2R3)P-NR4-, -(CR2R3)P-O-, -NR4(CR2R3)q-, -(CR2R3)qNR4-, -O-(CR2R3)P- or - S-(CR2R3)P-;

[0278] R2is H, D, halogen or Ci-C4alkyl;

[0279] R3is H, D, halogen, Ci-C4alkyl, Ci-C4alkoxy, OH, amino or t-Boc-amino; or R2and R3, together with the C atom to which they are attached, are linked to form C3- C4cycloalkyl which is unsubstituted or is substituted with a single substituent selected from Ci-C4alkyl and oxo; each R4is independently selected from the group consisting of H and Ci-C4alkyl; p is 1 , 2 or 3; q is 0, 1 or 2; Zi is N, Z2 is CRZ, Z3 is N, Z4 is C and Z5 is N; or Z1 is N, Z2 is CRZ, Z3 is N, Z4 is C and Z5 is CRZ; or Z1 is C, Z2 is CRZ, Z3 is N, Z4 is N and Z5 is CRZ; or Z1 is C, Z2 is N, Z3 is N, Z is N and Z5 is CRZ; or Z1 is N, Z2 is CRZ, Z3 is CRZ, Z4 is C and Z5 is N; each Rzis independently selected from the group consisting of H, halogen, Ci-C4alkyl and C1- C4fluoroalkyl; l_2 is a bond, -(CRsR7)n- or -(CR6R7)nO-*, where the * indicates the point of attachment to R8; each R6is independently selected from the group consisting of H, Ci-C4alkyl, Ci-C4fluoroalkyl and CrC4hydroxyalkyl; each R7is independently selected from the group consisting of H, Ci-C4alkyl, Ci-C4fluoroalkyl and CrC4hydroxyalkyl; or R6and R7, together with the C atom to which they are attached, are linked to form C3- Cecycloalkyl, oxetanyl, tetrahydrofuranyl or tetrahydropyranyl; n is 1 , 2 or 3;

[0280] R8is:

[0281] (i) 4-, 5- or 6-membered heterocycloalkyl having 1 , 2 or 3 ring members independently selected from N, NR9, O and S, wherein the heterocycloalkyl is unsubstituted or is substituted with 1 , 2, 3 or 4 substituents each independently selected from -OH, -CN, - N(R10)2, halogen, Ci-C4fluoroalkyl, Ci-C4alkyl, CrC4alkoxy, oxo and a 5- or 6- membered monocyclic heteroaryl having 1 , 2, 3 or 4 ring members independently selected from N, NR9, O and S, wherein the monocyclic heteroaryl is unsubstituted;

[0282] (ii) 4-, 5- or 6-membered heterocycloalkyl wherein one ring member is S(=O)2, S(=O) or S(=O)(=NH), and wherein the heterocycloalkyl is unsubstituted or is substituted with 1 , 2, 3 or 4 substituents, each independently selected from -OH, Ci-C4alkyl and oxo;

[0283] (iii) 4-, 5- or 6-membered heterocycloalkyl wherein one ring member is S(=O)2 or S(=O), and 1 , 2 or 3 other ring members are independently selected from N, NR9and O, and wherein the heterocycloalkyl is unsubstituted or is substituted with 1 , 2, 3 or 4 substituents each independently selected from Ci-C4alkyl and oxo;

[0284] (iv) a partially saturated 5- or 6-membered heterocyclyl having 1 or 2 ring members independently selected from N, NR9, O and S, wherein the partially saturated heterocyclyl is unsubstituted or is substituted with 1 , 2, 3 or 4 substituents independently selected from -OH, Ci-C4alkyl, and oxo;

[0285] (v) a partially saturated 5- or 6-membered heterocyclyl wherein one ring member is S(=O)2and 1 , 2 or 3 other ring members are independently selected from N, NR9, O and S, wherein the partially saturated heterocyclyl is unsubstituted or is substituted with 1 , 2, 3 or 4 substituents independently selected from -OH, Ci-C4alkyl, and oxo; (vi) a 5- or 6- membered monocyclic heteroaryl having 1 , 2, 3 or 4 ring members independently selected from N, NR9, O and S, wherein the monocyclic heteroaryl is unsubstituted or is substituted with 1 , 2, 3 or 4 substituents each independently selected from -OH, CrC4alkoxy and Ci-C4alkyl;

[0286] (vii) a 6- or 7-membered fused bicyclic heterocyclyl having 1 or 2 ring members independently selected from N, NR9, O and S, wherein the fused bicyclic heterocyclyl is unsubstituted or is substituted with 1 , 2, 3 or 4 substituents, each independently selected from -OH, -N(R10)2, Ci-C4alkyl-NH2, halogen, Ci-C4alkyl, and oxo;

[0287] (viii) a partially saturated 8-, 9-, 10-, 11 - or 12-membered fused bicyclic heterocyclyl having 1 , 2, 3 or 4 ring members independently selected from N, NR9, O and S, wherein the fused bicyclic heterocyclyl is unsubstituted or is substituted with 1 , 2, 3 or 4 substituents, each independently selected from -OH, -N(R10)2, Ci-C4alkyl-NH2, halogen, Ci-C4alkyl, and oxo;

[0288] (ix) a 6-, 7-, 8-, 9- or 10- membered spiro bicyclic heterocycloakyl having 1 , 2 or 3 ring members independently selected from N, NR9, O and S, wherein the spiro bicyclic heterocycloakyl is unsubstituted or is substituted with 1 , 2, 3 or 4 substituents, each independently selected from -OH, -N(R10)2, Ci-C4alkyl-NH2, halogen, Ci-C4alkyl, and oxo;

[0289] (x) a 6- membered heterocycloalkyl having 1 to 2 ring members independently selected from N, NR9, O and S, wherein the heterocycloalkyl has a Ci-Csalkyl bridge or a - CH2OCH2- bridge;

[0290] (xi) phenyl which is unsubstituted or is substituted with 1 , 2, 3 or 4 substituents, each independently selected from -S(=O)2N(R10)2, -OH, -N(R10)2, Ci-C4alkyl-NH2, halogen and Ci-C4alkyl; or

[0291] (xii) C4-C8cycloalkyl which is unsubstituted or is substituted with 1 , 2, 3 or 4 substituents independently selected from -OH, -N(R10)2, -S(=O)2R10, Ci-C alkyl-NH2, halogen, Ci- C4alkoxy, Ci-C4alkyl, and oxo;

[0292] R9is H, Ci-C4alkyl, benzyl, Ci-C4alkyl-OR10, -C(=O)OR10or -C(=O)R10, and

[0293] R10is H or Ci-C4alkyl.

[0294] In an embodiment of compounds of Formula (l-a) and Formula (l-b), or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof:

[0295] -X=Y- is -CRx=CRy-, -CRX=N- or -N=CRy-;

[0296] Rxis H, D or halogen;

[0297] Ryis H, D, halogen or -CN;

[0298] R5is halogen or -CN; each R1is independently selected from the group consisting of halogen, D, CD3, Ci-C4alkyl, Ci- C4fluoroalkyl, Ci-C4fluorolkoxy, Cs-Cecycloalkyl and pentafluorosulfanyl;

[0299] Li is -(CR2R3)P-, -NR4(CR2R3)q- or -O-(CR2R3)P-;

[0300] R2is H, D or halogen;

[0301] R3is H, D, halogen, OH or Ci-C4alkyl; or R2and R3, together with the C atom to which they are attached, are linked to form C3- C4cycloalkyl which is unsubstituted

[0302] R4is H or Ci-C4alkyl; p is 1 ; q is 0;

[0303] Zi is N, Z2is CRZ, Z3is N, Z4is C and Z5is N; or Zi is N, Z2is CRZ, Z3is N, Z4is C and Z5is CRZ; or Zi is C, Z2is CRZ, Z3is N, Z4is N and Z5is CRZ; or Zi is C, Z2is N, Z3is N, Z4is N and Z5is CRZ; each Rzis H; l_2is a bond, -(CR5R7)n- or -(CR6R7)nO-*, where the * indicates the point of attachment to R8; each R6is independently selected from the group consisting of H, Ci-C4alkyl, Ci-C4fluoroalkyl and Ci-C4hydroxyalkyl; each R7is independently selected from the group consisting of H, Ci-C4alkyl, Ci-C4fluoroalkyl and Ci-C4hydroxyalkyl; or R6and R7, together with the C atom to which they are attached, are linked to form tetrahydropyranyl; n is 1 or 2;

[0304] R8is:

[0305] (i) 4-, 5- or 6-membered heterocycloalkyl having 1 or 2 ring members independently selected from N, NR9, O and S, wherein the heterocycloalkyl is unsubstituted or is substituted with 1 , 2 or 3 substituents each independently selected from -OH, -CN, - N(R10)2, halogen, Ci-C4fluoroalkyl, Ci-C4alkyl, CrC4alkoxy, oxo and a 5- or 6- membered monocyclic heteroaryl having 1or 2 ring members independently selected from N and NR9, wherein the monocyclic heteroaryl is unsubstituted;

[0306] (ii) 5- membered heterocycloalkyl wherein one ring member is S(=O)2, S(=O) or S(=O)(=NH), and wherein the heterocycloalkyl is unsubstituted or is substituted with a substituent selected from -OH and Ci-C4alkyl;

[0307] (iii) 6-membered heterocycloalkyl wherein one ring member is S(=O)2or S(=O), and one other ring member is selected from N, NR9and O, and wherein the heterocycloalkyl is unsubstituted or is substituted with a substituent selected from Ci-C4alkyl; (iv) a partially saturated 6-membered heterocyclyl having 1 or 2 ring members independently selected from N, NR9, O and S, wherein the partially saturated heterocyclyl is unsubstituted or is substituted with an oxo;

[0308] (v) a partially saturated 6-membered heterocyclyl wherein one ring member is S(=O)2 and one other ring member is selected from N, NR4, and O, wherein the partially saturated heterocyclyl is unsubstituted or is substituted with an oxo;

[0309] (vi) a 5- or 6- membered monocyclic heteroaryl having 1 , 2, 3 or 4 ring members independently selected from N, NR9and O, wherein the monocyclic heteroaryl is unsubstituted or is substituted with a substituent selected from -OH, Ci-C4alkoxy and Ci-C4alkyl;

[0310] (vii) a 6- membered fused bicyclic heterocyclyl having 1 ring member selected from N and NR9, wherein the fused bicyclic heterocyclyl is unsubstituted or is substituted with an oxo;

[0311] (viii) a partially saturated 10- membered fused bicyclic heterocyclyl having 1 , 2, or 3 ring members independently selected from N, NR9, and O, wherein the fused bicyclic heterocyclyl is unsubstituted or is substituted with an oxo;

[0312] (ix) a 7- membered spiro bicyclic heterocycloakyl having 1 ring member selected from N, NR9, and O, wherein the spiro bicyclic heterocycloakyl is unsubstituted;

[0313] (x) a 6- membered heterocycloalkyl having 1 to 2 ring members independently selected from N, NR9and O, wherein the heterocycloalkyl has a Ci-C3alkyl bridge or a - CH2OCH2- bridge;

[0314] (xi) phenyl which is substituted with -S(=O)2N(RCl)2; or

[0315] (xii) C4-C8cycloalkyl which is substituted with 1 , 2 or 3 substituents independently selected from -OH, -N(R10)2, -S(=O)2R10, Ci-C4alkyl-NH2, halogen and Ci-C4alkoxy;

[0316] R9is H, Ci-C4alkyl, benzyl, Ci-C4alkyl-OR10, -C(=O)OR10or -C(=O)R10, and

[0317] R10is H or CrC4alkyl.

[0318] In an embodiment of compounds of Formula (l-a) and Formula (l-b), or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof:

[0319] -X=Y- is -CRx=CRy-, -CRX=N- or -N=CRy-;

[0320] Rxis H or F;

[0321] Ryis H, F or CN;

[0322] R5is F, Cl or CN; each R1is independently selected from the group consisting of F, Cl, Br, methyl, isopropyl, t- butyl, cyclopropyl, -CF3, CHF2, CF2CF3, OCF3, and SF5;

[0323] Li is -(CR2R3)P-, -NR4(CR2R3)q- or -O-(CR2R3)P-; R2is H or F;

[0324] R3is H, OH, F or methyl; or R2and R3, together with the C atom to which they are attached, are linked to form cyclopropyl which is unsubstituted;

[0325] R4is H, methyl or ethy; p is 1 ; q is 0;

[0326] Zi is N, Z2 is CRZ, Z3 is N, Z4 is C and Z5 is N; or Z1 is N, Z2 is CRZ, Z3 is N, Z4 is C and Z5 is CRZ; or Z1 is C, Z2is CRZ, Z3is N, Z4is N and Z5is CRZ; or Z1 is C, Z2is N, Z3is N, Z4is N and Z5is CRZ; each Rzis H;

[0327] L2is a bond, -(CR5R7)n- or -(CR6R7)nO-*, where the * indicates the point of attachment to R8; each R6is independently selected from the group consisting of H, methyl, isopropyl, -CH2OH and CH2CF3; each R7is independently selected from the group consisting of H, methyl, isopropyl, -CH2OH and CH2CF3; or R6and R7, together with the C atom to which they are attached, are linked to form tetrahydropyranyl; n is 1 or 2;

[0328] R8is:

[0329] (i) 4-, 5- or 6-membered heterocycloalkyl having 1 or 2 ring members independently selected from N, NR9, O and S, wherein the heterocycloalkyl is unsubstituted or is substituted with 1 , 2 or 3 substituents each independently selected from -OH, -CN, NH2, F, CF3, methyl, methoxy, oxo and a 5- or 6- membered monocyclic heteroaryl having 1 or 2 ring members independently selected from N and NR9, wherein the monocyclic heteroaryl is unsubstituted;

[0330] (ii) 5- membered heterocycloalkyl wherein one ring member is S(=O)2, S(=O) or S(=O)(=NH), and wherein the heterocycloalkyl is unsubstituted or is substituted with a substituent selected from OH and methyl;

[0331] (iii) 6-membered heterocycloalkyl wherein one ring member is S(=O)2 or S(=O), and one other ring member is selected from N, NR9and O, and wherein the heterocycloalkyl is unsubstituted or is substituted with a methyl,

[0332] (iv) a partially saturated 6-membered heterocyclyl having 1 or 2 ring members independently selected from N, NR9, O and S, wherein the partially saturated heterocyclyl is unsubstituted or is substituted with an oxo; (v) a partially saturated 6-membered heterocyclyl wherein one ring member is S(=O)3and one other ring member is selected from N, NR9, and O, wherein the partially saturated heterocyclyl is unsubstituted or is substituted with an oxo;

[0333] (vi) a 5- or 6- membered monocyclic heteroaryl having 1 , 2, 3 or 4 ring members independently selected from N, NR9and O, wherein the monocyclic heteroaryl is unsubstituted or is substituted with a substituent selected from -OH methoxy and methyl;

[0334] (vii) a 6- membered fused bicyclic heterocyclyl having 1 ring member selected from N and NR9, wherein the fused bicyclic heterocyclyl is unsubstituted or is substituted with an oxo;

[0335] (viii) a partially saturated 10- membered fused bicyclic heterocyclyl having 1 , 2, or 3 ring members independently selected from N, NR9, and O, wherein the fused bicyclic heterocyclyl is unsubstituted or is substituted with an oxo;

[0336] (ix) a 7- membered spiro bicyclic heterocycloakyl having 1 ring member selected from N, NR9, and O, wherein the spiro bicyclic heterocycloakyl is unsubstituted;

[0337] (x) a 6- membered heterocycloalkyl having 1 to 2 ring members independently selected from N, NR9and O, wherein the heterocycloalkyl has a Ci-C3alkyl bridge or a - CH2OCH2- bridge;

[0338] (xi) phenyl which is substituted with -S(=O)2NH2; or

[0339] (xii) cyclobutyl, cyclopentyl, or cyclohexyl which is substituted with 1 , 2 or 3 substituents independently selected from -OH, -NH2, -S(=O)2CH3, -CH2NH2, F, and methoxy; and

[0340] R9is H, methyl, benzyl, -C(=O)CH3, -C(=O)O(CH3)3, CH2CH2OH or CH2CH2OCH3.

[0341] In an embodiment of compounds of Formula (l-a) and Formula (l-b), or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof:

[0342] -X=Y- is -CRx=CRv- or -CRX=N-;

[0343] R* is H;

[0344] Ry is H, D, halogen or -CN;

[0345] R5is halogen or -CN; each R1is independently selected from the group consisting of halogen, Ci-C4alkyl, C1- C4fluoroalkyl and pentafluorosulfanyl;

[0346] Li is -(CR2R3)P-, -NR4(CR2R3)q- or -O-(CR2R3)P-;

[0347] R2is H;

[0348] R3is H, OH or Ci-C4alkyl;

[0349] R4is H or Ci-C4alkyl;

[0350] P is 1 ; q is 0;

[0351] Zi is N, Z2 is CRZ, Z3 is N, Z4 is C and Z5 is N; or Z1 is N, Z2 is CRZ, Z3 is N, Z4 is C and Z5 is CRZ; or Z1 is C, Z2 is CRZ, Z3 is N, Z4 is N and Z5 is CRZ; or Z1 is C, Z2 is N, Z3 is N, Z is N and Z5 is CRZ; each Rzis H; l_2 is a bond, -(CR6R7)n- or -(CR6R7)nO-*, where the * indicates the point of attachment to R8; each R6is independently selected from the group consisting of H, Ci-C4alkyl, and C1- C4hydroxyalkyl; each R7is independently selected from the group consisting of H, Ci-C4alkyl, and C1- C4hydroxyalkyl; n is 1 or 2;

[0352] R8is:

[0353] (i) 4-, 5- or 6-membered heterocycloalkyl having 1 or 2 ring members independently selected from N, NR9, O and S, wherein the heterocycloalkyl is unsubstituted or is substituted with 1 , 2 or 3 substituents each independently selected from -OH, -CN, - N(R10)2, halogen, Ci-C4fluoroalkyl, Ci-C4alkyl, CrC4alkoxy, oxo and a 5- or 6- membered monocyclic heteroaryl having 1or 2 ring members independently selected from N and NR9, wherein the monocyclic heteroaryl is unsubstituted;

[0354] (ii) 5- membered heterocycloalkyl wherein one ring member is S(=O)2, S(=O) or S(=O)(=NH), and wherein the heterocycloalkyl is unsubstituted or is substituted with a substituent selected from -OH and Ci -C4alkyl;

[0355] (iii) 6-membered heterocycloalkyl wherein one ring member is S(=O)2 or S(=O), and one other ring member is selected from N, NR9and O, and wherein the heterocycloalkyl is unsubstituted or is substituted with a substituent selected from Ci-C4alkyl ;

[0356] (iv) a partially saturated 6-membered heterocyclyl having 1 or 2 ring members independently selected from N, NR9, O and S, wherein the partially saturated heterocyclyl is unsubstituted or is substituted with an oxo;

[0357] (v) a partially saturated 6-membered heterocyclyl wherein one ring member is S(=O)2and one other ring member is selected from N, NR4, and O, wherein the partially saturated heterocyclyl is unsubstituted or is substituted with an oxo;

[0358] (vi) a 5- or 6- membered monocyclic heteroaryl having 1 , 2, 3 or 4 ring members independently selected from N, NR9and O, wherein the monocyclic heteroaryl is unsubstituted or is substituted with a substituent selected from -OH, Ci-C4alkoxy and Ci-C4alkyl;

[0359] (vii) a 6- membered fused bicyclic heterocyclyl having 1 ring member selected from N and NR9, wherein the fused bicyclic heterocyclyl is unsubstituted or is substituted with an oxo; (viii) a partially saturated 10- membered fused bicyclic heterocyclyl having 1 , 2, or 3 ring members independently selected from N, NR9, and O, wherein the fused bicyclic heterocyclyl is unsubstituted or is substituted with an oxo;

[0360] (ix) a 7- membered spiro bicyclic heterocycloakyl having 1 ring member selected from N, NR9, and O, wherein the spiro bicyclic heterocycloakyl is unsubstituted;

[0361] (x) a 6- membered heterocycloalkyl having 1 to 2 ring members independently selected from N, NR9and O, wherein the heterocycloalkyl has a Ci-Csalkyl bridge or a - CH2OCH2- bridge;

[0362] (xi) phenyl which is substituted with -S(=O)2N(R10)2; or

[0363] (xii) C4-C8cycloalkyl which is substituted with 1 , 2 or 3 substituents independently selected from -OH, -N(R10)2, -S(=O)2R10, Ci-C4alkyl-NH2, halogen and Ci-C4alkoxy;

[0364] R9is H, Ci-C4alkyl, benzyl, Ci-C4alkyl-OR10, -C(=O)OR10or -C(=O)R10, and

[0365] R10is H or CrC4alkyl.

[0366] In an embodiment of compounds of Formula (l-a) and Formula (l-b), or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof:

[0367] -X=Y- is -CRx=CRy- or -CRX=N-;

[0368] Rxis H;

[0369] Rv is H, F or GN;

[0370] R5is F or GN; each R1is independently selected from the group consisting of F, Cl, methyl, -CF3, and SF5;

[0371] Li is -(CR2R3)P-, -NR4(CR2R3)q- or -O-(CR2R3)P-;

[0372] R2is H;

[0373] R3is H, OH or methyl;

[0374] R4is H, methyl or ethy; p is 1 ; q is 0;

[0375] Z1 is N, Z2is CRZ, Z3is N, Z4is C and Z5is N; or Z1 is N, Z2is CRZ, Z3is N, Z4is C and Z5is CRZ; or Z1 is C, Z2is CRZ, Z3is N, Z4is N and Z5is CRZ; or Z1 is C, Z2is N, Z3is N, Z4is N and Z5is CRZ; each Rzis H;

[0376] L2is a bond, -(CRsR7)n- or -(CR6R7)nO-*, where the * indicates the point of attachment to R8; each R6is independently selected from the group consisting of H, methyl and -CH2OH; each R7is independently selected from the group consisting of H, methyl and -CH2OH; n is 1 or 2; R8is:

[0377] (i) 4-, 5- or 6-membered heterocycloalkyl having 1 or 2 ring members independently selected from N, NR9, O and S, wherein the heterocycloalkyl is unsubstituted or is substituted with 1 , 2 or 3 substituents each independently selected from -OH, -GN, NH2, F, CF3, methyl, methoxy, oxo and a 5- or 6- membered monocyclic heteroaryl having 1 or 2 ring members independently selected from N and NR9, wherein the monocyclic heteroaryl is unsubstituted;

[0378] (ii) 5- membered heterocycloalkyl wherein one ring member is S(=O)2, S(=O) or S(=O)(=NH), and wherein the heterocycloalkyl is unsubstituted or is substituted with a substituent selected from OH and methyl;

[0379] (iii) 6-membered heterocycloalkyl wherein one ring member is S(=O)z or S(=O), and one other ring member is selected from N, NR9and O, and wherein the heterocycloalkyl is unsubstituted or is substituted with a methyl,

[0380] (iv) a partially saturated 6-membered heterocyclyl having 1 or 2 ring members independently selected from N, NR9, O and S, wherein the partially saturated heterocyclyl is unsubstituted or is substituted with an oxo;

[0381] (v) a partially saturated 6-membered heterocyclyl wherein one ring member is S(=O)2 and one other ring member is selected from N, NR9, and O, wherein the partially saturated heterocyclyl is unsubstituted or is substituted with an oxo;

[0382] (vi) a 5- or 6- membered monocyclic heteroaryl having 1 , 2, 3 or 4 ring members independently selected from N, NR9and O, wherein the monocyclic heteroaryl is unsubstituted or is substituted with a substituent selected from -OH methoxy and methyl;

[0383] (vii) a 6- membered fused bicyclic heterocyclyl having 1 ring member selected from N and NR9, wherein the fused bicyclic heterocyclyl is unsubstituted or is substituted with an oxo;

[0384] (viii) a partially saturated 10- membered fused bicyclic heterocyclyl having 1 , 2, or 3 ring members independently selected from N, NR9, and O, wherein the fused bicyclic heterocyclyl is unsubstituted or is substituted with an oxo;

[0385] (ix) a 7- membered spiro bicyclic heterocycloakyl having 1 ring member selected from N, NR9, and O, wherein the spiro bicyclic heterocycloakyl is unsubstituted;

[0386] (x) a 6- membered heterocycloalkyl having 1 to 2 ring members independently selected from N, NR9and O, wherein the heterocycloalkyl has a Ci-Csalkyl bridge or a - CH2OCH2- bridge;

[0387] (xi) phenyl which is substituted with -S(=O)2NH2; or

[0388] (xii) cyclobutyl, cyclopentyl, or cyclohexyl which is substituted with 1 , 2 or 3 substituents independently selected from -OH, -NH2, -S(=O)2CHs, -CH2NH2, F, and methoxy; and

[0389] R9is H, methyl, benzyl, -C(=O)CH3, -C(=O)O(CH3)3, CH2CH2OH or CH2CH2OCH3.

[0390] In an embodiment of compounds of Formula (l-a) and Formula (l-b), or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof:

[0391] -X=Y- is -CRX=N-;

[0392] Rxis H;

[0393] R5is halogen; each R1is independently selected from the group consisting of halogen, Ci-C4alkyl and Ci- C4fluoroalkyl

[0394] Li is -(CR2R3)P-;

[0395] R2is H;

[0396] R3is H, or Ci-C4alkyl; p is 1 ;

[0397] Zi is N, Z2is CRZ, Z3is N, Z4 is C and Z5 is N; or Z1 is N, Z2is CRZ, Z3is N, Z4 is C and Z5 is CRZ; or Z1 is C, Z2is CRZ, Z3is N, Z4is N and Z5is CRZ; or Z1 is C, Z2is N, Z3is N, Z4is N and Z5is CRZ; each Rzis H; l_2is a bond or -(CRBR7)n-; each R6is independently selected from the group consisting of H and Ci C^alkyl; each R7is independently selected from the group consisting of H and Ci-C4alkyl; n is 1 or 2;

[0398] R8is:

[0399] (i) 4-, 5- or 6-membered heterocycloalkyl having 1 or 2 ring members independently selected from N, NR9, O and S, wherein the heterocycloalkyl is unsubstituted or is substituted with 1 , 2 or 3 substituents each independently selected from -OH, halogen, Ci-C4fluoroalkyl, Ci-C4alkyl, and oxo;

[0400] (ii) 5- membered heterocycloalkyl wherein one ring member is S(=O)2, or S(=O)(=NH), and wherein the heterocycloalkyl is unsubstituted or is substituted with a substituent selected from Ci-C4alkyl;

[0401] (iii) 6-membered heterocycloalkyl wherein one ring member is S(=O)2or S(=O), and one other ring member is selected from N, NR9and O, and wherein the heterocycloalkyl is unsubstituted or is substituted with a substituent selected from Ci-C4alkyl;

[0402] (iv) a partially saturated 6-membered heterocyclyl having 1 or 2 ring members independently selected from O and S, wherein the partially saturated heterocyclyl is unsubstituted; (v) a partially saturated 6-membered heterocyclyl wherein one ring member is S(=O)2and one other ring member is O, wherein the partially saturated heterocyclyl is unsubstituted;

[0403] (vi) a 5- membered monocyclic heteroaryl having 3 ring members independently selected from N, and O, wherein the monocyclic heteroaryl is unsubstituted;

[0404] (vii) a 6- membered fused bicyclic heterocyclyl having 1 ring member selected from NR9, wherein the fused bicyclic heterocyclyl is unsubstituted;

[0405] (viii) a 7- membered spiro bicyclic heterocycloakyl having 1 ring member selected from N, NR9, and O, wherein the spiro bicyclic heterocycloakyl is unsubstituted;

[0406] (ix) a 6- membered heterocycloalkyl having 1 ring members selected from NR9, wherein the heterocycloalkyl has a Ci-C3alkyl bridge; or

[0407] (x) CrCscycloalkyl which is substituted with 1 , 2 or 3 substituents independently selected from -OH, -N(R10)2, Ci-C4alkyl-NH2and halogen;

[0408] R9is H, Ci-C4alkyl, or -C(=O)R10, and

[0409] R10is H or Ci-C4alkyl.

[0410] In an embodiment of compounds of Formula (l-a) and Formula (l-b), or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof:

[0411] -X=Y- is -CRX=N-;

[0412] Rxis H;

[0413] R5is F; each R1is independently selected from the group consisting of F, Cl, methyl and -CF3;

[0414] Li is -(CR2R3)P-,

[0415] R2is H;

[0416] R3is H or methyl; p is 1 ;

[0417] Zi is N, Z2is CRZ, Z3is N, Z4is C and Z5is N; or Zi is N, Z2is CRZ, Z3is N, Z4is C and Z5is CRZ; or Zi is C, Z2is CRZ, Z3is N, Z4is N and Z5is CRZ; or Zi is C, Z2is N, Z3is N, Z4is N and Z5is CRZ; each Rzis H; l_2is a bond or -(CRsR7)n-; each R6is independently selected from the group consisting of H and methyl; each R7is independently selected from the group consisting of H and methyl; n is 1 or 2;

[0418] R8is: (i) 4-, 5- or 6-membered heterocycloalkyl having 1 or 2 ring members independently selected from N, NR9, O and S, wherein the heterocycloalkyl is unsubstituted or is substituted with 1 , 2 or 3 substituents each independently selected from -OH, F, CF3, methyl and oxo;

[0419] (ii) 5- membered heterocycloalkyl wherein one ring member is S(=O)2 or S(=O)(=NH), and wherein the heterocycloalkyl is unsubstituted or is substituted with a methyl;

[0420] (iii) 6-membered heterocycloalkyl wherein one ring member is S(=O)2 or S(=O), and one other ring member is selected from N, NR9and O, and wherein the heterocycloalkyl is unsubstituted or is substituted with a methyl,

[0421] (iv) a partially saturated 6-membered heterocyclyl having 1 or 2 ring members independently selected from O and S, wherein the partially saturated heterocyclyl is unsubstituted;

[0422] (v) a partially saturated 6-membered heterocyclyl wherein one ring member is S(=O)2 and one other ring member is and O, wherein the partially saturated heterocyclyl is unsubstituted;

[0423] (vi) a 5- membered monocyclic heteroaryl having 3 ring members independently selected from N and O, wherein the monocyclic heteroaryl is unsubstituted;

[0424] (vii) a 6- membered fused bicyclic heterocyclyl having 1 ring member selected from NR9, wherein the fused bicyclic heterocyclyl is unsubstituted;

[0425] (viii) a 7- membered spiro bicyclic heterocycloakyl having 1 ring member selected from NR9, and O, wherein the spiro bicyclic heterocycloakyl is unsubstituted;

[0426] (ix) a 6- membered heterocycloalkyl having 1 ring members selected from NR9, wherein the heterocycloalkyl has a Ci-C3alkyl bridge; or

[0427] (x) cyclobutyl, cyclopentyl, or cyclohexyl which is substituted with 1 , 2 or 3 substituents independently selected from -OH, -NH2, -CH2NH2, and F; and

[0428] R9is H, methyl or -C(=O)CH3.

[0429] In an embodiment of compounds of Formula (l-a) and Formula (l-b), or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof:

[0430] -X=Y- is -CRX=N-;

[0431] Rxis H;

[0432] R5is halogen; each R1is independently selected from the group consisting of halogen, Ci-C4alkyl and C1- C4fluoroalkyl

[0433] Li is -(CR2R3)P-;

[0434] R2is H; R3is H, or Ci-C4alkyl; p is 1 ;

[0435] Zi is N, Z2 is CRZ, Z3 is N, Z4 is C and Z5 is N; or Z1 is N, Z2 is CRZ, Z3 is N, Z4 is C and Z5 is CRZ; each Rzis H;

[0436] L2 is a bond or -(CRsR7)n-; each R6is independently selected from the group consisting of H and Ci-C4alkyl; each R7is independently selected from the group consisting of H and Ci-C alkyl; n is 1 or 2;

[0437] R8is:

[0438] (i) 4-, 5- or 6-membered heterocycloalkyl having 1 or 2 ring members independently selected from N, NR9, O and S, wherein the heterocycloalkyl is unsubstituted or is substituted with 1 , 2 or 3 substituents each independently selected from -OH, halogen, Ci-C4fluoroalkyl, CrC4alkyl, and oxo;

[0439] (ii) 5- membered heterocycloalkyl wherein one ring member is S(=O)2, or S(=O)(=NH), and wherein the heterocycloalkyl is unsubstituted or is substituted with a substituent selected from Ci-C4alkyl;

[0440] (iii) 6-membered heterocycloalkyl wherein one ring member is S(=O)2 or S(=O), and one other ring member is selected from N, NR9and O, and wherein the heterocycloalkyl is unsubstituted or is substituted with a substituent selected from Ci-C4alkyl ;

[0441] (iv) a partially saturated 6-membered heterocyclyl having 1 or 2 ring members independently selected from O and S, wherein the partially saturated heterocyclyl is unsubstituted;

[0442] (v) a partially saturated 6-membered heterocyclyl wherein one ring member is S(=O)2 and one other ring member is O, wherein the partially saturated heterocyclyl is unsubstituted;

[0443] (vi) a 5- membered monocyclic heteroaryl having 3 ring members independently selected from N, and O, wherein the monocyclic heteroaryl is unsubstituted;

[0444] (vii) a 6- membered fused bicyclic heterocyclyl having 1 ring member selected from NR9, wherein the fused bicyclic heterocyclyl is unsubstituted;

[0445] (viii) a 7- membered spiro bicyclic heterocycloakyl having 1 ring member selected from N, NR9, and O, wherein the spiro bicyclic heterocycloakyl is unsubstituted;

[0446] (ix) a 6- membered heterocycloalkyl having 1 ring members selected from NR9, wherein the heterocycloalkyl has a Ci-Csalkyl bridge; or

[0447] (x) C4-Cscycloalkyl which is substituted with 1 , 2 or 3 substituents independently selected from -OH, -N(R10)2, CrC4alkyl-NH2and halogen;

[0448] R9is H, Ci-C4alkyl, or -C(=O)R10, and

[0449] R10is H or CrC4alkyl.

[0450] In an embodiment of compounds of Formula (l-a) and Formula (l-b), or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof:

[0451] -X=Y- is -CRX=N-;

[0452] Rxis H;

[0453] R5is F; each R1is independently selected from the group consisting of F, Cl, methyl and -CF3;

[0454] Li is -(CR2R3)P-,

[0455] R2is H;

[0456] R3is H or methyl; p is 1 ;

[0457] Zi is N, Z2 is CRZ, Z3is N, Z4 is C and Z5 is N; or Z1 is N, Z2 is CRZ, Z3 is N, Z4 is C and Z5 is CRZ; each Rzis H;

[0458] L2is a bond or -(CRsR7)n-; each R6is independently selected from the group consisting of H and methyl; each R7is independently selected from the group consisting of H and methyl; n is 1 or 2;

[0459] R8is:

[0460] (i) 4-, 5- or 6-membered heterocycloalkyl having 1 or 2 ring members independently selected from N, NR9, O and S, wherein the heterocycloalkyl is unsubstituted or is substituted with 1 , 2 or 3 substituents each independently selected from -OH, F, CF3, methyl and oxo;

[0461] (ii) 5- membered heterocycloalkyl wherein one ring member is S(=O)z or S(=O)(=NH), and wherein the heterocycloalkyl is unsubstituted or is substituted with a methyl;

[0462] (iii) 6-membered heterocycloalkyl wherein one ring member is S(=O)2 or S(=O), and one other ring member is selected from N, NR9and O, and wherein the heterocycloalkyl is unsubstituted or is substituted with a methyl,

[0463] (iv) a partially saturated 6-membered heterocyclyl having 1 or 2 ring members independently selected from O and S, wherein the partially saturated heterocyclyl is unsubstituted;

[0464] (v) a partially saturated 6-membered heterocyclyl wherein one ring member is S(=O)2and one other ring member is and O, wherein the partially saturated heterocyclyl is unsubstituted;

[0465] (vi) a 5- membered monocyclic heteroaryl having 3 ring members independently selected from N and O, wherein the monocyclic heteroaryl is unsubstituted; (vii) a 6- membered fused bicyclic heterocyclyl having 1 ring member selected from NR9, wherein the fused bicyclic heterocyclyl is unsubstituted;

[0466] (viii) a 7- membered spiro bicyclic heterocycloakyl having 1 ring member selected from

[0467] NR9, and O, wherein the spiro bicyclic heterocycloakyl is unsubstituted;

[0468] (ix) a 6- membered heterocycloalkyl having 1 ring members selected from NR9, wherein the heterocycloalkyl has a Ci-C3alkyl bridge; or

[0469] (x) cyclobutyl, cyclopentyl, or cyclohexyl which is substituted with 1 , 2 or 3 substituents independently selected from -OH, -NH2, -CH2NH2, and F; and

[0470] R9is H, methyl or -C(=O)CH3.

[0471] In an embodiment of compounds of Formula (l-a) and Formula (l-b), or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof:

[0472] -X=Y- is -CRX=N-;

[0473] Rxis H;

[0474] R5is halogen; each R1is independently selected from the group consisting of halogen, Ci-C4alkyl and C1-

[0475] C4fluoroalkyl;

[0476] Li is -(CR2R3)P-;

[0477] R2is H;

[0478] R3is H;

[0479] P is 1 ;

[0480] Z1 is N, Z2is CRZ, Z3is N, Z4is C and Z5is N; each Rzis H;

[0481] L2is a bond;

[0482] R8is pyrrolidinyl which is substituted with 1 or 2 each independently selected from halogen and Ci-C4fluoroalkyl.

[0483] In an embodiment of compounds of Formula (l-a) and Formula (l-b), or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof:

[0484] -X=Y- is -CRX=N-;

[0485] Rxis H;

[0486] R5is F; each R1is independently selected from the group consisting of F, Cl, methyl, and CF3;

[0487] Li is -(CR2R3)P-;

[0488] R2is H;

[0489] R3is H; p is 1 ;

[0490] Zi is N, Z2 is CRZ, Z3 is N, Z4 is C and Z5 is N; each Rzis H; l_2 is a bond; R8is pyrrolidinyl which is substituted with 1 or 2 each independently selected from F and CF3.

[0491] In any one of the aforementioned embodiments the compound of Formula (I) is a compound of Formula (l-a), or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof: In any one of the aforementioned embodiments the compound of Formula (I) is a compound of Formula (l-b), or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof:

[0492] In an embodiment of compounds of Formula (I), the compounds provided herein are compounds of Formula (l-c), Formula (l-d), Formula (l-e) or Formula (l-f), or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof:

[0493] wherein:

[0494] -X=Y- is -CRx=CRy-, -CRX=N- or -N=CRy-;

[0495] Rxis H, D, halogen or Ci-C4alkyl;

[0496] Ryis H, D, halogen, -CN, C1-C4alkyl, C1-C4fluoroalkyl or C1-C4alkoxy;

[0497] R5is H, halogen, -CN, C1-C4alkyl, C1-C4fluoroalkyl or C1C4alkoxy; each R1is independently selected from the group consisting of halogen, Ci-C4alkyl, C2- C4alkenyl, C2-C4alkynyl, Ci-C4alkoxy, Ci-C4alkoxycarbonyl, C3-C6cycloalkyl, C1- C4fluoroalkyl, Ci-C4fluoroalkoxy, pentafluorosulfanyl, Ci-C4hydroxyalkyl, Ci-C4thioalkyl, azido, diCi-C4alkylamino, diCi-C4alkylaminocarbonyl, D, CD3, cyano, formyl, phenyl and a 5- to 6-membered heterocycloalkyl comprising 1 or 2 ring members independently selected from N, NR4, O and S;

[0498] Li is -(CR2R3)P-, -(CR2R3)p-NR4-, -(CR2R3)P-O-, -NR4(CR2R3)q-, -(CR2R3)qNR4-, -O-(CR2R3)P- or - S-(CR2R3)P-;

[0499] R2is H, D, halogen or C1-C4alkyl;

[0500] R3is H, D, halogen, C1-C4alkyl, Ci-C4alkoxy, OH, amino or t-Boc-amino; or R2and R3, together with the C atom to which they are attached, are linked to form C3- C4cycloalkyl which is unsubstituted or is substituted with a single substituent selected from C1-C4alkyl and oxo; each R4is independently selected from the group consisting of H and Ci-C4alkyl; p is 1 , 2 or 3; q is 0, 1 or 2;

[0501] Z1 is N or C; Z2is N or CRZ; Z3is N or CRZ; Z4is N or C; Z5is N or CRZ; wherein each Rzis independently selected from the group consisting of H, halogen, C1- C4alkyl and Ci-C4fluoroalkyl; and provided that at least two, and not more than four, of Z1 , Z2, Z3, Z4and Z5are N; each R6is independently selected from the group consisting of H, C1-C4alkyl, Ci-C4fluoroalkyl and Ci-C4hydroxyalkyl; each R7is independently selected from the group consisting of H, Ci-C4alkyl, Ci-C4fluoroalkyl and Ci-C4hydroxyalkyl; or R6and R7, together with the C atom to which they are attached, are linked to form C3- Cecycloalkyl, oxetanyl, tetrahydrofuranyl or tetrahydropyranyl; n is 1 , 2 or 3;

[0502] R8is:

[0503] (i) 4-, 5- or 6-membered heterocycloalkyl having 1 , 2 or 3 ring members independently selected from N, NR9, O and S, wherein the heterocycloalkyl is unsubstituted or is substituted with 1 , 2, 3 or 4 substituents each independently selected from -OH, -CN, - N(R10)2, halogen, Ci-C4fluoroalkyl, Ci-C4alkyl, Ci-C4alkoxy, oxo and a 5- or 6- membered monocyclic heteroaryl having 1 , 2, 3 or 4 ring members independently selected from N, NR9, O and S, wherein the monocyclic heteroaryl is unsubstituted;

[0504] (ii) 4-, 5- or 6-membered heterocycloalkyl wherein one ring member is S(=O)2, S(=O) or S(=O)(=NH), and wherein the heterocycloalkyl is unsubstituted or is substituted with 1 , 2, 3 or 4 substituents, each independently selected from -OH, Ci-C4alkyl and oxo;

[0505] (iii) 4-, 5- or 6-membered heterocycloalkyl wherein one ring member is S(=O)2or S(=O), and 1 , 2 or 3 other ring members are independently selected from N, NR9and O, and wherein the heterocycloalkyl is unsubstituted or is substituted with 1 , 2, 3 or 4 substituents each independently selected from CrC4alkyl and oxo;

[0506] (iv) a partially saturated 5- or 6-membered heterocyclyl having 1 or 2 ring members independently selected from N, NR9, O and S, wherein the partially saturated heterocyclyl is unsubstituted or is substituted with 1 , 2, 3 or 4 substituents independently selected from -OH, CrC4alkyl, and oxo;

[0507] (v) a partially saturated 5- or 6-membered heterocyclyl wherein one ring member is S(=O)2and 1 , 2 or 3 other ring members are independently selected from N, NR9, O and S, wherein the partially saturated heterocyclyl is unsubstituted or is substituted with 1 , 2, 3 or 4 substituents independently selected from -OH, Ci-C4alkyl, and oxo;

[0508] (vi) a 5- or 6- membered monocyclic heteroaryl having 1 , 2, 3 or 4 ring members independently selected from N, NR9, O and S, wherein the monocyclic heteroaryl is unsubstituted or is substituted with 1 , 2, 3 or 4 substituents each independently selected from -OH, Ci-C4alkoxy and Ci-C4alkyl;

[0509] (vii) a 6- or 7-membered fused bicyclic heterocyclyl having 1 or 2 ring members independently selected from N, NR9, O and S, wherein the fused bicyclic heterocyclyl is unsubstituted or is substituted with 1 , 2, 3 or 4 substituents, each independently selected from -OH, -N(R10)2, Ci-C4alkyl-NH2, halogen, Ci-C4alkyl, and oxo;

[0510] (viii) a partially saturated 8-, 9-, 10-, 11 - or 12-membered fused bicyclic heterocyclyl having 1 , 2, 3 or 4 ring members independently selected from N, NR9, O and S, wherein the fused bicyclic heterocyclyl is unsubstituted or is substituted with 1 , 2, 3 or 4 substituents, each independently selected from -OH, -N(R10)2, Ci-C4alkyl-NH2, halogen, Ci-C4alkyl, and oxo;

[0511] (ix) a 6-, 7-, 8-, 9- or 10- membered spiro bicyclic heterocycloakyl having 1 , 2 or 3 ring members independently selected from N, NR9, O and S, wherein the spiro bicyclic heterocycloakyl is unsubstituted or is substituted with 1 , 2, 3 or 4 substituents, each independently selected from -OH, -N(R10)2, Ci-C4alkyl-NH2, halogen, Ci-C4alkyl, and oxo;

[0512] (x) a 6- membered heterocycloalkyl having 1 to 2 ring members independently selected from N, NR9, O and S, wherein the heterocycloalkyl has a Ci-C3alkyl bridge or a - CH2OCH2- bridge;

[0513] (xi) phenyl which is unsubstituted or is substituted with 1 , 2, 3 or 4 substituents, each independently selected from -S(=O)2N(R10)2, -OH, -N(R10)2, Ci-C4alkyl-NH2, halogen and Ci-C4alkyl; or

[0514] (xii) C4-C8cycloalkyl which is unsubstituted or is substituted with 1 , 2, 3 or 4 substituents independently selected from -OH, -N(R10)2, -S(=O)2R10, C C4alkyl-NH2, halogen, Cr C4alkoxy, Ci-C4alkyl, and oxo;

[0515] R9is H, Ci-C4alkyl, benzyl, Ci-C4alkyl-OR10, -C(=O)OR10or -C(=O)R10, and

[0516] R10is H or CrC4alkyl.

[0517] In an embodiment of compounds of Formula (l-c), Formula (l-d), Formula (l-e) or Formula (I- f), or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof: -X=Y- is -CRx=CRy-, -CRX=N- or -N=CRy-;

[0518] Rxis H, D, halogen or Ci-C4alkyl;

[0519] Ryis H, D, halogen, -CN, Ci-C4alkyl, Ci-C4fluoroalkyl or Ci-C4alkoxy;

[0520] R5is H, halogen, -CN, Ci-C4alkyl, Ci-C4fluoroalkyl or Ci-C4alkoxy; each R1is independently selected from the group consisting of halogen, Ci-C4alkyl, C2- C4alkenyl, C2-C4alkynyl, Ci-C4alkoxy, Ci-C4alkoxycarbonyl, C3-C6cycloalkyl, C C4fluoroalkyl, Ci-C4fluoroalkoxy, pentafluorosulfanyl, Ci-C4hydroxyalkyl, Ci-C4thioalkyl, azido, diCi-C4alkylamino, diCi-C4alkylaminocarbonyl, D, CD3, cyano, formyl, phenyl and a 5- to 6-membered heterocycloalkyl comprising 1 or 2 ring members independently selected from N, NR4, O and S;

[0521] Li is -(CR2R3)P-, -(CR2R3)P-NR4-, -(CR2R3)P-O-, -NR4(CR2R3)q-, -(CR2R3)qNR4-, -O-(CR2R3)P- or - S-(CR2R3)P-;

[0522] R2is H, D, halogen or Ci-C4alkyl;

[0523] R3is H, D, halogen, Ci -C4alkyl, CrC4alkoxy, OH, amino or f-Boc-amino; or R2and R3, together with the C atom to which they are attached, are linked to form C3- C4cycloalkyl which is unsubstituted or is substituted with a single substituent selected from Ci-C4alkyl and oxo; each R4is independently selected from the group consisting of H and Ci-C4alkyl; p is 1 , 2 or 3; q is 0, 1 or 2;

[0524] Z1 is N, Z2 is CRZ, Z3 is N, Z4 is C and Z5 is N; or Z1 is N, Z2 is CRZ, Z3 is N, Z4 is C and Z5 is CRZ; or Z1 is C, Z2 is CRZ, Z3 is N, Z4 is N and Z5 is CRZ; or Z1 is C, Z2is N, Z3is N, Z4is N and Z5is CRZ; or Z1 is N, Z2is CRZ, Z3is CRZ, Z4is C and Z5is N; each Rzis independently selected from the group consisting of H, halogen, Ci-C4alkyl and C C4fluoroalkyl; each R6is independently selected from the group consisting of H, CrC4alkyl, CrC4fluoroalkyl and CrC4hydroxyalkyl; each R7is independently selected from the group consisting of H, CrC4alkyl, CrC4fluoroalkyl and Ci-C4hydroxyalkyl; or R6and R7, together with the C atom to which they are attached, are linked to form C3- Cecycloalkyl, oxetanyl, tetrahydrofuranyl or tetrahydropyranyl; n is 1 , 2 or 3;

[0525] R8is:

[0526] (i) 4-, 5- or 6-membered heterocycloalkyl having 1 , 2 or 3 ring members independently selected from N, NR9, O and S, wherein the heterocycloalkyl is unsubstituted or is substituted with 1 , 2, 3 or 4 substituents each independently selected from -OH, -CN, - N(R10)2, halogen, Ci-C4fluoroalkyl, Ci-C4alkyl, Ci-C4alkoxy, oxo and a 5- or 6- membered monocyclic heteroaryl having 1 , 2, 3 or 4 ring members independently selected from N, NR9, O and S, wherein the monocyclic heteroaryl is unsubstituted;

[0527] (ii) 4-, 5- or 6-membered heterocycloalkyl wherein one ring member is S(=O)2, S(=O) or S(=O)(=NH), and wherein the heterocycloalkyl is unsubstituted or is substituted with 1 , 2, 3 or 4 substituents, each independently selected from -OH, Ci-C4alkyl and oxo;

[0528] (iii) 4-, 5- or 6-membered heterocycloalkyl wherein one ring member is S(=O)2 or S(=O), and 1 , 2 or 3 other ring members are independently selected from N, NR9and O, and wherein the heterocycloalkyl is unsubstituted or is substituted with 1 , 2, 3 or 4 substituents each independently selected from CrC4alkyl and oxo;

[0529] (iv) a partially saturated 5- or 6-membered heterocyclyl having 1 or 2 ring members independently selected from N, NR9, O and S, wherein the partially saturated heterocyclyl is unsubstituted or is substituted with 1 , 2, 3 or 4 substituents independently selected from -OH, Ci-C4alkyl, and oxo; (v) a partially saturated 5- or 6-membered heterocyclyl wherein one ring member is S(=O)2and 1 , 2 or 3 other ring members are independently selected from N, NR9, O and S, wherein the partially saturated heterocyclyl is unsubstituted or is substituted with 1 , 2, 3 or 4 substituents independently selected from -OH, Ci-C4alkyl, and oxo;

[0530] (vi) a 5- or 6- membered monocyclic heteroaryl having 1 , 2, 3 or 4 ring members independently selected from N, NR9, O and S, wherein the monocyclic heteroaryl is unsubstituted or is substituted with 1 , 2, 3 or 4 substituents each independently selected from -OH, Ci-C4alkoxy and Ci-C4alkyl;

[0531] (vii) a 6- or 7-membered fused bicyclic heterocyclyl having 1 or 2 ring members independently selected from N, NR9, O and S, wherein the fused bicyclic heterocyclyl is unsubstituted or is substituted with 1 , 2, 3 or 4 substituents, each independently selected from -OH, -N(R10)2, Ci-C4alkyl-NH2, halogen, Ci-C4alkyl, and oxo;

[0532] (viii) a partially saturated 8-, 9-, 10-, 11 - or 12-membered fused bicyclic heterocyclyl having 1 , 2, 3 or 4 ring members independently selected from N, NR9, O and S, wherein the fused bicyclic heterocyclyl is unsubstituted or is substituted with 1 , 2, 3 or 4 substituents, each independently selected from -OH, -N(R10)2, Ci-C4alkyl-NH2, halogen, Ci-C4alkyl, and oxo;

[0533] (ix) a 6-, 7-, 8-, 9- or 10- membered spiro bicyclic heterocycloakyl having 1 , 2 or 3 ring members independently selected from N, NR9, O and S, wherein the spiro bicyclic heterocycloakyl is unsubstituted or is substituted with 1 , 2, 3 or 4 substituents, each independently selected from -OH, -N(R10)2, Ci-C4alkyl-NH2, halogen, Ci-C4alkyl, and oxo;

[0534] (x) a 6- membered heterocycloalkyl having 1 to 2 ring members independently selected from N, NR9, O and S, wherein the heterocycloalkyl has a Ci-Csalkyl bridge or a - CH2OCH2- bridge;

[0535] (xi) phenyl which is unsubstituted or is substituted with 1 , 2, 3 or 4 substituents, each independently selected from -S(=O)2N(R10)2, -OH, -N(R10)2, Ci-C4alkyl-NH2, halogen and Ci-C4alkyl; or

[0536] (xii) C4-C8cycloalkyl which is unsubstituted or is substituted with 1 , 2, 3 or 4 substituents independently selected from -OH, -N(R10)2, -S(=O)2R10, Ci-C4alkyl-NH2, halogen, Ci- C4alkoxy, Ci-C4alkyl, and oxo;

[0537] R9is H, Ci-C4alkyl, benzyl, Ci-C4alkyl-OR10, -C(=O)OR10or -C(=O)R10, and

[0538] R10is H or Ci-C4alkyl.

[0539] In an embodiment of compounds of Formula (l-c), Formula (l-d), Formula (l-e) or Formula (I- f), or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof: -X=Y- is -CRx=CRy-, -CRX=N- or -N=CRy-;

[0540] Rxis H, D or halogen;

[0541] Ryis H, D, halogen or -CN;

[0542] R5is halogen or -CN; each R1is independently selected from the group consisting of halogen, D, CDs, Ci-C4alkyl, Ci- C4fluoroalkyl, Ci-C4fluorolkoxy, Cs-Cecycloalkyl and pentafluorosulfanyl;

[0543] Li is -(CR2R3)P-, -NR4(CR2R3)q- or -O-(CR2R3)P-;

[0544] R2is H, D or halogen;

[0545] R3is H, D, halogen, OH or Ci-C4alkyl; or R2and R3, together with the C atom to which they are attached, are linked to form C3- C4cycloalkyl which is unsubstituted

[0546] R4is H or Ci-C4alkyl; p is 1 ; q is 0;

[0547] Zi is N, Z2is CRZ, Z3is N, Z4is C and Z5is N; or Zi is N, Z2is CRZ, Z3is N, Z4is C and Z5is CRZ; or Zi is C, Z2is CRZ, Z3is N, Z4is N and Z5is CRZ; or Zi is C, Z2is N, Z3is N, Z4is N and Z5is CRZ; each Rzis H; each R6is independently selected from the group consisting of H, Ci-C4alkyl, Ci-C4fluoroalkyl and Ci-C4hydroxyalkyl; each R7is independently selected from the group consisting of H, Ci-C4alkyl, Ci-C4fluoroalkyl and Ci-C4hydroxyalkyl; or R6and R7, together with the C atom to which they are attached, are linked to form tetrahydropyranyl; n is 1 or 2;

[0548] R8is:

[0549] (i) 4-, 5- or 6-membered heterocycloalkyl having 1 or 2 ring members independently selected from N, NR9, O and S, wherein the heterocycloalkyl is unsubstituted or is substituted with 1 , 2 or 3 substituents each independently selected from -OH, -CN, - N(R10)2, halogen, Ci-C4fluoroalkyl, Ci-C4alkyl, Ci-C4alkoxy, oxo and a 5- or 6- membered monocyclic heteroaryl having 1 or 2 ring members independently selected from N and NR9, wherein the monocyclic heteroaryl is unsubstituted;

[0550] (ii) 5- membered heterocycloalkyl wherein one ring member is S(=O)2, S(=O) or S(=O)(=NH), and wherein the heterocycloalkyl is unsubstituted or is substituted with a substituent selected from -OH and Ci-C4alkyl; (iii) 6-membered heterocycloalkyl wherein one ring member is S(=O)2 or S(=O), and one other ring member is selected from N, NR9and O, and wherein the heterocycloalkyl is unsubstituted or is substituted with a substituent selected from Ci-C4alkyl ;

[0551] (iv) a partially saturated 6-membered heterocyclyl having 1 or 2 ring members independently selected from N, NR9, O and S, wherein the partially saturated heterocyclyl is unsubstituted or is substituted with an oxo;

[0552] (v) a partially saturated 6-membered heterocyclyl wherein one ring member is S(=O)2 and one other ring member is selected from N, NR4, and O, wherein the partially saturated heterocyclyl is unsubstituted or is substituted with an oxo;

[0553] (vi) a 5- or 6- membered monocyclic heteroaryl having 1 , 2, 3 or 4 ring members independently selected from N, NR9and O, wherein the monocyclic heteroaryl is unsubstituted or is substituted with a substituent selected from -OH, Ci-C4alkoxy and Ci-C4alkyl;

[0554] (vii) a 6- membered fused bicyclic heterocyclyl having 1 ring member selected from N and NR9, wherein the fused bicyclic heterocyclyl is unsubstituted or is substituted with an oxo;

[0555] (viii) a partially saturated 10- membered fused bicyclic heterocyclyl having 1 , 2, or 3 ring members independently selected from N, NR9, and O, wherein the fused bicyclic heterocyclyl is unsubstituted or is substituted with an oxo;

[0556] (ix) a 7- membered spiro bicyclic heterocycloakyl having 1 ring member selected from N, NR9, and O, wherein the spiro bicyclic heterocycloakyl is unsubstituted;

[0557] (x) a 6- membered heterocycloalkyl having 1 to 2 ring members independently selected from N, NR9and O, wherein the heterocycloalkyl has a Ci-Csalkyl bridge or a - CH2OCH2- bridge;

[0558] (xi) phenyl which is substituted with -S(=O)2N(R10)2; or

[0559] (xii) C4-C8cycloalkyl which is substituted with 1 , 2 or 3 substituents independently selected from -OH, -N(R10)2, -S(=O)2R10, Ci-C alkyl-NH2, halogen and Ci-C4alkoxy;

[0560] R9is H, Ci-C4alkyl, benzyl, Ci-C4alkyl-OR10, -C(=O)OR10or -C(=O)R10, and

[0561] R10is H or Ci-C4alkyl.

[0562] In an embodiment of compounds of Formula (l-c), Formula (l-d), Formula (l-e) or Formula (I- f), or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof: -X=Y- is -CRx=CRy-, -CRX=N- or -N=CRy-;

[0563] Rxis H or F;

[0564] Ryis H, F or CN;

[0565] R5is F, Cl or CN; each R1is independently selected from the group consisting of F, Cl, Br, methyl, isopropyl, t- butyl, cyclopropyl, -CF3, CHF2, CF2CF3, OCF3, and SF5;

[0566] Li is -(CR2R3)P-, -NR4(CR2R3)q- or -O-(CR2R3)P-;

[0567] R2is H or F;

[0568] R3is H, OH, F or methyl; or R2and R3, together with the C atom to which they are attached, are linked to form cyclopropyl which is unsubstituted;

[0569] R4is H, methyl or ethy; p is 1 ; q is 0;

[0570] Z1 is N, Z2is CRZ, Z3is N, Z4is C and Z5is N; or Z1 is N, Z2is CRZ, Z3is N, Z4is C and Z5is CRZ; or Z1 is C, Z2is CRZ, Z3is N, Z4is N and Z5is CRZ; or Z1 is C, Z2is N, Z3is N, Z4is N and Z5is CRZ; each Rzis H; each R6is independently selected from the group consisting of H, methyl, isopropyl, -CH2OH and CH2CF3; each R7is independently selected from the group consisting of H, methyl, isopropyl, -CH2OH and CH2CF3; or R6and R7, together with the C atom to which they are attached, are linked to form tetrahydropyranyl; n is 1 or 2;

[0571] R8is:

[0572] (i) 4-, 5- or 6-membered heterocycloalkyl having 1 or 2 ring members independently selected from N, NR9, O and S, wherein the heterocycloalkyl is unsubstituted or is substituted with 1 , 2 or 3 substituents each independently selected from -OH, -CN, NH2, F, CF3, methyl, methoxy, oxo and a 5- or 6- membered monocyclic heteroaryl having 1 or 2 ring members independently selected from N and NR9, wherein the monocyclic heteroaryl is unsubstituted;

[0573] (ii) 5- membered heterocycloalkyl wherein one ring member is S(=O)2, S(=O) or S(=O)(=NH), and wherein the heterocycloalkyl is unsubstituted or is substituted with a substituent selected from OH and methyl;

[0574] (iii) 6-membered heterocycloalkyl wherein one ring member is S(=O)2or S(=O), and one other ring member is selected from N, NR9and O, and wherein the heterocycloalkyl is unsubstituted or is substituted with a methyl,

[0575] (iv) a partially saturated 6-membered heterocyclyl having 1 or 2 ring members independently selected from N, NR9, O and S, wherein the partially saturated heterocyclyl is unsubstituted or is substituted with an oxo; (v) a partially saturated 6-membered heterocyclyl wherein one ring member is S(=O)3and one other ring member is selected from N, NR9, and O, wherein the partially saturated heterocyclyl is unsubstituted or is substituted with an oxo;

[0576] (vi) a 5- or 6- membered monocyclic heteroaryl having 1 , 2, 3 or 4 ring members independently selected from N, NR9and O, wherein the monocyclic heteroaryl is unsubstituted or is substituted with a substituent selected from -OH methoxy and methyl;

[0577] (vii) a 6- membered fused bicyclic heterocyclyl having 1 ring member selected from N and NR9, wherein the fused bicyclic heterocyclyl is unsubstituted or is substituted with an oxo;

[0578] (viii) a partially saturated 10- membered fused bicyclic heterocyclyl having 1 , 2, or 3 ring members independently selected from N, NR9, and O, wherein the fused bicyclic heterocyclyl is unsubstituted or is substituted with an oxo;

[0579] (ix) a 7- membered spiro bicyclic heterocycloakyl having 1 ring member selected from N, NR9, and O, wherein the spiro bicyclic heterocycloakyl is unsubstituted;

[0580] (x) a 6- membered heterocycloalkyl having 1 to 2 ring members independently selected from N, NR9and O, wherein the heterocycloalkyl has a Ci-C3alkyl bridge or a - CH2OCH2- bridge;

[0581] (xi) phenyl which is substituted with -S(=O)2NH2; or

[0582] (xii) cyclobutyl, cyclopentyl, or cyclohexyl which is substituted with 1 , 2 or 3 substituents independently selected from -OH, -NH2, -S(=O)2CH3, -CH2NH2, F, and methoxy; and

[0583] R9is H, methyl, benzyl, -C(=O)CH3, -C(=O)O(CH3)3, CH2CH2OH or CH2CH2OCH3.

[0584] In an embodiment of compounds of Formula (l-c), Formula (l-d), Formula (l-e) or Formula (I- f), or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof: -X=Y- is -CRx=CRv- or -CRX=N-;

[0585] R* is H;

[0586] Ry is H, D, halogen or -CN;

[0587] R5is halogen or -CN; each R1is independently selected from the group consisting of halogen, Ci-C4alkyl, C1- C4fluoroalkyl and pentafluorosulfanyl;

[0588] Li is -(CR2R3)P-, -NR4(CR2R3)q- or -O-(CR2R3)P-;

[0589] R2is H;

[0590] R3is H, OH or Ci-C4alkyl;

[0591] R4is H or Ci-C4alkyl;

[0592] P is 1 ; q is 0;

[0593] Zi is N, Z2 is CRZ, Z3 is N, Z4 is C and Z5 is N; or Z1 is N, Z2 is CRZ, Z3 is N, Z4 is C and Z5 is CRZ; or Z1 is C, Z2 is CRZ, Z3 is N, Z4 is N and Z5 is CRZ; or Z1 is C, Z2 is N, Z3 is N, Z is N and Z5 is CRZ; each Rzis H; each R6is independently selected from the group consisting of H, Ci-C4alkyl, and C1- C4hydroxyalkyl; each R7is independently selected from the group consisting of H, Ci-C4alkyl, and C1- C4hydroxyalkyl; n is 1 or 2;

[0594] R8is:

[0595] (i) 4-, 5- or 6-membered heterocycloalkyl having 1 or 2 ring members independently selected from N, NR9, O and S, wherein the heterocycloalkyl is unsubstituted or is substituted with 1 , 2 or 3 substituents each independently selected from -OH, -CN, - N(R10)2, halogen, Ci-C4fluoroalkyl, C C4alkyl, Ci-C4alkoxy, oxo and a 5- or 6- membered monocyclic heteroaryl having 1 or 2 ring members independently selected from N and NR9, wherein the monocyclic heteroaryl is unsubstituted;

[0596] (ii) 5- membered heterocycloalkyl wherein one ring member is S(=O)2, S(=O) or S(=O)(=NH), and wherein the heterocycloalkyl is unsubstituted or is substituted with a substituent selected from -OH and Ci -C4alkyl;

[0597] (iii) 6-membered heterocycloalkyl wherein one ring member is S(=O)2 or S(=O), and one other ring member is selected from N, NR9and O, and wherein the heterocycloalkyl is unsubstituted or is substituted with a substituent selected from Ci-C4alkyl ;

[0598] (iv) a partially saturated 6-membered heterocyclyl having 1 or 2 ring members independently selected from N, NR9, O and S, wherein the partially saturated heterocyclyl is unsubstituted or is substituted with an oxo;

[0599] (v) a partially saturated 6-membered heterocyclyl wherein one ring member is S(=O)2 and one other ring member is selected from N, NR4, and O, wherein the partially saturated heterocyclyl is unsubstituted or is substituted with an oxo;

[0600] (vi) a 5- or 6- membered monocyclic heteroaryl having 1 , 2, 3 or 4 ring members independently selected from N, NR9and O, wherein the monocyclic heteroaryl is unsubstituted or is substituted with a substituent selected from -OH, Ci-C4alkoxy and Ci-C4alkyl;

[0601] (vii) a 6- membered fused bicyclic heterocyclyl having 1 ring member selected from N and NR9, wherein the fused bicyclic heterocyclyl is unsubstituted or is substituted with an oxo; (viii) a partially saturated 10- membered fused bicyclic heterocyclyl having 1 , 2, or 3 ring members independently selected from N, NR9, and O, wherein the fused bicyclic heterocyclyl is unsubstituted or is substituted with an oxo;

[0602] (ix) a 7- membered spiro bicyclic heterocycloakyl having 1 ring member selected from N, NR9, and O, wherein the spiro bicyclic heterocycloakyl is unsubstituted;

[0603] (x) a 6- membered heterocycloalkyl having 1 to 2 ring members independently selected from N, NR9and O, wherein the heterocycloalkyl has a Ci-C3alkyl bridge or a - CH2OCH2- bridge;

[0604] (xi) phenyl which is substituted with -S(=O)2N(R10)2; or

[0605] (xii) C4-C8cycloalkyl which is substituted with 1 , 2 or 3 substituents independently selected from -OH, -N(R10)2, -S(=O)2R10, Ci-C4alkyl-NH2, halogen and Ci-C4alkoxy;

[0606] R9is H, Ci-C4alkyl, benzyl, Ci-C4alkyl-OR10, -C(=O)OR10or -C(=O)R10, and

[0607] R10is H or CrC4alkyl.

[0608] In an embodiment of compounds of Formula (l-c), Formula (l-d), Formula (l-e) or Formula (I- f), or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof:

[0609] -X=Y- is -CRx=CRy- or -CRX=N-;

[0610] Rxis H;

[0611] Rv is H, F or CN;

[0612] R5is F or CN; each R1is independently selected from the group consisting of F, Cl, methyl, -CF3, and SF5;

[0613] Li is -(CR2R3)P-, -NR4(CR2R3)q- or -O-(CR2R3)P-;

[0614] R2is H;

[0615] R3is H, OH or methyl;

[0616] R4is H, methyl or ethy; p is 1 ; q is 0;

[0617] Z1 is N, Z2is CRZ, Z3is N, Z4is C and Z5is N; or Z1 is N, Z2is CRZ, Z3is N, Z4is C and Z5is CRZ; or Z1 is C, Z2is CRZ, Z3is N, Z4is N and Z5is CRZ; or Z1 is C, Z2is N, Z3is N, Z4is N and Z5is CRZ; each Rzis H; each R6is independently selected from the group consisting of H, methyl and -CH2OH; each R7is independently selected from the group consisting of H, methyl and -CH2OH; n is 1 or 2;

[0618] R8is: (i) 4-, 5- or 6-membered heterocycloalkyl having 1 or 2 ring members independently selected from N, NR9, O and S, wherein the heterocycloalkyl is unsubstituted or is substituted with 1 , 2 or 3 substituents each independently selected from -OH, -CN, NH2, F, CF3, methyl, methoxy, oxo and a 5- or 6- membered monocyclic heteroaryl having 1 or 2 ring members independently selected from N and NR9, wherein the monocyclic heteroaryl is unsubstituted;

[0619] (ii) 5- membered heterocycloalkyl wherein one ring member is S(=O)2, S(=O) or S(=O)(=NH), and wherein the heterocycloalkyl is unsubstituted or is substituted with a substituent selected from OH and methyl;

[0620] (iii) 6-membered heterocycloalkyl wherein one ring member is S(=O)2or S(=O), and one other ring member is selected from N, NR9and O, and wherein the heterocycloalkyl is unsubstituted or is substituted with a methyl,

[0621] (iv) a partially saturated 6-membered heterocyclyl having 1 or 2 ring members independently selected from N, NR9, O and S, wherein the partially saturated heterocyclyl is unsubstituted or is substituted with an oxo;

[0622] (v) a partially saturated 6-membered heterocyclyl wherein one ring member is S(=O)2and one other ring member is selected from N, NR9, and O, wherein the partially saturated heterocyclyl is unsubstituted or is substituted with an oxo;

[0623] (vi) a 5- or 6- membered monocyclic heteroaryl having 1 , 2, 3 or 4 ring members independently selected from N, NR9and O, wherein the monocyclic heteroaryl is unsubstituted or is substituted with a substituent selected from -OH methoxy and methyl;

[0624] (vii) a 6- membered fused bicyclic heterocyclyl having 1 ring member selected from N and NR9, wherein the fused bicyclic heterocyclyl is unsubstituted or is substituted with an oxo;

[0625] (viii) a partially saturated 10- membered fused bicyclic heterocyclyl having 1 , 2, or 3 ring members independently selected from N, NR9, and O, wherein the fused bicyclic heterocyclyl is unsubstituted or is substituted with an oxo;

[0626] (ix) a 7- membered spiro bicyclic heterocycloakyl having 1 ring member selected from N, NR9, and O, wherein the spiro bicyclic heterocycloakyl is unsubstituted;

[0627] (x) a 6- membered heterocycloalkyl having 1 to 2 ring members independently selected from N, NR9and O, wherein the heterocycloalkyl has a Ci-Csalkyl bridge or a - CH2OCH2- bridge;

[0628] (xi) phenyl which is substituted with -S(=O)2NH2; or

[0629] (xii) cyclobutyl, cyclopentyl, or cyclohexyl which is substituted with 1 , 2 or 3 substituents independently selected from -OH, -NH2, -S(=O)2CH3, -CH2NH2, F, and methoxy; and R9is H, methyl, benzyl, -C(=O)CH3, -C(=O)O(CH3)3, CH2CH2OH or CH2CH2OCH3.

[0630] In an embodiment of compounds of Formula (l-c), Formula (l-d), Formula (l-e) or Formula (I- f), or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof:

[0631] -X=Y- is -CRX=N-;

[0632] Rxis H;

[0633] R5is halogen; each R1is independently selected from the group consisting of halogen, Ci-C4alkyl and Ci- C4fluoroalkyl

[0634] Li is -(CR2R3)P-;

[0635] R2is H;

[0636] R3is H, or Ci-C4alkyl; p is 1 ;

[0637] Zi is N, Z2is CRZ, Z3is N, Z4 is C and Z5 is N; or Z1 is N, Z2is CRZ, Z3is N, Z4 is C and Z5 is CRZ; or Z1 is C, Z2is CRZ, Z3is N, Z4 is N and Z5 is CRZ; or Z1 is C, Z2is N, Z3is N, Z4is N and Z5is CRZ; each Rzis H; each R6is independently selected from the group consisting of H and Ci-C4alkyl; each R7is independently selected from the group consisting of H and Ci-C4alkyl; n is 1 or 2;

[0638] R8is:

[0639] (i) 4-, 5- or 6-membered heterocycloalkyl having 1 or 2 ring members independently selected from N, NR9, O and S, wherein the heterocycloalkyl is unsubstituted or is substituted with 1 , 2 or 3 substituents each independently selected from -OH, halogen, Ci-C4fluoroalkyl, Ci-C4alkyl, and oxo;

[0640] (ii) 5- membered heterocycloalkyl wherein one ring member is S(=O)2, or S(=O)(=NH), and wherein the heterocycloalkyl is unsubstituted or is substituted with a substituent selected from Ci-C4alkyl;

[0641] (iii) 6-membered heterocycloalkyl wherein one ring member is S(=O)2or S(=O), and one other ring member is selected from N, NR9and O, and wherein the heterocycloalkyl is unsubstituted or is substituted with a substituent selected from Ci-C4alkyl ;

[0642] (iv) a partially saturated 6-membered heterocyclyl having 1 or 2 ring members independently selected from O and S, wherein the partially saturated heterocyclyl is unsubstituted;

[0643] (v) a partially saturated 6-membered heterocyclyl wherein one ring member is S(=O)2and one other ring member is O, wherein the partially saturated heterocyclyl is unsubstituted; (vi) a 5- membered monocyclic heteroaryl having 3 ring members independently selected from N, and O, wherein the monocyclic heteroaryl is unsubstituted;

[0644] (vii) a 6- membered fused bicyclic heterocyclyl having 1 ring member selected from NR9, wherein the fused bicyclic heterocyclyl is unsubstituted;

[0645] (viii) a 7- membered spiro bicyclic heterocycloakyl having 1 ring member selected from N, NR9, and O, wherein the spiro bicyclic heterocycloakyl is unsubstituted;

[0646] (ix) a 6- membered heterocycloalkyl having 1 ring members selected from NR9, wherein the heterocycloalkyl has a Ci-C3alkyl bridge; or

[0647] (x) C4-C8cycloalkyl which is substituted with 1 , 2 or 3 substituents independently selected from -OH, -N(R10)2, Ci-C4alkyl-NH2and halogen;

[0648] R9is H, Ci-C4alkyl, or -C(=O)R10, and

[0649] R10is H or Ci-C4alkyl.

[0650] In an embodiment of compounds of Formula (l-c), Formula (l-d), Formula (l-e) or Formula (I- f), or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof:

[0651] -X=Y- is -CRX=N-;

[0652] Rxis H;

[0653] R5is F; each R1is independently selected from the group consisting of F, Cl, methyl and -CF3;

[0654] Li is -(CR2R3)P-,

[0655] R2is H;

[0656] R3is H or methyl; p is 1 ;

[0657] Zi is N, Z2is CRZ, Z3is N, Z4is C and Z5is N; or Zi is N, Z2is CRZ, Z3is N, Z4is C and Z5is CRZ; or Zi is C, Z2is CRZ, Z3is N, Z4is N and Z5is CRZ; or Zi is C, Z2is N, Z3is N, Z4is N and Z5is CRZ; each Rzis H; each R6is independently selected from the group consisting of H and methyl; each R7is independently selected from the group consisting of H and methyl; n is 1 or 2;

[0658] R8is:

[0659] (i) 4-, 5- or 6-membered heterocycloalkyl having 1 or 2 ring members independently selected from N, NR9, O and S, wherein the heterocycloalkyl is unsubstituted or is substituted with 1 , 2 or 3 substituents each independently selected from -OH, F, CF3, methyl and oxo; (ii) 5- membered heterocycloalkyl wherein one ring member is S(=O)2 or S(=O)(=NH), and wherein the heterocycloalkyl is unsubstituted or is substituted with a methyl;

[0660] (iii) 6-membered heterocycloalkyl wherein one ring member is S(=O)2 or S(=O), and one other ring member is selected from N, NR9and O, and wherein the heterocycloalkyl is unsubstituted or is substituted with a methyl,

[0661] (iv) a partially saturated 6-membered heterocyclyl having 1 or 2 ring members independently selected from O and S, wherein the partially saturated heterocyclyl is unsubstituted;

[0662] (v) a partially saturated 6-membered heterocyclyl wherein one ring member is S(=O)2 and one other ring member is and O, wherein the partially saturated heterocyclyl is unsubstituted;

[0663] (vi) a 5- membered monocyclic heteroaryl having 3 ring members independently selected from N and O, wherein the monocyclic heteroaryl is unsubstituted;

[0664] (vii) a 6- membered fused bicyclic heterocyclyl having 1 ring member selected from NR9, wherein the fused bicyclic heterocyclyl is unsubstituted;

[0665] (viii) a 7- membered spiro bicyclic heterocycloakyl having 1 ring member selected from NR9, and O, wherein the spiro bicyclic heterocycloakyl is unsubstituted;

[0666] (ix) a 6- membered heterocycloalkyl having 1 ring members selected from NR9, wherein the heterocycloalkyl has a Ci-Csalkyl bridge; or

[0667] (x) cyclobutyl, cyclopentyl, or cyclohexyl which is substituted with 1 , 2 or 3 substituents independently selected from -OH, -NH2, -CH2NH2, and F; and

[0668] R9is H, methyl or -C(=O)CH3.

[0669] In an embodiment of compounds of Formula (l-c), Formula (l-d), Formula (l-e) or Formula (I- f), or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof:

[0670] -X=Y- is -CRX=N-;

[0671] R* is H;

[0672] R5is halogen; each R1is independently selected from the group consisting of halogen, Ci-C4alkyl and Ci- C4fluoroalkyl

[0673] Li is -(CR2R3)P-;

[0674] R2is H;

[0675] R3is H, or Ci-C4alkyl;

[0676] P is 1 ;

[0677] Zi is N, Z2is CRZ, Z3is N, Z4is C and Z5is N; or Zi is N, Z2 is CRZ, Z3 is N, Z4is C and Z5 is CRZ; each Rzis H; each R6is independently selected from the group consisting of H and Ci-C4alkyl; each R7is independently selected from the group consisting of H and Ci-C4alkyl; n is 1 or 2;

[0678] R8is:

[0679] (i) 4-, 5- or 6-membered heterocycloalkyl having 1 or 2 ring members independently selected from N, NR9, O and S, wherein the heterocycloalkyl is unsubstituted or is substituted with 1 , 2 or 3 substituents each independently selected from -OH, halogen, Ci-C4fluoroalkyl, Ci-C4alkyl, and oxo;

[0680] (ii) 5- membered heterocycloalkyl wherein one ring member is S(=O)z, or S(=O)(=NH), and wherein the heterocycloalkyl is unsubstituted or is substituted with a substituent selected from Ci-C4alkyl;

[0681] (iii) 6-membered heterocycloalkyl wherein one ring member is S(=O)a or S(=O), and one other ring member is selected from N, NR9and O, and wherein the heterocycloalkyl is unsubstituted or is substituted with a substituent selected from Ci-C4alkyl ;

[0682] (iv) a partially saturated 6-membered heterocyclyl having 1 or 2 ring members independently selected from O and S, wherein the partially saturated heterocyclyl is unsubstituted;

[0683] (v) a partially saturated 6-membered heterocyclyl wherein one ring member is S(=O)2 and one other ring member is O, wherein the partially saturated heterocyclyl is unsubstituted;

[0684] (vi) a 5- membered monocyclic heteroaryl having 3 ring members independently selected from N, and O, wherein the monocyclic heteroaryl is unsubstituted;

[0685] (vii) a 6- membered fused bicyclic heterocyclyl having 1 ring member selected from NR9, wherein the fused bicyclic heterocyclyl is unsubstituted;

[0686] (viii) a 7- membered spiro bicyclic heterocycloakyl having 1 ring member selected from N, NR9, and O, wherein the spiro bicyclic heterocycloakyl is unsubstituted;

[0687] (ix) a 6- membered heterocycloalkyl having 1 ring members selected from NR9, wherein the heterocycloalkyl has a Ci-C3alkyl bridge; or

[0688] (x) C4-C8cycloalkyl which is substituted with 1 , 2 or 3 substituents independently selected from -OH, -N(R10)2, Ci-C4alkyl-NH2 and halogen;

[0689] R9is H, Ci-C4alkyl, or -C(=O)R10, and

[0690] R10is H or CrC4alkyl.

[0691] In an embodiment of compounds of Formula (l-c), Formula (l-d), Formula (l-e) or Formula (I- f), or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof: -X=Y- is -CRX=N-;

[0692] Rxis H;

[0693] R5is F; each R1is independently selected from the group consisting of F, Cl, methyl and -CF3;

[0694] Li is -(CR2R3)P-,

[0695] R2is H;

[0696] R3is H or methyl; p is 1 ;

[0697] Z1 is N, Z2 is CRZ, Z3 is N, Z4 is C and Z5 is N; or Z1 is N, Z2is CRZ, Z3is N, Z4is C and Z5is CRZ; each Rzis H; each R6is independently selected from the group consisting of H and methyl; each R7is independently selected from the group consisting of H and methyl; n is 1 or 2;

[0698] R8is:

[0699] (i) 4-, 5- or 6-membered heterocycloalkyl having 1 or 2 ring members independently selected from N, NR9, O and S, wherein the heterocycloalkyl is unsubstituted or is substituted with 1 , 2 or 3 substituents each independently selected from -OH, F, CF3, methyl and oxo;

[0700] (ii) 5- membered heterocycloalkyl wherein one ring member is S(=O)2or S(=O)(=NH), and wherein the heterocycloalkyl is unsubstituted or is substituted with a methyl;

[0701] (iii) 6-membered heterocycloalkyl wherein one ring member is S(=O)2or S(=O), and one other ring member is selected from N, NR9and O, and wherein the heterocycloalkyl is unsubstituted or is substituted with a methyl,

[0702] (iv) a partially saturated 6-membered heterocyclyl having 1 or 2 ring members independently selected from O and S, wherein the partially saturated heterocyclyl is unsubstituted;

[0703] (v) a partially saturated 6-membered heterocyclyl wherein one ring member is S(=O)2and one other ring member is and O, wherein the partially saturated heterocyclyl is unsubstituted;

[0704] (vi) a 5- membered monocyclic heteroaryl having 3 ring members independently selected from N and O, wherein the monocyclic heteroaryl is unsubstituted;

[0705] (vii) a 6- membered fused bicyclic heterocyclyl having 1 ring member selected from NR9, wherein the fused bicyclic heterocyclyl is unsubstituted;

[0706] (viii) a 7- membered spiro bicyclic heterocycloakyl having 1 ring member selected from NR9, and O, wherein the spiro bicyclic heterocycloakyl is unsubstituted;

[0707] (ix) a 6- membered heterocycloalkyl having 1 ring members selected from NR9, wherein the heterocycloalkyl has a Ci-C3alkyl bridge; or

[0708] (x) cyclobutyl, cyclopentyl, or cyclohexyl which is substituted with 1 , 2 or 3 substituents independently selected from -OH, -NH2, -CH2NH2, and F; and

[0709] R9is H, methyl or -C(=O)CH3.

[0710] In an embodiment of compounds of Formula (l-c), Formula (l-d), Formula (l-e) or Formula (I- f), or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof:

[0711] -X=Y- is -CRX=N-;

[0712] Rxis H;

[0713] R5is halogen; each R1is independently selected from the group consisting of halogen, Ci-C4alkyl and C1-

[0714] C4fluoroalkyl;

[0715] Li is -(CR2R3)P-;

[0716] R2is H;

[0717] R3is H; p is 1 ;

[0718] Z1 is N, Z2is CRZ, Z3is N, Z4is C and Z5is N; each Rzis H;

[0719] R8is pyrrolidinyl which is substituted with 1 or 2 each independently selected from halogen and CrC4fluoroalkyl.

[0720] In an embodiment of compounds of Formula (l-c) and Formula (l-d), or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof:

[0721] -X=Y- is -CRX=N-;

[0722] Rxis H;

[0723] R5is F; each R1is independently selected from the group consisting of F, Cl, methyl, and CF3;

[0724] Li is -(CR2R3)P-;

[0725] R2is H;

[0726] R3is H; p is 1 ;

[0727] Z1 is N, Z2is CRZ, Z3is N, Z4is C and Z5is N; each Rzis H;

[0728] R8is pyrrolidinyl which is substituted with 1 or 2 each independently selected from F and CF3.

[0729] In any one of the aforementioned embodiments the compound of Formula (I) is a compound of Formula (l-c) or Formula (l-d), or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof:

[0730] In any one of the aforementioned embodiments the compound of Formula (I) is a compound of Formula (l-c), or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof:

[0731] In any one of the aforementioned embodiments the compound of Formula (I) is a compound of Formula (l-d), or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof:

[0732] In any one of the aforementioned embodiments the compound of Formula (I) is a compound of Formula (l-e), or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof:

[0733] In any one of the aforementioned embodiments the compound of Formula (I) is a compound of Formula (l-f), or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof:

[0734] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, -X=Y- is -CRx=CRy-, -CRX=N- or -N=CRy-.

[0735] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, -X=Y- is -CRX=N- or -N=CRy-.

[0736] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, -X=Y- is -CRX=N-.

[0737] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, -X=Y- is -N=CRy-.

[0738] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, -X=Y- is -N=CRy-;

[0739] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, Rxis H, D, halogen or Ci-C4alkyl.

[0740] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, Rxis H.

[0741] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, Rxis D.

[0742] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, Rxis halogen. In certain embodiments, Rxis F.

[0743] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, Rxis CX alkyL In certain embodiments, Rxis methyl or ethyl.

[0744] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, Rxis H, D, F or methyl. In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, Rxis H or F.

[0745] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, Rxis H, D or F.

[0746] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, Ryis H, D, halogen, CN, Ci-C4alkyl, Ci-C4fluoroalkyl or Ci-C4alkoxy.

[0747] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, Ryis H, D, halogen or CN.

[0748] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, Ryis H, halogen or CN.

[0749] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, Ryis H, F or CN.

[0750] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, Ryis H.

[0751] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, Ryis D.

[0752] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, Ryis halogen. In certain embodiments, Ryis F.

[0753] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, Ryis Ci-C4alkyl.

[0754] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, Ryis Ci-C4fluoroalkyl.

[0755] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, Ryis Ci-C4alkoxy.

[0756] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, R5is H, halogen, Ci-C4alkyl, Ci-C4fluoroalkyl or Ci- C4alkoxy.

[0757] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, R5is H, halogen or CN.

[0758] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, R5is H, F, Cl or CN.

[0759] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, R5is H.

[0760] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, R5is halogen. In certain embodiments, R5is F or Cl. In other embodiments, R5is F.

[0761] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, R5is Ci-C4alkyl.

[0762] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, R5is Ci-C4fluoroalkyl.

[0763] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, R5is Ci-C4alkoxy.

[0764] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, each R1is independently selected from the group consisting of of halogen, Ci-C4alkyl, C2-C4alkenyl, C2-C4alkynyl, Ci-C4alkoxy, Ci- C4alkoxycarbonyl, C3-C6cycloalkyl, Ci-C4fluoroalkyl, Ci-C4fluoroalkoxy, pentafluorosulfanyl, C C4hydroxyalkyl, Ci -C4thioalkyl, azido, diCi-C4alkylamino, diCi-C4alkylaminocarbonyl, D, CD3, cyano, formyl, phenyl and a 5- to 6-membered heterocycloalkyl comprising 1 or 2 ring members independently selected from N, NR4, O and S.

[0765] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, each R1is independently selected from the group consisting of halogen, D, CD3, Ci-C4alkyl, Cs-Cecycloalkyl, Ci-C4fluoroalkyl, Ci-C4fluoroalkoxy and pentafluorosulfanyl. In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, each R1is independently selected from the group consisting of halogen, Ci-C4alkyl, Cs-Cecycloalkyl, Ci-C4fluoroalkyl, Ci-C4fluoroalkoxy and pentafluorosulfanyl.

[0766] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, each R1is independently selected from the group consisting of halogen, Ci-C4alkyl, Ci-C4fluoroalkyl and pentafluorosulfanyl.

[0767] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, each R1is independently selected from halogen. In certain embodiments, each R1is independently selected from F, Cl or Br. In other embodiments, R1is For Cl. In other embodiments, R1is F. In other embodiments, R1is Cl. In other embodiments, R1is Br.

[0768] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, each R1is independently selected from Ci-C4alkyl. In certain embodiments, each R1is independently selected from methyl, ethyl, isopropyl, and t- butyl. In other embodiments, each R1is independently selected from methyl, isopropyl, and t- butyl. In other embodiments, each R1is methyl.

[0769] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, each R1is independently selected from C3- C6cycloalkyl. In certain embodiments, R1is cyclopropyl.

[0770] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, R1is -CD3.

[0771] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, R1is D.

[0772] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, each R1is independently selected from C1- C4fluoroalkyl. In certain embodiments, each R1is independently selected from -CF3, -CHF2, and -CF2CF3. In certain embodiments, each R1is -CF3.

[0773] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, each R1is independently selected from Ci- C4fluoroalkoxy. In certain embodiments, each R1is independently selected from -OCF3, - OCHF2, and -OCF2CF3. In other embodiments, R1is -OCF3.

[0774] In an embodiment of compounds of Formula (I) or Formula (l-a), or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, R1is pentafluorosulfanyl.

[0775] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, each R1is independently selected from the group consisting of Ci-C4alkyl, C2-C4alkenyl, C2-C4alkynyl, Ci-C4hydroxyalkyl and Ci-C4thioalkyl.

[0776] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, each R1is independently selected from the group consisting of Ci-C4alkoxy and CrC4alkoxycarbonyl.

[0777] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, each R1is independently selected from the group consisting of azido, diCi-C4alkylamino, diCi-C4alkylaminocarbonyl, cyano and formyl.

[0778] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, each R1is independently selected from the group consisting of phenyl and a 5- to 6-membered heterocycloalkyl comprising 1 or 2 ring members independently selected from N, NR4, O and S.

[0779] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, Li is a bond, -(CR2R3)P-, -(CR2R3)P-NR4-, -(CR2R3)P-O- , -NR4(CR2R3)q-, -(CR2R3)qNR4-, -O-(CR2R3)P- or -S-(CR2R3)P-.

[0780] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, Li is a bond, -(CR2R3)P-, -NR4(CR2R3)q- or -O- (CR2R3)P-.

[0781] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, Li is a bond.

[0782] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, Li is -(CR2R3)P-,. In certain embodiments Li is -CH2-, - CH(OH), -CH(CH3)-, -CF2- or . In other embodiments Li is -CH2-. In other embodiments X Li is -CH(CH3)-. In other embodiments Li is -CH(OH)-. In other embodiments Li is . In other embodiments Li is -CF2-.

[0783] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, Li is -NR4-(CR2R3)q- or -(CR2R3)PNR4-.

[0784] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, Li is -NR4-(CR2R3)q-. In certain embodiments, Li is - NR4-. In other embodiments Li is -NH-, -N(CH3)-or -N(CH2CH3)-. In other embodiments Li is - NH-. In other embodiments Li is -N(CH3)-. In other embodiments Li is -N(CH2CH3)-.

[0785] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, Li is -O-(CR2R3)P-. In certain embodiments Li is-O- (CR2R3)-. In certain embodiments Li is -O-CH2-.

[0786] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, Li is -(CR2R3)P-O-. In other embodiments Li is - (CR2R3)-O-. In other embodiments Li is -CH2-O-.

[0787] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, Li is a -(CR2R3)P-NR4-. In other embodiments Li is - (CR2R3)-NR4-. In other embodiments Li is -CH2-NR4-.

[0788] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, Li is -S-(CR2R3)P-. In certain embodiments Li is-S- (CR2R3)-. In certain embodiments Li is -S-CH2-.

[0789] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, R2is H, D, halogen or Ci-C4alkyl.

[0790] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, R2is H, halogen or Ci-C4alkyl.

[0791] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, R2is H. In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, R2is D.

[0792] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, R2is halogen. In certain embodiments R2is F.

[0793] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, R3is H, D, halogen, Ci-C4alkyl Ci-C4alkoxy, OH, amino or t-Boc-amino.

[0794] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, R3is H, halogen, Ci-C4alkyl Ci-C4alkoxy, OH, amino or t-Boc-amino.

[0795] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, R3is H, Ci-C4alkyl or OH.

[0796] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, R3is H.

[0797] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, R3is D.

[0798] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, R3is halogen. In certain embodiments R3is F.

[0799] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, R3is Ci-C4alkyl. In certain embodiments R3is methyl.

[0800] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, R3is Ci-C4alkoxy.

[0801] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, R3is hydroxy.

[0802] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, R3is amino. In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, R3is t-Boc-amino.

[0803] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, R2is Ci-C4alkyl. In certain embodiments R2is methyl.

[0804] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, R2and R3, together with the C atom to which they are attached, are linked to form C3-C4cycloalkyl which is unsubstituted or is substituted with a single substituent selected from CX alkyl and oxo. In other embodiments R2and R3, together with the C atom to which they are attached, are linked to form C3-C4cycloalkyl which is unsubstituted.

[0805] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, each R4is independently selected from the group consisting of H and Ci-C4alkyl.

[0806] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, R4is H.

[0807] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, R4is Ci-C4alkyl. In other embodiments R4is methyl or ethyl. In other embodiments R4is methyl. In other embodiments R4is ethyl.

[0808] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, L2is a bond, -(CR6R7)n- or -(CR6R7)rO-*, where the * indicates the point of attachment to R8.

[0809] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, L2is a bond.

[0810] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, L2is -(CR6R7)r- or -(CR6R7)nO-.

[0811] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, L2is -(CR6R7)r-. In certain embodiments l_2is - (CR6R7)-. In other embodiments l_2is -CH2- or -CH2CH2-. In other embodiments L2is -CH2-. In other embodiments L2is -CH2CH2-. In other embodiments L2is -C(CH3)2-. In other embodiments L2is -CH(CH2OH)-.

[0812] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, L2is -(CR6R7)rO-*, where the * indicates the point of attachment to R8. In certain embodiments L2is -(CR6R7)O-. In other embodiments L2is -CH2O- or -(CR6R7)O-*, where the * indicates the point of attachment to R8. In other embodiments L2is - CH2O-. In other embodiments L2is -CH2CH2O-. In other embodiments L2 is -C(CH3)2O-.

[0813] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, each R6is independently selected from the group consisting of H, Ci-C4alkyl, Ci-C4fluoroalkyl and Ci-C4hydroxyalkyl.

[0814] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, R6is H.

[0815] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, R6is Ci-C4alkyl. In other embodiments, R6is methyl, ethyl or isopropyl. In other embodiments, R6is methyl or isopropyl. In other embodiments, R6is methyl. In other embodiments, R6is isopropyl.

[0816] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, R6is Ci-C4fluoroalkyl. In other embodiments, R6is - CF3or -CH2CF3. In other embodiments, R6is -CH2CF3. In other embodiments, R5is -CF3.

[0817] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, R6is Ci-C4hydroxyalkyl. In certain embodiments R6is -CH2OH.

[0818] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, each R7is independently selected from the group consisting of H, Ci-C4alkyl, Ci-C4fluoroal yl and Ci-C4hydroxyalkyl.

[0819] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, R7is H.

[0820] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, R7is Ci-C4alkyl. In other embodiments, R7is methyl, ethyl or isopropyl. In other embodiments, R7is methyl or isopropyl. In other embodiments, R7is methyl. In other embodiments, R7is isopropyl.

[0821] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, R7is Ci-C4fluoroalkyl. In other embodiments, R7is - CF3 or -CH2CF3. In other embodiments, R7is -CH2CF3. In other embodiments, R7is -CF3.

[0822] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, R7is Ci-C4hydroxyalkyl. In certain embodiments R7is -CH2OH.

[0823] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, R6and R7, together with the C atom to which they are attached, are linked to form Cs-Cecycloalkyl, oxetanyl, tetrahydrofuranyl or tetrahydropyranyl.

[0824] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, R6and R7, together with the C atom to which they are attached, are linked to form tetrahydropyranyl.

[0825] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, R6and R7, together with the C atom to which they are attached, are linked to form Cs-Cecycloalkyl. In certain embodiments R6and R7, together with the C atom to which they are attached, are linked to form cyclopropyl. In certain embodiments R6and R7, together with the C atom to which they are attached, are linked to form cyclobutyl. In certain embodiments R6and R7, together with the C atom to which they are attached, are linked to form cyclopentyl. In certain embodiments R6and R7, together with the C atom to which they are attached, are linked to form cyclohexyl.

[0826] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, R6and R7, together with the C atom to which they are attached, are linked to form oxetanyl.

[0827] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, R6and R7, together with the C atom to which they are attached, are linked to form tetrahydrofuranyl.

[0828] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, R8is (i) 4-, 5- or 6-membered heterocycloalkyl having 1 , 2 or 3 ring members independently selected from N, NR9, O and S, wherein the heterocycloalkyl is unsubstituted or is substituted with 1 , 2, 3 or 4 substituents each independently selected from -OH, -CN, -N(R10)2, halogen, Ci-C4fluoroalkyl, Ci-C4alkyl, Ci- C4alkoxy, oxo and a 5- or 6- membered monocyclic heteroaryl having 1 , 2, 3 or 4 ring members independently selected from N, NR9, O and S, wherein the monocyclic heteroaryl is unsubstituted;

[0829] (ii) 4-, 5- or 6-membered heterocycloalkyl wherein one ring member is S(=O)2, S(=O) or S(=O)(=NH), and wherein the heterocycloalkyl is unsubstituted or is substituted with 1 , 2, 3 or 4 substituents, each independently selected from - OH, Ci-C4alkyl and oxo;

[0830] (iii) 4-, 5- or 6-membered heterocycloalkyl wherein one ring member is S(=O)2 or S(=O), and 1 , 2 or 3 other ring members are independently selected from N, NR9and O, and wherein the heterocycloalkyl is unsubstituted or is substituted with 1 , 2, 3 or 4 substituents each independently selected from C C4alkyl and oxo;

[0831] (iv) a partially saturated 5- or 6-membered heterocyclyl having 1 or 2 ring members independently selected from N, NR9, O and S, wherein the partially saturated heterocyclyl is unsubstituted or is substituted with 1 , 2, 3 or 4 substituents independently selected from -OH, Ci-C4alkyl, and oxo;

[0832] (v) a partially saturated 5- or 6-membered heterocyclyl wherein one ring member is S(=O)2and 1 , 2 or 3 other ring members are independently selected from N, NR9, O and S, wherein the partially saturated heterocyclyl is unsubstituted or is substituted with 1 , 2, 3 or 4 substituents independently selected from -OH, Ci- C4alkyl, and oxo;

[0833] (vi) a 5- or 6- membered monocyclic heteroaryl having 1 , 2, 3 or 4 ring members independently selected from N, NR9, O and S, wherein the monocyclic heteroaryl is unsubstituted or is substituted with 1 , 2, 3 or 4 substituents each independently selected from -OH, Ci-C4alkoxy and Ci-C4alkyl;

[0834] (vii) a 6- or 7-membered fused bicyclic heterocyclyl having 1 or 2 ring members independently selected from N, NR9, O and S, wherein the fused bicyclic heterocyclyl is unsubstituted or is substituted with 1 , 2, 3 or 4 substituents, each independently selected from -OH, -N(R10)2, Ci-C4alkyl-NH2, halogen, Ci- C4alkyl, and oxo;

[0835] (viii) a partially saturated 8-, 9-, 10-, 11 - or 12-membered fused bicyclic heterocyclyl having 1 , 2, 3 or 4 ring members independently selected from N, NR9, O and S, wherein the fused bicyclic heterocyclyl is unsubstituted or is substituted with 1 , 2, 3 or 4 substituents, each independently selected from -OH, -N(R10)2, Cr C4alkyl-NH2, halogen, Ci-C4alkyl, and oxo;

[0836] (ix) a 6-, 7-, 8-, 9- or 10- membered spiro bicyclic heterocycloakyl having 1 , 2 or 3 ring members independently selected from N, NR9, O and S, wherein the spiro bicyclic heterocycloakyl is unsubstituted or is substituted with 1 , 2, 3 or 4 substituents, each independently selected from -OH, -N(R10)2, Ci-C alkyl-NH2, halogen, Ci-C4alkyl, and oxo;

[0837] (x) a 6- membered heterocycloalkyl having 1 to 2 ring members independently selected from N, NR9, O and S, wherein the heterocycloalkyl has a Ci-Csalkyl bridge or a -CH2OCH2- bridge;

[0838] (xi) phenyl which is unsubstituted or is substituted with 1 , 2, 3 or 4 substituents, each independently selected from -S(=O)2N(R10)2, -OH, -N(R10)2, Ci-C4alkyl- NH2, halogen and Ci-C4alkyl; or

[0839] (xii) C4-C8cycloalkyl which is unsubstituted or is substituted with 1 , 2, 3 or 4 substituents independently selected from -OH, -N(R10)2, -S(=O)2R10, 01 - C4alkyl-NH2, halogen, Ci-C4alkoxy, Ci-C4alkyl, and oxo.

[0840] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, R8is 4-, 5- or 6-membered heterocycloalkyl having 1 , 2 or 3 ring members independently selected from N, NR9, O and S, wherein the heterocycloalkyl is unsubstituted or is substituted with 1 , 2, 3 or 4 substituents each independently selected from -OH, -CN, -N(R10)2, halogen, Ci-C4fluoroalkyl, Ci-C4alkyl, Ci-C4alkoxy, oxo and a 5- or 6- membered monocyclic heteroaryl having 1 , 2, 3 or 4 ring members independently selected from N, NR9, O and S, wherein the monocyclic heteroaryl is unsubstituted.

[0841] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, R8is 4-, 5- or 6-membered heterocycloalkyl having 1 or 2 ring members independently selected from N, NR9, O and S, wherein the heterocycloalkyl is unsubstituted or is substituted with 1 , 2 or 3 substituents each independently selected from - OH, -CN, -N(R10)2, halogen, Ci-C4fluoroalkyl, Ci-C4alkyl, Ci-C4alkoxy, oxo and a 5- or 6- membered monocyclic heteroaryl having 1 or 2 ring members independently selected from N and NR9, wherein the monocyclic heteroaryl is unsubstituted.

[0842] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, R8is 4-, 5- or 6-membered heterocycloalkyl having 1 or 2 ring members independently selected from N, NR9, O and S, wherein the heterocycloalkyl is unsubstituted or is substituted with 1 , 2 or 3 substituents each independently selected from - OH, -CN, NH2, F, CF3, methyl, methoxy, oxo and a 5- or 6- membered monocyclic heteroaryl having 1or 2 ring members independently selected from N and NR9, wherein the monocyclic heteroaryl is unsubstituted.

[0843] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, R8is 4-, 5- or 6-membered heterocycloalkyl having 1 or 2 ring members independently selected from N, NR9, O and S, wherein the heterocycloalkyl is unsubstituted or is substituted with 1 , 2 or 3 substituents each independently selected from - OH, halogen, Ci-C4fluoroalkyl, Ci-C4alkyl, and, oxo.

[0844] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, R8is 4-, 5- or 6-membered heterocycloalkyl having 1 or 2 ring members independently selected from N, NR9, O and S, wherein the heterocycloalkyl is unsubstituted or is substituted with 1 , 2 or 3 substituents each independently selected from - OH, - F, CF3, methyl and oxo.

[0845] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically

[0846]

[0847] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof,

[0848] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, R8is 4-, 5- or 6-membered heterocycloalkyl wherein one ring member is S(=O)2, S(=O) or S(=O)(=NH), and wherein the heterocycloalkyl is unsubstituted or is substituted with 1 , 2, 3 or 4 substituents, each independently selected from - OH, Ci-C4alkyl and oxo.

[0849] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, R8is a 5- membered heterocycloalkyl wherein one ring member is S(=O)2, S(=O) or S(=O)(=NH), and wherein the heterocycloalkyl is unsubstituted or is substituted with a substituent selected from -OH and Ci-C4alkyl.

[0850] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, R8is a 5- membered heterocycloalkyl wherein one ring member is S(=O)2, S(=O) or S(=O)(=NH), and wherein the heterocycloalkyl is unsubstituted or is substituted with a substituent selected from OH and methyl.

[0851] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, R8is a 5- membered heterocycloalkyl wherein one ring member is S(=O)2, or S(=O)(=NH), and wherein the heterocycloalkyl is unsubstituted or is substituted with a substituent selected from Ci-C4alkyl.

[0852] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, R8is a 5- membered heterocycloalkyl wherein one ring member is S(=0)2 or S(=O)(=NH), and wherein the heterocycloalkyl is unsubstituted or is substituted with a methyl.

[0853] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, R8

[0854] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, R8 or

[0855] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, R8is 4-, 5- or 6-membered heterocycloalkyl wherein one ring member is S(=0)2 or S(=0), and 1 , 2 or 3 other ring members are independently selected from N, NR9and O, and wherein the heterocycloalkyl is unsubstituted or is substituted with 1 , 2, 3 or 4 substituents each independently selected from Ci-C4alkyl and oxo.

[0856] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, R8is a 6-membered heterocycloalkyl wherein one ring member is S(=0)2 or S(=0), and one other ring member is selected from N, NR9and O, and wherein the heterocycloalkyl is unsubstituted or is substituted with a a substituent selected from Ci-C4alkyl.

[0857] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, R8is a 6-membered heterocycloalkyl wherein one ring member is S(=0)2 or S(=0), and one other ring member is selected from N, NR9and O, and wherein the heterocycloalkyl is unsubstituted or is substituted with a methyl.

[0858] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically

[0859] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, R8is a partially saturated 5- or 6-membered heterocyclyl having 1 or 2 ring members independently selected from N, NR9, O and S, wherein the partially saturated heterocyclyl is unsubstituted or is substituted with 1 , 2, 3 or 4 substituents independently selected from -OH, Ci-C4alkyl, and oxo.

[0860] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, R8is a partially saturated 6-membered heterocyclyl having 1 or 2 ring members independently selected from N, NR9, O and S, wherein the partially saturated heterocyclyl is unsubstituted or is substituted with an oxo.

[0861] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, R8is a partially saturated 6-membered heterocyclyl having 1 or 2 ring members independently selected from O and S, wherein the partially saturated heterocyclyl is unsubstituted.

[0862] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, R8

[0863] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, R8

[0864] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, R8is a partially saturated 5- or 6-membered heterocyclyl wherein one ring member is S(=O)2 and 1 , 2 or 3 other ring members are independently selected from N, NR9, O and S, wherein the partially saturated heterocyclyl is unsubstituted or is substituted with 1 , 2, 3 or 4 substituents independently selected from -OH, Ci-C4alkyl, and oxo.

[0865] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, R8is a partially saturated 6-membered heterocyclyl wherein one ring member is S(=O)z and one other ring member is selected from N, NR9, and O, wherein the partially saturated heterocyclyl is unsubstituted or is substituted with an oxo.

[0866] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, R8is a partially saturated 6-membered heterocyclyl wherein one ring member is S(=O)z and one other ring member is and O, wherein the partially saturated heterocyclyl is unsubstituted.

[0867] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, R8is

[0868] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, R8is a 5- or 6- membered monocyclic heteroaryl having 1 , 2, 3 or 4 ring members independently selected from N, NR9, O and S, wherein the monocyclic heteroaryl is unsubstituted or is substituted with 1 , 2, 3 or 4 substituents each independently selected from -OH, Ci-C4alkoxy and Ci-C4alkyl.

[0869] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, R8is a 5- or 6- membered monocyclic heteroaryl having 1 , 2, 3 or 4 ring members independently selected from N, NR9and O, wherein the monocyclic heteroaryl is unsubstituted or is substituted with a substituent selected from -OH methoxy and methyl.

[0870] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, R8is a 5- membered monocyclic heteroaryl having 3 ring members independently selected from N and O, wherein the monocyclic heteroaryl is unsubstituted.

[0871] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically

[0872] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, R8is

[0873] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, R8is a 6- or 7-membered fused bicyclic heterocyclyl having 1 or 2 ring members independently selected from N, NR9, O and S, wherein the fused bicyclic heterocyclyl is unsubstituted or is substituted with 1 , 2, 3 or 4 substituents, each independently selected from -OH, -N(R10)2, Ci-C4alkyl-NH2, halogen, Ci-C4alkyl, and oxo.

[0874] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, R8is a 6- membered fused bicyclic heterocyclyl having 1 ring member selected from N and NR9, wherein the fused bicyclic heterocyclyl is unsubstituted or is substituted with an oxo.

[0875] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, R8is a 6- membered fused bicyclic heterocyclyl having 1 ring member selected from NR9, wherein the fused bicyclic heterocyclyl is unsubstituted.

[0876] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically

[0877] H H acceptable salt of a stereoisomer thereof, R8

[0878] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, R8is a partially saturated 8-, 9-, 10-, 11 - or 12- membered fused bicyclic heterocyclyl having 1 , 2, 3 or 4 ring members independently selected from N, NR9, O and S, wherein the fused bicyclic heterocyclyl is unsubstituted or is substituted with 1 , 2, 3 or 4 substituents, each independently selected from -OH, -N(R10)2, Ci-C4alkyl-NH2, halogen, Ci-C4alkyl, and oxo.

[0879] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, R8is a partially saturated 10- membered fused bicyclic heterocyclyl having 1 , 2, or 3 ring members independently selected from N, NR9, and O, wherein the fused bicyclic heterocyclyl is unsubstituted or is substituted with an oxo.

[0880] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof,

[0881] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, R8is a 6-, 7-, 8-, 9- or 10- membered spiro bicyclic heterocycloakyl having 1 , 2 or 3 ring members independently selected from N, NR9, O and S, wherein the spiro bicyclic heterocycloakyl is unsubstituted or is substituted with 1 , 2, 3 or 4 substituents, each independently selected from -OH, -N(R10)2, CrC4alkyl-NH2, halogen, Ci- C4alkyl, and oxo.

[0882] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, R8is a 7- membered spiro bicyclic heterocycloakyl having 1 ring member selected from NR9, and O, wherein the spiro bicyclic heterocycloakyl is unsubstituted.

[0883] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, R8

[0884] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, R8

[0885] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, R8is a 6- membered heterocycloalkyl having 1 to 2 ring members independently selected from N, NR9, O and S, wherein the heterocycloalkyl has a Ci-C3alkyl bridge or a -CH2OCH2- bridge

[0886] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, R8is a 6- membered heterocycloalkyl having 1 ring members selected from NR9, wherein the heterocycloalkyl has a Ci-Cgalkyl bridge.

[0887] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, R8

[0888] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, R8is

[0889] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, R8is phenyl which is unsubstituted or is substituted with 1 , 2, 3 or 4 substituents, each independently selected from -S(=O)2N(R10)2, -OH, -N(R10)2, Ci-C4alkyl-NH2, halogen and Ci-C4alkyl.

[0890] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, R8is phenyl which is substituted with -S(=O)2NH2.

[0891] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, R8isHzN

[0892] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, R8is C4-Cscycloalkyl which is unsubstituted or is substituted with 1 , 2, 3 or 4 substituents independently selected from -OH, -N(R10)2, -S(=O)2R10, C1 -C4alkyl-NH2, halogen, Ci-C4alkoxy, Ci-C4alkyl, and oxo.

[0893] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, R8is C4-C8cycloalkyl which is substituted with 1 , 2 or 3 substituents independently selected from -OH, -N(R10)2, -S(=O)2R10, Ci-C4alkyl-NH2, halogen and Ci-C4alkoxy.

[0894] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, R8is cyclobutyl, cyclopentyl, or cyclohexyl which is substituted with 1 , 2 or 3 substituents independently selected from -OH, -NH2, -S(=O)2CH3, - CH2NH2, F, and methoxy.

[0895] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, R8is C4-C8cycloalkyl which is substituted with 1 , 2 or 3 substituents independently selected from -OH, -N(R10)2, Ci-C4alkyl-NH2and halogen.

[0896] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, R8is cyclobutyl, cyclopentyl, or cyclohexyl which is substituted with 1 , 2 or 3 substituents independently selected from -OH, -NH2, -CH2NH2, and F.

[0897] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof,

[0898] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically

[0899] NH2PHO- XFr> acceptable salt of a stereoisomer thereof, R8isH0,H2N F, , ,or

[0900] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, R9is H, Ci-C4alkyl, benzyl, Ci-C4alkyl-OR10, - C(=O)OR10or -C(=O)R10. In certain embodiments, R9is H, methyl, benzyl, -C(=O)CH3, - C(=O)O(CH3)3, CH2CH2OH or CH2CH2OCH3.

[0901] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, R9is H, Ci-C4alkyl or -C(=O)R10. In certain embodiments, R9is H, methyl or -C(=O)CH3.

[0902] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, R9is H.

[0903] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, R9is Ci-C4alkyl. In other embodiments, R9is methyl.

[0904] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, R9is -C(=O)R10. In certain embodiments, R9is - C(=O)CH3.

[0905] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, R9is -C(=O)OR10. In certain embodiments, R9is - C(=O)O(CH3)3. In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, R9is benzyl.

[0906] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, R9is Ci-C4alkyl-OR10. In other embodiments, R9is - CH2OH. In other embodiments, R9is -CH2CH2OH. In other embodiments, R9is -CH2CH2OCH3.

[0907] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, R10is H or Ci-C4alkyl.

[0908] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, R10is H.

[0909] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, R10is Ci-C4alkyl. In other embodiments, R10is methyl, ethyl or t-butyl. In other embodiments, R10is methyl or t-butyl. In other embodiments, R10is methyl. In other embodiments, R10is ethyl. In other embodiments, R10is t-butyl.

[0910] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, n is 1 , 2 or 3. In other embodiments, n is 1 or 2. In other embodiments, n is 1 .

[0911] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, p is 1 , 2 or 3. In other embodiments, p is 1 or 2. In other embodiments, p is 1 .

[0912] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, q is 0, 1 or 2. In other embodiments, q is 0 or 1 . In other embodiments, q is 0.

[0913] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, Z1 is N or C; Z2 is N or CRZ; Z3 is N or CRZ; Z4 is N or C; Z5is N or CRZ; wherein each Rzis independently selected from the group consisting of H, halogen, CrC4alkyl and Ci-C4fluoroalkyl; and provided that at least two, and not more than four, of Z1 , Z2, Z3, Z4and Z5are N.

[0914] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof,

[0915] Zi is N, Z2 is CRZ, Z3 is N, Z4 is C and Z5 is N; or Z1 is N, Z2 is CRZ, Z3 is N, Z4 is C and Z5 is CRZ; or Z1 is C, Z2 is CRZ, Z3 is N, Z is N and Z5 is CRZ; or Z1 is C, Z2 is N, Z3 is N, Z4 is N and Z5 is CRZ; or Z1 is N, Z2 is CRZ, Z3 is CRZ, Z4 is C and Z5 is N; where each Rzis independently selected from the group consisting of H, halogen, C1- C alkyl and Ci-C4fluoroalkyl.

[0916] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof,

[0917] Z1 is N, Z2is CRZ, Z3is N, Z4is C and Z5is N; or Z1 is N, Z2is CRZ, Z3is N, Z4is C and Z5is CRZ; or Z1 is C, Z2is CRZ, Z3is N, Z4is N and Z5is CRZ; or Z1 is C, Z2is N, Z3is N, Z4is N and Z5is CRZ; where each Rz is H.

[0918] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof,

[0919] Z1 is N, Z2is CRZ, Z3is N, Z4is C and Z5is N; or Z1 is N, Z2is CRZ, Z3is N, Z4is C and Z5is CRZ; where each Rz is H.

[0920] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, Z1 is N, Z2is CRZ, Z3is N, Z4is C and Z5is N, where each Rzis independently selected from the group consisting of H, halogen, Ci-C4alkyl and C1- C4fluoroalkyl.

[0921] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, Z1 is N, Z2is CRZ, Z3is N, Z4is C and Z5is CRZ, where each Rzis independently selected from the group consisting of H, halogen, C C4alkyl and Ci-C4fluoroalkyl.

[0922] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, Z1 is C, Z2is CRZ, Z3is N, Z4is N and Z5is CRZ, where each Rzis independently selected from the group consisting of H, halogen, CrC4alkyl and CrC4fluoroalkyl.

[0923] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, Zi is C, Z2is N, Z3is N, Z4is N and Z5is CRZ, where each Rzis independently selected from the group consisting of H, halogen, Ci-C4alkyl and Ci- C4fluoroalkyl.

[0924] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, Zi is N, Z2is CRZ, Z3is CRZ, Z4is C and Z5 is N, where each Rzis independently selected from the group consisting of H, halogen, CrC4alkyl and Ci-C4fluoroalkyl.

[0925] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, each Rzis independently selected from the group consisting of H, halogen, Ci-C4alkyl or Ci-C4fluoroalkyl.

[0926] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, each Rzis independently selected from the group consisting of H or halogen.

[0927] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, each Rzis independently selected from the group consisting of H or F.

[0928] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, Rzis H.

[0929] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, Rzis halogen. In other embodiments, Rzis F.

[0930] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a

[0931] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof,

[0932] RAis:

[0933] (i) phenyl which is unsubstituted or is substituted with 1 , 2, 3 or 4 R1groups;

[0934] (ii) a partially saturated 9-, 10-, 11 - or 12-membered bicyclic carbocyclyl which is unsubstituted or is substituted with 1 to 4 R1groups;

[0935] (iii) a 5- or 6- membered monocyclic heteroaryl having 1 , 2, 3 or 4 ring members independently selected from N, NR4, O and S, wherein the monocyclic heteroaryl is unsubstituted or is substituted with 1 , 2, 3 or 4 R1groups; or

[0936] (iv) a partially saturated 8-, 9-, 10-, 11 - or 12-membered fused bicyclic heterocyclyl having 1 , 2, 3 or 4 ring members independently selected from N, NR4, O and S, wherein the fused bicyclic heterocyclyl is unsubstituted or is substituted with 1 , 2, 3 or 4 R1groups.

[0937] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, RAis phenyl which is unsubstituted or is substituted with 1 , 2, 3 or 4 R1groups.

[0938] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, RAis phenyl which is unsubstituted

[0939] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, RAis phenyl which substituted with 1 or 2 R1groups.

[0940] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, RAis phenyl which substituted with 1 or 2 substituents independently selected from halogen, Ci-C4alkyl, Ci-C4fluoroalkyl, and pentafluorosulfanyl.

[0941] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, RAis phenyl which substituted with 1 or 2 substituents independently selected from F, CF3, CF2CF3and SF5.

[0942] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, RAis a partially saturated 9-, 10-, 11 - or 12- membered bicyclic carbocyclyl which is unsubstituted or is substituted with 1 to 4 R1groups.

[0943] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, RAis a 5- or 6- membered monocyclic heteroaryl having 1 , 2, 3 or 4 ring members independently selected from N, NR4, O and S, wherein the monocyclic heteroaryl is unsubstituted or is substituted with 1 , 2, 3 or 4 R1groups.

[0944] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, RAis a 5- or 6- membered monocyclic heteroaryl having 1 or 2 ring members independently selected from N and NR4, wherein the monocyclic heteroaryl is substituted with 1 or 2 R1groups.

[0945] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, RAis a 5- or 6- membered monocyclic heteroaryl having 1 or 2 ring members independently selected from N and NR4, wherein the monocyclic heteroaryl is substituted with 1 or 2 substituents independently selected from halogen, Ci- C4alkyl and Ci-C4fluoroalkyl.

[0946] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, RAis a 5- or 6- membered monocyclic heteroaryl having 1 or 2 ring members independently selected from N and NR4, wherein the monocyclic heteroaryl is substituted with 1 or 2 substituents independently selected from F, Cl, CF3, and methyl.

[0947] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, RAis pyrazolyl or pyridinyl which are substituted with 1 or 2 R1groups.

[0948] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, RAis pyrazolyl or pyridinyl which are substituted with 1 or 2 substituents independently selected from halogen, Ci-C alkyl and Ci-C4fluoroalkyl.

[0949] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, RAis pyrazolyl or pyridinyl which are substituted with 1 or 2 substituents independently selected from F, Cl, CF3, and methyl.

[0950] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, RAis a partially saturated 8-, 9-, 10-, 11 - or 12- membered fused bicyclic heterocyclyl having 1 , 2, 3 or 4 ring members independently selected from N, NR4, O and S, wherein the fused bicyclic heterocyclyl is unsubstituted or is substituted with 1 , 2, 3 or 4 R1groups.

[0951] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, RAis a partially saturated 8-, 9- or 10-membered fused bicyclic heterocyclyl having 1 , 2 or 3 ring member independently selected from N, NR4and O, wherein the fused bicyclic heterocyclyl is substituted with 1 , 2 or 3 R1groups.

[0952] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, RAis a partially saturated 8-, 9- or 10-membered fused bicyclic heterocyclyl having 1 , 2 or 3 ring member independently selected from N, NR4and O, wherein the fused bicyclic heterocyclyl is substituted with 1 , 2 or 3 substituents independently selected from halogen, C C4alkyl and Ci-C4fluoroalkyl.

[0953] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, RAis chromanyl, 3,4-dihydro-2H-pyrano[2,3- b]pyridinyl, 3,4-dihydro-2H-benzo[b][1 ,4]oxazinyl, 6,7-dihydro-5H-pyrazolo[5,1-b][1 ,3]oxazinyl, 5,6-dihydrocyclopenta[c]pyrazol-1 (4H)-yl), 2,3-dihydrobenzo[b][1 ,4]dioxinyl , 4,5,6,7-tetrahydro- 1 H-indazolyl, 1 H-benzo[d]imidazolyl, or 2,3-dihydrobenzofuranyl, each of which is unsubstituted or substituted with 1 or 2 R1groups.

[0954] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, RAis a partially saturated 10-membered fused bicyclic heterocyclyl having 1 or 2 ring members independently selected from N and O, wherein the fused bicyclic heterocyclyl is substituted with 1 substituent selected from halogen, Ci-C4alkyl and Ci-C4fluoroalkyl.

[0955] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, RAis chromanyl or 3,4-dihydro-2H-pyrano[2,3- b]pyridinyl substituted with CF3.

[0956] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, RAis

[0957] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically

[0958] ( acceptable salt of a stereoisomer thereof, RAis

[0959] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically

[0960] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically

[0961]

[0962] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, RAis

[0963] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof,

[0964] In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically In certain embodiments of compounds of Formula (I), or a subformula thereof, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof,

[0965] In an embodiment of compounds of Formula (I), or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, compounds of Formula (I) are selected from:

[0966]

[0967] In an embodiment of compounds of Formula (I), or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, compounds of Formula (I) are selected from: N-(5-fluoro-6-(4-(2-methyl-1 , 1 -dioxidotetrahydrothiophen-2-yl)-1 H-imidazol-1 -yl)pyridin-3-yl)-7- (trifluoromethyl)chromane-3-carboxamide;

[0968] (R or S)-N-(5-fluoro-6-(4-((R or S)-2-methyl-1 ,1-dioxidotetrahydrothiophen-2-yl)-1 H-imidazol-1 - yl)pyridin-3-yl)-7-(trifluoromethyl)chromane-3-carboxamide;

[0969] (R)-N-(5-fluoro-6-(4-((R or S)-2-methyl-1 ,1 -dioxidotetrahydrothiophen-2-yl)-1 H-imidazol-1 - yl)pyridin-3-yl)-7-(trifluoromethyl)chromane-3-carboxamide;

[0970] (S)-N-(5-fluoro-6-(4-((R or S)-2-methyl-1 ,1 -dioxidotetrahydrothiophen-2-yl)-1 H-imidazol-1 - yl)pyridin-3-yl)-7-(trifluoromethyl)chromane-3-carboxamide;

[0971] N-(6-(3-(4,4-difluoropiperidin-2-yl)-1 H-1 ,2,4-triazol-1-yl)-5-fluoropyridin-3-yl)-2-(5-methyl-3-

[0972] (trif I uoromethy I) - 1 H-pyrazol-1 -yl)acetamide;

[0973] (R or S)-N-(6-(3-(4,4-difluoropiperidin-2-yl)-1 H-1 ,2 ,4-triazol- 1 -yl) -5-f I u oropy ridi n -3-y l)-2-(5- methyl-3-(trifluoromethyl)-1 H-pyrazol-1 -yl)acetamide;

[0974] (R)-N-(6-(3-(4,4-difluoropiperidin-2-yl)-1 H-1 ,2,4-triazol-1-yl)-5-fluoropyridin-3-yl)-2-(5-methyl-3- (trif I uoromethy I) - 1 H-pyrazol-1 -yl)acetamide;

[0975] (S)-N-(6-(3-(4,4-difluoropiperidin-2-yl)-1 H-1 ,2,4-triazol-1 -yl)-5-fluoropyridin-3-yl)-2-(5-methyl-3- (trif I uoromethy I) - 1 H-pyrazol-1 -yl)acetamide;

[0976] N-(5-cyano-6-(1 -(3,3-difluoropiperidin-4-yl)-1 H-pyrazol-4-yl)pyridin-3-yl)-2-(3- (trifluoromethyl)phenoxy)acetamide;

[0977] N-(3-fluoro-4-(1 -(2-oxopyrrolidin-3-yl)-1 H-pyrazol-4-yl)phenyl)-2-(3- (trifluoromethyl)phenyl)acetamide;

[0978] (R or S)-N-(3-fluoro-4-(1 -(2-oxopyrrol idi n-3-y I )- 1 H-pyrazol-4-yl)phenyl)-2-(3- (trifluoromethyl)phenyl)acetamide;

[0979] (R)-N-(3-fluoro-4-(1-(2-oxopyrrolidin-3-yl)-1 H-pyrazol-4-yl)phenyl)-2-(3- (trifluoromethyl)phenyl)acetamide; (S)-N-(3-fluoro-4-(1 -(2-oxopyrrolidin-3-yl)-1 H-pyrazol-4-yl)phenyl)-2-(3- (trifluoromethyl)phenyl)acetamide;

[0980] N-(3-cyano-5-fluoro-4-(1 -(tetrahydro-2H-pyran-4-yl)-1 H-pyrazol-4-yl)phenyl)-2-(3-(pentafluoro- A6-sulfaneyl)phenyl)acetamide;

[0981] N-(3,5-difluoro-4-(1-(piperidin-4-yl)-1 H-pyrazol-4-yl)phenyl)-2-(3-

[0982] (trifluoromethyl)phenyl)acetamide;

[0983] N-(3,5-difluoro-4-(1 -((1 R,2R)-2-hydroxycyclopentyl)-1 H-1 ,2,3-triazol-4-yl)phenyl)-2-(2-fluoro-3-

[0984] (trifluoromethyl)phenyl)acetamide;

[0985] 1-(2-fluoro-3-(trifluoromethyl)phenyl)-3-(5-fluoro-6-(4-(2-methyl-1 J-dioxidotetrahydrothiophen-2- y I )- 1 H-imidazol-1 -y l)pyridi n -3-y I)- 1 -methylurea;

[0986] (R or S)-1 -(2-fluoro-3-(trifluoromethyl)phenyl)-3-(5-fluoro-6-(4-(2-methyl-1 ,1 - dioxidotetrahydrothiophen-2-yl)-1 H-imidazol-1 -yl)py rid i n-3-yl)- 1 -methylurea;

[0987] N-(6-(4-(1 ,1 -dioxidothiomorpholino)-1 H-imidazol-1 -yl)-5-fluoropyridin-3-yl)-2-(5-methyl-3-

[0988] (trif I uoromethy I) - 1 H-pyrazol-1 -yl)acetamide;

[0989] N-(6-(4-(3,6-dihydro-2H-pyran-4-yl)-1 H-imidazol-1 -yl)-5-fluoropyridin-3-yl)-2-(2-fluoro-3-

[0990] (trifluoromethyl)phenyl)acetamide;

[0991] N-(5-fluoro-6-(4-(morpholin-3-yl)-1 H-imidazol-1 -yl)pyridin-3-yl)-2-(5-methyl-3-(trifluoromethyl)-

[0992] 1 H-pyrazol-1 -yl)acetamide;

[0993] N-(6-(4-(4-acetylmorpholin-3-yl)-1 H-imidazol-1 -yl)-5-fluoropyridin-3-yl)-2-(5-methyl-3-

[0994] (trif I uoromethy I) - 1 H-pyrazol-1 -yl)acetamide;

[0995] (R or S)-N-(6-(4-(4-acetylmorpholin-3-yl)-1 H-imidazol-1 -yl)-5-fluoropyridin-3-yl)-2-(5-methyl-3-

[0996] (trif I uoromethy I) - 1 H-pyrazol-1 -yl)acetamide;

[0997] (R)-N-(6-(4-(4-acetylmorpholin-3-yl)-1 H-imidazol-1 -yl)-5-fluoropyridin-3-yl)-2-(5-methyl-3-

[0998] (trif I uoromethy I) - 1 H-pyrazol-1 -yl)acetamide;

[0999] (S)-N-(6-(4-(4-acetylmorpholin-3-yl)-1 H-imidazol-1 -yl)-5-fluoropyridin-3-yl)-2-(5-methyl-3-

[1000] (trifluoromethyl)-l H-pyrazol-1 -yl)acetamide;

[1001] N-(5-fluoro-6-(4-(morpholin-3-yl)-1 H-imidazol-1 -yl)pyridin-3-yl)-2-(6-(trifluoromethyl)pyridin-2- yl)acetamide;

[1002] (R or S)-N-(5-fluoro-6-(4-(morpholin-3-yl)-1 H-imidazol-1 -yl)pyridin-3-yl)-2-(6- (trifluoromethyl)pyridin-2-yl)acetamide;

[1003] (R)-N-(5-fluoro-6-(4-(morpholin-3-yl)-1 H-imidazol-1 -yl)pyridin-3-yl)-2-(6-(trifluoromethyl)pyridin-

[1004] 2-yl)acetamide;

[1005] (S)-N-(5-fluoro-6-(4-(morpholin-3-yl)-1 H-imidazol-1 -yl)pyridin-3-yl)-2-(6-(trifluoromethyl)pyridin-

[1006] 2-yl)acetamide;

[1007] N-(3-cyano-5-fluoro-4-(1 -(isoxazolidin-4-yl)-1 H-pyrazol-4-yl)phenyl)-2-(6-(trifluoromethyl)pyridin-

[1008] 2-yl)acetamide;

[1009] N-(3-cyano-5-fluoro-4-(1 -(2-methylisoxazolidin-4-yl)-1 H-pyrazol-4-yl)phenyl)-2-(6-

[1010] (trifluoromethyl)pyridin-2-yl)acetamide;

[1011] N-(5-fluoro-6-(4-(2-(3-hydroxypyrrolidin-1 -yl)propan-2-yl)-1 H-imidazol-1 -yl)pyridin-3-yl)-2-(5- methyl-3-(trifluoromethyl)-1 H-pyrazol-1 -yl)acetamide;

[1012] N-(5-fluoro-6-(4-(2-(2-oxopyrrolidin-1-yl)propan-2-yl)-1 H-imidazol-1 -yl)pyridin-3-yl)-2-(5-methyl-

[1013] 3-(trifluoromethyl)-1 H-pyrazol-1 -yl)acetamide;

[1014] N-(5-fluoro-6-(4-(2-oxopyrrolidin-1 -yl)-1 H-imidazol-1 -yl)pyridin-3-yl)-2-(5-methyl-3-

[1015] (trif I uoromethy I) - 1 H-pyrazol-1 -yl)acetamide;

[1016] N-(6-(4-(5,6-dihydro-1 ,4-oxathiin-2-yl)-1 H-imidazol-1 -yl)-5-fluoropyridin-3-yl)-2-(5-methyl-3-

[1017] (trifluoromethyl)-l H-pyrazol-1 -yl)acetamide;

[1018] N-(6-(4-(4,4-dioxido-5,6-dihydro-1 ,4-oxathiin-2-yl)-1 H-imidazol-1 -yl)-5-fluoropyridin-3-yl)-2-(5- methyl-3-(trifluoromethyl)-1 H-pyrazol-1 -yl)acetamide;

[1019] N-(6-(4-(4,4-dioxido-1 ,4-oxathian-2-yl)-1 H-imidazol-1 -yl)-5-fluoropyridin-3-yl)-2-(5-methyl-3-

[1020] (trif I uoromethy I) - 1 H-pyrazol-1 -yl)acetamide;

[1021] 2-(2-fluoro-3-(trifluoromethyl)phenyl)-N-(5-fluoro-6-(4-(3-methoxypyridin-2-yl)-1 H-imidazol-1 - yl)pyridin-3-yl)acetamide;

[1022] N-(5-fluoro-6-(4-(4-methyl-3-oxopiperazin-1 -yl)-1 H-imidazol-1 -yl)pyridin-3-yl)-2-(6-

[1023] (trifluoromethyl)pyridin-2-yl)acetamide;

[1024] 2-(2-fluoro-3-(trifluoromethyl)phenyl)-N-(5-fluoro-6-(4-(morpholin-3-yl)-1 H-imidazol-1 -yl)pyridin- 3-yl)acetamide; N-(6-(4-(3-(aminomethyl)-1 -hydroxycyclobutyl)-1 H-imidazol-1 -y l)-5-f I uo ropy rid i n-3-yl) -2- (5- methyl-3-(trifluoromethyl)-1 H-pyrazol-1 -yl)acetamide;

[1025] N-(6-(4-((1 r or 1 s,3r or 3s)-3-(Aminomethyl)-1 -hydroxycyclobutyl)-1 H-imidazol-1 -yl)-5- fluoropyridin-3-yl)-2-(5-methyl-3-(trifluoromethyl)-1 H-pyrazol-1 -yl)acetamide;

[1026] N-(5-fluoro-6-(4-(2-hydroxycyclopentyl)-1 H-imidazol-1 -yl)pyridin-3-yl)-2-(5-methyl-3-

[1027] (trif I uoromethy I) - 1 H-pyrazol-1 -yl)acetamide;

[1028] N-(5-fluoro-6-(4-(((1 R or 1 S),(2R or 2S))-2-hydroxycyclopentyl)-1 H-imidazol-1 -y I) py rid i n-3-y I )-2- (5-methyl-3-(trifluoromethyl)-1 H-pyrazol-1 -yl)acetamide;

[1029] N-(5-fluoro-6-(4-(((1 R),(2R))-2-hydroxycyclopentyl)-1 H-imidazol-1 -yl)pyridin-3-yl)-2-(5-methyl-3- (trif I uoromethy I) - 1 H-pyrazol-1 -yl)acetamide;

[1030] N-(5-fluoro-6-(4-(((1 R),(2S))-2-hydroxycyclopentyl)-1 H-imidazol-1 -yl)pyridin-3-yl)-2-(5-methyl-3- (trifluoromethyl)-l H-pyrazol-1 -yl)acetamide;

[1031] N-(5-fluoro-6-(4-(((1 S),(2R))-2-hydroxycyclopentyl)-1 H-imidazol-1 -yl)pyridin-3-yl)-2-(5-methyl-3- (trif I uoromethy I) - 1 H-pyrazol-1 -yl)acetamide;

[1032] N-(5-fluoro-6-(4-(((1 S),(2S))-2-hydroxycyclopentyl)-1 H-imidazol-1 -yl)pyridin-3-yl)-2-(5-methyl-3- (trif I uoromethy I) - 1 H-pyrazol-1 -yl)acetamide;

[1033] (S)-3-(6-(3-(4,4-difluoropyrrolidin-2-yl)-1 H-1 ,2,4-triazol-1 -yl)-5-fluoropyridin-3-yl)-1 -(2-fluoro-3- (trifluoromethyl)phenyl)-1 -methylurea;

[1034] N-(4-(1 -((1 -benzyl-1 H-imidazol-2-yl)methyl)-1 H-pyrazol-4-yl)-3-cyano-5-fluorophenyl)-2-(2- fluoro-3-(trifluoromethyl)phenyl)acetamide;

[1035] N-(6-(4-(2-(1 ,3,4-oxadiazol-2-yl)propan-2-yl)-1 H-imidazol-1 -yl)-5-fluoropyridin-3-yl)-2-(5-methyl- 3-(trifluoromethyl)-1 H-pyrazol-1 -yl)acetamide;

[1036] N-(4-(1 -((1 H-imidazol-2-yl)methyl)-1 H-pyrazol-4-yl)-3-cyano-5-fluorophenyl)-2-(2-fluoro-3- (trifluoromethyl)phenyl)acetamide;

[1037] N-(3-cyano-5-fluoro-4-(1 -((1 -methyl-1 H-imidazol-2-yl)methyl)-1 H-pyrazol-4-yl)phenyl)-2-(2- fluoro-3-(trifluoromethyl)phenyl)acetamide;

[1038] N-(6-(4-(1 , 1 -Dioxidothiomorpholin-2-yl)-1 H-imidazol-1 -yl)-5-fluoropyridin-3-yl)-2-(5-methyl-3- (trif I uoromethy I) - 1 H-pyrazol-1 -yl)acetamide;

[1039] (R or S)-N-(6-(4-(1 ,1 -Dioxidothiomorpholin-2-yl)-1 H-imidazol-1 -yl)-5-f luoropyridin-3-yl)-2-(5- methyl-3-(trifluoromethyl)-1 H-pyrazol-1 -yl)acetamide;

[1040] (R)-N-(6-(4-(1 ,1 -Dioxidothiomorpholin-2-yl)-1 H-imidazol-1 -yl)-5-fluoropyridin-3-yl)-2-(5-methyl-3- (trifluoromethyl)-l H-pyrazol-1 -yl)acetamide;

[1041] (S)-N-(6-(4-( 1 ,1 -Dioxidothiomorpholin-2-yl)-1 H-imidazol-1 -yl)-5-fluoropyridin-3-yl)-2-(5-methyl-3- (trif I uoromethy I) - 1 H-pyrazol-1 -yl)acetamide;

[1042] N-(6-(3-(4,4-difluoropyrrolidin-2-yl)-1 H-1 ,2,4-triazol-1 -yl)-5-fluoropyridin-3-yl)-2-(5-methyl-3-

[1043] (trif I uoromethy I) - 1 H-pyrazol-1 -yl)acetamide;

[1044] (S)-N-(6-(3-(4,4-difluoropyrrolidin-2-yl)-1 H-1 ,2,4-triazol-1 -yl)-5-fluoropyridin-3-yl)-2-(5-methyl-3- (trif I uoromethy I) - 1 H-pyrazol-1 -yl)acetamide;

[1045] (R)-N-(6-(3-(4,4-difluoropyrrolidin-2-yl)-1 H-1 ,2,4-triazol-1 -yl)-5-fluoropyridin-3-yl)-2-(5-methyl-3- (trifluoromethyl)-l H-pyrazol-1 -yl)acetamide;

[1046] N-(5-fluoro-6-(4-(2-(trifluoromethyl)oxetan-2-yl)-1 H-imidazol-1 -yl)pyridin-3-yl)-2-(5-methyl-3-

[1047] (trif I uoromethy I) - 1 H-pyrazol-1 -yl)acetamide;

[1048] 2-(2-fluoro-3-(trifluoromethyl)phenyl)-N-(5-fluoro-6-(3-(1 -imino-1 -oxidotetrahydro-1 H-1A6- th iophen-2-yl)- 1 H-1 ,2,4-triazol-1 -yl)pyridin-3-yl)acetamide;

[1049] N-(3-cyano-5-fluoro-4-(1 -(2-(5-methyl-4H-1 ,2,4-triazol-3-yl)propan-2-yl)-1 H-pyrazol-4-yl)phenyl)- 2-(6-(trifluoromethyl)pyridin-2-yl)acetamide;

[1050] N-(3-cyano-5-fluoro-4-(1 -(2-(5-methyl-1 ,3,4-oxadiazol-2-yl)propan-2-yl)-1 H-pyrazol-4-yl)phenyl)-

[1051] 2-(6-(trifluoromethyl)pyridin-2-yl)acetamide;

[1052] N-(6-(4-((1 H-tetrazol-5-yl)methyl)-1 H-imidazol-1 -yl)-5-fluoropyridin-3-yl)-2-(2-fluoro-3- (trifluoromethyl)phenyl)acetamide;

[1053] 2-(2-fluoro-3-(trifluoromethyl)phenyl)-N-(5-fluoro-6-(4-((3-oxopiperazin-1 -yl)methyl)-1 H-imidazol-

[1054] 1 -yl)pyridin-3-yl)acetamide; tert-butyl (2R,4R)-2-cyano-4-(4-(3-cyano-5-(2-(3-(trifluoromethyl)phenoxy)acetamido)pyridin-2- yl)-1 H-pyrazol-1 -yl)pyrrolidine- 1 -carboxylate;

[1055] N-(5-fluoro-6-(4-(3-methyl-1 -oxido-1 , 2-th iazi nan-3-yl)- 1 H-imidazol-1 -yl )py ridi n-3-yl)-2-(5-methy I-

[1056] 3-(trifluoromethyl)-1 H-pyrazol-1 -yl)acetamide; (R or S)-N-(5-fluoro-6-(4-(3-methyl-1 -oxido-1 ,2-thiazinan-3-yl)-1 H-imidazol-1 -yl)pyridin-3-yl)-2- (5-methyl-3-(trifluoromethyl)-1 H-pyrazol-1 -yl)acetamide;

[1057] (R)-N-(5-fluoro-6-(4-(3-methyl-1 -oxido-1 ,2-thiazinan-3-yl)-1 H-imidazol-1 -yl) py ridi n-3-yl)-2-(5- methyl-3-(trifluoromethyl)-1 H-pyrazol-1 -yl)acetamide;

[1058] (S)-N-(5-fluoro-6-(4-(3-methyl-1 -oxido-1 ,2-thiazinan-3-yl)-1 H-imidazol-1 -yl)pyridi n-3-yl)-2-(5- methyl-3-(trifluoromethyl)-1 H-pyrazol-1 -yl)acetamide;

[1059] N-(5-fluoro-6-(3-(2-(2-oxopyrrolidin-1-yl)propan-2-yl)-1 H-1 ,2,4-triazol- 1 -yl)pyridin-3-yl)-2-(5- methyl-3-(trifluoromethyl)-1 H-pyrazol-1 -yl acetamide;

[1060] N-(6-(4-(3,6-dihydro-2H-pyran-4-yl)-1 H-imidazol-1 -yl)-5-fluoropyridin-3-yl)-2-(6- (trifluoromethyl)pyridin-2-yl)acetamide;

[1061] 2-(5-chloro-3-(trifluoromethyl)-1 H-pyrazol-1 -yl)-N-(5-fluoro-6-(4-(3-methylmorpholin-3-yl)-1 H- imidazol-1-yl)pyridin-3-yl)acetamide;

[1062] (R or S)-2-(5-chloro-3-(trifluoromethyl)-1 H-pyrazol-1 -yl)-N-(5-fluoro-6-(4-(3-methylmorpholin-3- yl)-1 H-imidazol-1 -yl)pyridin-3-yl)acetamide;

[1063] (R)-2-(5-chloro-3-(trifluoromethyl)-1 H-pyrazol-1 -yl)-N-(5-fluoro-6-(4-(3-methylmorpholin-3-yl)-1 H- imidazol-1-yl)pyridin-3-yl)acetamide;

[1064] (S)-2-(5-chloro-3-(trifluoromethyl)-1 H-pyrazol-1 -yl)-N-(5-fluoro-6-(4-(3-methylmorpholin-3-yl)-1 H- imidazol-1-yl)pyridin-3-yl)acetamide;

[1065] 2-(3-chloro-5-(trifluoromethyl)-1 H-pyrazol-1 -yl)-N-(5-fluoro-6-(4-(3-methylmorpholin-3-yl)-1 H- imidazol-1-yl)pyridin-3-yl)acetamide;

[1066] N-(5-fluoro-6-(4-(3-methylmorpholin-3-yl)-1 H-imidazol-1 -yl)pyridin-3-yl)-2-(6-

[1067] (trifluoromethyl)pyridin-2-yl)acetamide;

[1068] (R or S)-N-(5-fluoro-6-(4-(3-methylmorpholin-3-yl)-1 H-imidazol-1 -yl)pyridin-3-yl)-2-(6- (trifluoromethyl)pyridin-2-yl)acetamide;

[1069] (R)-N-(5-fluoro-6-(4-(3-methylmorpholin-3-yl)-1 H-imidazol-1 -yl)pyridin-3-yl)-2-(6-

[1070] (trifluoromethyl)pyridin-2-yl)acetamide;

[1071] (S)-N-(5-fluoro-6-(4-(3-methylmorpholin-3-yl)-1 H-imidazol-1 -yl)pyridin-3-yl)-2-(6-

[1072] (trifluoromethyl)pyridin-2-yl)acetamide;

[1073] 2-(2-fluoro-3-(trifluoromethyl)phenyl)-N-(5-fluoro-6-(4-(morpholin-2-yl)-1 H-imidazol-1 -yl)pyridin- 3-yl)acetamide;

[1074] (R or S)-2-(2-fluoro-3-(trifluoromethyl)phenyl)-N-(5-fluoro-6-(4-(morpholin-2-yl)-1 H-imidazol-1 - yl)pyridin-3-yl)acetamide;

[1075] (R)-2-(2-fluoro-3-(trifluoromethyl)phenyl)-N-(5-fluoro-6-(4-(morpholin-2-yl)-1 H-imidazol-1 - yl)pyridin-3-yl)acetamide;

[1076] (S)-2-(2-fluoro-3-(trifluoromethyl)phenyl)-N-(5-fluoro-6-(4-(morpholin-2-yl)-1 H-imidazol-1 - yl)pyridin-3-yl)acetamide;

[1077] 2-(2-fluoro-3-(trifluoromethyl)phenyl)-N-(5-fluoro-6-(4-(5-oxomorpholin-2-yl)-1 H-imidazol-1 - yl)pyridin-3-yl)acetamide;

[1078] 2-(2-fluoro-3-(trifluoromethyl)phenyl)-N-(5-fluoro-6-(4-(4-methylmorpholin-3-yl)-1 H-imidazol-1 - yl)pyridin-3-yl)acetamide;

[1079] N-(5-fluoro-6-(4-(pyrrolidin-3-yl)-1 H-imidazol-1 -yl)pyridin-3-yl)-2-(5-methyl-3-(trifluoromethyl)-1 H- pyrazol-1 -yl)acetamide;

[1080] (R or S)-2-(2-fluoro-3-(trifluoromethyl)phenyl)-N-(5-fluoro-6-(4-(morpholin-3-yl)-1 H-imidazol-1 - yl)pyridin-3-yl)acetamide;

[1081] (R)-2-(2-fluoro-3-(trifluoromethyl)phenyl)-N-(5-fluoro-6-(4-(morpholin-3-yl)-1 H-imidazol-1 - yl)pyridin-3-yl)acetamide;

[1082] (S)-2-(2-fluoro-3-(trifluoromethyl)phenyl)-N-(5-fluoro-6-(4-(morpholin-3-yl)-1 H-imidazol-1 - yl)pyridin-3-yl)acetamide;

[1083] N-(5-fluoro-6-(4-(3-methylmorpholin-3-yl)-1 H-imidazol-1 -yl)pyridin-3-yl)-2-(5-methyl-3-

[1084] (trif I uoromethy I) - 1 H-pyrazol-1 -yl)acetamide;

[1085] (R or S)-N-(5-fluoro-6-(4-(3-methylmorpholin-3-yl)-1 H-imidazol-1 -yl)pyridin-3-yl)-2-(5-methyl-3- (trif I uoromethy I) - 1 H-pyrazol-1 -yl)acetamide;

[1086] (R)-N-(5-fluoro-6-(4-(morpholin-3-yl)-1 H-imidazol-1 -yl)pyridin-3-yl)-2-(5-methyl-3-

[1087] (trifluoromethyl)-l H-pyrazol-1 -yljacetamide;

[1088] (S)-N-(5-fluoro-6-(4-(morpholin-3-yl)-1 H-imidazol-1 -yl)pyridin-3-yl)-2-(5-methyl-3-

[1089] (trif I uoromethy I) - 1 H-pyrazol-1 -yl)acetamide; N-(5-fluoro-6-(4-(morpholin-2-yl)-1 H-imidazol-1 -yl)pyridin-3-yl)-2-(5-methyl-3-(trifluoromethyl)- 1 H-pyrazol-1 -yl)acetamide;

[1090] (R or S)-N-(5-fluoro-6-(4-(morpholin-2-yl)-1 H-imidazol-1 -yl)pyridin-3-yl)-2-(5-methyl-3- (trifluoromethyl)-l H-pyrazol-1 -yl)acetamide;

[1091] (R)-N-(5-fluoro-6-(4-(morpholin-2-yl)-1 H-imidazol-1 -yl)pyridin-3-yl)-2-(5-methyl-3-

[1092] (trif I uoromethy I) - 1 H-pyrazol-1 -yljacetamide;

[1093] (S)-N-(5-fluoro-6-(4-(morpholin-2-yl)-1 H-imidazol-1 -yl)pyridin-3-yl)-2-(5-methyl-3-

[1094] (trif I uoromethy I) - 1 H-pyrazol-1 -yl)acetamide;

[1095] N-(5-fluoro-6-(4-(2-methyl-1 ,1 -dioxidotetrahydrothiophen-2-yl)-1 H-imidazol-1 -yl)pyridin-3-yl)-2- (5-methyl-3-(trifluoromethyl)-1 H-pyrazol-1 -yl)propanamide;

[1096] (R or S)-N-(5-fluoro-6-(4-((R or S)-2-methyl-1 ,1-dioxidotetrahydrothiophen-2-yl)-1 H-imidazol-1 - yl)pyridin-3-yl)-2-(5-methyl-3-(trifluoromethyl)-1 H-pyrazol-1 -yl)propanamide;

[1097] (R)-N-(5-fluoro-6-(4-((R)-2-methyl-1 ,1 -dioxidotetrahydrothiophen-2-yl)-1 H-imidazol-1 -yl)pyridin- 3-yl)-2-(5-methyl-3-(trifluoromethyl)-1 H-pyrazol-1 -yl)propanam ide;

[1098] (S)-N-(5-fluoro-6-(4-((R)-2-methyl-1 ,1 -dioxidotetrahydrothiophen-2-yl)-1 H-imidazol-1 -yl)pyridin- 3-yl)-2-(5-methyl-3-(trifluoromethyl)-1 H-pyrazol-1 -yl)propanam ide;

[1099] (R)-N-(5-fluoro-6-(4-((S)-2-methyl-1 ,1 -dioxidotetrahydrothiophen-2-yl)-1 H-imidazol-1 -yl)pyridin- 3-yl)-2-(5-methyl-3-(trifluoromethyl)-1 H-pyrazol-1 -yl)propanam ide;

[1100] (S)-N-(5-fluoro-6-(4-((S)-2-methyl-1 ,1-dioxidotetrahydrothiophen-2-yl)-1 H-imidazol-1 -yl)pyridin- 3-yl)-2-(5-methyl-3-(trifluoromethyl)-1 H-pyrazol-1 -yl)propanam ide;

[1101] N-(6-(4-(4,4-difluoropiperidin-2-yl)-1 H-imidazol-1 -yl)-5-fluoropyridin-3-yl)-2-(5-methyl-3-

[1102] (trifl uoromethy I) - 1 H-pyrazol-1 -yl)acetamide;

[1103] (R or S)-N-(6-(4-(4,4-difluoropiperidin-2-yl)-1 H-imidazol-1 -yl)-5-fluoropyridin-3-yl)-2-(5-methyl-3-

[1104] (trif I uoromethy I) - 1 H-pyrazol-1 -yl)acetamide;

[1105] (R)-N-(6-(4-(4,4-difluoropiperidin-2-yl)-1 H-imidazol-1 -yl)-5-fluoropyridin-3-yl)-2-(5-methyl-3-

[1106] (trifluoromethyl)-l H-pyrazol-1 -yl)acetamide;

[1107] (S)-N-(6-(4-(4,4-difluoropiperidin-2-yl)-1 H-imidazol-1 -yl)-5-fluoropyridin-3-yl)-2-(5-methyl-3-

[1108] (trif I uoromethy I) - 1 H-pyrazol-1 -yl)acetamide;

[1109] N-(6-(4-(1 ,1 -dioxidotetrahydrothiophen-2-yl)-1 H-imidazol-1 -yl)-5-fluoropyridin-3-yl)-2-(5-methyl- 3-(trifluoromethyl)-1 H-pyrazol-1 -yl)acetamide;

[1110] (R or S)-N-(6-(4-(1 ,1 -dioxidotetrahydrothiophen-2-yl)-1 H-imidazol-1 -yl)-5-f luoropyridin-3-yl)-2-(5- methyl-3-(trifluoromethyl)-1 H-pyrazol-1 -yl)acetamide;

[1111] (R)-N-(6-(4-(1 ,1 -dioxidotetrahydrothiophen-2-yl)-1 H-imidazol-1 -yl)-5-f luoropyridin-3-yl)-2-(5- methyl-3-(trifluoromethyl)-1 H-pyrazol-1 -yl)acetamide;

[1112] (S)-N-(6-(4-(1 ,1 -dioxidotetrahydrothiophen-2-yl)-1 H-imidazol-1 -yl)-5-fluoropyridin-3-yl)-2-(5- methyl-3-(trifluoromethyl)-1 H-pyrazol-1 -yl)acetamide;

[1113] N-(5-fluoro-6-(4-morpholino-1 H-imidazol-1 -yl)pyridin-3-yl)-2-(4-methyl-3-(trifluoromethyl)-1 H- pyrazol-1 -yl)acetamide;

[1114] 2-(2-fluoro-3-(trifluoromethyl)phenyl)-N-(5-fluoro-6-(4-(tetrahydrothiophen-3-yl)-1 H-imidazol-1 - yl)pyridin-3-yl)acetamide;

[1115] N-(6-(4-(3,3-dimethylpiperazin-1 -yl)- 1 H-imidazol-1 -yl)-5-fluoropyridin-3-yl)-2-(5-methyl-3-

[1116] (trif I uoromethy I) - 1 H-pyrazol-1 -yl)acetamide;

[1117] 2-(2-fluoro-3-(trifluoromethyl)phenyl)-N-(5-fluoro-6-(4-morpholino-1 H-imidazol-1 -yl)pyridin-3- yl)acetamide;

[1118] 2-(2-fluoro-3-(trifluoromethyl)phenyl)-N-(5-fluoro-6-(4-(4-methylpiperazin-1 -yl)-1 H-imidazol-1 - yl)pyridin-3-yl)acetamide;

[1119] N-(6-(4-(1 ,1 -dioxidotetrahydrothiophen-3-yl)-1 H-imidazol-1 -yl)-5-f luoropyridin-3-yl)-2-(2-fluoro-3- (trifluoromethyl)phenyl)acetamide;

[1120] (R or S)-N-(6-(4-(1 ,1 -dioxidotetrahydrothiophen-3-yl)-1 H-imidazol-1 -yl)-5-f luoropyridin-3-yl)-2-(2- fluoro-3-(trifluoromethyl)phenyl)acetamide;

[1121] (R)-N-(6-(4-(1 ,1 -dioxidotetrahydrothiophen-3-yl)-1 H-imidazol-1 -yl)-5-f luoropyridin-3-yl)-2-(2- fluoro-3-(trifluoromethyl)phenyl)acetamide;

[1122] (S)-N-(6-(4-(1 ,1 -dioxidotetrahydrothiophen-3-yl)-1 H-imidazol-1 -yl)-5-fluoropyridin-3-yl)-2-(2- fluoro-3-(trifluoromethyl)phenyl)acetamide;

[1123] N-(5-fluoro-6-(4-(4-methyl-2-oxopiperazin-1 -yl)- 1 H-imidazol-1 -yl)pyridin-3-yl)-2-(6- (trifluoromethyl)pyridin-2-yl)acetamide; 2-(2-fluoro-3-(trifluoromethyl)phenyl)-N-(5-fluoro-6-(4-(2-oxopiperazin-1 -yl)-1 H-imidazol-1 - yl)pyridin-3-yl)acetamide;

[1124] N-(5-fluoro-6-(4-(1-methyl-5-oxopyrrolidin-2-yl)-1 H-imidazol-1 -yl)pyridin-3-yl)-2-(5-methyl-3- (trifluoromethyl)-l H-pyrazol-1 -yl)acetamide;

[1125] (R or S)-N-(5-fluoro-6-(4-(1-methyl-5-oxopyrrolidin-2-yl)-1 H-imidazol-1 -yl)pyridin-3-yl)-2-(5- methyl-3-(trifluoromethyl)-1 H-pyrazol-1 -yl)acetamide;

[1126] (R)-N-(5-fluoro-6-(4-(1-methyl-5-oxopyrrolidin-2-yl)-1 H-imidazol-1 -yl)pyridin-3-yl)-2-(5-methyl-3-

[1127] (trif I uoromethy I) - 1 H-pyrazol-1 -yl)acetamide;

[1128] (S)-N-(5-fluoro-6-(4-(1 -methyl-5-oxopyrrolidin-2-yl)-1 H-imidazol-1 -yl)pyridin-3-yl)-2-(5-methyl-3-

[1129] (trif I uoromethy I) - 1 H-pyrazol-1 -yl)acetamide;

[1130] N-(5-fluoro-6-(4-(2-oxopyrrolidin-1 -yl)-1 H-imidazol-1 -yl)pyridin-3-yl)-2-(6-(trifluoromethyl)pyridin- 2-yl)acetamide;

[1131] 2-(2-fluoro-3-(trifluoromethyl)phenyl)-N-(5-fluoro-6-(4-(4-hydroxy-2-oxopyrrolidin-1 -yl)-1 H- imidazol-1-yl)pyridin-3-yl)acetamide;

[1132] 2-(2-fluoro-3-(trifluoromethyl)phenyl)-N-(5-fluoro-6-(4-(pyrrolidin-1 -yl)-1 H-imidazol-1 -yl)pyridin-3- yl)acetamide;

[1133] N-(5-fluoro-6-(4-morpholino-1 H-imidazol-1 -yl)pyridin-3-yl)-2-(5-methyl-3-(trifluoromethyl)-1 H- pyrazol-1 -yl)acetamide;

[1134] N-(6-(4-(5,6-dihydro-1 ,4-dioxin-2-yl)-1 H-imidazol-1 -yl)-5-fluoropyridin-3-yl)-2-(2-fluoro-3-

[1135] (trifluoromethyl)phenyl)acetamide;

[1136] N-(6-(4-(1 ,4-dioxan-2-yl)-1 H-imidazol-1 -yl)-5-fluoropyridin-3-yl)-2-(2-f luoro-3-

[1137] (trifluoromethyl)phenyl)acetamide;

[1138] (R or S)-N-(6-(4-(1 ,4-dioxan-2-yl)-1 H-imidazol-1 -yl )-5-f I uo ropy rid i n -3-y l)-2-(2-f I uoro-3- (trifluoromethyl)phenyl)acetamide;

[1139] (R)-N-(6-(4-(1 ,4-dioxan-2-yl)-1 H-imidazol-1 -yl)-5-fluoropyridin-3-yl)-2-(2-f luoro-3-

[1140] (trifluoromethyl)phenyl)acetamide;

[1141] (S)-N-(6-(4-(1 ,4-dioxan-2-yl)-1 H-imidazol-1 -yl)-5-fluoropyridin-3-yl)-2-(2-fluoro-3-

[1142] (trifluoromethyl)phenyl)acetamide;

[1143] N-(6-(4-(4,4-difluoropyrrolidin-2-yl)-1 H-imidazol-1 -yl)-5-fluoropyridin-3-yl)-2-(2-fluoro-3-

[1144] (trifluoromethyl)phenyl)acetamide;

[1145] (R or S)-N-(6-(4-(4,4-dif lu oropy rrol idi n-2-yl) - 1 H-imidazol-1 -yl )-5-f I uoropy ridi n -3-y l)-2-(2-f I uoro-3- (trifluoromethyl)phenyl)acetamide;

[1146] (R)-N-(6-(4-(4,4-difluoropyrrolidin-2-yl)-1 H-imidazol-1 -yl)-5-fluoropyridin-3-yl)-2-(2-fluoro-3-

[1147] (trifluoromethyl)phenyl)acetamide;

[1148] (S)-N-(6-(4-(4,4-difluoropyrrolidin-2-yl)-1 H-imidazol-1 -yl)-5-fluoropyridin-3-yl)-2-(2-fluoro-3-

[1149] (trifluoromethyl)phenyl)acetamide;

[1150] N-(5-cyano-6-(1 -(3,3-dif luoro- 1 -methylpiperidin-4-yl)- 1 H-pyrazol-4-yl)pyridin-3-yl)-2-(3- (trifluoromethyl)phenoxy)acetamide;

[1151] N-(6-(4-(4,4-difluoropiperidin-2-yl)-1 H-imidazol-1 -yl)-5-fluoropyridin-3-yl)-2-(6-

[1152] (trifluoromethyl)pyridin-2-yl)acetamide;

[1153] (R or S)-N-(6-(4-(4,4-difluoropiperidin-2-yl)-1 H-imidazol-1 -yl)-5-fluoropyridin-3-yl)-2-(6-

[1154] (trifluoromethyl)pyridin-2-yl)acetamide;

[1155] (R)-N-(6-(4-(4,4-difluoropiperidin-2-yl)-1 H-imidazol-1 -yl)-5-fluoropyridin-3-yl)-2-(6-

[1156] (trifluoromethyl)pyridin-2-yl)acetamide;

[1157] (S)-N-(6-(4-(4,4-difluoropiperidin-2-yl)-1 H-imidazol-1 -yl)-5-fluoropyridin-3-yl)-2-(6-

[1158] (trifluoromethyl)pyridin-2-yl)acetamide;

[1159] N-(6-(3-(5,5-difluoropiperidin-2-yl)-1 H-1 ,2,4-triazol-1-yl)-5-fluoropyridin-3-yl)-2-(5-methyl-3-

[1160] (trif I uoromethy I) - 1 H-pyrazol-1 -yl)acetamide;

[1161] (R or S)-N-(6-(3-(5,5-dif lu oropi peridi n-2-y I)- 1 H-1 ,2 ,4-triazol- 1 -yl) -5-f I u oropy ridi n -3-y l)-2-(5- methyl-3-(trifluoromethyl)-1 H-pyrazol-1 -yl)acetamide;

[1162] (R)-N-(6-(3-(5,5-difluoropiperidin-2-yl)-1 H-1 ,2,4-triazol-1-yl)-5-fluoropyridin-3-yl)-2-(5-methyl-3-

[1163] (trif I uoromethy I) - 1 H-pyrazol-1 -yl)acetamide;

[1164] (S)-N-(6-(3-(5,5-difluoropiperidin-2-yl)-1 H-1 ,2,4-triazol-1 -yl)-5-fluoropyridin-3-yl)-2-(5-methyl-3- (trifluoromethyl)-l H-pyrazol-1 -yl)acetamide;

[1165] N-(5-fluoro-6-(4-(2-methyl-1 ,1 -dioxidotetrahydrothiophen-2-yl)-1 H-imidazol-1 -yl)pyridin-3-yl)-7- (trifluoromethyl)-3,4-dihydro-2H-pyrano[2,3-b]pyridine-2-carboxamide; N-(5-fluoro-6-(4-(2-methyl-1 ,1 -dioxidotetrahydrothiophen-2-yl)-1 H-imidazol-1 -yl)pyridin-3-yl)-2- (6-(trifluoromethyl)pyridin-2-yl)acetamide;

[1166] (R or S)-N-(5-fluoro-6-(4-(2-methyl-1 ,1 -dioxidotetrahydrothiophen-2-yl)-1 H-imidazol-1 -yl)pyridin- 3-yl)-2-(6-(trifluoromethyl)pyridin-2-yl)acetamide;

[1167] (R)-N-(5-fluoro-6-(4-(2-methyl-1 , 1 -dioxidotetrahydrothiophen-2-yl)-1 H-imidazol-1 -yl)pyridin-3-yl)- 2-(6-(trifluoromethyl)pyridin-2-yl)acetamide;

[1168] (S)-N-(5-fluoro-6-(4-(2-methyl-1 ,1 -dioxidotetrahydrothiophen-2-yl)-1 H-imidazol-1 -yl)pyridin-3-yl)-

[1169] 2-(6-(trifluoromethyl)pyridin-2-yl)acetamide;

[1170] N-(6-(4-(4,4-difluoropiperidin-2-yl)-1 H-imidazol-1 -yl)-5-fluoropyridin-3-yl)-2-(4-methyl-3-

[1171] (trif I uoromethy I) - 1 H-pyrazol-1 -yl)acetamide;

[1172] N-(6-(4-(1 -amino-3,3-difluorocyclobutyl)-1 H-imidazol-1 -yl)-5-fluoropyridin-3-yl)-2-(5-methyl-3- (trifluoromethyl)-l H-pyrazol-1 -yl)acetamide;

[1173] N-(5-fluoro-6-(4-(2-methyltetrahydrothiophen-2-yl)-1 H-imidazol-1 -yl)pyridin-3-yl)-7-

[1174] (trifluoromethyl)-3,4-dihydro-2H-pyrano[2,3-b]pyridine-2-carboxamide;

[1175] N-(6-(3-(5,5-difluoropiperidin-2-yl)- 1 H-1 ,2,4-triazol-1 -yl)-5-fluoropyridin-3-yl)-2-(2-fluoro-3- (trifluoromethyl)phenyl)acetamide;

[1176] (R or S)-N-(6-(3-(5,5-dif lu oropi peridi n-2-y I)- 1 H-1 ,2 ,4-triazol- 1 -yl) -5-f I u oropy ridi n -3-y l)-2-(2-f I u oro-

[1177] 3-(trifluoromethyl)phenyl)acetamide;

[1178] (R)-N-(6-(3-(5,5-difluoropiperidin-2-yl)-1 H-1 ,2,4-triazol-1 -yl)-5-fluoropyridin-3-yl)-2-(2-fluoro-3- (trifluoromethyl)phenyl)acetamide;

[1179] (S)-N-(6-(3-(5,5-difluoropiperidin-2-yl)-1 H-1 ,2,4-triazol-1 -yl)-5-fluoropyridin-3-yl)-2-(2-fluoro-3- (trifluoromethyl)phenyl)acetamide;

[1180] N-(5-fluoro-6-(4-(1 -hydroxycyclohexyl)-1 H-imidazol-1 -y I) pyridi n-3-y I )-2-(6- (trifluoromethyl)pyridin-2-yl)acetamide;

[1181] N-(5-fluoro-6-(4-(1 -hydroxycyclopentyl)-1 H-imidazol-1 -yl)pyridin-3-yl)-2-(5-methyl-3- (trifluoromethyl)-l H-pyrazol-1 -yl)acetamide;

[1182] 2-(2-fluoro-3-(trifluoromethyl)phenyl)-N-(5-fluoro-6-(4-(2-oxopiperidin-1-yl)-1 H-imidazol-1 - yl)pyridin-3-yl)acetamide;

[1183] N-(5-fluoro-6-(4-(3-hydroxy-1-methylpyrrolidin-2-yl)-1 H-imidazol-1 -yl)pyridin-3-yl)-2-(5-methyl-3- (trif I uoromethy I) - 1 H-pyrazol-1 -yl)acetamide;

[1184] N-(6-(3-(5,5-difluoropiperidin-2-yl)-1 H-1 ,2,4-triazol-1 -yl)-5-fluoropyridin-3-yl)-2-(6- (trifluoromethyl)pyridin-2-yl)acetamide;

[1185] (R or S)-N-(6-(3-(5,5-diflu oropi peridi n-2-y I)- 1 H-1 ,2 ,4-triazol- 1 -yl) -5-f I u oropy ridi n -3-y l)-2-(6- (trifluoromethyl)pyridin-2-yl)acetamide;

[1186] ( R)- N-(6-(3-(5 ,5-d if I uoropiperid i n -2-y I)- 1 H-1 ,2 ,4-triazol - 1 -y l)-5-f I uoropy ridi n -3-yl )-2-(6- (trifluoromethyl)pyridin-2-yl)acetamide;

[1187] (S)-N-(6-(3-(5,5-dif luoropiperidin-2-yl)- 1 H-1 ,2,4-triazol-1 -yl)-5-f luoropyridin-3-yl)-2-(6- (trifluoromethyl)pyridin-2-yl)acetamide;

[1188] 2-(2-fluoro-3-(trifluoromethyl)phenyl)-N-(5-fluoro-6-(4-(3-hydroxy-1 ,1 -dioxidotetrahydrothiophen- 3-y I)- 1 H-imidazol-1 -yl)pyridin-3-yl)acetam ide;

[1189] (R or S)-2-(2-fluoro-3-(trifluoromethyl)phenyl)-N-(5-fluoro-6-(4-(3-hydroxy-1 ,1- dioxidotetrahydrothiophen-3-yl)-1 H-imidazol-1 -yl)pyridin-3-yl)acetamide;

[1190] (R)-2-(2-fluoro-3-(trifluoromethyl)phenyl)-N-(5-fluoro-6-(4-(3-hydroxy-1 ,1- dioxidotetrahydrothiophen-3-yl)-1 H-imidazol-1 -yl)pyridin-3-yl)acetamide;

[1191] (S)-2-(2-fluoro-3-(trifluoromethyl)phenyl)-N-(5-fluoro-6-(4-(3-hydroxy-1 ,1 - dioxidotetrahydrothiophen-3-yl)-1 H-imidazol-1 -yl)pyridin-3-yl)acetamide;

[1192] 1-(2-fluoro-3-(trifluoromethyl)phenyl)-3-(5-fluoro-6-(4-(morpholin-3-yl)-1 H-imidazol-1 -yl)pyridin-3- yl)-1 -methylurea;

[1193] (R or S)-1 -(2-fluoro-3-(trifluoromethyl)phenyl)-3-(5-fluoro-6-(4-(morpholin-3-yl)-1 H-imidazol-1 - yl)pyridin-3-yl)-1 -methylurea;

[1194] (R)-1-(2-fluoro-3-(trifluoromethyl)phenyl)-3-(5-fluoro-6-(4-(morpholin-3-yl)-1 H-imidazol-1 - yl)pyridin-3-yl)-1 -methylurea;

[1195] (S)-1 -(2-fluoro-3-(trifluoromethyl)phenyl)-3-(5-fluoro-6-(4-(morpholin-3-yl)-1 H-imidazol-1 - yl)pyridin-3-yl)-1 -methylurea;

[1196] N-(6-(4-(3,9-dioxa-7-azabicyclo[3.3.1]nonan-7-yl)-1 H-imidazol-1 -yl)-5-fluoropyridin-3-yl)-2-(2- fluoro-3-(trifluoromethyl)phenyl)acetamide; N-(5-fluoro-6-(4-(piperidin-2-yl)-1 H-imidazol-1 -yl)pyridin-3-yl)-2-(6-(trifluoromethyl)pyridin-2- yl)acetamide;

[1197] (R or S)-N-(5-fluoro-6-(4-(piperidin-2-yl)-1 H-imidazol-1 -yl)pyridin-3-yl)-2-(6-

[1198] (trifluoromethyl)pyridin-2-yl)acetamide;

[1199] (R)-N-(5-fluoro-6-(4-(piperidin-2-yl)-1 H-imidazol-1 -yl)pyridin-3-yl)-2-(6-(trifluoromethyl)pyridin-2- yl)acetamide;

[1200] (S)-N-(5-fluoro-6-(4-(piperidin-2-yl)-1 H-imidazol-1 -yl)pyridin-3-yl)-2-(6-(trifluoromethyl)pyridin-2- yl)acetamide;

[1201] (2-(4-chloro-3-(trifluoromethyl)-1 H-pyrazol-1 -yl)-N-(5-fluoro-6-(4-(morpholin-3-yl)-1 H-imidazol-1 - yl)pyridin-3-yl)acetamide;

[1202] (R or S)-2-(4-chloro-3-(trifluoromethyl)-1 H-pyrazol-1 -yl)-N-(5-fluoro-6-(4-(morpholin-3-yl)-1 H- imidazol-1-yl)pyridin-3-yl)acetamide;

[1203] (R)-2-(4-chloro-3-(trifluoromethyl)-1 H-pyrazol-1 -yl)-N-(5-fluoro-6-(4-(morpholin-3-yl)-1 H- imidazol-1-yl)pyridin-3-yl)acetamide;

[1204] (S)-2-(4-chloro-3-(trifluoromethyl)-1 H-pyrazol-1 -yl)-N-(5-fluoro-6-(4-(morpholin-3-yl)-1 H- imidazol-1-yl)pyridin-3-yl)acetamide;

[1205] 2-(2-fluoro-3-(trifluoromethyl)phenyl)-N-(5-fluoro-6-(4-(1 ,2,3,6-tetrahydropyridin-4-yl)-1 H- imidazol-1-yl)pyridin-3-yl)acetamide;

[1206] N-(5-fluoro-6-(4-(piperidin-4-yl)-1 H-imidazol-1 -yl)pyridin-3-yl)-2-(6-(trifluoromethyl)pyridin-2- yl)acetamide;

[1207] N-(5-fluoro-6-(4-(4-hydroxytetrahydro-2H-pyran-4-yl)-1 H-imidazol-1 -yl)pyridin-3-yl)-2-(6-

[1208] (trifluoromethyl)pyridin-2-yl)acetamide;

[1209] N-(3-cyano-5-fluoro-4-(1 -(oxazol-2-ylmethyl)-1 H-pyrazol-4-yl)phenyl)-2-(2-fluoro-3-

[1210] (trifluoromethyl)phenyl)acetamide;

[1211] N-(6-(4-(3-aminooxetan-3-yl)-1 H-imidazol-1 -yl)-5-fluoropyridin-3-yl)-2-(2-fluoro-3-

[1212] (trifluoromethyl)phenyl)acetamide;

[1213] N-(5-cyano-6-(1 -(tetrahydro-2H-pyran-2-yl)-1 H-pyrazol-4-yl)pyridin-3-yl)-2-hydroxy-2-(3-

[1214] (trifluoromethyl)phenyl)acetamide;

[1215] N-(3-cyano-4-(1 -(3,3-difluoropiperidin-4-yl)-1 H-pyrazol-4-yl)-5-fluorophenyl)-2-(6-

[1216] (trifluoromethyl)pyridin-2-yl)acetamide;

[1217] N-(3-cyano-4-(1 -(3,3-difluoro-1 -methylpiperidin-4-yl)-1 H-pyrazol-4-yl)-5-fluorophenyl)-2-(6-

[1218] (trifluoromethyl)pyridin-2-yl)acetamide;

[1219] 2-(2-fluoro-3-(trifluoromethyl)phenyl)-N-(5-flLioro-6-(4-(piperidiri-4-yl)-1 H-imidazol-1 -yl)pyridin-3- yl)acetamide;

[1220] 2-(5-chloro-3-(trifluoromethyl)-1 H-pyrazol-1 -yl)-N-(5-fluoro-6-(4-(2-methyl-1 ,1 - dioxidotetrahydrothiophen-2-yl)-1 H-imidazol-1 -yl)pyridin-3-yl)acetamide;

[1221] (R or S)-2-(5-chloro-3-(trifluoromethyl)-1 H-pyrazol-1 -yl)-N-(5-fluoro-6-(4-(2-methyl-1 ,1- dioxidotetrahydrothiophen-2-yl)-1 H-imidazol-1 -yl)pyridin-3-yl)acetamide;

[1222] (R)-2-(5-chloro-3-(trifluoromethyl)-1 H-pyrazol-1 -yl)-N-(5-fluoro-6-(4-(2-methyl-1 ,1 - dioxidotetrahydrothiophen-2-yl)-1 H-imidazol-1 -yl)pyridin-3-yl)acetamide;

[1223] (S)-2-(5-chloro-3-(trifluoromethyl)-1 H-pyrazol-1 -yl)-N-(5-fluoro-6-(4-(2-methyl-1 ,1- dioxidotetrahydrothiophen-2-yl)-1 H-imidazol-1 -yl)pyridin-3-yl)acetamide;

[1224] N-(5-fluoro-6-(4-(2-methyl-1 ,1 -dioxidotetrahydrothiophen-2-yl)-1 H-imidazol-1 -yl)pyridin-3-yl)-2- (5-methyl-3-(trifluoromethyl)-1 H-pyrazol-1 -yl)acetamide;

[1225] (R or S)-N-(5-fluoro-6-(4-(2-methyl-1 ,1 -dioxidotetrahydrothiophen-2-yl)-1 H-imidazol-1 -yl)pyridin- 3-yl)-2-(5-methyl-3-(trifluoromethyl)-1 H-pyrazol-1 -yl)acetamide;

[1226] (R)-N-(5-fluoro-6-(4-(2-methyl-1 ,1 -dioxidotetrahydrothiophen-2-yl)-1 H-imidazol-1 -yl)pyridin-3-yl)- 2-(5-methyl-3-(trifluoromethyl)-1 H-pyrazol-1 -yl)acetamide;

[1227] (S)-N-(5-fluoro-6-(4-(2-methyl-1 ,1 -dioxidotetrahydrothiophen-2-yl)-1 H-imidazol-1 -yl)pyridin-3-yl)-

[1228] 2-(5-methyl-3-(trifluoromethyl)-1 H-pyrazol-1 -yl)acetamide;

[1229] 2-(2-fluoro-3-(trifluoromethyl)phenyl)-N-(5-fluoro-6-(4-(2-methyl-1 ,1-dioxidotetrahydrothiophen-

[1230] 2-y I)- 1 H-imidazol-1 -yl)pyridin-3-yl)acetam ide;

[1231] (R)-2-(2-fluoro-3-(trifluoromethyl)phenyl)-N-(5-fluoro-6-(4-(2-methyl-1 ,1 - dioxidotetrahydrothiophen-2-yl)-1 H-imidazol-1 -yl)pyridin-3-yl)acetamide;

[1232] (S)-2-(2-fluoro-3-(trifluoromethyl)phenyl)-N-(5-fluoro-6-(4-(2-methyl-1 ,1- dioxidotetrahydrothiophen-2-yl)-1 H-imidazol-1 -yl)pyridin-3-yl)acetamide; 2-(2-fluoro-3-(trifluoromethyl)phenyl)-N-(5-fluoro-6-(4-(2-methyl-1 -oxidotetrahydrothiophen-2-yl)-

[1233] 1 H-imidazol-1 -yl)pyridin-3-yl)acetamide;

[1234] N-(5-fluoro-6-(4-(tetrahydrofuran-2-yl)-1 H-imidazol-1 -yl)pyridin-3-yl)-2-(5-methyl-3- (trifluoromethyl)-l H-pyrazol-1 -yl)acetamide;

[1235] (R or S)-N-(5-fluoro-6-(4-(tetrahydrofuran-2-yl)-1 H-imidazol-1 -yl)pyridin-3-yl)-2-(5-methyl-3-

[1236] (trif I uoromethy I) - 1 H-pyrazol-1 -yl)acetamide;

[1237] (R)-N-(5-fluoro-6-(4-(tetrahydrofuran-2-yl)-1 H-imidazol-1 -yl)pyridin-3-yl)-2-(5-methyl-3-

[1238] (trif I uoromethy I) - 1 H-pyrazol-1 -yl)acetamide;

[1239] (S)-N-(5-fluoro-6-(4-(tetrahydrofuran-2-yl)-1 H-imidazol-1 -yl)pyridin-3-yl)-2-(5-methyl-3-

[1240] (trif I uoromethy I) - 1 H-pyrazol-1 -yl)acetamide;

[1241] N-(5-fluoro-6-(4-(2-methyltetrahydrothiophen-2-yl)-1 H-imidazol-1 -yl)pyridin-3-yl)-2-(5-methyl-3- (trifluoromethyl)-l H-pyrazol-1 -yl)acetamide;

[1242] 2-(2-fluoro-3-(trifluoromethyl)phenyl)-N-(5-fluoro-6-(4-(2-methyltetrahydrothiophen-2-yl)-1 H- imidazol-1-yl)pyridin-3-yl)acetamide;

[1243] N-(6-(4-(4,4-difluoro-2-methylpyrrolidin-2-yl)-1 H-imidazol-1 -yl)-5-fluoropyridin-3-yl)-2-(5-methyl- 3-(trifluoromethyl)-1 H-pyrazol-1 -yl)acetamide;

[1244] (R or S)-N-(6-(4-(4,4-difluoro-2-methylpyrrolidin-2-yl)-1 H-imidazol-1 -yl)-5-f luoropyridin-3-yl)-2-(5- methyl-3-(trifluoromethyl)-1 H-pyrazol-1 -yl)acetamide;

[1245] (R)-N-(6-(4-(4,4-difluoro-2-methylpyrrolidin-2-yl)-1 H-imidazol-1 -yl)-5-fluoropyridin-3-yl)-2-(5- methyl-3-(trifluoromethyl)-1 H-pyrazol-1 -yl)acetamide;

[1246] (S)-N-(6-(4-(4,4-difluoro-2-methylpyrrolidin-2-yl)-1 H-imidazol-1 -yl)-5-fluoropyridin-3-yl)-2-(5- methyl-3-(trifluoromethyl)-1 H-pyrazol-1 -yl)acetamide;

[1247] 2-(5-chloro-3-(trifluoromethyl)-1 H-pyrazol-1 -yl)-N-(6-(4-(4,4-difluoro-2-methylpyrrolidin-2-yl)-1 H- imidazol-1-yl)-5-fluoropyridin-3-yl)acetamide;

[1248] N-(6-(4-(4,4-difluoropyrrolidin-2-yl)-1 H-imidazol-1 -yl)-5-fluoropyridin-3-yl)-2-(5-methyl-3- (trifluoromethyl)-l H-pyrazol-1 -yl)acetamide;

[1249] (R or S)-N-(6-(4-(4,4-dif lu oropy rrol idi n-2-yl) - 1 H-imidazol-1 -yl)-5-fluoropyridin-3-yl)-2-(5-methyl-3- (trif I uoromethy I) - 1 H-pyrazol-1 -yl)acetamide;

[1250] (R)-N-(6-(4-(4,4-difluoropyrrolidin-2-yl)-1 H-imidazol-1 -yl)-5-fluoropyridin-3-yl)-2-(5-methyl-3-

[1251] (trif I uoromethy I) - 1 H-pyrazol-1 -yl)acetamide;

[1252] (S)-N-(6-(4-(4,4-difluoropyrrolidin-2-yl)-1 H-imidazol-1 -yl)-5-fluoropyridin-3-yl)-2-(5-methyl-3- (trifluoromethyl)-l H-pyrazol-1 -yl)acetamide;

[1253] N-(5-fluoro-6-(4-(pyrrolidin-2-yl)-1 H-imidazol-1 -yl)pyridin-3-yl)-2-(5-methyl-3-(trifluoromethyl)-1 H- pyrazol-1 -yl)acetamide;

[1254] (R or S)-N-(5-fluoro-6-(4-(pyrrolidin-2-yl)-1 H-imidazol-1 -yl)pyridin-3-yl)-2-(5-methyl-3-

[1255] (trif I uoromethy I) - 1 H-pyrazol-1 -yl)acetamide;

[1256] (R)-N-(5-fluoro-6-(4-(pyrrolidin-2-yl)-1 H-imidazol-1 -yl)pyridin-3-yl)-2-(5-methyl-3-

[1257] (trif I uoromethy I) - 1 H-pyrazol-1 -yl)acetamide;

[1258] (S)-N-(5-fluoro-6-(4-(pyrrolidin-2-yl)-1 H-imidazol-1 -yl)pyridin-3-yl)-2-(5-methyl-3-

[1259] (trifluoromethyl)-l H-pyrazol-1 -yl)acetamide;

[1260] 2-(2-fluoro-3-(trifluoromethyl)phenyl)-N-(5-fluoro-6-(4-(pyrrolidin-2-yl)-1 H-imidazol-1 -yl)pyridin-3- yl)acetamide;

[1261] (R or S)-2-(2-fluoro-3-(trifluoromethyl)phenyl)-N-(5-fluoro-6-(4-(pyrrolidin-2-yl)-1 H-imidazol-1 - yl)pyridin-3-yl)acetamide;

[1262] (R)-2-(2-fluoro-3-(trifluoromethyl)phenyl)-N-(5-fluoro-6-(4-(pyrrolidin-2-yl)-1 H-imidazol-1 - yl)pyridin-3-yl)acetamide;

[1263] (S)-2-(2-fluoro-3-(trifluoromethyl)phenyl)-N-(5-fluoro-6-(4-(pyrrolidin-2-yl)-1 H-imidazol-1 - yl)pyridin-3-yl)acetamide;

[1264] N-(6-(4-(1 -acetyl-2-methylpyrrolidin-2-yl)-1 H-imidazol-1 -yl)-5-fluoropyridin-3-yl)-2-(5-methyl-3-

[1265] (trif I uoromethy I) - 1 H-pyrazol-1 -yl)acetamide;

[1266] 2-(2-fluoro-3-(trifluoromethyl)phenyl)-N-(5-fluoro-6-(3-(2-methyl-1 ,1-dioxidotetrahydrothiophen-

[1267] 2-yl)-1 H-1 ,2,4-triazol-1 -yl)pyridin-3-yl)acetamide;

[1268] (R or S)-2-(2-fluoro-3-(trifluoromethyl)phenyl)-N-(5-fluoro-6-(3-(2-methyl-1 ,1 - dioxidotetrahydrothiophen-2-yl)-1 H-1 ,2,4-triazol- 1 -yl)pyridin-3-yl)acetamide;

[1269] (R)-2-(2-fluoro-3-(trifluoromethyl)phenyl)-N-(5-fluoro-6-(3-(2-methyl-1 ,1 - dioxidotetrahydrothiophen-2-yl)-1 H-1 ,2,4-triazol- 1 -yl)pyridin-3-yl)acetamide; (S)-2-(2-fluoro-3-(trifluoromethyl)phenyl)-N-(5-fluoro-6-(3-(2-methyl-1 ,1- dioxidotetrahydrothiophen-2-yl)-1 H-1 ,2,4-triazol- 1 -yl)pyridin-3-yl)acetamide;

[1270] N-(5-fluoro-6-(3-(morpholin-3-yl)-1 H-1 ,2,4-triazol- 1 -yl)pyridin-3-yl)-2-(5-methyl-3-

[1271] (trifluoromethyl)-l H-pyrazol-1 -yl)acetamide;

[1272] (R or S)-N-(5-fluoro-6-(3-(morpholin-3-yl)-1 H-1 ,2,4-triazol- 1 -yl)pyridin-3-yl)-2-(5-methyl-3-

[1273] (trif I uoromethy I) - 1 H-pyrazol-1 -yl)acetamide;

[1274] (R)-N-(5-fluoro-6-(3-(morpholin-3-yl)-1 H-1 ,2,4-triazol- 1 -yl)pyridin-3-yl)-2-(5-methyl-3-

[1275] (trif I uoromethy I) - 1 H-pyrazol-1 -yljacetamide;

[1276] (S)-N-(5-fluoro-6-(3-(morpholin-3-yl)-1 H-1 ,2,4-triazol- 1 -yl)pyridin-3-yl)-2-(5-methyl-3-

[1277] (trif I uoromethy I) - 1 H-pyrazol-1 -yl)acetamide;

[1278] N-(6-(3-(1 -amino-3,3-difluorocyclobutyl)-1 H-1 ,2,4-triazol-1 -yl)-5-fluoropyridin-3-yl)-2-(5-methyl-3-

[1279] (trifluoromethyl)-l H-pyrazol-1 -yl)acetamide;

[1280] N-(5-fluoro-6-(3-(3-methylmorpholin-3-yl)-1 H-1 ,2,4-triazol-1 -yl)pyridin-3-yl)-2-(5-methyl-3-

[1281] (trif I uoromethy I) - 1 H-pyrazol-1 -yl)acetamide;

[1282] (R or S)-N-(5-fluoro-6-(3-(3-methylmorpholin-3-yl)-1 H-1 ,2,4-triazol-1 -yl)pyridin-3-yl)-2-(5-methyl-

[1283] 3-(trifluoromethyl)-1 H-pyrazol-1 -yl)acetamide;

[1284] (R)-N-(5-fluoro-6-(3-(3-methylmorpholin-3-yl)-1 H-1 ,2,4-triazol-1 -yl)pyridin-3-yl)-2-(5-methyl-3-

[1285] (trifluoromethyl)-l H-pyrazol-1 -yl)acetamide;

[1286] (S)-N-(5-fluoro-6-(3-(3-methylmorpholin-3-yl)-1 H-1 ,2,4-triazol-1 -yl)pyridin-3-yl)-2-(5-methyl-3-

[1287] (trif I uoromethy I) - 1 H-pyrazol-1 -yl)acetamide;

[1288] N-(6-(3-(3,3-difluoropyrrolidin-2-yl)-1 H-1 ,2,4-triazol-1-yl)-5-fluoropyridin-3-yl)-2-(5-methyl-3-

[1289] (trif I uoromethy I) - 1 H-pyrazol-1 -yl)acetamide;

[1290] (R or S)-N-(6-(3-(3,3-difluoropyrrol idin-2-yl)-1 H-1 ,2,4-triazol- 1 -yl)-5-f luoropyridin-3-yl)-2-(5- methyl-3-(trifluoromethyl)-1 H-pyrazol-1 -yl)acetamide;

[1291] (R)-N-(6-(3-(3,3-difluoropyrrolidin-2-yl)-1 H-1 ,2,4-triazol-1 -yl)-5-fluoropyridin-3-yl)-2-(5-methyl-3-

[1292] (trifluoromethyl)-l H-pyrazol-1 -yl)acetamide;

[1293] (S)-N-(6-(3-(3,3-difluoropyrrolidin-2-yl)-1 H-1 ,2,4-triazol-1 -yl)-5-fluoropyridin-3-yl)-2-(5-methyl-3-

[1294] (trif I uoromethy I) - 1 H-pyrazol-1 -yl)acetamide;

[1295] (S)-N-(6-(3-(4,4-difluoro-2-methylpyrrolidin-2-yl)-1 H-1 ,2,4-triazol-1 -yl)-5-fluoropyridin-3-yl)-2-(5- methyl-3-(trifluoromethyl)-1 H-pyrazol-1 -yl)acetamide;

[1296] (S)-N-(6-(3-(4,4-difluoropyrrolidin-2-yl)-1 H-1 ,2,4-triazol-1 -yl)-5-fluoropyridin-3-yl)-2-(6-

[1297] (trifluoromethyl)pyridin-2-yl)acetamide;

[1298] (S)-N-(6-(3-(4,4-difluoropyrrolidin-2-yl)-1 H-1 ,2,4-triazol-1 -yl)-5-fluoropyridin-3-yl)-2-(2-fluoro-3-

[1299] (trifluoromethyl)phenyl)acetamide;

[1300] N-(6-(4-(1 , 1 -dioxidothiomorpholin-3-yl)-1 H-imidazol-1 -yl)-5-fluoropyridin-3-yl)-2-(5-methyl-3-

[1301] (trif I uoromethy I) - 1 H-pyrazol-1 -yl)acetamide;

[1302] (R or S)-N-(6-(4-(1 ,1 -dioxidothiomorpholin-3-yl)-1 H-imidazol-1 -yl)-5-fluoropyridin-3-yl)-2-(5- methyl-3-(trifluoromethyl)-1 H-pyrazol-1 -yl)acetamide;

[1303] (R)-N-(6-(4-(1 ,1 -dioxidothiomorpholin-3-yl)-1 H-imidazol-1 -yl)-5-fluoropyridin-3-yl)-2-(5-methyl-3-

[1304] (trifluoromethyl)-l H-pyrazol-1 -yl)acetamide;

[1305] (S)-N-(6-(4-(1 , 1 -dioxidothiomorpholin-3-yl)-1 H-imidazol-1 -yl)-5-fluoropyridin-3-yl)-2-(5-methyl-3-

[1306] (trif I uoromethy I) - 1 H-pyrazol-1 -yl)acetamide;

[1307] N-(5-fluoro-6-(4-(tetrahydro-2H-pyran-4-yl)-1 H-imidazol-1 -yl)pyridin-3-yl)-2-(5-methyl-3-

[1308] (trif I uoromethy I) - 1 H-pyrazol-1 -yl)acetamide;

[1309] 2-(2-fluoro-3-(trifluoromethyl)phenyl)-N-(5-fluoro-6-(4-(tetrahydro-2H-pyran-4-yl)-1 H-imidazol-1 - yl)pyridin-3-yl)acetamide;

[1310] N-(6-(4-(1 ,1 -dioxidothiomorpholin-3-yl)-1 H-imidazol-1 -yl)-5-fluoropyridin-3-yl)-2-(2-fluoro-3- (trifluoromethyl)phenyl)acetamide;

[1311] (R or S)-N-(6-(4-(1 ,1 -dioxidothiomorpholin-3-yl)-1 H-imidazol-1 -yl)-5-fluoropyridin-3-yl)-2-(2- fluoro-3-(trifluoromethyl)phenyl)acetamide;

[1312] (R)-N-(6-(4-(1 ,1 -dioxidothiomorpholin-3-yl)-1 H-imidazol-1 -yl)-5-fluoropyridin-3-yl)-2-(2-fluoro-3-

[1313] (trifluoromethyl)phenyl)acetamide;

[1314] (S)-N-(6-(4-(1 ,1 -dioxidothiomorpholin-3-yl)-1 H-imidazol-1 -yl)-5-fluoropyridin-3-yl)-2-(2-fluoro-3-

[1315] (trifluoromethyl)phenyl)acetamide;

[1316] N-(6-(4-(1 ,1 -dioxidothiomorpholin-2-yl)-1 H-imidazol-1 -yl)-5-fluoropyridin-3-yl)-2-(2-fluoro-3-

[1317] (trifluoromethyl)phenyl)acetamide; (R or S)-N-(6-(4-(1 ,1 -dioxidothiomorpholin-2-yl)-1 H-imidazol-1 -yl)-5-fluoropyridin-3-yl)-2-(2- fluoro-3-(trifluoromethyl)phenyl)acetamide;

[1318] (R)-N-(6-(4-(1 ,1 -dioxidothiomorpholin-2-yl)-1 H-imidazol-1 -yl)-5-fluoropyridin-3-yl)-2-(2-fluoro-3- (trifluoromethyl)phenyl)acetamide;

[1319] (S)-N-(6-(4-(1 , 1 -dioxidothiomorpholin-2-yl)-1 H-imidazol-1 -yl)-5-fluoropyridin-3-yl)-2-(2-fluoro-3- (trifluoromethyl)phenyl)acetamide;

[1320] N-(6-(4-((1 R,3S,5R)-2-azabicyclo[3.1 ,0]hexan-3-yl)-1 H-imidazol-1 -yl)-5-fluoropyridin-3-yl)-2-(5- methyl-3-(trifluoromethyl)-1 H-pyrazol-1-yl)acetamide;

[1321] N-(6-(4-(5-azaspiro[2.4]heptan-6-yl)-1 H-imidazol-1 -yl)-5-fluoropyridin-3-yl)-2-(5-methyl-3-

[1322] (trif I uoromethy I) - 1 H-pyrazol-1 -yl)acetamide;

[1323] (R or S)-N-(6-(4-(5-azaspiro[2.4]heptan-6-yl)-1 H-imidazol-1 -yl)-5-f luoropyridi n-3-yl)-2-(5-methyl- 3-(trifluoromethyl)-1 H-pyrazol-1 -yl)acetamide;

[1324] (R)-N-(6-(4-(5-azaspiro[2.4]heptan-6-yl)-1 H-imidazol-1 -yl)-5-fluoropyridin-3-yl)-2-(5-methyl-3-

[1325] (trif I uoromethy I) - 1 H-pyrazol-1 -yl)acetamide;

[1326] (S)-N-(6-(4-(5-azaspiro[2.4]heptan-6-yl)-1 H-imidazol-1 -yl)-5-fluoropyridin-3-yl)-2-(5-methyl-3-

[1327] (trif I uoromethy I) - 1 H-pyrazol-1 -yl)acetamide;

[1328] N-(6-(4-((1 S,3R,4R)-2-azabicyclo[2.2.1]heptan-3-yl)-1 H-imidazol-1 -yl)-5-fluoropyridin-3-yl)-2-(5- methyl-3-(trifluoromethyl)-1 H-pyrazol-1 -yl)acetamide;

[1329] N-(6-(4-((1 R,3S,4S)-2-azabicyclo[2.2.1]heptan-3-yl)-1 H-imidazol-1 -yl)-5-fluoropyridin-3-yl)-2-(5- methyl-3-(trifluoromethyl)-1 H-pyrazol-1 -yl)acetamide;

[1330] N-(5-fluoro-6-(4-(4-hydroxytetrahydro-2H-pyran-4-yl)-1 H-imidazol-1 -yl)pyridin-3-yl)-2-(5-methyl- 3-(trifluoromethyl)-1 H-pyrazol-1 -yl)acetamide;

[1331] N-(3-cyano-5-fluoro-4-(1 -(tetrahydro-2H-pyran-4-yl)-1 H-pyrazol-4-yl)phenyl)-2-(3- (perfluoroethyl)phenyl)acetamide;

[1332] N-(3-cyano-5-fluoro-4-(1 -(piperidin-4-yl)-1 H-pyrazol-4-yl)phenyl)-2-(3-(pentafluoro-l6- sulfaneyl)phenoxy)acetamide;

[1333] N-(5-Fluoro-6-(3-(1 -imino-1 -oxidotetrahydro-1 H-1 l6-thiophen-2-yl)-1 H-1 ,2,4-triazol- 1 -yl)pyridin- 3-yl)-2-(5-methyl-3-(trifluoromethyl)-1 H-pyrazol-1 -yl)acetamide;

[1334] N-(6-(4-(1 -acetylpyrrol idi n -2-y I)- 1 H-imidazol-1 -yl)-5-fluoropyridin-3-yl)-2-(5-methyl-3-

[1335] (trif I uoromethy I) - 1 H-pyrazol-1 -yl)acetamide;

[1336] (R or S)-N-(6-(4-(1 -acetylpyrrolidin-2-yl)- 1 H-imidazol-1 -yl)-5-fluoropyridin-3-yl)-2-(5-methyl-3- (trifluoromethyl)-l H-pyrazol-1 -yl)acetamide;

[1337] N-(3-cyano-5-fluoro-4-(1 -((1-methyl-1 H-tetrazol-5-yl)methyl)-1 H-pyrazol-4-yl)phenyl)-2-(6-

[1338] (trifluoromethyl)pyridin-2-yl)acetamide;

[1339] N-(4-(1 -(2-(4H-1 ,2,4-triazol-3-yl)propan-2-yl)-1 H-pyrazol-4-yl)-3-cyano-5-fluorophenyl)-2-(6-

[1340] (trifluoromethyl)pyridin-2-yl)acetamide;

[1341] N-(4-(1 -(2-(1 ,3,4-oxadiazol-2-yl)propan-2-yl)-1 H-pyrazol-4-yl)-3-cyano-5-fluorophenyl)-2-(6- (trifluoromethyl)pyridin-2-yl)acetamide;

[1342] N-(3-cyano-5-fluoro-4-(1 -(tetrahydro-2H-pyran-4-yl)-1 H-pyrazol-4-yl)phenyl)-2-hydroxy-2-(3-

[1343] (trifluoromethyl)phenyl)acetamide;

[1344] N-(3-cyano-5-fluoro-4-(1 -(tetrahydro-2H-pyran-3-yl)-1 H-pyrazol-4-yl)phenyl)-2-hydroxy-2-(3-

[1345] (trifluoromethyl)phenyl)acetamide;

[1346] N-(3-cyano-5-fluoro-4-(1 -(piperidin-3-yl)-1 H-pyrazol-4-yl)phenyl)-2-(3-(pentafluoro-l6- sulfaneyl)phenoxy)acetamide;

[1347] 2-(2-fluoro-3-(trifluoromethyl)phenyl)-N-(5-fluoro-6-(4-(1 ,2,5,6-tetrahydropyridin-3-yl)-1 H- imidazol-1-yl)pyridin-3-yl)acetamide;

[1348] 2-(2-fluoro-3-(trifluoromethyl)phenyl)-N-(5-fluoro-6-(4-(piperidin-3-yl)-1 H-imidazol-1 -yl)pyridin-3- yl)acetamide;

[1349] N-(6-(4-(1 -acetylpiperidin-3-yl)- 1 H-imidazol-1 -yl)-5-fluoropyridin-3-yl)-2-(2-fl uoro-3- (trifluoromethyl)phenyl)acetamide;

[1350] (R or S)-N-(6-(4-(1 -acetylpiperidin-3-yl)-1 H-imidazol-1 -yl)-5-f luoropyridin-3-yl)-2-(2-fluoro-3- (trifluoromethyl)phenyl)acetamide;

[1351] 2-(2-fluoro-3-(trifluoromethyl)phenyl)-N-(5-fluoro-6-(4-(piperidin-2-yl)-1 H-imidazol-1 -yl)pyridin-3- yl)acetamide;

[1352] (R or S)-2-(2-fluoro-3-(trifluoromethyl)phenyl)-N-(5-fluoro-6-(4-(piperidin-2-yl)-1 H-imidazol-1 - yl)pyridin-3-yl)acetamide; (R)-2-(2-fluoro-3-(trifluoromethyl)phenyl)-N-(5-fluoro-6-(4-(piperidin-2-yl)-1 H-imidazol-1 - yl)pyridin-3-yl)acetamide;

[1353] (S)-2-(2-fluoro-3-(trifluoromethyl)phenyl)-N-(5-fluoro-6-(4-(piperidin-2-yl)-1 H-imidazol-1 - yl)pyridin-3-yl)acetamide;

[1354] N-(6-(4-(1 -acetylpiperidin-2-yl)- 1 H-imidazol-1 -yl)-5-fluoropyridin-3-yl)-2-(2-fl uoro-3- (trifluoromethyl)phenyl)acetamide;

[1355] N-(5-fluoro-6-(4-(2-methylpyrrolidin-2-yl)-1 H-imidazol-1 -yl)pyridin-3-yl)-2-(5-methyl-3-

[1356] (trif I uoromethy I) - 1 H-pyrazol-1 -yl)acetamide;

[1357] (R or S)-N-(5-fluoro-6-(4-(2-methylpyrrolidin-2-yl)-1 H-imidazol-1 -yl)pyridin-3-yl)-2-(5-methyl-3-

[1358] (trif I uoromethy I) - 1 H-pyrazol-1 -yl)acetamide;

[1359] (R)-N-(5-fluoro-6-(4-(2-methylpyrrolidin-2-yl)-1 H-imidazol-1 -yl)pyridin-3-yl)-2-(5-methyl-3-

[1360] (trifluoromethyl)-l H-pyrazol-1 -yl)acetamide;

[1361] (S)-N-(5-fluoro-6-(4-(2-methylpyrrolidin-2-yl)-1 H-imidazol-1 -yl)pyridin-3-yl)-2-(5-methyl-3-

[1362] (trif I uoromethy I) - 1 H-pyrazol-1 -yl)acetamide;

[1363] 2-(2-fluoro-3-(trifluoromethyl)phenyl)-N-(5-fluoro-6-(4-(morpholinomethyl)-1 H-imidazol-1 - yl)pyridin-3-yl)acetamide;

[1364] N-(3-fluoro-4-(1 -(tetrahydro-2H-pyran-2-yl)-1 H-pyrazol-4-yl)phenyl)-2-(3-

[1365] (trifluoromethyl)phenyl)acetamide; tert-butyl 4-(4-(2-cyano-6-fluoro-4-(2-(2-fluoro-3-(trifluoromethyl)phenyl)acetamido)phenyl)-1 H- pyrazol-1 -yl)piperidine-1 -carboxylate;

[1366] N-(3-cyano-5-fluoro-4-(1 -(piperidin-4-yl)-1 H-pyrazol-4-yl)phenyl)-2-(2-fluoro-3-

[1367] (trifluoromethyl)phenyl)acetamide;

[1368] N-(3-cyano-5-fluoro-4-(1 -(1 -(2-hydroxyethyl)piperidin-4-yl)-1 H-pyrazol-4-yl)phenyl)-2-(2-fluoro-3-

[1369] (trifluoromethyl)phenyl)acetamide;

[1370] N-(3,5-difluoro-4-(1-(2-hydroxy-1 -(1 -methoxycyclobutyl)ethyl)-1 H-1 ,2,3-triazol-4-yl)phenyl)-2-(2- fluoro-3-(trifluoromethyl)phenyl)acetamide;

[1371] N-(3,5-difluoro-4-(1-((3R,4S)-4-methoxytetrahydrofuran-3-yl)-1 H-1 ,2,3-triazol-4-yl)phenyl)-2-(2- fluoro-3-(trifluoromethyl)phenyl)acetamide;

[1372] N-(4-(1 -((2,3-dihydrobenzo[b][1 ,4]dioxin-2-yl)methyl)-1 H-1 ,2,3-triazol-4-yl)-3,5-difluorophenyl)-2- (2-fluoro-3-(trifluoromethyl)phenyl)acetamide;

[1373] N-(3,5-difluoro-4-(1 -(4-sulfamoylphenyl)-1 H-1 ,2,3-triazol-4-yl)phenyl)-2-(2-fluoro-3-

[1374] (trifluoromethyl)phenyl)acetamide;

[1375] N-(4-(1 -(( 1 -benzylpyrrolidin-3-yl)methyl)- 1 H-1 ,2,3-triazol-4-yl)-3 ,5-difl uorophenyl)-2-(2-f luoro-3- (trifluoromethyl)phenyl)acetamide;

[1376] N-(4-(1 -(4,4-dimethyl-2-oxotetrahydrofuran-3-yl)-1 H-1 ,2,3-triazol-4-yl)-3,5-difluorophenyl)-2-(2- fluoro-3-(trifluoromethyl)phenyl)acetamide;

[1377] N-(3,5-difluoro-4-(1-((3-methyloxetan-3-yl)methyl)-1 H-1 ,2,3-triazol-4-yl)phenyl)-2-(2-fluoro-3- (trifluoromethyl)phenyl)acetamide;

[1378] N-(3,5-difluoro-4-(1 -((1 -(methylsulfonyl)cyclohexyl)methyl)-1 H-1 ,2,3-triazol-4-yl)phenyl)-2-(2- fluoro-3-(trifluoromethyl)phenyl)acetamide;

[1379] N-(3 , 5-dif I uo ro-4- ( 1 -(1 -methyl-2-oxopyrrolidin-3-yl)-1 H-1 ,2,3-triazol-4-yl)phenyl)-2-(2-fluoro-3- (trifluoromethyl)phenyl)acetamide;

[1380] N-(3,5-difluoro-4-(1 -(pyrrol idi n-2-yl methyl )- 1 H-1 ,2,3-triazol-4-yl)phenyl)-2-(2-fluoro-3- (trifluoromethyl)phenyl)acetamide;

[1381] N-(4-(1 -((3S,4R)-4-(1 H-pyrazol-1 -yl)tetrahydrofuran-3-yl)-1 H-1 ,2,3-triazol-4-yl)-3 ,5- difluorophenyl)-2-(2-fluoro-3-(trifluoromethyl)phenyl)acetamide;

[1382] N-(3,5-difluoro-4-(1-(2-morpholinoethyl)-1 H-1 ,2,3-triazol-4-yl)phenyl)-2-(2-fluoro-3-

[1383] (trifluoromethyl)phenyl)acetamide;

[1384] N-(3,5-difluoro-4-(1-(2-((tetrahydrofuran-3-yl)oxy)ethyl)-1 H-1 ,2,3-triazol-4-yl)phenyl)-2-(2-fluoro- 3-(trifluoromethyl)phenyl)acetamide;

[1385] N-(3,5-difluoro-4-(1 -(2-( 1 -methyl-1 H-1 ,2,3-triazol-4-yl)ethyl)- 1 H-1 ,2,3-triazol-4-yl)phenyl)-2-(2- fluoro-3-(trifluoromethyl)phenyl)acetamide;

[1386] N-(3,5-difluoro-4-(1-(1-methylpiperidin-4-yl)-1 H-1 ,2,3-triazol-4-yl)phenyl)-2-(2-fluoro-3-

[1387] (trifluoromethyl)phenyl)acetamide;

[1388] N-(3,5-difluoro-4-(1-((5-oxotetrahydrofuran-2-yl)methyl)-1 H-1 ,2,3-triazol-4-yl)phenyl)-2-(2-fluoro- 3-(trifluoromethyl)phenyl)acetamide; (R)-N-(3,5-difluoro-4-(1 -((6-oxopiperidin-2-yl)methyl)- 1 H-1 ,2,3-triazol-4-yl)phenyl)-2-(2-fluoro-3- (trifluoromethyl)phenyl)acetamide;

[1389] N-(3,5-difluoro-4-(1 -(2-(2-oxopyridin-1 (2H)-yl)ethyl)-1 H-1 ,2,3-triazol-4-yl)phenyl)-2-(2-fluoro-3- (trifluoromethyl)phenyl)acetamide;

[1390] (R)-N-(3,5-difluoro-4-(1-(1-(1 -methyl-1 H-1 ,2,3-triazol-5-yl)ethyl)-1 H-1 ,2,3-triazol-4-yl)phenyl)-2-

[1391] (2-fluoro-3-(trifluoromethyl)phenyl)acetamide;

[1392] N-(4-(1 -(2-( 1 H-pyrazol-1 -yl)ethyl)-1 H-1 ,2,3-triazol-4-yl)-3,5-difluorophenyl)-2-(2-fluoro-3-

[1393] (trifluoromethyl)phenyl)acetamide;

[1394] N-(3,5-difluoro-4-(1-((4-oxo-3,5,7,8-tetrahydro-4H-pyrano[4,3-d]pyrimidin-2-yl)methyl)-1 H-1 ,2,3- triazol-4-yl)phenyl)-2-(2-fluoro-3-(trifluoromethyl)phenyl)acetamide;

[1395] N-(5-fluoro-6-(4-(morpholin-3-yl)-1 H-imidazol-1 -yl)pyridin-3-yl)-2-(5-methyl-3-(trifluoromethyl)-

[1396] 1 H-pyrazol-1 -yl)propanamide;

[1397] N-(6-(4-((3-aminooxetan-3-yl)methyl)-1 H-imidazol-1 -yl)-5-fluoropyridin-3-yl)-2-(6-

[1398] (trifluoromethyl)pyridin-2-yl)acetamide;

[1399] N-(3-fluoro-4-(1 -(tetrahydro-2H-pyran-4-yl)-1 H-pyrazol-4-yl)phenyl)-2-(3-

[1400] (trifluoromethyl)phenyl)acetamide;

[1401] N-(6-(1 -(2-azaspiro[3.3]heptan-6-yl)-1 H-pyrazol-4-yl)-5-cyanopyridin-3-yl)-2-(2-fluoro-3-

[1402] (trifluoromethyl)phenyl)acetamide;

[1403] N-(6-(1 -(2-oxaspiro[3.3]heptan-6-yl)-1 H-pyrazol-4-yl)-5-cyanopyridin-3-yl)-2-(2-fluoro-3-

[1404] (trifluoromethyl)phenyl)acetamide;

[1405] N-(3-cyano-5-fluoro-4-(1 -(piperidin-4-yl)-1 H-pyrazol-4-yl)phenyl)-2-(6-(trifluoromethyl)pyridin-2- yl)acetamide;

[1406] N-(3-cyano-5-fluoro-4-(1 -(1 -(2-methoxyethyl)piperidin-4-yl)-1 H-pyrazol-4-yl)phenyl)-2-(6- (trifluoromethyl)pyridin-2-yl)acetamide;

[1407] N-(3-cyano-5-fluoro-4-(1 -(pyrrolidin-3-yl)-1 H-pyrazol-4-yl)phenyl)-2-(6-(trifluoromethyl)pyridin-2- yl)acetamide;

[1408] N-(3-fluoro-4-(1 -(piperidin-4-yl)-1 H-pyrazol-4-yl)phenyl)-2-(3-(trifluoromethyl)phenyl)acetamide;

[1409] N-(3-fluoro-4-(1 -(2-oxopiperidin-4-yl)-1 H-pyrazol-4-yl)phenyl)-2-(6-(trifluoromethyl)pyridin-2- yl)acetamide;

[1410] N-(4-(1 -(2,2-dimethylpiperidin-4-yl)-1 H-pyrazol-4-yl)-3-fluorophenyl)-2-(6-(trifluoromethyl)pyridin- 2-yl)acetamide;

[1411] N-(3-fluoro-4-(1 -(6-oxopiperidin-3-yl)-1 H-pyrazol-4-yl)phenyl)-2-(6-(trifluoromethyl)pyridin-2- yl)acetamide;

[1412] N-(3-fluoro-4-(1 -(2-(4-methyl piperazin-1 -yl)ethyl)-1 H-pyrazol-4-yl)phenyl)-2-(3- (trifluoromethyl)phenyl)acetamide;

[1413] N-(3-fluoro-4-(1 -((4-hydroxypiperidin-4-yl)methyl)-1 H-pyrazol-4-yl)phenyl)-2-(3-

[1414] (trifluoromethyl)phenyl)acetamide;

[1415] N-(4-(1 -(2-(4H-1 ,2,4-triazol-3-yl)propan-2-yl)- 1 H-pyrazol-4-yl)-3,5-difluorophenyl)-2-(3-

[1416] (trifluoromethyl)phenyl)acetamide;

[1417] N-(3,5-difluoro-4-(1-(pyridin-2-yl)-1 H-pyrazol-4-yl)phenyl)-2-(3-

[1418] (trifluoromethyl)phenyl)acetamide;

[1419] N-(6-(4-(3,6-dihydro-2H-pyran-4-yl)-1 H-imidazol-1 -yl)-5-fluoropyridin-3-yl)-2-(5-methyl-3-

[1420] (trifluoromethyl)-l H-pyrazol-1 -yl)acetamide;

[1421] 2-(2-fluoro-3-(trifluoromethyl)phenyl)-N-(5-fliioro-6-(4-(4-methoxypiperidin-1-yl)-1 H-imidazol-1 - yl)pyridin-3-yl)acetamide;

[1422] 2-(2-fluoro-3-(trifluoromethyl)phenyl)-N-(5-fliioro-6-(4-(2-oxopyrrolidin-1 -yl)-1 H-imidazol-1 - yl)pyridin-3-yl)acetamide;

[1423] 2-(2-fluoro-3-(trifluoromethyl)phenyl)-N-(5-fliioro-6-(4-(3-oxomorpholino)-1 H-imidazol-1 - yl)pyridin-3-yl)acetamide;

[1424] 2-(2-fluoro-3-(trifluoromethyl)phenyl)-N-(5-fliioro-6-(4-(4-hydroxytetrahydro-2H-pyran-4-yl)-1 H- imidazol-1-yl)pyridin-3-yl)acetamide;

[1425] N-(6-(3-(1 -amino-3,3-difluorocyclobutyl)-1 H-1 ,2,4-triazol-1 -yl)-5-fluoropyridin-3-yl)-2-(2-f luoro-3- (trifluoromethyl)phenyl)acetamide;

[1426] N-(3-cyano-5-fluoro-4-(1 -(tetrahydro-2H-pyran-3-yl)-1 H-pyrazol-4-yl)phenyl)-2-(3-(pentafluoro- l6-sulfaneyl)phenoxy)acetamide;

[1427] N-(3,5-difluoro-4-(1-(piperidin-3-yl)-1 H-pyrazol-4-yl)phenyl)-2-(3-

[1428] (trifluoromethyl)phenyl)acetamide; and N-(5-fluoro-6-(4-(tetrahydrofuran-3-yl)-1 H-imidazol-1 -yl)pyridin-3-yl)-2-(5-methyl-3-

[1429] (trif I uoromethy I) - 1 H-pyrazol-1 -yl)acetamide.

[1430] In an embodiment of compounds of Formula (I), Formula (l-a) and Formula (l-c), or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, the compound is (S)-N-(6-(3-(4,4-difluoropyrrolidin-2- yl)-1 H-1 ,2,4-triazol- 1 -yl)-5-f luoropyridin-3-yl)-2-(5-methyl-3-(trif luoromethyl)- 1 H-pyrazol-1 - yl)acetamide and has the structure

[1431] In an embodiment of compounds of Formula (I), Formula (l-a) and Formula (l-c), or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, the compound of is crystalline (S)-N-(6-(3-(4,4- difluoropyrrolidin-2-yl)-1 H-1 ,2,4-triazol-1 -yl)-5-fluoropyridin-3-yl)-2-(5-methyl-3-(trifluoromethyl)- 1 H-pyrazol-1 -yl)acetamide.

[1432] In an embodiment of compounds of Formula (I), Formula (l-a) and Formula (l-c), or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, wherein the crystalline (S)-N-(6-(3-(4,4- difluoropyrrolidin-2-yl)-1 H-1 ,2,4-triazol-1 -yl)-5-fluoropyridin-3-yl)-2-(5-methyl-3-(trifluoromethyl)- 1 H-pyrazol-1 -yl)acetamide is characterized by having a powder X-ray diffractogram comprising at least four reflections at 2-Theta angles selected from the group consisting of (12.36 ± 0.2)°, (16.90 ± 0.2)°, (17.49 ± 0.2)°, (19.21 ± 0.2)°, (20.15 ± 0.2)°, (21 .77 ± 0.2)°, (23.01 ± 0.2)°, (23.47 ± 0.2)°, (25.91 ± 0.2)° and (29.88 ± 0.2)°, when measured at a temperature in the range of from 20 to 40 °C with Cu-Kalpha radiation having a wavelength of 0.15406 nm.

[1433] In an embodiment of compounds of Formula (I), Formula (l-a) and Formula (l-c), or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, wherein the crystalline (S)-N-(6-(3-(4,4- difluoropyrrolidin-2-yl)-1 H-1 ,2,4-triazol-1 -yl)-5-fluoropyridin-3-yl)-2-(5-methyl-3-(trifluoromethyl)- 1 H-pyrazol-1 -yl)acetamide is characterized by having a powder X-ray diffractogram comprising reflections at 2-Theta angles of (16.90 ± 0.2)°, (17.49 ± 0.2)°, (23.01 ± 0.2)°, (25.91 ± 0.2)° and (29.88 ± 0.2)°, when measured at a temperature in the range of from 20 to 40 °C with Cu- Kalpha radiation having a wavelength of 0.15406 nm.

[1434] In an embodiment of compounds of Formula (I), Formula (l-a) and Formula (l-c), or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, wherein the crystalline (S)-N-(6-(3-(4,4- difluoropyrrolidin-2-yl)-1 H-1 ,2,4-triazol-1 -yl)-5-fluoropyridin-3-yl)-2-(5-methyl-3-(trifluoromethyl)- 1 H-pyrazol-1 -yl)acetamide is characterized by having a powder X-ray diffractogram shown in Figure 1 .

[1435] In an embodiment of compounds of Formula (I), Formula (l-a) and Formula (l-c), or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, wherein the crystalline (S)-N-(6-(3-(4,4- difluoropyrrolidin-2-yl)-1 H-1 ,2,4-triazol-1 -yl)-5-fluoropyridin-3-yl)-2-(5-methyl-3-(trifluoromethyl)- 1 H-pyrazol-1 -yl)acetamide is characterized by having a differential scanning calorimetry curve comprising an endothermic peak having a peak temperature of (176.8 +0.5) °C, when measured at a heating rate of 10 °C / min.

[1436] In an embodiment of compounds of Formula (I), Formula (l-a) and Formula (l-c), or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, wherein the crystalline (S)-N-(6-(3-(4,4- difluoropyrrolidin-2-yl)-1 H-1 ,2,4-triazol-1 -yl)-5-fluoropyridin-3-yl)-2-(5-methyl-3-(trifluoromethyl)- 1 H-pyrazol-1 -yl)acetamide is characterized by having a differential scanning calorimetry curve as shown in Figure 2.

[1437] In an embodiment of compounds of Formula (I), Formula (l-a) and Formula (l-c), or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, wherein the crystalline (S)-N-(6-(3-(4,4- difluoropyrrolidin-2-yl)-1 H-1 ,2,4-triazol-1 -yl)-5-fluoropyridin-3-yl)-2-(5-methyl-3-(trifluoromethyl)- 1 H-pyrazol-1 -yl)acetamide is characterized by having a thermogravimetric analysis curve showing a mass loss of not more than 3.56 weight%, based on the weight of the crystalline (S)- N-(6-(3-(4,4-difluoropyrrolidin-2-yl)-1 H-1 ,2,4-triazol-1 -yl)-5-fluoropyridin-3-yl)-2-(5-methyl-3- (trifluoromethyl)-l H-pyrazol-1 -yl)acetamide, when heated from 20 °C to 350 °C at a rate of 10 °C / min.

[1438] In an embodiment of compounds of Formula (I), Formula (l-a) and Formula (l-c)v, or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, wherein the crystalline (S)-N-(6-(3-(4,4- difluoropyrrolidin-2-yl)-1 H-1 ,2,4-triazol-1 -yl)-5-fluoropyridin-3-yl)-2-(5-methyl-3-(trifluoromethyl)- 1 H-pyrazol-1 -yl)acetamide is characterized by having a thermogravimetric analysis curve as shown in Figure 3.

[1439] In an embodiment of compounds of Formula (I), Formula (l-a) and Formula (l-c), or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, wherein the crystalline (S)-N-(6-(3-(4,4- difluoropyrrolidin-2-yl)-1 H-1 ,2,4-triazol-1 -yl)-5-fluoropyridin-3-yl)-2-(5-methyl-3-(trifluoromethyl)- 1 H-pyrazol-1 -yl)acetamide is (S)-N-(6-(3-(4,4-difluoropyrrolidin-2-yl)-1 H-1 ,2 ,4-triazol- 1 -yl)-5- fluoropyridin-3-yl)-2-(5-methyl-3-(trifluoromethyl)-1 H-pyrazol-1 -yl)acetamide monohydrate.

[1440] In an embodiment of compounds of Formula (I), Formula (l-a) and Formula (l-c), or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, the compound is (S)-N-(6-(3-(4,4-difluoropyrrolidin-2- yl)-1 H-1 ,2,4-triazol- 1 -yl)-5-fluoropyridin-3-yl)-2-(5-methyl-3-(trifluoromethyl)-1 H-pyrazol-1 - yl)acetamide monohydrate and has the structure

[1441] In an embodiment of compounds of Formula (I), Formula (l-a) and Formula (l-c), or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt of a stereoisomer thereof, the compound is amorphous (S)-N-(6-(3-(4,4- difluoropyrrolidin-2-yl)-1 H-1 ,2,4-triazol-1 -yl)-5-fluoropyridin-3-yl)-2-(5-methyl-3-(trifluoromethyl)- 1 H-pyrazol-1 -yl)acetamide.

[1442] Depending on the choice of the starting materials and procedures, the compounds can be present in the form of one of the possible isomers or as mixtures thereof, for example as pure optical isomers, or as isomer mixtures, such as racemates and diastereoisomer mixtures, depending on the number of asymmetric carbon atoms. The present invention is meant to include all such possible isomers, including racemic mixtures, diasteriomeric mixtures and optically pure forms. Optically active (R)- and (S)- isomers may be prepared using chiral synthons or chiral reagents, or resolved using conventional techniques. If the compound contains a double bond, the substituent may be E or Zconfiguration. If the compound contains a disubstituted cycloalkyl, the cycloalkyl substituent may have a cis- or trans-configuration. All tautomeric forms are also intended to be included.

[1443] As used herein, the terms “salt” or “salts” refers to an acid addition or base addition salt of a compound of the invention. “Salts” include in particular “pharmaceutical acceptable salts”. The terms “pharmaceutically acceptable salt” or “pharmaceutically acceptable salts”, as used herein, refers to a salt or salts that retain the biological effectiveness and properties of the compounds of this invention and, which typically are not biologically or otherwise undesirable. In many cases, the compounds of the present invention are capable of forming acid and / or base salts by virtue of the presence of amino and / or carboxyl groups or groups similar thereto.

[1444] Pharmaceutically acceptable acid addition salts can be formed with inorganic acids and organic acids. The organic acid or inorganic acids used to form pharmaceutically acceptable acid addition salts of compounds of the present invention include, but are not limited to, acetic acid, adipic acid, ascorbic acid, aspartic acid, benzoic acid, benzenesulfonic acid, carbonic acid, camphor sulfonic acid, capric acid, chlorotheophyllinate, citric acid, ethanedisulfonic acid, fumaric acid, D-glycero-D-gulo-Heptonicacid, galactaric aid, galactaric acid / mucic acid, gluceptic acid, glucoheptonoic acid, gluconic acid, glucuronic acid, glutamatic acid, glutaric acid, glycolic acid, hippuric acid, hydrobromic acid, hydrochloric acid, hydroiodic acid, isethionic acid, lactic acid, lactobionic acid, lauryl sulfuric acid, malic acid, maleic acid, malonic acid, mandelic acid, mesylic acid, methanesulfonic acid, mucic acid, naphthoic acid, 1 -hydroxy-2-naphthoic acid, naphthalenesulfonic acid, 2-naphthalenesulfonic acid, nicotinic acid, nitric acid, octadecanoic acid, oleaic acid, oxalic acid, palmitic acid, pamoic acid, phosphoric acid, polygalacturonic acid, propionic acid, sebacic acid, stearic acid, succinic acid, sulfosalicylic acid, sulfuric acid, tartaric acid, p-toluenesulfonic acid, trifluoroacetic acid and triphenylacetic acid.

[1445] Salt forms of the compounds of the present invention can be converted into the free compounds by treatment with a suitable basic agent.

[1446] Pharmaceutically acceptable acid addition salts of compounds of the present invention include, but are not limited to, a acetate, adipate, ascorbate, aspartate, benzoate, besylatye, benzenesulfonate, bicarbonate / carbonate, bisulfate / sulfate, bromide / hydrobromide, camphor sulfonate, camsylate, caprate, chloride / hydrochloride, chlorotheophyllinate, citrate, edisylate, ethanedisulfonate, fumarate, gluceptate, glucoheptonate, gluconate, glucuronate, glutamate, glutarate, glycolate, hippurate, hydroiodide / iodide, isethionate, lactate, lactobionate, laurylsulphate, malate, maleate, malonate, mandelate, mesylate, methanesulfonate, methylsulfate, mucate, naphthoate, napsylate, 2-napsylate, naphthalenesulfonate, 2- naphthalenesulfonate, nicotinate, nitrate, octadecanoate, oleate, oxalate, palmitate, pamoate, phosphate / hydrogen phosphate / dihydrogen phosphate, polygalacturonate, propionate, sebacate, stearate, succinate, sulfosalicylate, sulfate, tartrate, tosylate, p-toluenesulfonate, trifluoroacetate, trifenatate, triphenylacetete and xinafoate salt forms.

[1447] The pharmaceutically acceptable salts of the present invention can be synthesized from a basic or acidic moiety, by conventional chemical methods. Generally, such salt...

Claims

1. A compound of Formula (I), or a pharmaceutically acceptable salt thereof, (I)wherein:-X=Y- is -CRx=CRy-, -CRx=N- or -N=CRy-;Rx is H, D, halogen or C1-C4alkyl;Ry is H, D, halogen, -CN, C1-C4alkyl, C1-C4fluoroalkyl or C1-C4alkoxy;R5 is H, halogen, -CN, C1-C4alkyl, C1-C4fluoroalkyl or C1-C4alkoxy;RA is:(i) phenyl which is unsubstituted or is substituted with 1, 2, 3 or 4 R1 groups;(ii) a partially saturated 9-, 10-, 11- or 12-membered bicyclic carbocyclyl which is unsubstituted or is substituted with 1 to 4 R1 groups;(iii) a 5- or 6- membered monocyclic heteroaryl having 1, 2, 3 or 4 ring members independently selected from N, NR4, O and S, wherein the monocyclic heteroaryl is unsubstituted or is substituted with 1, 2, 3 or 4 R1 groups; or(iv) a partially saturated 8-, 9-, 10-, 11- or 12-membered fused bicyclic heterocyclyl having 1, 2, 3 or 4 ring members independently selected from N, NR4, O and S, wherein the fused bicyclic heterocyclyl is unsubstituted or is substituted with 1, 2, 3 or 4 R1 groups;each R1 is independently selected from the group consisting of halogen, C1-C4alkyl, C2-C4alkenyl, C2-C4alkynyl, C1-C4alkoxy, C1-C4alkoxycarbonyl, C3-C6cycloalkyl, C1-C4fluoroalkyl, C1-C4fluoroalkoxy, pentafluorosulfanyl, C1-C4hydroxyalkyl, C1-C4thioalkyl, azido, diC1-C4alkylamino, diC1-C4alkylaminocarbonyl, D, CD3, cyano, formyl, phenyl and a 5- to 6-membered heterocycloalkyl comprising 1 or 2 ring members independently selected from N, NR4, O and S;L1 is a bond, -(CR2R3)p-, -(CR2R3)p-NR4-, -(CR2R3)p-O-, -NR4(CR2R3)q-, -(CR2R3)qNR4-, -O-(CR2R3)p- or -S-(CR2R3)p-;R2 is H, D, halogen or C1-C4alkyl;R3 is H, D, halogen, C1-C4alkyl C1-C4alkoxy, OH, amino or t-Boc-amino; or R2 and R3, together with the C atom to which they are attached, are linked to form C3-C4cycloalkyl which is unsubstituted or is substituted with a single substituent selected from C1-C4alkyl and oxo;each R4 is independently selected from the group consisting of H and C1-C4alkyl;p is 1, 2 or 3;q is 0, 1 or 2;Z1 is N or C; Z2is N or CRz; Z3is N or CRz; Z4 is N or C; Z5is N or CRz; wherein each Rz is independently selected from the group consisting of H, halogen, C1-C4alkyl and C1-C4fluoroalkyl; and provided that at least two, and not more than four, of Z1, Z2,Z3, Z4 and Z5 are N;L2 is a bond, -(CR6R7)n- or -(CR6R7)nO-*, where the * indicates the point of attachment to R8;each R6 is independently selected from the group consisting of H, C1-C4alkyl, C1-C4fluoroalkyl and C1-C4hydroxyalkyl;each R7 is independently selected from the group consisting of H, C1-C4alkyl, C1-C4fluoroalkyl and C1-C4hydroxyalkyl; or R6 and R7, together with the C atom to which they are attached, are linked to form C3-C6cycloalkyl, oxetanyl, tetrahydrofuranyl or tetrahydropyranyl;n is 1, 2 or 3;R8 is:(i) 4-, 5- or 6-membered heterocycloalkyl having 1, 2 or 3 ring members independently selected from N, NR9, O and S, wherein the heterocycloalkyl is unsubstituted or is substituted with 1, 2, 3 or 4 substituents each independently selected from -OH, -CN, -N(R10)2, halogen, C1-C4fluoroalkyl, C1-C4alkyl, C1-C4alkoxy, oxo and a 5- or 6- membered monocyclic heteroaryl having 1, 2, 3 or 4 ring members independently selected from N, NR9, O and S, wherein the monocyclic heteroaryl is unsubstituted;(ii) 4-, 5- or 6-membered heterocycloalkyl wherein one ring member is S(=O)2, S(=O)or S(=O)(=NH), and wherein the heterocycloalkyl is unsubstituted or is substituted with 1, 2, 3 or 4 substituents, each independently selected from -OH, C1-C4alkyl and oxo;(iii) 4-, 5- or 6-membered heterocycloalkyl wherein one ring member is S(=O)2 or S(=O),and 1, 2 or 3 other ring members are independently selected from N, NR9 and O, and wherein the heterocycloalkyl is unsubstituted or is substituted with 1, 2, 3 or 4 substituents each independently selected from C1-C4alkyl and oxo;(iv) a partially saturated 5- or 6-membered heterocyclyl having 1 or 2 ring members independently selected from N, NR9, O and S, wherein the partially saturated heterocyclyl is unsubstituted or is substituted with 1, 2, 3 or 4 substituents independently selected from -OH, C1-C4alkyl, and oxo;(v) a partially saturated 5- or 6-membered heterocyclyl wherein one ring member is S(=O)2 and 1, 2 or 3 other ring members are independently selected from N, NR9, O and S, wherein the partially saturated heterocyclyl is unsubstituted or is substituted with 1, 2, 3 or 4 substituents independently selected from -OH, C1-C4alkyl, and oxo;(vi) a 5- or 6- membered monocyclic heteroaryl having 1, 2, 3 or 4 ring members independently selected from N, NR9, O and S, wherein the monocyclic heteroaryl is unsubstituted or is substituted with 1, 2, 3 or 4 substituents each independently selected from -OH, C1-C4alkoxy and C1-C4alkyl; (vii) a 6- or 7-membered fused bicyclic heterocyclyl having 1 or 2 ring members independently selected from N, NR9, O and S, wherein the fused bicyclic heterocyclyl is unsubstituted or is substituted with 1, 2, 3 or 4 substituents, each independently selected from -OH, -N(R10)2, C1-C4alkyl-NH2, halogen, C1-C4alkyl, and oxo;(viii) a partially saturated 8-, 9-, 10-, 11- or 12-membered fused bicyclic heterocyclyl having 1, 2, 3 or 4 ring members independently selected from N, NR9, O and S, wherein the fused bicyclic heterocyclyl is unsubstituted or is substituted with 1, 2, 3 or 4 substituents, each independently selected from -OH, -N(R10)2, C1-C4alkyl-NH2, halogen, C1-C4alkyl, and oxo;(ix) a 6-, 7-, 8-, 9- or 10- membered spiro bicyclic heterocycloakyl having 1, 2 or 3 ring members independently selected from N, NR9, O and S, wherein the spiro bicyclic heterocycloakyl is unsubstituted or is substituted with 1, 2, 3 or 4 substituents, each independently selected from -OH, -N(R10)2, C1-C4alkyl-NH2, halogen, C1-C4alkyl, and oxo;(x) a 6- membered heterocycloalkyl having 1 to 2 ring members independently selected from N, NR9, O and S, wherein the heterocycloalkyl has a C1-C3alkyl bridge or a -CH2OCH2- bridge;(xi) phenyl which is unsubstituted or is substituted with 1, 2, 3 or 4 substituents, each independently selected from -S(=O)2N(R10)2, -OH, -N(R10)2, C1-C4alkyl-NH2, halogen and C1-C4alkyl;or(xii) C4-C8cycloalkyl which is unsubstituted or is substituted with 1, 2, 3 or 4 substituents independently selected from -OH, -N(R10)2, -S(=O)2R10, C1-C4alkyl-NH2, halogen, C1-C4alkoxy, C1-C4alkyl, and oxo;R9 is H, C1-C4alkyl, benzyl, C1-C4alkyl-OR10, -C(=O)OR10 or -C(=O)R10,andR10 is H or C1-C4alkyl.

2. The compound of Formula (I) of claim 1 having the structure if Formula (I-a) or Formula (I-b), or a pharmaceutically acceptable salt thereof, (I-a) (I-b).

3. The compound of Formula (I) of claim 1 having the structure if Formula (I-c) or Formula (I-d), or a pharmaceutically acceptable salt thereof, (I-c) (I-d).

4. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein:-X=Y- is -CRx=CRy-, -CRx=N- or -N=CRy-;Rx is H, D, or halogen;Ry is H, D, halogen or -CN;R5 is halogen or -CN;each R1 is independently selected from the group consisting of halogen, D, CD3, C1-C4alkyl, C1-C4fluoroalkyl, C1-C4fluorolkoxy, C3-C6cycloalkyl and pentafluorosulfanyl;L1 is -(CR2R3)p-, -NR4(CR2R3)q- or -O-(CR2R3)p-;R2 is H, D or halogen;R3 is H, D, halogen, OH or C1-C4alkyl;or R2 and R3, together with the C atom to which they are attached, are linked to form C3-C4cycloalkyl which is unsubstituted R4 is H or C1-C4alkyl;p is 1;q is 0;Z1 is N, Z2is CRz, Z3 is N, Z4 is C and Z5 is N;or Z1 is N, Z2is CRz, Z3 is N, Z4 is C and Z5 is CRz;or Z1 is C, Z2is CRz, Z3 is N, Z4 is N and Z5 is CRz;or Z1 is C, Z2is N, Z3 is N, Z4 is N and Z5 is CRz;each Rz is H;L2 is a bond, -(CR6R7)n- or -(CR6R7)nO-*, where the * indicates the point of attachment to R8;each R6 is independently selected from the group consisting of H, C1-C4alkyl, C1-C4fluoroalkyl and C1-C4hydroxyalkyl;each R7 is independently selected from the group consisting of H, C1-C4alkyl, C1-C4fluoroalkyl and C1-C4hydroxyalkyl;or R6 and R7, together with the C atom to which they are attached, are linked to form tetrahydropyranyl;n is 1 or 2;R8 is:(i) 4-, 5- or 6-membered heterocycloalkyl having 1 or 2 ring members independently selected from N, NR9, O and S, wherein the heterocycloalkyl is unsubstituted or is substituted with 1, 2 or 3 substituents each independently selected from -OH, -CN, -N(R10)2, halogen, C1-C4fluoroalkyl, C1-C4alkyl, C1-C4alkoxy, oxo and a 5- or 6- membered monocyclic heteroaryl having 1or 2 ring members independently selected from N and NR9, wherein the monocyclic heteroaryl is unsubstituted;(ii) 5- membered heterocycloalkyl wherein one ring member is S(=O)2, S(=O)or S(=O)(=NH), and wherein the heterocycloalkyl is unsubstituted or is substituted with a substituent selected from -OH and C1-C4alkyl;(iii) 6-membered heterocycloalkyl wherein one ring member is S(=O)2 or S(=O),and one other ring member is selected from N, NR9 and O, and wherein the heterocycloalkyl is unsubstituted or is substituted with a substituent selected from C1-C4alkyl;(iv) a partially saturated 6-membered heterocyclyl having 1 or 2 ring members independently selected from N, NR9, O and S, wherein the partially saturated heterocyclyl is unsubstituted or is substituted with an oxo;(v) a partially saturated 6-membered heterocyclyl wherein one ring member is S(=O)2 and one other ring member is selected from N, NR4, and O, wherein the partially saturated heterocyclyl is unsubstituted or is substituted with an oxo;(vi) a 5- or 6- membered monocyclic heteroaryl having 1, 2, 3 or 4 ring members independently selected from N, NR9 and O, wherein the monocyclic heteroaryl is unsubstituted or is substituted with a substituent selected from -OH, C1-C4alkoxy and C1-C4alkyl;(vii) a 6- membered fused bicyclic heterocyclyl having 1 ring member selected from N and NR9, wherein the fused bicyclic heterocyclyl is unsubstituted or is substituted with an oxo;(viii) a partially saturated 10- membered fused bicyclic heterocyclyl having 1, 2, or 3 ring members independently selected from N, NR9, and O, wherein the fused bicyclic heterocyclyl is unsubstituted or is substituted with an oxo;(ix) a 7- membered spiro bicyclic heterocycloakyl having 1 ring member selected from N, NR9, and O, wherein the spiro bicyclic heterocycloakyl is unsubstituted;(x) a 6- membered heterocycloalkyl having 1 to 2 ring members independently selected from N, NR9 and O, wherein the heterocycloalkyl has a C1-C3alkyl bridge or a -CH2OCH2- bridge;(xi) phenyl which is substituted with -S(=O)2N(R10)2;or(xii) C4-C8cycloalkyl which is substituted with 1, 2 or 3 substituents independently selected from -OH, -N(R10)2, -S(=O)2R10, C1-C4alkyl-NH2, halogen and C1-C4alkoxy;R9 is H, C1-C4alkyl, benzyl, C1-C4alkyl-OR10, -C(=O)OR10 or -C(=O)R10, andR10 is H or C1-C4alkyl.

5. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein:-X=Y- is -CRx=CRy- or -CRx=N-;Rx is H;Ry is H, halogen or -CN;R5 is halogen or -CN;each R1 is independently selected from the group consisting of halogen, C1-C4alkyl, C1-C4fluoroalkyl and pentafluorosulfanyl;L1 is -(CR2R3)p-, -NR4(CR2R3)q- or -O-(CR2R3)p-;R2 is H;R3 is H, OH or C1-C4alkyl;R4 is H or C1-C4alkyl;p is 1;q is 0;Z1 is N, Z2is CRz, Z3 is N, Z4 is C and Z5 is N;or Z1 is N, Z2is CRz, Z3 is N, Z4 is C and Z5 is CRz;or Z1 is C, Z2is CRz, Z3 is N, Z4 is N and Z5 is CRz;or Z1 is C, Z2is N, Z3 is N, Z4 is N and Z5 is CRz;each Rz is H;L2 is a bond, -(CR6R7)n- or -(CR6R7)nO-*, where the * indicates the point of attachment to R8;each R6 is independently selected from the group consisting of H, C1-C4alkyl, and C1-C4hydroxyalkyl;each R7 is independently selected from the group consisting of H, C1-C4alkyl, and C1-C4hydroxyalkyl;n is 1 or 2;R8 is:(i) 4-, 5- or 6-membered heterocycloalkyl having 1 or 2 ring members independently selected from N, NR9, O and S, wherein the heterocycloalkyl is unsubstituted or is substituted with 1, 2 or 3 substituents each independently selected from -OH, -CN, -N(R10)2, halogen, C1-C4fluoroalkyl, C1-C4alkyl, C1-C4alkoxy, oxo and a 5- or 6- membered monocyclic heteroaryl having 1or 2 ring members independently selected from N and NR9, wherein the monocyclic heteroaryl is unsubstituted;(ii) 5- membered heterocycloalkyl wherein one ring member is S(=O)2, S(=O)or S(=O)(=NH), and wherein the heterocycloalkyl is unsubstituted or is substituted with a substituent selected from -OH and C1-C4alkyl;(iii) 6-membered heterocycloalkyl wherein one ring member is S(=O)2 or S(=O),and one other ring member is selected from N, NR9 and O, and wherein the heterocycloalkyl is unsubstituted or is substituted with a substituent selected from C1-C4alkyl;(iv) a partially saturated 6-membered heterocyclyl having 1 or 2 ring members independently selected from N, NR9, O and S, wherein the partially saturated heterocyclyl is unsubstituted or is substituted with an oxo;(v) a partially saturated 6-membered heterocyclyl wherein one ring member is S(=O)2 and one other ring member is selected from N, NR4, and O, wherein the partially saturated heterocyclyl is unsubstituted or is substituted with an oxo;(vi) a 5- or 6- membered monocyclic heteroaryl having 1, 2, 3 or 4 ring members independently selected from N, NR9 and O, wherein the monocyclic heteroaryl is unsubstituted or is substituted with a substituent selected from -OH, C1-C4alkoxy and C1-C4alkyl;(vii) a 6- membered fused bicyclic heterocyclyl having 1 ring member selected from N and NR9, wherein the fused bicyclic heterocyclyl is unsubstituted or is substituted with an oxo;(viii) a partially saturated 10- membered fused bicyclic heterocyclyl having 1, 2, or 3 ring members independently selected from N, NR9, and O, wherein the fused bicyclic heterocyclyl is unsubstituted or is substituted with an oxo;(ix) a 7- membered spiro bicyclic heterocycloakyl having 1 ring member selected from N, NR9, and O, wherein the spiro bicyclic heterocycloakyl is unsubstituted;(x) a 6- membered heterocycloalkyl having 1 to 2 ring members independently selected from N, NR9 and O, wherein the heterocycloalkyl has a C1-C3alkyl bridge or a -CH2OCH2- bridge;(xi) phenyl which is substituted with -S(=O)2N(R10)2;or(xii) C4-C8cycloalkyl which is substituted with 1, 2 or 3 substituents independently selected from -OH, -N(R10)2, -S(=O)2R10, C1-C4alkyl-NH2, halogen and C1-C4alkoxy;R9 is H, C1-C4alkyl, benzyl, C1-C4alkyl-OR10, -C(=O)OR10 or -C(=O)R10, andR10 is H or C1-C4alkyl.

6. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein:-X=Y- is -CRx=N-;Rx is H;R5 is halogen;each R1 is independently selected from the group consisting of halogen, C1-C4alkyl and C1-C4fluoroalkylL1 is -(CR2R3)p-;R2 is H;R3 is H, or C1-C4alkyl;p is 1;Z1 is N, Z2is CRz, Z3 is N, Z4 is C and Z5 is N;or Z1 is N, Z2is CRz, Z3 is N, Z4 is C and Z5 is CRz;or Z1 is C, Z2is CRz, Z3 is N, Z4 is N and Z5 is CRz;or Z1 is C, Z2is N, Z3 is N, Z4 is N and Z5 is CRz;each Rz is H;L2 is a bond or -(CR6R7)n-;each R6 is independently selected from the group consisting of H and C1-C4alkyl;each R7 is independently selected from the group consisting of H and C1-C4alkyl;n is 1 or 2;R8 is:(i) 4-, 5- or 6-membered heterocycloalkyl having 1 or 2 ring members independently selected from N, NR9, O and S, wherein the heterocycloalkyl is unsubstituted or is substituted with 1, 2 or 3 substituents each independently selected from -OH, halogen, C1-C4fluoroalkyl, C1-C4alkyl, and oxo;(ii) 5- membered heterocycloalkyl wherein one ring member is S(=O)2, or S(=O)(=NH), and wherein the heterocycloalkyl is unsubstituted or is substituted with a substituent selected from C1-C4alkyl;(iii) 6-membered heterocycloalkyl wherein one ring member is S(=O)2 or S(=O),and one other ring member is selected from N, NR9 and O, and wherein the heterocycloalkyl is unsubstituted or is substituted with a substituent selected from C1-C4alkyl;(iv) a partially saturated 6-membered heterocyclyl having 1 or 2 ring members independently selected from O and S, wherein the partially saturated heterocyclyl is unsubstituted;(v) a partially saturated 6-membered heterocyclyl wherein one ring member is S(=O)2 and one other ring member is O, wherein the partially saturated heterocyclyl is unsubstituted;(vi) a 5- membered monocyclic heteroaryl having 3 ring members independently selected from N, and O, wherein the monocyclic heteroaryl is unsubstituted;(vii) a 6- membered fused bicyclic heterocyclyl having 1 ring member selected from NR9, wherein the fused bicyclic heterocyclyl is unsubstituted;(viii) a 7- membered spiro bicyclic heterocycloakyl having 1 ring member selected from N, NR9, and O, wherein the spiro bicyclic heterocycloakyl is unsubstituted;(ix) a 6- membered heterocycloalkyl having 1 ring members selected from NR9, wherein the heterocycloalkyl has a C1-C3alkyl bridge;or(x) C4-C8cycloalkyl which is substituted with 1, 2 or 3 substituents independently selected from -OH, -N(R10)2, C1-C4alkyl-NH2 and halogen;R9 is H, C1-C4alkyl, or -C(=O)R10, andR10 is H or C1-C4alkyl.

7. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein:-X=Y- is -CRx=N-;Rx is H;R5 is F;each R1 is independently selected from the group consisting of F, Cl, methyl and -CF3;L1 is -(CR2R3)p-,R2 is H;R3 is H or methyl; p is 1;Z1 is N, Z2is CRz, Z3 is N, Z4 is C and Z5 is N;or Z1 is N, Z2is CRz, Z3 is N, Z4 is C and Z5 is CRz;each Rz is H;L2 is a bond or -(CR6R7)n-;each R6 is independently selected from the group consisting of H and methyl;each R7 is independently selected from the group consisting of H and methyl;n is 1 or 2;R8 is:(i) 4-, 5- or 6-membered heterocycloalkyl having 1 or 2 ring members independently selected from N, NR9, O and S, wherein the heterocycloalkyl is unsubstituted or is substituted with 1, 2 or 3 substituents each independently selected from -OH, F, CF3, methyl and oxo;(ii) 5- membered heterocycloalkyl wherein one ring member is S(=O)2or S(=O)(=NH), and wherein the heterocycloalkyl is unsubstituted or is substituted with a methyl;(iii) 6-membered heterocycloalkyl wherein one ring member is S(=O)2 or S(=O),and one other ring member is selected from N, NR9 and O, and wherein the heterocycloalkyl is unsubstituted or is substituted with a methyl,(iv) a partially saturated 6-membered heterocyclyl having 1 or 2 ring members independently selected from O and S, wherein the partially saturated heterocyclyl is unsubstituted;(v) a partially saturated 6-membered heterocyclyl wherein one ring member is S(=O)2 and one other ring member is and O, wherein the partially saturated heterocyclyl is unsubstituted;(vi) a 5- membered monocyclic heteroaryl having 3 ring members independently selected from N and O, wherein the monocyclic heteroaryl is unsubstituted;(vii) a 6- membered fused bicyclic heterocyclyl having 1 ring member selected from NR9, wherein the fused bicyclic heterocyclyl is unsubstituted;(viii) a 7- membered spiro bicyclic heterocycloakyl having 1 ring member selected from NR9, and O, wherein the spiro bicyclic heterocycloakyl is unsubstituted;(ix) a 6- membered heterocycloalkyl having 1 ring members selected from NR9, wherein the heterocycloalkyl has a C1-C3alkyl bridge;or(x) cyclobutyl, cyclopentyl,or cyclohexyl which is substituted with 1, 2 or 3 substituents independently selected from -OH, -NH2, -CH2NH2, and F;andR9 is H, methyl or -C(=O)CH3.

8. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein:-X=Y- is -CRx=N-;Rx is H;R5 is halogen;each R1 is independently selected from the group consisting of halogen, C1-C4alkyl and C1-C4fluoroalkyl;L1 is -(CR2R3)p-;R2 is H;R3 is H;p is 1;Z1 is N, Z2is CRz, Z3 is N, Z4 is C and Z5 is N;each Rz is H;L2 is a bond;R8 is pyrrolidinyl which is substituted with 1 or 2 substituents, each independently selected from halogen and C1-C4fluoroalkyl.

9. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein:-X=Y- is -CRx=N-;Rx is H;R5 is F;each R1 is independently selected from the group consisting of F, Cl, methyl, and CF3;L1 is -(CR2R3)p-;R2 is H;R3 is H;p is 1;Z1 is N, Z2is CRz, Z3 is N, Z4 is C and Z5 is N;each Rz is H;L2 is a bond;R8 is pyrrolidinyl which is substituted with 1 or 2 substituents, each independently selected from F and CF3.

10. The compound of claim 1, or a pharmaceutically acceptable salt thereof, selected from:; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; and .

11. The compound of claim 1, or a pharmaceutically acceptable salt thereof, selected from:, and .

12. A pharmaceutical composition comprising a compound of any one of claims 1 to 11, or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable carriers.

13. A pharmaceutical composition comprising a compound of any one of claims 1 to 11, or a pharmaceutically acceptable acid addition salt thereof, and one or more pharmaceutically acceptable carriers.

14. A compound of any one of claims 1 to 11, or a pharmaceutically acceptable salt thereof for use in treating a PNPLA3I148M associated disease.

15. A compound of any one of claims 1 to 11, or a pharmaceutically acceptable salt thereof for use in treating a PNPLA3I148M associated disease by normalizing lipolysis.

16. A compound of any one of claims 1 to 11, or a pharmaceutically acceptable salt thereof, for use in the manufacture of a medicament for the treatment of a PNPLA3I148M associated disease.

17. The compound for use of claim 14, wherein the PNPLA3I148M associated disease is a liver disease.

18. The compound for use of claim 15 , wherein the PNPLA3I148M associated disease is a liver disease.

19. The compound for use of claim 16 , wherein the PNPLA3I148M associated disease is a liver disease.   20. The compound for use of any one of claims 17-19, wherein the PNPLA3I148M associated disease is a metabolic dysfunction-associated steatotic liver disease (MASLD).

21. The compound for use of any one of claims 17-19, wherein the PNPLA3I148M associated disease is a nonalcoholic fatty liver disease (NAFLD).

22. The compound for use of any one of claims 17-19, wherein the PNPLA3I148M associated disease is metabolic dysfunction–associated steatohepatitis (MASH), nonalcoholic steatohepatitis (NASH), alcoholic steatohepatitis (ASH), cirrhosis with liver fibrosis or hepatocellular carcinoma (HCC).

23. The compound for use of any one of claims 17-19, wherein the PNPLA3I148M associated disease is metabolic dysfunction–associated steatohepatitis (MASH).

24. A compound of any one of claims 1 to 11, or a pharmaceutically acceptable salt thereof for use in normalizing lipolysis.

25. A compound of any one of claims 1 to 11, or a pharmaceutically acceptable salt thereof for use in normalizing lipolysis by disrupting a PNPLA3I148M-ABHD5 complex.

26. The compound of Formula (I) of claim 1, wherein the compound is (S)-N-(6-(3-(4,4-difluoropyrrolidin-2-yl)-1H-1,2,4-triazol-1-yl)-5-fluoropyridin-3-yl)-2-(5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl)acetamide and has the structure.

27. The compound of claim 26, which is crystalline (S)-N-(6-(3-(4,4-difluoropyrrolidin-2-yl)-1H-1,2,4-triazol-1-yl)-5-fluoropyridin-3-yl)-2-(5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl)acetamide.

28. The compound of claim 26, which is characterized by having a powder X-ray diffractogram comprising at least four reflections at 2-Theta angles selected from the group consisting of (12.36 ± 0.2)°, (16.90 ± 0.2)°, (17.49 ± 0.2)°, (19.21 ± 0.2)°, (20.15 ± 0.2)°, (21.77 ± 0.2)°, (23.01 ± 0.2)°, (23.47 ± 0.2)°, (25.91 ± 0.2)° and(29.88 ± 0.2)°, when measured at a temperature in the range of from 20 to 40 °C with Cu-Kalpharadiation having a wavelength of 0.15406 nm.

29. The compound of claim 26, which is characterized by having a powder X-ray diffractogram comprising reflections at 2-Theta angles of (16.90 ± 0.2)°, (17.49 ± 0.2)°, (23.01 ± 0.2)°, (25.91 ± 0.2)° and(29.88 ± 0.2)°, when measured at a temperature in the range of from 20 to 40 °C with Cu-Kalpharadiation having a wavelength of 0.15406 nm.

30. The compound of any one of claims 26 to 29, which is characterized by having a differential scanning calorimetry curve comprising an endothermic peak having a peak temperature of (176.8 °C ±0.5) °C, when measured at a heating rate of 10°C / min.

31. The compound of any one of claims 26 to 30, which is characterized by having a thermogravimetric analysis curve showing a mass loss of not more than 3.56 weight%, based on the weight of the (S)-N-(6-(3-(4,4-difluoropyrrolidin-2-yl)-1H-1,2,4-triazol-1-yl)-5-fluoropyridin-3-yl)-2-(5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl)acetamide monohydrate, when heated from 20°C to 350°C at a rate of 10°C / min.

32. The compound of any one of claims 26 to 30, which is (S)-N-(6-(3-(4,4-difluoropyrrolidin-2-yl)-1H-1,2,4-triazol-1-yl)-5-fluoropyridin-3-yl)-2-(5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl)acetamide monohydrate.

33. The compound of claim 32, which is (S)-N-(6-(3-(4,4-difluoropyrrolidin-2-yl)-1H-1,2,4-triazol-1-yl)-5-fluoropyridin-3-yl)-2-(5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl)acetamide monohydrate and has the structure .

34. The compound of claim 26, wherein the compound is amorphous (S)-N-(6-(3-(4,4-difluoropyrrolidin-2-yl)-1H-1,2,4-triazol-1-yl)-5-fluoropyridin-3-yl)-2-(5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl)acetamide. 

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